Journal of Cancer Research and Therapeutics

Estimation and comparison of integral dose to target and organs at risk in three-dimensional computed tomography image-based treatment planning of carcinoma uterine cervix with two high-dose-rate brachytherapy sources

Background: Iridium-192 (192Ir) has been a widely accepted radioisotope for high-dose-rate (HDR) brachytherapy. Recently, Cobalt-60 (60Co) radioisotope with a longer half-life (5.26 years) has been gaining popularity due to economic and logistical reasons as compared with the traditional 192Ir. Aim: This study aimed to evaluate and compare the integral dose (ID) to the target and organs at risk (OARs) with two HDR brachytherapy sources in brachytherapy treatment of carcinoma uterine cervix to find appropriate HDR radioisotopes for clinical benefit. Materials and Methods: This is a retrospective analysis of 52 computed tomography image-based brachytherapy plans of 52 patients who have received intracavitary treatment with 192Ir HDR source. For each patient plan, one additional set of plan was created using 60Co source in place of 192Ir source keeping the same dwell position, and again dose was optimized. The volume and mean dose for target, OARs, and volume structures of 400%, 200%, 150%, 100%, and 50% were recorded for the estimation and comparison of ID. Results: The mean ID to high-risk clinical target volume was significantly higher by 5.84% in 60Co plan than that in 192Ir plan. For OARs, the mean ID to the rectum was significantly higher by 2.60% in 60Co plan as compared to 192Ir plan, whereas for bladder and sigmoid colon, it was lower in 60Co plan than that in 192Ir plan. The mean ID of central dose volume structures of 400%, 200%, 150%, 100%, and 50% was higher by 12.97%, 9.77%, 8.16%, 6.10%, and 3.22%, respectively, in 60Co plan than that of 192Ir plan. Conclusion: The results of our study concluded that 192Ir HDR radioisotope should be preferred for intracavitary brachytherapy due to its ideal physical characteristics for better clinical outcomes.

Epidemiological characteristics of endometrial cancer patients treated at a tertiary health center in National Capital Territory of India

ABSTRACT Settings and Design: A retrospective study which analyzed the data of female patients attending a tertiary care center in National Capital Territory for the treatment of endometrial cancer. Materials and Methods: Eighty-six histopathologically confirmed cases of carcinoma endometrium were taken from January 2016 to December 2019. Detailed information was collected regarding patient’s case history, sociodemographic data (age of presentation, occupation, religion, residence, and substance addiction), clinical presentation, diagnostic and therapeutic procedures, and known risk factors (age at menarche and menopause, parity, obesity, use of oral contraceptive pills, hormone replacement therapy, and comorbidities such as hypertension and diabetes). Statistical Analysis Used: After analysis, results were presented as mean ± standard deviation and frequency. Results: Eighty-six percent of the patients (n = 73) were in the age group of 40–70 years; the mean age of the patients at diagnosis of endometrial cancer was 54 years. Eighty-one percent (n = 70) of the patients were from urban areas. Sixty-seven percent of the females (n = 54) were Hindu. All the patients were housewives with nonsedentary lifestyles. Most patients (88%; n = 76) presented with bleeding per vaginum. Fifty-nine percent (n = 51) had stage I disease, followed by 15% (n = 13) with stage II, 14% (n = 12) with stage III, and 12% (n = 10) with stage IV disease. Eighty-two percent (n = 72) of the patients had endometrioid carcinoma. Other less common variants were mixed Mullerian malignant tumor, squamous, adenosquamous, serous, and endometrioid stromal. Forty-four percent (n = 38), 39% (n = 34), and 16% (n = 14) of the patients had grade I, grade II, and grade III tumor, respectively. 53.5% of the cases (n = 46) had >50% myometrial invasion at the time of presentation. Eighty-two percent (n = 71) of the patients were postmenopausal. The mean age at menarche and menopause was 13 years and 47 years, respectively. Fifteen percent (n = 13) of the females were nulliparous. Forty-six percent (n = 40) of the patients were overweight. Most patients (82%) had no history of addiction. Twenty-five percent (n = 22) of the patients had hypertension, and 27% (n = 23) has diabetes as comorbidity. Conclusions: The incidence of endometrium cancer is showing a steady rise in the recent past. Early age of menarche, late age of menopause, nulliparity, obesity, and diabetes mellitus are well-documented risk factors for uterine cancer. Better outcome and control of disease is possible by understanding of endometrial cancer etiology, risk factors, and its preventive measures. Thus, a robust screening program is warranted to detect the disease in early stage and for increased survival.

BRCA mutation carriers suffering from ovarian cancer as a model for treatment decision in higher lines – Place for platinum reinduction

ABSTRACT Context: Ovarian carcinoma is a malignancy with the highest mortality among gynecological cancers. Mutations in BRCA1/2 genes are believed to be a favorable prognostic factor and that, in general, the biological behavior of ovarian cancer in BRCA-positive individuals differs from others. However, some clinically relevant issues (i.e., prediction of response to chemotherapy and treatment of platinum-resistant BRCA-positive patients) remain unclear. Aims: (1) The aim of this study was to examine the prevalence of germline BRCA mutations in unselected recurrent ovarian cancer patient population, (2) analyze whether biological behavior of BRCA-positive tumors differs from others, and (3) analyze the effect of platinum reinduction in platinum-resistant BRCA-positive patients. Settings and Design: This was a single-institution retrospective analysis. Subjects and Methods: Consecutive recurrent ovarian cancer patients from years 2012 to 2020 were included; their BRCA1/2 mutational status was analyzed and correlated with progression-free survival (PFS), type of treatment, and response to treatment. Statistical Analysis Used: Statistical significance of differences between and among patients was tested for continuous variables by the Mann–Whitney U-test or the Kruskal–Wallis test; a maximum likelihood Chi-square test was used for categorical variables. Results: Two hundred and forty-three recurrent ovarian cancer patients were included. The median follow-up was 37 months. Pathogenic mutation in BRCA1 or BRCA2 gene was found in 18.1% of patients. There was no difference in PFS comparing BRCA-positive to BRCA-negative patients (median PFS: 10.2 vs. 10.1 months, P = 0.874); there was a difference in PFS comparing BRCA-negative versus BRCA-positive platinum-sensitive patients (9.4 vs. 14.3 months, P = 0.002). BRCA-positive platinum-resistant patients reinduced with platinum achieved a median PFS of 8 months (compared to those receiving nonplatinum treatment, median PFS: 4 months, P = 0.062). Conclusions: Germline BRCA mutations are not exclusive to platinum-sensitive ovarian cancer patients; even in platinum-resistant patients, mutation can be detected. We found no difference in PFS for platinum-sensitive BRCA-positive and BRCA-negative patients. Platinum reinduction may be considered for BRCA-positive platinum-resistant ovarian cancer patients to prolong PFS. Even these data describe only a small population, it supports the clinical practice of platinum-based chemotherapy use in platinum-resistant BRCA-positive patients.

Primary fallopian tube endometroid carcinoma: A rare case report

ABSTRACT Primary fallopian tube carcinoma is an extremely rare tumor accounting for only 0.14–1.8% of genital tract cancers. A 47-year-old female presented with post-menopausal bleeding and heaviness in the lower abdomen. Imaging revealed the right adnexal mass, suggestive of neoplastic origin. She was prepared for surgery. Per-operatively, there was a solid irregular mass, firm to hard in consistency, around 8 × 5 cm involving the whole of the right fallopian tube, and the right ovary appeared normal. Histopathological examination of the specimen showed endometroid adenocarcinoma of the right fallopian tube. Endometroid carcinoma is important to recognize because it carries the best prognosis of all the fallopian tube cancers. The patient underwent surgery, followed by adjuvant chemotherapy, and was doing well in follow-up.

Predicting the incidence of hematologic toxicity in concurrent chemoradiotherapy for cervical cancer using pelvic MRI imaging

ABSTRACT Background and Objectives: Cervical cancer is one of the most common malignancies in women. Concurrent chemoradiotherapy (CRT) is the standard treatment approach for this disease; however, it can result in severe hematologic toxicity (HT), affecting the treatment outcomes and prognosis. This study aimed to use pelvic magnetic resonance imaging (MRI) to delineate the red bone marrow and analyze its relationship with HT. The objective was to limit the red bone marrow dose and reduce the incidence of HT in CRT for cervical cancer, thereby improving the treatment efficacy and survival rates. Methods: Detailed hematological assessments were performed on 34 patients undergoing CRT for cervical cancer. The dose–volume parameters of active bone marrow regions (BMact) and whole bone marrows (BMtot) were analyzed using pelvic MRI. Univariate and multivariate logistic regression analyses were conducted to investigate the correlations between these parameters and HT. Results: Decreases in white blood cells, neutrophils, platelets, and hemoglobin were observed after CRT. Univariate analysis revealed significant correlations between HT occurrence and the dose–volume parameters of BMact and BMtot. Notably, BMact V15, BMtot V10, and BMtot V15 were significantly associated with grade 2 or higher HT incidence. Conclusion: These findings suggest that limiting the dose to red bone marrow may reduce the incidence of HT in CRT for cervical cancer. BMact V15 and BMtot V15 levels may be associated with HT risk. Reducing the occurrence of HT contributes to the completion of the treatment regimen, thereby improving the treatment efficacy and survival rates.

Comparison of postoperative adjuvant therapy for early-stage cervical cancer: A surveillance, epidemiology, and end results analysis

ABSTRACT Objectives: To compare the effects of different adjuvant treatments for different pathological types of early-stage cervical cancer post-surgery. Materials and Methods: Patients with International Federation of Gynecology and Obstetrics (FIGO) stages I–II squamous cell carcinoma (SCC), adenocarcinoma (ADC), and adenosquamous carcinoma (ASC) who underwent hysterectomy and postoperative radiotherapy (RT) from 2004 to 2015 in the surveillance, epidemiology, and end results program database were analyzed. The clinicopathological characteristics and survival rates were compared. Results: A total of 5444 cases were included. ADC had the highest 5-year overall survival (OS) and cervical carcinoma-specific survival (CCSS) rates, followed by SCC and ASC. No significant difference in prognosis was noted among the three histological subtypes when treated with chemoradiation therapy (CRT). However, the survival benefit for ASC was significantly lower than that for SCC (hazard ratio [HR], 1.625; 95% confidence interval [CI], 1.024–2.579; P = 0.039) when treated with RT alone. The prognosis of FIGO stage I patients was significantly better with RT than with CRT (HR, 0.766; 95% CI, 0.622–0.943; P = 0.012). No significant differences in CCSS were observed between patients (stages I and II) treated with external beam RT (EBRT) and EBRT + intracavity brachytherapy. Conclusion: No significant differences in OS and CCSS were observed among the three histological subtypes. The prognosis of ASC patients who received CRT was better than that of those who received RT alone. Patients with stage I tumors could obtain better survival with RT alone. The addition of brachytherapy to EBRT yielded no benefits across the three histological subtypes.

Bilateral ovarian mature cystic teratoma with unilateral malignant transformation to adenocarcinoma: A case report

ABSTRACT Mature cystic teratoma (MCT) is the most common germ cell tumor of the ovary, comprising 20% of all ovarian neoplasms. Malignant transformation (MT) is an uncommon complication and occurs in approximately 1–3% of all MCTs. The most common histological type of MT is squamous cell carcinoma. Other rare transformations include – carcinoid tumors, melanoma, adenocarcinoma, and sarcoma. We present one such rare case of bilateral MCT with unilateral MT into mucinous adenocarcinoma of intestinal type.

Dosimetric implications of omitting vaginal loading in hybrid brachytherapy for carcinoma cervix without vaginal infiltration

ABSTRACT Purpose: To compare the dosimetric parameters in hybrid brachytherapy with and without using the vaginal component for carcinoma cervix patients that do not have disease extending to the vagina. Materials and Methods: Patients without vaginal involvement who received chemoradiation and hybrid brachytherapy were prospectively included for analysis. Two plans were created for each patient. The first plan (Plan 1) was created by loading the interstitial component to 10–20% of the tandem loading and reducing the vaginal loading to 30%. The second plan (Plan 2) was created by loading the tandem and interstitial component only and eliminating the vaginal loading (ovoid’s). The dose delivered with brachytherapy was 21 Gy in 3 fractions. The dosimetric parameters compared between the two plans were D90 HRCTV, D98 IRCTV, TRAK, D2cc to bladder, rectum, sigmoid, and dose to the ICRU 89 RV point. Results: Thirty patients were included for analysis. The mean HRCTV volume was 30 cc. The mean D90 HRCTV was 88.1 Gy EQD2 for Plan 1 vs 87.8 Gy EQD2 for Plan 2, respectively (P = 0.113). On statistical analysis, there was a significant difference between Rectum D2cc (72.4 Gy vs 67.3 Gy) and ICRU 89 RV point dose (71.3 Gy vs 61.2 Gy) between the two plans (P = 0.0001). The mean D2cc to bladder and sigmoid was similar between the two plans. Conclusion: In carcinoma cervix patients without vaginal involvement, omission of vaginal loading in tandem and ovoid hybrid brachytherapy reduces rectum and RV point doses while maintaining target coverage.

Imatinib in c-KIT-mutated metastatic solid tumors: A multicenter trial of Korean Cancer Study Group (UN18-05 Trial)

ABSTRACT Introduction: We conducted an open-label, single-arm, multi-center phase II trial to evaluate the efficacy and safety of imatinib chemotherapy-refractory or metastatic solid tumor patients with c-KIT mutations and/or amplification. Methods: c-KIT mutations and amplification were detected using NGS. Imatinib (400 mg daily) was administered continuously in 28-day cycles until disease progression, unacceptable adverse events, or death by any cause. The primary endpoint was the objective response rate (ORR). Result: In total, 18 patients were enrolled on this trial. The most common tumor type was melanoma (n = 15, 83.3%), followed by ovarian cancer, breast cancer, and metastasis of unknown origin (MUO) (each n = 1, 5.5%). The total number of evaluable patients was 17, of which one patient had a complete response, six patients had partial response, and two patients had stable disease. The overall response rate (ORR) of 41.2% (95% CI 17.80–64.60) and a disease control rate of 52.9% (95% CI 29.17–76.63). The median progression-free survival was 2.2 months (95% CI 1.29–3.20), and median overall survival was 9.1 months (95% CI 2.10–16.11). The most common adverse events were edema (31.3%), anorexia (25.0%), nausea (18.8%), and skin rash (18.8%). Conclusion: Imatinib demonstrated modest anti-tumor activity and a manageable safety profile in chemotherapy-refractory solid tumors with c-KIT mutation, especially in melanoma patients.

Coexisting ovarian serous cystadenoma with fibroma: A very unusual combination

ABSTRACT Surface epithelial neoplasms are the most common ovarian tumors, constituting around 60% of all ovarian malignancies. They are classified as benign, borderline, and malignant. Ovarian cystadenomas are common benign epithelial neoplasms which carry an excellent prognosis. Ovarian thecoma-fibroma groups are uncommon sex cord-stromal neoplasms, constituting 1.0%–4.0% of all ovarian tumors. Most of them are benign and often found in postmenopausal patients. Combination tumors in the ovary are known. The most common combination is mucinous cystadenoma which occurs in association with Brenner tumor, mature cystic teratoma, Sertoli-Leydig cell tumor, or even a serous cystadenoma. A combination of surface epithelial and thecoma-fibroma group is very rarely encountered. A case of one such combination of serous cystadenoma and fibroma of the ovary is being presented here in a postmenopausal woman.

Low-dose (7.5 mg/kg) bevacizumab may be a viable option in recurrent ovarian cancer: A retrospective study

ABSTRACT Objective: Bevacizumab (BEV) is a humanized monoclonal antibody of vascular endothelial growth factor receptors and, as a result of clinical trials, was approved for the treatment of recurrent ovarian cancer (ROC). The aim of this study was to assess the clinical utility of BEV in patients with ROC in real-world practice beyond clinical trials. Materials and Methods: In this single-center retrospective cohort study, we evaluated the medical data of all patients with ROC who were treated with BEV between October 2013 and March 2020. Results: A total of 76 females were evaluated. Forty-nine (64.5%) patients were platinum sensitive and 27 (35.5%) patients were platinum resistant. BEV was used in combination with chemotherapy agents in all patients, and the most preferred combinations were gemcitabine/carboplatin (GC) (78.9%) and carboplatin/paclitaxel (14.5%). In all patients, the BEV dose was 7.5 mg/kg every 3 weeks. The median progression-free survival (PFS) was 11.1 months (95% confidence interval [CI]: 9.6–12.6), and the median overall survival (OS) was 22.3 months (95% CI: 17.5–27.2). In multivariate analysis, serous histological type (P = 0.01), maintenance BEV administration (P = 0.001), and combination of GC-BEV (P < 0.001) were associated with better PFS, while serous histological type (P = 0.016) and good performance status (P = 0.006) were associated with prolonged OS. Conclusions: Low-dose (7.5 mg/kg) BEV was found to be effective in the second-line treatment of patients with ROC in our real-life study. In addition, the combination of BEV with GC was shown to be a viable option, especially in the treatment selection of platinum-resistant patients.

Genetic polymorphisms of CYP1A, CYP1B, CYP2C and risk of cervical cancer among rural population of Maharashtra: Findings from a hospital-based case-control study

ABSTRACT Background: Last few decades, multiple studies all over the world revealed the association of genetic polymorphism in cytochrome P450 (CYP) genes with risk of developing different type of cancers, but contradictory outcomes were evidenced in case of cervical cancer (CC) risk. Therefore, the discrepancies in earlier reports influenced us to evaluate the association of CYP1A1*2A rs4646903, CYP1B1*3 rs1056836, CYP2C8*2 rs11572103, CYP2C9*2 rs1799853, CYP2C9*3 rs1057910, and CYP2C19*2 rs4244285 polymorphisms and CC susceptibility in the women of rural population of Maharashtra. Materials and Methods: In this case-control study, genetic association of the polymorphisms in CYP genes was studied by using polymerase chain reaction and restriction fragment length polymorphism (PCR–RFLP) method. The study was conducted among 350 clinically confirmed CC patients and 350 healthy volunteers in a population of south-western Maharashtra. The odds ratio (OR) with 95% confidence interval (CI) and P value were evaluated to get the level of association where P ≤ 0.005 was considered as statistically significant. Results: After the analysis of single-nucleotide polymorphism (SNPs) of CYP1A1, CYP1B1, CYP2C8, CYP2C9, and CYP2C19, we noticed that CYP1B1*3 rs1056836 (Leu4326Val) polymorphism possessed a significantly elevated risk (OR = 3.28; 95% CI: 2.18–4.94; P < 0.0001), whereas CYP2C19*2 rs4244285 showed significantly lower risk (OR: 0.53, 95% CI: 0.33–0.85 P < 0.009) of CC in the studied rural population. Conclusion: The findings from this study supported that rs1056836 SNP of CYP1B1*3 increase CC development, whereas rs4244285 of CYP2C19*2 lowers the CC risk in the studied population.

A comparative study between two different dose fractionation schedules of cobalt-60-based HDR intracavitary brachytherapy in carcinoma cervix stages IIB-IIIC1

ABSTRACT Introduction: High dose rate (HDR) intracavitary brachytherapy (ICBT) is an integral element in the treatment of carcinoma uterine cervix. The main objective of brachytherapy in carcinoma cervix is to deliver a lethal dose to tumor cells without inducing unacceptable damage to the surrounding normal tissue. Because the absorbed dose falls off rapidly, higher doses can be safely delivered to the targeted tissue over a short time. The quest for optimum dose and fractionation schedule in HDR ICBT is still ongoing, and there is no uniform consensus. This study aimed to assess the acute dose-related toxicities of HDR brachytherapy schedule of 7 Gy x 3 fractions over 6 Gy x 4 fractions in the treatment of cervical cancer. Objective: The aim of this study was to study the acute treatment-related gastrointestinal (GI) and genitourinary (GU) toxicities between two HDR brachytherapy regimens. Material and Methods: This is a prospective institutional study carried out from May 2018 to September 2018. In this time period, 66 patients of cervical cancers fulfilling our inclusion criteria were treated with concurrent chemoradiation (CCRT) following brachytherapy. During treatment, patients were randomized to arm A—7 Gy per fraction for three fractions and arm B—6 Gy per fraction for four fractions. Acute GI and GU toxicities were assessed using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. All patients were kept for follow-up for 3 months in this study. Results: There is no statistically significant difference between the two arms for acute GI and GU toxicities, and the results were comparable. Conclusions: Considering the increased hospital burden of locally advanced cervical cancer patients in the Indian context, the HDR brachytherapy schedule of 7 Gy per fraction is preferable to 6 Gy per fraction for a lesser fractionation schedule.

A prospective randomized trial comparing accelerated concurrent chemoradiotherapy with conventional concurrent chemoradiotherapy in locally advanced carcinoma cervix (IIA–IVA)

Introduction: Cervical cancer ranks fourth in women worldwide. The management requires a multidisciplinary approach. Concomitant chemoradiotherapy with cisplatin, followed by brachytherapy, is the standard approach. Accelerated radiotherapy (ART) can be used to decrease the treatment duration which can further lead to better outcomes. Materials and Methods: Stages II, III, and IVA of carcinoma cervix were studied for 1 year. Ninety patients were randomized in control and study arms, 45 patients in each arm. The total dose of radiation was 50 Gy/25#/5 weeks from Monday to Friday in the control arm and 50 Gy/25#/4 weeks from Monday to Saturday in the study arm, with injection cisplatin 40 mg/m2 intravenous infusion weekly in both the arms. Results: The response was similar in both the arms at the first follow-up as well as at median follow-up. However, acute toxicities in the ART arm were more, but they were managed conservatively. Conclusion: ART can be used in patients of cervical cancers to decrease the total treatment time. The results were similar in both the groups but need to be studied over more number of patients.

The tolerance to chemoradiation for cervical cancer patients

Context: Rural versus urban cervical cancer. Aims: This study aims to study the difference in toxicities and clinical outcome of chemoradiation in urban and rural cervical cancer patient. Settings and Design: This was a prospective study. Subjects and Methods: In a double-arm prospective study, cervical cancer patients were treated with chemoradiation followed by brachytherapy. Patients were monitored weekly for hematological, gastrointestinal toxicities, and electrolyte imbalance. Acute toxicities and long-term outcome were compared between the two groups. Statistical Analysis Used: Kaplan–Meier survival curves for analysis of disease free and overall survival and Pearson's Chi-square test and Fisher's exact tests for analysis of toxicities were used. Results: Fifty-seven patients from urban and 114 from rural region were studied. There were no difference between the two groups as far as the patient characteristics, overall treatment time (OTT), hematological, electrolyte imbalance, local control, and disease-free survival between the two groups. Associated comorbidities were significantly higher (53% vs. 17%) with P < 0.0001 in urban population. Grade II and III enteritis were significantly higher 15.78% versus 21.05% (P = 0.00001) and 12.28% versus 11.40% (P = 0.03) in urban patients, respectively. Conclusions: Tolerance to chemoradiation, disease-free survival, and overall survival are similar in both urban and rural patients of cervical cancer, with more enteritis in urban group. However, this did not increase OTT.

Post hysterectomy mesonephric carcinoma: A case report and literature review

Mesonephric carcinoma is a rare type of carcinoma seen in the female genital tract. It arises from the mesonephric remnants situated in the broad ligament, lateral wall of the cervix, vagina, and uterine corpus. Very few cases of mesonephric carcinoma have been reported so far in the literature. The sites mentioned in various literatures include the cervix, vagina, or uterus, but we could not find any literature that mentions posthysterectomy vault as a site for mesonephric carcinoma. Here, we report a case of 40-years-old hysterectomised female who presented in the hospital with nodular growth on the vault and complaints of bleeding per vaginum. Microscopy of the lesion did not show typical morphology of mesonephric carcinoma, but immunohistochemistry played a vital role in the diagnosis of this rare tumor.

Assessment and implication of rectal filling on vaginal motion in postoperative carcinoma endometrium patients during image guided radiotherapy

Aim: While delivering radiotherapy it is utmost important to minimize target motion to decrease margins in postoperative gynaecological patients. Hence certain bladder and rectum filling protocols are followed by each institute. During cone beam computed tomography (CBCT) verification, we observed that this motion was more affected by rectal filling. To verify, we retrospectively analysed the vaginal movement and its relation with bladder and rectum filling. Materials and Methods: We evaluated CBCTs of 15 patients of carcinoma endometrium. Bladder and rectum both were contoured offline on each scan. To assess the motion of vagina, two reference points were selected. Posterior movement of bladder and anterior movement of rectum were noted on these points on each scan. Results: Total 150 scans (135 KV-CBCT scans and 15 planning computed tomography) of 15 patients were studied. Stepwise regression analysis reported that bladder wall changes has a nonsignificant relationship with bladder volume among all the individuals. The significant rectal wall changes both at Point X and Y were observed in six patients and only at Point X in three patients. Rest of the patients showed no significant relationship in their CBCT scans. Thus 60% patients showed significant relation between rectal volume and rectal wall changes. Conclusion: Hence we suggest to advice our patients more regarding volume of rectum to decrease vaginal motion. Bladder volume is needed to decrease the dose to small intestine. However prospective data with large number of patients in the study is required to confirm these findings.

Correlation of menstrual hygiene management with cervical intraepithelial neoplasia and cervical cancer

ABSTRACT Purpose: To find the correlation of menstrual hygiene management (MHM) with cervical intraepithelial neoplasia and cervical cancer. Materials and Methods: This case-control study was conducted in a tertiary care teaching hospital for 1 year. One hundred cases (CIN or cervical cancer) and 135 controls (normal cervical cytology, Swede’s score below 5, or normal cervical histology) were surveyed about MHM practices through a predesigned, semi-structured questionnaire by interview method. Data were analyzed on SPSS version 17.0 statistical analysis software through Chi-square test and bivariate regression analysis. Results: All Poor MHM practices except frequency of change of absorbent were significantly more commonly seen in women with CIN or Cervical cancer as compared to controls (P < 0.001). The bivariate regression analysis showed that old age, illiteracy, and the use of old cloth are significant risk factors for cervical cancer. Conclusion: Poor menstrual hygiene practices of using old cloth and disposal in open are significant risk factors of cervical cancer. Good MHM practices should be widely publicized and implemented in the community to reduce the risk of cervical cancer.

Coverage rate of Pap smear for cervix cancer screening during COVID-19 outbreak: Importance of continuing preventive health care

Dermatomyositis: Look beyond skin

Rucabarib

Background: Rucaparib is a drug with potential as maintenence monotherapy in ovarian cancers irrespective of genetic mutation. Methods: The results of the ARIEL 3 trial were analysed for the drug's prospects towards cure in ovarian and other pelvic malignancies. Results: Ovarian cancer patients with highly malignant tumors and relapses on platinum based chemotherapy exhibited statistically significant reductions in tumor size with maintenance Rucaparib therapy vis a vis placebo. Conclusion: Genetic heterogeneity of the tumor did not have an impact upon Rucaparib efficacy in ovarian carcinoma. More malignant and relapsed variants can effectively be treated with Rucaparib, thereby improving survival rates and quality of life.

Regulatory effects of miRNA in epithelial ovarian cancer patients: A case–control study from Eastern India

ABSTRACT Introduction: Current biomarkers of epithelial ovarian cancer (EOC) lack the required sensitivity and specificity for early detection. MicroRNAs (miRNAs) are implicated in cancer progression, and their serum expression could serve as a non-invasive diagnostic tool. This study focuses on evaluating the expression of serum miR-200a, miR-200b, and miR-200c and their association with clinico-pathological characteristics in EOC patients. Materials and Methods: Ninety-eight EOC patients and 96 age-matched healthy women participated. RNA was extracted from serum, and reverse transcription followed by quantitative real-time polymerase chain reaction (qPCR) assessed miRNA (miR) expression. Correlations with clinico-pathological parameters, including FIGO staging and tumor, node, and metastasis (TNM) grading, were explored. Results: Serum levels of miR-200a, miR-200b, and miR-200c were significantly higher in EOC compared to controls ( P < 0.01). When correlated with clinico-pathological parameters, miR-200c positively correlated with cancer severity (FIGO staging and TNM grading). In contrast, miR-200a and miR-200b showed no significant associations with clinical severity. Receiver operating characteristic curve analysis demonstrated miR-200a_Ct as the most promising parameter (area under the curve [AUC] = 0.997, P < 0.001), with high sensitivity (100%) and specificity (99%) at a cut-off value of >19.50. Conclusion: The study reveals the overexpression of miR-200a, miR-200b, and miR-200c in EOC patients. MiR-200a and miR-200b expression was correlating with early stage, while miR-200c emerged as a prognostic marker, correlating with cancer severity. This suggests regulatory role; however, further investigation into epithelial-to-mesenchymal transition-related factors is warranted to have a deeper understanding of the differential expression of miRNAs. The study underscores the diagnostic potential of serum miRNAs in EOC and the need for a reliable early detection method.

Isolated humeral metastasis in cervical cancer: A case report and review of the literature

There are a few reported cases of isolated localized metastasis to bone arising from cancer of uterine cervix in the literature. This is a case of uterine cervix cancer with isolated metastasis to the humerus. A 57-year-old female with a diagnosis of FIGO Stage IIB invasive squamous cell carcinoma of uterine cervix underwent neoadjuvant chemoradiation therapy (CRT) and radical surgery with complete pathological response. Nine months after the surgery, a total body positron emission tomography/computed tomography (PET/CT) scan documented a lesion localized in the proximal part of the right humerus, whereas no evidence of skeletal metastasis found elsewhere. The biopsy from the bone lesion showed a metastatic squamous cell carcinoma of the uterine cervix. A surgical excision of the humeral lesion plus chemotherapy and zoledronic acid was performed. After 9 months, the patient experienced liver metastases and died 2 months later. Bone metastasis is not so infrequent in patients with locally advanced cervical cancer. Total body PET/CT scan should be included in staging work up, and an appropriate treatment should have the primary objective of quality of life preservation.

Efficacy and safety of poly (ADP-ribose) polymerase inhibitors therapy for BRCA-mutated breast cancer

Background: To evaluate the efficacy, safety, and potential advantages of Poly (ADP-ribose) polymerase inhibitors (PARPi) in treating BRCA-mutated breast cancer, we performed a meta-analysis of published studies. Materials and Methods: Four randomized controlled trials (RCTs) were included in the meta-analysis. Data analysis was conducted in Review Manager 5.4. Results: The progression-free survival (PFS) of the patients with triple-negative (hazard ratio [HR] 0.81; 95% confidence interval [CI] 0.74–0.88; P < 0.00001) or hormone receptor-positive (HR 0.83; 95% CI 0.77-0.91; P < 0.0001) BRCA-mutated breast cancer was significantly extended in the containing PARPi therapy arm versus the chemotherapy arm. PFS of the patients who did not receive platinum-based therapy (HR 0.78; 95% CI 0.70–0.86; P < 0.0001) was significantly extended in the PARPi monotherapy arm versus the chemotherapy arm. The objective response rate of patients treated by PARPi monotherapy (risk ratio [RR] 2.51; 95% CI 1.81–3.47; P < 0.00001) was significantly higher than that of patients treated by chemotherapy. The incidence of thrombocytopenia in patients received PARPi combined therapy was obviously increased compared with chemotherapy group (RR 1.36; 95% CI 1.07–1.72; P = 0.01). PARPi monotherapy markedly increased the incidence of anemia (RR 5.83; 95% CI 2.64–12.88; P < 0.0001) versus chemotherapy. However, the risk of neutropenia (RR 0.48; 95% CI 0.29–0.81; P = 0.006) was reduced in the PARPi monotherapy arm. There were no statistical differences in other adverse events among these three groups. Conclusions: PARPi combined therapy and monotherapy improved PFS of patients with BRCA-mutated breast cancer compared with standard chemotherapy, which was unrelated to type of BRCA mutation and status of hormone receptor. PARPi therapy has slightly higher hematological toxicity and better overall safety and tolerance. Prospero registration number: CRD42020204385.

Breast cancer in young and very young women; Is age related to outcome?

Background: Breast cancer in young women is associated with aggressive biology. We analyzed histopathological and clinical properties of breast cancer patients diagnosed at ≤40 years of age. Methods: Breast cancer patients who were admitted between 2015 and 2019 were included. Baseline characteristics of the patients with treatment-related outcomes were assessed. The study group was divided into two subgroups; <35 years old as “very young” and ≥35 years old as “young.” Results: The data of 137 patients (60 patients <35 years) were reviewed. The mean age was 34.7 years. The mean follow-up duration was 44.45 ± 26.39 months, and the mean disease-free survival was 36.17 ± 21.97 months. 11.4% of the patients were diagnosed with Stage 4 disease. Pathologic subtype was invasive ductal carcinoma in 86% of patients. 16.8% of the patients were luminal A, 38.7% luminal B, 30.5% were human epidermal growth factor receptor-2–positive type, and 15.3% were triple-negative. Only 5 (3.3%) patients had given birth after chemotherapy. During the follow-up period of early-staged diagnosed patients, metastatic disease occurred in 24.6%. The rate of distant metastasis development was statistically higher in the very young group (31% vs. 11%; P = 0.004). Thirteen patients (10.7%) died due to disease progression. Thirty-seven percent of the patients had a positive family history for either breast or ovarian cancer. Conclusions: Very young breast cancer patients seem to have a more aggressive disease course. The low rate of childbearing in this young patient population is conspicuous. An interdisciplinary approach for the management of this special patient population should be taken into consideration.

CXCR4 and RIF1 overexpression induces resistance of epithelial ovarian cancer to cisplatin-based chemotherapy

Introduction: The chemoresistance of epithelial ovarian cancer (EOC) is a major problem. Thus, the search for novel biomarkers associated with cisplatin sensitivity is overwhelming. Previous studies have shown that CXC chemokine receptor 4 (CXCR4) is associated with tumor growth, angiogenesis, and distant metastases, and replication timing regulatory factor 1 (RIF1) is responsible for the repair of double-strand DNA breaks. This study, thus, aimed to identify the correlation between CXCR4 and RIF1 overexpression and cisplatin sensitivity in EOC. Materials and Methods: Fifty-five EOC patients were recruited to assess the chemosensitivity of EOC to cisplatin-based chemotherapy at the Oncology Department in Tanta University Hospitals, Egypt. Results: The results showed that patients with a higher CXCR4 and RIF1 expression exhibited a significantly lower chemosensitivity, worse overall survival, and poorer progression-free survival. The only prognostic associated with overall survival was CXCR4. Conclusion: Our study showed that CXCR4 and RIF1expression levels are not associated only with poor prognostic features of epithelial ovarian cancer but also with its chemoresistance to cisplatin, and consequently, with worse overall survival and progression free survival.

Syzygium cumini (jamun) fruit-extracted phytochemicals exert anti-proliferative effect on ovarian cancer cells

Background: The medicinal properties of Syzygium sp., especially the antidiabetic property, date back to the ancient times. However, in the recent past, extracts from different parts of the Syzygium sp. have demonstrated promising anticancer activities in diverse cancer types, and now, attempts are being made to identify the active phytochemicals. Aims and Objectives: In this study, we intended to test the anticancer properties of phytochemicals extracted from the fruit of Syzygium cumini plant in ovarian cancer cells. Materials and Methods: A total of nine phytochemicals extracted from the S. cumini fruits using chloroform were tested for their anticancer activity in the ovarian cancer cell line PA-1. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium assay was performed to calculate the 50% inhibition (IC50) concentration and cell cytotoxicity values. Cell scratch assay was performed to assess the proliferation inhibition activity of the phytochemicals. Cisplatin was used as positive control. Results: Out of the nine phytochemicals tested, quercetin (QC), gallic acid (GA), and oleanolic acid (OA) were found active. QC and GA were most effective with more than 90% cell cytotoxicity at 2.5 µ g/ml and above concentrations and OA moderately effective up to 5 µg/ml serial concentrations. Cell proliferation was significantly inhibited by QC and GA and moderately but significantly by OA. Conclusion: Our data demonstrate the anticancer activity of QC, GA, and OA phytochemicals, which is consistent with the previous reports. However, this is the first report showing the anticancer activity of these phytochemicals derived from S. cumini in the ovarian cancer cells. These data suggest that there is a potential to develop these phytochemicals as anticancer therapeutic agents either as monotherapeutic agents or in combination with commonly used chemotherapeutic agents, which needs to be explored.

Frequency and risk factors of bleomycin-induced pulmonary toxicity in South Indian patients with germ-cell tumors

Aim: Bleomycin, etoposide, and cisplatin (BEP) regimen is the standard treatment for germ-cell tumors (GCTs). Bleomycin-induced pulmonary toxicity (BPT) is fatal and dose-limiting toxicity associated with this regimen. In this study, we aimed to identify the frequency and risk factors of BPT in South Indian GCT patients receiving BEP regimen. Patients and Methods: The study was carried out in the Department of Medical Oncology, Regional Cancer Centre at a tertiary care hospital in South India. All the patients with GCT (testicular and ovarian) who were receiving BEP regimen from December 2014 to May 2018 were included in the study. BPT was defined as the presence of radiological features and/or clinical symptoms during or post-treatment. Results: BPT was observed in 11 (27%) patients of 41 analyzed patients. Five (12%) patients developed BPT during treatment whereas six (15%) patients developed BPT post-treatment. Cumulative bleomycin dose ≥240 mg (relative risk 3.8, confidence interval: 1.2–12.2,P =0.02) was found to increase the risk of BPT. Three-year overall survival in patients with and without toxicity was 82% and 93%, respectively. Conclusions: The frequency of BPT in the study population is 27%, and cumulative bleomycin dose ≥240 mg has been found to be associated with increased risk of developing BPT. BPT does not negatively impact survival outcome in GCT patients receiving BEP regimen.

Role of maintenance paclitaxel in epithelial ovarian cancer

Purpose: The purpose of the study is to assess the benefits of maintenance chemotherapy (CT) in epithelial ovarian cancer with CT and surgery. The primary and secondary endpoints of the study were progression-free survival (PFS) and overall survival (OS), respectively. Patients and Methods: Three hundred patients with ovarian cancer (registered between January 2012 and December 2013) received 6 cycles of 3 weekly CT (injection paclitaxel 175 mg/m2 + injection carboplatin 6 AUC) and surgery. After 4 weeks of completion of the above treatment, patients were assessed for response with radiological imaging and serum CA125. Then, these patients were randomly allotted in two arms; 150 patients in Arm A received 6 cycles of single agent, 3 weekly injection paclitaxel 175 mg/m2 as maintenance therapy while 150 patients in Arm B, were on observation. The follow-up was done at 1 month, then 3 monthly in the 1st year and 6 monthly in the 2nd year to evaluate PFS and annually up to 5 years for OS. Results: The PFS at 1 and 2 years was 91% and 80% in study arm and 65% and 50% in control arm; the differences were statistically significant (P = 0.010). The 5-year overall survival was 43% versus 38% in study and control arms, respectively (P = 0.410) and 5-year PFS was 28% versus 18% (P = 0.039) in maintenance and observation arm, respectively. Except for peripheral neuropathy, there was no statistically significant difference in toxicities between the two arms. Conclusion: The study suggests that 6 cycles of single-agent paclitaxel maintenance therapy significantly prolongs the duration of PFS and better trends toward OS, though a large study is needed to come to a conclusion.

Evaluation of promoter hypermethylation of tumor suppressor gene BRCA1 in epithelial ovarian cancer

Context: Epithelial ovarian cancer (EOC) is a serious gynecological issue worldwide and its late detection is the major encumbrance in treatment procedures. Hypermethylation-mediated BRCA1 gene silencing results in failure of the repair system of damaged DNA playing an important role in ovarian carcinogenesis. BRCA1 gene hypermethylation can serve as a safe and highly specific clinical marker for EOC. Aims: The present study was conducted to evaluate the promoter hypermethylation of BRCA1 gene in EOC patients. Settings and Design: This hospital-based case–control study carried out in the tertiary care hospital in New Delhi. Subjects and Methods: Promoter hypermethylation of BRCA1 gene was examined in 30 EOC diagnosed untreated cases confirmed by histopathological examinations and compared with 30 normal healthy controls matched for age using methylation specific-polymerase chain reaction. Results: We found significantly higher BRCA1 promoter hypermethylation in the serum of EOC cases as compared to controls with P < 0.0001. BRCA1 gene methylation was found to have 70% sensitivity for the diagnosis of EOC with 100% specificity. A significant difference was observed in the range of CA125 levels, B12 and Folate levels between EOC cases and controls. Conclusions: We conclude that BRCA1 gene is significantly hypermethylated in EOC patients and thus can prove to be a noninvasive diagnostic tool. Our results provide prefatory evidence that epithelial ovarian epigenome can be influenced by dietary nutrients.

First-line chemotherapy analysis on survival in carcinoma ovary patients

Aims: This study aims to assess the survival and identify the prognostic factors in ovarian cancer patients treated with surgery and carboplatin/paclitaxel based first-line chemotherapy (CT). Settings and Design: The electronic medical records of all ovarian cancer patients registered during January 2009 and December 2017 were screened retrospectively. Subjects and Methods: A total of 440 cases were included in accordance with the inclusion/exclusion criteria of study. The comprehensive data regarding demography, treatment, chemotoxicities, recurrence, and others were collated and analyzed. Statistical Analysis Used: Cox regression analysis was used for univariate and multivariate analyses of prognostic factors. Results: The median age at diagnosis was 50.6 years. All cases had got CT-related morbidity but no associated mortality. The median recurrence-free survival (RFS) and mean overall survival (OS) were 30 (95% confidence interval [CI]: 24.65–35.38) months and 40.4 months, respectively. A significant difference was observed among the RFS (P < 0.001); and OS (P = 0.036) in relation to the stage of disease. Furthermore, patients who relapsed post first-line CT had 36%, 9%, 3% recurrence in second-, third-, and fourth-line CT regimens, respectively. Multivariate analysis proved the histology, low-grade serous, to be the favorable prognostic factor for RFS (hazard ratio = 0.18; 95% CI: 0.04–0.82). Conclusions: Surgery and first-line CT with carboplatin/paclitaxel lead-to-moderate long-term survival in ovarian cancer. The likelihood of relapse is fairly high as stage advances. Low-grade serous histology is an independent prognostic factor for RFS.

Comparison of treatment response in cervical carcinoma patients infected with human papillomavirus 16 and human papillomavirus 18 who are treated with chemoradiation

Objectives: The primary objective of this study was to compare the treatment response of cervical carcinoma patients infected with human papillomavirus (HPV) 16 and HPV 18 who are treated with chemoradiation. Materials and Methods: Ninety-six biopsy-proven cervical cancer patients, suitable for curative treatment with definitive radio-chemotherapy with International Federation of Gynecology and Obstetrics Stage IB2–IIIB, were included in this prospective study. HPV testing was done using TRUPCR® HPV 16 and 18 real-time polymerase chain reaction kit. All the patients received a dose of 83–90 Gy total equieffective dose to the high risk clinical target volume(HRCTV) using tele- and brachytherapy. Results: Of the 96 patients, 79 (82.3%) patients were positive for HPV DNA. Seventy-three patients showed HPV genotype 16 positivity and six patients were positive for genotype 18. The response was correlated with HPV genotype. There was a statistically significant increase in complete radiological response in HPV 16 compared to HPV 18 and negative groups at 3 months, 80.8%, 50%, and 52.9%, respectively (χ2= 36.5, P < 0.001). There was also a statistically significant increase in clinical response at 3 months in HPV 16 group compared to HPV 18 and negative groups, 87.5%, 50%, and 50%, respectively (χ2= 29.9, P < 0.001). The age, volume of the disease, overall treatment time, average hemoglobin level, and the number of blood transfusions did not have any correlation. Conclusion: HPV genotype 16 positivity shows higher complete response in cervical carcinoma patients treated with definitive chemoradiation compared to HPV 18 genotype. Further HPV genotyping could potentially help stratify cervical cancer patients for more effective therapeutic regimens.

Successful treatment results of external radiotherapy without brachytherapy in advanced uterine cervical cancer

In advanced uterine cervical cancer, external radiotherapy with intracavitary brachytherapy has been established as a curative treatment method. However, in an environment where brachytherapy is difficult to perform, there has been an attempt to use only external radiotherapy. We report the results of eight patients over 65 years of age with advanced uterine cervical cancer who refused brachytherapy and obtained successful results through external radiotherapy alone.

Dose–volume analysis of acute gastrointestinal complications in cervical cancer undergoing definitive concurrent chemoradiation

Context: Definitive concurrent chemoradiation with brachytherapy is the prime modality of treatment of cervical cancer. The small bowel is one of the critical organs responsible for gastrointestinal complications. Aims: This study aims to analyze the relation of small bowel dosimetric parameters with the incidence of acute gastrointestinal complications. Subjects and Methods: The study analyzed 40 patients of stage IIB–IVA who underwent concurrent chemoradiation with three-dimensional conformal radiotherapy and weekly cisplatin from June 2017 to June 2018. The small bowel was contoured as the organ of risk. Dose–volume histogram parameters of the small bowel subjected to analysis were mean dose, maximum dose, the total volume of organ receiving 20 Gy, 40 Gy, and 45 Gy (V20-45), and the volume of V20-45 to total volume (V20-45 ratio). Gastrointestinal toxicity was graded using CTCAE version 5.0 criteria. Association between dosimetric parameters and incidence of 1–2 gastrointestinal complications were evaluated. Results: A total of forty patients treated with concurrent chemoradiation were analyzed. Seven patients reported Grade 1, whereas three patients reported Grade 2 gastrointestinal complications. None of the patients reported Grade 3 or higher gastrointestinal complication. Patients with gastrointestinal complications had greater V30-45 and mean dose as compared to those without gastrointestinal complication. Conclusions: Dosimetric parameters of small bowel should be evaluated to reduce the incidence of gastrointestinal complications.

Chemoradiation in locally advanced Ca Cx

Introduction: neutrophil gelatinase-associated lipocalin (nGAL) has been reported to be unregulated in many cancers and to suppress tumor suppressor genes like p53 leading to cell proliferation. Studies to report its relationship with carcinoma cervix (Ca Cx) are still scant. Materials and Methods: Serum nGAL levels were analyzed in 30 patients of histopathologically proven locally advanced Ca Cx at the time of diagnosis and 3 weeks after standard chemoradiation by enzyme-linked immunosorbent assay. These patients underwent either brachytherapy or supplementary external beam radiotherapy (EBRT) depending on the response of treatment. The results were analyzed statistically by applying Student's paired t-test. Results: no statistically significant difference (P > 0.05) was observed in patients of Ca Cx before and after treatment or when compared stage wise, histopathological grade wise, or response wise. But the levels were found to increase when duration of treatment was ≥8 weeks (P = 0.040) and to decrease significantly when duration of treatment was <8 weeks (P = 0.0052). The nGAL levels also increased significantly after treatment in patients who received EBRT and supplementary radiotherapy (P = 0.019) while the pre- and post-treatment difference in nGAL levels was not statistically significant in patients who received EBRT + intracavitary brachytherapy (P > 0.05). Conclusion: As the duration as well as modality of treatment is quite important in Ca Cx, shorter duration associated with better results and lower nGAL levels, nGAL might prove to be a useful biomarker although further studies are needed to support the claim.

Endoscopic and clinical correlation with dose to sigmoid colon in carcinoma cervix patients treated with radical radiotherapy

Context: Sigmoid colon, due to its close proximity to central tandem in intracavitary brachytherapy (BT), is at risk of receiving high dose, the clinical significance of which is not documented. Aim: This study was designed to assess the dose received by sigmoid colon following radical treatment and to correlate clinically with the sigmoid mucosal changes seen on sigmoidoscopy. Settings and Design: This is a prospective study. Subjects and Methods: Thirty histologically proven carcinoma cervix patients treated with radical radiotherapy were accrued. A baseline sigmoidoscopy was done and repeated at 6 months following completion of BT. The dose–volume parameters (DVP) were used to calculate the dose received by the sigmoid colon and correlate with symptoms along with the sigmoid mucosal changes. Statistics: The following were the statistical methods used: frequency; percentages; and descriptive statistics such as mean ± standard deviation, Chi-square test, Kolmogorov–Smirnov test, and independent sample t-test. P < 0.05 was considered statistically significant. Results: The dose of the sigmoid colon in patients with a sigmoidoscopy score of ≥2 was significantly high compared to that of patients with a score of <2 for DVP such as D0.1cc, D1cc, D2cc, D5cc, and mean dose, whereas max dose was not significantly high. Conclusions: The dose received by the sigmoid colon is directly proportional to the mucosal changes and hence possibly a higher morbidity. Tighter dose–volume constraints, better optimization techniques, and close follow-up sigmoidoscopy will help in the prevention and early treatment of long-term morbidity.

Role of various screening techniques in detecting preinvasive lesions of the cervix among symptomatic women and women having unhealthy cervix

Introduction: Cervical cancer which is preventable, occurs due to humanpapiloma virus infection and results in a preinvasive condition called cervical intraepithelial neoplasm (CIN) before the development of cancer. Majority of the patients with CIN or early stage of cervical cancer present with symptoms such as abnormal vaginal discharge or bleeding, and unhealthy looking cervix. Selectively screening these symptomatic patients, can detect more number of positive cases and also most effective screening technique for these selective patients can be advocated. Materials and Methods: All married women between 21 and 65 years attending gynecology outpatient department of a tertiary care health center in Central India and having unhealthy cervix or abnormal vaginal discharge were included. All women were subjected to Pap smear, visual inspection under acetic acid (VIA), visual inspection under Lugol's iodine (VILI) and colposcopy. Biopsy was taken in all cases. Diagnostic value of each screening method was determined in terms of sensitivity, specificity, positive predictive value and negative predictive value. Results: Out of 352 patients, around 20% of them were found to have abnormal cytology. The sensitivity and specificity of Pap smear was found to be 34% and 94%. But colposcopy has high sensitivity and low specificity, i.e., 99% and 31%, respectively. On the other hand the sensitivity and specificity of VIA and VILI are comparable i.e., 65% and 45% and 64% and 48% respectively. Pap smear shows high positive predictive value among all, i.e., 85% and colposcopy shows 58% for the same. Conclusion: Pap smear carries low sensitivity but high positive predictive value. As compared to Pap smear, VIA and VILI are more sensitive and are of low cost. Colposcopy can be considered as a preferred method of screening due to its extremely high sensitivity.

Volumetric image guidance for intravaginal brachytherapy

Background: The present retrospective dosimetric and clinical study aims to explore the subset of patients who will benefit from volumetric image guidance in intravaginal brachytherapy (IVBT). Materials and Methods: Sixty-three consecutive patients who underwent IVBT using single-channel intravaginal cylinder were analyzed. The most common IVBT dose protocol was 1100 cGy in two fractions (with external beam radiotherapy [EBRT]) and 2200 cGy in four fractions (when used alone). The factors affecting the dose to organs at risk (OARs) (such as treated length, orientation of applicator, EBRT) and target volume were analyzed. Local control rate and late toxicities were reported. Results: There was a statistically significant increase in equivalent dose at 2 Gy per fraction (EQD2) doses of all OARs with the addition of EBRT. In 39.4%, EQD2 D2cc dose of rectum was more than 65 Gy. There was a statistically significant positive correlation with increasing treated length in D5cc (Gy) of rectum and D5cc (Gy) of urethra (Pearson's correlation coefficient of 0.375, P = 0.002 and Pearson's correlation coefficient of 0.394, P = 0.001, respectively). There was a statistically significant increase in D2cc and D5cc of rectum with posterior orientation. Air gaps were noted in 81% of applications. Median duration of follow-up was 30 months. One patient had vaginal recurrence in lower third of vagina. One patient was recorded with grade 2 hemorrhagic radiation proctitis. Conclusion: Computed tomography (CT)-based volumetric planning is an effective method to evaluate doses to OARs and confirm the adequacy of dose coverage, and we recommend routine use of the same. Image guidance is most beneficial in patients being treated with a combination of IVBT and EBRT, posterior orientation, and those who are treated for the entire length of vagina.

Correlation of skeletal muscle depletion with acute toxicities for cervical cancer patients undergoing concurrent chemoradiation

Context: Pelvic radiation with concurrent chemotherapy is associated with toxicities that worsen the cachectic state of the patient. Aims: The aim of this study is to quantify skeletal muscle changes on computed tomography (CT) images helps in assessing the same which could be correlated with the toxicities. Settings and Design: The study design was s prospective study. Subjects and Methods: Forty-one patients were treated with chemoradiation followed by brachytherapy (BT) for cervical cancer. Preexternal beam and preBT CT scans were used to assess skeletal muscle index (SMI). The changes in the SMI were correlated with enteritis, dyselectrolytemia, and hematological toxicities. Statistical Analysis Used: Paired t-test was used to compare pre- and post-treatment SMI. Chi-square test would be used to study the association between toxicity and SMI change. Results: The mean SMI was 57.41 cm2/m2 (42.5–73) in the preexternal beam radiotherapy (EBRT) scans and 54.5 cm2/m2 (40.9–71.07) in the post-EBRT scans. Twenty-two patients (53.7%), 14 patients (34.1%), and five patients (12.2%) belonged to <5%, 5%–10%, and >10% loss in SMI groups, respectively. Grade III enteritis was seen in 31.7% of the patients, hyponatremia in 26.8% of the patients in the 4th week, and leukopenia and neutropenia were seen in 26.8% of cases in the 5th week. Enteritis correlated significantly with the change in SMI (P = 0.047). Conclusion: Patients with cancer cachexia are at higher risk for radiation enteritis during chemoradiation for cervical cancer.

Use of misoprostol before tandem application for intracavitary brachytherapy in patients of carcinoma cervix

Aim: To investigate the ease of tandem application and external os identification by giving sublingual misoprostol before initiation of intracavitary brachytherapy in cancer cervix patients. Materials and Methods: 36 patients with cervical cancer stage IIIB which were supposed to undergo intracavitary brachytherapy(ICBT) were randomly divided into 2 subgroups, group A patients receiving misoprostol and group B not receiving misoprostol. Misoprostol 400 mcg was given sublingually 3 hrs prior to the procedure. The efficacy of the drug was measured as per the ease of identification of os and easier tandem application and amount of bleeding during procedure. Results: Application of tandem and identification of external os was easier and amount of bleeding was also less in patients that were administered sublingual misoprostol. Conclusion: Sublingual Misoprostol given before ICBT helps in cervical ripening and thus leads to easier os recognition and central tandem application and reduce overall anaesthesia time.

Comparing the knowledge and awareness of cervical and breast cancer among medical and nonmedical students of a private institution in South India

Context: Cervical and breast cancer is the most leading cause of death among women globally. Cervical and breast cancer can be cured if detected early. Aims: The aim of the study was to compare the knowledge and awareness of cervical and breast cancer among medical and nonmedical students of a private institution in South India. Settings and Design: A cross-sectional study was done on 600 female students of a private institution comprising both medical and nonmedical for a period of 6 months. Subjects and Methods: A study was done to assess the awareness and knowledge on cervical and breast cancer by using a standardized questionnaire. Statistical Analysis Used: The data were statistically analyzed with Mann–Whitney test by using GraphPad prism. Results: Out of the 600 female students, there were each of 300 female students in medical and nonmedical. Majority of the student population was seen in 17–19 years: 143 (47.6%) in medical and 206 (68.6%) in nonmedical. A total of 235 (78.3%) medical students have heard of cervical cancer and its screening (164 [54.6%]). Many nonmedical students have never heard of cervical cancer (248 [82.6%]) and its screening (283 [94.3%]). Nearly 61% of the medical students and 1.1% nonmedical have heard of Pap smear. Both medical students (276 [92%]) and nonmedical students (179 [53.2%]) were aware of the breast cancer but have less awareness about the age of occurrence. Awareness on breast self-examination was poor among medical (137 [45.6%]) and nonmedical (19 [5.6%]) students. The P < 0.0001 (<0.05) showed a statistically significant difference between the medical and nonmedical students. Conclusions: Through the findings of our study, we analyzed that the knowledge and awareness of cervical and breast cancer among medical students was better than that of the nonmedical students.

Reason for improper simple hysterectomy in invasive cervical cancer in Northeast India

Objective: The objective of the study was to determine the reasons for improper simple hysterectomy in the presence of invasive cervical cancer in Northeast India. Materials and Methods: The medical records of 52 patients who had undergone improper simple hysterectomy in the presence of invasive cervical cancer and were referred to a tertiary regional cancer Institute at Guwahati, Assam, between January 2015 and December 2019 were reviewed. Results: Most of the patients presented with abnormal vaginal bleeding (40.4%). The failure to perform cervical cytology before the operation was quite high at 48.1% (25 patients). Interestingly, normal cytologic smear could still be found in 15.4% (8 patients) despite the presence of invasive cervical cancer. Failure to perform preoperative Papanicolaou smear, incomplete evaluation of cervical intraepithelial neoplasia (CIN) on cervical biopsy, and negative Papanicolaou smear accounted for 75% of the patients undergoing inappropriate simple hysterectomy. The most common indications for inappropriate operation were abnormal vaginal bleeding (40.4%) and CIN (19.2%). The reasons for inappropriate simple hysterectomy included lack of preoperative cervical cytology (48.1%), false-negative cervical cytology (15.4%), incomplete evaluation of cervical dysplasia or microinvasion on biopsy (11.5%). failure to perform indicated conization(5.8%), emergency hysterectomy (3.8%), errors in colposcopic examination (3.8%), incomplete evaluation of an abnormal cervical cytology (3.8%), failure to review slide (3.8%) and failure to biopsy a gross cervica lesion (3.8%). Conclusion: Most improper simple hysterectomy resulted from deviation from guideline for cervical cancer detection protocols. Improper simple hysterectomy in the presence of invasive cervical cancer can be avoided if one sticks to the diagnostic guideline for patients with an abnormal cervical cytology.

Concurrent chemotherapy with high-dose rate brachytherapy after treatment with chemoradiotherapy in cases of locally advanced carcinoma cervix

Aim: This study aims to evaluate the efficacy, feasibility, tolerability, and toxicity of concurrent chemotherapy and brachytherapy for locally advanced cervical carcinoma. Materials and Methods: Forty patients of cervical carcinoma were included in this study. The study period ranges from October 2016 to September 2019. Patients were evaluated and treated as per the protocol: external beam radiotherapy (50 Gy in 25 fractions) and concurrent weekly chemotherapy with injection (Inj.) cisplatin (30 mg/m2) followed by high-dose rate brachytherapy (3 fractions of 7 Gy each) and concurrent chemotherapy Inj. cisplatin (30 mg/m2). Results: Out of 40 patients enrolled in the study, 36 patients completed the treatment (17 Stage II and 19 Stage III). The incidence of Grade I and II skin toxicities were 78% and 10%, respectively. The incidence of genitourinary toxicities with respect to Grade I and II were 72% and 12%, respectively. There were Grade III hematological toxicities in two patients and the brachytherapy treatment was delayed for 4–6 days. The overall complete response was found in 28 (78%) patients, partial response in six (16.7%) patients, and progressive disease in two (5.6%) patients at 3 months of follow-up. On the last follow-up, 21 (58%) patients were disease-free and there was disease failure in seven patients (5 local recurrence and 2 with distant metastasis). Conclusion: Brachytherapy with the addition of concurrent chemotherapy is effective and feasible with acceptable toxicity for advanced stages of carcinoma cervix. This study upholds an interesting approach that can be regarded as feasible and tolerable for cervical cancer patients.

Type C1 radical hysterectomy in advanced squamous cell carcinoma of the cervix postdefinitive concurrent chemoradiation

Aims: This study aimed to evaluate the feasibility and outcomes of patients with advanced cervical cancer treated with definitive concurrent chemoradiotherapy followed by Type C 1 nerve-sparing radical hysterectomy. Settings and Design: This is a prospective study to assess the feasibility of Type C 1 nerve-sparing radical hysterectomy postdefinitive chemoradiation in advanced carcinoma cervix. Subjects and Methods: We analyzed 25 patients with cervical cancer evaluated and treated with concurrent chemoradiation followed by surgery. Twenty patients underwent Type C 1 nerve-sparing radical hysterectomy by open surgery and five patients by laparoscopic approach. Postoperative morbidity and pathology were analyzed. Statistical Analysis Used: Analysis of the outcomes was done by arithmetical calculations. Results: Eight patients (32%) had persistent residual disease after definitive chemoradiation followed by surgery. Rest of the patients had pathological complete response. Two patients (8%) had node-positive disease. None of the patients in the laparoscopic group had bladder morbidity. One patient in the laparoscopic group had persistent vaginal discharge. Conclusions: Type C1 nerve-sparing radical hysterectomy is technically feasible with minimal morbidity following definitive chemoradiation in advanced squamous cell carcinoma of the cervix.

Preoperative prediction of retroperitoneal lymph node involvement in clinical stage IB and IIA cervical cancer

Objective: Lymph node metastasis (LNM) is the most important factor affecting survival in early-stage cervical cancer (CC). International Federation of Gynecology and Obstetrics revised the staging of CC in 2018 and reported LNM as a staging criterion. We investigated the preoperatively assessable risk factors associated with LNM in surgically treated stage IB1-IIA2 CC patients. Materials and Methods: This was a retrospective cohort study of women who underwent radical hysterectomy and pelvic lymphadenectomy with or without para-aortic lymphadenectomy for CC stage IB1–IIA2 from 2004 to 2019. All patients included in this study were examined with speculum inspection, parametrial assessment by rectovaginal palpation under general anesthesia, transvaginal ultrasonography, magnetic resonance imaging (MRI), and chest radiography. Clinical staging was done according to the preoperative findings. MRI was used to measure tumor and lymph node dimensions. Results: Out of the 149 women included in the study, 29 (19.4%) had LNM. Univariate analysis revealed that larger tumor size (≥30 mm), lymphovascular space invasion (LVSI) detected with diagnostic biopsy, parametrial involvement, and deep stromal invasion status were significantly different between the group with LNM and the group without LNM. In multivariate analysis, specific preoperative risk factors such as MRI based tumor diameter ≥30 mm and LVSI (+) on the diagnostic biopsy were found to be independent risk factors for LNM in the multivariate analysis. Conclusion: The rate of LNM is high in patients with CC with a tumor size ≥30 mm and preoperative biopsy LVSI status even if they are clinically in early stages. Surgeons can take this into account while deciding between primary surgery and chemoradiotherapy in the treatment of CC.

Single step “See and Treat” strategy might be replacing the “conventional three step strategy” in management of preinvasive cervical lesions at tertiary center

Introduction: The aim of this study was to compare overtreatment rates of see and treat colposcopy-based single step protocol with cytology and colposcopy-guided biopsy-based conventional three-step protocol using loop electrosurgical excision procedure (LEEP) for treatment of preinvasive lesions of cervix. Materials and Methods: Prospective interventional study was carried out over a period of 1 year. Recruitment of cases was done from the 664 diagnostic colposcopies performed for various gynecological indications. Among 496 colposcopies performed exclusively for unhealthy cervix on per speculum examination, 74 women had high-grade colposcopy (Swede score ≥5). Subsequently, 50 women were enrolled under the see and treat arm, arm 1 and underwent LEEP. In study arm 2, conventional three-step strategy, concurrently 22 women with abnormal cytology. ≥ Atypical squamous cells of undetermined significance and unhealthy cervix were enrolled for colposcopy and if indicated, guided biopsy was obtained and tissue was sent for histopathology. Only 12 such women having HPE reports of cervical intraepithelial neoplasia (CIN) 2 or 3 were subjected to LEEP. Overtreatment was defined as CIN 1 or less on final LEEP tissue histopathology. Results: The overtreatment rate in See and Treat protocol was 44% when colposcopy Swede score cutoff was considered 5, which fell down to 0% when Swede score cutoff was taken 7. Conventional three step protocol had an overtreatment rate of 8.3%. Incidentally diagnosed high-grade CIN or invasive cancer was found in 24%. Discrepancy between biopsy tissue and LEEP tissue histopathology was 50% in conventional arm. Conclusion: Women with unhealthy cervix having high-grade colposcopy (Swede score ≥7) can be directly subjected to LEEP without waiting for results of any initial screening modality. Advantages include minimal over treatment coupled with reduced patient visits and interventions.

Oncology treatment outcome in human immunodeficiency virus-positive cancer cervix patients

Objective: To find out the epidemiological factors and oncology treatment outcome in human immunodeficiency virus-positive cancer cervix patients (HPCCP). Materials and Methods: After institutional ethics committee approval, hospital case records of HPCCP registered at the radiation oncology department from January 2011 to December 2018 were retrospectively studied. Results: The case records of 22 eligible HPCCP were studied. Median age at presentation was 42.5 years. 90.90% of the patients were below 55 years of age. The duration of symptom was <3 months in 63.64% of patients. 68.18% of the patients were FIGO Stage III. Only 11 patients completed the planned treatment. Total target equivalent dose of 2 Gy per fraction delivered was 66 Gy. Seven patients had complete response. Four patients had local recurrence. Median disease-free and overall survival was 27 (14–38) and 18 months (2–48), respectively. Conclusion: HPCCP present at relatively early age and advanced stage despite short symptom duration. Poor patient compliance and treatment alteration have led to suboptimal outcome.

A study for evaluating clinical relevance of circulating cell-free DNA in cervical cancer

Introduction: Recent techniques available for the detection of cervical cancer (CC) are highly invasive and costly, which makes it a rate-limiting step toward early diagnosis of this fatal disease. Evaluation of circulating cell-free DNA (ccfDNA) through liquid biopsy is a minimally invasive and cost-effective method that may serve as a unique tumor marker for early detection, treatment monitoring, the status of residual disease, and distant tumor metastasis in CC patients. Materials and Methods: In this study, initially, ccfDNA was measured in serum samples from 11 histopathologically proven cervix carcinoma patients and 8 controls. On successful screening, it was further extended to 2 more patients with a series of serum samples extracted at 3 different phases of the concurrent chemoradiotherapy (i.e., before, during, and after 6 months of follow-up). Results: Agarose gel electrophoresis profile for ccfDNA of CC patients showed that of 11 patients, 4 patients had a comparatively higher tumor burden (ccfDNA) than the other 7 patients. Notably, during concurrent chemoradiotherapy, ccfDNA load disappeared and, after 6 months of follow-up, appeared back due to distant metastasis. Conclusion: Hence, we propose that this method could be an affordable and reliable way to diagnose/screen CC.

Relationship of irradiated bone marrow volume and neutropenia in patients undergoing concurrent chemoradiation therapy for cervical cancer

Introduction: Concurrent chemoradiation therapy (CCRT) is the standard of care in the management of cervical cancer (International Federation of Gynecology and Obstetrics [FIGO] 2008 Stages IB2-IVA). Apart from the myelotoxic effects of chemotherapy, irradiation of pelvic bone marrow (BM) in the radiation field, can also contribute to hematological toxicity. Objectives: We examined the relationship of irradiated BM volume and neutropenia in cervical cancer patients undergoing CCRT. Materials and Methods: This prospective study was conducted in a tertiary cancer center with a longitudinal study design. A total of 43 patients undergoing CCRT for cervical cancer were included. Using auto bone segmentation, the external contour of pelvic bones from L4 vertebral body to ischial tuberosities were delineated as BM. The volume of BM receiving 10, 20, 40, 50 Gy was calculated. Complete blood counts were done weekly to evaluate the neutropenia and were graded according to Common Terminology Criteria for Adverse Events, version 3.0. The risk of developing neutropenia was analyzed using logistic regression. Results: Twenty-seven patients (62.8%) received 5 cycles of chemotherapy, 14 patients (32.6%) received 4 cycles of chemotherapy and 2 patients (4.7%) received 3 cycles of chemotherapy. Overall, 22 patients (51.2%) experienced acute neutropenia. On multivariate analysis increased BM V50Gy had a statistically significantly odds of developing any grade of neutropenia (odds ratio [OR] =1.43; 95% confidence interval [CI], 1.03–1.97; P = 0.028). When comparing patients receiving BM V40Gy ≥40% with BM V40Gy <40% odds of any grade of neutropenia was increased (OR = 2.03; 95% CI, 0.55–7.42; P = 0.28). Moreover, when comparing patients receiving BM V50Gy ≥15% with BM V50Gy <15% odds of any grade of neutropenia was increased (OR = 2.13; 95% CI, 0.57–7.97; P = 0.26). Conclusions: High-dose irradiation to the larger volume of BM prevents compensatory hyperplasia which leads to neutropenia in patients undergoing CCRT for cervical cancer.

Cisplatin versus gemcitabine as concurrent chemoradiotherapy in squamous cell carcinoma cervix

Cervical cancer ranks as the four leading cause of cancer death in women worldwide. It is the third most common cancer in India. Most patients present in advanced stages. Concurrent chemoradiation is the standard of treatment for locally advanced cervical cancer. Aims: The aim of the study was to compare the treatment response and hematological, gastrointestinal, and skin toxicity of cisplatin versus gemcitabine as concurrent chemoradiotherapy. Materials and Methods: This study was conducted from February 2017 to August 2018. Sixty patients of squamous cell carcinoma cervix with Stage IIB to IIIB were randomly allocated to either weekly gemcitabine (observation arm) 150 mg/m2 or cisplatin (control arm) in the dose of 35 mg/m2 along with concurrent radiotherapy. Treatment response and toxicities of both drugs were evaluated. Statistical Method: Statistical analysis was conducted using the Statistical Package for the Social Sciences version 20. Descriptive statistics such as frequency, percentages, mean, standard deviation, and range were used to describe the treatment characteristics. Results: Gemcitabine arm has more Grade 2 (23.3% vs. 10%) and Grade 3 (3.3% vs. none) hematological toxicity as compared to cisplatin arm. For gastrointestinal toxicity, Grade 2 toxicity was observed more in cisplatin arm (23.3%) as compared to 13.3% in gemcitabine arm. Skin toxicity was found to be insignificant. There was complete response of 86.7% in cisplatin arm, while 73.3% in gemcitabine arm. Conclusion: Cisplatin has a better treatment response as compared to gemcitabine as concomitant chemotherapy agent with external beam radiation therapy. Hematological toxicity was more in gemcitabine arm and gastrointestinal toxicity was more in cisplatin arm. The skin toxicities were comparable in both the arms.

The immunohistochemical biomarker B-cell lymphoma-2 expression in malignant and premalignant lesions of the uterine cervix and its association with human papillomavirus infection

Introduction: Cervical cancer is one of the leading causes of cancer deaths among women. It results due to human papillomavirus (HPV) infection. Cervical intraepithelial neoplasia (CIN) is the preinvasive condition of cervical cancer. Various objective immunohistochemical (IHC) markers have been studied for cervical cancer. This study is aimed at studying the expression of B-cell lymphoma-2 (Bcl-2) IHC marker among preinvasive and invasive lesions of cervical cancer and its association with HPV infection. Methodology: This prospective study was conducted over a period of 1 year in a tertiary care hospital in central India, included 73 women suffering from CIN and cancer cervix. The expression of Bcl-2 and the presence of HPV genotypes were studied. Results: Out of 73 patients, 34 had cancer cervix, out of which 15 (44%) had Bcl-2 positivity, 24 had CIN 1, out of which 13 (54%) had Bcl-2 positivity, 10 had CIN 2, out of which 4 (40%) had Bcl-2 positivity and 5 had CIN 3, out of which 3 (60%) had Bcl-2 positivity. No significant difference was found in Bcl-2 positivity among CIN-1, CIN-2, CIN-3, and cancer cervix cases with a Chi-square value of 1.116 and P = 0.77. HPV positivity was found in 41 (56%) out of 73 patients where HPV 16 subtype was the most common (31.5%), followed by HPV 18 (13.7%). No significant association between HPV positivity and Bcl-2 positivity was found with P = 0.34. Conclusion: Bcl-2 IHC seems to have variable expression among CIN cases. Although its expression is low among invasive cancer cases when compared with preinvasive lesions, the difference is not significant. Similarly, no significant association was found between Bcl-2 expression and HPV infections.

Dosimetric analysis of intensity-modulated radiation therapy and volumetric-modulated arc therapy in comparison with conventional box technique in the treatment of carcinoma cervix

Introduction: The number of patients for carcinoma cervix with implanted hip prostheses has been increasing worldwide during the past several decades. Technological advancements are useful for delivering higher doses, i.e., dose escalation to the target, but the presence of high-density implanted hip prosthesis creates challenges for the planner. Materials and Methods: A population of 25 patients was selected for the study. Plans were generated using the MONACO treatment planning system keeping the isocenter same. The parameters evaluated for planning target volume (PTV) were D98%, D50%, D2%, Dmax, Dmean, V107%, and V110%. Similarly, the parameters Dmax, Dmean, and D2cc were evaluated for the delineated critical organs. Average monitor units (TMUmean) were also assessed. Results: D98% of PTV was 44.51 (standard deviation [SD]: 0.13) Gy, 44.41 (SD: 0.38) Gy, 44.58 (SD: 0.14) Gy, 44.08 (SD: 0.41) Gy and 44.46 (SD: 0.32) Gy for 4F, intensity-modulated radiation therapy (IMRT), IMRT_WP, volumetric-modulated arc therapy (VMAT), and VMAT_WP techniques, respectively, where WP stands for “without prosthesis”. Volume of bowel receiving 45 Gy was 86.82 (SD: 66.38) cm3, 6.97 (SD: 5.77) cm3, 14.11 (SD: 14.29) cm3, 13.31 (SD: 6.57) cm3, and 10.31 (SD: 10.94) cm3 for 4F, IMRT, IMRT_WP, VMAT and VMAT_WP techniques, respectively. Discussion: Radiotherapy is standard care of practice for known cases of cervical malignancies. As per our investigations, VMAT has generated comparable plans in terms of target coverage (D98%) as compared to IMRT and 4F techniques (P = 0.015 and P = 0.002) and with prosthesis also (P = 0.024). The mean dose to the bladder was significantly lesser with IMRT and VMAT. Our results highlight that VMAT has reduced the mean dose to the rectum (P = 0.001) in presence of high-density implant. The mean dose to femoral heads was also reduced when compared with the 4-field technique. Conclusion: VMAT has an edge over other techniques in terms of target coverage and sparing of critical organs in the presence of metallic prosthesis. Information about the geometry and density of prosthesis will be beneficial for treatment planning.

Precision prediction of cervical cancer outcomes: A machine learning approach to recurrence and survival analysis

ABSTRACT Cervical cancer remains a significant global health challenge, with high rates of recurrence and mortality, particularly in low-resource regions. Effective prediction of recurrence and survival is crucial for optimizing treatment and improving patient outcomes. Recently, artificial intelligence (AI) has emerged as a transformative tool in oncology, providing advanced methodologies for analyzing large-scale medical data and offering predictive insights into patient outcomes. This review comprehensively explores the role of AI in predicting cervical cancer recurrence and survival, focusing on techniques such as machine learning, deep learning, and natural language processing. The integration of AI with medical imaging, genomics, and clinical data is discussed, along with the associated challenges and limitations. Future directions and the potential impact of AI on personalized medicine in cervical cancer care are also examined.

Artificial intelligence in brachytherapy for cervical cancer

Brachytherapy (BT) consists in the insertion of radioactive implants directly into the tissue through an applicator, in order to kill tumor cells. This is for the tumor tissue to receive a higher dose, whereas the surrounding normal tissues receive a lower dose of radiation because of the rapid fall of the dose. Because of the special anatomical position of the cervix, smaller organ mobility, and higher tolerable doses of radiotherapy in the vagina and uterus, BT has been most widely used to treat cervical cancer and is an important part of radical radiotherapy for this type of cancer. Furthermore, it is closely related to the prognosis of patients. However, the treatment process, including target area delineation, applicator reconstruction, plan design, and optimization, is time-consuming, which may lead to changes in patient's bladder filling or gastrointestinal peristalsis. Therefore, this not only yields a poor patient experience, but may also affect the accuracy of the treatment and prognosis. With the development of computer hardware, deep learning has been gradually applied in different fields and different networks have been developed to solve various problems. By combining deep learning technology with three-dimensional BT technology, the automation of BT planning can be realized, which, in turn, can significantly shorten the treatment time, alleviate the pain of the patient, and improve treatment efficacy. This article summarizes and gives the prospects of the application of artificial intelligence in the context of BT for cervical cancer.

Clinical impact of extended field radiation therapy in Stage III carcinoma cervix versus conventional field techniques

Aim: The aim of the study was to examine tumor control and clinical outcomes of extended field irradiation and compare it with those treated with conventional field in same disease profile and also to determine toxicities associated with radiation treatment. Methods: This study included 50 biopsy-proven and registered International Federation of Gynecology and Obstetrics Stage III cases of carcinoma cervix treated with concurrent computed tomography (injection cisplatin 40 mg/m2 weekly) + external beam radiotherapy (EBRT) upto 50 Gy + high-dose-rate intracavitary brachytherapy (ICBT) (22.5 Gy). Twenty-five patients were randomized to each arm. Arm A: Conventional field EBRT 50 Gy with concurrent weekly chemotherapy followed by ICBT. Arm B: Extended field EBRT 50 Gy with concurrent weekly chemotherapy followed by ICBT. Results: At 12-month follow-up, 43 patients (86%) had attained CR. Overall, seven patients (14%) were in noncomplete response (CR) group (non-CR = patients with partial response, stable disease, or progressive disease). The non-CR rate was 16% for Arm A and 20% for Arm B. Among seven patients of non-CR group, six had local disease and one had failure at distant site. Five (10%) patients died in this study, 2 (8%) in Arm A and 3 (12%) patients in Arm B. Residual disease was seen in 2 (4%) patients. Grade III diarrhea was seen in eight patients (16%), 3 in Arm A (12%) and 5 in Arm B (20%). Fifteen patients (30%) developed Grade III skin toxicity. Seven patients in Arm A (28%) and 8 patients (32%) in Arm B developed Grade III toxicity. Twenty-five (50%) cases presented with varying stages of vaginal adhesions and stenosis. Conclusion: Majority of patients achieved CR with minimal acute and late toxicities with similar results in both arms. No patient had pelvic or para-aortic metastasis until recent follow-up.

A mathematical model to predict the different isodose volumes using TRAK value in HDR intracavitary brachytherapy for revised Manchester and ICRU-89 based Point A plans using computer tomography images

Purpose: To find out the simple relationship between Total Reference Air Kerma (TRAK) and various isodose volumes. Calculated isodose volumes were compared with experimental data for revised Manchester and International Commission on Radiation Units and measurements (ICRU)-89 Point A-based treatment plans. The accuracy of the formula was compared with the results of other relationships available in the literature. Materials and Methods: Dosimetric data from 62 intracavitary brachytherapy (ICBT) treatment plans of 31 patients with cervical cancer were studied. Each patient had treatment plans normalized to revised Manchester and ICRU-89 Points A (Aflange and Aicru89). For each treatment plan, TRAK values, V350, V700, V1050, and V1400 were obtained. The modeling curve was plotted between Isodose volume (Vd) and the ratio of d/TRAK obtained from Aflange plans to get a mathematical relation. The results of this formula were compared with the experimental data and outcomes of other formulas available in the literature. A paired-sample t-test was performed to assess the statistical significance. Results: In the case of revised Manchester-based Aflange normalization plans, the mean isodose volume of V350, V700, V1050, and V1400 were 285.98 ± 32.3 cm3, 101.96 ± 10.63 cm3, 52.71 ± 4.72 cm3, and 31.44 ± 2.33 cm3 respectively. Likewise, for ICRU-89 based Aicru89 normalization plans, the mean isodose volumes of V350, V700, V1050, and V1400 were 304.11 ± 26.17 cm3, 108.88 ± 8.29 cm3, 56.62 ± 3.69 cm3 and 34 ± 2.23 cm3 respectively. The mean difference was significant. The Mathematical relationship developed was [INLINE:1]. No correlation was found between TRAK and D0.1cm 3,D2cm 3 for organs at risk. Conclusions: The developed formula calculated isodose volumes within the accuracy of ± 3% in ICBT plans.

Randomized controlled study for comparison of efficacy and safety between thermocoagulation and cryotherapy in visual inspection with acetic acid positive cervical lesions

Background: Less literature is available on the performance of thermocoagulation for treatment of premalignant cervical lesions and its comparison with cryotherapy from low- and middle-income countries like India. Materials and Methods: A prospective randomized controlled study was done in the Department of Obstetrics and Gynecology from August 2018 to September 2019 after obtaining ethical clearance from Institutional Review Board (Reg no: ECR/262/Inst/Up/2013/RR/16) Ref no: 278/Ethics/R. cell-18). A total of 68 women with Visual inspection with acetic acid (VIA) positive cervical lesion were randomized into two groups. Group A was treated with cryotherapy and Group B was treated with thermocoagulation. Estimates of cure, adverse effects or complications were presented as frequencies, percentages, and mean ± standard deviation. Results: Out of 667 patients, 624 patients underwent VIA testing among which 68 were VIA positive (10.89%, 68/624). The efficacy of thermocoagulation was 93.54% and that of cryotherapy was 90.32%. Immediate side effects were significantly lesser in thermocoagulation group (P = 0.008) in comparison to cryotherapy. Conclusion: Thermocoagulation is better treatment modality than cryotherapy for VIA-positive cervical lesions may not be in terms of efficacy but definitely in terms of patient comfort and safety.

To evaluate the use of tandem and cylinder as an intracavitary brachytherapy device for carcinoma of the cervix with regard to local control and toxicities

Introduction: Brachytherapy always remains a keystone in the treatment of gynecological carcinoma for both definitive and adjuvant treatments. Due to the rapid fall-off nature of brachytherapy, the target gets a high dose with a low dose to the normal organs nearby and thereby increasing the tumor control probability. Aims and Objectives: This study aims at the evaluation of local control and toxicities in the carcinoma of the cervix using tandem and cylinder as brachytherapy applicator. Materials and Methods: The study was conducted between January 2014 and December 2018 in a tertiary care hospital. Thirty-one patients who fulfilled our set criterion of Clinical stage IB3–IVA, Performance status Eastern Cooperative Oncology Group 0–2 were selected. All patients were treated initially with external beam radiotherapy and later by high dose rate intracavitary brachytherapy after completion of external beam radiation therapy (EBRT). A dose of 18–21 Gy was delivered to the residual disease in three sessions with a 1-week interval between each session. The dose was optimized in such a way that the organs at risk (OAR), namely bladder and rectum received doses within their tolerance levels. The patients were continuously monitored using Common Terminology Criteria for Adverse Events version 5.0 for both acute and late toxicities and by imaging for local control. Statistical analysis using SPSS Version 20.0 (SPSS Inc., Chicago, Illinois, USA) was used to evaluate the results. Continuous variables were expressed as mean ± standard deviation, and categorical variables were summarized as frequencies and percentages. Results: Out of the 31 patients, 5 (16.1%) experienced radiation-induced Grade 1 skin changes which were due to EBRT, 1 (3.2%) had Grade 1 G. I. T toxicity, 1 (3.2%) had Grade 1 radiation-induced vaginal mucositis after brachytherapy. At 6–8-week follow-up, all the patients showed no evidence of disease on radiological imaging. At 3 months of follow-up, 1 (3.2%) patient had radiation-induced proctitis of Grades 2 and 3 (9.7%) had radiation-induced cystitis of Grades 1 and 1 (3.2%) had Grade 2 cystitis. At 6 months of follow-up, 1 (3.2%) had Grade 1, 1 (3.2%) had Grade 2, and 1 (3.2%) had Grade 3 radiation-induced proctitis. At 3 months of follow-up, 29 (93.5%) patients had no evidence of disease, while 2 (6.5%) were having residual disease on imaging. At 6 months of follow-up, all the patients were disease-free. At 12 months of follow-up, 26 (83.9%) patients were disease-free, 1 (3.2%) had local recurrence, 2 (6.5%) had distant metastasis, and 2 (6.5%) had expired. At 24 months of follow-up, 26 patients were disease-free. Acute and late toxicities were similar to those used in the treatment of carcinoma cervix by standard brachytherapy applicators. Local control was achieved in 83.87% of cases. Two-year survival was 93.5%. Conclusion: We observed that the tandem and cylinder applicator is an acceptable applicator to be used for intracavitary brachytherapy. It is safe and simple besides this; the toxicities and local control are similar to the other standard applicators used in brachytherapy in carcinoma cervix. However, the required dose prescription to point A was not possible in all the patients due to limitations of OARs. Furthermore, long-term follow-up is needed to see the patterns of failure, recurrence-free survival, overall survival, and long-term toxicities in the treated patients.

Pantoprazole promotes the sensitivity of cervical cancer cells to cisplatin by inhibiting cisplatin-induced autophagy

Aim: This study aimed to explore the role of pantoprazole (PPZ) in affecting the sensitivity of cervical cancer (CC) cells to cisplatin. Methods: HeLa and CaSki cells were exposed to cisplatin and/or PPZ treatment. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation, flow cytometry, wound healing, and transwell assays were performed to detect cell viability, proliferation, apoptosis, migration, and invasion of CC cells, respectively. Then, expressions of Beclin-1, LC3, and p62 were measured by western blot. Rapamycin (Rapa), acting as an autophagy activator, was applied to confirm the effect of autophagy on the sensitivity of CC cells to cisplatin. Results: Cisplatin treatment suppressed cell viability and proliferation and accelerated apoptosis of CC cells. Combination of cisplatin and PPZ or PPZ alone significantly inhibited cell viability, proliferation, migration, and invasion, and increased cell apoptosis of CC cells. Cisplatin enhanced expression levels of Beclin1 and LC3II/I, and reduced p62 expression. Combination of cisplatin and PPZ significantly decreased the expression levels of Beclin1 and LC3II/I, but increased p62 expression. The autophagy activator, Rapa, eliminated the inhibitory effects of the combination of cisplatin and PPZ on autophagy, and enhanced cell viability, but inhibited apoptosis of CC cells. Conclusion: PPZ promotes the sensitivity of CC cells to cisplatin by inhibiting cisplatin-induced cell autophagy.

Camrelizumab (SHR-1210) with carboplatin and albumin-binding paclitaxel in patients with metastatic or recurrent cervical cancer

Aims: This study evaluates the safety and preliminary antitumor efficacy of camrelizumab with albumin-binding paclitaxel and cisplatin as first-line therapy for patients with recurrent or metastatic cervical carcinoma. Methods and Material: In this phase 2, open-label, prospective study, 35 patients with recurrent or metastatic cervical carcinoma with no previous systemic chemotherapy were included. The patients were treated with a maximum of six cycles of camrelizumab on day 1, albumin-binding paclitaxel, and carboplatin on day 2, every 3 weeks, followed by camrelizumab once every 3 weeks. The primary outcomes were objective response rate (ORR) and disease control rate (DCR). Secondary outcomes were duration of response (DoR) and safety. Furthermore, 27 patients were included in the per-protocol set for efficacy analysis, whereas for the safety analysis, all patients were included. Results: The median follow-up was 4.53 months, and the complete response, partial response, and stable disease were also achieved in 4 (14.81%), 6 (22.22%), and 13 (48.15%) patients. The ORR and DCR were 40.00% (95% confidence interval: 21.13–61.33%) and 92.00% (73.97–99.01%), respectively. The median DoR was 6.70 months. In addition, the most common adverse events (AEs) were reactive cutaneous capillary endothelial proliferation (RCCEP) (23, 65.71%), gastrointestinal reaction (8, 22.86%), and fever (8, 22.86%). Grade 3 AEs included 5 (14.29%) myelosuppression, and grade 4 AEs included 1 (2.86%) RCCEP and 1 (2.86%) bladder inflammation. Conclusions: Combination therapy of camrelizumab and albumin-bound paclitaxel and carboplatin shows promising efficacy and manageable toxicities in patients with recurrent or metastatic cervical cancer.

When to use dual staining in cervical cancer screening?

Tumor control after palliative hypofractionated, “Quad-shot,” external beam radiotherapy followed by brachytherapy: An effective approach in medically compromised and/or elderly patients with cervix cancer

Context: Cervix cancer is still a leading cause of death in developing countries. Concurrent chemoradiation (CCRT) over 5 weeks followed by brachytherapy is standard of care in locoregionally advanced cervix cancer. Such prolonged treatment may not be tolerated in medically compromised patients. High-dose interrupted hypofractionated Quad-Shot (QS) radiotherapy with brachytherapy treatment was well tolerated. Aims: This study aims to assess the locoregional tumor control in cervix cancer patients who were treated with QS regimen. Settings and Design: Retrospective. Subjects and Methods: Newly diagnosed histologically confirmed cervix cancer patients who were unfit for conventional CCRT and who were treated with QS protocol between 1999 and 2016 were analyzed. Tumor stage, treatment, and follow-up details were retrieved from an ethics-approved prospective departmental database. Statistical Analysis Used: Descriptive statistics and Kaplan–Meier method were used for estimating survival. Results: Thirty-six patients were available for analysis. The median age was 70.5 (32–92) years. Twenty-two of 36 (61.1%) patients had nodal disease while 33% of all patients had distant metastasis. Of 27 patients who died during follow-up, the local and pelvic control was 75% and 60%, respectively. The median overall survival and progression-free survival were 18.6 months. Grade 3–4 toxicity was observed (16%) in the bowel only. Conclusions: Hypofractionated QS radiotherapy with brachytherapy resulted in an overall 82.1% at least stable disease at the primary site. This treatment regimen was well tolerated and may be considered appropriate for patients who may not be suitable for conventional fully fractionated CCRT.

Evaluation of enzyme-linked immunosorbent assay plasma p16INK4a protein in squamous cell carcinoma in uterine cervix: A case–control study

Background: Cervical cancer is one of the common cancers in females. The common method of screening is Pap test which has low sensitivity. Hence, better methods are explored with different biomarkers, of which estimation of P16 protein can be opted in early detection of cervical cancer. Materials and Methods: Seventy cases and seventy controls were considered for the study. Cases were invasive squamous cell carcinoma (SCC) of cervix confirmed by histopathology. Controls were healthy age-matched females. The blood sample of cases and controls was collected in K2 Ethylenediaminetetraacetic acid vacutainer, and the separated plasma was subjected to estimation of P16 protein by quantitative sandwich Enzyme-Linked ImmunoSorbent Assay method. The data were analyzed for the association between p16 protein in plasma in cases and controls. Results: The age among cases and controls ranged from 30 to 80 years. The P16 levels among cases ranged from 3.4 to 19.6 ng/ml with a mean of 7.24 ± 2.35 ng/ml. The plasma P16 level in controls ranged between 0.9 and 9.7 ng/ml with mean of 4.1 ± 2.22 ng/ml. At cutoff more than 4.8 ng/ml in cases, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 92.86%, 72.86%, 77.4%, 91.1%, and 82.86%, respectively. The specificity increased with increase in plasma p16 levels. The P16 levels were maximum in stage IV disease. Conclusion: This was a pilot study to detect the plasma p16INK4a levels in SCC of cervix. The levels of plasma p16 protein between 3.9 and 5 ng/ml can be considered as the range for the test to be positive. In clinically suspected cases of cervical cancer, levels more than 4.8 ng/ml can be considered for the diagnosis as point of care test.

Primary ovarian rhabdomyosarcoma: A diagnostic dilemma in an uncommon tumor

ABSTRACT Primary ovarian rhabdomyosarcoma (RMS) is an extremely rare and aggressive malignancy, with limited reported cases and no standardized treatment protocol. We present the case of a 17-year-old female who initially presented with progressive abdominal distension and was diagnosed with ovarian RMS. Imaging revealed a large solid-cystic pelvic mass, and histopathological evaluation, along with immunohistochemical markers such as desmin, myogenin, and WT1, confirmed the diagnosis. The patient underwent surgical resection, but recurrence occurred within 3 months, necessitating further evaluation. Early relapse suggested the aggressive nature of the tumor, requiring chemotherapy with VAC (vincristine, actinomycin D, and cyclophosphamide). This case highlights the importance of early diagnosis, and the urgent need for standardized therapeutic approaches to improve patient outcomes in ovarian RMS.

Both Kras gene mutation and Her2 gene mutation tend to exist in an inverse manner but not mutually exclusive in mucinous ovarian carcinoma: An analysis of 21 taiwanese women

Detection of human papillomavirus high-risk genotypes in rural women of Lucknow, North India

Background: Human papilloma virus (HPV) has been widely implicated in cervical carcinogenesis and 90% of carcinoma cervix cases are due to high-risk HPV infection. This study was done to find the high-risk HPV genotypes in the rural women of Lucknow, North India. Materials and Methods: HPV-DNA testing has been carried out in 130 cases of squamous intraepithelial lesions (SILs) of the cervix to find HPV status and type of high-risk HPV genotype infecting the rural women. These cases were collected from the rural cervical cancer screening program carried out in the villages of West Lucknow, North India. Results: HPV status in 130 SIL cases revealed HPV positivity in only 17 cases (13.1%), whereas the remaining 113 cases were HPV negative (86.9%). HPV genotypes detected in the study were HPV-18, HPV-31, HPV-33, and HPV-35. HPV positivity was found highly associated with the young and sexually active group of women complaining of vaginal discharge. High HPV infection rate was also seen with multiparity and illiteracy as majority of women attending the camps were multiparous and illiterate. Conclusions: The present study revealed highly oncogenic HPV-18 alone or in combination with multiple infections of high-risk genotypes – 31, 33, and 35 – in the rural women of Lucknow, North India. Since HPV vaccine currently available in India is for HPV-16 and HPV-18 combined, efforts should be made to make region-specific vaccine according to their prevalence in that particular state of the country to provide effective HPV vaccination.

A randomized study for dosimetric assessment and clinical impact of bone marrow sparing intensity-modulated radiation therapy versus 3-dimensional conformal radiation therapy on hematological and gastrointestinal toxicities in cervical cancer

Background: Cervical cancer requires multimodality therapy, resulting in acute toxicities. Intensity-modulated radiation therapy (IMRT) is postulated to spare bone marrow (BM) and bowel to reduce acute hematological and gastrointestinal (GI) toxicities of chemoradiotherapy. Patients and Methods: This is a prospective randomized phase III study enrolling patients with Stage IB to IVA cervical carcinoma in two arms receiving either three-dimensional conformal radiotherapy (3DCRT) or IMRT from December 2017 to December 2019. The primary objective was to compare the hematologic toxicities (Grade 2 or more neutropenia as the primary factor) and the secondary objectives were to compare GI toxicities, and dosimetric analysis for volumes of BM, and bowel irradiated. SPSS version 20 was used for all statistical calculations. Results: Eighty patients with histopathologically confirmed cervical cancer were randomized to receive IMRT or 3DCRT (40 in each arm). The median age of the patients was 56.5 (36–67) and 59.5 (37–68) years, respectively, in IMRT and 3DCRT arms. The median dose of external radiation was 50 Gy in 25 fractions, and of brachytherapy was 24 Gy in 3 fractions in both the arms. The incidence of grade ≥2 neutropenia was 42.5% and 15% in the 3DCRT and IMRT arms, respectively (P < 0.001). All patients received concurrent chemotherapy with cisplatin, with the median number of cycles being 5 (range 3–5) in both the arms. All five cycles of concurrent chemotherapy could be completed in 25 (62.5%) patients in the IMRT arm and 24 (60%) patients in the 3DCRT arm. Conclusions: IMRT significantly reduces acute hematologic and GI toxicities compared with 3DCRT with a better dosimetry profile.

Report of tall cell variant of papillary thyroid carcinoma in struma ovarii: An exceptional histology finding

ABSTRACT Malignant struma ovarii (SO) is very rare, and the tall cell variant (TCV) of papillary thyroid carcinoma (PTC) arising in SO is even rarer and an exceptionally unique morphological observation. A 39-year-old woman presented with lower abdominal pain and abdominal swelling. Contrast-enhanced computed tomography (CECT) of the whole abdomen revealed a multiloculated cystic mass with peripheral amorphous calcification, which was arising from the right ovary. The patient underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. In histology, the ovary was completely replaced by thyroid parenchyma (SO) with areas of papillary thyroid carcinomatous transformation morphologically consistent with tall cell features. On immunohistochemistry (IHC), tumor cells showed expression for TTF-1 and thyroglobulin and were negative for CK19. The patient underwent total thyroidectomy, postoperative radioactive iodine ablation, and levothyroxine suppressive therapy. A three-month follow-up is uneventful. The current case not only provides insight into the diagnosis and morphological aspect of this interestingly rare occurrence but also emphasizes the need for a careful and extensive sampling of ovarian specimens.

Genetic analysis of polymorphism rs10937405 of TP63 gene in breast and ovarian cancer patients of North Indian Cohort

ABSTRACT Introduction: Ovarian and breast cancers are highly prevalent in the population of Jammu and Kashmir (J&K). However, case–control association studies on breast and ovarian cancers are lacking in this population. Moreover, no case–control study is available on variant rs10937405 of TP63 in breast and ovarian cancers. Thus, we designed to replicate the cancer susceptible variant rs10937405 of TP63 in ovarian and breast cancers in the population of J&K because the TP63 gene act as a tumor suppressor gene and was previously associated with various cancers. Materials and Methods: This case–control association study conducted at the Shri Mata Vaishno Devi University, includes 150 breast, 150 ovarian cancer cases, and 210 healthy controls (age and sex-matched). Variant rs10937405 of the TP63 gene was determined by the TaqMan assay. Hardy–Weinberg equilibrium for the variant was assessed using the Chi-square test. The allele and genotype-specific risks were estimated by odds ratios (ORs) with 95% confidence intervals (CI). Results: In this study, variant rs10937405 of TP63 gene did not show any risk with ovarian and breast cancer with (P-value = 0.70) having OR 0.94, (0.69–1.28 at 95% CI) and (P-value = 0.16) having OR 0.80, (0.59–1.10). Discussion: Our results indicate that the variant rs10937405 of the TP63 gene did not impart any risk of breast and ovarian cancer in the population of J&K. Our results indicate that a larger sample size is needed for further statistical validation. As the study was for a particular variant, it warrants the analysis of other variants of this gene.

Endometrial cancer risk factors, treatment, and survival outcomes as per the European Society for Medical Oncology (ESMO) - European Society of Gynaecological Oncology (ESGO) - European Society for Radiotherapy and Oncology (ESTRO) risk groups and International Federation of Gynecology and Obstetrics (FIGO) staging: An experience from developing world

ABSTRACT Introduction: There is limited data on endometrial cancer from developing countries. The risk groups as defined by the ESMO-ESGO-ESTRO and their recommendations for adjuvant treatment have redefined the management protocols. In this retrospective analysis, the outcomes are assessed in the light of the new risk groups and FIGO staging. Material Methods: One hundred and two patients of endometrial cancer reporting to the Department of Radiation Oncology from 2015 to 2019 were analysed retrospectively. Patients were stratified as per the ESMO-ESGO-ESTRO risk groups and FIGO staging. Patients were analysed for demographic profile, histopathology details, FIGO stage, treatment modalities received as per the ESMO-ESGO-ESTRO risk groups and the outcomes in terms of disease free survival and overall survival. Results: A total of 102 patients were analysed. The mean age at presentation was 57.7 years. Seventy four percent (74.41%) were stage I patients, 14.7 % were stage II, 8.8% were stage III and remaining 2% were stage IV. The mean disease free survival for the patients in FIGO stage I, II, III and IV were found to be 63.5 (59.9 – 67) months, 60.5 (54.2 – 66.9) months, 30.9 (21.5 – 40.2) months and 15.4 (7.8 – 23.0) months respectively. The 5-year overall survival of patients in Stage I was 90.3%. The 3-year mortality of Stage III patients was 58.3%. While there was no mortality observed among Stage II patients, none of the Stage IV patient survived beyond 20 months. The 5-year disease-free survival for patients in Low Risk (LR) group, Intermediate Risk (IR) group and High Risk (HR) group was found to be 91.3%, 90% and 87% respectively. None of the patient in High Intermediate Risk (HIR) group experienced progression of disease and 33.3% patients in advanced group were disease free at 2 years follow-up. The multivariate analysis showed that lymph node involvement is significantly associated with disease-free (p=0.03) and overall survival (p=0.04). Conclusion: Even in the developing world, majority of patients present in early stage with survival outcomes comparable to the West. FIGO stage and lymph node involvement continue to be the most important prognostic markers for disease outcomes.

Endometrial stromal sarcoma with sex cord differentiation

Endometrial stromal sarcoma with sex cord differentiation is a very unusual neoplasm affecting the uterine cavity with an incidence of only 0.25%. They can cause difficulties in diagnosis due to it is histologic appearance and rarity of occurrence. Histopathological diagnosis still remains the cornerstone of diagnosis. Immunohistochemistry and molecular studies are also very helpful. We report a case of a 47-year-old patient who was diagnosed clinically and radiologically as intramural leiomyoma, but on histopathology examination and immunohistochemically proved to be endometrial stromal sarcoma with sex cord differentiation.

A prospective comparative study on conformal pelvic radiation with 6 MV vs. mixed energy beam for carcinoma cervix

ABSTRACT Background: Both low and high energy beams have their own pros and cons. But, there are very limited data available in the literature comparing monoenergetic and mixed energy beam for radiotherapy of carcinoma cervix. This study was aimed at comparing monoenergetic (6 MV) versus mixed energy beam (6 MV and 10 MV) used for treatment of carcinoma cervix in terms of dosimetric parameters and acute toxicity profile. Materials and Methods: It was a single-institutional, prospective, comparative study among 60 patients with non-metastatic carcinoma cervix who received radical Radiotherapy between March 2021 and September 2022. Two radiotherapy planning were performed for each patient, one with mixed energy beam and another with 6MV energy, and treated with one of the treatment plans in a 1:1 fashion using two different energies. We compared the two plans in terms of dosimetric parameters and clinically by the acute toxicity profile. Results: The mean V95 of planning target volume (PTV) was numerically higher in the mixed beam arm (99.83 ± 0.11% vs. 99.28 ± 0.21%, P value – 0.812). Bowel sparing was slightly better in mixed beam therapy in terms of V20 of bowel (63.88% ± 8.26 vs. 64.03% ± 10.23, P value – 0.067). Mean V50 of the urinary bladder was also almost the same in both mixed and monoenergetic beam arms. Skin toxicity was significantly less in mixed beam treatment (P value < 0.05). Conclusion: For pelvic irradiation, mixed energy beam has better planning target volume coverage, better sparing of organ at risks (OARs), and better acute toxicity profile than monoenergetic beam.

Carcinoma cervix: A single institute experience from Kashmir, Northern India

ABSTRACT Background: Carcinoma cervix is the fourth most commonly diagnosed cancer worldwide, with an estimated 604,000 new cases and 342,000 deaths worldwide in 2020. Carcinoma cervix is an uncommon malignancy in Kashmir. In this retrospective study, we have tried to find clinicopathological characteristics of carcinoma cervix along with the survival rates at our tertiary care hospital. Materials and Methods: Case records of cervical cancer patients registered from January 1, 2015, to January 1, 2019, were retrieved. A total of 138 patients was registered. 22 had undergone surgery, and out of these 17 had received postoperative radiotherapy. 109 patients were treated with definitive chemoradiation and 13 with palliative radiotherapy. Descriptive statistics were used to summarize patient and treatment-related variables, and Kaplan–Meier analysis was performed for survival analysis. Results: A total of 138 cases that were registered from 2015 to 2019 were included in this study. The median age at the presentation was 56 years. Most of the patients had a performance status of 1 (98 patients (71.01)). Most of the patients 110 (79.71%) were married before 20 years of age, only 1 patient was unmarried, and 85 (61.59) patients were multiparous in our study group. Only 14 (10.14%) patients in our study group had a history of oral contraceptive use and most of them were non-smokers [124 (89.80%)]. Multiple marriages were present in 8 (5.79%) patients only. The most common presenting symptom was bleeding per vagina (78.26%), and the maximum number of patients fall in the post-menopausal group (67.39%). 116 patients had squamous cell carcinoma histology while 10 patients had adenocarcinoma histology. Most of the patients had stage II and stage III disease (85 patients). At last, follow up out of 138 patients 75 (54.35) were alive. 3 year disease-free survival was 54.34% and 3-year overall survival was 72.46%. Conclusion: Carcinoma cervix is an uncommon malignancy in Kashmir because of different socio-cultural and religious practices but the response to treatment, toxicity profile, and survival are similar to the rest of the world.

Squamous cell carcinoma of vulva during pregnancy- A rare case report with review of literature

ABSTRACT Vulval carcinoma accounts for just 4% of all gynecological malignancies. It rarely occurs in women under the age of 40 years and diagnosis during pregnancy is extremely rare. This is a case of vulval carcinoma in a 31-year-old multiparous woman diagnosed in the third trimester of pregnancy and had successful pregnancy outcome. There are no clear recommendations on management of vulvar cancer during pregnancy. However surgical resection and lymphadenectomy during pregnancy has comparable outcomes to that observed in non-pregnant women.

Predictors and treatment of ısolated recurrence in vulvar cancer confined to the vulva or perineum

ABSTRACT Aim: This study evaluated predictors and treatment of isolated vulvar recurrence (IVR) in patients with stage I–II tumors locally confined to the vulva. Methods: We retrospectively collected data from patients with stage I–II vulvar squamous cell carcinoma (VSCC) who underwent surgery for vulvar cancer between 2005 and 2021. The IVR group comprised patients with stage I–II tumors at the time of initial diagnosis who developed recurrence confined to the vulvar region after initial treatment. Results: This study included 416 patients with early-stage (stage I–II) VSCC. IVR was developed in 67 (16.1%) patients; the remaining 349 patients were included in the control group. Independent predictors of IVR were depth of invasion, perineural invasion, and positive surgical margins. Among patients with tumors confined to the vulva at the time of initial diagnosis, the 5-year overall survival rates were 59.0% and 87.0% in the IVR and control groups, respectively (P < 0.001). In the IVR group, the cumulative rates of local relapse were 38.8% in the first year, 58.2% in the second year, and 74.6% in the third year. Conclusion: Independent predictors of IVR in early-stage VSCC were depth of invasion, perineural invasion, and positive surgical margins. Approximately two-thirds of local recurrences occurred in the first 3 years after treatment.

Schwannoma of Labia Minora: A common neoplasm with an unusual anatomical twist

ABSTRACT Schwannoma is a benign mesenchymal tumor that arises from the Schwann cells. It can occur in both males and females with an equal incidence (M: F-1:1), with the most common age being the third to fourth decade. The tumors show a predilection for the head and neck region, flexural surfaces of extremities, posterior mediastinum, and retroperitoneum. However, the external female genitals are an extremely rare anatomical site for their occurrence. Herein, we outline one such rare case of a benign vulvar schwannoma on the labia minora in a 34-year-old woman. Most patients of vulvar schwannoma present with a characteristically painless mass, making clinical diagnosis difficult. Hematoxylin and Eosin staining of a conventional schwannoma reveals a characteristic pattern of Antoni type A and B areas along with Verocay bodies. On IHC, schwannomas characteristically stain positive for S-100, indicating the neural origin of the tumor. Surgical removal of the mass is the standard treatment of choice with an excellent prognosis.

Lymph node metastasis in grossly apparent early-stage epithelial ovarian cancer: A retrospective clinical study at a tertiary institute

ABSTRACT Objective: This study aimed to evaluate the incidence and predict the risk factors of lymph node (LN) metastasis among patients with grossly apparent early-stage epithelial ovarian cancer (EOC). Methods: We retrospectively reviewed the clinicopathologic data and follow-up information of 266 patients who underwent LN dissection for apparent early-stage EOC between January 2018 and September 2022 at the Obstetrics and Gynecology Hospital of Fudan University. Results: Among 266 patients, 44 (16.5%) showed LN metastasis, of which 65.9% and 59.1% presented in the pelvic region and para-aortic region, respectively. Univariate analysis revealed higher LN positivity in patients with high-grade serous carcinoma (HGSC), preoperative imaging suggestive of LN metastasis, bilateral adnexal involvement, lymphovascular space invasion (LVSI), positive peritoneal cytology, and clinical stage IIA. LN metastases were identified in 7.9%, 10.2%, and 39.7% of clinical stage IA/B, IC, and IIA disease cases, respectively. Multivariate analysis confirmed significantly higher LN positivity rates in patients with HGSC, LVSI, and clinical stage IIA. In clinical stage IIA EOC, the 3-year progression-free survival (PFS) rates were 65.8% and 77.4% (P = 0.360) for LN-negative and LN-positive groups, respectively. In clinical stage I EOC, the 3-year PFS rates were 93.5% and 59.4% (P < 0.001) for LN-negative and LN-positive groups, respectively. Conclusions: High-grade serous histology, LVSI, and clinical stage IIA disease are predictive factors for LN involvement in early-stage EOC. In addition, LN metastasis appears to be associated with worse PFS in clinical stage I EOC compared with clinical stage IIA EOC.

Tandem mass tag-based quantitative proteomic analysis of metformin’s inhibitory effects on ovarian cancer cells

ABSTRACT Purpose: Metformin (MET), a type 2 diabetes treatment, has attracted increased attention for its potential antitumor properties; however, the precise mechanism underlying this activity remains unclear. Our previous in vivo and in vitro studies revealed MET’s inhibitory effect on ovarian cancer, with the synergistic effects of MET and the MDM2 inhibitor RG7388 contributing to ovarian cancer treatment. This study further explores the mechanism underlying MET’s inhibition of ovarian cancer. Materials and Methods: Following MET treatment, we analyzed the differentially expressed proteins in ovarian cancer cells using a tandem mass tag (TMT)-based proteomic approach coupled with bioinformatics. Results: Using A2780 and SKOV3 ovarian cancer cells, we identified six upregulated and two downregulated proteins after MET treatment. Bioinformatics analysis revealed that these proteins predominately affect ovarian cancer cells by regulating iron ion transport, iron ion homeostasis, and mitochondrial and ribosomal functions. Validation via western blot confirmed MET-induced elevation of hydroxybutyrate dehydrogenase type 2 (BDH2) protein expression levels in A2780 and SKOV3 cells. Conclusions: Overall, our findings suggest that combining MET with other metabolic drugs, such as iron-chelating agents and mitochondrial inhibitors, may result in synergistic antitumor effects, thereby offering novel avenues for ovarian cancer treatment development.

Histomorphologic analysis of ovarian tumors according to the New 2020 WHO classification of female genital tumors

ABSTRACT Introduction: In terms of female genital tract-related cancers, ovarian tumors account for 3% of all tumors. On the basis of gross, radiological, and clinical features alone, ovarian neoplasms cannot be diagnosed. Therefore, a clear histological diagnosis is necessary before beginning a permanent course of therapy. Settings and Design: Cross-sectional analytical study. Material and Methods: In this ambispective study, a total of 480 patients with ovarian tumors were included from January 2015 to July 2022 at a tertiary care center in western Maharashtra. Statistical Analysis Used: Descriptive statistics-percentages, mean, and Chi-square test (to calculate P value) were used to analyze the collected data. Aim: To determine clinical presentation, age distribution and incidence of various morphological and histological variants of ovarian tumors. Results: Out of 480, 250 cases (52%) in 41–50 years of age, followed by 154 cases (32%) in 21–30 years of age. Our study showed 301 cases of benign, 42 cases of borderline, and 137 cases of malignant neoplasms of ovary out of 480 cases studied. Out of 480 cases, 244 cases (50.83%) were cystic, 138 cases (28.75%) were solid, and 98 cases (20.42%) were mixed (cystic/solid). Out of 480 cases, 326 cases (67.91%) were surface epithelial ovarian neoplasms. In this research, most frequent ovarian neoplasms were serous tumors in 216 cases (45%) followed by mucinous tumors in 78 cases (16.25%). In 96% cases, clinical diagnosis matched with histopathological diagnosis. Conclusion: In our research, benign ovarian neoplasms were most frequent. Serous tumors were the most frequent type of surface epithelial neoplasms followed by mucinous tumors. Peak incidence was seen in fifth decade. Higher risk of malignancy was seen in nulliparity or low parity and early menarche not associated with risk of malignancy. Cystic morphology more common in benign neoplasms and complex or solid morphology showed greatest increase in incidence of malignancy. Latest WHO classification has important impact on prognosis and therapy of the patient.

Epithelial ovarian cancer in younger age versus older age groups: Survival and clinicopathological features

Objectives: This study aimed to analyze the survivals and clinicopathological features of epithelial ovarian cancer (EOC) in younger age patients and to determine the impact of age on survival. Methods: EOC patients aged ≤40 years were matched to patients aged >40 years at a 1:4 ratio. Disease-specific survival (DSS), progression-free survival (PFS), and clinicopathological and treatment features were compared between patients aged ≤40 and >40 years. Results: A total of 763 EOC patients were reviewed. During a median follow-up period of 41 (range, 1–195) months, EOC patients aged ≤40 and >40 years did not show any statistically significant difference in median DSS (120 versusversus 84.7 months; hazard ratio, 0.78; 95% confidence interval, 0.58, 1.06); however, the median PFS was better in patients aged ≤40 years (median PFS not reached versusversus 41 months; HR, 0.65; 95% CI, 0.5, 0.85). Age ≤40 years was an independent favorable prognostic factor for DSS at 3 years after diagnosis. In contrast, younger age was an independent poor prognostic factor prior to this time point. EOC patients aged ≤40 years exhibited a significantly higher rate of early-stage disease, a higher proportion of mucinous subtype, and lower cancer antigen-125 level. Conclusion: Overall, EOC patients in the younger age group were associated with more favorable prognostic factors and showed better PFS, but not DSS, than those in the older age group. Younger age was identified as an unfavorable prognostic factor within 3 years of diagnosis and became a favorable prognostic factor after 3 years.

Endometrial stromal tumors: A clinico-histomorphological spectrum of endometrial stromal tumors with review of literature

Background: Endometrial stromal tumors (ESTs) are rare subset of mesenchymal uterine neoplasms. There are heterogeneous morphological, immunohistochemical, and genetic features. Approximately 50% of ESTs occur in perimenopausal women. In 2020, WHO sub-categorized ESTs into four groups: endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LGESS), high-grade endometrial stromal sarcoma (HGESS), and undifferentiated uterine sarcoma (UUS). Objective: To review the morphological spectrum of endometrial stromal tumors. Method: This retrospective study reviewed the histomorphological features of 15 endometrial stromal tumors with respect to atypia, necrosis, mitosis, collagen bands, whorling around vessels, myometrial invasion, and inflammatory cells. Immunohistochemistry markers (CD10, SMA, and ER) along with special stains (Masson’s trichrome, toluidine blue) were also studied. Results: The age of the patients ranged from 32 to 60 years. Three patients were postmenopausal. The most common presenting symptom was vaginal bleeding. Five patients were operated with a clinical diagnosis of uterine fibroid. One patient presented with prolapse with no other complaint. All the 15 patients had total abdominal hysterectomy and salpingo-oophorectomy. One case showed necrosis, eight cases showed collagen bands, all the 15 cases showed whorling around vessels, one case showed vascular emboli, and seven cases showed inflammatory cells. In low-grade cases, one case showed focal atypia and one case showed focal coagulative necrosis indicating infarction. Thirteen cases were LGESS, and one case of ESN and HGESS. All cases were positive for ER and CD10. Conclusion: Endometrial stromal tumors demonstrate extensive permeation of the myometrium as irregular islands with frequent vascular invasion, whorling around vessels, collagen bands, and inflammatory cells. All these features should be observed thoroughly on microscopy by pathologists to clearly differentiate the low-grade and high-grade endometrial stromal tumors, and to understand the overlapping gray areas morphologically as it affects the prognosis of the patient.

Highly cellular leiomyoma – A great histopathological masquerader of endometrial stromal sarcoma

ABSTRACT Leiomyoma is the most common benign uterine tumor, whereas endometrial stromal tumors are rare uterine tumors with limited clinical experience. The distinction between highly cellular leiomyoma and endometrial stromal sarcoma can pose a diagnostic challenge to the pathologists as both these tumors have considerable overlapping features on histology.

The serum levels of leptin and adiponectin in endometrial carcinoma and their association with histopathological factors

ABSTRACT Introduction: Adipokines like leptin and adiponectin are hypothesized to play a role in the development of obesity-related cancers like endometrial cancers by influencing inflammation, angiogenesis, apoptosis, and tumorigenesis. We aimed to study the association between serum leptin and adiponectin and the risk of endometrial cancer. Methods: We conducted a case-control study to determine the serum levels of leptin and adiponectin in 55 cases of newly diagnosed endometrial cancer and 25 cases of matched controls. We also sought to determine the association between serum adipokine levels and histopathological factors such as grade, myometrial invasion, and tumor metastasis after categorizing them into tertile datasets. Results: Compared to controls, patients with endometrial cancer had higher median levels of leptin (59.7 vs 38.0 ng/mL, P = 0.001) and lower levels of adiponectin (8.5 vs 9.5 ug/mL, P = 0.906). Leptin to adiponectin (L: A) ratio in cases was significantly higher than those in controls (8.6 vs 4.2, P = 0.001). The receiver operating curve for L: A ratio at a cut-off of 5.4 was able to reliably differentiate between cases and controls with a sensitivity of 69.1% and specificity of 64.0%. Higher levels of leptin and L: A ratio were significantly associated with the risk of endometrial cancer after adjusting for age and BMI (OR T3 vs T1 = 8.53, 95% CI, 1.26–57.75; P = 0.028 and OR T3 vs T1 = 7.93, 95% CI, 1.62–38.85; P = 0.011, respectively). Neither prognostic indicators (grade, stage, and myometrial invasion) nor survival outcomes were significantly affected by serum leptin and adiponectin levels. Conclusion: Higher levels of serum leptin and Leptin to adiponectin (L: A) ratio significantly correlated with endometrial cancer risk. Though adiponectin levels were lower in cases than in controls, this did not reach statistical significance. Adipokine levels did not show any correlation with prognostic histopathological factors.

Predicting myometrial invasion in endometrial cancer based on whole-uterine magnetic resonance radiomics

The objective of this study was to evaluate whether whole-uterine magnetic resonance imaging (MRI) radiomic features can predict myometrial invasion (MI) depth in endometrial cancer (EC). The preoperative 3.0 T magnetic resonance examinations of EC patients were retrospectively reviewed. Whole-uterus segmentation was performed, and features were extracted based on sagittal T2-weighted imaging (T2WI) and axial diffusion-weighted imaging (DWI). The logistic regression (LR) classifier algorithm was used to establish the radiomic model, which was verified by ten times five-fold cross-validation. The areas under the receiver operating characteristic (ROC) curves (AUCs) were assessed by the DeLong test to compare differences among the models based on different sequences. The LR model was compared with the subjective diagnosis results by the Chi-square test. Of the 163 EC patients included, 44 had deep myometrial invasion (DMI). The feature consistency of the whole uterus was higher than that of the lesion (P 0.05). The single-sequence LR models had lower specificity and accuracy than the corresponding subjective diagnostic results (P 0.05). The combined model included 24 radiomic features, and the accuracy, sensitivity, and specificity were 0.83, 0.77, and 0.85 for DMI, respectively. There was no significant difference compared with subjective diagnosis (P > 0.05). Whole-uterine MRI radiomic features based on sagittal T2WI and axial DWI show potential in predicting MI in EC.

Uterine sarcomas: Computed tomography and magnetic resonance imaging findings

ABSTRACT Purpose: To summarize and analyze the computed tomography (CT) and magnetic resonance imaging (MRI) features of uterine sarcoma. Methods and Material: This retrospective study reviewed the clinical data and CT/MRI findings of 15 patients with uterine sarcomas confirmed by surgery and pathology, focusing on their characteristic imaging manifestations. Results: Among the 15 patients, eight had uterine smooth muscle sarcoma (four with lesions confined to the uterine cavity and four presenting as large pelvic masses; all were cystic); one had undifferentiated uterine sarcoma [low signal on TI-weighted imaging (T1WI), high signal on T2-weighted imaging (T2WI) with the clear border, and marginal ring-shaped high signals on diffusion-weighted image (DWI)]; two had uterine adenosarcoma (mixed-density nodular and mass-like lesions with marked heterogeneous enhancement); three had low-grade endometrial stromal sarcoma (iso- or hypointense on T1WI, hyper- or slightly hyperintense on T2WI, and markedly hyperintense on DWI); and one had high-grade endometrial stromal sarcoma (a large cystic–solid pelvic mass). Pathology confirmed that this last lesion invaded the plasma membrane and involved local sub-plasma tissue of the intestinal wall. Conclusion: Uterine sarcoma commonly presents as the large cystic pelvic mass with indistinct margins, irregular shape, and possible invasion of adjacent structures. MRI typically shows iso- or slightly low T1WI signals, mixed high T2WI signals, high or slightly high DWI signals, and heterogeneous enhancement. These findings may aid in improving diagnostic accuracy and guiding clinical management of uterine sarcoma.

Intracavitary brachytherapy challenge in cervical cancer with a large cervical fibroid: A case report

ABSTRACT Among women, cervical cancer continues to be a significant cause of cancer-related death, especially in low- and middle-income nations. Brachytherapy (BT), which provides excellent tumor dose delivery while preserving surrounding tissues, is an essential part of the treatment for locally advanced cervical cancer. Anatomical issues, such as large cervical fibroids, may complicate the placement of the intracavitary brachytherapy (ICBT) applicator. We describe a 74-year-old woman whose stage IIIB cervical cancer was complicated by a large cervical fibroid, which presented a significant BT issue. The successful management of this case, which involved careful uterine sounding and tandem placement under general anesthesia using transrectal and transabdominal ultrasound guidance, and the patient’s completion of three high-dose-rate ICBT sessions with favorable outcomes, is a testament to the expertise and dedication of the medical professionals involved. This case underscores the importance of their specialized skills, image-guided techniques, and meticulous planning in overcoming anatomical barriers and ensuring effective BT delivery in complex cervical cancer cases.

A dosimetric study to evaluate the inverse planning simulated annealing (IPSA) and hybrid inverse planning optimization (HIPO) algorithms in HDR brachytherapy of cervical cancer

ABSTRACT Purpose: To compare the effectiveness of the inverse planning simulated annealing (IPSA) and hybrid inverse planning optimization (HIPO) algorithms in interstitial HDR brachytherapy for treatment of cervical cancer. Methods and Materials: A dosimetric study was conducted on 46 cervical cancer patients who underwent multi catheter interstitial cervical HDR brachytherapy using the Martinez Universal Perineal Interstitial Template (MUPIT). Dosimetric parameters, plan evaluation indices, and mean treatment time were assessed for each algorithm. All the parameters were compared using statistical analysis. Results: With HIPO, significant improvements were observed in D90, D100, V100, and V200 (P < 0.05). Additionally, HIPO plans demonstrated lower doses to the bladder (B2cc) as compared to IPSA plans, whereas IPSA plans exhibited lower rectum (R2cc) and sigmoid (S2cc) doses, with statistical significance observed only for sigmoid doses. HIPO plans had better results in the plan evaluation indices such as CI, COIN, DHI, DNR, ODI, EI, NV100, GFB, GFR, GF, PQI1, PQI2, and PQS with statistical significance (P < 0.05) except for GFS. Moreover, HIPO plans had shorter mean treatment time compared to IPSA plans by 5.52 seconds, although this difference did not reach statistical significance. It was found that HIPO plans demonstrated superior dose-volumetric parameters for the high-risk clinical target volume (HR-CTV). Conclusions: In conclusion, HIPO emerged as the preferred algorithm for interstitial cervical HDR brachytherapy due to improved dose distribution in HR-CTV and plan quality as well.

Pediatric granular cell tumor of the larynx: A case report and literature review

ABSTRACT An 8-year-old child was admitted to our ENT department for a year because of a hoarse voice. An endoscopic examination displayed that a cystic, solid lesion can be seen in the right subglottis. The lesion was removed using a CO2 laser under general anesthesia. Postoperative histopathology confirmed granular cell tumor (GCT), S-100(+), vimentin (+), and SOX-10(+). GCT, also known as the Abrikossoff tumor, is a rare benign tumor that rarely occurs in the larynx, particularly in children. This case report emphasizes that considerable attention should be given to the differential diagnosis of the laryngeal granulosa cell tumor. Given the recurrence risk of GCT, long-term postoperative follow-up is necessary.

Supine/prone position fixation treatment in cervical cancer radiotherapy

ABSTRACT Objective: This study aimed to determine the correlation between bladder volume changes and set-up accuracy in cervical cancer patients undergoing radiotherapy. Methods: Forty patients who underwent intensity-modulated radiotherapy were divided into two groups based on their position during treatment: group A (supine) and group B (prone). Correlations between bladder volume changes and set-up accuracy were retrospectively analyzed using archived data and image files. Results: The rate of bladder volume change in group A (–3.99% [–24.51–31.53]) was significantly higher (Z = –2.724; P = 0.006) than that in group B (–14.95% [–41.63–7.64]). The set-up errors in the X (left-right), Y (cranial-caudal), and Z (anterior-posterior) directions were 0.05 ± 2.25 mm, 0.84 ± 2.63 mm, and 0.41 ± 2.35 mm, respectively, in group A and –0.31 ± 2.22 mm, –0.38 ± 2.88 mm, and 0.78 ± 3.41 mm, respectively, in group B. No significant differences in the X and Z directions were detected between the two groups; however, a significant difference was detected in the Y direction. The set-up error in the X direction was positively correlated with the rate of bladder volume change (r = 0.284; P = 0.010) in group A; no correlations were observed in the X, Y, and Z directions in group B. Conclusion: Patients in the prone position demonstrated better performance in the Y direction than those in the supine position. The set-up error in the X direction was positively correlated with the rate of bladder volume change among patients in the supine position.

The current status of cervical cancer awareness and HPV Vaccination among rural women of India: An impediment to the WHO cervical cancer elimination initiative

ABSTRACT Background: Cervical cancer screening and the HPV (human papillomavirus) vaccination rates are low in India, with widespread socio-economic disparities and inadequate awareness about the symptoms, risk factors, and available preventive methods. The problem is more concerning in rural areas. So, the present study aimed to precisely assess the awareness of the women (18–65 years) residing in rural areas regarding cervical cancer and HPV vaccines. Methods: A community-based cross-sectional study was conducted in three districts of Punjab in 2021 and included 600 participants through a multistage random sampling technique. Data were collected using a pretested semistructured questionnaire. Awareness was assessed using a comprehensive scoring system. Descriptive statistics and Bivariate analyses were used to present the results. Results: Ninety percent of participants had heard of cervical cancer, but only 1.8% had comprehensive knowledge. About 55.5% of the participants were not ready for screening, and most (34.2%) were confident they would not have cancer in their lifetime. Only 5.3% had heard of the HPV vaccine, and very few (0.5%) participants were vaccinated. The most commonly cited reasons were lack of knowledge (90.1%) and the high cost of vaccines (5.9%). Conclusions: The present study depicts diffuse knowledge about cervical cancer and low uptake of HPV vaccination in rural areas, not affected by sociodemographic characteristics. This calls for large-scale health advocacy programs to promote regular screening to generate demand and improve acceptance of the soon-to-be-launched indigenous HPV vaccine in the Universal Immunization program and achieve the WHO global target of eliminating cervical cancer by 2030.

A rare case of synchronous cervical squamous cell carcinoma and invasive ductal carcinoma of breast

ABSTRACT Multiple primary neoplasms in the same patient can be of synchronous and metachronous types and are related to common etiologies and common genetic factors. We present a case report of 56-year-old female with the synchronous primary of breast and cervix and the unique challenges we faced in the management. Breast and cervical malignancies have contrasting risk factors and hence lies the significance of this synchronous presentation. The only identifiable commonality lies in the STK gene. We also present a review of the literature regarding similar presentations and a discussion on the possible source of origin of such a unique scenario.

Positron emission tomography versus computed tomography -guided intracavitary brachytherapy for locally advanced cervical cancer: A prospective randomized study

ABSTRACT Purpose: To compare early clinical outcomes in patients with locally advanced cervical cancer (LACC) treated with positron emission tomography–computed tomography (PET-CT) versus CT-guided intracavitary brachytherapy (ICBT) after external beam radiation therapy (EBRT). Materials and Methods: Patients with carcinoma cervix, stage IIB to IIIB, receiving EBRT with concurrent weekly cisplatin were randomized into two arms: PET-CT versus CT-guided ICBT arms. High-risk clinical target volume (HRCTV), rectum, bladder, and sigmoid colon were contoured. Planning, local control (LC), overall survival (OS), and toxicities were evaluated. Results: Fifty patients (25 in each arm) were recruited from September 2019 to April 2021. The mean dose to HRCTV D90 and D95 was 87.7 Gy (SD 6.1 Gy) and 83.04 Gy (SD 5.5 Gy) in PET-CT and 85.6 Gy (SD 6.4 Gy) and 80.6 Gy (SD 5.7 Gy) in CT arm (P value 0.13). The mean dose to bladder, rectum, and sigmoid colon was 80.3 Gy (SD 8.2 Gy), 70 Gy (SD 6.1 Gy), and 66.2 Gy (SD 7.4 Gy) in PET-CT and 79 Gy (SD 6.9 Gy), 70.2 Gy (SD 7.2 Gy), and 64.9 Gy (SD 6.3 Gy) in the CT arm (P value 0.58, 0.88, and 0.55). On intention to treat analysis, the 6 months LC rate was 79.1% in PET-CT and 72.7% in CT arm (P value 0.3). On per protocol analysis of 46 patients, OS was 82.9% in PET-CT and 89% in CT arm at 2 years (P value- 0.6). No Grade III/IV Bowel/Bladder toxicities were reported. Conclusion: Results of our study have shown comparable outcomes in terms of LC, OS, and toxicities between both arms; however, LC was slightly better in PET-CT arm, though not statistically significant. Further studies with a larger sample size should be conducted to establish the role of PET-CT-guided ICBT in LACC.

Anxiety and depression among those experiencing cervical cancer in India: A neglected theme for research

Adenoid basal carcinoma cervix – A rare epithelial neoplasm

ABSTRACT Adenoid basal carcinoma of the uterine cervix is a rare epithelial neoplasm. Adenoid basal carcinoma constitutes less than 1% of all cervical adenocarcinomas and has a favorable prognosis. Adenoid basal carcinoma is assumed to arise from a multipotential basal or reserve cell layer in the cervical epithelium. We report a case of adenoid basal carcinoma of the uterine cervix with complaints of bleeding per vagina in a 40-year-old female. The carbohydrate antigen 125 level was elevated (100 U/ml), and the MRI abdomen and pelvis revealed increased signal intensity in the anterior lip of the cervix. The local examination revealed thickening of the anterior lip of the cervix and induration in the left fornix. The patient was diagnosed with carcinoma cervix stage IB2 (FIGO Stage). The patient was operated by a radical robotic hysterectomy. Microscopic examination revealed small basaloid tumor cell nests with peripheral cell palisading and microcyst formation. The tumor cells showed p63 immunoreactivity in basaloid tumor cells and were negative for CD117 and S-100P. This tumor should be differentiated from adenoid basal cell hyperplasia, which has a favorable outcome, and adenoid cystic carcinoma, with a dismal course.

The prevalence of multiple or single HPV infection and genotype distribution in healthy Chinese women: A systemic review

ABSTRACTBackground:We analyzed the prevalence and genotype distribution of multiple- or single-type cervical human papillomavirus (HPV) infections in a population of women in mainland China.Methods:PubMed, MEDLINE, and Chinese databases (CNKI, VIP, and Wan Fang) were searched for studies on HPV prevalence and the examination of this relationship. All analyses were performed using STATA (version 12.0). Data from selected studies were extracted into tables, and all included studies were weighted and summarized.Results:Thirty studies were included. The prevalence of single types (10.4%) and multiple types (4.7%) primarily occurred in healthy Chinese women, in which the dominant single-type infection was HPV16 (1.6%), 52 (1.5%), 58 (1.0%), and 18 (0.5%), and the dominant type of multiple infection was HPV16 (0.7%), 52 (0.7%), 58 (0.6%), and 18 (0.3%). The prevalence in North and South China was 14.3%, in which the prevalence of the single type was 10.41% and 8.27%, and the prevalence of multiple types was 4.00% and 6.52%, respectively.Conclusion:Mainland China exhibits unique type-specific single and multiple HPV infections. Overall single or multiple HPV prevalence varied across regions of China, whereas type-specific HPV differences were relatively small.

Factors that contribute to the recurrence of mucinous ovarian cancer: Monocenter retrospective evaluation

ABSTRACT Purpose: In this study, we aimed to put forth the factors that contribute to the recurrence of mucinous ovarian cancer. Materials and Methods: Forty-four mucinous ovarian cancer patients who have presented to our clinic between February 2006 and May 2018 took part in the study. In order to predict the factors that contribute to recurrence, the univariate and the multivariate logistic regressions were utilized. The Kaplan–Meier survival analysis was utilized for survival and the log-rank test was used for the discrepancies between the groups. In the analysis of the data, the Statistical Package for the Social Sciences 22 program was used. It was acknowledged to have statistical meaning when the P value in all the tests was lower than 0.05. Findings: Recurrence was detected in 20 out of 44 patients who participated in the study. The ages of the patients who did not experience recurrence were significantly lower ( P = 0.001). The patients were detected mostly in Stage 1 (36.4%). In the group of patients without recurrence, systemic lymphadenectomy (43.2%) was greater ( P = 0.019). Lymph node metastasis was three times higher in the group that experienced recurrence ( P = 0.047). When the two groups were compared, the platinum resistance was considerably greater in the group with recurrence ( P = 0.005). In terms of residual tumor, the rate of complete resection was (9%) better in the group that experienced recurrence compared to the group that did not experience recurrence, with a rate of 45.5%. While 12 patients who experienced recurrence died, 6 people died in the other group. From the factors that contribute to recurrence, in terms of residual tumor quantity, this was grouped as complete (R0) resection and optimal + suboptimal (R1 + R2) resection and the following were determined: odds ratio (OR) – 5.7 (95% confidence interval [CI]: 1.56–20.9) and P = 0.008 for R1 + R2. In univariate analysis, the OR was determined as 1.16 (95% CI: 1.06–1.27) for age. Possessing a Stage 2 and higher disease statistically contributed considerably to the recurrence compared to Stage 1 disease (OR: 6.33; 95% CI: 1.59–25.22; P = 0.009). Age was determined as an independent prognostic risk factor in the multivariate analysis (OR: 1.10 [95% CI: 1.04–1.25]), P = 0.018. Furthermore, the OR for the advanced-stage (Stage 2 or higher) patients in the multivariate analysis was determined as 7.88 (95% CI: 0.78–78.8) and was found to be statistically significant at limits ( P = 0.079). Results: We have put forth that the genetic, biological, and clinical characteristics of mucinous ovarian cancers differ from that of other epithelial ovarian cancers, and that age, advanced stage, and residual tumor quantity are prognostic risk factors in terms of recurrence, and that age is an independent prognostic risk factor. Conclusion: Biological and clinical characteristics of mucinous ovarian cancers differ from those of other epithelial ovarian cancers, and we observed that the age, advanced stage, and the amount of residual tumor regarding recurrence are prognostic risk factors, while age was determined as an independent prognostic risk factor.

Significance of platelet parameters in invasive squamous cell carcinoma of uterine cervix

Background: Cervical cancer is the second most common cancer among females worldwide. The role of platelets in cancer progression and metastasis have been evaluated in various cancers. This study is done to assess the association between platelet parameters and invasive squamous cell carcinoma of the cervix. Materials and Methods: Eighty cases of squamous cell carcinoma of the cervix were retrospectively collected from the medical record department. Values of platelet parameters such as platelet count, mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), platelet-large cell ratio (P-LCR), platelet-lymphocyte ratio (PLR), platelet-neutrophil ratio (PNR), and platelet-monocyte ratio (PMR) are collected from automated hematology analyzer. These values were compared with 80 healthy controls which were randomly selected. Values of platelet parameters were also compared among Federation Internationale de Gynecolgie et d’Obstetrique (FIGO) stages in 80 cases. Result: Mean ± standard deviation (SD) for platelet count, MPV, PDW, PCT, P-LCR, PLR, PNR, and PMR among cases were 316 ± 100.37 × 109/L, 9.98 ± 0.96, 11.11 ± 2.27, 0.31 ± 0.092, 24.09 ± 7.62, 179.35 ± 85.53, 63.89 ± 42.10, and 492.29 ± 192.86, respectively, and in controls were 300.30 ± 79.40 × 109/L, 9.97 ± 0.83, 10.97 ± 1.80, 0.59 ± 2.65, 23.94 ± 6.81, 137.72 ± 50.52, 60.07 ± 26.68, and 563.65 ± 602.55, respectively. The PLR between cases and controls was statistically significant. The platelet count and PCT between stages was statistically significant wherein the values increased from stage II to stage IV. Conclusion: Platelet parameters are importance in cervical cancer. PLR, platelet count, and PCT are platelet parameters that can be used as predictors and prognostic parameters in cervical cancer. These parameters are cost-effective and can be considered in low resource settings. However, a multicentric study with a larger sample size should be done to extrapolate the findings for patient care.

Assessment and clinicopathological correlation of p16 expression in cervical squamous cell carcinoma of Indian population: Diagnostic implications

ABSTRACT Background: Our aim was to assess the p16 expression in normal cervical epithelium and cervical lesions and how it correlated with HPV oncoprotein E7 and other etiological parameters of cervical cancer. Methods: For this purpose, we analyzed protein expression of p16 and E7 oncoprotein in total 20 normal cervical epithelium tissue (as control) and 62 cervical lesions. Next, the result was correlated with different clinico-pathological parameters. Results: Out of 62 cases of cervical lesions, we found around 75%–100% of the cervical lesion samples exhibited E7 nuclear protein expression, whereas around 33.33%–75% samples were p16 positive. On the other hand, p16 expression showed strong association with E7 oncoprotein and other clinico-pathological parameters (like high parity, early age of sextual debut) in the same set of samples of our study. Conclusion: We concluded that overexpression of p16 is very practical and can be readily implemented in most diagnostic pathology laboratories.

The effect of lower urinary tract substructure doses on side effects of cervical cancer image-guided adaptive brachytherapy

ABSTRACT Objective: Image-Guided Adaptive Brachytherapy (IGABT) provides a survival advantage in locally advanced cervical cancer (LACC). Although side effects are seen less with this technique, dose parameters that cause urinary side effects are still questionable. We aim to investigate whether the radiotherapy doses of the lower urinary tract substructures (LUSS) affect the urinary system side effects (USSE) of cervical cancer external beam radiotherapy (EBRT) and the IGABT. Methods: LUSS (bladder, trigone, bladder neck, and urethra) doses were calculated in 40 patients diagnosed with LACC and receiving primary EBRT, IGABT, and concomitant chemotherapy. D0.1cc, D2cc, and D50% values were examined by contouring the bladder, trigone, bladder neck, and urethra from the intracavitary BT planning computed tomography (CT) images taken every 4 BT fractions, retrospectively. Besides, late USSE (urgency, dysuria (recurrent), frequency, obstruction, incontinence, hematuria, fistula, cystitis) were queried and categorized according to Common Toxicity Criteria for Adverse Events version 5.0. Statistical Analysis Used: The Chi-square and Fisher’s exact tests, Mann–Whitney U-test. Results: For the whole study population, for both incontinence and dysuria, trigone (D50%), urethra (D50%, D0.1cc,), and bladder neck (D50%, D0.1cc, D2cc) volume and hot spot doses remained significant. For cystitis, urethra (D50%, D0.1cc,) and bladder neck doses (D0.1cc, D50%, D2cc) are worth investigating. Conclusions: Although USSE is less common in the intensity-modulated radiation therapy and IGABT era, it may be meaningful to take the doses of LUSS into account when planning IGABT. In addition, delineation of LUSS using only CT seems feasible. More proof is needed to determine delineation technique and dose constraints for LUSS for IGABT.

Sexual function status after adjuvant radiation including vaginal cuff brachytherapy in survivors of cancer cervix

ABSTRACT Context: Adjuvant radiation therapy plays an important role in the management of high-risk cervical cancer after radical hysterectomy or inadvertent hysterectomy. The prime concern with the use of dual modality is steep decline in sexual well-being in cervical cancer survivors. Intravaginal brachytherapy (IVBT) delivered by vaginal cylinder or ovoids is essential for local control but at the cost of impairment of sexual function. Aim: The purpose of this study was to assess the sexual well-being of cervical cancer survivors, who underwent surgery followed by adjuvant radiation and compare the subgroups of ovoids with sorbo brachytherapy. Settings and Design: This was an observational, cross-sectional, and analytical study, whereby we evaluated sexual function of cervical cancer survivors by the Female Sexual Function Index (FSFI) instrument. Subjects and Methods: Seventy-five women, identified as cervical cancer survivors who had received adjuvant radiation and IVBT, were administered FSFI questionnaire in face-to-face interviews. Results: The mean age of 75 interviewed women was 48.64 years. Fifty survivors had received IVBT with a sorbo applicator and twenty-five with ovoids. FSFI full score ranged from 4.4 to 32.40. The mean full score for the whole group was 11.3. The mean FSFI full score was 24.91 (± standard deviation [SD] 5.71) in the ovoid group versus 4.49 (± SD 0.35) in the sorbo group. On Pearson’s correlation analysis, age and type of brachytherapy were significantly correlated with FSFI full score (P = 0.006) with correlation coefficient of − 0.312 and − 0.948, respectively. Conclusions: Sexual dysfunction was found prevalent in 83% of cervical cancer survivors. The patients treated with IVBT with sorbo had worse sexual functioning than those treated with ovoids.

Diagnostic and prognostic value of circulating tumor cells in Indian women with suspected ovarian cancer

ABSTRACT Background: “Liquid biopsy,” where body fluids are screened for biomarkers, is gathering substantial research. We aimed to examine women with suspected ovarian cancer for the presence of circulating tumor cells (CTCs) and study its role in prediction of chemoresistance and survival. Methods: Magnetic powder labeled monoclonal antibodies for epithelial cell adhesion molecule (EpCAM), mucin 1 cell surface associated, mucin 16 cell surface associated, or carbohydrate antigen 125 (CA125), were prepared according to the manufacturer’s protocol. Expression of three ovarian cancer related genes was detected in CTCs using multiplex reverse transcriptase-polymerase chain reaction. CTCs and serum CA125 were measured in 100 patients with suspected ovarian cancer. Correlations with clinicopathological parameters and treatment were analyzed. Results: CTCs were detected in 18/70 (25.7%) of women with malignancy compared to 0/30 (0.0%) in those with benign gynecologic diseases (P = 0.001). The sensitivity and specificity of the CTC test for predicting a malignant histology in pelvic masses were 27.7% (95% CI: 16.3%, 37.7%) and 100% (95% CI: 85.8%, 100%), respectively. The number of CTCs correlated with stage of ovarian cancer (P = 0.030). The presence of EpCAM + CTC at primary diagnosis in ovarian cancer was found to be an independent predictor of a poor progression free survival (HR, 3.3; 95% CI, 1.3–8.4; P = 0.010), overall survival (HR, 2.6; 95% CI,1.1–5.6; P = 0.019), and resistance to chemotherapy (OR 8.6; 95% CI, 1.8–43.7; P = 0.009). Conclusion: Expression of EpCAM + CTC in ovarian cancer predicts platinum resistance and poor prognosis. This information could be further used in investigating anti-EpCAM-targeted therapies in ovarian cancer.

USP7 mediates TRAF4 deubiquitination to facilitate the malignant phenotype of ovarian cancer via the RSK4/PI3K/AKT axis

ABSTRACT Background: Ubiquitin-specific peptidase 7 (USP7) is upregulated in multiple human cancers, including ovarian cancer; however, its functional role in the latter remains largely unknown. Methods: We conducted quantitative real-time PCR to detect the expression of USP7, TRAF4, and RSK4 in ovarian cancer cell lines. In addition, Western blotting served to determine USP7, TRAF4, RSK4, PI3K, and AKT (protein kinase B,PKB) protein levels and USP7 expression in the tissues was detected by immunohistochemical staining. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was used to evaluate cell viability, transwell assays to evaluate cell migration and invasion, and co-immunoprecipitation to evaluate TRAF4 ubiquitination. Results: The results showed USP7 and TRAF4 upregulation, and RSK4 downregulation in ovarian cancer cell lines. Knocking down USP7 suppressed viability, migration, and invasion of ovarian cancer cells; TRAF4 knockdown and RSK4 overexpression had similar effects in ovarian cancer cells. TRAF4 is deubiquitinated and stabilized by USP7, whereas RSK4 is negatively regulated by TRAF4. A mouse xenograft model confirmed that knocking down USP7 suppressed ovarian tumor growth by regulating the TRAF4/RSK4/PI3K/AKT axis. Conclusion: Knocking down USP7 decreased the proliferation, migration, and invasion of ovarian cancer cells and suppressed ovarian tumor growth in mice. Mechanistically, USP7 increased TRAF4 ubiquitination, promoting its degradation and leading to RSK4 upregulation.

The ability of contrast-enhanced ultrasound with Sonazoid to differentiate endometrial carcinoma from benign endometrial lesions: A preliminary, prospective, and multicenter clinical study

ABSTRACT Objective: To examine the diagnostic efficacy of contrast-enhanced ultrasound (CEUS) with Sonazoid (Sonazoid-CEUS) for endometrial lesions. Methods: In this prospective and multicenter study, data were collected from 84 patients with endometrial lesions from 11 hospitals in China. All the patients received a conventional US and Sonazoid-CEUS examination. The lesion characteristics based on US and Sonazoid-CEUS imaging were collected from the case report forms. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were determined using histopathologic diagnosis as the gold standard. Results: Of the 79 patients included, 29 were diagnosed with benign lesions and 50 with endometrial carcinoma (EC). The accuracy, sensitivity, specificity, PPV, and NPV for Sonazoid-CEUS and US at differentiating EC from benign endometrial lesions were 82.2%, 94%, 62.1%, 81.0%, and 85.7%, and 79.7%, 96%, 51.7%, 92.3%, and 88.2%, respectively, with no significant differences observed for any of the values. For Sonazoid-CEUS, the best delineators of EC versus benign lesions were early enhancement and hyperenhancement (74% vs 53.3%, P = 0.029, 68% vs 45%, P < 0.001), and lesion size enlargement (76% vs 48%, P = 0.001). Despite finding no significant difference in the enhancement patterns (P = .367), a faster wash-in pattern with the contrast agent entering before the surrounding myometrium was more common in the EC vs benign cases (92% vs 48.3%). Conclusions: Sonazoid-CEUS has higher accuracy, specificity, and comparable sensitivity for differentiating EC from benign endometrial lesions compared with conventional US. It provides complementary hemodynamics information reflective of tissue vascularization, which may improve the overall diagnostic efficiency.

Cost-utility analysis of different dose of HPV vaccination regimen for prevention HPV-related cancer

Interfraction variations in doses at OARs during three-dimensional high dose rate brachytherapy planning of cervix cancer

ABSTRACT Objective: The American Brachytherapy (BT) Society recommends that BT must be included as a component of the definitive radiation therapy for cervical carcinoma because recurrences and complications are decreased when BT is used in addition to external beam radiotherapy. The aim of this study is to quantify the interfraction dose variations (VARacts) during high dose rate (HDR) BT, the effect of variation in dose in terms of excess “unrecognized” dose to OAR and to conclude the reason of the variation in reference of applicator position/geometry versus deformation of the organ at risk (OAR) concerned. Materials and Methods: Total 30 patients of carcinoma cervix, biopsy proven, between June 2018 and May 2019, were taken for the study. All patients were treated with external beam radiation therapy to a dose of 50 Gy in 25 fractions over 5 weeks, followed by three fractions of HDR intracavitary brachytherapy (ICBT) (7.5 Gy to point A in each fraction) by two-dimensional (2D) X-ray-based planning. Before treatment in the first and last fraction of BT, computed tomography (CT) scan was done for every patient. Then, a 3D-based planning was performed with CT images on our HDR Plus software with image sequence option. VARact was calculated. Rigid image registration of consecutive fraction images was used for quantification of the hypothetical variation in dose (VARhypo) arising exclusively due to changes in applicator placement and geometry. Results: The mean contoured rectal volumes for the first and third fractions were 41.49 cc and 44.72 cc, respectively, while the respective volumes for bladder were 9.33 cc and 9.35 cc cm. These differences were statistically insignificant (P value: 0.263 and 0.919 for rectum and bladder, respectively). The mean equivalent dose in 2 Gy fraction (EQD2) bladder D2cc was 5.68 Gy and 5.79 Gy in the first and third fraction ICBT, respectively. The mean EQD2 for the rectal D2cc was 11.63 Gy and 12.85 Gy in the first and third fraction ICBT, respectively. None of the patients had an actual cumulative EQD2 more than 90 Gy for bladder, but 36.66% of the patients had a rectal dose exceeding the tolerance (75 Gy). Regression plots showed that VARhypo alone could predict about 42.2% of the VARact in the rectum and 19.2% of the VARact in the bladder. Thus, the remaining variation was due to the organ deformation-related dose variations between the two fractions. Conclusions: There were no statistically significant variations in the volumes or doses of OAR between the two fractions. However, a significant proportion of patients may have a higher dose to the OAR in the third fraction in the absence of individualized planning. This increase is likely to be more detrimental where higher doses per fraction are used. Variations in OAR doses may be caused by organ deformation and/or changes in applicator placement/geometry.

Is postoperative radiotherapy (PORT) a viable option in high-risk early-stage cervical cancer after upfront or downstaged radical surgery? A comparative study

ABSTRACT BACKGROUND: Radical surgery for cervical cancer has inherent benefits, and as upfront or post neoadjuvant chemotherapy (NACT), is extendable to locally advanced cancer cervix (LACC), with postoperative radiotherapy (PORT) for high-risk factors. Objective of the study was to compare the effectiveness and survival between non-PORT and PORT in high-risk early stages. MATERIALS AND METHODS: Radical hysterectomies conducted between January 2014 and December 2017 were evaluated and followed till December 2019. Clinical, surgical–pathologic characteristics, and oncological outcomes were compared between non-PORT and PORT groups. A similar comparison was made between alive and dead patients within each group. The impact of PORT was assessed. RESULTS: Of 178 radical surgeries, early-LACC constituted 70%. Most (37%) of the patients belonged to stage 1b2, while stage 2b formed 5%. Mean age of patients was 46.5 years; 69% were below 50 years of age. Abnormal bleeding (41%) was the predominant symptom, followed by postcoital (20%) and postmenopausal bleeding (12%). Upfront surgeries formed 70.2%, and the average waiting period was 1.93 months (range: 1–10 months). PORT patients were 97 (54.5%) in number and the remaining formed the non-PORT group. Mean follow-up was 34 months, with 118 (66%) alive patients. Significant adverse prognostic factors were tumors >4 cm (44.4% patients), positive margins (10%), lymphatic vascular space invasion (LVSI; 42%), malignant nodes (33%), multiple metastatic nodes averaging seven (range: 3–11), and delayed (>6 months) presentation, but not deep stromal invasion (77% patients) and positive parametrium (8.4% patients). PORT overcame the adverse effects of tumors >4 cm, multiple metastatic nodes, positive margins, and LVSI. Total recurrences (25%) were balanced for both groups, but recurrences within 2 years were significantly more for PORT. Two-year overall survival (78%) and recurrence-free survival (72%), median overall survival (21 months), and median recurrence-free interval (19 months) were significantly better for PORT, with the complication rates being similar. CONCLUSION: PORT had significantly better oncological outcomes compared to non-PORT. Multimodal management is worthwhile.

Ovarian cancer with osteoblastic bone metastasis – A rare case report

ABSTRACT Ovarian cancer with bone involvement occurs rarely with an incidence of 0.1–0.12%. The common sites of bone metastasis are vertebrae, pelvic bones, and the skull. Patients present with severe localized bone pain, swelling, and difficulty in walking. We report a rare case of a 53-year-old female with metastatic epithelial serous adenocarcinoma of the ovary presented with multiple bony lesions in pelvic bones involving the sacrum, bilateral ilium, ischium and pubic bones and the right femur in the region of greater trochanter, smaller lesions in the left femur, and dorso lumbar vertebral metastasis while undergoing treatment as a part of distant spread. Radiologically, the osteolytic lesions are the most common, but in our case, the lesions are osteoblastic, which is rare.

Ovarian cancer: A report from population-based cancer registry at central rural India

ABSTRACT Introduction: Ovarian neoplasms affect a huge part of the female population and, simultaneously, have the worst prognosis among all gynecological malignancies. In most of the population-based cancer registries (PBCR) in India, ovarian cancer is the third leading site of cancer among women, trailing behind cervix and breast cancer. Materials and Methods: In the present study, we have summarized the number of new cases of ovarian malignancy and its profile observed in the PBCR in central India during 7 years. Reports: During a 7-year duration (2010–2016), 6,515 cancer patients were recorded at PBCR, and 228 cases were of ovarian malignancy. It was observed that most of the cases in this study were in 41–50 years of life. The age-standardized incidence rate of ovarian cancers in the present study was 4.61 per 100,000, and the crude incidence rate was 5.08 per 100,000. The crude mortality rate and age-standardized mortality rate of ovarian cancer were 2.3 and 2.02 per 100,000, respectively. Serous carcinoma was our study’s most common histological subtype (43.75%), followed by mucinous carcinoma. Conclusion: A steady increase has been observed in the incidence of ovarian cancer in several registries. A significant goal in managing ovarian cancer is to develop an effective test to detect the disease at its earlier stages, resulting in reduced mortality.

Primary neuroendocrine tumors of ovary: A clinicopathological spectrum in a tertiary care hospital with review of literature

ABSTRACTS Aim: Primary neuroendocrine tumors in the ovary are rare. These tumors arise from the neuroendocrine cell system of ovarian stroma and surface epithelium, and may also arise from teratoma. We present four primary ovarian neuroendocrine tumors and discuss clinical, histomorphological, and immunohistochemical findings. Methods: Four primary ovarian neuroendocrine tumors were identified from our 4-year departmental archives. H and E slides and immunostains were reviewed. Clinical history, imaging studies, and follow-up data were obtained from medical records. Results: Patients’ age ranged from 37 to 45 years. All the patients presented with abdominal discomfort, abnormal uterine bleeding, and unilateral or bilateral ovarian masses. Two of the cases were primary ovarian carcinoid tumors, one being the pure primary ovarian carcinoid tumor (PPOCT), and the other being associated with mature cystic teratoma, while the other two cases were neuroendocrine carcinoma. All the cases showed expression of neuroendocrine markers, namely, synaptophysin, chromogranin, and NSE. Conclusions: Primary neuroendocrine tumors in the ovary are rare and consist of a group of heterogeneous tumors that express similar immunohistochemical markers.

Central nervous system metastasis in gynecologic cancers: Seeking the prognostic factors

ABSTRACTS Objective: Central nervous system (CNS) metastasis originating from gynecological cancer is a very rare and late manifestation of the disease. Therefore, there is still limited data on prognostic factors for survival. The objective of the present study is to identify prognostic factors for survival in patients with CNS metastasis originating from gynecological cancer. Study Design: The present retrospective study analyzed the patients with gynecological cancers who were treated due to CNS metastases between January 1999 and December 2019 at Istanbul University Hospital. Results: Forty-seven patients with CNS metastasis of gynecological origin were included in the study. The median age at the time of CNS metastasis was 59 (range 34–93). The median time from initial cancer diagnosis to CNS metastasis was 24.9 (range: 0–108.2) months. Most patients had epithelial ovarian cancer (EOC) (76.6%), followed by endometrial cancer (EC) (14.8%), cervical cancer (CC) (4.3%), and vulvar cancer (VC) (4.3%). By multivariate analysis, the presence of extracranial metastasis (HR: 5.10; 95% CI: 1.71-15.18), Eastern Cooperative Oncology Group (ECOG) performance status ≥3 (HR: 2.92; 95% CI: 1.36-6.26), palliative care only for the treatment of CNS metastasis (HR: 1.47; 95% CI: 0.58-4.11), and treatment-free interval (TFI) <6 months (HR: 2.74; 95% CI: 1.23-6.08) were independent factors that associated with worse survival. Conclusion: Patients with CNS metastasis who have favorable prognostic factors are considered to be appropriate candidates for aggressive and long-term treatment strategies. Extracranial metastasis, ECOG performance status, treatment history of CNS metastasis, and TFI were determined as independent prognostic factors that improved survival. TFI might be taken into account as a prognostic factor for patients with CNS metastasis in gynecological cancer.

High dose rate brachytherapy for vaginal rhabdomyosarcoma in a 10-month-old child using custom-made multi-channel applicator: Initial experience and challenges

ABSTRACT Brachytherapy plays an important role in the organ preservation strategy in vaginal rhabdomyosarcoma (RMS). Here we report our experience and challenges of high dose rate (HDR) intravaginal brachytherapy (IVBT) in a 10-month-old child, a diagnosed case of localized vaginal RMS with a custom-made applicator and immobilization device. The index case is the first pediatric patient, treated with brachytherapy at our institute.

Prospective evaluation of small bowel dose and acute gastrointestinal toxicity during pelvic radiotherapy for gynaecologic malignancies

ABSTRACT Introduction: Acute gastrointestinal (GI) toxicity is common in patients receiving pelvic radiotherapy (RT) and the small bowel (SB) is a dose-limiting organ at risk. There is a quandary in the dose constraints for SB while using intensity-modulated radiotherapy (IMRT) for gynecological malignancies. Objectives: To investigate the correlation between the radiation dose received by SB and the incidence of acute lower GI toxicities, and to identify dose parameters that may reduce toxicity risk. Materials and Methods: Fifty-eight patients diagnosed with gynecological cancers and received RT with IMRT technique were analyzed in this prospective observational study. Oral contrast was administered during the simulation scan as per institution protocol. The individual SB loops were delineated as per Radiation Therapy Oncology Group (RTOG) consensus guidelines. The volume of SB (cc) receiving 10, 15, 20, 30, and 40 Gy were analyzed. Grades of acute GI toxicities were assessed weekly according to RTOG scoring criteria. The odds of developing GI toxicities were analyzed using a logistic regression test. Results: Out of the study population, 26 patients (45%) were diagnosed with carcinoma of the cervix, and 32 patients (55%) were diagnosed with carcinoma of the endometrium. 33 patients (57%) also received concurrent chemotherapy. Overall, Grade I, II, and III GI toxicities were observed in 32%, 62%, and 5% of patients, respectively. None of the patients developed GI toxicity during weeks 1 and 2 of RT. A significantly higher incidence of ≥grade 2 GI toxicity was observed with a mean SB-V30 Gy >210 cc (P = 0.001) and SB-V40 Gy >103 cc (P = 0.001). Patients with SB-V30 Gy ≥210 cc had 2.2 times higher odds of developing ≥ grade 2 enteritis compared to those with SB-V30 Gy <210 cc (OR = 2.2; 95% CI, 1.5–6.3; P = 0.003). Likewise, the odds of developing ≥grade 2 enteritis were 2.9 times higher in patients with SB-V40 Gy ≥103 cc compared to those with SB-V40 Gy <103 cc (OR = 2.90; 95% CI, 2.1–5.1; P = 0.002). Conclusions: Higher radiation doses to individual SB loops lead to a decrease in cellular reserves of intestinal mucosa resulting in ≥grade 2 acute GI toxicity in patients receiving IMRT for gynecological malignancies.

Survival pattern in cervical cancer patients in North West India

Background: Cervical cancer is most common malignancy of female reproductive system worldwide. As per GLOBOCAN 2020, there are 604,127 (6.5%) new cases of cervical cancer in the world, among women it is fourth most common and eighth most common in both sexes. In India, there are 123,907 total new cervical cancer cases (18.3% in female sex whereas 9.4% in both sexes). There are several etiological factors and the most significant is due to persistent infection of specific human papilloma virus (HPV) strains, particularly type 16 and 18 which are most common. Screening and early detection is likely to improve mortality and incidence also. Aims and Objectives: The objective of this retrospective study was to determine the survival rates of cervical cancer and its associated factors in North-West region. Materials and Methods: A total of 520 newly diagnosed cases of cervical cancer were enrolled at Acharya Tulsi Regional Cancer Treatment and Research Centre, Bikaner from January 1, 2014 to December 31, 2014 were included in this study. The main source of information was patient's medical records from which the data were abstracted and cases were followed up for next five years periodically from the date of diagnosis to access their survival status. Results: Kaplan Meier analyses were conducted to identify overall survival and median survival time. Among 520 cases, 130 (25%) had lost to follow up so excluded from the study and the study sample was about 390 patients. The median survival time for cervical cancer in this study was 60 (32-60) months and the overall survival rates at 1, 3 and 5 years were 93.07%, 72.3% and 54.9% respectively. Education, use of oral contraceptive pills (OCP), tobacco chewing (good survival in tobacco non-chewers) and staging were significantly associated with survival. Conclusion: The 1, 3 and 5 year survival rates for cervical cancer were found to be 93.07%, 72.3% and 54.9% respectively. Various factors determining survival rates were potentially modifiable. Early diagnosis and prevention strategies are keys to obtain better outcomes.

Characteristics of patients with late recurrence endometrial cancer

Aim: We planned this study to assess endometrial cancer (EC) patients who had late metastasis. Materials and Methods: This retrospective study constituted a review of the records of patients who were diagnosed with EC and underwent hysterectomy at the Gynecologic Oncology Clinic between 1996 and 2018. Relapses occurring after the first three years following primary treatment of EC are considered late recurrences. Post-relapse survival (PRS) refers to the time to the last follow-up or the patient’s death after relapse. Results: Late metastases were identified in 42 patients, 20 (47.6%) of whom had locoregional recurrence and 22 of whom (52.4%) had extrapelvic recurrence. Median disease-free survival (DFS) times were 61 (range: 43–78) and 65 (range: 48–81) months for the groups with locoregional and extrapelvic recurrences, respectively (P = 0.462). The 5-year PRS rate for the patients was 61.1%, with 63.8% having locoregional and 59.4% having extrapelvic late metastasis (P = 0.969). Conclusion: Among the patients with late metastases, those with endometrioid type EC were found to have a better prognosis. It has been shown that locoregional or extrapelvic organ recurrence does not significantly affect survival in patients with late relapse. Although our results are not statistically significant for cases of locoregional late metastases, surgical resection increases survival rates.

Primary vaginal squamous cell carcinoma—the coeffect of vaginal leiomyoma and Human papillomavirus (HPV); A case report

ABSTRACT Primary vaginal squamous cell carcinoma (SCC) is extremely rare. Primer vaginal SSC developed by the coeffect of leiomyoma and Human papillomavirus (HPV) is presented. We report a case of primary vaginal SCC in a 62-year-old woman presenting dyspareunia. On macroscopic examination, the surface of the operation material was partly ulcerated. On the cut surface, the material was solid, firm, white, and whorled. Microscopic examination revealed leiomyoma ulcerating the mucosa and SCC at the base of the ulcer. The case, in which vaginal SCC developed in the vagina due to the irritation of the leiomyoma, as well as its relationship with HPV, is important to be the first to our knowledge.

Age-wise cancer incidence in western Uttar Pradesh in India: An observational study

ABSTRACT Context: According to the World Health Organization report of 2011, the main cause of death was cancer rather than heart diseases. 14.1 million new cases and about 8.2 million deaths occur due to cancer according to the report given by GLOBOCAN 2012. Aims: This study was conducted to highlight the age-wise cancer incidence in western Uttar Pradesh. Materials and Methods: This was a cross-sectional study conducted in the department of radiotherapy from 2018-2020. Data were collected from the hospital records of histopathologically confirmed cases of malignancies from 2018 to 2020. Details regarding age, sex and site of the tumor were collected from the clinical records. Statistical analysis used: Descriptive statistics were used for data calculation as well as summarization, Mean ± SD, percentage, and proportions were calculated. Results: Age-wise cancer incidence in the head and neck region among both the genders shows that the highest percentage of mouth cancer of 23.19% (409) was found among males above 40 years of age as compared to females with 4.76% (84), the prevalence of breast cancer was increasing with increasing age reaching 42.79% (603) prevalence above the age of 40 years. The highest percentage of lung cancer was found above the age of 40 years 32.57% (459) in the case of males. Gallbladder carcinoma in females was 37.882% (161) and liver malignancies in males were found at 9.41% (40). In the case of the female reproductive system, highest percentage of cervical malignancies having 56.85% (485) next to the cervix it was the ovarian malignancy with a significant percentage of 19.22% (164).

The role of GADD45G methylation in endometrial cancer: Insights into CDK1/CCNB1 activation and therapeutic opportunities

ABSTRACT Introduction: Accumulating evidence suggests the significant involvement of GADD45G in the development of various cancers. This study investigates GADD45G’s involvement and methylation status in endometrial cancer (EC), along with molecular mechanisms and potential therapies. Methods: The expression of GADD45G in EC tissues and controls was evaluated using RNA-seq, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting (WB). Methylation-specific PCR (MSP) evaluated GADD45G’s methylation status. Protein-protein interaction (PPI) prediction identified potential interactors of GADD45G, and co-immunoprecipitation (co-IP) confirmed GADD45G interact with Cyclin-dependent kinase 1 (CDK1) and cyclin B1 (CCNB1). Several cell behavior assays were conducted in both in vitro and in vivo settings to comprehensively understand the impact of GADD45G dysregulation in EC. Results: Our findings revealed a significant decrease in the expression of GADD45G in endometrial cancer tissues and cells, which was attributed to its methylation status. Reduced GADD45G expression correlated with increased invasive behaviors in EC cells. Furthermore, GADD45G negatively regulated CDK1 and CCNB1, promoting invasive behaviors at transcript and protein levels. Conclusion: This study demonstrated that the downregulation of GADD45G, mediated by methylation, facilitates the invasive behaviors of EC cells through interaction with the CDK1/CCNB1. These findings enhance understanding of the molecular mechanisms underlying endometrial cancer and suggest potential therapeutic strategies targeting GADD45G for treatment.

Paraneoplastic syndromes in ovarian cancer: Clinical manifestations, mechanisms and management challenges

ABSTRACT Paraneoplastic syndromes encompass an enigmatic spectrum of clinical manifestations precipitated by various malignancies but not attributable to direct tumor invasion, metastatic dissemination, or hormone secretion from the affected organ. In ovarian cancer, a notably heterogeneous malignancy with a predilection for presentation at the advanced stage, paraneoplastic manifestations may arise from multiple organ systems, thereby complicating diagnosis, altering clinical trajectories, and exerting profound impact on both short- and long-term patient outcomes. These phenomena, observed across both epithelial and nonepithelial ovarian tumors, are often mediated through immune cross-reactivity, ectopic hormone secretion, or cytokine dysregulation. Notable manifestations include neurological syndromes, such as cerebellar degeneration, anti-N-methyl-D-aspartate receptor encephalitis, and metabolic disturbances like hypercalcemia, Cushing’s syndrome, and thromboembolic states. Despite significant advancements, the diverse clinical presentations of paraneoplastic syndromes continue to pose substantial diagnostic ambiguities, with challenges in surgical planning and operative intricacies. This narrative review aims to elucidate an expansive analysis of the extant data on epidemiological patterns of ovarian cancer-associated paraneoplastic syndromes, their underlying molecular and immunological drivers, and management strategies. The review utilized extensive search across PubMed, EMBASE, Medline, Scopus, and Cochrane Library databases from January 2000 to March 2024. Inclusion criteria included peer-reviewed studies reporting ovarian cancer patients with clinically confirmed paraneoplastic syndromes, definite investigations, and clinical outcomes. Furthermore, it emphasizes the critical importance of multidisciplinary approaches to deliver holistic perioperative care, while addressing the systemic perturbations induced by paraneoplastic processes.

Development and validation of a risk signature based on disulidptosis-related ferroptosis genes in ovarian cancer

ABSTRACT Background: Disulfidptosis and ferroptosis, newly identified forms of cell death, have attracted widespread attention; however, their relationship with ovarian cancer (OC) prognosis remains unclear. Methods: We constructed a multivariate Cox risk signature comprising three key genes: CREB3, PIEZO1, and SLC7A11. Patients were stratified into high- and low-risk groups based on the optimal cutoff value of the risk score. Subsequently, survival analysis was conducted in the training group (TCGA-OV) and external databases (GSE26712 and GSE63885), with the predictive efficiency of the risk signature evaluated through ROC curves. Results: Prognosis was significantly better for patients in the low-risk group than in the high-risk group. Compared to single clinical features such as age and stage, the risk score had the highest diagnostic value for prognostic evaluation. Based on gene function and pathway analyses, differential genes were found to be related to oxidative stress. Immune infiltration analysis indicated that risk scores were associated with immunosuppressive cells such as M2 macrophages. Finally, the protein expression levels of the key gene CREB3 in OC tissues were evaluated in vitro. Conclusion: This study might provide significant value for exploring the relationship between disulfidptosis-related ferroptosis genes and OC, and its results may provide insights on new therapeutic targets for OC.

Fibrothecoma/Fibroma of ovary-rare ovarian tumors with varied presentation and different modes of management: 14 years’ experience from tertiary care hospitals

ABSTRACT Context: Fibrothecomas are a rare group of tumors of stromal cell origin, accounting for approximately 5%–8% of all ovarian tumors. These tumors are frequently mistaken as malignant due to solid consistency, association with ascites, and pleural effusion leading to unnecessary radical surgery. Due to the relative rarity of these tumors, we want to highlight eleven cases of fibrothecoma/fibromas encountered in our experience with different clinical presentations in various age groups requiring different treatment strategies based on the clinical, radiological, cytological, histopathological, and immunochemical characteristics. Aims: Our primary aim is to emphasize the diverse presentation of rare tumors, such as fibrothecoma/fibromas, and their management across different age groups. Settings and Design: The present study was conducted over 14 years in the Department of Obstetrics and Gynecology and the Department of Pathology at Guru Gobind Singh Medical College and Hospital, Faridkot, as well as at All India Institute of Medical Sciences Bathinda. Materials and Methods: Among 526 patients with ovarian masses who were surgically managed over 14 years at our institute, we identified only 11 cases that were diagnosed as fibrothecomas or fibromas based on histopathology. We studied the detailed clinical presentations, diagnostic modalities, and management of all these patients, who were all normal at a mean follow-up of 2 years and 5 months. Results: Over 14 years, we evaluated 526 patients presenting with ovarian masses diagnosed through clinical examination, imaging techniques, fine-needle aspiration cytology (FNAC), histopathology, and immunohistochemistry. Only 11 cases (2.09%) were identified as fibroma or fibrosarcoma. Age of the patients ranged from 14 to 76 years, with a mean age of 44.22 years. Of the 11 cases, nine patients presented with an abdominopelvic mass. Ultrasonography and contrast-enhanced CT scans typically revealed solid masses accompanied by ascites. FNAC was effective in eight cases, identifying spindle cells upon microscopic examination. Final diagnoses were confirmed through histopathology, which classified two cases as fibroma and nine as fibrothecoma. Immunohistochemistry results showed vimentin positivity in nine cases. All patients remained healthy during a mean follow-up period of 2 years and 5 months. Statistical Analysis Used: Observational study. Conclusions: This article highlights a rare ovarian tumor with details of its different clinical presentations, radiological details, cytological findings, and histopathological and immunochemical findings. According to the patient’s age, these can be treated using minimally invasive and fertility-sparing techniques.

Case report of an adult with rhabdomyosarcoma of lung with ovarian metastases or the other way around: Do’s and don’ts with review of literature

ABSTRACT Primary pulmonary rhabdomyosarcoma (RMS) is extremely rare (0.07%) in persons aged >45 years and is frequently misdiagnosed as small-cell lung cancer. Little information is available regarding the management of patients, with available literature only limited to a few case reports. We report a rare case of RMS of the lung with multiple metastases with an extensive literature review on the subject. A 52-year-old woman presented with shortness of breath, orthopnea, and chest pain for one and a half months. She also developed abdominal distension in the last month. Imaging showed a large, ill-defined solid cystic mass arising from the retroperitoneum abutting the urinary bladder with multiple adjacent small nodular deposits in serosa and peritoneum with gross ascites along with two large mass lesions in the lower lobe of the left lung and bilateral lung parenchymal metastatic deposits. The biopsy of the adnexal and lung lesions was performed along with immunohistochemistry, which was suggestive of rhabdomyosarcoma. The patient was planned for palliative chemotherapy with biweekly vincristin, adriamycin, cyclophosphamide/ifosphamide, etoposide (VAC/IE) regimen with prophylactic granulocyte-colony stimulating factor support followed by response assessment after 3–4 cycles. However, dose-compressed VAC/IE is highly myelosuppressive and lead to febrile neutropenia in our patient and thus culminated in her death. Hence, the Indian patients should be challenged with dose-compressed VAC/IE with extreme caution. Three-weekly IE/VAC regimen is an alternative.

Cancers in adolescents and young adults (AYA) population: 5-year experience from a cancer registry in India

ABSTRACT Introduction: The distribution of cancer burden is unequal across the different age groups. The AYA age group have been defined by the National Cancer Institute as diagnoses occurring between the ages of 15 and 39. This age group shows the different features in terms of cancer biology, risk factors, prognosis etc., as compare to the other age groups. Material and Methods: This was a retrospective observational study. Data collection was done from 2017 to 2021. Data was collected from Hospital Based Cancer Registry (HBCR) that registers all new histopathologically proven cancers reporting to its various clinical departments. Data regarding age, gender and site were collected. A standardized hospital-based cancer registries core form was used for the collection of the data. Result: From the year 2017–2021 a total of 12,827 cancer patients were registered in our HBCR. From the total number 7,583 (59.12%) were males and 5,244 (40.88%) were females. In these 5 years 2,874 (22.4%) were registered in our hospital in the age group of 15–39 years (AYA) and 9953 (77.59%) were 40 and above the 40 years of age. In case of females breast cancer in adolescents (15–29) accounts about 6.77% next to breast cancer ovarian cancer accounts about 3.38%, while as in case of adults (29–39) the breast cancer remains at the highest percentage of 12.12% but uterine cancer comes at the second number with 6.63% this picture continues in the older adults with breast cancer (9.7%) at the highest percentage and next to breast cancer uterine cancer remains at the second number. Head and neck cancer cases were highest in males in both the age groups of AYA population that is adolescents (15–29) and in adults (29–39) with 17.41% and 35.7% respectively. The time trends of AYA cancers and old age cancers from 2017 to 2021 in males was showing an increasing trend with 18.45% to 21.53% except for the year 2019 when the drop was found and it might be because of the Covid-19 pandemic in India. The time trend of AYA cancers and old age cancers from 2017 to 2021 in female patients was showing an increasing trend from 19.34% to 27.05%. Conclusion: This study was done to find out the cancer burden of AYAs. The purpose of this study was to find out the specific AYA cancer profile and highlight the need of targeted cancer control measures to reduce the cancer burden in this age group.

Early endometrial carcinoma: Experience and outcomes

ABSTRACT Aim: Endometrial carcinoma (EC) data from India are very sparse. We did a retrospective analysis of our patients registered at this peripheral cancer center based in rural Punjab and studied their outcome. Materials and Methods: Ninety-eight Stage I and II EC patients with endometroid histology registered at our institute from January 2015 to April 2020 were studied for demography, histopathology, treatment received, and outcomes. FIGO 2009 staging and new European Society for Medical Oncology (ESMO) risk group classification was used. Results: Our patients had a median age of 60 years (range 32–93 years). There were 39 (39.8%), 41 (42.0%), 4 (4.1%), 12 (12.2%) patients in the low risk, intermediate risk (IR), high intermediate risk, and high risk groups, respectively, as per new ESMO risk classification. Two (2.0%) patients had incomplete information to assign them to a particular risk group. Fifty (46.7%) patients underwent complete surgical staging and 54 (50.5%) patients received adjuvant RT. With a median follow-up of 27.0 months, there were 1 locoregional and 2 distant recurrences. There were 8 deaths in total. Three-year overall survival for the entire group is 90.6%. Conclusions: The risk group determines adjuvant treatment in endometrial cancer. Patients operated at dedicated cancer center tend to have better surgical staging and thus better outcome because of better risk stratification and grouping for adjuvant therapy. IR histology was more common in our group of patients, which is variable as compared to available literature.

Role of squamous cell carcinoma antigen in prognostication, monitoring of treatment response, and surveillance of locally advanced cervical carcinoma

ABSTRACT Introduction: Squamous cell carcinoma antigen (SCC Ag) is a sub-fraction of the tumor antigen TA-4, first isolated by Kato and Torigoe, the most commonly used tumor marker in cervical cancer. It can be used as a serum marker to detect residual disease, early local recurrence, or distant metastasis in locally advanced cervical cancer even before the clinical symptoms of recurrence or metastasis. Methods and Materials: Between January 2018 and August 2018, 30 patients with squamous cell carcinoma cervix (FIGO) stages IB2-IVA, who received concurrent chemoradiation, followed by brachytherapy, were included in the study. Serum SCC Ag levels were collected at four time points during the course of the treatment, and their correlation with tumor and treatment factors were analyzed. Results: As the FIGO stage increases, mean pre-treatment SCC Ag also increases. Node-positive patients had higher pre-treatment SCC Ag as compared to those who were negative (P = 0.05). There was a statistically significant decreasing trend in the mean SCC Ag at the end of EBRT (P = 0.015). After completion of treatment, 78% had a complete response, 8% had a partial response, and 14% had progressive disease with statistically significant elevation of SCC Ag at 6 weeks of follow-up (P = 0.01). Patients who progressed or had the residual disease at follow-up were found to have high pre-treatment SCC Ag values. Conclusion: SCC Ag can be potentially used as a reference indicator of biological behavior of cervical cancer, to monitor the treatment response, and as a prognostic marker, especially in those with node-positive disease.

Diagnostic potential of differentially regulated microRNAs among endometriosis, endometrioid ovarian cancer, and endometrial cancer

Background: There is an increased risk of developing endometrioid ovarian and endometrial cancer in patients with endometriosis and there are no definitive diagnostic biomarkers available for these three associated diseases. Therefore, we evaluated the diagnostic potential of differentially expressed microRNAs (miRNAs) from the tissue samples of endometriosis, endometrioid ovarian cancer, and endometrial cancer to establish them as biomarkers for these diseases. Materials and Methods: Ten samples of each, i.e., endometriosis, endometrioid ovarian cancer, endometrial cancer and control healthy endometrium were enrolled after obtaining ethical clearance. Differential expression of miR-16, miR-20a, miR-99b, miR-125a, miR-143, and miR-145 and some of their target genes, i.e., vascular endothelial growth factor (VEGF), hypoxia inducible factor 1A (HIF1A), cyclooxygenase 2 (COX2), and tumor necrosis factor (TNF) were quantified using quantitative reverse transcription polymerase chain reaction. Receiver operating characteristic (ROC) curve analysis was performed to predict the diagnostic potential. Results: miR-16 and miR-20a were significantly downregulated, whereas miR-99b, miR-125a, and miR-143 were significantly upregulated in all three diseased samples. miR-145 was significantly upregulated in endometriosis and endometrioid ovarian cancer but significantly downregulated in endometrial cancer. mRNA levels of VEGF, HIF1A, COX2, and TNF were significantly increased in all three diseased samples as compared to control samples. ROC curve analysis revealed that for endometriosis, miR-99b, and miR-125a were giving highest area under curve (AUC) (0.950 and 0.733, respectively), for endometrioid carcinoma of ovary miR-143 was giving highest AUC (0.933) and for endometrioid endometrial cancer miR-16 (AUC = 0.815), miR-99b (AUC = 0.920), and miR-145 (AUC = 0.985) were found to be best predictors. Conclusion: These findings suggest that these miRNAs can act as good predictors and discriminators of these three diseases and might serve as potential biomarkers for them.

Synchronous benign Brenner's tumor of the ovary with leiomyoma and endometrial adenocarcinoma in a postmenopausal female

Radiation cystitis

We report the case of a 22-year old female presenting with an embryonal rhabdomyosarcoma of the cervix that was successfully treated by surgery followed by adjuvant radiation therapy and chemotherapy. She subsequently developed radiation cystitis after 10 years of follow-up. She was successfully treated with cystoscopic fulguration. In this report, we discuss a review of management strategies for cervical rhabdomyosarcoma and also throw some light on incidence and management of radiation cystitis after pelvic radiotherapy. We discuss the dose independence of radiation cystitis, which can be seen after as low as 4500 cGy of pelvic radiation.

Expression of epithelial–mesenchymal transition biomarkers

Context: Discoidin domain receptor 2 (DDR-2), which belongs to the receptor tyrosine kinase family, Snail-1, which is a member of zinc-finger transcription factor family, and Ovol-2, which is a member of Ovol family, are incriminated in epithelial–mesenchymal transition (EMT) during cancer progression. Aim: In the current study, we aim to clarify the extent to which EMT biomarkers, DDR-2, Snail-1, and Ovol-2 expression, are involved in the progression of EOC aiming at identification of novel markers for predicting the prognosis of EOC patients. Settings and Design: This was a prospective cohort that was performed in the Faculty of Medicine, Zagazig University. Materials and Methods: We evaluated DDR-2, Snail-1, and Ovol-2 expression in 60 patients of EOC using immunohistochemistry. We followed our patients for about 36 months and analyzed the relationship between markers expression and the prognosis of patients. Statistical Analysis Used: SPSS program (Statistical Package for the Social Sciences). Results: High expression of both DDR-2 and Snail-1 was related to higher grade (P = 0.006) and advanced FIGO stage of the tumor (P < 0.001). Ovol-2 high expression was associated with lower grade of the tumor (P = 0.002) and early stage of the tumor (P < 0.001). High Ovol-2 and low DDR2 and Snail-1 expression were strongly correlated with better response to therapy (P = 0.003 and 0.005, respectively) and increased 3-year survival rates (P < 0.001). Conclusion: DDR-2 and Snail-1 are markers of poor prognosis in EOC while Ovol-2 is a marker of good prognosis.

Dosimetric impact of dwell time deviation constraint on inverse brachytherapy treatment planning and comparison with conventional optimization method for interstitial brachytherapy implants

Purpose: High-dose rate remote afterloading brachytherapy machine and advanced treatment planning system help in getting optimum dose to tumor and low dose to normal structures. Inverse planning simulated annealing (IPSA) optimization technique has a unique feature of dwell time deviation constraint (DTDC). In this study, six IPSA-based plans having different DTDC values with routinely practiced geometric plus graphical optimization (GO + GrO) have been compared using various dosimetric parameters. Materials and Methods: For this retrospective study, we have generated IPSA-optimized interstitial brachytherapy plans for ten cancer cervix patients. Routinely practiced GO + GrO-based plans were compared with six different IPSA plans having varying DTDC values from 0.0 to 1.0 using different dosimetric indices. Results: Conformity index and homogeneity index (HI) were higher in GO + GrO plans, compared to IPSA-optimized plans. However, HI of IPSA plans was increasing with increasing DTDC values. High-dose volumes were well controllable using DTDC parameter in IPSA-optimized plans. Dose to the rectum and bladder was smaller for IPSA-optimized plans than GO + GrO plans. Conclusions: One of the benefits of applying DTDC in IPSA-optimized plan is that it reduces high-dose volumes. Another advantage is the reduction in rectum and bladder dose.

Ovarian squamous cell carcinoma

Ovarian squamous cell carcinoma is a rare and aggressive ovarian neoplasm, where most of the cases arise from mature teratoma, which represents up to 20% of all ovarian tumors. Moreover, primary squamous cell carcinoma is considered to be related to human papillomavirus infection. The diagnosis is difficult and metastasis from bladder, genital tract, lung, and digestive tract cancers must be ruled out. There are no guidelines for treatment, however, radical surgery combined with adjuvant chemotherapy and radiation therapy, are the most common approach. We present the case of a young women diagnosed with a de novo ovarian squamous cell carcinoma, as well as the treatment and follow-up that she received.

Golgi phosphoprotein 3 promotes ovarian cancer progression and is associated with cisplatin resistance

Background: Golgi phosphoprotein-3 (GOLPH 3) is involved in the development of several human cancers. However, the clinical significance and biological role of GOLPH 3 in ovarian cancer (OC) remains unknown. Methods: The expression of GOLPH 3 in OC cell lines was quantified using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The role of GOLPH 3 in tumorigenicity, migration, and invasion of OC cell lines by small interference RNA, scratch wound-healing assays, and transwell assays was detected. In addition, western blotting was used to determine whether GOLPH 3 is associated with the PI3K/AKT/mTOR signaling pathway. Furthermore, RT-qPCR verified whether GOLPH 3 is associated with drug resistance. Results: GOLPH 3-positive expression rate was higher in OC. Downregulation of GOLPH 3 markedly inhibited the migration and invasion and may be related to the PI3K/AKT/mTOR signal pathway. Moreover, the result of the experiment proved that GOLPH 3 enhances the sensitivity of OC to cisplatin by regulating ATP7A/B. GOLPH 3 promoted the invasion and migration of OC, and the mechanism may be related to the PI3K/Akt/mTOR pathway. In addition, inhibition of GOLPH 3 increased the sensitivity of OC cells to cisplatin, which may be associated with ATP7A/B. Conclusion: This study found that GOLPH3 may promote the migration and invasion of OC cells through PI3K/Akt/mTOR pathway. At the same time, low expression of GOLPH3 increased the sensitivity of OC cells to cisplatin.

DNA base excision repair gene variants and susceptibility to ovarian cancer

Human papilloma virus infection of uterine cervix and spectrum of cervical pathology in human immunodeficiency virus/AIDS

Background: Human papilloma virus (HPV) is one of the most common causes of sexually transmitted viral diseases worldwide. High-risk HPV types such as HPV16 and 18 are known to cause cervical dysplasia and carcinoma. In human immunodeficiency virus (HIV)-positive individual, chance of HPV coinfection and risk of cervical dysplasia/carcinoma have been found to be significantly more than in HIV-negative individuals. Aim: In this institution-based, cross-sectional, observational study, we aim to find out the relationship of HPV infection of the uterine cervix with cervical dysplasia and neoplasia in HIV-infected/AIDS patients. Materials and Methods: Conventional Pap smears were taken from HIV-infected individuals admitted in the department of gynecology and obstetrics and reported by the Bethesda system. A second sample was sent to the virology unit of ICMR for detection and typing of HPV. Control samples were taken from HIV-negative individuals. Results: Fifty HIV-positive patients were included in this study. On cervical Pap smear examination, 32 cases were cytologically benign and 18 cases showed atypical cytomorphology. Twenty-four cases were HPV positive, among which 16 were cytologically atypical and 8 were benign. HPV 16 was the most common subtype (50%) followed by HPV 18 (37.5%) and others (12.5%) in HIV-positive patients. Chance of cervical dysplasia increased with age independent of HIV infection and with progressive lower CD4 count. Koilocytosis was a significant predictor of HPV infection. Majority of patients were asymptomatic. Peak incidence of HPV infection occurred in reproductive age group (20–40 years). The association between HIV and HPV coinfection (P = 0.002) and between HPV infection and cytology atypia (P < 0.0001) was statistically significant. Conclusion: Present study highlights the necessity of routine cervical Pap smear screening in HIV infected reproductive age-group women. Early detection enables dysplasia to revert or be effectively managed.

Proteomic analysis of the influence of CO2 pneumoperitoneum in cervical cancer cells

Objective: The effect of CO2 pneumoperitoneum (CDP) on the oncology outcomes of patients undergoing laparoscopic radical hysterectomy for cervical cancer remains unclear. In this study, we investigated the effects of CDP on the proliferation of cervical cancer cells and examined the molecular mechanism. Materials and Methods: We established an in vitro CDP model to study the effects of CDP on the proliferation of cervical cancer cells by Cell Counting Kit-8 (CCK-8) assay, xenografted tumor assay. Tandem mass tag-based quantitative proteomics were used to study the proteomic changes in HeLa cells after CDP treatment. Western blot assay was used to detect the expressions of PI3K/Akt signaling pathway proteins. Results: CDP increased cell proliferation after a short period of inhibition in vitro and promoted tumorigenesis in vivo. Proteomic analysis showed that the expression levels of 177 and 309 proteins were changed significantly 24 and 48 h after CDP treatment, respectively. The acidification caused by CO2 inhibited the proliferation of cervical cancer cells by inhibiting the phosphorylation of PI3K and Akt. Conclusions: CDP promoted the proliferation of human cervical cancer cells after a short time of inhibition. The mechanism of which is related to the inhibition of phosphorylation of the PI3K/Akt signaling pathway.

Retrospective analysis of surgically treated cases of squamous cell carcinoma vulva

Context: Vulvar carcinoma accounts for 3%–5% of gynecologic malignancies. The past three decades has observed changes in the trends of clinical characteristics and treatment modalities used in managing this disease. Aims: The aim of the present study is to analyze the clinic-pathological characteristics and survival of women with squamous cell carcinoma vulva who underwent primary surgical management. Settings and Design: This was a retrospective observational study. Subjects and Methods: Case records of 30 consecutive patients with squamous cell carcinoma of vulva during the period of 2010–2016 were retrospectively reviewed and their clinical profile, treatment details, complications, and survival were analyzed. Statistical Analysis Used: Kaplan–Meier survival analysis, followed by logrank test, was used for survival outcome, and Cox proportional hazard model was used to assess significant risk factors. Results: The mean age of patients was 58 ± 12.9 years. The most common symptom was growth over vulva (73.3%), itching (63.3%), and nonhealing vulval ulcer (26.6%). The most common site for disease was labia majora. The surgical treatments ranged from wide local excision to radical vulvectomy. Postoperative adjuvant therapy was required for 16 patients. The median (95% confidence interval [CI]) overall survival was 27 (21.7–32.2) months. Five-year survival probability for early-stage disease (I + II) was 49% (95% CI: 12.9, 78.4) and for advanced disease (III + IV) was 24.8% (95% CI: 4.8, 42.6). Lymph node-positive status was found to have a significant impact on survival (hazard ratio of 4.9 [95% CI: 1.15–21.02, P = 0.02]). Conclusions: Despite advances in detection and management modalities, the survival for vulval malignancies has not improved.

Recurrent mucinous cystic neoplasm of the mesentery in a young nullipara mimicking as ovarian carcinoma

Inroduction: Mucinous cystic neoplasms are rare tumors. They may originate from either ovaries, pancreas, or other intra-abdominal sites, but rarely from the mesentery. Case History: A 22-year-old nulliparaous woman, who had undergone laparascopic bilateral cystectomy for recurrent ovarian mass, presented with pain in abdomen, backache, and menstrual irregularities. Provisionally diagnosed as ovarian carcinoma, she underwent bilateral salpingo-oophorectomy and sigmoid colectomy. However, the histopathological examination revealed mucinous cystic neoplasm of the mesentery. Discussion: Thus, complete resection of the cysts with meticulous gross and histopathological examination remains the gold standard to differentiate mucinous cystic neoplasm (MCN) of the mesentery from its mimics, especially malignant counterparts, enabling clinicians to adequately manage such patients. Here, we present a case of recurrent MCN of mesentery (mesocolon), mimicking as ovarian carcinoma confirmed on histopathological examination, in a young adult.

MRI assessment of ovarian masses and correlating with CA-125

ABSTRACT Background: The combined use of appropriate imaging modalities and serum biomarkers like serum Carcinoembryonic Antigen-125 (CA-125) helps plan treatment strategies and reduce overall mortality. Aims and Objectives: To assess ovarian masses on Magnetic Resonance Imaging (MRI) and correlate them with serum CA-125 values. To derive a new serum CA-125 cut-off value for differentiating benign from malignant ovarian masses. Materials and Methods: This cross-sectional study was conducted from August 2020 to January 2021 on patients with suspected pelvic masses referred to the department of radio-diagnosis and meeting inclusion and exclusion criteria. Serum CA-125 values and imaging features on MRI were recorded. Results: A total of 37 ovarian masses were included in the study, of which 14 were malignant and 23 were benign. The mean CA-125 values among benign [35.95 ± 25.42 (mean ± SD) IU/ml] and malignant ovarian masses [444.82 ± 232.9 (mean ± SD) IU/ml] were statistically significant (<0.001). Using the reference serum CA-125 value of 35 IU/ml, specificity and accuracy were 61% and 75.68%. A cut-off value of 80.5 IU/ml recorded specificity and accuracy of 95.7% and 94.59%, respectively, with a sensitivity of 92.86% in differentiating benign from malignant ovarian masses. Conclusion: The serum CA-125 cut-off value of 80.5 IU/ml is a sensitive and specific serum biomarker for ovarian malignancies. A combined approach of MR imaging and serum CA-125 correlation can be used in characterizing ovarian malignancies in routine clinical practice.

Promoter methylation status of key genes and its implications in the pathogenesis of endometriosis, endometrioid carcinoma of ovary and endometrioid endometrial cancer

Background: Epigenetic processes play an important role in various physiological processes as well as in the pathogenesis of many diseases. The role of altered DNA methylation in the pathogenesis of endometriosis and associated ovarian and endometrial cancers has not been explored in detail. Therefore, this study aimed to determine the promoter methylation status of genes involved in key biological processes in the pathogenesis of these three gynecological diseases. Methods: Tissue samples of endometriosis, endometrioid carcinoma of the ovary, endometrioid endometrial cancer, and control endometrium (n = 10 each) were obtained. DNA was extracted and subjected to bisulfite conversion using commercially available kits. The methylation status of COX2, VEGF, HIF1A, TNF, MYC, and TP53 genes was checked by methylation-specific PCR. The mRNA levels of MYC and TP53 were determined using qRT-PCR in all tissue samples. Results: The promoter methylation status of COX2, VEGF, HIF1A, and TNF genes was significantly reduced in all three diseased study subjects (P < 0.05), whereas no significant difference was observed in the promoter methylation frequency of MYC and TP53 genes. Transcriptional expression of the MYC gene was significantly increased in all diseased groups (P < 0.001) whereas, transcriptional expression of the TP53 gene was significantly reduced in endometriosis and endometrioid carcinoma of the ovary and significantly increased in endometrioid endometrial cancer subjects compared to control subjects (P < 0.001). Conclusion: The findings suggest that the promoter regions of pro-inflammatory and pro-angiogenic genes involved in the common molecular pathophysiology of these three disorders were significantly hypomethylated and could be the reason for their over-expression associated with them. This indicates the role of epigenetics in the pathogenesis of these three diseases.

Solitary humerus metastasis in a young endometrial cancer patient

Solitary bone metastasis in endometrial cancer is very rare. We report a young 29-year-old nulliparous female of endometrial cancer who developed solitary humerus metastasis after 8 months of primary treatment of surgery and adjuvant radiotherapy and chemotherapy. She was treated with local radiotherapy and combination chemotherapy and bisphosphonates. At 6 months follow-up the patient is doing well and is asymptomatic. Even though rare, keeping a high index of suspicion and sincere evaluation in patients on follow-up presenting with bone pains can detect early recurrences. Timely start of multimodality treatment helps relieve symptoms and improves quality of life.

Pattern of care and clinical outcome of patients with carcinoma endometrium and the impact of central histopathological review on management: A tertiary cancer centre experience

Abstract Purpose/Objective: Endometrial carcinoma (EC) is the third most common gynecological malignancy in India. Recent PORTEC-3 analysis emphasized the role of central histopathological review. We aimed to retrospectively analyze the demographic and histopathological characteristics of EC patients treated at our institute and assess the impact of the central histopathological review on management and also analyze clinical outcomes in this cohort of patients. Materials and Methods: Data of 75 EC patients treated at our center between 2013 and 2022 were retrieved from our departmental archives. Patients were analyzed for demographic details, histopathological findings, details of surgery and histopathology (HPE), results of a review of HPE, adjuvant treatment details, and clinical outcomes. All patients with HPE outside of our institute were reviewed at our center prior to initiation of treatment. In cases of discordance, patients were discussed in the multidisciplinary tumor board for the final treatment decisions. Patients were staged as per International Federation of Gynaecology and Obstetrics 2018. Result: The median age was 57 years (range: 37-74 years). Twenty-seven patients with HPE reported from the outside center were reviewed at our institute and changes were observed in 26 patients (96.3%). HPE review changes were observed in terms of histological grade, histological type, myometrial invasion, and lymph node involvement in five (18.5%), three (11.1%), seven (25.9%), and three (42.8%), respectively. HPE review leads to changes in the management of 19/26 patients. Stage distribution was I: II: III in 48 (64%): 9 (13.3%): 18 (24%) patients, respectively. The median external beam radiotherapy dose was 50 Gray (range: 45-50.4 Gray at 1.8-2 Gray per fraction). The median brachytherapy dose for patients treated with brachytherapy alone was 7 Gray each for three sessions and in combination with EBRT was 6 Gray each in two sessions. At a median follow-up of 51 months (range: 6-116 months), seven (9.3%) patients developed distant metastasis, two (2.7%) patients had local plus distant metastasis, and two (2.7%) patients had local recurrence. The overall survival and disease-free survival rates at 3 years were 93.5% and 86.7%, respectively. Conclusion: EC patients treated at our center have excellent local control rates with a combination of external beam radiotherapy and brachytherapy. The central histopathological review may result in changes impacting patient management and should be routinely done prior to initiation of treatment in EC.

A histopathological and immunohistochemistry analysis of endometrial lesions among women presenting with abnormal uterine bleeding

Objectives: We aimed to histopathologically evaluate the morphological spectrum, apoptotic index (AI), and mitotic index (MI) of endometrial lesions in patients presenting with abnormal uterine bleeding (AUB). Methods: A cross-sectional study was done over a period of 18 months where a total of 60 newly diagnosed cases of perimenopausal women presenting with AUB were included. All H and E stained pathology slides from the specimens were reviewed for initial histopathological evaluation and diagnosis. Immunohistochemistry for Bcl-2 and Bax was done. The study subjects were divided into two groups: Group 1 included 30 cases of histologically proven proliferative endometrium (PE) and endometrial polyps and Group 2 included 30 cases of hyperplasia, endometrial epithelial neoplasia (EIN)/or carcinoma. For all cases, AI and MI were calculated and compared among the two groups. Statistical Analysis: Quantitative variables were compared using the Independent t-test/Mann–Whitney test between the two groups and Kruskal–Wallis test for comparison between more than two groups. Qualitative variables were correlated using the Chi-square test. P < 0.05 was considered statistically significant. Results: In our study of 60 patients of AUB, the mean age was 45.87 years with a parity of 2 or more in most of the patients. Most of the patients in our study had heavy menstrual bleeding (66.67%) with associated complaints of weakness, pallor, and low backache. Out of 60 patients of AUB, Endometrial carcinoma was diagnosed in 13 (21.67%) patients, with the most common histopathological type being Endometrioid carcinoma. There was a significant difference in the AI, MI, and the ratio of AI/MI among various histopathological diagnoses. AI was highest for Endometrial carcinoma and lowest for hyperplasia and polyps. MI was also highest for Endometrial carcinoma and lowest for hyperplasia and polyps. However, the ratio was incongruent as it was highest for hyperplasia without atypia and lowest for PE with endometrial carcinoma being midway. The Bcl-2 expression of relatively benign conditions (Group 1) was significantly higher than Group 2 (Endometrial epithelial neoplasia/carcinoma). Bax intensity showed an almost inverse pattern, being highest in endometrial carcinoma and lower in hyperplasia and polyps with the lowest expression in PE. Even the Bcl-2:Bax ratio was also highest for PE and lowest for endometrial carcinoma with others falling in between them. Conclusion: It can be concluded that the combination of the proliferative and apoptotic markers and the ratio will help as a tool in aiding the diagnosis of endometrial lesions for patients presenting with AUB.

Use of methylene blue dye for sentinel lymph node mapping in early-stage gynecological cancers – An option for low resource settings

Context: Sentinel lymph node (SLN) mapping is a standard of care in gynecological cancers but with limited resources and equipment, intraoperative use of methylene blue for SLN mapping may be more useful. Aims: To authenticate the use of methylene blue dye for intraoperative SLN mapping in cases of early-stage gynecological cancers. Settings and Design: This pilot study was conducted in a tertiary care teaching hospital. Subjects and Methods: The cases included 14 cervical, 4 endometrial, 1 vulvar, and 1 synchronous cervical-vulvar cancer wherein 21 SLN mappings were done. Four ml of methylene blue was injected submucosally in the cervix in cervical and endometrial cancer. It was injected around the tumor in vulvar cancer. The pelvic lymphatic drainage area was examined in cervical and endometrial cancer while inguinofemoral area was examined in vulvar cancer for any blue LNs. Histopathological examination results were compared for the presence of metastasis in stained and unstained LNs. Statistical Analysis Used: The observations were presented as numbers and percentages. Results: The SLN mappings showed a detection rate of 76%. The mean number of LNs removed in each case was 10.3 with an average of 2.4 stained and 7.6 unstained LNs. SLN was most commonly found among right external iliac nodes. All stained and unstained nodes among the 16 SLN detections did not show any histological evidence of metastasis suggesting a negative predictive value of 100%. Conclusions: Methylene blue is an efficient, feasible, and safe dye for SLN mapping in early-stage gynecological cancer.

Effect of coexisting adenomyosis on patients with endometrioid adenocarcinoma: Determination of intraoperative risk factors for tumor metastasis and estimation of prognosis

Context: We sought to clarify the impact of adenomyosis on the clinical and pathological prognosis of endometrial cancer to aid the selection of appropriate surgical intervention based on the diagnosis of adenomyosis. Aims: Our study aimed to report the frequency of adenomyosis in patients with endometrioid cancer and correlate its incidence rate with the survival and prognostic factors. Materials and Methods: This retrospective study included 357 patients. Patients with endometrioid adenocarcinoma were divided into two groups based on the presence of adenomyosis. The groups were compared in terms of tumor diameter, lymphovascular space invasion (LVSI), low-high risk pathologic status, stage of the disease, and survival outcome. Statistical Analysis Used: Continuous variables were analyzed using the Student's t or Mann–Whitney U-test. Survival data were analyzed using the Kaplan–Meier test. Results: The average age was similar between the two groups. In total, 47 (13.2%) of 357 patients had adenomyosis. A total of 43 (91.4%) cases with adenomyosis and 258 (83.2%) cases without adenomyosis had Stage I endometrioid adenocarcinoma (n = 301, 84.3%). Moreover, 32 (68.1%) cases with adenomyosis and 187 (60.3%) cases without adenomyosis were in the low-risk group. There was no statistically significant correlation between the risk groups (P = 0.309) and overall survival between the two groups (P = 0.416). Conclusion: No correlation was seen between the characteristics of endometrioid type endometrial cancer and survival rates in patients with or without adenomyosis. The impact of adenomyosis as a factor in evaluating the perioperative prognosis and planning postoperative adjuvant therapy for endometrial cancer should be assessed by further studies.

The association between diabetes and cancer in Mexico

Context: Previous studies have shown that diabetes mellitus (DM) is a risk factor of some type-specific cancers. However, no data are available on the association between cancer and DM in Latin America. Aims: The aim of this study is to determine which type-specific cancers are associated with DM using multiple cause of death data. Settings and Design: Whole country of Mexico, cross-sectional design. Materials and Methods: Analysis of all cancer deaths (2009–2017) using death certificate databases of Mexican adults aged ≥20 years. Statistical Analysis Used: Multivariable logistic regression. Results: There were 710,292 total cancer deaths. DM increased the risk of pancreatic (adjusted odds ratio [aOR] = 1.7), liver (aOR = 1.6), kidney (aOR = 1.4), gallbladder (aOR = 1.2) and endometrial (aOR = 1.1) cancers, all P < 0.05. Type 2 or unknown-type DM were associated with the same cancer types with little variation of estimates. Higher estimates were found in males than females (except for kidney cancer). Type 1 DM was associated with pancreatic cancer only (aOR = 1.9). Conclusions: DM in Mexico is associated with gastrointestinal (pancreatic, liver, gallbladder), kidney and endometrial cancers. Dissemination of knowledge to both health-care workers and diabetics regarding potential cancer risks including adequate diet, regular exercise, weight reduction if obese/overweight, cessation of smoking, and good glucose control and medication compliance should be reinforced. Specific cancer preventative measures should be implemented for patients with DM.

Role of WT1, B-cell lymphoma 2, Ki-67 (Mib1), and Her2/Neu as diagnostic and prognostic immunomarkers in ovarian serous and endometroid carcinoma

Background: Ovarian cancer is the fifth common cause of death due to cancer in women. It constitutes 3% of all cancers in females and 15%–20% of genital malignancy. Most of the ovarian cancers are serous type followed by the endometrioid type. Sometimes, glands of these two carcinomas are indistinguishable histologically. It also becomes difficult to differentiate these two types when they are poorly differentiated. Aims: The aim of this study was to find differences in immunomarker expressions between serous and endometrioid carcinomas and the association of their staining patterns with other clinicopathological prognostic factors. Materials and Methods: Immunohistochemical staining for WT1, B-cell lymphoma 2 (Bcl2), Ki67 (MIB1), and Her2/Neu were done in paraffin-embedded tissues of histologically diagnosed 38 cases of ovarian serous and endometrioid carcinomas and staining patterns were correlated with other clinicopathological prognostic factors. Results: Of these 38 cases (21 serous and 17 endometrioid), 24 cases were in Stage I/II and 14 cases Stage III/IV. On the other hand, 16 cases were in low grade, 12 cases intermediate grade, and 10 cases high grade. Twenty of 21 serous carcinomas were strongly positive for WT1, whereas most of the endometrioid carcinomas were negative. Ki67 (MIB1) labeling index and Her2/Neu were higher in both higher grade and stages. On the contrary, the intensity of Bcl2 staining was lower in higher grades and stages lesions. Conclusions: The use of WT1 may be useful in resolving diagnostic dilemma between serous and endometrioid carcinoma, especially in difficult cases. Ki67, Bcl2, and Her2/Neu may be used as prognostic markers.

Observational study of cone beam computed tomography based interfractional urinary bladder filling variation during image guided radiation therapy in pelvic malignancies

Background: Organ motion is an important factor that limits the precision of radiation treatment. Bladder filling variation has significant impact on the position of target volumes in pelvic malignancies. Aims and Objective: This study was an effort to maintain a consistent urinary bladder volume after following a bladder protocol, which was then analyzed by in-room cone-beam computed tomography (CBCT) imaging. Material and Methods: A total number of 26 patients/300 scans, i.e. 26 planning scan and 274 CBCT were analyzed. The bladder volumes and bladder wall dimension were analyzed comprehensively, thus adding considerable understanding to the bladder wall motions. Result: The mean bladder volume for all 26 patients was 183.07 cc with standard deviation of 90.43 cc. The mean +/- standard deviation of transverse, anteroposterior and longitudinal diameter was 8.35+/- 1.03, 6.69+/-1.05 and 5.59+/-1.79 cm. Conclusion: This study showed considerable reduction of margin could be done on the lateral side, as there is less displacement on transverse diameter and more liberal margins should be considered in anteroposterior dimension and longitudinal dimensions. This study has reached the conclusion that bladder-filling protocol is necessary to maintain the consistent bladder volume, but it is too preliminary to state that it will translate into reduction of margin.

Immune abscopal effect of microwave ablation for lung metastases of endometrial carcinoma

Increasing evidence support that microwave ablation (MWA) induces spontaneous abscopal regression of the tumor, also called as the abscopal effect. Although the abscopal effect after MWA is a rare event, several studies have suggested that this effect is the result of the activation of the immune system induced by the death of immunogenic tumor cells. Here, we have presented the case of a 65-year-old woman with primary endometrial cancer who developed bilateral pulmonary metastases. After local MWA of one lesion in her right lung, progressive regression of the other lesions in the right and left lungs was recorded. This case supports the hypothesis that the abscopal effect is attributable to the activation of the systemic immune response.