Tube Carcinoma Research Articles

Prognostic Significance of Chemotherapy Response Score in Patients Undergoing Interval Debulking Surgery and Attained Complete Cytoreduction for High-Grade Serous Tubal and Ovarian Carcinoma

Objectives The chemotherapy response score (CRS) has been described to assess the pathological response to chemotherapy in patients with high-grade serous tubal and ovarian carcinoma. The main aim of this study was to assess the prognostic significance of CRS in patients who underwent interval debulking surgery and attained complete cytoreduction. Materials and Methods A retrospective study was conducted on patients with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage IIIC and IV high-grade serous tubal and ovarian carcinomas who had undergone surgery after three to four cycles of neoadjuvant chemotherapy and attained complete cytoreduction from January 2015 to July 2018. Results A total of 125 patients were included in the study. The median age of the patients was 52 years. There were 21 patients (16.8%) with a CRS of 1, 53 patients (42.4%) with a CRS of 2, and 51 (40.8%) patients with a CRS of 3. The median follow-up period was 77 months. The CRS applied on the omental samples showed significant correlation with progression-free survival (PFS; CRS of 1 vs. 2: median PFS, 17 vs. 22 months; hazard ratio, 1.73; and CRS of 2 vs. 3: median PFS, 22 vs. 54 months; hazard ratio, 2.32) and overall survival (OS; CRS of 1 vs. 2: median OS, 19 vs. 40 months; hazard ratio, 2.13; CRS of 2 vs. 3: median OS, 40 months vs. not reached; hazard ratio, 2.19). Conclusion Our study confirms that the omental CRS is significantly associated with PFS and OS in patients who attained complete cytoreduction during interval debulking surgery.

Vitamin D Significantly Inhibits Carcinogenesis in the Mogp-TAg Mouse Model of Fallopian Tube Ovarian Cancer.

Epidemiological and observational studies suggest that vitamin D has potential for the chemoprevention of ovarian cancer. The anticancer effect of vitamin D in the fallopian tube epithelium (FTE), which is now thought to harbor the precursor cells for high grade ovarian cancer, is not known. The purpose of this study was to investigate whether vitamin D can inhibit carcinogenesis in the mogp-TAg fallopian tube (FT) ovarian cancer mouse model and examine underlying mechanisms. To test this hypothesis, 3 groups of 40 5-week-old female mogp-TAg mice were divided equally into two cohorts of 20 mice, treated with either vehicle (vitamin D solvent) or the active 1,25(OH)2D3 analogue EB1089, delivered via mini-pump or IP injection or cholecalciferol delivered in the feed. The FTs were characterized histologically and pathologically after 3 and 7 weeks of treatment. The effect of vitamin D on cultured human FTE cells was also examined. After 3 weeks, vitamin D, delivered as either cholecalciferol or EB1089 significantly inhibited FT carcinogenesis. After 7 weeks, cholecalciferol significantly reduced p53 signatures, serous tubal epithelial carcinoma, FT cancer, and plasma CA125 while increasing apoptosis in the FTE. EB1089 had no significant effect on FT carcinogenesis at 7 weeks. Cholecalciferol significantly reduced proliferation and increased apoptosis in vitro in p53-altered FTE cells. In conclusion, vitamin D inhibited FT carcinogenesis by clearing cells with p53 alterations. These data suggest that vitamin D has merit for the chemoprevention of fallopian tube/ovarian cancer. The optimal chemopreventive effect may be dependent on the route of vitamin D administration.

Unusual Pattern of Spread of High-Grade Serous Fallopian Tubal Carcinoma in a Woman with BRCA1 Gene Mutation

A 40-year-old woman presented with chronic watery vaginal discharge for one-month and right pelvic pain radiating to the right flank for 2 weeks. Physical and pelvic examination revealed a right pelvic mass. Computerized tomography and magnetic resonance of whole abdomen revealed a 6-cm of heterogeneous mass at the right adnexa and a larger mass of 8-cm with internal cystic portions compressing on the inferior vena cava. Her serum cancer antigen (CA) 125 elevated to 540 U/ml. Surgical intervention revealed a right fallopian tube mass with an intact serosal surface, several enlarged pelvic and para-aortic nodes, and a bulky precaval node. No gross peritoneal nor other organ invasion was found. Complete surgical staging was performed by gynecologic oncologists and a surgeon, resulting in optimal surgery. Pathology revealed high-grade serous carcinoma of the right fallopian tube with metastasis to all resected nodes and a positive peritoneal cytology. Subsequent blood testing showed BReast CAncer (BRCA) 1 gene mutation. Adjuvant therapy with paclitaxel/carboplatin/bevacizumab was given for six cycles. Maintenance therapy with bevacizumab/olaparib, and periodic surveillance for other cancers, including breast magnetic resonance imaging were planned. This case presented an unusual pattern fallopian tubal cancer spread to a large precaval lymph node which was bulkier than the primary tumor. A thorough pre-operative evaluation and a surgical team specialized in cancer surgery are crucial for successful surgical management. Appropriate adjuvant treatment and follow-up for a woman with BRCA mutation were also to be emphasized.

Tubal Cancer Clinical Management: Two Exceptional Scenarios and a Review of the Literature.

This article provides a literature review on tubal carcinoma to offer an updated insight into its preventative strategies, diagnosis, treatment and oncological surveillance. In addition to the search string utilized, the authors' focus extended to key scientific studies, consensus statements, guidelines and relevant case reports essential for the proper clinical management of the disease, providing a methodologically well-structured literature review combined with practical expertise in the oncological field. This article also includes two special clinical cases that emphasize the importance of understanding the physiopathology and the current state of the art in the anatomopathological advancements in tubal/ovarian/peritoneal carcinoma, often assimilated into a single clinical entity and to which many of the concepts extracted from the literature can apply.

The impact of Paclitaxel-based hyperthermic intraperitoneal chemotherapy in advanced high-grade serous ovarian cancer patients - interim analysis of safety and immediate efficacy of a randomized control trial (C-HOC trial)

ObjectiveThis study evaluates the potential superiority of combining paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) with sequential intravenous neoadjuvant chemotherapy over intravenous neoadjuvant chemotherapy alone in Chinese patients with Federation of Gynecology and Obstetrics (FIGO) stage IIIC, IVA and IVB high-grade serous ovarian/fallopian tube carcinoma (HGSOC). This interim analysis focuses on the safety and immediate efficacy of both regimens to determine the feasibility of the planned trial (C-HOC Trial).MethodsIn a single-center, open-label, randomized control trial, FIGO stage IIIC, IVA, and IVB HGSOC patients (FAGOTTI score ≥ 8 during laparoscopic exploration) unsuitable for optimal cytoreduction in primary debulking surgery (PDS) were randomized 2:1 during laparoscopic exploration. The Experiment Group (HIPEC Group) received one cycle of intraperitoneal neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (paclitaxel) followed by three cycles of intravenous chemotherapy (paclitaxel plus carboplatin), while the Control Group received only three cycles of intravenous chemotherapy. Both groups subsequently underwent interval debulking surgery (IDS). The adverse effects of chemotherapy, postoperative complications, and pathological chemotherapy response scores (CRS) after IDS were compared.ResultsAmong 65 enrolled patients, 39 HIPEC Group and 21 Control Group patients underwent IDS. Grade 3–4 chemotherapy-related adverse effects were primarily hematological with no significant differences between the two groups. The HIPEC Group exhibited a higher proportion of CRS 3 (20.5% vs. 4.8%; P = 0.000). R0 resection rates in IDS were 69.2% (HIPEC Group) and 66.7% (Control Group). R2 resection occurred in 2.6% (HIPEC Group) and 14.3% (Control Group) cases. No reoperations or postoperative deaths were reported, and complications were managed conservatively.ConclusionsCombining HIPEC with IV NACT in treating ovarian cancer demonstrated safety and feasibility, with no increased chemotherapy-related adverse effects or postoperative complications. HIPEC improved tumor response to neoadjuvant chemotherapy, potentially enhancing progression-free survival (PFS). However, the final overall survival results are pending, determining if HIPEC combined with IV NACT is superior to IV NACT alone.

Diagnosis Shift in Site of Origin of Tubo-Ovarian Carcinoma.

To assess population-level trends, characteristics, and outcomes of high-grade serous tubo-ovarian carcinoma in the United States. This retrospective cohort study queried the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population was 27,811 patients diagnosed with high-grade serous tubo-ovarian carcinoma from 2004 to 2020. The exposure was the primary cancer site (ovary or fallopian tube). Main outcome measures were temporal trends, clinical characteristics, and overall survival associated with primary cancer site assessed in multivariable analysis. The study population comprised 23,967 diagnoses of high-grade serous ovarian carcinoma and 3,844 diagnoses of high-grade serous fallopian tubal carcinoma. The proportion of diagnoses of high-grade serous fallopian tubal carcinoma increased from 365 of 7,305 (5.0%) in 2004-2008 to 1,742 of 6,663 (26.1%) in 2017-2020. This increase was independent in a multivariable analysis (adjusted odds ratio [aOR] vs 2004-2008, 2.28 [95% CI, 1.98-2.62], 3.27 [95% CI, 2.86-3.74], and 6.65 [95% CI, 5.84-7.57] for 2009-2012, 2013-2016, and 2017-2020, respectively). This increase in high-grade serous fallopian tubal carcinoma was seen across age groups (4.3-5.8% to 22.7-28.3%) and across racial and ethnic groups (4.1-6.0% to 21.9-27.5%) (all P for trend <.001). Among the cases of tumors smaller than 1.5 cm, the increase was particularly high (16.9-67.6%, P for trend <.001). Primary-site tumors in the high-grade serous fallopian tubal carcinoma group were more likely to be smaller than 1.5 cm (aOR 8.26, 95% CI, 7.35-9.28) and unilateral (aOR 7.22, 95% CI, 6.54-7.96) compared with those in high-grade serous ovarian carcinoma. At the cohort level, the diagnosis shift to high-grade serous fallopian tubal carcinoma was associated with narrowing differences in survival over time between the two malignancy groups: adjusted hazard ratio 0.84 (95% CI, 0.74-0.96), 0.91 (95% CI, 0.82-1.01), 1.01 (95% CI, 0.92-1.12), and 1.12 (95% CI, 0.98-1.29) for 2004-2008, 2009-2012, 2013-2016, and 2017-2020, respectively. This population-based assessment suggests that diagnoses of high-grade serous tubo-ovarian carcinoma in the United States have been rapidly shifting from high-grade serous ovarian to fallopian tubal carcinoma in recent years, particularly in cases of smaller, unilateral tumors.

A Perplexing Case of Genito-urinary Tuberculosis in an 83-Year-Old Woman with Increased Levels of Tumor Markers: A Case Report

Background: Tuberculosis (TB) is a significant global health problem, and extrapulmonary TB can present with no specific clinical or radiographic findings. Genito-urinary TB is often associated with elevated tumor markers and can be misdiagnosed as ovarian/fallopian tube carcinomas, especially in elderly female patients, as genitourinary TB commonly affects women of reproductive age. Objective: We present a rare case of genito-urinary TB in an elderly female patient who was initially misdiagnosed with ovarian cancer with metastasis. Case presentation: An 83-year-old woman with a medical history of diabetes and hypertension presented with complaints of abdominal distension. Diagnostic imaging revealed lesions in the ovaries and omentum and tumor markers were elevated, leading to a suspicion of ovarian cancer with metastases to the omentum. The patient underwent a diagnostic laparotomy and surgical removal of ovaries, fallopian tubes, and the lesion of the greater omentum. However, no malignancy was found during the morphological evaluation. Further histopathological examination confirmed the final diagnosis of genito-urinary tuberculosis, and the patient received anti-TB drugs. The postoperative period was uneventful, and tumor marker levels decreased. Conclusion: As the clinical presentation of genito-urinary TB can mimic ovarian cancer, a histopathological examination should be performed for differential diagnosis, thereby reducing the possibility of inaccurate treatment. This case report highlights the importance of considering genito-urinary TB as a differential diagnosis in elderly female patients presenting with elevated tumor markers, abdominal distension, and suspected genital malignancy. It is crucial to carefully evaluate these cases and explore the possibility of genital TB as an alternative diagnosis, given the overlapping clinical presentation. This highlights the importance of a comprehensive diagnostic approach that includes considering TB in addition to malignancy, even in the context of elderly female patients.

Application of genetic counseling and preventive surgery in hereditary breast-ovarian cancer syndrome based on a rare family

Objective: To investigate the genetic, clinical and pathological characteristics of families with hereditary breast-ovarian cancer syndrome (HBOCS) and to explore the implementation of genetic counseling and preventive surgery. Methods: Four siblings with HBOCS in Cancer Hospital/Chinese Academy of Medical Sciences were selected as the study subjects. BRCA gene testing and genetic counseling were performed, family history was traced and family map was drawn. Results: There were 7 cancer patients (Ⅰ 2, Ⅱ 4, Ⅱ 8, Ⅲ 7, Ⅲ 10, Ⅲ 11, Ⅲ 12) in three generations in the family. One patient (Ⅲ 7) had breast cancer and ovarian cancer successively. The first generation (Ⅰ 2) developed cancer at age 60, the second generation (Ⅱ4 and Ⅱ8) developed cancer at 55. The third generation (Ⅲ 7, Ⅲ 10, Ⅲ 11, Ⅲ 12) developed cancer at the age of 42-50 years. Four HBOCS patients were treated in our hospital, and all of them were found to have deleterious BRCA1 mutation. Two had already developed ovarian cancer (Ⅲ 10, Ⅲ 12), while in one case (Ⅲ 11), tubal carcinoma was found during preventive total hysterectomy and pelvic lymph node metastasis was found after the supplementary staging surgery. The other patient without cancer underwent preventive bilateral salpingectomy(Ⅲ 15). Conclusion: The HBOCS family reported in this study is relatively rare, the onset time of tumor was younger generation by generation. It is very important to pay attention to the genetic counseling of ovarian cancer patients and to timely detect the HBOCS families for genetic testing and prophylactic surgery.

Trends in gynecologic oncology before and during COVID - 19 pandemic in Tuzla Canton

Aim: The aim of this study was to assess the impact of the COVID-19 pandemic and its management on the rate of newly diagnosed cancers from the perspective of a tertiary referral center in Tuzla Canton.Methods: All patients diagnosed with gynecological cancer at Department of Gynecology and Obstetrics, University Clinical Center Tuzla, in prepandemic, pandemic and postpandemic period, were presented in this study. Gynecological cancer was defined as one of the following diagnoses: ovarian or tubal carcinoma, cervical carcinoma, endometrial carcinoma, uterine sarcoma, vulvar carcinoma, vaginal carcinoma, and germ cell tumors.A total of 579 patients with newly diagnosed cancers were collected in 2020. There were 109 newly diagnosed gynecological cancers in 2020., while in 2019 there were 134, and 136 in 2021. Numbers of gynecological cancers diagnosed during pandemic were compared to numbers in prepandemic and postpandemic period. Results: There was a total of 579 patients with newly diagnosed cancer in Clinical Center of Tuzla during 2020. That showes strong decline of newly diagnosed cancers compared to 2019 with 1030 newly diagnosed cancers. Of these 579 patients, 109 presented in 2020 with newly diagnosed gynecological cancers. That shows strong decrease compared to 2019. with 134 newly diagnosed gynecological cancers and 2021 with 136 gynecological cancers. In 2019. 4015 PAP tests were examined, with only 1917 PAP tests examined in 2020 (diagram 4). In 2019. we did 199 HPV typisation test, while in 2020. there were only 34.Conclusion: The lockdown coused by COVID - 19 pandemic led to decreased number of routine examinations including annual PAP smear testing and HPV typisation tests. It also led to decrease number of other checkups. All of that led to decreased number of newly diagnosed gynecological cancers.

Apendektomi sonrası tesadüfen teşhis edilen tubal yüksek dereceli seröz karsinom olgu sunumu

Primary tubal carcinoma is a uncommon tumor of female ganitale system. The clinical approach of primary tubal cancers is similar to primary ovarian cancers. Fallopian tube carcinoma is hard to diagnosed preoperatively because of its uncertain symptoms. Providing optimal cytoreductive surgery is the most important treatment step in ovarian, tubal and peritoneal carcinomas.&#x0D; We report a case of serous tubal intraepithelial carcinoma and appendix metastasis. A 65 years old post-menopausal woman (gravida 4, para 3) submitted to an external hospital with lower abdominal pain and acute abdominal symptoms. Appendectomy was performed on the patient with preliminary diagnosis of appenditis. The pathology result was reported as high grade serous carcinoma infiltration. Staging surgery was performed with the diagnosis of carcinoma. Until the final pathology result, the diagnosis was considered as appendiceal metastasis of serous tubal cancer. Our clinical and surgical approach to the case, which was diagnosed incidentally with an appendectomy specimen and reported as high grade tubal serous carcinoma, is presented as a case study.

Risk-Reducing Salpingectomy And Other Strategies For Prevention Of Ovarian And Tubal Carcinoma

Objective: To provide a review of most current evidence and data for risk-reducing strategies used in prevention of ovarian cancer. Methods of study selection: PubMed was used as a search tool for articles with key words focusing on current strategies on prevention of ovarian cancer such as “risk-reducing salpingectomy, “risk-reducing salpingo-oophorectomy, “salpingectomy with delayed oophorectomy”. General consensus and society guidelines from leading organizations such as Society of Gynecologic Oncology, American Cancer Society, and American College of Obstetricians and Gynecologists were reviewed and summarized in this review article with supporting evidence and research studies on most current riskreduction strategies for prevention of ovarian and tubal carcinoma. Result: There is growing evidence that high-grade serous ovarian carcinoma arises in the fallopian tube in the form of serous tubal intraepithelial carcinoma (STIC). Therefore, opportunistic salpingectomy has been increasingly offered at the time of routine benign gynecologic surgery. Risk-reducing bilateral salpingo-oophorectomy has been shown to reduce risk of ovarian cancer up to 90% and offered to women with high hereditary predisposition for ovarian cancer. Riskreducing salpingectomy with delayed oophorectomy (SDO) has been suggested in younger women to balance the effects of infertility and surgically induced menopause resulting from oophorectomy. Conclusion: Combined oral Contraceptive COCs confer long-term protection against ovarian cancer with reported 20% reduction for every 5 years of use, which have been cited as a confounding factor in most of the published studies. Women who used HRT (estrogen alone or combined estrogen and progesterone) carry 20% higher risk of ovarian cancer compared to never-users. The associated increased risk of cervical and breast cancer with COCs/HTR use, have recently let women prefer the RRSO over COCs for prevention of ovarian cancer. Bilateral risk reducing Salpingo-oophorectomy (RRSO) at the age of 40–45 in BRCA1 and 45–50 in BRCA2 mutation carriers is recommended to be the primary approach for risk reduction of ovarian cancer. There is well-supported evidence of lowering the risk of ovarian cancer in high-risk population by 90%. The American college of obstetrics and gynecology committee opinion, recommended opportunistic salpingectomy for the primary prevention of ovarian cancer in a woman already undergoing pelvic surgery for another indication. Bilateral salpingectomy at the time of cesarean delivery is recommended to replace the tubal ligation as the method of choice for sterilization performed with cesarean delivery. The novel alternative procedure of Risk-reducing Salpingectomy with delayed risk-reducing oophorectomy (RRSO-RRO) have growing attention as a better alternative to improve the menopause-related morbidity and quality of life.

Prophylactic Radical Fimbriectomy with Delayed Oophorectomy in Women with a High Risk of Developing an Ovarian Carcinoma: Results of a Prospective National Pilot Study.

Risk-reducing salpingo-oophorectomy is the gold standard for the prophylaxis of ovarian cancer in high-risk women. Due to significant adverse effects, 20-30% of women delay or refuse early oophorectomy. This prospective pilot study (NCT01608074) aimed to assess the efficacy of radical fimbriectomy followed by a delayed oophorectomy in preventing ovarian and pelvic invasive cancer (the primary endpoint) and to evaluate the safety of both procedures. The key eligibility criteria were pre-menopausal women ≥35 years with a high risk of ovarian cancer who refused a risk-reducing salpingo-oophorectomy. All the surgical specimens were subjected to the SEE-FIM protocol. From January 2012 to October 2014, 121 patients underwent RF, with 51 in an ambulatory setting. Occult neoplasia was found in two cases, with one tubal high-grade serous ovarian carcinoma. Two patients experienced grade 1 intraoperative complications. No early or delayed grade ≥3 post-operative complications occurred. After 7.3 years of median follow-up, no cases of pelvic invasive cancer have been noted. Three of the fifty-two patients developed de novo breast cancer. One BRCA1-mutated woman delivered twins safely. Twenty-five patients underwent menopause, including fifteen who had received chemotherapy for breast cancer, and twenty-three underwent menopause before the delayed oophorectomy, while two did not undergo a delayed oophorectomy at all. Overall, 46 women underwent a delayed oophorectomy. No abnormalities were found in any delayed oophorectomy specimens. Radical fimbriectomy followed by delayed oophorectomy appears to be a safe and well-tolerated risk-reducing approach, which avoids early menopause for patients with a high risk of breast and ovarian cancer.

Patterns of palliative care referral in platinum resistant ovarian cancer demonstrate reactive rather than proactive approach

ObjectiveTo evaluate patterns of palliative care (PC) integration in patients with platinum resistant ovarian cancer. MethodsSingle institution retrospective study of patients with ovarian, tubal, or peritoneal high-grade carcinoma treated 2011–2020. Platinum resistance was identified by chemotherapy regimen or provider definition. Data was extracted evaluating treatment regimens, time to progression, PC and hospice referrals, and survival. Descriptive statistics and survival analyses were performed. ResultsWe identified 258 patients with platinum resistant ovarian cancer. Median survival from diagnosis of platinum resistance was 15 months (range 0–161). Most (71 %) patients were referred to PC, with 43 % of referrals within 3 months of death. Fourteen percent of patients were referred directly to hospice without PC involvement. Of 46 patients living with platinum resistant disease, 93 % meet criteria for early PC referral, but less than half have seen PC. Median time from platinum resistance to PC referral was 9 months (range 0–157) and from PC referral to death was 3 months (range 0–110). Median time from platinum resistance to hospice referral was 7 months (range 1–57) and from hospice referral to death was < 1 month (range 0–12). ConclusionWhile rates of PC referral in our cohort are high compared with other single institution cohorts, timing of PC referral suggests referral patterns that are reactive to clinical decline rather than proactive as per national recommendations. A significant percentage of patients are directly referred to hospice for end-of-life care, reflecting missed opportunity for concurrent PC and oncology care earlier in the disease course. Diagnosis of platinum resistance should serve as a stimulus for PC involvement.

OBESITY AND GYNECOLOGICAL MALIGNANCIES: A MULTI-CENTRIC CROSS SECTIONAL STUDY

Introduction: Obesity is a growing problem and has signicant implications for a variety of diseases, including human cancers. Obesity has now become an epidemic so is the increase of gynecological malignancies in this era. So we review the association of obesity and gynecological malignancies like breast, endometrial, cervical, ovarian, tubal and Vulvo-vaginal carcinoma as an independent etiological risk factor. ToAims and objectives: estimate the prevalence of overweight and obese female in western Indian population. To nd the association of different gynecological malignancies and obesity. To evaluate the effect of obesity on different gynecological malignancies in accordance with age, reproductive life and socioeconomic status A cross sectional study in western. Materials and methods: Indian states Gujarat, Maharashtra and Rajasthan from January 2019 to December 2021, 10245 sample size and with overweight and obese post menarchal women up to 70 years of age with BMI &gt;25 kg/m2 were compared to matched controls. All the consented subjects were initially screened by questionnaire by eld worker and examined for routine and advanced screening and examinations like Manual Palpation of breast, per abdomen, per speculum per vaginal examination and Pap smear by certied professionals according to standard protocols. Investigation was performed when required like mammography, Ultrasonography and laboratory investigations. Positive association of breast and endometrialResults: carcinoma especially in postmenopausal women and cervical carcinoma. Weak positive association for ovarian carcinoma only in premenopausal woman (not statistically signicant). We do not nd enough cases to conclude anything for vulvo vaginal and tubal carcinoma. Growing epidemic of obesity can be statistically correlated with increasingConclusion: incidence of gynecological malignancies like breast, endometrial, ovarian and cervical. Large scale studies further needed for evaluation of correlation of vulvo vaginal and tubal carcinomas.

ENGOT-ov65/KEYNOTE-B96: Phase 3, randomized, double-blind study of pembrolizumab versus placebo plus paclitaxel with optional bevacizumab for platinum-resistant recurrent ovarian cancer.

TPS5617 Background: Despite therapeutic advances in ovarian cancer, platinum-resistant recurrent ovarian cancer (PROC) remains an area of high unmet clinical need and there is an urgent need for new treatments to further improve clinical outcomes. Addition of bevacizumab to non-platinum-based chemotherapy significantly improved PFS in patients with PROC but did not show a clear OS benefit. Thus far, the combination of paclitaxel and bevacizumab has shown the most promise in treatment of PROC, although the proportion of patients eligible for bevacizumab is limited by treatment-associated toxicities. Combination of the anti-PD-1 antibody pembrolizumab with weekly paclitaxel showed antitumor activity and manageable toxicity in patients with PROC in a single-arm, phase 2 study (Wenham Int J Gynecol Cancer 2018). The current study ENGOT-ov65/KEYNOTE-B96 (NCT05116189) compares the efficacy and safety of the addition of pembrolizumab to standard of care chemotherapy (weekly paclitaxel) with/without bevacizumab vs placebo plus weekly paclitaxel with/without bevacizumab in patients with PROC. Methods: In this randomized, placebo-controlled, double-blind, phase 3 study, eligible patients are aged ≥18 y with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with 1-2 prior lines of systemic therapy, including at least 1 prior platinum-based therapy with ≥4 cycles in first line. Patients must have platinum-resistant disease (radiographic evidence of PD ≤6 mo after last platinum-based therapy dose), be eligible for paclitaxel (with/without bevacizumab per investigator discretion), have ECOG PS ≤1, radiographically evaluable disease per RECIST v1.1, and have a tumor sample for central evaluation of PD-L1 status. Approximately 616 patients will be randomized 1:1 to receive pembrolizumab 400 mg IV or placebo Q6W for up to 18 cycles (̃2 y) plus paclitaxel 80 mg/m2 on days 1, 8, and 15 of each Q3W cycle (with/without bevacizumab 10 mg/kg Q2W per investigator discretion) until PD or unacceptable toxicity. Randomization is stratified by planned bevacizumab use (yes vs no), region (US vs Europe vs rest of world), and PD-L1 status (combined positive score [CPS] &lt; 1 vs CPS 1- &lt; 10 vs CPS ≥10). Tumor PD-L1 status is determined using the PD-L1 IHC 22C3 pharmDx (Investigational Use Only) diagnostic kit. Tumor imaging is performed Q9W from randomization to week 54 and Q12W thereafter. The primary endpoint is PFS per RECIST version 1.1 by investigator review in patients with tumor PD-L1 CPS ≥1 and in all patients. Secondary endpoints are OS in patients with tumor PD-L1 CPS ≥1 and in all patients, PFS per RECIST version 1.1 by blinded independent central review in patients with tumor PD-L1 CPS ≥1 and in all patients, safety, and patient-reported outcomes. Enrollment is ongoing. Clinical trial information: NCT05116189.

Improved survival after implementation of ultra-radical surgery in advanced epithelial ovarian cancer: Results from a tertiary referral center

ObjectiveTo compare survival rates of surgically treated advanced epithelial ovarian cancer patients before and after a programmatic change in surgical approach from standard surgery towards ultra-radical surgery. Methods247 patients with FIGO stage IIIB-IV ovarian, tubal, and primary peritoneal carcinoma were operated during 2013–2019 either by primary or interval cytoreduction in Tampere University Hospital, Finland. Group 1 (n = 122) patients were operated during 2013 and February 2016. Group 2 patients (n = 125) were operated between March 2016 and March 2019, when a systematic change in surgical approach towards more extensive surgery was implemented. ResultsThe complete resection (R0) rate increased significantly from 17.2% (21/122) to 52.0% (65/125) within the study period (p < 0.001). The median progression-free survival (PFS) was 15.6 months vs 19.3 months (p = 0.037), and the median overall survival (OS) was 33.5 months vs 54.5 months in Groups 1 and 2, respectively (p = 0.028). Median OS for stage III patients in Group 1 was 36.1 months (95% CI 27.4–44.8) but could not be reached in Group 2 (p = 0.009). In Stage IV patients, OS was 32.0 months (16.4–47.7) and 39.3 months (24.8–53.8) in Group 1 and 2, respectively (p = 0.691). Multivariable Cox regression analysis revealed that OS was independently affected by the amount of residual tumor and complication grade. ConclusionsThe change of surgical approach towards maximal surgical effort improved both progression-free and overall survival. The survival benefit was unquestionable for stage III patients but did not reach statistical significance in stage IV patients.

Assessing frequency and clinical outcomes of BRCA mutated ovarian cancer in Saudi women

PurposeBRCA gene mutations (BRCAm) have an impact on patients’ characteristics and clinical outcomes of ovarian cancer (OC). The frequency and patterns of BRCAm vary among countries and ethnicities. There are limited data from Saudi Arabia (SA); thus, this study aims to determine the frequency, pattern, and impact on patient characteristics and outcomes of BRCAm OC compared to wild-type BRCA (BRCAw) in Saudi women.MethodsThis retrospective study evaluated women diagnosed with non-mucinous OC, fallopian tube, or peritoneal carcinoma who had BRCA status tested in an accredited lab between January 2016 and December 2017. The associations between various parameters and BRCAm were estimated using logistic regression. Statistical analysis performed with SPSS (Version 27).ResultSixty-one women with a median age of 52 at diagnosis were analyzed. Germline BRCA mutations were found in 41% of cases (25/61). The most common deleterious germline BRCA1 mutation was c.1140dupG (39%). Most women (72%) had no family history of cancers and 82% had advanced stage. Regardless of BRCA mutations, an optimal overall response rate (ORR) to first-line treatment has been achieved although most cases relapsed (84%) and the majority were platinum-sensitive relapse (85%). Higher ORR to subsequent lines and better survival were obtained in women with BRCA-mutation.ConclusionThe prevalence of BRCAm of OC was higher in Saudi women compared to regional and most of the international figures. The better clinical outcomes of BRCAm women agreed with the reported evidence. Further studies on BRCA mutations of OC and genetic counseling are highly recommended.Trial registrationTrial approved by the Institutional Review Board of King Faisal Specialist Hospital and Research Center (RAC # 2171137) and conducted at King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh 11,211, Saudi Arabia.

Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A\u2009>\u2009T: a case report

BackgroundRAD51D (RAD51 paralog D) is an intermediate cancer susceptibility gene for primary ovarian cancer, including fallopian tube and peritoneal carcinomas and breast cancer. Although gynecological non-epithelial tumors such as uterine sarcomas are associated with genomic instability, including BRCA impairment, there is no clear evidence of the relationship between RAD51D variants and the risk of sarcoma development.Case presentationA Japanese woman in her 50s underwent multiple surgical resections and several regimens of chemotherapy for tumors that originated in the retroperitoneum and recurred in the peritoneum over a clinical course of approximately 4 years. The peritoneal tumor was histologically diagnosed as a leiomyosarcoma and was genetically identified to show a splice variant of RAD51D c.904-2A > T [NM_002878] through tumor profiling performed as a part of cancer precision medicine. The confirmatory genetic test performed after genetic counseling revealed that the RAD51D splicing variant detected in her tumor was of germline origin. In silico analyses supported the possible pathogenicity of the detected splice variant of RAD51D with a predicted attenuation in mRNA transcription and truncated protein production due to frameshifting, which was attributed to a single-nucleotide alteration in the splicing acceptor site at the 3′-end of intron 9 of RAD51D. Considering her unfavorable clinical outcome, which showed a highly aggressive phenotype of leiomyosarcoma with altered RAD51D, this case provided novel evidence for the relationship of a RAD51D splicing variant with malignant tumor development or progression. We report the findings of this rare case with possible involvement of the germline variant of RAD51D c.904-2A > T as a potential predisposing factor for malignant tumors, including leiomyosarcoma.ConclusionsWe present the findings of a case of leiomyosarcoma in the peritoneum of a female patient with a novel germline splicing variant of RAD51D as potential evidence for the pathogenicity of the variant and its involvement in the risk of sarcoma etiology and/or development. To the best of our knowledge, this is the first case report describing a leiomyosarcoma carrying a germline RAD51D splicing variant and elucidating its pathogenicity on the basis of computational prediction of the impairment of normal transcription and the presumed loss of functional protein production.

Metachronous carcinoma of the gastric tube following tumour-associated oesophagectomy.

The prognosis of oesophageal carcinoma has improved during the last years. Thereby, the increasing survival has led to increasing occurrence of secondary gastric tube carcinoma (gastric conduit cancer, GTC) following oesophageal tumour resection. A literature review (EMBASE, PubMed), spanning the years 2000 to 2020, identified 342 patients worldwide with a GTC following tumour-related oesophagectomy, of which 306 patients could be included for further analysis. The median age of 306 patients with GTC was 66.4 (39-80) years. 91.2% of patients (n = 279) were male. The median interval between oesophagectomy and GTC was 60.3 (4-236) months. 73.8% of patients (n = 226) were diagnosed as early cancer (EGC, T1) and 26.2% as advanced carcinoma (AGC, > T2; n = 80). Primary oesophagectomy was performed in 97.4% of patients (N = 298) for squamous cell carcinoma. AEG I carcinoma was present in only 5 patients (1.6%). In contrast, 99% (n = 303) of the GTC were found to be adenocarcinomas. One hundred eighty patients (58.8%) could be treated by endoscopic resection (ER). R0 resection was achieved in 82.8% (n = 149). The complication rate was 13.3% (n = 24) and the 30-day mortality 1.1% (n = 2) for ER. Eighty-three patients (27.1%) were treated surgically. These included 13 wedge resections, 25 partial resections and 45 total gastric graft resections with predominantly colon interposition. The R0 rate was 98.8% (n = 82). The postoperative morbidity was 24.1% (n = 20); the 90-day mortality was 6% (n = 5). In 43 patients (14%), palliative chemotherapy or radiotherapy or best supportive care took place. GTC diagnosed early in the EGC stage can be safely managed with ER. In cases of advanced GTC, surgical resection can be a potentially curative approach. Survival times of up to 120months have been described after intervention for GTC.

Dual germline and somatic testing in women with high-grade epithelial ovarian, tubal, and peritoneal cancer: a prospective systemic quality improvement initiative

<h3>Objectives:</h3> Germline and somatic genetic testing can have significant implications for women with ovarian, fallopian tube or peritoneal carcinoma, including therapeutic decisions, prognostic counseling and cascade testing. However, there are obstacles to universal implementation of testing when it is dependent on clinician initiative. Therefore, we implemented a prospective quality improvement (QI) initiative that aimed to assure universal germline and somatic testing in women with newly diagnosed advanced stage, high grade disease. <h3>Methods:</h3> A systematic program was established to ensure that all patients with newly diagnosed, advanced stage ovarian, tubal or peritoneal carcinoma who were scheduled for formal genetics consultation underwent dual Myriad MyRisk multigene germline testing and Myriad MyChoice somatic testing for <i>BRCA1/2</i> mutations and genomic instability. The primary objective was to compare the frequency of germline and somatic testing between the pre-initiative (1/1/2015 - 3/31/2018) and post-initiative (4/1/2018- 7/1/2020) periods. Secondary objectives included comparison of time intervals between diagnosis and testing, incidence of ‘insufficient samples' for somatic testing, and clinical utilization of results. Descriptive statistics were used. Paired Student's T test was used to compare continuous variables; chi-square test was used to compare discrete variables. <h3>Results:</h3> There were 209 women in this study: 122 in the pre-intervention cohort and 87 in the post-intervention cohort. Among women in the pre-intervention group, 90 (74%) and 48 (39%) underwent germline and somatic testing, respectively, compared to 77 (89%) and 66 (76%) in the post-intervention cohort. Implementation of a systemic referral system with dual testing doubled the rate of somatic testing (p<0.01). Among all women who underwent germline testing, 10.1% had a g<i>BRCA1</i> mutation and 2.4% a g<i>BRCA2</i> mutation. Of all who underwent somatic testing, 6.2% had a s<i>BRCA1</i> mutation and 4.3% a s<i>BRCA2</i> mutation. All germline <i>BRCA1</i> and <i>BRCA2</i> mutations were also identified on somatic testing. There were 20 cases (9.5%) with negative germline multigene panels also lacking somatic <i>BRCA1/2</i> mutations that were found to have genomic instability. Among the 114 patients who received somatic testing, 29 (25.4%) had biomarkers (<i>BRCA1/2</i> mutation or genomic instability) predictive of major benefit from poly-ADP ribose polymerase inhibitors (PARPi) despite lacking germline mutations. Median time from diagnosis to germline testing decreased to 3.7 months in the post-intervention compared to 6.2 months in the pre-intervention cohort. <h3>Conclusions:</h3> Systematic referral for both germline and somatic genetic testing significantly increased the frequency of somatic testing, and results were obtained sooner in patients with advanced ovarian, fallopian tube and peritoneal cancers. In patients who underwent dual testing and lacked germline mutations, 25% had either a somatic <i>BRCA1</i> or <i>BRCA2</i> mutation or genomic instability that could help direct therapy. Since both germline and somatic mutations and genomic instability status increasingly play a role in directing therapy, earlier and consistent testing is of the upmost importance.