Tumori Journal

The e-BRAVE study: A prospective web-based cohort and biobank of women carriers of BRCA mutations

Background: Women carriers of BRCA1/2 mutations face a very high lifetime risk (penetrance) of developing breast and/or ovarian cancer. A sizeable proportion of carriers, however, does not develop cancer at all or develop it only late in life, thus suggesting a potential modulation of this risk. Epidemiological studies have suggested that other genetic (polymorphisms) and environmental factors (lifestyle) affect penetrance. However, data regarding these associations mainly come from retrospective case-control analyses and the results are likely to be distorted by bias. Aims: The e-BRAVE (Brca, ReseArch, Virtual, Education) study aims to create a web-based prospective cohort and biological bank of unaffected women carriers of BRCA1/2 mutations to investigate the role of polymorphisms and environmental factors, and their interaction, in the occurrence of primary BRCA-related cancers. Methods: An innovative digital platform (including a mobile App) will be used to empower the synergy between participants and researchers, supporting engagement with women, adherence to intervention plan, self-empowerment, flanked by activities tracking and monitoring. Results: Based on the incidence data in previous studies, we estimate to observe an overall incidence of ~3.7% year. Conclusion: The success of this study will ensure the definition of further predictive risk models and comprehensive recommendations aimed at improving management and health of BRCA women.

Combined dynamic DCE-MRI and diffusion-weighted imaging to evaluate the effect of neoadjuvant chemotherapy in cervical cancer

Purpose: To prospectively investigate changes in quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and the apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) in patients with cervical cancer before and after neoadjuvant chemotherapy (NACT). Methods: Thirty-eight patients with cervical cancer underwent DCE-MRI and DWI 1 week before and 4 weeks after NACT. The patients were classified into 2 groups: significant reaction (sCR) group and the non-sCR group. DCE-MRI parameters and ADC values were measured and compared between the 2 groups. Results: Before NACT, the mean Ktrans value was higher, but the mean Ve was lower, in the sCR group compared with the non-sCR group; these differences were statistically significant ( p<0.05). After NACT, the mean Ktrans value and the delta (i.e., changed) value of Ktrans were significantly lower in the sCR group compared with the non-sCR group ( p<0.05). However, the mean ADC and the delta value of the mean ADC between the 2 groups were slightly higher in the sCR group compared with the non-sCR group ( p<0.05). The area under the curve of pre-mean Ktrans, DKtrans, and pre-mean Ktrans combined with post-mean ADC values were 0.801, 0.955, and 0.878, respectively ( p<0.05). The optimal cutoff values for distinguishing sCR from non-sCR were pretreatment Ktrans (0.7020 min−1) and DKtrans (0.0437 min−1). Conclusions: Quantitative parameters (pre-mean Ktrans, DKtrans, and pre-mean Ktrans) combined with post-mean ADC could predict treatment efficacy more precisely. However, quantitative DCE-MRI combined with DWI could not significantly improve prognostic efficacy.

European Cancer Organisation Essential Requirements for Quality Cancer Care for ovarian cancer: Focus on the multidisciplinary team

European Cancer Organisation Essential Requirements for Quality Cancer Care (ERQCC) are written by experts representing all disciplines involved in cancer care in Europe. They give patients, health professionals, managers and policymakers a guide to essential care. Here, the essential requirements to treat ovarian cancer patients are described. Ovarian cancer patients continue to have low cure rates with wide variation in treatment and care in Europe and beyond. They require complex treatment that should be carried out in specialised ovarian/gynaecological cancer centres by professionals with the appropriate expertise interacting in a multidisciplinary team. Such centralisation is still not well established in many European countries. A patient-centred pathway from diagnosis through treatment to survivorship, managed in dedicated centres, is key to achieving optimal care and a successful clinical outcome.

Prognostic CT findings of malignant bowel obstruction in patients with advanced ovarian cancer

Objective: To evaluate computed tomography (CT) findings able to predict outcome in patients with ovarian cancer (OC) and concomitant bowel occlusion. Methods: This institutional review board–approved retrospective study included 31 patients with OC and clinical evidence of bowel occlusion who underwent CT at presentation between February 2013 and June 2015. Two radiologists recorded various qualitative CT features. Correlations between CT and survival data were made with Mann-Whitney test, Wilcoxon test, and χ2 test, as appropriate. Receiver operating characteristic curves were generated for statistically significant CT findings using logistic regression model. Results: Two of 31 patients (6.5%) were alive at the end of this study; 29 patients (93.5%) died of disease. Median overall survival was 90 days. CT features associated with short life expectancy were bowel mural thinning ( p=0.03), mesenteric tumor deposits ( p=0.009), mesenteric infiltration ( p=0.02), and ascites ( p=0.04). Area under the curve was 0.728 ( p=0.03) for mesenteric tumor deposits in predicting malignant bowel obstruction. Conclusions: Accurate interpretation of CT features may guide decisions in care of women with OC and bowel obstruction.

Treating rare tumors with the assistance of the expert virtual consultation system: two cases of juvenile granulosa cell tumors

Background: The lack of internationally recognized guidelines for very rare tumors, such as juvenile granulosa cell tumors (JGCTs), which are nonepithelial, unusual ovarian tumors, is a challenge for pediatric oncologists, especially in developing countries with limited resources and experience in treating rare tumors. Methods: We report clinical data of 2 girls with JGCTs treated at the Pediatric Cancer and Blood Disorders Center of Armenia with the assistance of the EXPeRT (European Cooperative Study Group for Pediatric Rare Tumors) international cooperation panel. Case presentation: Two girls (16 and 15 years old) with JGCTs of the ovaries, stage Ic, underwent surgery and, with consultation through an online advisory board ( http://vrt.cineca.it/ ), received 4 cycles of chemotherapy according to the PEI regimen (cisplatin, etoposide, ifosfamide). Conclusion: Very rare tumors, especially in advanced stages, have limited data and a low survival rate. International collaboration with the EXPeRT group is beneficial for physicians with limited experience and facilitates research in pediatric oncology.

Granulosa cell ovarian cancer with synchronous multiple bone metastases: case report of extreme rarity

Background: Adult granulosa cell tumor (AGCT) of the ovary generally has a good prognosis. Recurrences tend to be late and confined to the abdominopelvis. Bone metastases are extremely rare. We report an extremely rare case of AGCT with synchronous multiple bone metastases and discuss diagnostic procedures and management. Case description: A 35-year-old woman presented with abdominal bloating. On the day of surgery, acting on the complaint of right shoulder pain, an X-ray revealed a permeative lesion involving the neck of humerus, suggestive of a metastatic pathologic fracture. The patient underwent a full staging debulking surgery. Further imaging demonstrated multiple bone metastases. Histology confirmed an AGCT of the ovary. Diagnosis was established by a core bone biopsy from the left femur showing cells consistent with those seen with granulosa cell tumor. The patient received adjuvant chemotherapy with concurrent zoledronic acid as targeted therapy for her bone metastases. Endocrine systemic maintenance treatment was given. The patient rapidly deteriorated and died from her disease at 20 months from the initial diagnosis. Conclusion: Unpredictable biological behavior and clinical manifestations raise a high degree of suspicion for accurate AGCT diagnosis. Management of bone metastases often warrants input from the multidisciplinary team, and treatment may involve chemotherapy, palliative radiotherapy, or orthopaedic interventions.

Olaparib as a single agent treatment in pre-treated metastatic pancreatic cancer patient harboring BRCA2 mutation: What could we expect?

Background: Despite ongoing developments, pancreatic cancer remains one of the most difficult tumors to treat. Even the most effective chemotherapy regimens, only marginally improve the outcome of Pancreatic cancer patients, which rarely exceeds one year. A small subset of Pancreatic cancer patients, carriers of germline variants of BRCA1/2, are clinically relevant as therapeutic targets in pancreatic cancer, both for the first-line and maintenance therapy, as they are more responsive to platinum-based chemotherapy agents and PARP inhibitors. Though, a little is known about the efficacy of olaparib monotherapy in later lines, or in poor responders to platinum-based regimens. Methods: We describe a case of a patient with pancreatic cancer harboring BRCA2 mutation, treated with radical surgery, adjuvant treatment and three different palliative chemotherapy regimens at disease recurrence (FOLFOX in first line with progression-free survival of five months, gemcitabine and nab-paclitaxel in the second line with progression-free survival of six months and FOLFIRI in the third line with progression-free survival of three months) before olaparib off-label treatment. Results: Interestingly, the patient remained 10 months on olaparib treatment, without disease progression, and without any side effects from the treatment. Conclusion: In conclusion, this case highlights the clinically relevant progression-free survival with olaparib treatment in later line and the potential of better health-related quality of life in this small subset of Pancreatic cancer patients.

HPV nonrelated endocervical adenocarcinoma in hereditary cancer syndromes

Introduction: The relationship between endocervical cancer and cancer susceptibility syndromes is not yet fully understood. We present 2 cases of endocervical cancer: 1 arising in a patient carrier with a pathogenic BRCA1 variant and the second detected in a Lynch syndrome family carrying the MSH2 germline pathogenic variant. Case description: Somatic analyses including loss of heterozygosity and fluorescent in situ hybridization demonstrated that the second hit in patient 1 is BRCA1-related. Mismatch repair somatic analyses in the second family demonstrated that the endocervical cancers of patient 2 and of her sister are MSH2-related. These data confirm the relationship between the pathogenesis of endocervical cancer and the presence of germline BRCA1 and MSH2 mutations. Conclusions: Our study confirms that gynecologic cancers including rare entities such as non–human papillomavirus–related endocervical cancer (NHPVA) are sentinels for inherited cancer syndromes. Endocervical cancer NHPVAs might be considered for cancer genetic counseling in order to improve cancer prevention. For this reason, the role of pathologists is particularly important for the correct identification of the cervical tumor site.

Correlations of UICC tumor stage and tumor regression on T2-weighted MRI sequences during definitive radiotherapy of cervical cancer

Background: The purpose of this study is to detect a correlation between the preradiation tumor staging and the relative volumetric regression of the primary tumor through external beam radiation therapy (EBRT). Methods: Clinical data of 32 patients with a mean age of 60±12 years treated with primary radiation therapy (RT) of cervical carcinoma were analyzed. Union Internationale Contre le Cancer (UICC) stages were T1 = 4 patients, T2 = 15 patients, T3 = 8 patients, T4 = 5 patients; N1 = 26 patients, N0 = 6 patients; and M0 = 25 patients, M1 = 7 patients. All patients received pelvic magnetic resonance imaging (MRI) before RT as well as during RT. The cervical primary tumor was delineated as gross tumor volume (ptGTV) in T2-weighted MRI sequences. We compared ptGTV reduction by stage, lymph node status, metastatic status, and grading. Results: Mean ptGTV reduction during RT was 61.4±28.9%. T1 tumors shrank by 88.2±13.4%, T2 by 67.6±28.7%, T3 by 50.8±23.6%, and T4 by 38.7±27.2%. The difference in tumor shrinkage was statistically significant between the lower T stages and the higher T stages ( p < 0.05). There was no statistical difference in the mean ptGTV before treatment in the group with lymph node metastases (LNM) (54.1±47.7 cm3) as compared to the group without LNM (76.6±52.2 cm3). Nonetheless, ptGTV shrank significantly differently: by 68.9±25.7% (N1 patients) and by 29.0±17.7% (N0 patients). No significant differences in ptGTV shrinkage were observed in M0 versus M1 and G2 versus G3 tumors. Conclusion: There is a correlation between mean ptGTV reduction during EBRT and tumor stages. Tumors with higher T stages shrank less under radiation treatment, and the ptGTV of N1 patients responded better than that of N0 patients.

Primary leiomyosarcoma of the uterine cervix: report of 4 cases, systematic review, and meta-analysis

Background: Primary cervical leiomyosarcomas (CLMS) constitute 21% of all cervical sarcomas. Because of their rarity, to our knowledge, fewer than 40 cases have been reported. The aim of this study is to evaluate the clinical and surgical–pathological features, prognosis, treatment options, and survival of primary CLMS. Methods: A systematic review of the medical literature was conducted to evaluate articles about primary CLMS. The literature was searched between 1959 and May 2019. On final evaluation, there were 29 articles (one consisted of 8 cases; one consisted of 3 cases) and 42 cases with the addition of our 4 cases. Results: Age (⩾48 versus ⩽47 years) (hazard ratio.HR], 4.528; 95% confidence interval.CI], 1.550–13.227; p=0.006) and mitoses count (<10/10 high-power field [HPF] versus ⩾10/10 HPF) (HR, 3.865; 95% CI, 1.046–14.278; p=0.043) are independent prognostic factors for recurrence and age (HR, 5.318; 95% CI, 1.671–16.920; p=0.005) and hysterectomy (performed versus not performed) (HR, 4.377; 95% CI, 1.341–14.283; p=0.014) are independent prognostic factors for death because of disease on multivariate analysis. Conclusions: Information on primary CLMS is sparse and obtained from rare case reports and case series. Hysterectomy must be the first choice of treatment in these patients according to our results on multivariate analysis. The type of hysterectomy does not have an effect on oncologic outcome. Radical hysterectomy is not obligatory and more data are needed to make more accurate conclusions.

Low Tesla magnetic resonance guided radiotherapy for locally advanced cervical cancer: first clinical experience

Objective: Magnetic resonance–guided radiotherapy (MRgRT) represents an innovative approach for personalized radiotherapy treatments and its applications are being explored in various anatomical sites to fully understand its potential advantages. This study describes the first clinical experience of MRgRT application in patients with locally advanced cervical cancer (LACC) undergoing neoadjuvant chemoradiotherapy. The feasibility of the technique is evaluated and its toxicity profile and clinical outcomes are reported. Methods: Patients with LACC (International Federation of Gynecology and Obstetrics stage IIA–IVA) undergoing neoadjuvant chemoradiotherapy (CRT) on a 0.35T Tri-60-Co hybrid unit (ViewRay) were retrospectively compared with randomly selected patients treated with a standard linear accelerator. Total prescribed dose was 50.6 Gy (2.3 Gy/fraction) to planning target volume 1 (PTV1) and 39.6 Gy (1.8 Gy/fraction) to PTV2, delivered using a simultaneous integrated boost. Surgery was performed 8 weeks after the end of CRT. The effect of magnetic resonance guidance on replanning approaches, treatment-related toxicities, and pathologic response were assessed for each patient. Patient outcomes were noted and dosimetric comparisons performed between the 2 arms. Results: Nine patients with LACC treated from May 2018 to November 2018 were retrospectively enrolled and their records compared with the records of an equivalent cohort of randomly selected patients. Five replanning cases were performed in the MRgRT group and 0 in the linear accelerator group. Acute G1–G2 gastrointestinal toxicities were observed in 33.3% of MRgRT patients and in 55.5% of linear accelerator patients; acute G1–G2 genitourinary toxicities in 22.2% and 33.3%, respectively. No G3 toxicity was found except for neutropenia in 2 patients. No differences were observed in pathologic response between the 2 groups. Conclusions: Despite the retrospective nature of the observations and the low number of enrolled patients, the application of MRgRT in LACC appears to be safe and feasible with a favorable toxicity profile and response rates comparable to gold standard, supporting the setup of larger prospective studies to investigate the potentialities of this new technology.

Management of primary and recurrent Bartholin’s gland carcinoma: A systematic review on behalf of MITO Rare Cancer Group

Bartholin gland carcinoma is an extremely rare disease. Information regarding treatment is scarce and there is no strict consensus on best practice. All studies reporting cases of Bartholin’s gland cancer were screened and evaluated for inclusion. Baseline characteristics of studies were extracted. A total number of 290 manuscripts collected were available for the review process. Studies included in a previous systematic review were not duplicated. In total, details of 367 patients were collected, as follows: histological features, clinical presentation, treatment, recurrent rate, treatment of recurrence and outcome. About 35% of Bartholin gland carcinoma were squamous cell carcinoma. Almost 50% of patients presented with advanced stage. The therapeutic approach was mainly surgery, and in 61% of those women lymph node assessment was performed. Recurrence occurred in 21% of cases. Bartholin gland cancer remains a challenge for gynecologic oncologists. Guidelines, centralization to referral centers and standardized therapy are needed.

Neoadjuvant chemotherapy followed by radical surgery in locally advanced vulvar carcinoma: a single-institution experience

Background: Squamous cell carcinoma of the vulva is a rare malignancy that affects elderly women. About one-third of vulvar cancers are diagnosed in an advanced stage, requiring extensive surgery. Neoadjuvant chemotherapy (NACT) has been introduced to reduce local tumor burden. In this retrospective study, we analyze the efficacy and toxicity of NACT followed by radical surgery. Methods: Patients with locally advanced vulvar cancer (LAVC) treated at our institution with neoadjuvant platinum and paclitaxel-based chemotherapy ± ifosfamide followed by surgery at our institution were retrospectively identified. Results: Fourteen patients (93%) completed NACT with tolerable toxicities (G3–G4 toxicity: 30%). Thirteen patients (87%) underwent surgery. The overall clinical response rate on vulvar disease was 66% (20% complete response, 46% partial response), confirmed by histopathologic analysis, while on inguinal lymph nodes it was 69% (23% complete response, 46% partial response). At the pathologic examination, all patients had negative surgical margins. Three out of 9 patients (33%) with lesions infiltrating the urethral meatus and 4 patients out of 7 (57%) with anal involvement did not require urethral amputation or colostomy, respectively, after NACT. No severe postoperative complications were described. Overall survival at 5 years was 60%, and median overall survival was 76 months. Conclusion: NACT followed by surgery in locally advanced vulvar cancer is well tolerated and allows surgical modulation.

Chemo-surgical approach in vulvar leiomyosarcoma: A case report

Introduction: Primary sarcoma of the vulva is an extremely rare entity, representing only 1%–3% of all vulvar malignant neoplasms. Among sarcomas, leiomyosarcoma (LMS) is the most prevalent histologic variant. Due to the rarity of LMS, guidelines are lacking and phase III trials have not been carried out, so clinical management is based on local clinical practice and physician experience. Case presentation: Here, we described a case of primary LMS of the vulva and its successful management, with the adoption of neoadjuvant chemotherapy and surgery. We report a case of a 74-year-old woman with 12.5 cm vulvar LMS. The patient received three cycles of neoadjuvant chemotherapy with a partial response. Radical vulvectomy with vulvar reconstruction with V-F flap was carried out. Surgical margins were negative. Three additional cycles of adjuvant chemotherapy were delivered. Results: One year after treatment, the patient was disease-free. Conclusion: There are no approved therapeutic protocols for this rare neoplasia. Surgery is the mainstay of treatment. However, it is not always feasible, so neoadjuvant chemotherapy was delivered for downstaging the vulvar lesion. We suppose that neoadjuvant chemotherapy has optimized the possibilities of radical surgery. Despite the anectodical nature of this case presentation, neoadjuvant chemotherapy seems a valid therapeutic option for managing patients with bulky vulvar sarcoma. Further large collaborative studies are warranted to identify the best therapeutic option for these patients.

MRI-based radiomics: promise for locally advanced cervical cancer treated with a tailored integrated therapeutic approach

Objective: To assess prognostic factors by analyzing clinical and radiomic data of patients with locally advanced cervical cancer (LACC) treated with definitive concurrent cisplatin-based chemoradiotherapy (CCRT) using magnetic resonance imaging (MRI). Methods: We analyzed radiomic features from MRI in 60 women with FIGO (International Federation of Gynecology and Obstetrics) stage IB2–IVA cervical cancer who underwent definitive CCRT 45–50.4 Gy (in 25–28 fractions). Thirty-nine (65.0%) received EBRT sequential boost (4–20 Gy) on primary tumor site and 56 (93.3%) received high-dose-rate brachytherapy boost (6–28 Gy) (daily fractions of 5–7 Gy). Moreover, 71.7% of patients received dose-dense neoadjuvant chemotherapy for 6 cycles. The gross tumor volume was defined on T2-weighted sequences and 29 features were extracted from each MRI performed before and after CCRT, using dedicated software, and their prognostic value was correlated with clinical information. Results: In univariate analysis, age ⩾60 years and FIGO stage IB2–IIB had significantly better progression-free survival (PFS) ( p = 0.022 and p = 0.009, respectively). There was a trend for significance for worse overall survival (OS) in patients with positive nodes ( p = 0.062). In multivariate analysis, only age ⩾60 years and FIGO stage IB2–IIB reached significantly better PFS ( p = 0.020 and p = 0.053, respectively). In radiomic dataset, in multivariate analysis, pregray level p75 was significantly associated with PFS ( p = 0.047), pre-D3D value with OS ( p = 0.049), and preinformation measure of correlation value with local control ( p = 0.031). Conclusion: The combination of clinical and radiomics features can provide information to predict behavior and prognosis of LACC and to make more accurate treatment decisions.

The distinct experience of supportive care needs among cervical cancer patients: A qualitative study

Introduction: Patients with cervical cancer report experiencing physical, psychological, economic, and social problems daily. An exploration of supportive care needs is important for patients and their families to cope with diagnosis, treatment, recovery or even death. Objective: This study explores the perceived supportive care needs of Nepali patients with cervical cancer who are undergoing cancer treatment. Methods: A descriptive qualitative research design was utilized with semi-structured interviews to probe patients with cervical cancer’s supportive care needs. The study was conducted at a cancer-specific hospital in Nepal. Purposive sampling was used to recruit 30 patients with cervical cancer. Qualitative thematic analysis techniques were employed to identify the supportive care needs of Nepalese patients with cervical cancer. Results: Supportive care needs were identified with five main themes and sixteen sub-themes: 1) psychological trauma (regret on delaying medical consultation, fear of disease, death and dying, ambivalence about the future and treatment, feeling of loss, caring/rearing of children, feeling and burden to partner/family); 2) financial distress (loss of income and challenges with treatment costs); 3) sexual disharmony; 4) physical dependency on others for day-to-day care and; 5) hunger for information (cause of disease, prognosis of disease, dietary counseling, and information on sexuality). Conclusion: Recognizing the supportive care needs of patients with cervical cancer during treatment by health care professional and family members is vital to facilitate optimal care at the hospital and home for overall improvement in the patient’s quality of life. Acknowledgment that the expensive treatment regime creates an economic and psychological burden for the patients.

BYL719 (alpelisib) for the treatment of PIK3CA-mutated, recurrent/advanced cervical cancer

Purpose: Advanced/recurrent cervical cancer has limited therapeutic options, with a median progression-free survival after the failure of systemic treatments ranging between 3.5 and 4.5 months. Here, we reported our preliminary experience in the use of BYL719 (alpelisib) in advanced/recurrent cervical cancer after failure of at least 2 lines of treatment. The Istituto Nazionale dei Tumori di Milano approved this investigation. Methods: From April 2020 to September 2020, 17 consecutive patients with recurrent cervical cancer had Next Generation Sequencing (NGS). Of these, six patients harboring the PIK3CA mutation were included in the study. All patients had been treated with at least 2 previous lines of systemic treatment: 3 patients received >2 prior lines of treatment in the recurrent or metastatic setting; 60% had received prior bevacizumab in combination with chemotherapy. All patients started alpelisib at the daily dosage of 300 mg. Results: Investigator-assessed confirmed objective response rate (ORR) was 33%. The disease control rate (DCR) was 100%. According to RECIST 1.1, two patients had a partial response (PR), and four patients had stable disease (SD). No complete response was observed. The mean duration of response (DOR) was 11.5 (SD 3.75) months; five patients had PR lasting for >9 months. One patient stopped the treatment at 0.82 months due to the onset of a grade 2 adverse event (AE) (skin rash). Grade 3 treatment-related AEs included: lymphoedema (n = 1, 17%) and rash (n = 1, 17%). No treatment-related grade 4-5 AEs occurred. Conclusions: Our preliminary data highlighted a high level of efficacy in this setting of patients. Further trials are needed to assess the safety and effectiveness of alpelisib in PIK3CA-mutated recurrent/advanced cervical cancer.

Letrozole for hormone receptor–positive low-grade ovarian cancer: Preliminary toxicity results of a phase III trial

Background: Epidemiological and retrospective studies suggest that letrozole may improve outcomes in low-grade serous carcinoma of the ovary (LGSCO) by targeting estrogen-driven tumor progression. Methods: We designed a multicenter, randomized, open-label, phase III trial to compare letrozole versus standard chemotherapy (carboplatin plus paclitaxel) in prolonging progression-free survival (PFS). Secondary endpoints include overall survival (OS), objective response rate (ORR), quality of life (MENQoL), and musculoskeletal pain (BPI-SF). Translational objectives explore mutational and expression profiles (NGS, RAD51/BRCA1 foci) and circulating tumor DNA (ctDNA) as markers of treatment response. Eligible patients are postmenopausal women with stage III–IV ER/PgR-positive LGSCO after primary cytoreductive surgery. Patients are randomized 1:1 to letrozole 2.5 mg daily until progression or unacceptable toxicity, or to carboplatin-paclitaxel for 6–8 cycles. Disease progression is assessed by RECIST, CA-125, and imaging every 3–6 months. Results: As of March 2025, 46 patients have been randomized (23 per arm). Preliminary analysis shows a favorable safety profile for letrozole compared with chemotherapy. Conclusions: Early findings suggest letrozole is well tolerated and may represent a viable therapeutic option for hormone receptor-positive LGSCO. Ongoing molecular and clinical analyses will clarify its role in this rare subtype. Trial registration: ClinicalTrials.gov Identifier: NCT05601700; https://clinicaltrials.gov/study/NCT05601700

Prevalence of breast cancer in ovarian cancer patients and its impact on patient survival: An analysis of the surveillance, epidemiology, and end results data

Background: Patients with high-grade serous ovarian carcinoma (HGSOC) often have a personal and/or family history of breast cancers. However, the clinical association and underlying molecular interaction between breast cancer and HGSOC is not well understood. In this study, the clinical characteristics and outcomes of HGSOC patients with or without breast cancer were compared. Methods: Eligible patient information was extracted from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier and Cox proportional hazards regression models were used to determine survival outcomes and prognostic factors. Results: A total of 3065 HGSOC (ICD-O-3 code 8461/3) patients were identified from 1975 to 2020, among whom 239 (9.56%) had co-existing breast cancers. HGSOC with breast cancers tended to have more stage I-II ovarian cancer (20.92% vs 13.79%), less metastatic diseases (25.1% vs 32.13%) and had a higher probability of undergoing surgery (94.1% vs 87.9%). The overall survival of HGSOC patients with breast cancer was better than that of patients without breast cancer (HR = 0.77, 95% CI 0.65 to 0.91; P = 0.0015). Further, patients who developed ovarian cancer before breast cancer had better overall survival than those who developed breast cancer before or simultaneously with ovarian cancer (HR = 0.35, 95% CI 0.23 to 0.52; P < 0.001). Conclusion: HGSOC combined with breast cancer is a common phenomenon. HGSOC patients with breast cancer, especially those diagnosed with ovarian cancer before breast cancer have a better prognosis. Further validation is warranted and more genetic and mechanistical study is needed.

Abdominal specimen retrieval in endometrial cancer patients with large uteri

Objective: Endometrial cancer surgery has a low risk of specimen fragmentation, but removing large uteri can be challenging. This study aimed to assess whether the use of minilaparotomic incision for specimen retrieval compromises the benefits of minimally invasive surgery in endometrial cancer patients with a large uterus or utero-vaginal discrepancy. Methods: This is a retrospective multi-institutional study, including endometrial cancer patients with FIGO 2009 clinical stage I–II, undergoing minimally invasive staging surgery (laparoscopic or robot-assisted) followed by minilaparotomic specimen retrieval. A propensity-matched algorithm was used to compare outcomes of minimally invasive staging with open surgery. Results: The study included 45 propensity-matched pairs (90 patients): 45 underwent minimally invasive staging with minilaparotomic specimen retrieval and 45 underwent open staging. Patients undergoing minimally invasive surgery plus trans-abdominal specimen retrieval experienced longer median operative time (95 vs. 85 minutes; p=0.0017), lower blood loss (50 vs. 100 ml; p<0.001), and shorter length of hospital stay (3 vs. 5 days; p<0.001) in comparison to patients undergoing open surgery. No intraoperative complication occurred. No intraoperative transfusions were administered in both cohorts. No statistically significant differences in complications rates were registered between groups (p=0.266). No differences in term of disease-free (p=0.833, log-rank test) and overall (p=0.723, log-rank test) survival was noted between groups. Conclusions: Transabdominal specimen retrieval does not reduce the benefits of minimally invasive staging in endometrial cancer with large uteri or utero-vaginal disproportion. Uterine size is not a limitation for minimally invasive surgery. Further studies are needed to confirm these results and define the optimal approach.

Is a tailored strategy using proton beam radiotherapy for reirradiation advantageous for elderly women? A case report

Background: The management of primary or recurrent vaginal tumours in an aging population is challenging for gynecologic and radiation oncologists. In patients unsuited for surgery and already irradiated on the pelvis, proton beam radiotherapy may be worthwhile due to its ballistic advantages. Case report: We report the case of an 80-year-old woman with a squamous cell carcinoma of the vagina after a history of pelvic radiation and vaginal brachytherapy delivered for a previous endometrial adenocarcinoma. She received proton beam radiotherapy with a complete response after 12 months and mild toxicity. Conclusions: The complexity of reirradiation management in the frail and elderly population requires attention. Efforts should be focused on maintaining autonomy and quality of life in order to improve adherence and clinical compliance to the treatment. In the era of the tailored approach, hadrontherapy can play an important role to minimize toxicity, obtain good local control, and reduce the overall treatment time.

Clinicopathological characteristics and prognosis of cervical adenocarcinoma across diverse histological subtypes

Objective: To investigate the clinical features and prognostic implications of different subtypes of cervical adenocarcinoma. Methods: We examined 13,353 adenocarcinoma (AC) cases from the SEER database to identify distinct clinical characteristics and prognostic factors among various histological subtypes. Using the WHO classification and International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3) codes, we categorized patients and assessed overall survival (OS) and cancer-specific survival (CSS) via Kaplan-Meier and Cox regression analyses. A nomogram was constructed to predict patient survival across subtypes. Results: Patients with non-usual type show a significantly poorer prognosis. Our analysis revealed that serous carcinoma patients had the most adverse outcomes (OS: hazard ratio (HR) = 2.69, 95% confidence interval (CI): 2.23-3.23, P < 0.001; CSS: HR = 1.78, 95% CI: 1.34-2.36, P < 0.001), while villous adenocarcinoma patients had the most favorable (OS: HR = 0.43, 95% CI: 0.29-0.65, P < 0.001; CSS: HR = 0.32, 95% CI: 0.17-0.60, P < 0.001), compared to the usual type. Multivariable Cox regression identified age, marital status, race, tumor grade, FIGO stage, and treatment as independent prognostic factors. In patients with serous carcinoma, advanced FIGO stage was a risk factor (stage IV vs stage I: HR = 4.06, 95% CI: 1.35-12.22, P = 0.013), and surgery was a protective factor (HR = 0.22, 95% CI: 0.10-0.49, P < 0.001). We also created a prognostic model incorporating diverse histological subtypes, internally validated for high predictive accuracy and discrimination via the receiver operating characteristic (ROC) curve and calibration plots. Conclusion: Clinical characteristics and prognostic features in cervical adenocarcinoma vary significantly by histological subtype, with serous carcinoma being associated with the worst outcomes.

Expectant management or conization for persistent low-grade cervical intraepithelial neoplasia: Analysis of 5-year outcomes

Objective: To investigate to describe outcomes of conization or expectant management for women with persistent (>24 months) low-grade cervical intra-epithelial neoplasia. Methods: This is a retrospective analysis focusing on five-year outcomes after persistent, histologically confirmed, low-grade cervical intra-epithelial neoplasia undergoing conization or expectant management. Results: Charts of 219 women with persistent low-grade cervical lesions were retrieved. Overall, 98 (44.7%) and 121 (55.3%) women had conization and observation, respectively. Patients receiving conization were older than patients having observation (43 (range, 24-77) vs. 39 (range, 25-68) years; p=0.013). Focusing on the group of patients receiving conization, 16 (16.3%) women were diagnosed with CIN2+. The five-year risk of secondary conization was 5% (n=5). Focusing on patients having observation (n=121), 18 (14.8%) patients received conization, after a median of 16.5 (range, 6-30) months. Seven (5.8%) and 11 (9.1%) patients were diagnosed with persistent CIN1 and CIN2+, respectively. Not fully visible squamous-columnar junction at colposcopic examination (p=0.035) was associated with CIN2+ occurrence. No invasive cancer was observed Conclusions: Conization for persistent low-grade cervical intra-epithelial neoplasia revealed “occult” CIN2+ in 16% of patients. However, expectant management appears safe and effective in this context, in women with fully visible squamous columnar junction. The decision between conization and expectant management should be discussed on an individual basis.

18F-FDG PET/CT guided salvage radiotherapy strategies for lymph-nodal relapses in gynecological cancers: SBRT vs ENRT

Objective: To identify outcome differences between extended nodal radiotherapy (ENRT) with simultaneous integrated boost (SIB) and stereotactic body radiotherapy (SBRT), performed with advanced radiotherapy techniques, both of which were 18F-Fluoro-Deoxy-Glucose (FDG) PET/CT guided, for lymph-node (LN) relapses of gynecological tumors, and to identify the most important determining factors. Methods: Records of gynecologic patients treated in a single-institution with FDG PET/CT guided intensity-modulated radiotherapy (IMRT), image-guided radiotherapy (IGRT), or SBRT, were reviewed, and only patients at first salvage radiotherapy for LN relapses were considered. Local relapse-free- (LRFS), regional relapse-free- (RRFS), distant metastasis-free- (DMFS), disease-free-(DFS) and overall-survival (OS), as well as acute and late toxicity (with CTCAE v5.0 score), were determined. Results: Fifty-eight patients (23 ENRT+SIB; 35 SBRT) treated for 178 LNs from February 2007-April 2023, were identified. Median biological equivalent dose (BED10) delivered to PET-positive LNs was 76.5 Gy (Interquartile range-IQR- 74.4;78.7) for ENRT, and 72 Gy (IQR 59.5;75.6) for SBRT. Median follow-up was 81.1(IQR 48.5; 117.2) and 37.0 (IQR 21.3; 58.4) months for ENRT and SBRT, respectively. Thirty-six-month estimated LRFS was 90.2% for ENRT and 82.6% for SBRT; RRFS was 69% and 63.4%, DMFS 26.1% and 44.3%, and OS 73.7% and 60.4%; no statistically significant differences were found between the two groups (logrank test, p= 0.29). ENRT recorded more acute (p⩽0.033), but not late, toxicities. Conclusions: ENRT+SIB and SBRT for gynecological LN tumor relapses obtain similar results in terms of disease-free and OS, with fair toxicity. Prospective studies with higher patient numbers are needed.

HPV-related lesions after hysterectomy for high-grade cervical intraepithelial neoplasia and early-stage cervical cancer: A focus on the potential role of vaccination

Objective: To date, no data supports the execution of vaccination after hysterectomy for high-grade cervical intraepithelial neoplasia (CIN2+) and early-stage cervical cancer. We aim to evaluate the potential effect of vaccination after hysterectomy for high-grade cervical intraepithelial neoplasia and early-stage cervical cancer. Methods: This is a multi-center retrospective study evaluating data of women who develop lower genital tract dysplasia (including anal, vulvar and vaginal intra-epithelial neoplasia) after having hysterectomy for CIN2+ and FIGO stage IA1- IB1 cervical cancer. Results: Overall, charts for 77 patients who developed lower genital tract dysplasia were collected. The study population included 62 (80.5%) and 15 (19.5%) patients with CIN2+ and early-stage cervical cancer, respectively. The median (range) time between hysterectomy and diagnosis of develop lower genital tract dysplasia was 38 (range, 14-62) months. HPV types covered by the nonavalent HPV vaccination would potentially cover 94.8% of the development of lower genital tract dysplasia. Restricting the analysis to the 18 patients with available HPV data at the time of hysterectomy, the beneficial effect of nonvalent vaccination was 89%. However, considering that patients with persistent HPV types (with the same HPV types at the time of hysterectomy and who developed lower genital tract dysplasia) would not benefit from vaccination, we estimated the potential protective effect of vaccination to be 67% (12 out of 18 patients; four patients had a persistent infection for the same HPV type(s)). Conclusions: Our retrospective analysis supported the adoption of HPV vaccination in patients having treatment for HPV-related disease. Even in the absence of the uterine cervix, HPV vaccination would protect against develop lower genital tract dysplasia. Further prospective studies have to confirm our preliminary research.

Prescribing pattern of anticoagulants in patients with cancer associated thrombosis: Results of a survey among MITO group and AIOM society

Introduction: Low molecular weight heparin (LMWH) has been the backbone of the treatment of cancer associated thrombosis (CAT). Direct-acting oral anticoagulants (DOACs) have shown efficacy and safety not inferior to LMWH and guidelines included DOACs as an option for CAT treatment. Nevertheless, DOACs are still poorly prescribed in patients with cancer. The aim of this survey was to better understand prescription patterns of anticoagulants, in particular of DOACs, especially in gynecological cancers (GCs). Methods: Our survey was made up of 21 questions, the last four questions addressed to medical doctors (MDs) involved in GCs. An invitation to complete the survey was sent by e-mail to 691 MITO (Multicentre Italian Trials in Ovarian cancer and gynaecologic malignancies) and 2093 AIOM (Associazione Italiana di Oncologia Medica) members. Results: Overall, 113 MDs completed the questionnaire, 69 involved in GCs. Most respondents (46, 41%) were aged 30-40 years old, worked in public hospitals (59, 52.2%), were medical oncologists (86, 76.1%). LMWH was the preferred choice for the treatment of CAT (104, 92%). However, 89 respondents (78.8%) prescribed or asked to prescribe a DOAC for CAT. The major concern about DOACs was the difficulty in verifying the therapeutic effect and the absence of antidotes in case of bleeding (37.9%). In patients with GCs, DOACs were used with niraparib, olaparib, rucaparib and immune checkpoint inhibitors (ICIs) in less than 10 patients by 23%, 20%, 9% and 10.2% of respondents, respectively. Conclusion: The responders are aware of the Direct-acting oral anticoagulants option and would like to use them

Management of ovarian cancer: guidelines of the Italian Medical Oncology Association (AIOM)

Introduction: Ovarian cancer is the most lethal gynecologic malignancy. Over 5200 new cases of this tumor are diagnosed yearly in Italy, resulting in more than 3600 deaths. In terms of molecular biology, five different ovarian cancer subtypes should be distinguished. Method: This article summarizes the evidence-based guidelines that the Italian Medical Oncology Association (AIOM) has developed with a multidisciplinary panel of experts, including pathologists, gynecologic oncologists, medical oncologists, and radiotherapists, with the support of methodologists, to help clinicians involved in the management of patients with ovarian cancer in their daily clinical practice. Results: The most relevant randomized clinical trials regarding surgery, chemotherapy, and molecularly targeted agents (bevacizumab and PARP inhibitors) in early, advanced, and recurrent disease have been critically analyzed. The levels of evidence and strength of recommendation have been reported for any issue. Conclusion: Women with a clinical suspicion of ovarian cancer should be centralized in referral centers. The BRCA test should be requested for all women with nonmucinous and nonborderline tumors, regardless of age and family history. BRCA testing could be preferentially performed on neoplastic tissue. In the presence of a positive tumor test, a genetic test should always be performed on a blood sample to differentiate between germline mutations, which require counseling and genetic testing of family members, and somatic mutations.

Pulmonary and pleural metastasis mimicking COVID-19 infection in stage IV ovarian cancer: a case report

Background: The differential diagnosis of lung and pleural metastases and coronavirus disease 2019 (COVID-19) can be challenging. Case: We report a case of a 41-year-old woman with FIGO (International Federation of Gynecology and Obstetrics) stage IV ovarian cancer with pleural and pulmonary spread. After primary cytoreduction was performed, she developed a high fever and worsening dyspnea with desaturation (92% in ambient air). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was suspected, but three swabs gave negative results. Computed tomographic scan showed radiologic imaging strongly suspect for COVID-19 and the patient was transferred to a COVID-19 ward. The final diagnosis was paraneoplastic fever. Conclusion: Lung and pleural metastases can mimic SARS-CoV-2 infection.

Long-term palliation of lymph node oligometastatic ovarian carcinoma after repeated stereotactic body radiotherapy: case report

Introduction: Oligometastatic disease has emerged as an intermediate state between localized and systemic cancer. Improvements in diagnostic modalities such as functional imaging allow a greater frequency of oligometastases diagnosis. Patients with selected oligometastatic epithelial ovarian carcinoma (EOC) may be treated with metastasis-directed stereotactic body radiotherapy (SBRT) rather than chemotherapy. Case description: We describe a 58-year-old woman who underwent surgery and chemotherapy for an EOC. The patient underwent 3 chemotherapy lines for recurrence of disease, but had allergic reactions and serious hematologic toxicity. During follow-up, lymph node oligometastases were diagnosed and treated with repeated SBRT because the patient refused further chemotherapy. No side effects were observed after each course of SBRT and the patient obtained complete response of all irradiated sites. Conclusions: SBRT is a promising treatment approach for recurrent oligometastatic EOC with a high control rate and irrelevant iatrogenic toxicity. The possibility to repeat SBRT courses when new oligometastases are encountered in other sites resulted in an adequate long-term palliation approach.

Ovarian metastasis from malignant pleural mesothelioma

Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive disease of the pleura with a dismal prognosis. Distant metastases most commonly occur in the liver, spleen, and thyroid gland. To our knowledge, ovarian metastases have never been described. Case description: We describe a case of a woman with recurrent malignant pleural mesothelioma presenting a single ovarian metastasis, surgically resected. Conclusions: This case report highlights the importance of using a complete staging protocol in patients with MPM to improve patient management. A whole-body computed tomography (CT) scan with contrast enhancement and possibly positron emission tomography–CT should be performed to identify any distant metastases before deciding on treatment strategy.

Vaginal cancer treated with curative radiotherapy with or without concomitant chemotherapy: oncologic outcomes and prognostic factors

Background: Vaginal cancer is a rare disease for which prospective randomized trials do not exist. We aimed to assess survival outcomes, patterns of recurrence, prognostic factors, and toxicity in the curative treatment using image-guided radiotherapy (RT). Methods: In this retrospective review, we identified 53 patients who were treated at a single center with external beam radiotherapy and brachytherapy with or without concomitant chemotherapy from 2000 to 2021. Results: With a median follow-up of 64.5 months, the Kaplan-Meier 2-, 5-, and 7-year overall survival (OS) was found to be 74.8%, 62.8%, and 58.9%, respectively. Local and distant control were 67.8%, 65.0%, and 65.0% and 74.4%, 62.6%, and 62.6% at 2, 5, and 7 years, respectively. In univariate Cox proportional hazards ratio analysis, OS was significantly correlated to FIGO stage (hazard ratio [HR] 1.78, p = 0.042), postoperative RT (HR 0.41, p = 0.044), and concomitant chemotherapy (HR 0.31, p = 0.009). Local control rates were superior when an equivalent dose in 2-Gy fractions (EQD2) of ⩾65 Gy was delivered (HR 0.216, p = 0.028) and with the use of concurrent chemotherapy (HR 0.248, p = 0.011). Not surprisingly, local control was inferior for patients with a higher TNM stage (HR 3.303, p = 0.027). Minimal toxicity was observed with no patients having documentation of high-grade toxicity (CTCAE grade 3+). Conclusion: In treatment of vaginal cancer, high-dose RT in combination with brachytherapy is well tolerated and results in effective local control rates, which significantly improve with an EQD2(α/β=10) ⩾65 Gy. Multivariate analyses revealed concomitant chemotherapy was a positive prognostic factor for overall and progression-free survival.

A case series of non-small cell lung cancer patients with EGFR or HER2 exon 20 insertion in Li Fraumeni syndrome

Introduction: Germline pathogenic mutations in TP53 gene are associated with a cancer predisposition syndrome known as Li Fraumeni syndrome. Albeit infrequently, non-small cell lung cancer, especially as oncogene-addicted disease, may be diagnosed in young patients with Li Fraumeni syndrome. Case description: We report three cases of patients affected by Li Fraumeni syndrome who developed non-small cell lung cancer with EGFR or HER2 exon 20 insertions. The first patient suffered from liposarcoma and, then, brain metastases from HER2-mutated non-small cell lung cancer: after stereotactic radiotherapy, he benefited from enrollment in a clinical trial with a HER2-targeted therapy. The second young patient was a female with personal history of rhabdomyosarcoma, diagnosed with brain metastases from EGFR-mutated non-small cell lung cancer: enrollment in a clinical trial led to a temporary clinical benefit. The last case was a female diagnosed with breast carcinoma, ovarian granulosa cell tumor and advanced EGFR-mutated non-small cell lung cancer at a young age. Conclusions: Young patients affected by oncogene-addicted non-small cell lung cancer and with a positive familial cancer history should be referred for an accurate genetic counselling to look for Li Fraumeni syndrome. The underlying molecular connection between TP53 and HER family receptor tyrosine kinases remains unclear, but an extensive molecular characterization of tumors from patients with Li Fraumeni syndrome should always be performed, to offer patients a personalized therapeutic approach.