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High-grade serous ovarian cancer (HGSOC) is an archetypal cancer of genomic instability1-4 patterned by distinct mutational processes5,6, tumour heterogeneity7-9 and intraperitoneal spread7,8,10. Immunotherapies have had limited efficacy in HGSOC11-13, highlighting an unmet need to assess how mutational processes and the anatomical sites of tumour foci determine the immunological states of the tumour microenvironment. Here we carried out an integrative analysis of whole-genome sequencing, single-cell RNA sequencing, digital histopathology and multiplexed immunofluorescence of 160 tumour sites from 42 treatment-naive patients with HGSOC. Homologous recombination-deficient HRD-Dup (BRCA1 mutant-like) and HRD-Del (BRCA2 mutant-like) tumours harboured inflammatory signalling and ongoing immunoediting, reflected in loss of HLA diversity and tumour infiltration with highly differentiated dysfunctional CD8+ T cells. By contrast, foldback-inversion-bearing tumours exhibited elevated immunosuppressive TGFß signalling and immune exclusion, with predominantly naive/stem-like and memory T cells. Phenotypic state associations were specific to anatomical sites, highlighting compositional, topological and functional differences between adnexal tumours and distal peritoneal foci. Our findings implicate anatomical sites and mutational processes as determinants of evolutionary phenotypic divergence and immune resistance mechanisms in HGSOC. Our study provides a multi-omic cellular phenotype data substrate from which to develop and interpret future personalized immunotherapeutic approaches and early detection research.
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Evasión Inmune , Mutación , Neoplasias Ováricas , Femenino , Humanos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/inmunología , Cistadenocarcinoma Seroso/patología , Recombinación Homóloga , Evasión Inmune/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patología , Microambiente Tumoral , Factor de Crecimiento Transformador beta , Genes BRCA1 , Genes BRCA2RESUMEN
INTRODUCTION: Homologous recombination deficiency (HRD) testing is used to determine the appropriateness of poly ADP-ribose polymerase inhibitors for patients with epithelial ovarian cancer and no germline/somatic BRCA1/2 alterations. Myriad MyChoice CDx reports a genomic instability score (GIS) to quantify the level of HRD, with a positive score defined as ≥42. The authors sought to define factors associated with obtaining an inconclusive HRD test result. METHODS: GIS was retrieved for patients at their institution with epithelial ovarian cancer without germline/somatic BRCA1/2 deleterious alterations who underwent HRD testing from April 2020-August 2023. Clinical data were abstracted from the medical record. RESULTS: Of 477 HRD test results identified, 57 (12%) were inconclusive. High-grade serous ovarian cancers had higher GIS than other histologic types (median 29 vs. 21, p < .001). Most HRD cases were of high-grade serous histology; no cases with clear cell or endometrioid histology were HRD-positive. On univariate analysis, interval versus primary cytoreductive surgery, other specimen sources versus surgical specimens, and chemotherapy exposure were risk factors for inconclusive HRD testing. On multivariable analysis, chemotherapy exposure, and tissue source were associated with an inconclusive test result, with surgical specimens more likely to yield a conclusive result than other sources (biopsy, cytology, other). Age, stage, self-reported race, and histology were not associated with an inconclusive result. CONCLUSIONS: Surgical tissue was more likely to yield a conclusive HRD test result versus other sources of epithelial ovarian cancer tissue acquisition. When feasible, laparoscopic biopsy before initiation of neoadjuvant chemotherapy may increase the likelihood of obtaining interpretable HRD test results.
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OBJECTIVES: The surgical training of gynecologic oncology (GO) fellows is critical to providing excellent care to women with gynecologic cancers. We sought to evaluate changes in techniques and surgical volumes over an 18-year period among established GO fellowships across the US. METHODS: We emailed surveys to 30 GO programs that had trained fellows for at least 18 years. Surveys requested the number of surgical cases performed by a fellow for seventeen surgical procedures over each of five-time intervals. A One-Way Analysis of Variance was conducted for each procedure, averaged across institutions, to examine whether each procedure significantly changed over the 18-year span. RESULTS: 14 GO programs responded and were included in the analysis using SPSS. We observed a significant increase in the use of minimally invasive (MIS) procedures (robotic hysterectomy (p < .001), MIS pelvic (p = .001) and MIS paraaortic lymphadenectomy (p = .008). There was a concurrent significant decrease in corresponding "open" procedures. There was a significant decrease in all paraaortic lymphadenectomies. Complex procedures (such as bowel resection) remained stable. However, there was a wide variation in the number of cases reported with extremely small numbers for some critical procedures. CONCLUSIONS: The experience of GO fellows has shifted toward increased use of MIS. While these trends in care are appropriate, they do not diminish the need in many patients for complex open procedures. These findings should help spur the development of innovative training to maintain the ability to provide these core, specialty-defining procedures safely.
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Becas , Procedimientos Quirúrgicos Ginecológicos , Ginecología , Oncología Médica , Humanos , Femenino , Becas/tendencias , Becas/estadística & datos numéricos , Ginecología/educación , Ginecología/tendencias , Procedimientos Quirúrgicos Ginecológicos/educación , Procedimientos Quirúrgicos Ginecológicos/tendencias , Oncología Médica/educación , Oncología Médica/tendencias , Neoplasias de los Genitales Femeninos/cirugía , Estados Unidos , Histerectomía/educación , Histerectomía/tendencias , Histerectomía/estadística & datos numéricos , Histerectomía/métodos , Educación de Postgrado en Medicina/tendencias , Educación de Postgrado en Medicina/métodos , Encuestas y CuestionariosRESUMEN
OBJECTIVES: To evaluate procedures performed during primary debulking surgery (PDS) and interval debulking surgery (IDS) for ovarian cancer. METHODS: Patients surgically treated at our institution for newly diagnosed stage IIIC/IV epithelial ovarian cancer between 6/1/2015-12/31/2021 were identified using a prospectively collected database. Patients were triaged to PDS or neoadjuvant chemotherapy (NACT) followed by IDS using an institutional algorithm. Data on specific procedures performed, including consultants called, were collected from operative and pathology reports. Appropriate statistical analyses were applied. RESULTS: Overall, 467 patients underwent PDS and 434 underwent IDS; 76% (PDS) and 71% (IDS) of cases achieved complete gross resection. Comparing PDS vs IDS cohorts, median age was 63 years (range, 23-86) vs 67 years (range, 35-95), 79% vs 86% of patients had high-grade serous histology, and 38% vs 70% had stage IV disease. Most procedures (except ostomy, distal pancreatectomy) were more common during PDS (P < .05). Bowel surgery was performed during 65% of PDS and 33% of IDS, and upper abdominal surgery during 72% of PDS and 52% of IDS; both were more common during PDS (P < .001). Estimated blood loss (median, 500 mL [PDS] vs 300 mL [IDS]) and operative time (median, 362 min [PDS] vs 267 min [IDS]) were higher for PDS (P < .001). A consulting surgeon was utilized during 31% of PDS and 18% of IDS, with hepatopancreaticobiliary as the most commonly called service (61% and 65%, respectively). CONCLUSIONS: In our study of patients with advanced-stage ovarian cancer, while most procedures were more often performed during PDS, NACT did not obviate the need for radical surgical resection. Thus, advanced surgical skills remain essential.
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Carcinoma Epitelial de Ovario , Procedimientos Quirúrgicos de Citorreducción , Terapia Neoadyuvante , Neoplasias Ováricas , Humanos , Femenino , Procedimientos Quirúrgicos de Citorreducción/métodos , Procedimientos Quirúrgicos de Citorreducción/estadística & datos numéricos , Persona de Mediana Edad , Anciano , Adulto , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/patología , Neoplasias Ováricas/tratamiento farmacológico , Anciano de 80 o más Años , Carcinoma Epitelial de Ovario/cirugía , Carcinoma Epitelial de Ovario/patología , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Adulto Joven , Terapia Neoadyuvante/estadística & datos numéricos , Estadificación de Neoplasias , Quimioterapia Adyuvante/estadística & datos numéricosRESUMEN
OBJECTIVES: We evaluated the performance of a chatbot compared to the National Comprehensive Cancer Network (NCCN) Guidelines for the management of ovarian cancer. METHODS: Using NCCN Guidelines, we generated 10 questions and answers regarding management of ovarian cancer at a single point in time. Questions were thematically divided into risk factors, surgical management, medical management, and surveillance. We asked ChatGPT (GPT-4) to provide responses without prompting (unprompted GPT) and with prompt engineering (prompted GPT). Responses were blinded and evaluated for accuracy and completeness by 5 gynecologic oncologists. A score of 0 was defined as inaccurate, 1 as accurate and incomplete, and 2 as accurate and complete. Evaluations were compared among NCCN, unprompted GPT, and prompted GPT answers. RESULTS: Overall, 48% of responses from NCCN, 64% from unprompted GPT, and 66% from prompted GPT were accurate and complete. The percentage of accurate but incomplete responses was higher for NCCN vs GPT-4. The percentage of accurate and complete scores for questions regarding risk factors, surgical management, and surveillance was higher for GPT-4 vs NCCN; however, for questions regarding medical management, the percentage was lower for GPT-4 vs NCCN. Overall, 14% of responses from unprompted GPT, 12% from prompted GPT, and 10% from NCCN were inaccurate. CONCLUSIONS: GPT-4 provided accurate and complete responses at a single point in time to a limited set of questions regarding ovarian cancer, with best performance in areas of risk factors, surgical management, and surveillance. Occasional inaccuracies, however, should limit unsupervised use of chatbots at this time.
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OBJECTIVES: To compare oncologic outcomes of secondary cytoreductive surgery (SCS) before and after FDA approval of Poly(ADP-ribose) polymerase inhibitor (PARPi) and bevacizumab maintenance therapies for platinum-sensitive recurrent ovarian cancer (PS-ROC). METHODS: Patients who underwent SCS for first recurrence of PS-ROC from 1/1/2013-1/1/2020 were identified. Exclusion criteria included prior chemotherapy for recurrence, bowel obstruction procedures, and palliative surgery. Data were dichotomized pre/post 1/2017, relative to FDA approval of PARPi and bevacizumab maintenance for ROC. Second progression-free survival (PFS2), the primary endpoint, was estimated using Kaplan-Meier method. RESULTS: Overall, 245 patients underwent SCS-131 (53%) pre- and 114 (47%) post-approval. Most patients had high-grade serous tumors (83% and 90%, respectively; p = 0.13). Deleterious BRCA1/2 alterations were identified in 27% (32/120) and 28% (32/113) of tested patients, respectively (p = 0.88). Disease-free intervals pre- and post-approval were: 6-12 months, 16% and 18%; 12-30 months, 56% and 59%; and >30 months, 28% and 24%, respectively (p = 0.73). Overall, 85% and 86% of patients, respectively, achieved complete gross resection (CGR; p > 0.99). PARPi maintenance use increased from 3.8% to 27% (p < 0.001) following approval, and bevacizumab from 1.5% to 12% (p < 0.001). Median PFS2 was 19 and 20.1 months, respectively. In the post group, 1-year PFS2 rate was 84.5% (95% CI, 75.7-90.4%) for patients with CGR vs 56.2% (95% CI, 29.5-76.2%) for those with residual disease; 3-year PFS2 rates were 31.3% (95% CI, 21.6-41.4%) and 12.5% (95% CI, 2.1-32.8%), respectively (p = 0.001). CONCLUSIONS: CGR during SCS is associated with improved PFS2 compared to suboptimal resection. Prospective randomized trials are warranted to elucidate the role of SCS as more therapeutics become available.
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Bevacizumab , Procedimientos Quirúrgicos de Citorreducción , Recurrencia Local de Neoplasia , Neoplasias Ováricas , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Humanos , Femenino , Procedimientos Quirúrgicos de Citorreducción/métodos , Persona de Mediana Edad , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/patología , Neoplasias Ováricas/mortalidad , Bevacizumab/administración & dosificación , Bevacizumab/uso terapéutico , Anciano , Recurrencia Local de Neoplasia/tratamiento farmacológico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/administración & dosificación , Adulto , Supervivencia sin Progresión , Quimioterapia de Mantención/métodos , Anciano de 80 o más Años , Estudios Retrospectivos , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/cirugía , Carcinoma Epitelial de Ovario/mortalidad , Carcinoma Epitelial de Ovario/patologíaRESUMEN
OBJECTIVES: Mesonephric (MA) and mesonephric-like (MLA) adenocarcinomas are rare cancers, and data on clinical behavior and response to therapy are limited. We sought to report molecular features, treatment, and outcomes of MA/MLA from a single institution. METHODS: Patients with MA (cervix) or MLA (uterus, ovary, other) treated at Memorial Sloan Kettering Cancer Center (MSK) from 1/2008-12/2021 underwent pathologic re-review. For patients with initial treatment at MSK, progression-free survival (PFS1) was calculated as time from initial surgery to progression or death; second PFS (PFS2) was calculated as time from start of treatment for recurrence to subsequent progression or death. Overall survival (OS) was calculated for all patients. Images were retrospectively reviewed to determine treatment response. Somatic genetic alterations were assessed by clinical tumor-normal sequencing (MSK-Integrated Mutation Profiling of Actionable Cancer Targets [MSK-IMPACT]). RESULTS: Of 81 patients with confirmed gynecologic MA/MLA, 36 received initial treatment at MSK. Sites of origin included cervix (n = 9, 11%), uterus (n = 42, 52%), ovary (n = 28, 35%), and other (n = 2, 2%). Of the 36 patients who received initial treatment at MSK, 20 (56%) recurred; median PFS1 was 33 months (95% CI: 17-not evaluable), median PFS2 was 8.3 months (95% CI: 6.9-14), and median OS was 87 months (95% CI: 58.2-not evaluable). Twenty-six of the 36 patients underwent MSK-IMPACT testing, and 25 (96%) harbored MAPK pathway alterations. CONCLUSION: Most patients diagnosed with early-stage disease ultimately recurred. Somatic MAPK signaling pathway mutations appear to be highly prevalent in MA/MLA, and therapeutics that target this pathway are worthy of further study.
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Adenocarcinoma , Humanos , Femenino , Estudios Retrospectivos , Adenocarcinoma/genética , Adenocarcinoma/terapia , Adenocarcinoma/patología , Mutación , Ovario/patología , Cuello del Útero/patologíaRESUMEN
OBJECTIVE: Mirvetuximab soravtansine may be a potentially effective therapeutic option for ovarian low-grade serous carcinoma (LGSC), but the prevalence of folate receptor alpha (FRα) overexpression in this tumor type is unknown. We sought to characterize FRα expression in LGSC and its association with clinical and molecular features. METHODS: FRα immunohistochemistry was performed on a tissue microarray comprised of 89 LGSCs and 42 ovarian serous borderline tumors (SBTs). Clinical tumor-normal panel-based sequencing was performed on 78 LGSCs. Associations between FRα-high status and clinicopathologic characteristics and survival outcomes were examined. RESULTS: Of 89 LGSCs, 36 (40%) were FRα-high (≥75% of viable tumor cells exhibiting moderate-to-strong membranous expression). Of 9 patients with LGSC and samples from different timepoints, 4 (44%) had discordant results, with conversion from FRα-negative to FRα-high in 3 (33%) cases. There was no association between FRα-high status with age, race, or progression-free/overall survival. A MAPK pathway genetic alteration, most commonly involving KRAS (n = 23), was present in 45 (58%) LGSCs. Those lacking MAPK pathway alterations were more likely to be FRα-high compared to MAPK-altered LGSCs (61% vs 20%, p < 0.001). In SBTs, FRα-high expression was associated with high-risk (micropapillary) histology and/or subsequent LGSC recurrence compared to conventional SBTs without malignant recurrence (53% vs 9%, p = 0.008). CONCLUSIONS: Future studies of FRα-directed therapy in patients with LGSC are warranted. Discordant FRα status at recurrence suggests potential benefit for retesting. A biomarker-driven approach to direct treatment selection in LGSC is recommended. As high FRα expression is more common amongst tumors lacking MAPK pathway genetic alterations, FRα testing to determine eligibility for mirvetuximab soravtansine therapy is particularly recommended for this subgroup.
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OBJECTIVE: To evaluate the theoretical impact of regionalizing cytoreductive surgery for ovarian cancer (OC) to high-volume facilities on patient travel. METHODS: We retrospectively identified patients with OC who underwent cytoreduction between 1/1/2004-12/31/2018 from the New York State Cancer Registry and Statewide Planning and Research Cooperative System. Hospitals were stratified by low-volume (<21 cytoreductive surgical procedures for OC annually) and high-volume centers (≥21 procedures annually). A simulation was performed; outcomes of interest were driving distance and time between the centroid of the patient's residence zip code and the treating facility zip code. RESULTS: Overall, 60,493 patients met inclusion criteria. Between 2004 and 2018, 210 facilities were performing cytoreductive surgery for OC in New York; 159 facilities (75.7%) met low-volume and 51 (24.3%) met high-volume criteria. Overall, 10,514 patients (17.4%) were treated at low-volume and 49,979 (82.6%) at high-volume facilities. In 2004, 78.2% of patients were treated at high-volume facilities, which increased to 84.6% in 2018 (P < .0001). Median travel distance and time for patients treated at high-volume centers was 12.2 miles (IQR, 5.6-25.5) and 23.0 min (IQR, 15.2-37.0), and 8.2 miles (IQR, 3.7-15.9) and 16.8 min (IQR, 12.4-26.0) for patients treated at low-volume centers. If cytoreductive surgery was centralized to high-volume centers, median distance and time traveled for patients originally treated at low-volume centers would be 11.2 miles (IQR, 3.8-32.3; P < .001) and 20.2 min (IQR, 13.6-43.0; P < .001). CONCLUSIONS: Centralizing cytoreductive surgery for OC to high-volume centers in New York would increase patient travel burden by negligible amounts of distance and time for most patients.
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Procedimientos Quirúrgicos de Citorreducción , Neoplasias Ováricas , Humanos , Femenino , New York , Estudios Retrospectivos , Accesibilidad a los Servicios de Salud , Hospitales de Alto Volumen , Viaje , Neoplasias Ováricas/cirugíaRESUMEN
OBJECTIVE: To determine the safety and efficacy of the oral progesterone antagonist onapristone extended release (onapristone-XR) in patients with recurrent progesterone receptor (PR)-positive adult-type granulosa cell tumor (aGCT), low-grade serous ovarian cancer (LGSOC), or endometrioid endometrial cancer (EEC). METHODS: This single-institution phase II study included patients with PR-positive aGCT, LGSOC, or EEC who received ≥1 prior line of chemotherapy. Patients were enrolled from 5/2019-5/2020. PR status was evaluated via immunohistochemistry. Eligible patients had PR expression ≥1% on tissue collected within 3 years of enrollment. Patients received 50 mg of onapristone-XR twice daily until disease progression or treatment discontinuation. Adverse events were graded by Common Terminology Criteria for Adverse Events version 5.0. The primary endpoint was overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints were response duration, clinical benefit rate (CBR), and safety. RESULTS: Five patients with LGSOC and 1 with EEC enrolled, but both cohorts closed early due to slow accrual. Fourteen patients with aGCT enrolled and completed stage 1 accrual. No responses were observed. Four patients with LGSOC were evaluable, with median PFS of 4.4 months (range, 1.8-NE) and CBR of 50% (range, 6.8%-93.2%). All 14 patients with aGCT were evaluable, with median PFS of 2.8 months (range, 1.6-4.9), 6-month PFS rate of 21.4% (range, 5.2%-44.8%), 12-month PFS rate of 14.3% (range, 2.3%-36.6%), and a CBR of 35.7% (range, 12.8%-64.9%). CONCLUSIONS: The study did not meet its primary endpoint. While onapristone-XR was well tolerated in all 3 arms, no objective responses were observed.
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OBJECTIVE: To define molecular features of ovarian cancer (OC) with germline pathogenic variants (PVs) in non-BRCA homologous recombination (HR) genes and analyze survival compared to BRCA1/2 and wildtype (WT) OC. METHODS: We included patients with OC undergoing tumor-normal sequencing (MSK-IMPACT) from 07/01/2015-12/31/2020, including germline assessment of BRCA1/2 and other HR genes ATM, BARD1, BRIP1, FANCA, FANCC, NBN, PALB2, RAD50, RAD51B, RAD51C, and RAD51D. Biallelic inactivation was assessed within tumors. Progression-free (PFS) and overall survival (OS) were calculated from pathologic diagnosis using the Kaplan-Meier method with left truncation. Whole-exome sequencing (WES) was performed in a subset. RESULTS: Of 882 patients with OC, 56 (6.3%) had germline PVs in non-BRCA HR genes; 95 (11%) had BRCA1-associated OC (58 germline, 37 somatic); and 59 (6.7%) had BRCA2-associated OC (40 germline, 19 somatic). High rates of biallelic alterations were observed among germline PVs in BRIP1 (11/13), PALB2 (3/4), RAD51B (3/4), RAD51C (3/4), and RAD51D (8/10). In cases with WES (27/35), there was higher tumor mutational burden (TMB; median 2.5 [1.1-6.0] vs. 1.2 mut/Mb [0.6-2.6]) and enrichment of HR-deficient (HRD) mutational signatures in tumors associated with germline PALB2 and RAD51B/C/D compared with BRIP1 PVs (p < 0.01). Other features of HRD, including telomeric-allelic imbalance (TAI) and large-scale state transitions (LSTs), were similar. Although there was heterogeneity in PFS/OS by gene group, only BRCA1/2-associated OC had improved survival compared to WT OC (p < 0.01). CONCLUSIONS: OCs associated with germline PVs in non-BRCA HR genes represent a heterogenous group, with PALB2 and RAD51B/C/D associated with an HRD phenotype.
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Proteína BRCA1 , Neoplasias Ováricas , Humanos , Femenino , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias Ováricas/patología , Mutación de Línea Germinal , Recombinación Homóloga , Fenotipo , Células Germinativas/patología , Predisposición Genética a la EnfermedadRESUMEN
OBJECTIVES: Although genetic testing (GT) is universally recommended for patients with epithelial ovarian cancer (EOC), rates are low (34%). In 1/2019, we implemented mainstreaming-GT in parallel with tumor testing via MSK-IMPACT within oncology clinics. We sought to determine GT rates pre/post-mainstreaming and patient characteristics associated with GT. METHODS: Patients with newly diagnosed EOC seen at our institution from 7/1/2015-3/31/2022 were included. Clinical data were abstracted including social determinants of health (SDOH) variables, race/ethnicity, marital status, insurance, language, comorbidities, employment, and Yost index, a measure of socioeconomic status. GT rates were calculated overall and pre-/post-mainstreaming (1/2019). Logistic regression models were fit to identify variables associated with GT. RESULTS: Of 1742 patients with EOC, 1591 (91%) underwent GT. Rates of GT increased from 87% to 95% after mainstreaming (p < 0.001). Among 151 patients not undergoing GT, major reasons were lack of provider recommendation (n = 76, 50%) and logistical issues (n = 38, 25%) with few declining (n = 14, 9%) or having medical complications preventing GT (n = 7, 4.6%). High-grade serous histology, advanced stage (III/IV), and having a spouse/partner were associated with increased GT uptake (p < 0.01). Among SDOH variables, there were no differences by insurance, Yost score, language, comorbidities, employment, or race/ethnicity. In multivariable models, likelihood of GT increased with mainstreaming, even after adjustment for histology, stage, and marital status (OR 3.77; 95% CI: 2.56-5.66). CONCLUSIONS: Mainstreaming increased the likelihood of GT in patients with EOC. We found lower testing rates in patients without partners/spouses, non-high-grade serous histology, and early-stage disease, representing potential areas for future interventions.
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Carcinoma Epitelial de Ovario , Pruebas Genéticas , Neoplasias Ováricas , Humanos , Femenino , Persona de Mediana Edad , Carcinoma Epitelial de Ovario/genética , Carcinoma Epitelial de Ovario/diagnóstico , Carcinoma Epitelial de Ovario/patología , Pruebas Genéticas/estadística & datos numéricos , Pruebas Genéticas/métodos , Neoplasias Ováricas/genética , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/patología , Anciano , Adulto , Aceptación de la Atención de Salud/estadística & datos numéricosRESUMEN
Complex surgery is an essential component in the management of advanced ovarian cancer. Furthermore, achieving complete gross resection in cytoreductive surgery appears to be associated with significant survival benefits in patients with advanced ovarian cancer. The goal of this review is to demonstrate the advancement of surgical techniques in gynecologic oncology surgery, including resection of disease within the intrathoracic and inguinal regions. This progress has expanded the option of surgery to more patients, especially those who would have previously been deemed inoperable. In this review we describe the most notable studies and reports of surgical resection of ovarian cancer involving cardiophrenic/supradiaphragmatic lymph nodes, mediastinum, lung pleura or parenchyma, and the inguinal region. We also describe the growing role that video-assisted thoracic surgery has played in advanced ovarian cancer diagnosis and management. The studies, series, and reports described demonstrate that comprehensive surgical procedures outside of the abdomen or pelvis can be both safe and feasible in properly selected patients. They also suggest that resection of disease outside of the abdomen or pelvis may benefit appropriately selected patients. Future studies are necessary to identify which patients may benefit most from upfront surgery versus neoadjuvant chemotherapy when ovarian cancer metastasis is present in the thoracic or inguinal regions.
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Procedimientos Quirúrgicos de Citorreducción , Neoplasias Ováricas , Humanos , Femenino , Abdomen , Neoplasias Ováricas/cirugía , Carcinoma Epitelial de Ovario , PelvisRESUMEN
BACKGROUND: Ovarian cancer with extensive metastatic disease involving pelvic structures often requires rectosigmoid resection for complete gross resection; however, it is associated with increased surgical morbidity. There are limited data, and none in ovarian cancer, on near-infrared assessment of perfusion in rectosigmoid resections with anastomosis. PRIMARY OBJECTIVE: To compare the rate of pelvic complications (pelvic abscesses, anastomotic leaks, and infections) within 30 days of surgery with and without near-infrared assessment of perfusion at time of rectosigmoid resection and re-anastomosis in patients undergoing cytoreductive surgery for ovarian cancer. STUDY HYPOTHESIS: We hypothesize the use of near-infrared technology (intravenous indocyanine green and endoscopic near-infrared fluorescence imaging), compared with standard intra-operative assessment, to evaluate anastomotic perfusion at time of rectosigmoid resection and re-anastomosis will result in lower rates of post-operative pelvic complications. TRIAL DESIGN: This is a planned multicenter randomized controlled trial. Patients who undergo rectosigmoid resection as part of their ovarian cytoreductive surgery will be randomized 1:1 to standard assessment of anastomosis with the surgeon's usual technique (control arm) or assessment with near-infrared angiography using indocyanine green and endoscopic fluorescence imaging (experimental arm). Randomization will occur after rectosigmoid resection has been completed and the surgeon declares their plan to create a diverting ostomy. Randomization will be stratified by plan for diverting ostomy. MAJOR INCLUSION/EXCLUSION CRITERIA: Main inclusion criteria include patients with primary or recurrent ovarian, fallopian tube, or primary peritoneal cancer who are scheduled for cytoreductive surgery with suspected need for low-anterior rectosigmoid resection. PRIMARY ENDPOINT: Rate of 30-day post-operative pelvic complications. SAMPLE SIZE: 310 (155 per arm) ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Q2 2027 and Q4 2027, respectively. TRIAL REGISTRATION: NCT04878094.
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Anastomosis Quirúrgica , Neoplasias Ováricas , Femenino , Humanos , Anastomosis Quirúrgica/métodos , Anastomosis Quirúrgica/efectos adversos , Angiografía/métodos , Colon Sigmoide/cirugía , Colon Sigmoide/diagnóstico por imagen , Procedimientos Quirúrgicos de Citorreducción/métodos , Verde de Indocianina/administración & dosificación , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/patología , Complicaciones Posoperatorias , Ensayos Clínicos Controlados Aleatorios como Asunto , Recto/cirugía , Recto/diagnóstico por imagen , Espectroscopía Infrarroja Corta/métodosRESUMEN
OBJECTIVES: To develop a pre-operative tool to estimate the risk of peri-operative packed red blood cell transfusion in primary debulking surgery. METHODS: We retrospectively reviewed an institutional database to identify patients who underwent primary debulking surgery for ovarian cancer at a single center between January 1, 2001 and May 31, 2019. Receiver operating characteristic curve and area under the receiver operating characteristic curve (AUC) were calculated. Five-fold cross-validation was applied to the multivariate model. Significant variables were assigned a 'BLOODS' (BLood transfusion Over an Ovarian cancer Debulking Surgery) score of +1 if present. A total BLOODS score was calculated for each patient, and the odds of receiving a transfusion was determined for each score. RESULTS: Overall, 1566 patients met eligibility criteria; 800 (51%) underwent a peri-operative blood transfusion. Odds ratios (OR) were statistically significant for American Society of Anesthesiologists scores of 3 and 4 (OR 1.34, 95% confidence interval (95% CI) 1.09 to 1.63), pre-operative levels of cancer antigen 125 (CA125) (OR 2.43, 95% CI 1.98 to 2.99), platelets (OR 1.59, 95% CI 1.45 to 1.74), obesity (OR 0.76, 95% CI 0.60 to 0.96), presence of carcinomatosis (OR 2.45, 95% CI 1.93 to 3.11), bulky upper abdominal disease (OR 2.86, 95% CI 2.32 to 3.54), pre-operative serum albumin level (OR 0.31, 95% CI 0.24 to 0.40), and pre-operative hemoglobin level (OR 0.56, 95% CI 0.51 to 0.61). The corrected AUC was 0.748 (95% CI 0.693 to 0.804). BLOODS scores of 0 and 5 corresponded to 11% and 73% odds, respectively, of receiving a peri-operative blood transfusion. CONCLUSIONS: We developed a universal pre-operative scoring system, the BLOODS score, to help identify patients with ovarian cancer who would benefit from surgical planning and blood-saving techniques. The BLOODS score was directly proportional to the American Society of Anesthesiologists score, presence of upper abdominal disease, carcinomatosis, CA125 level, and platelets level. We believe this model can help physicians with surgical planning and can benefit patient outcomes.
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Procedimientos Quirúrgicos de Citorreducción , Neoplasias Ováricas , Humanos , Femenino , Estudios Retrospectivos , Neoplasias Ováricas/sangre , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/patología , Persona de Mediana Edad , Procedimientos Quirúrgicos de Citorreducción/métodos , Anciano , Transfusión Sanguínea/estadística & datos numéricos , Transfusión Sanguínea/métodos , Medición de Riesgo/métodos , AdultoRESUMEN
OBJECTIVE: To evaluate the feasibility and outcomes of performing procedural interventions, defined as surgical resection, tumor ablation, or targeted radiation therapy, for oligoprogressive disease among patients with gynecologic malignancies who are treated with immune checkpoint blockade. METHODS: Patients with gynecologic cancers treated with immune checkpoint blockade between January 2013 and October 2021 who underwent procedural interventions including surgical resection, interventional radiology ablation, or radiation therapy for oligoprogressive disease were identified. Procedures performed before immune checkpoint therapy initiation or ≥6 months after therapy completion were excluded. Long immunotherapy duration prior to intervention was defined as ≥6 months. Progression-free survival and overall survival were calculated from procedure date until disease progression or death, respectively. RESULTS: During the study period, 886 patients met inclusion criteria and received immune checkpoint blockade therapy. Of these, 34 patients underwent procedural interventions for oligoprogressive disease; 7 underwent surgical resection, 3 underwent interventional radiology ablation, and 24 underwent radiation therapy interventions. Primary disease sites included uterus (71%), ovary (24%), and cervix (6%). Sites of oligoprogression included abdomen/pelvis (26%), bone (21%), lung (18%), distant lymph node (18%), brain (9%), liver (6%), and vagina (3%). Most tumors (76%) did not exhibit microsatellite instability or mismatch repair deficiency. Approximately half (53%) of the patients had long immune checkpoint therapy duration prior to intervention. Median progression-free survival following the procedure was 5.3 months (95% CI, 3.1-9.9), and median overall survival was 21.7 months (95% CI, 14.9-not estimable). Long versus short immune checkpoint therapy duration prior to procedure and length of immune checkpoint therapy had no effect on progression-free or overall survival. CONCLUSIONS: Procedural interventions for patients with oligoprogression on immune checkpoint blockade therapy are feasible and demonstrate favorable outcomes. With expanding use of immune checkpoint therapy, it is important to investigate combined modalities to maximize therapeutic benefit for patients with gynecologic cancers.
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Neoplasias Encefálicas , Neoplasias de los Genitales Femeninos , Humanos , Femenino , Neoplasias de los Genitales Femeninos/radioterapia , Inhibidores de Puntos de Control Inmunológico , Terapia Combinada , Supervivencia sin Progresión , Estudios RetrospectivosRESUMEN
High-grade serous tubo-ovarian carcinoma (HGSC) is a major cause of cancer-related death. Treatment is not uniform, with some patients undergoing primary debulking surgery followed by chemotherapy (PDS) and others being treated directly with chemotherapy and only having surgery after three to four cycles (NACT). Which strategy is optimal remains controversial. We developed a mathematical framework that simulates hierarchical or stochastic models of tumor initiation and reproduces the clinical course of HGSC. After estimating parameter values, we infer that most patients harbor chemoresistant HGSC cells at diagnosis and that, if the tumor burden is not too large and complete debulking can be achieved, PDS is superior to NACT due to better depletion of resistant cells. We further predict that earlier diagnosis of primary HGSC, followed by complete debulking, could improve survival, but its benefit in relapsed patients is likely to be limited. These predictions are supported by primary clinical data from multiple cohorts. Our results have clear implications for these key issues in HGSC management.
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Simulación por Computador , Detección Precoz del Cáncer , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/terapia , Anciano , Estudios de Cohortes , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/terapia , Procedimientos Quirúrgicos de Citorreducción , Femenino , Humanos , Persona de Mediana Edad , Modelos Biológicos , Terapia Neoadyuvante , Clasificación del Tumor , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Análisis de Supervivencia , Resultado del Tratamiento , Carga TumoralRESUMEN
BACKGROUND: Data on platinum sensitivity of low-grade serous ovarian carcinoma (LGSOC) in the upfront setting is lacking, and there is limited and contradictory information on chemotherapy responses in recurrent disease. METHODS: Patients with LGSOC seen at a comprehensive cancer center from January 1, 1998 to September 30, 2021 were identified from institutional databases. Response to neoadjuvant chemotherapy (NACT) or adjuvant platinum-based chemotherapy and to second- to fifth-line regimens was retrospectively characterized by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Wilcoxon rank-sum and two-tailed Fisher exact tests were employed. RESULTS: Of 50 patients, 12 received platinum doublets for suboptimal residual disease and 11 as NACT. Of 12 patients with suboptimal residual disease, seven (58%) achieved objective responses (five partial responses [PRs] and two complete responses); of the 11 patients who underwent NACT, one (9%) achieved a PR (p = .027). The 15 remaining patients had stable disease on first-line platinum chemotherapy. Of 44 patients who recurred, 20 had RECIST-evaluable responses to second-line and 27 to third-line chemotherapy. Objective response rates to platinum-based chemotherapy were 22% (two of nine) in the second line and 10% (one of 10) in the third. In second and third lines, highest response rates were observed with nonplatinum chemotherapy with bevacizumab, at 100% (two of two) and 30% (three of 10), respectively. CONCLUSIONS: Primary platinum-based chemotherapy has moderate activity in LGSOC and minimal activity in the recurrent setting, suggesting standard definitions of platinum sensitivity may not apply in LGSOC. In the second and third lines, nonplatinum chemotherapy/bevacizumab elicited the highest response rates.
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Cistadenocarcinoma Seroso , Neoplasias Ováricas , Neoplasias Peritoneales , Femenino , Humanos , Neoplasias Ováricas/patología , Bevacizumab/uso terapéutico , Platino (Metal)/uso terapéutico , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Cistadenocarcinoma Seroso/tratamiento farmacológico , Neoplasias Peritoneales/terapiaRESUMEN
OBJECTIVE: We sought to document current surgical practices among gynecologic oncologists in the United States. METHODS: In March/April 2020, we conducted a cross-sectional survey among members of the Society of Gynecologic Oncology to identify gynecologic oncology practice trends in the United States. The survey collected demographic data and queried participants on types of surgical procedures performed and chemotherapy use. Univariant and multivariant analyses were used to evaluate the association between surgeon practice type, region of practice, working with gynecologic oncology fellows, time in practice, and dominant surgical modality of practice on performance of specific procedures. RESULTS: Among 1199 gynecologic oncology surgeons who were emailed the survey, 724 completed the survey (60.4% response rate). Of these respondents, 170 (23.5%) were within 6 years of fellowship graduation, 368 (50.8%) identified as female; and 479 (66.2%) worked in an academic setting. Surgeons who worked with gynecologic oncology fellows were more likely to perform bowel surgery, upper abdominal surgery, complex upper abdominal surgery, and prescribe chemotherapy. Surgeons who were ≥ 13 years out from fellowship graduation were more likely to perform bowel surgery and complex abdominal surgery and less likely to prescribe chemotherapy and perform sentinel lymph node dissections (P < 0.05). CONCLUSIONS: These findings highlight the variation in surgical procedures performed by gynecologic oncologists in the United States. These data support that there are practice variations that would benefit from further investigation.
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Ginecología , Oncólogos , Femenino , Humanos , Estados Unidos , Estudios Transversales , Escisión del Ganglio Linfático , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To assess long-term outcomes of patients with advanced-stage ovarian cancer by treatment type. METHODS: Patients with newly diagnosed stage III-IV ovarian cancer who underwent primary treatment at our tertiary cancer center from 01/01/2015-12/31/2015 were included. We reviewed electronic medical records for clinicopathological, treatment, and survival characteristics. RESULTS: Of 153 patients, 88 (58%) had stage III and 65 (42%) stage IV disease. Median follow-up was 65.8 months (range, 3.6-75.3). Eighty-nine patients (58%) underwent primary debulking surgery (PDS), 50 (33%) received neoadjuvant chemotherapy followed by interval debulking surgery (IDS), and 14 (9%) received chemotherapy alone, without surgery (NSx). Median PFS to first recurrence was 26.2 months (range, 20.1-36.2), 13.5 months (range, 12-15.1), and 4.2 months (range, 1.1-5.8) in the PDS, IDS, and NSx groups, respectively (P < .001). At first recurrence/progression, 80 patients (72.7%) were treated with chemotherapy, 28 (25.5%) underwent secondary cytoreductive surgery (CRS) followed by chemotherapy, and 2 (1.8%) received no treatment. Seven patients (4.6%) underwent palliative surgery for malignant bowel obstruction. Overall, 62.7% received 1-3 lines of chemotherapy. The 5-year OS rates were 53.2% (95% CI: 44.7%-61%) for the entire cohort, 71.5% (95% CI: 60.2%-80%) for the PDS group, 35.2% (95% CI: 22.2-48.5%) for the IDS group, and 7.9% (95% CI: 0.5%-29.9%) for the NSx group. CONCLUSION: The longitudinal treatment modalities and outcomes of patients with advanced ovarian cancer described here can be useful for patient counseling, long-term planning, and future comparison studies.