Tube Cancer Research Articles

Primary fallopian tube cancer followed by primary breast cancer in RAD51C mutation carrier treated with niraparib as first line maintenance therapy: a case report

Given the rarity of RAD51C mutations, the risk and treatment of metachronous breast cancer after the diagnosis of ovarian cancer in RAD51C mutation carriers is not clear, especially for those who have received PARPi treatment. We report the case of a 65-year-old woman diagnosed with stage IIIC high-grade serous primary fallopian tube cancer. The patient had no family history of breast or ovarian cancer. The patient received three cycles of neoadjuvant chemotherapy with paclitaxel and carboplatin and achieved a complete response. After interval debulking surgery, the patient received three cycles of adjuvant chemotherapy. Collection and extraction of saliva DNA for next-generation sequencing identified a RAD51C mutation c.838-2 A > G. The patient received niraparib as front-line maintenance treatment. After 36 months of niraparib treatment, the patient had grade II invasive ductal carcinoma of the left breast that was positive for estrogen receptor (90%) and Ki-67 (30%) and negative for progesterone receptor and human epidermal growth factor receptor 2. Computed tomography revealed the absence of distant metastases. Modified radical mastectomy and axillary lymph node dissection were then performed. The final pathological report of the breast showed a 1.8 cm Bloom-Richardson grade II invasive ductal carcinoma in the left breast with axillary lymph node metastasis (1/21). Finally, the breast cancer was stage IIA, pT1cN1M0. The metachronous breast cancer in this case may be the first report of second primary cancer in fallopian tube cancer patient harboring a RAD51C mutation during niraparib treatment. Further studies are required to determine optimal treatment.

Genetic Basis of Breast and Ovarian Cancer: Approaches and Lessons Learnt from Three Decades of Inherited Predisposition Testing.

Germline variants occurring in BRCA1 and BRCA2 give rise to hereditary breast and ovarian cancer (HBOC) syndrome, predisposing to breast, ovarian, fallopian tube, and peritoneal cancers marked by elevated incidences of genomic aberrations that correspond to poor prognoses. These genes are in fact involved in genetic integrity, particularly in the process of homologous recombination (HR) DNA repair, a high-fidelity repair system for mending DNA double-strand breaks. In addition to its implication in HBOC pathogenesis, the impairment of HR has become a prime target for therapeutic intervention utilizing poly (ADP-ribose) polymerase (PARP) inhibitors. In the present review, we introduce the molecular roles of HR orchestrated by BRCA1 and BRCA2 within the framework of sensitivity to PARP inhibitors. We examine the genetic architecture underneath breast and ovarian cancer ranging from high- and mid- to low-penetrant predisposing genes and taking into account both germline and somatic variations. Finally, we consider higher levels of complexity of the genomic landscape such as polygenic risk scores and other approaches aiming to optimize therapeutic and preventive strategies for breast and ovarian cancer.

Single-Agent Trabectedin Versus Physician's Choice Chemotherapy in Patients With Recurrent Ovarian Cancer With BRCA-Mutated and/or BRCAness Phenotype: A Randomized Phase III Trial.

Literature evidence suggests that trabectedin monotherapy is effective in patients with recurrent ovarian cancer (OC) presenting BRCA mutation and/or BRCAness phenotype. A prospective, open-label, randomized phase III MITO-23 trial evaluated the activity and safety of trabectedin 1.3 mg/m2 given once every 3 weeks (arm A) in BRCA 1/2 mutation carriers or patients with BRCAness phenotype (ie, patients who responded to ≥two previous platinum-based treatments) with recurrent OC, primary peritoneal carcinoma, or fallopian tube cancer in comparison with physician's choice chemotherapy in the control arm (arm B; pegylated liposomal doxorubicin, topotecan, gemcitabine, once-weekly paclitaxel, or carboplatin). The primary end point was overall survival (OS) evaluated in the intention-to-treat population. Overall, 244 patients from 21 MITO centers were randomly assigned (arm A = 122/arm B = 122). More than 70% of patients received ≥three previous chemotherapy lines and 35.7% had received a poly (ADP-ribose) polymerase inhibitor (PARPi) before enrollment. Median OS was not significantly different between the arms: arm A: 15.8 versus arm B: 17.9 months (P = .304). Median progression-free survival was 4.9 months in arm A versus 4.4 months in arm B (P = .897). Among 208 patients evaluable for efficacy, the objective response rate was 17.1% in arm A and 21.4% in arm B, with comparable median duration of response (5.62 v 5.66 months, respectively). No superior effect was observed for trabectedin in the prespecified subgroup analyses according to BRCA mutational status, chemotherapy type, and pretreatment with a PARPi and/or platinum-free interval. Trabectedin showed a higher frequency of grade ≥3 adverse events (AEs), serious AEs, and serious adverse drug reactions compared with control chemotherapy. Trabectedin did not improve median OS and showed a worse safety profile in comparison with physician's choice control chemotherapy.

High-Grade Serous Ovarian Cancer-A Risk Factor Puzzle and Screening Fugitive.

High-grade serous ovarian cancer (HGSOC) is the most lethal tumor of the female genital tract. Despite extensive studies and the identification of some precursor lesions like serous tubal intraepithelial cancer (STIC) or the deviated mutational status of the patients (BRCA germinal mutation), the pathophysiology of HGSOC and the existence of particular risk factors is still a puzzle. Moreover, a lack of screening programs results in delayed diagnosis, which is accompanied by a secondary chemo-resistance of the tumor and usually results in a high recurrence rate after the primary therapy. Therefore, there is an urgent need to identify the substantial risk factors for both predisposed and low-risk populations of women, as well as to create an economically and clinically justified screening program. This paper reviews the classic and novel risk factors for HGSOC and methods of diagnosis and prediction, including serum biomarkers, the liquid biopsy of circulating tumor cells or circulating tumor DNA, epigenetic markers, exosomes, and genomic and proteomic biomarkers. The novel future complex approach to ovarian cancer diagnosis should be devised based on these findings, and the general outcome of such an approach is proposed and discussed in the paper.

Prognostic value of HE4 in advanced-stage, high-grade serous ovarian cancer: Analysis of HE4 kinetics during NACT, predicting surgical outcome and recurrence in comparison to CA125

ObjectivesTo assess the prognostic value of human epididymis protein 4 (HE4) kinetics during and after neoadjuvant chemotherapy (NACT) cycles compared with cancer antigen 125 (CA-125), in predicting the surgical outcomes of interval debulking surgery (IDS) in patients with advanced-stage, high-grade serous ovarian cancer. MethodsThis retrospective cohort study was conducted at Severance Hospital in Seoul, South Korea and involved 123 women with high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who were diagnosed between April 2015 and July 2020. Three outcomes were considered: the chemotherapy response score (CRS) by omentum, residual disease after IDS, and recurrence. Other clinical, imaging, and biological parameters at baseline, during NACT cycles, and pre- and postoperative time were collected and analyzed. ResultsWe observed a substantial and gradual decrease in both CA-125 level (median from 1612 to 85.55 U/mL; p < 0.001) and HE4 level (514.7 to 87.7 pmol/L; p < 0.001) during NACT cycles, while pre-to-postoperative reduction was only significant for HE4 (median from 77.3 to 62.0 pmol/L (p < 0.001)). Of the total patients, 4.1% showed no response to NACT (chemoresistance) and 65.9% had a partial response. Residual disease was observed in 55 (44.7%) patients. Recurrence occurred in 90 patients (73.2%), with a median progression-free survival of 15.28 months. The percent reduction in CA-125 level– but not HE4 – during NACT was significantly associated with CRS (by omentum); the reduction in CA-125 during NACT cycles was higher when the CRS was found to be 3 and 2 (median = 96.4 [IQR = 8.3] and 93.7 [12.2] respectively) compared to score 1 (68.3 [34.1]), and the difference was statistically significant (p = 0.004). However, no significant association was observed between the percent reduction in CA-125 or HE4 levels during NACT and residual disease or recurrence. The normalization of HE4 – but not CA-125 – before surgery was predictive for surgery outcome; that is, an abnormal preop HE4 level was associated with a residual disease risk ratio of 2.72 (95% CI = 1.27–5.79). ConclusionMonitoring HE4 or CA-125 levels has low prognostic value in patients with advanced-stage, high-grade serous ovarian cancer who are treated with NACT followed by IDS. However, the preoperative level of the HE4 biomarker may be useful in identifying patients at higher risk for suboptimal cytoreductive surgery or who may require more extensive surgery. Further prospective studies are warranted to explore the prognostic utility of eventual combinations of clinical, radiological, and biological parameters, notably by using artificial intelligence-based models.

PREVENTION OF OVARIAN, FALLOPIAN TUBE, AND PERITONEAL SEROUS CANCERS (LITERATURE REVIEW)

This literature review presents an analysis of the incidence and state of prevention of highly malignant tumors that are difficult to diagnose: serous ovarian cancer, primary fallopian tube cancer, and primary peritoneal cancer. In this group of patients, ovarian cancer amounts to 82.0%, fallopian tube cancer – 6.4%, and peritoneal cancer – 10.7%. The problem is very urgent, since, according to the International Agency for Research on Cancer (IARC), more than 225,000 new cases of ovarian cancer alone are registered annually in the world, and more than half of the patients die during the year. No more than 30% of the treated patients survive for up to 10 years. Such poor results are due to the lack of effective methods of prevention and the difficulties of diagnosing this group of diseases. Methods. The author selected from the world literature more than 45 scientific works on the problems of incidence and prevention of ovarian cancer, primary fallopian tube cancer, and peritoneal cancer and carried out a detailed analysis of them. Results and Discussion. At the beginning of the 21st century, after a number of morphological, immunohistochemical, and molecular genetic examinations, the global scientific community clearly proved that the root cause of serous ovarian, fallopian tube, and peritoneal cancers is the pathology of the fallopian tube mucosa. Practical observations revealed that women who underwent salpingectomy or tubal sterilization had a much lower risk of serous pelvic cancers. As a result of these examinations and observations, clinical recommendations were made: in order to prevent ovarian cancer, women should be suggested opportunistic bilateral salpingectomy during their operations in the post-reproductive age. Sterilization should be done by removing the fallopian tubes, not by ligation, because of the lower efficiency of the latter. According to the reports of some authors, this method can reduce the risk of ovarian cancer by 90–98%. There is a lack of reports on the prevention of fallopian tube and peritoneal cancers in the periodical scientific literature, but we can assume that they will not be worse than those for ovarian cancer.

First-line bevacizumab plus chemotherapy in Chinese patients with stage III/IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer: a phase III randomized controlled trial.

First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer. ClinicalTrials.gov Identifier: NCT03635489.

Effect of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on epithelial ovarian, fallopian tube, and peritoneal cancer: An institutional review of outcomes and its clinical implications

BACKGROUND: Ovarian, fallopian tube, and peritoneal cancer patients with advanced-stage diagnosis or recurrences spread to the peritoneal surface of the abdomen. Hyperthermic intraperitoneal chemotherapy (HIPEC) can penetrate and eradicate tumors that are microscopic up to those with a diameter of 2.5 cm from the peritoneal surface following cytoreductive surgery (CRS). OBJECTIVES: The study aimed to determine the efficacy and safety of CRS with HIPEC versus CRS alone for patients with epithelial ovarian, fallopian tube, and peritoneal cancer. MATERIALS AND METHODS: This retrospective cohort study included 50 patients (20 patients underwent CRS + HIPEC, while 30 patients underwent CRS alone). Records of these patients from January 2014 to June 2020 were reviewed, tabulated, and analyzed. RESULTS: The difference in recurrence rate between CRS with HIPEC and CRS alone was not statistically significant (50% vs. 43%, P = 0.774). The median time to recurrence was 10 and 9 months, respectively (P = 0.636). Five percent in the HIPEC group succumbed to the disease, while 13% died in the CRS alone group (P = 0.636). More post-operative complications were noted in the HIPEC group (45% vs. 10%, P = 0.007), but among these, only 2 cases had grade 3 to 4 complications (10%). The addition of HIPEC in the management of these patients resulted in a longer operative time (360 vs. 240 min, P &lt; 0.001) and postoperative hospital stay (8 vs. 6 days, P = 0.026). There were no intra- or peri-operative mortalities in both groups. CONCLUSION: CRS with HIPEC and CRS alone showed similar time to recurrence and recurrence rate. CRS with HIPEC had low risk of grade 3-4 complications and may still be considered as a treatment option for advanced, progressive, and recurrent epithelial ovarian, fallopian tube, and peritoneal cancer.

Niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer: final results of a multicenter phase 2 study.

To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3-4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4-78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9-26.9) and the disease control rate was 90.0% (95% CI=68.3-98.8). The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified. ClinicalTrials.gov Identifier: NCT03759600.

Prevention of symptomatic pulmonary embolism for gynecologic malignancies with preoperative asymptomatic venous thromboembolism: GOTIC-VTE trial.

In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Between February 2018 and September 2020, 99 patients were enrolled; of these, 82 patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE. JRCT Identifier: jRCTs031180124.

Lymphadenectomy and optimal excise lymph nodes count for early-stage primary fallopian tube cancer: a SEER-based study

BackgroundsThere is still no consensus on the significance of Lymphadenectomy (LD) and the number of lymph nodes that need to be excised (ELNs) for adequate LD in patients with early-stage primary fallopian tube cancer (PFTC). Our endeavor is geared towards deepening comprehension of LD in early-stage PFTC and identify the optimal cut-off of ELNs.MethodsThis SEER-based study analyzed the clinical data of patients with early-stage PFTC between 2000 and 2018. X-tile was employed to confirm the optimal cut-off of ELNs. The survival data between groups were analyzed by the Kaplan-Meier estimates, Log-rank test and Cox proportional hazards model.ResultsThere was significant improvement in both mean cancer-specific survival (CSS, p < 0.001) and overall survival (OS, p < 0.001) in LD group. Regardless of matched or not, LD was identified as an independent protective factor of CSS and OS. The optimal 3-year CSS-based cutoff of ELNs was 11 (p = 0.026) as determined by X-tile. Both the mean CSS (p = 0.001) and mean OS (p = 0.002) in adequate LD group (ELNs > 11, n = 574) were significantly longer than these in inadequate LD group (ELNs ≤ 11, n = 738). Adequate LD, FIGO stage, tumor grade and histology were significant prognostic factors for CSS and OS.ConclusionLD is an independent protective prognostic factor of patients with early-stage PFTC. The association between ELNs > 11 and an improved prognosis is evident. Future studies are needed to further clarify the results above.

Increase in creatinine levels associated with niraparib maintenance therapy in ovarian cancer.

In Japan, Niraparib maintenance therapy for primary and recurrent ovarian cancer was approved in September 2020 and is expected to improve the prognosis of ovarian cancer. However, the safety of niraparib maintenance therapy in Japanese patients has not been fully evaluated. Patients with ovarian cancer (including fallopian tube and peritoneal cancer) treated with niraparib at Jichi Medical University Hospital from September 2020 to August 2022 were enrolled in this study. Patient background, starting dose, rates of interruption, reduction, or discontinuation, adverse events (AEs) during treatment, and estimated glomerular filtration rate (eGFR) trends were retrospectively analyzed. Twenty-nine patients received niraparib maintenance therapy during the study period, including 21 with primary cancer and 8 patients with recurrent cancer. Seventeen patients (58.6%) required dose interruptions and 16 patients (55.2%) required dose reductions. Only two patients (6.9%) discontinued treatment due to fatigue and nausea. The most frequent AE was creatinine increases in 18 patients (62.1%, all grades). Although eGFR levels decreased significantly after niraparib therapy compared to before niraparib therapy (59.3 vs. 50.3 mL/min/1.73 m2 , p < 0.001), the levels returned to pre-niraparib initiation levels after discontinuation of niraparib (64.6 vs. 64.6 mL/min/1.73 m2 , p = 0.96). Multivariate regression analysis showed that diabetes was independently associated with decreased eGFR (p = 0.013). Niraparib maintenance therapy frequently increased serum creatinine, but the change was reversible. Further studies are needed to determine the effects of niraparib on renal function in Japanese patients.

Small-scale mutations are infrequent as mechanisms of resistance in post-PARP inhibitor tumour samples in high grade serous ovarian cancer

While the introduction of poly-(ADP)-ribose polymerase (PARP) inhibitors in homologous recombination DNA repair (HR) deficient high grade serous ovarian, fallopian tube and primary peritoneal cancers (HGSC) has improved patient survival, resistance to PARP inhibitors frequently occurs. Preclinical and translational studies have identified multiple mechanisms of resistance; here we examined tumour samples collected from 26 women following treatment with PARP inhibitors as part of standard of care or their enrolment in clinical trials. Twenty-one had a germline or somatic BRCA1/2 mutation. We performed targeted sequencing of 63 genes involved in DNA repair processes or implicated in ovarian cancer resistance. We found that just three individuals had a small-scale mutation as a definitive resistance mechanism detected, having reversion mutations, while six had potential mechanisms of resistance detected, with alterations related to BRCA1 function and mutations in SHLD2. This study indicates that mutations in genes related to DNA repair are detected in a minority of HGSC patients as genetic mechanisms of resistance. Future research into resistance in HGSC should focus on copy number, transcriptional and epigenetic aberrations, and the contribution of the tumour microenvironment.

Added value of regional 18F-FDG PET/MRI-assisted whole-body 18F-FDG PET/CT in malignant ascites with unknown primary origin

BackgroundComparing to PET/CT, integrative PET/MRI imaging provides superior soft tissue resolution. This study aims to evaluate the added value of regional delayed 18F-FDG PET/MRI-assisted whole-body 18F-FDG PET/CT in diagnosing malignant ascites patients.ResultsThe final diagnosis included 22 patients with ovarian cancer (n = 11), peritoneal cancer (n = 3), colon cancer (n = 2), liver cancer (n = 2), pancreatic cancer (n = 2), gastric cancer (n = 1), and fallopian tube cancer (n = 1). The diagnosis of the primary tumor using whole-body PET/CT was correct in 11 cases. Regional PET/MRI-assisted whole-body PET/CT diagnosis was correct in 18 cases, including 6 more cases of ovarian cancer and 1 more case of fallopian tube cancer. Among 4 cases that were not diagnosed correctly, 1 case had the primary tumor outside of the PET/MRI scan area, 2 cases were peritoneal cancer, and 1 case was colon cancer. The diagnostic accuracy of regional PET/MRI-assisted whole-body PET/CT was higher than PET/CT alone (81.8% vs. 50.0%, κ 2 = 5.14, p = 0.023). The primary tumor conspicuity score of PET/MRI was higher than PET/CT (3.67 ± 0.66 vs. 2.76 ± 0.94, P < 0.01). In the same scan area, more metastases were detected in PET/MRI than in PET/CT (156 vs. 86 in total, and 7.43 ± 5.17 vs. 4.10 ± 1.92 per patient, t = 3.89, P < 0.01). Lesion-to-background ratio in PET/MRI was higher than that in PET/CT (10.76 ± 5.16 vs. 6.56 ± 3.45, t = 13.02, P < 0.01).ConclusionComparing to whole-body PET/CT alone, additional delayed regional PET/MRI with high soft tissue resolution is helpful in diagnosing the location of the primary tumor and identifying more metastases in patients with malignant ascites. Yet larger sample size in multicenter and prospective clinical researches is still needed.

Abstract C005: Inferring global ancestry using scRNA sequencing reads of the fallopian tube and ovarian cancer

Abstract Introduction Single cell RNA sequencing (scRNA-seq) is a powerful technique to profile the transcriptome of each single cell in the sample to characterize its gene expression profile. Final 10x scRNA-seq libraries are comprised of standard Illumina paired end constructs. Read 2 encodes the sequence of the actual cDNA fragment used in library preparation to amplify the RNA sequences, so read 2 is a result of transcription from the DNA encoded in a particular gene. We hypothesize that single nucleotide polymorphisms (SNPs) and global ancestry can be inferred from read 2. Methods Using the read 2, FASTQ files were mapped to the reference genome using the STAR algorithm (2-pass), subsequent steps were performed according to GATK best practices. For reference populations, we selected 2142 unrelated individuals from the 1000 genomes project with admixture &amp;gt;80% in a single ancestral population using k=5 ancestral populations. SNPs quality control for the FT samples and reference included call rates of &amp;lt; 95% or minor allele frequency (MAF) &amp;lt; 1% which were filtered out. Genotypes of fallopian tube (FT) cases were merged with pruned reference genotypes (markers) and intersecting SNPs were used for further analysis. Data was visualized using PCA and ADMIXTURE (k=5). Clinical and demographic variables available in our dataset included age at time of surgery, race, ethnicity, country of birth and specific germline mutation. Whole genome sequencing on the matched germline DNA of the same samples was performed as a validation step. Results A total of 34 cases underwent scRNA-seq. FT with germline mutations included seven BRCA1, seven BRCA2, five PALB2, two RAD51, two MLH1 and one ATM. Additionally, we sequenced six FT with no germline mutations and four ovarian cancer tumors. Self-identified race included 2 Asian, 9 Black, 16 White Hispanic and 6 White non-hispanic. A total of 730 382 SNPs intersected between all samples and pruned references. PCA visualization showed correlation between self-identified race and inferred global ancestry using five ancestral populations. Furthermore, there was high correlation between country of birth, position of cases in the PCA and ADMIXTURE with K=5. Conclusion Inferring global ancestry from scRNA seq reads will help estimate the genetic ancestry from data in which this variable is missing or was not captured. Genetic ancestry is a powerful tool that should be considered when generalizing gene expression results to populations. Citation Format: Alex P. Sanchez-Covarrubias, Ashlee Sealy, Dylan Thompson, David Samuel, Ayodele Omotoso, Destiny Burnett, Matthew Schlumbrecht, Sophia George. Inferring global ancestry using scRNA sequencing reads of the fallopian tube and ovarian cancer [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C005.

Rare non-serous fallopian tube cancers: institutional experience and literature review.

We reviewed 63reports from the literature on rare non-serous tumors of the fallopian tubes and carried out acomparative analysis of clinical manifestations and diagnostic methods. We also report our observations from patients with these tumors. Of 157 patients with primary fallopian tube cancer (FTC) treated in our regional oncological hospital between 1970 and 2020, there were nine (6%) cases of rare non-serous cancers, including one case each of choriocarcinoma, carcinosarcoma, and neuroendocrine tumor, and two cases each of non-keratinizing squamous cell carcinoma, mucinous adenocarcinoma, and clear cell adenocarcinoma. For carcinosarcoma and squamous cell, clear cell, and transitional cell carcinomas, clinical history, patient age, and clinical manifestations were similar to the main group of FTCs. Choriocarcinoma differed significantly from other cancers of the fallopian tubes in terms of patient age and clinical course. Mucinous adenocarcinoma, mesothelioma, and borderline tumors, with rare exceptions, were almost always asymptomatic and were found only incidentally during surgery. Choriocarcinoma and carcinosarcoma had an aggressive course, while squamous cell, transitional cell, clear cell, and mucinous carcinomas were less aggressive. Since most rare non-serous tumors have asimilar disease course to typical FTCs and there is alack of appropriate treatment protocols for rare tumors, treatment options developed for ovarian tumors and FTC are justified for these tumors. Rare non-serous malignant fallopian tube tumors are very similar to serous and endometrioid FTC in terms of clinical manifestations and diagnosis.

A review and metanalysis of metronomic oral single-agent cyclophosphamide for treating advanced ovarian carcinoma in the era of precision medicine.

Oral metronomic cyclophosphamide has been used as a single agent or in combination with other drugs for several solid tumors with interesting results in disease palliation and mild to moderate toxicity, notably in patients with recurrent epithelial ovarian cancer (EOC) progressing after systemic chemotherapy. In this paper, we report a review and a metanalysis of heterogeneous data published up to date. The literature search was restricted to single-agent MOC. The analysis was conducted through March 2023 by consulting PubMed, Embase, Google Scholar, and The Cochrane Library databases. Research string and Medical Subject Headings included "ovarian tumor," "ovarian carcinoma," or "ovarian cancer," "fallopian tube cancer," "primary peritoneal cancer," "oral chemotherapy," and "metronomic cyclophosphamide." All articles were assessed for quality by at least two investigators independently, and a < 18 patients sample size cutoff was chosen as a lower limit with a Cohen's kappa statistical coefficient for accuracy and reliability. Metanalysis of selected papers was carried out according to a fixed model. The percentage of agreement between investigators on literature study selection was very high, reaching 96.9% with a Cohen's k of 0.929. MOC pooled objective response rate (ORR) and disease control rate for recurrent or platinum-refractory ovarian cancer were 18.8% (range 4-44%) and 36.2% (range 16-58.8%), respectively. The mean progressive-free survival and overall survival were 3.16 months (range 1.9 to 5.0 months) and 8.7 months (range 8 to 13 months), respectively. The fixed model metanalysis of selected studies showed a 16% median ORR (12-20% CI, p < 0.001). Single-agent oral cyclophosphamide in EOC holds promise as a treatment option, even in the era of precision medicine. Genetic factors, such as DNA repair gene polymorphisms, may influence treatment response. Combining cyclophosphamide with biological agents such as PARP inhibitors or immunotherapy agents is an area of active investigation.

A retrospective study of Pipelle endometrial biopsy for ovarian, fallopian tube, and peritoneal cancers

Objectives Although the Pipelle endometrial biopsy is widely performed as a practical and minimally invasive test for endometrial disease(s), its effectiveness in ovarian cancer has not been explored. The aim of the present study was to evaluate the results of Pipelle endometrial biopsy for ovarian, fallopian tube, and peritoneal cancers. Methods A pre-treatment Pipelle-endometrial biopsy was performed in 90 patients with ovarian, fallopian tube, or peritoneal cancers between January 2014 and November 2021. We retrospectively analysed the association between the results of Pipelle endometrial biopsy and clinicopathological data. Moreover, we evaluated their impact on the following treatment in advanced cases initially treated with chemotherapy. Results The sensitivity and false-negative rates for Pipelle endometrial biopsy were 25/90 (27.8%) and 65/90 (72.2%) in all patients, respectively, and 23/56 (41.0%) and 33/56 (58.9%) in cases with advanced disease (stages III and IV), respectively. Pipelle-positive endometrial biopsy-positive (Pipelle-positive) was not observed in 29 patients with clinical stage I disease, and Pipelle-positive patients exhibited significantly more high-grade serous carcinomas, and positive peritoneal, endometrial, and cervical cytologies than Pipelle-endometrial biopsy-negative cases. Surgical pathology was confirmed in 23 Pipelle-positive patients, and 17/23 (74.0%) had the same diagnosis as that for Pipelle endometrial biopsy. Conversely, 6/23 (26.0%) patients exhibited a minor diagnostic discrepancy between Pipelle endometrial biopsy and surgical pathology. Nineteen of the 38 (50.0%) patients initially treated with chemotherapy were identified as Pipelle-positive, contributing to a prompt histological diagnosis and pre-treatment tumour sampling. Companion diagnostic tests were performed using Pipelle endometrial biopsy samples from 4 inoperable patients. Conclusion Although the positive rate of Pipelle endometrial biopsy in ovarian, fallopian tube, and peritoneal cancers is low, Pipelle endometrial biopsy may enable prompt histological diagnosis and initiation of chemotherapy while collecting tumour tissue for genetic testing in some cases with advanced disease.

An Unusual Presentation: High-Grade Serous Carcinoma of the Fallopian Tube Manifesting With Altered Mental Status Secondary to a Single Brain Metastasis—A Case Report and Review of the Literature

Epithelial ovarian and fallopian cancers are aggressive lesions that rarely metastasize to the central nervous system. Brain metastases usually occur in the setting of known primary disease or widespread metastatic disease. However, in extremely rare cases, an isolated intracranial neoplasm may be the first presentation of fallopian cancer. To the best of our knowledge, only one such case has been reported previously. We present an illustrative case with multimodality imaging and histopathologic correlation of a fallopian tube carcinoma first presenting with altered mental status secondary to an isolated brain metastasis. A 64-year-old female with no pertinent medical history presented with altered mentation. Initial workup identified a 1.6 cm avidly enhancing, solitary brain lesion at the gray-white junction with associated vasogenic edema concerning for either central nervous system lymphoma or metastatic disease. Additional imaging identified a 7.5×3 cm left adnexal lesion, initially thought to be a hydrosalpinx with hemorrhage, but magnetic resonance imaging suggested gynecologic malignancy. No lesions elsewhere in the body were identified. Given the lack of locoregional or systemic disease, the intracranial and pelvic lesions were assumed to represent synchronous but distinct processes. The intracranial lesion was biopsied. Preliminary results were suggestive of lymphoma, but further analysis was consistent with high-grade serous carcinoma of müllerian origin. Positron emission tomography/computed tomography was performed to evaluate for other neoplastic lesions, only highlighting the intracranial and pelvic lesions. At this point, a diagnosis of metastatic fallopian cancer was made. The patient was taken for robot-assisted laparoscopy with surgical debulking of the pelvic neoplasm, pathology demonstrating high-grade serous carcinoma of the fallopian tube, matching that of the intracranial lesion. Even though rare, metastatic fallopian cancer should be considered in patients with isolated brain lesions and adnexal lesions, even in the absence of locoregional or systemic disease.

Abstract 14175: Risk of Cardiovascular Disease in Women Who Underwent Salpingo-Oophorectomy to Prevent Hereditary Breast Ovarian Cancer: A Systematic Review and Meta-Analysis

Introduction: Hereditary breast and ovarian cancer (HBOC) syndrome is defined by family history and identification of germline pathogenic variants (PVs). In particular, the mutations in BRCA1/2 (BRCAm) increased approximately 44% and 17% risk of ovarian cancer or fallopian tube cancer and 72% and 69% risk of breast cancer. Risk-reducing salpingo-oophorectomy (RRSO), the physiologic removal of the ovaries and fallopian tubes, effectively reduces the risk of ovarian cancer by 80-95% in women with HBOC. Hypothesis: Is performing a RRSO in women with HBOC or BRCAm associated with the development of cardiac and metabolic diseases? Aims: To assess the risk of myocardial infarction (MI)/coronary artery disease (CAD), hypertension, diabetes mellitus (DM), and hypercholesterolemia/dyslipidemia among women with HBOC or BRCA1/2 mutation after performing RRSO. Methods: We searched in PubMed, Scopus, and Web of Science databases for studies that assessed cardiovascular and metabolic events following RRSO in women with HBOC or BRCAm. Statistical analysis was performed using RStudio v4.4.2 using the DerSimonian and Laird random-effects model. Heterogeneity was examined using the Cochran Q test and I 2 statistics. Significance for heterogeneity was set at a p-value&lt;0.01. Results: Five studies were included with a total of 1320 patients. Among them, 956/1320 (72.4%) had BRCAm: 469 (35.5%) had BRCA1 and 400 (30.3%) had BRCA2. The majority of patients (928;69.3%) had RRSO&lt;50 years, and the mean age of the study sample was 54.3 years (41.45-57, 2.35). The incidence of MI events was reported in 18/1126 patients (1.4%, 95% Cl, 5-2.3%; I 2 =40.15%). Most common metabolic comorbidities were hypercholesterolemia. Observed in 170/994 women (19.6%, 95% Cl, 4.6-34.6%; I 2 =97.88%), hypertension, in 125/994 women (12.9%, 95% Cl, 4-21.8%; I 2 =96.93%), and DM, reported in 46/1320 patients (3%, 95% Cl, 1.2-4.7%; I 2 =75.41%). Conclusions: This meta-analysis provides evidence to support that patients with HBOC or BRCAm who undergo RRSO have an increased risk of developing heart and metabolic diseases. Larger studies with longer follow-up are required to further explore these associations.