Asia-Pacific Journal of Clinical Oncology

Comparison of Epidemiology, Demography, Treatment (Surgery and Radiotherapy), and Survival Between Aboriginal and Torres Strait Islander and Non‐Indigenous Women With Cervical Cancer in NSW, Australia in 2009–2018

ABSTRACT Background Health outcomes for Aboriginal and Torres Strait Islander people in Australia are significantly worse than in the non‐Indigenous population. Aim To evaluate demographic factors and treatment (surgery and radiotherapy) rates for cervical cancer and to compare these between the Aboriginal and non‐Aboriginal populations to identify any differences in outcomes or modifiable treatment differences between the populations. Methods Retrospective cohort analysis of all patients in the state of New South Wales, Australia, diagnosed with cervical cancer between 2009 and 2018 using linked registry, treatment, and death data. Results The crude incidence rate for cervical cancer in Aboriginal women in NSW (17.29/100,000) was more than double the rate among non‐Aboriginal women (6.77/100,000). Aboriginal women were diagnosed with cervical cancer, including metastatic disease, at a younger age. There was no significant difference in presentation stage, surgery or radiotherapy treatment rates, or overall survival at 5 years between the two populations. Conclusion Although access to cancer care looks similar as an aggregate in Aboriginal versus non‐Aboriginal populations, there were disparities with reduced access to care (patients who did not receive either radiotherapy or surgery) among Aboriginal patients who were socioeconomically disadvantaged or residing in remote areas. The lower age of cancer diagnosis among Aboriginal women may have effects on survivorship, including negative effects on fertility, loss of income, and other personal, social, and economic consequences. Efforts to improve access to care, including screening, diagnosis, and treatment, should be targeted toward younger Aboriginal women and those who are socioeconomically disadvantaged or those residing in remote areas.

Current practices and challenges in genetic testing and counseling for women with breast and ovarian cancer in Asia

AbstractAimThis study assesses current practices and challenges in genetic testing and counseling (GT and C) for breast cancer gene (BRCA)1/2 mutations in Asia, considering the increased risk of ovarian cancer (OC) and breast cancer (BC) in women carrying these mutations.MethodsInsights were gathered through a questionnaire from breast surgeons, gynecologists, oncologists, and genetic clinicians in 10 Asian countries: Thailand, Hong Kong, South Korea, India, Vietnam, Malaysia, the Philippines, Taiwan, Singapore, and Indonesia. The questionnaire covered their knowledge, attitudes, and practices in GT and C for BRCA1/2 mutations, along with information on perceived gaps and unmet needs in the region.ResultsA total of 61 specialists participated in the survey. GT and C for BRCA1/2 mutations were less frequently offered in Asia compared to Western countries. Among the guidelines used, the National Comprehensive Cancer Network (NCCN) guidelines alone or in combination with other guidelines (American Society of Clinical Oncology [ASCO], National Institute for Health and Clinical Excellence [NICE], and European Society for Medical Oncology [ESMO]) were preferred for both BC and OC. Limited access to genetic counselors posed a significant challenge, resulting in delayed or no GT. Pretest genetic counseling was provided by the respondents themselves. Germline testing was preferred for BC, whereas both germline and somatic testing were preferred for OC, with the most preferred option being a multipanel germline test.ConclusionDisparities exist in GT and C practices between Asian and Western countries. To address this, steps, such as patient and doctor education, increased accessibility and affordability of GT and C services, and improved infrastructure for identifying gene mutations, should be taken.

An Australian mainstream genetic testing program: Clinicians views about current and future practices

AbstractPurposeGermline genetic testing results can guide treatment decisions for oncology patients and are now offered to many cancer patients. Mainstream testing refers to genetic testing arranged by a non‐genetics specialist. This repeated cross‐sectional study aimed: (1) to capture clinician views on the existing mainstreaming genetic testing program for ovarian, breast, prostate, and endometrial cancer patients, and (2) to ascertain the interest of clinicians to consider changing practice to adopt mainstream testing.MethodsMainstreaming has occurred since 2015 for patients with ovarian and some breast cancer patients, expanding to include prostate cancer patients in 2019, and endometrial cancer patients in 2020. Two web‐based surveys were administered within two health districts, covering seven hospitals in NSW.ResultsFifty‐four clinicians (70% response rate) participated. Clinicians who had arranged mainstream genetic testing (n = 30) were overall satisfied (76%), viewed the process as time‐efficient and accessible for patients, and desired continuation of the program. Of those clinicians yet to engage in the program (n = 24), 88% expressed an interest in learning about mainstream testing. These clinicians identified time constraints, maintenance of current genetic knowledge, and completing the consenting and counseling process as barriers to mainstreaming. Future mainstreaming models are discussed.ConclusionFrom the clinician's perspective, the mainstreaming program is considered a desirable pathway for germline testing of oncology patients. Access to ongoing education and resources is needed for the ongoing success of the program.

Olaparib dose re‐escalation in ovarian cancer patients who experienced severe and/or uncommon adverse events: A case series

AbstractAimFew real‐world studies have reported detailed management and dose adjustment strategies of adverse events (AEs) of ovarian cancer (OC) patients treated with the poly(adenosine diphosphate‐ribose) polymerase inhibitor olaparib. This case series aimed to describe olaparib AEs in Chinese OC patients in real‐life settings and to explore dose modification strategies.MethodsWe conducted a detailed examination of the clinical records of OC patients who were treated with olaparib at the Gynecologic Oncology Unit in Hong Kong from September 2015 to December 2019, including baseline characteristics, treatment outcomes, AEs, and management strategies, particularly dose modifications.ResultsNineteen patients were included, with a median olaparib treatment duration of 12 (range: 3–30) months. For recurrent platinum‐sensitive cases (n = 16), the median progression‐free survival was 16.0 months (95% confidence interval: 9.5–22.5). Eighteen (95%) patients experienced AE(s) of any grade, including four (21%) who experienced grade ≥3 AE(s). The most common AEs were as follows: nonhematologic fatigue (68%), nausea (42%), vomiting (26%), decreased appetite (26%), dyspepsia (21%), dizziness (21%), anemia (37%), neutropenia (26%), and thrombocytopenia (21%). Four specific cases involving anemia, lower limb lymphedema, myeloid neoplasm, and erythema nodosum are discussed separately. Eight patients required dose interruption or reduction due to AEs, of which five patients attempted and tolerated dose re‐escalation.ConclusionIn this study, most AEs were mild, but rare AEs were observed. In OC patients, olaparib AE management with dose reductions followed by re‐escalations was feasible, including for anemia.

miR‐425 regulates ovarian cancer proliferation, metastasis, and apoptosis by repressing PAK4 expression

AbstractAimTo explore the biological function of miR‐425/PAK4 axis in proliferation, metastasis, and apoptosis of ovarian cancer (OC) cells.MethodsqRT‐PCR and Western blot were adopted to examine miR‐425 and PAK4 expressions in OC tissues and cell lines. Cell counting kit‐8 (CCK‐8) and BrdU assays were applied to detect the proliferation ability of OC cells, and Transwell assay was adopted to assess the migration and invasion of OC cells. Flow cytometry was employed to evaluate the apoptosis of OC cells. The interaction between miR‐425 and PAK4 was predicted and verified by bioinformatics analysis and dual luciferase reporter gene assay, respectively.ResultsmiR‐425 was reduced in OC tissues and cell lines, and its underexpression was in evident correlation with the shorter overall survival time of OC patients. miR‐425 impeded OC cell proliferation, migration, and invasion, and accelerated apoptosis. Additionally, PAK4 was validated as the target of miR‐425, and the cotransfection of PAK4 reversed the antitumor effect of miR‐425.ConclusionmiR‐425 suppresses the proliferation, migration, and invasion of OC cells and enhances apoptosis via inhibiting PAK4, and it is expected to be a prognostic indicator and therapeutic target for the patients with OC.

Olaparib maintenance monotherapy in Chinese patients with platinum‐sensitive relapsed ovarian cancer: China cohort from the phase III SOLO2 trial

AbstractAimThe phase III SOLO2 global study demonstrated the efficacy and safety of maintenance olaparib, a poly(adenosine diphosphate‐ribose) polymerase inhibitor, in platinum‐sensitive relapsed ovarian cancer patients with a BRCA mutation. This separate China cohort of SOLO2 investigated the efficacy and safety of maintenance olaparib in Chinese patients.MethodsPatients received olaparib (300 mg twice daily, oral, tablets) or matched placebo. Primary endpoint was investigator‐assessed progression‐free survival (Response Evaluation Criteria in Solid Tumors version 1.1). Safety and tolerability were also assessed.ResultsThirty‐two patients were treated. Olaparib treatment led to an improvement in progression‐free survival compared with placebo (hazard ratio = 0.44, 95% confidence interval: 0.17–1.19; median = 13.8 vs. 5.5 months). Results of secondary efficacy endpoints of time to first subsequent treatment/death and time to treatment discontinuation/death were consistent with progression‐free survival results. Time to second progression/death and time to second subsequent treatment/death data were immature at data cutoff. The most common adverse events in the olaparib arm were nausea (81.8%), anemia (45.5%), and decreased appetite (36.4%). Grade ≥3 adverse events were experienced by 36.4% of olaparib and 10.0% of placebo patients. No adverse events led to discontinuation of treatment. There were six deaths (olaparib, five; placebo, one); one death in the olaparib arm was due to an unknown cause, all others were related to disease progression.ConclusionsEfficacy and safety findings in the China SOLO2 cohort support the use of olaparib (300 mg twice daily) as maintenance treatment for Chinese patients with platinum‐sensitive relapsed ovarian cancer and a BRCA mutation.

Evaluation of a mainstream genetic testing program for women with ovarian or breast cancer

AbstractIntroductionMainstream genetic testing refers to genetic testing arranged by a patient's treating specialist. The aim of this study was to retrospectively review a Sydney‐based ovarian cancer mainstream genetic testing program.MethodsA Cancer Genetics Service (CGS)‐supported mainstream genetic testing program was commenced in 2015. The CGS provided training, paperwork and ongoing and adaptable advice regarding appropriate genes for testing and interpretation of results. Written and electronic medical records were reviewed until August 2019 to assess patient and family history characteristics, genetic testing eligibility, results and posttest management for women who had testing coordinated via mainstreaming or by the CGS.ResultsGenetic testing was arranged for 289 women with ovarian cancer. Prior to 2017, 44% of genetic tests were mainstreamed, compared with 76% of tests from 2017 onwards. CGS was more likely to arrange testing for women with a strong family history of cancer and nonserous pathology. Germline pathogenic variants were detected in 13.7% (19/138) of women who had mainstream testing and 20.3% (14/69) of women tested by the CGS. Referral for posttest counseling occurred for pathogenic variant carriers identified through mainstreaming.ConclusionThis study demonstrated successful uptake of a mainstream ovarian cancer genetic testing program by medical oncologists, as evidenced by higher proportion and absolute numbers of eligible ovarian cancer patients accessing genetic testing through this pathway over time. The genetic testing criteria were appropriately assessed by oncologists and posttest referral occurred where required.

LINC01133 promotes the progression of cervical cancer via regulating miR‐30a‐5p/FOXD1

Abstract Background The prognosis of patients with recurrent or metastatic cervical cancer (CC) remains poor, and its incidence is especially high in developing countries. Multiple long noncoding RNAs are recently identified as crucial oncogenic factors or tumor suppressors. In this study, we explored the function and mechanism of LINC01133 during the progression of CC. Methods Expression levels of LINC01133 and miR‐30a‐5p in 50 CC tissue samples were measured using quantitative real‐time polymerase chain reaction. Immunohistochemistry and Western blot analysis were used to detect the expression of oncogene forkhead box D1 (FOXD1). The association between pathological indices and the expression level of LINC01133 was also analyzed. Human CC cell lines HeLa and SiHa were used as cell models. CCK‐8 and bromodeoxyuridine assays were used to assess the effect of LINC01133 on CC cell line proliferation. Flow cytometry was used to study the effect of LINC01133 on CC apoptosis. Transwell assay was conducted to detect the effect of LINC01133 on migration and invasion. Furthermore, luciferase reporter assay was used to confirm the targeting relationship between miR‐30a‐5p to LINC01133. Results We observed that LINC01133 expression in CC clinical samples was significantly increased, with high expression associated with higher T stage and negative HPV infection of the patients. Its overexpression remarkably accelerated proliferation and metastasis of CC cells, with reduced apoptosis. LINC01133 knockdown suppressed the malignant phenotypes of CC cells. Overexpression of LINC01133 significantly reduced the expression of miR‐30a‐5p by sponging it and enhanced the expression of FOXD1. Conclusions We report the overexpression of LINC01133 in CC sample and cell lines, which correlated with unfavorable pathological indices. LINC01133 was a sponge of tumor suppressor miR‐30a‐5p, and it enhanced the expression of FOXD1 indirectly and functioned as an oncogenic lncRNA in CC.

A systematic review of the barriers to implementing human papillomavirus vaccination programs in low‐ and middle‐income countries in the Asia‐Pacific

AbstractAim: The increasing burden of human papillomavirus (HPV)‐related diseases in low‐ and middle‐income countries (LMICs) could be alleviated by effective HPV vaccination programs. In this systematic review, we examined barriers to introduction, implementation, and/or sustainability of HPV vaccination programs in LMICs in the Asia‐Pacific region (AP‐LMICs).Methods: A systematic search of literature from the past 10 years (2010‐2019) was performed through PubMed, Cochrane CENTRAL, and Google Scholar. Studies were included if they reported barriers to HPV vaccination in AP‐LMICs. All study designs were included except commentaries and editorials. The journal articles were assessed using the Joanna Briggs Institute critical appraisal checklists.Results: A total of 46 eligible articles were included. An increase in publications was noted from 2010 to 2019. Barriers were diverse and were classified into four levels––government, healthcare providers (HCPs), society, and individual. The top specific barriers that were identified across AP‐LMICs are lack of funding and political support at the government level, lack of awareness among HCP and lack of vaccination programs at the level of health providers, and the perceived cost/benefit ratio for the individual level.Conclusion: Barriers to successful implementation of HPV vaccination programs differ among Asia‐Pacific LMICs. Policymakers will need to evaluate the relative importance of these barriers in their target areas and population in order to draft an effective dissemination and implementation strategy.

Clinical outcomes after positron emission tomography/computed tomography‐based image‐guided brachytherapy for cervical cancer

AbstractIntroductionAlthough positron‐emission tomography (PET) plays an integral role in cervix cancer diagnosis, there are limited data on PET‐based image‐guided brachytherapy (IGBT). We aimed to report the long‐term outcomes of PET‐based IGBT.MethodsWe reviewed 151 patients treated with definitive radiotherapy (RT), including PET‐based IGBT between 2009 and 2018. After median 45 Gy of external beam RT with the four‐field technique, a median 24 Gy of high‐dose‐rate iridium‐192 IGBT was delivered in six fractions with Fletcher‐Suit tandem and ovoids. All patients underwent 18F‐fluorodeoxyglucose‐PET/computed tomography planning with a brachytherapy applicator. Multivariable analysis of local control (LC) was performed using Cox regression analysis.ResultsThe median high‐risk clinical target volume (HRCTV) and HRCTV D90% were 51.8 (interquartile range [IQR] 35.9–79.4) cm3 and 77.7 (IQR 74.7–81.2) Gy, respectively. With a median follow‐up of 57 (IQR 24.3–81.4) months, the 5‐year LC rate was 89.2%. HRCTV ≥72 cm3 was associated with inferior LC (hazard ratio, 3.72, p = .017) after multivariable analysis: the 5‐year LC rates were 94.0% and 77.9% for HRCTVs ≥72 and < 72 cm3, respectively (p = .002). The impact of HRCTV D90% ≥70 Gy on LC was significant in patients with an HRCTV ≥72 cm3 compared to that in those with HRCTV < 72 cm3. Patients with adeno/adenosquamous carcinoma demonstrated inferior LC in both groups. There were 13 (8.6%) and 11 (7.3%) patients with acute and late severe toxicities after RT.ConclusionPET‐based IGBT leads to favorable LC, and HRCTV ≥72 cm3 requires further dose escalation to improve outcomes.

Relationship between human epididymal protein 4 and depth of tumor invasion, postoperative recurrence, and metastasis of epithelial epithelial ovarian cancer

AbstractThis study aimed to analyze the relationship between human epididymal protein 4 (HE4) and infiltration depth, postoperative recurrence, and metastasis of epithelial ovarian cancer (OVCA). Immunohistochemistry was used to detect the expression level of HE4 in cancer tissues and adjacent tissues of 90 patients with epithelial OVCA admitted to our hospital from May 2017 to January 2018. Cox regression was used to analyze the factors affecting the prognosis of epithelial OVCA. The relationship between HE4 and the prognosis of epithelial OVCA was analyzed by the receiver operating characteristic curve and Kaplan‐Meier survival curve. The positive expression rate of HE4 in epithelial OVCA was 85.56%, which was higher than 34.44% in adjacent tissues (p < 0.01). The International Federation of Gynecology and Obstetrics stage, infiltration depth, lymph node metastasis, postoperative recurrence and metastasis, and HE4 positivity were independent risk factors for the prognosis, and platinum‐based chemotherapy sensitivity was an independent protective factor for the prognosis of patients with epithelial OVCA (p < 0.05). The area under the curve of HE4 in diagnosing epithelial OVCA and predicting recurrence was 0.863 and 0.700, the sensitivity was 91.60% and 85.60%, and the specificity was 90.20% and 65.60%. The median progression‐free survival and overall survival were 26.1 and 30.2 months in HE4‐positive epithelial OVCA patients, while these were 31.4 and 35.6 months in HE4‐negative epithelial OVCA patients (p < 0.05). In conclusion, HE4 was highly expressed in epithelial OVCA tissues. Its expression level was related to the depth of tumor invasion, postoperative recurrence and metastasis, and other clinicopathological characteristics of patients with epithelial OVCA.

The Role of Surgery in Management of Primary Metastatic Endometrial Cancer

ABSTRACT For the majority of patients with endometrial cancer who are diagnosed at an early stage, high‐quality evidence directs mainstay initial surgical treatment, which confers excellent long‐term survival. Conversely, the 8%–15% of endometrial cancers diagnosed at a clinically advanced stage with primary metastatic disease have a significantly worse prognosis and a 5‐year relative survival rate of 15%–20%. The management of primary advanced endometrial cancer is understudied with the majority of relevant evidence being retrospective, single institution, and in heterogenous populations (combined with management of recurrent endometrial cancer), and there are few prospective studies that focus solely on primary advanced disease. It appears that hysterectomy and surgical cytoreduction may improve long‐term survival in metastatic endometrial cancer; however, it remains unclear which patients are most likely to benefit. Furthermore, the new integration of molecular classifications to the management of endometrial cancer has opened up new prognosis and treatment perspectives; however, the majority of current trials investigating new management paradigms based on molecular features exclude advanced‐stage disease, so the implications for practice regarding this patient group are understudied. This review analyzes the current available evidence regarding surgical management of primary metastatic endometrial cancer, including current international guideline recommendations, evidence for primary cytoreductive surgery and neoadjuvant systemic treatment followed by surgery, surgical resection of distant metastases, and lymph node management.

Expression of WW domain‐containing oxidoreductase and its clinical implication in endometrial adenocarcinoma patients with metabolic syndrome

AbstractAimMetabolic syndrome (MS) is tightly associated with the oncogenesis and prognosis of endometrioid adenocarcinoma, but the underlying mechanism is unclear. Here, we studied the relation between the expression status of WW domain‐containing oxidoreductase (WWOX) and the clinicopathological features of endometrioid adenocarcinoma patients with MS.MethodsFifty‐seven samples of endometrial adenocarcinoma were chosen for detection of expression level of WWOX. Overall survival (OS) time of these patients was analyzed by univariate and multivariate analysis. Survival analysis of patients with different WWOX expression levels from the Cancer Genome Atlas (TCGA) database was also performed.ResultsThe WWOX expression is significantly higher in MS group than that in non‐MS group (36.4% vs 65.7%, P = .03). WWOX was closely related to MS (P = .03) and muscle invasion of tumor cells (P = .04), but age, tumor grade, status of lymphatic metastasis, and FIGO (International Federation of Gynecology and Obstetrics) stage were not significantly different between the two WWOX expression status. Univariate analysis revealed that lymphatic metastasis (P = .023) and lower stage (P = .006) are significantly associated with OS. Multivariate analysis demonstrated that stage was an independent prognostic factor for OS (hazard ratio = 0.197; 95% CI, 0.043‐0.896). Downregulation of WWOX was statistically associated with OS in patients from TCGA database (P = .04).ConclusionWWOX may play an important role in the progression of endometrial cancer with MS.

A simple method of quantifying chemotherapy‐induced peripheral neuropathy using PainVision PS‐2100®

AbstractAimThis study aimed to validate a simplified method of quantifying chemotherapy‐induced peripheral neuropathy using the PainVision PS‐2100® (PV) electrical perception system.MethodsWe assessed patients diagnosed with epithelial ovarian cancer, fallopian tube cancer, or peritoneal cancer and were about to undergo first‐time paclitaxel and carboplatin chemotherapy. Peripheral neuropathy was assessed before and after chemotherapy administration in all patients according to the National Cancer Institute‐Common Terminology Criteria for Adverse Events Version 4.0 (NCI‐CTCAE4.0), using a conventional assessment in combination with the PV system. The PV device comprises electrodes attached to the ulnar side of the forearm and the first joint of index fingers on both the left and right sides to measure the electrical perceptual threshold. The average of three threshold measurements was recorded for each patient.ResultsThirty female patients (age 51.6 ± 12.2 [mean ± SD]) were included, and median number of chemotherapy drug treatments was 5 (first quartile: 4, second quartile: 5, and third quartile: 5). Twenty‐seven patients (90%) reported posttreatment numbness; NCI‐CTCAE4.0 perceptual anomaly grades were as follows: G1, 57 (40%); G2, 19 (13%); and G3, 7 (5%). A positive correlation was identified between right medial side PV threshold score and perceptual anomaly grade on measurements of the inner right‐hand side only.ConclusionOur preliminary results suggest that peripheral neuropathy may be quantified using PV. As CIPN often lowers QOL, it needs to be appropriately evaluated. Future studies with a larger patient cohort and methodological refinements to improve accuracy are warranted.

Dynamics of Serum Inflammatory Markers Predict Survival After Definitive Chemoradiotherapy for Locally Advanced Cervical Cancer

ABSTRACT Aim Cervical cancer is caused by persistent infection with the human papillomavirus. This study aimed to investigate whether the changes in serum inflammatory markers between baseline and posttreatment can predict survival in cervical cancer undergoing definitive chemoradiotherapy (CCRT). Methods Eighty‐one Stage IB–IVA cervical cancer patients treated with definitive CCRT, with serum inflammatory markers obtained at diagnosis and after completion of pre‐planned therapy, were included. The percent changes of post‐/pretreatment levels × 100% were calculated for neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), monocyte‐to‐lymphocyte ratio (MLR), systemic inflammation response index (SIRI), and systemic immune‐inflammation index (SII). The cutoffs were obtained with the maximal chi‐square statistics. Results At a median follow‐up of 28 months, the 2‐year overall survival (OS) was 75.4%. The 2‐year OS for patients with low versus high percent change was as follows: post‐/pre‐NLR (87.7% vs. 67.8%), post‐/pre‐MLR (75.9% vs. 71.1%), post‐/pre‐SIRI (76.5% vs. 61.7%), and post‐/pre‐SII (91.7% vs. 67.2%) (all p < 0.05). The hazard ratios (HR) in multivariate analysis were as follows: post‐/pre‐NLR (5.53, 95% confidence interval [CI]: 1.65–18.52), post‐/pre‐MLR (3.39, 95% CI: 1.39–8.26), post‐/pre‐SIRI (5.11, 95% CI: 1.92–13.57), and post‐/pre‐SII (6.57, 95% CI: 1.77–24.36) (all p < 0.05). Conclusion This study demonstrates the impact of the dynamics of serum inflammatory markers on survival. It has been consistently demonstrated across the markers. To adopt these markers for personalized treatment decisions, a better understanding of their relation with the actual tumor microenvironment is warranted.

Tamoxifen use in recurrent ovarian cancer in a Chinese population: A 15 ‐year clinical experience in a tertiary referral center

AbstractAimTo review the clinical use and the effectiveness of tamoxifen in patients with advanced or recurrent ovarian cancer.MethodsA retrospective review of clinical records was conducted in patients who received tamoxifen for the treatment of ovarian cancer between 2002 and 2016. We reviewed the clinical setting that it was given, duration of use, patients' tolerability, clinical benefit and progression‐free survival. We also attempted to identify predictive markers for response.ResultsA total of 92 patients received tamoxifen during this 15‐year period. The patients received a median of 2.5 lines of chemotherapy before switching to tamoxifen, and they remained on tamoxifen for a median of 5.6 months (range 0–85 months), with 24 patients receiving it for more than 12 months. Seventy‐six patients continued on tamoxifen for more than 2 months. In this group, 75 patients had an evaluable response, either by CA 125 or clinically and clinical benefit rate (defined as complete, partial response and static disease) was seen in 42 patients (56%), with majority of patients having static disease. The median progression‐free survival was 5.3 months (95% confidence interval, 2.6–8.1). Tamoxifen was well tolerated. Hormone receptor status was not demonstrated to predict response.ConclusionPatients with advanced ovarian cancer who have failed previous lines of chemotherapy may achieve static disease with tamoxifen with minimal side effects. Tamoxifen may still have a role in the era of molecular target therapy.

Diagnostic efficacy of combining diffusion‐weighted magnetic resonance imaging with serum Mucin 1, Mucin 13, and Mucin 16 in distinguishing borderline from malignant epithelial ovarian tumors

AbstractAimsTo enhance ovarian tumor diagnosis beyond conventional methods, this study explored combining diffusion‐weighted magnetic resonance imaging (DWI‐MRI) and serum biomarkers (Mucin 1 [MUC1], MUC13, and MUC16) for distinguishing borderline from malignant epithelial ovarian tumors.MethodsA total of 126 patients, including 71 diagnosed with borderline (BEOTs) and 55 with malignant epithelial ovarian tumors (MEOTs), underwent preoperative DWI‐MRI. Region of interest (ROI) was manually drawn along the solid component's boundary of the largest tumor, focusing on areas with potentially the lowest apparent diffusion coefficient (ADC). For entirely cystic tumors, a free‐form ROI enclosed the maximum number of septa while targeting the lowest ADC. Serum biomarkers were determined using enzyme‐linked immunosorbent assay.ResultsBasic morphological traits proved inadequate for malignancy diagnosis, warranting this investigation. BEOTs had an ADC mean of (1.670 ± 0.250) × 103 mm2/s, while MEOTs had a lower ADC mean of (1.332 ± 0.481) × 103 mm2/s, with a sensitivity of 63.6% and specificity of 90.1%. Median MUC1 (167.0 U/mL vs. 87.3 U/mL), MUC13 (12.44 ng/mL vs. 7.77 ng/mL), and MUC16 (180.6 U/mL vs. 36.1 U/mL) levels were higher in MEOTs patients. The biomarker performance was: MUC1, sensitivity 50.9%, specificity 100%; MUC13, sensitivity 56.4%, specificity 78.9%; MUC16, sensitivity 83.64%, specificity 100%. Combining serum biomarkers and ADC mean resulted in a sensitivity of 96.4% and specificity of 100%.ConclusionThe integration of DWI‐MRI with serum biomarkers (MUC1, MUC13, and MUC16) achieves exceptional diagnostic accuracy, offering a powerful tool for the precise differentiation between borderline and malignant epithelial ovarian tumors.

Preoperative serum CA125 level and age at diagnosis: An effective prognosis prediction tool for patients with early‐stage endometrial cancer

AbstractObjectiveTo investigate the combined predictive value of the preoperative serum cancer antigen 125 (CA125) level and age at diagnosis among patients with early‐stage endometrial cancer (EC) after initial treatment.MethodsWe retrospectively analyzed data from patients with early‐stage EC from 1999 to 2015 in multiple institutions in China. All 447 patients received postoperative adjuvant radiotherapy for FIGO 2009 stage I and II EC with complete data on preoperative serum CA125 levels. All patients were divided into four groups according to the ESMO‐ESGO‐ESTRO risk classification. The predictive probability of 5‐year overall survival (OS) and the sensitivity and specificity of CA125 and age were calculated.ResultsThe median follow‐up time was 59 months (3–201 months). The 5‐year OS and disease‐free survival rates were 94.4% and 89.1%. Multivariate analysis showed that the preoperative CA125 level and age at diagnosis were independent prognostic factors for 5‐year OS. The area under the curve for CA125 combined with age at diagnosis for 5‐year OS was .692, and the corresponding sensitivity and specificity were 68.2% and 68.2% (p < .002), which were significantly better than the corresponding values for CA125 or age alone. After all 447 patients were divided into four groups according to CA125 combined with age, the 5‐year OS of the elderly and higher CA125 group was only 73.7%.ConclusionsAlthough preoperative CA125 had limited sensitivity in predicting the prognosis for early‐stage EC after initial treatment, it remains a useful serum marker for risk assessment of early‐stage EC. Combining CA125 with age may increase its predictive sensitivity.

Cost‐effectiveness analysis of human papillomavirus vaccines for the prevention of cervical cancer in India

AbstractBackgroundHuman papillomavirus (HPV) vaccines represent an important strategic opportunity to prevent cervical cancer in low‐middle income countries, such as India. The economic evaluation of HPV vaccines is crucial to inform public‐health decisions; however, the scarce economic evaluations from India have focused on the value for money of bivalent vaccines and took a healthcare perspective. The aim of this study is to conduct a cost‐effectiveness analysis of all available HPV vaccines in India.Material and methodsThe Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model was used to evaluate the cost‐effectiveness of HPV vaccination of 12‐year‐old girls in India, from both healthcare and societal perspectives. Cervical cancer cases, deaths averted and the incremental cost per Disability Adjusted Life Years (DALY) averted were reported as primary outcomes. Sensitivity analysis was undertaken to handle any uncertainty or variability in the results.ResultsCompared with no vaccination, the incremental cost per DALY averted was USD 362.78 for nonavalent vaccine, USD 393.16 for quadrivalent vaccine and USD 432.24 for bivalent vaccine from a healthcare perspective. From a societal perspective, the incremental cost per DALY averted was USD 334.28 for nonavalent vaccine, USD 364.67 for quadrivalent vaccine and USD 403.75 for bivalent vaccine. Assuming constant prices per dose for all vaccines, the nonavalent vaccine dominated both quadrivalent and bivalent vaccines, indicating that it is the more cost‐effective strategy.ConclusionVaccinating girls against HPV is a cost‐effective strategy to reduce the incidence of cervical cancer and mortality due to cervical cancer in India.

Cancer stem cell biomarkers SOX2 and Oct4 in cervical cancer patients undergoing chemoradiotherapy

AbstractBackgroundCancer stem cell biomarkers SRY (sex‐determining region Y)‐box 2 (SOX2) and octamer‐binding transcription factor 4 (Oct4) account for radioresistance in cervical squamous cell cancers (CSCCs). Their clinical implications are limited and contradictory.MethodsIn this prospective cohort study, we recruited patients with FIGO IB2‐IVA CSCC treated with primary chemoradiotherapy on regular follow‐up. Tissue biopsy specimens were evaluated for SOX2 and Oct4 expression by immunohistochemistry, quantified by a product of proportion and intensity scores.ResultsA total of 59 patients were included. Most had a moderately differentiated (81%), keratinizing (59%) CSCC, and ≥FIGO stage IIB disease (95%). SOX2 expression (high:low 21:38 patients) and Oct4 expression (high:low 4:55 patients) had a significant interrelation (p = 0.005, odds ratio (95% CI) − 1.23 (1.004–1.520)). At a median follow‐up of 36 months, the 3‐year overall survival (OS) was 60% and 53% for low and high SOX2 expression (p = 0.856), and 54% and 100% for low and high Oct4 expression (p = 0.114). The 3‐year disease‐frese survival (DFS) was 65% and 50% in the low and high SOX2 expression (p = 0.259), and 59% and 75% for low and high Oct4 expression (p = 0.598). SOX2 expression was the only variable significantly associated with a lower OS and DFS on regression analysis.ConclusionOur study demonstrated a trend toward improved OS and DFS with low SOX2 and high Oct4 expression in CSCC patients undergoing chemoradiotherapy.

Is adjuvant chemotherapy necessary for 2014 FIGO stage IC adult granulosa cell tumor?: Multicentric Turkish study

AbstractAimThe aim of our study is to examine the clinical, surgical, and pathological factors of stage 1C adult granulosa cell tumor (AGCT) patients and to investigate the effects of adjuvant therapy on recurrence and survival rates in this patient group.MethodsOut of a total of 415 AGCT patients treated by 10 tertiary oncology centers participating in the study, 63 (15.2%) patients with 2014 FIGO stage IC constituted the study group. The FIGO 2014 system was used for staging. Patient group who received adjuvant chemotherapy was compared with patient group who did not receive adjuvant chemotherapy in terms of disease‐free survival (DFS), and disease‐specific survival.ResultsThe 5‐year DFS of the study cohort was 89%, and the 10‐year DFS was 85%. Those who received adjuvant chemotherapy and those who did not were similar in terms of clinical, surgical and pathological factors, except for peritoneal cytology. In the univariate analysis, none of the clinical, surgical or pathological factors were significant for DFS. Adjuvant chemotherapy and type of treatment protocol had no impact on DFS.ConclusionAdjuvant chemotherapy was not associated with improved DFS and overall survival in stage IC AGCT. Multicentric and randomized controlled studies are needed for early stage AGCT in order to confirm these results and reach accurate conclusions.

Challenges and opportunities in the implementation of advanced brachytherapy programs for cervical cancer in the Philippines

AbstractCervical cancer is the second most common cancer cause of morbidity and mortality in Filipino women; the age‐standardized annual incidence is 15.2 as of March 2023. The majority are diagnosed at a locally advanced stage and in the reproductive and working age group. This results in important treatment and productivity costs. The importance of image‐guided and interstitial brachytherapy (BRT) in local control and toxicity outcomes has been shown in recent meta‐analyses. We review the status of advanced BRT program training and implementation in the Philippines and important challenges and opportunities to move forward.

Carboplatin and hypomagnesemia: Is it really a problem?

AbstractBackgroundCarboplatin has largely replaced cisplatin in ovarian/peritoneal/tubal cancer (OC) due to comparable activity and reduced toxicity, particularly nephrotoxicity and hypomagnesemia. Anecdotally hypomagnesemia occurs commonly with carboplatin, however there are limited data available regarding frequency or severity.AimsTo quantify incidence and severity of hypomagnesemia in patients receiving carboplatin‐based chemotherapy for OC; to explore a dose‐response relationship with carboplatin and assess potential confounding variables.MethodsA retrospective single‐center review of all OC patients receiving carboplatin‐based chemotherapy as first/subsequent line between 2012 and 2018 was performed. Data on patient/disease characteristics, potential confounders (gastrointestinal/renal impairment, premorbid hypomagnesemia and concomitant medications), dose, electrolytes, and magnesium replacement were collected.ResultsOne hundred four of 144 (72%) patients had at least one hypomagnesemia event, 11 of 104 (11%) grade 2, and 11 of 104 (11%) grade 3/4 in severity. Multivariate analysis showed a significant association between hypomagnesemia and treatment duration (P < .001). Premorbid hypomagnesemia was associated with a significantly longer duration and higher grade of hypomagnesemia (P = .021 and P < .001, respectively). Vomiting, diarrhea, and confounding medications were associated with hypomagnesemia (P = .019 and P = .028, respectively). Fourteen percent of hypomagnesemia events never resolved suggesting a significant cohort post‐carboplatin are at risk of long‐term renal toxicity. The effect of magnesium replacement could not be accurately assessed due to limited documentation of replacement.ConclusionHypomagnesemia is common in patients receiving carboplatin‐based chemotherapy for OC, and although generally mild, a significant minority were severe. Several high‐risk groups were identified including patients with premorbid hypomagnesemia, vomiting, diarrhea, or taking certain medications. Further research is warranted to understand when hypomagnesemia is clinically relevant and determine the impact of interventions.

Safety of AS04‐HPV‐16/18 vaccine in Chinese women aged 26 years and older and long‐term protective effect in women vaccinated at age 18–25 years: A 10‐year follow‐up study

AbstractIntroductionThe pivotal efficacy study assessed efficacy and safety of GSK's AS04‐HPV‐16/18 vaccine in Chinese women aged 18–25 years up to 6 years. The present extension study, performed 4 years later, offered AS04‐HPV‐16/18 vaccination to placebo recipients. Vaccine safety and its long‐term protective effect were assessed at Year 10.MethodsAll 6051 women who received AS04‐HPV‐16/18 or the placebo during the initial study (NCT00779766) were invited to phase III/IV, open‐label, partially controlled extension Year 10 study (NCT03629886). Placebo recipients were offered three‐dose AS04‐HPV‐16/18 vaccination and followed up over 12 months to assess the safety. Cervical samples from all women were examined. Vaccine efficacy (VE) against incident infections and cytological lesions associated with HPV‐16/18 and other oncogenic types was assessed as exploratory objective.ResultsAmong 3537 women (out of 6051) enrolled in the extension study, 1791 women (mean age 32.7 years; standard deviation 1.8 years) received AS04‐HPV‐16/18 and reported no serious adverse events, potential immune‐mediated diseases, or adverse pregnancy outcomes related to vaccination. Among 6051 women, VE against incident HPV‐16, ‐18, and ‐16/18 infections up to Year 10 was 82.8% (95% confidence interval: 72.5–89.7), 79.8% (64.5–89.2), and 80.8% (72.4–87.0), respectively. VE against HPV‐16/18 ASC‐US+, CIN1+, and CIN2+ was 92.7% (82.2–97.7), 94.8% (67.4–99.9), and 90.5% (34.6–99.8), respectively.ConclusionAS04‐HPV‐16/18 vaccine showed an acceptable safety profile in Chinese women vaccinated at age 26 years or above, and a long‐term protection similar to other efficacy trials worldwide.