Trends in specific procedures performed at the time of cytoreduction for ovarian cancer: Is interval debulking surgery truly less radical? A Memorial Sloan Kettering Cancer Center Team Ovary study.

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.

ARIA II: a randomized controlled trial of near-infrared Angiography during RectosIgmoid resection and Anastomosis in women with ovarian cancer.

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.

Development and perception of surgery-specific goals of care discussions in the preoperative setting: A learning pilot.

BACKGROUND: Goals of care discussions are infrequently documented in the preoperative period. Furthermore, documentation does not consistently address what matters most to patients, although patient values (PV) are central to person-centered care. METHODS: A multidisciplinary working group was formed. An electronic note comprised of (1) topics of discussion, (2) PV, and (3) advance care planning (ACP), was created and embedded into existing note templates for Gynecologic Surgical Oncology. Surgeons and advanced practice providers (APPs) were educated to conduct and document these conversations in preoperative clinic for patients undergoing cancer surgery for a pilot period. Data were collected regarding usage of the template. Focus groups with surgeons, APPs, and patients were conducted. Qualitative analysis was performed on transcripts. RESULTS: During the pilot, 7 surgeon/APP teams utilized the template on a total of 55 notes. Average number of notes completed per surgeon was 7.8 (SD 8.5). Forty-six notes (84%) included topics of discussion, 15 (27%) included PV, 4 (7%) included ACP. Qualitative analysis of focus group transcripts revealed that clinicians and patients perceived the initiative to be useful and important, although implementation barriers were identified. CONCLUSION: Creating a surgery-specific GOC template is feasible. Iterative revisions are needed to increase utility in clinic workflows.

Bridging Communication Gaps Between Radiologists, Referring Physicians, and Patients Through Standardized Structured Cancer Imaging Reporting: The Experience with Female Pelvic MRI Assessment Using O-RADS and a Simulated Cohort Patient Group.

RATIONALE AND OBJECTIVES: This study aimed to evaluate whether implementing structured reporting based on Ovarian-Adnexal Reporting and Data System (O-RADS) magnetic resonance imaging (MRI) in women with sonographically indeterminate adnexal masses improves communication between radiologists, referrers, and patients/caregivers and enhances diagnostic performance for determining adnexal malignancy. MATERIALS AND METHODS: We retrospectively analyzed prospectively issued MRI reports in 2019-2022 performed for characterizing adnexal masses before and after implementing O-RADS MRI; 56 patients/caregivers and nine gynecologic oncologists ("referrers") were surveyed about report interpretability/clarity/satisfaction; responses for pre- and post-implementation reports were compared using Fisher's exact and Chi-squared tests. Diagnostic performance was assessed using receiver operating characteristic curves. RESULTS: A total of 123 reports from before and 119 reports from after O-RADS MRI implementation were included. Survey response rates were 35.7% (20/56) for patients/caregivers and 66.7% (6/9) for referrers. For patients/caregivers, O-RADS MRI reports were clearer (p < 0.001) and more satisfactory (p < 0.001) than unstructured reports, but interpretability did not differ significantly (p = 0.14), as 28.0% (28/100) of postimplementation and 38.0% (38/100) of preimplementation reports were considered difficult to interpret. For referrers, O-RADS MRI reports were clearer, more satisfactory, and easier to interpret (p < 0.001); only 1.3% (1/77) were considered difficult to interpret. For differentiating benign from malignant adnexal lesions, O-RADS MRI showed area under the curve of 0.92 (95% confidence interval [CI], 0.85-0.99), sensitivity of 0.81 (95% CI, 0.58-0.95), and specificity of 0.91 (95% CI, 0.83-0.96). Diagnostic performance of reports before implementation could not be calculated due to many different phrases used to describe the likelihood of malignancy. CONCLUSION: Implementing standardized structured reporting using O-RADS MRI for characterizing adnexal masses improved clarity and satisfaction for patients/caregivers and referrers. Interpretability improved for referrers but remained limited for patients/caregivers.

Impact of postoperative morbidity on outcomes in patients with advanced epithelial ovarian cancer undergoing intestinal surgery at the time of primary or interval cytoreductive surgery: A Memorial Sloan Kettering Cancer Center Team Ovary study.

OBJECTIVE: To assess the impact of short-term postoperative complications on oncologic outcomes for patients with epithelial ovarian cancer undergoing primary cytoreductive surgery (PCS) or interval cytoreductive surgery (ICS) with intestinal resection. METHODS: A retrospective chart review was performed for patients with ovarian cancer who underwent PCS or ICS with at least one intestinal resection at our institution from 1/1/2015 to 12/31/2020. Progression-free survival (PFS) and overall survival (OS) were analyzed for the PCS and ICS cohorts separately. Short-term complications within 30 days of surgery (surgical secondary events [SSEs]) were graded by a validated institutional SSE system. RESULTS: Among 437 patients who underwent intestinal resections during PCS (n = 289) or ICS (n = 148), 183 (42%) had one, 180 (41%) had two, and 74 (17%) had three intestinal resections. Six (1.4%) of 437 patients experienced an anastomotic leak postoperatively. There were no perioperative deaths. There was no difference in PFS and OS for patients who underwent PCS with any SSE vs. no SSE within 30 days of surgery (HR, 1.05; 95% CI: 0.76-1.47; p = 0.75 and HR, 0.79; 95% CI: 0.49-1.26; p = 0.32, respectively). There was no difference in PFS and OS for patients who underwent ICS with any SSE vs. no SSE within 30 days of surgery (HR, 1.43; 95% CI: 0.99-2.07; p = 0.055 and HR. 1.18; 95% CI: 0.72-1.93; p = 0.52, respectively. CONCLUSION: Short-term postoperative morbidity for patients who underwent intestinal surgery during primary surgical management for advanced ovarian cancer did not impact oncologic outcomes.

Oncologic outcomes of robot-assisted laparoscopy versus conventional laparoscopy for the treatment of apparent early-stage endometrioid adenocarcinoma of the uterus.

OBJECTIVE: To compare long-term oncologic outcomes in patients with clinically uterine-confined endometrioid endometrial cancer who underwent surgical staging with robot-assisted (RA) versus conventional laparoscopy. METHODS: We performed a retrospective chart review of patients with newly diagnosed, uterine-confined endometrioid endometrial cancer who were treated and had primary surgery at our institution between 1/1/2009-1/1/2018. Clinicopathologic, surgical, and survival data were collected. Appropriate statistical methods were applied. RESULTS: Of 1728 patients identified, 1389 (80.4%) underwent RA and 339 (19.6%) conventional laparoscopy. At diagnosis, median age was 60 years (range, 24-92) and median BMI was 30.2 kg/m2 (range, 15.1-71.5). In the RA group, patients had longer operative time (170 vs 152 min, P < .001), lower conversion rate to laparotomy (0.6% vs 4.7%, P < .001), and a higher proportion had a BMI > 40 kg/m2 (17.2% vs 11.5%, P = .01) and same-day discharge (19.2% vs 5.3%, P < .001). Overall, 93% (RA) and 90% (conventional) of patients underwent lymph node assessment (P = .1). Comparing the RA versus conventional groups, final surgical stage on pathology (P = .6), median follow-up (55.7 vs 52.9 months, P = .4), and rates of perioperative complications (9.9% vs 7.7%, P = .6), recurrence (9.5% vs 7.4%, P = .3), 5-year PFS (88.5% vs 91.0%, P = .3), and 5-year OS (92.5% vs 92.4%, P = .7) were not significantly different. No significant increase in risk of recurrence (HR = 1.2, 95% CI: 0.8-1.9, P = .3) or poorer OS outcomes (HR = 0.9, 95% CI: 0.6-1.4, P = .7) were observed in the RA group. CONCLUSION: In uterine-confined endometrioid endometrial cancers, surgical staging using RA laparoscopy was not associated with adverse survival outcomes compared to conventional laparoscopy.

Assessing the Genomic Landscape of Cervical Cancers: Clinical Opportunities and Therapeutic Targets.

PURPOSE: Tumor genomic profiling is increasingly used to guide treatment strategy in patients with cancer. We integrated tumor genomic, clinical demographic, and treatment response data to assess how prospective tumor-normal sequencing impacted treatment selection in patients with cervical cancer. EXPERIMENTAL DESIGN: Cervical cancers were prospectively analyzed using the MSK-IMPACT (Memorial Sloan Kettering Cancer Center - Integrated Mutation Profiling of Actionable Cancer Targets) next-generation sequencing panel. Clinical data, including histology, stage at diagnosis, treatment history, clinical trial enrollment and outcomes, date of last follow-up, and survival status were obtained from medical records. RESULTS: A total of 177 patients with cervical cancer (squamous, 69; endocervical adenocarcinoma, 50; gastric type, 22; adenosquamous, 21; and other, 15) underwent MSK-IMPACT testing. The most prevalent genomic alterations were somatic mutations or amplifications in PIK3CA (25%), ERBB2 (12%), KMT2C (10%), and KMT2D (9%). Furthermore, 13% of patients had high tumor mutational burden (TMB >10 mut/Mb), 3 of which were also microsatellite instability-high (MSI-H). Thirty-seven percent of cases had at least one potentially actionable alteration designated as a level 3B mutational event according to the FDA-recognized OncoKB tumor mutation database and treatment classification system. A total of 30 patients (17%) were enrolled on a therapeutic clinical trial, including 18 (10%) who were matched with a study based on their MSK-IMPACT results. Twenty patients (11%) participated in an immune checkpoint inhibition study for metastatic disease; 2 remain progression free at >5 years follow-up. CONCLUSIONS: Tumor genomic profiling can facilitate the selection of targeted/immunotherapies, as well as clinical trial enrollment, for patients with cervical cancer.

Leave it in the past - primary treatment modality for high-grade epithelial ovarian cancer is not associated with secondary cytoreduction outcomes: A Memorial Sloan Kettering Cancer Center Team Ovary study.

OBJECTIVES: To compare outcomes of patients with high-grade epithelial ovarian cancer (EOC) who underwent secondary cytoreduction surgery (SCS) after up-front treatment with neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) versus primary debulking surgery (PDS). METHODS: Patients with high-grade EOC who underwent SCS from 2/1/2004-10/31/2021 were classified by up-front treatment. Clinical and treatment characteristics were compared between cohorts. Progression-free survival (PFS2) and overall survival (OS2) following SCS were compared using a Cox model adjusted for stage, age at SCS, and number of years between end of chemotherapy and SCS. RESULTS: Of 374 patients, 62 (17%) underwent NACT-IDS and 312 (83%) PDS. Justification for NACT was disease extent (n = 57, 92%), comorbidities (n = 3, 5%), and thromboembolism (n = 2, 3%). The NACT-IDS cohort had a higher median age at SCS (64 years [IQR: 56-70] vs 59 years [IQR: 53-66]; P = .03), higher proportion of stage III/IV disease (100% vs 81%; P < .001), and shorter median interval between end of chemotherapy and SCS (1.5 years [IQR: 1.1-2.3] vs 1.9 years [IQR: 1.3-3.1]; P = .01). Achievement of complete gross resection at SCS did not differ between NACT-IDS and PDS (84% vs 88%; P = .18). PFS2 (HR: 1.19, 95% CI: 0.83-1.71) and OS2 (HR: 0.96, 95% CI: 0.57-1.63) did not vary by primary treatment modality after adjusting for clinically relevant covariates. CONCLUSIONS: Despite more extensive disease at presentation, patients with high-grade EOC who recur after NACT-IDS seem to have similar surgical and survival outcomes after SCS compared to patients who recur after PDS, suggesting that prior NACT-IDS should not preclude SCS.

Patient-reported symptoms after minimally invasive hysterectomy and association with postoperative complications.

OBJECTIVE: To describe patient-reported postoperative symptoms and to evaluate the use of digital symptom tracking and alerts to detect postoperative complications. METHODS: We retrospectively reviewed patients who underwent a minimally invasive hysterectomy and enrolled in our Recovery Tracker program from 4/5/17-12/31/21. The Recovery Tracker is an at-home virtual tool used to track patient-reported postoperative symptoms for 10 days. Predefined thresholds for "red" and "yellow" alerts are based on symptom severity and timing. Data on patient demographics, surgery, and postoperative course were collected to evaluate the association of alerts with complications and compare outcomes of patients who did/did not enroll in the program. RESULTS: Of 2362 eligible patients, 1694 (71.7%) enrolled in the Recovery Tracker program. Pain was the most severe symptom, followed by fatigue. Eighty-seven patients experienced 102 complications (5.1% complication rate) and 32 experienced 39 grade ≥ 2 complications (1.9% severe complication rate). Excluding complications that occurred prior to Recovery Tracker use, 1673 patients experienced 28 grade ≥ 2 complications. Of 345 patients (20.6%) who triggered a red alert, 13 (3.8%) had a grade ≥ 2 complication. Of 1328 patients (79.4%) with no red alerts, 15 (1.13%) had a grade ≥ 2 complication. Relative risk of a grade ≥ 2 complication if a red alert was triggered was 3.25 (95% CI: 1.6-6.9, P = .002). Rate of severe complications was significantly higher among patients who did not use the tool (3.3% vs 1.9%; P = .04). CONCLUSIONS: The Recovery Tracker tool may assist in early identification of postoperative symptoms after minimally invasive hysterectomy.

Laparoscopy with or without robotic assistance does not negatively impact long-term oncologic outcomes in patients with uterine serous carcinoma.

OBJECTIVES: We sought to compare outcomes between minimally invasive surgery (MIS) and laparotomy in patients with clinical stage I uterine serous carcinoma (USC). METHODS: Patients who underwent surgery for newly diagnosed USC between 11/1/1993 and 12/31/2017 were retrospectively identified and assigned to either the MIS cohort or the laparotomy cohort. Patients with conversion to laparotomy were analyzed with the MIS cohort. Chi-square and Mann-Whitney tests were used to compare categorical and continuous variables, respectively. Kaplan-Meier curves were used to estimate survival and compared using the log-rank test. RESULTS: In total, 391 patients met inclusion criteria; 242 underwent MIS (35% non-robotic and 65% robotic-assisted laparoscopies) and 149 underwent laparotomy. Age, BMI, stage, and washings status did not differ between cohorts. Patients who underwent MIS were less likely to have lymphovascular space invasion (LVSI; 35.1% vs 48.3%), had fewer nodes removed (median, 9 vs 15), and lower rates of paraaortic nodal dissection (44.6% vs 65.1%). Rates of adjuvant therapy did not differ between cohorts. Median follow-up times were 63.0 months (MIS cohort) vs 71.0 months (laparotomy cohort; P = .04). Five-year PFS rates were 58.7% (MIS) vs 59.8% (laparotomy; P = .1). Five-year OS rates were 65.2% (MIS) compared to 63.5% (laparotomy; P = .2). On multivariable analysis, higher stage, deep myometrial invasion, and positive washings were associated with decreased PFS. Age ≥ 65 years, higher stage, LVSI, and positive washings were associated with shorter OS. CONCLUSIONS: MIS does not compromise outcomes in patients with newly diagnosed USC and should be offered to these patients to minimize surgical morbidity.

Association of bowel preparation with surgical-site infection in gynecologic oncology surgery: Post-hoc analysis of a randomized controlled trial.

OBJECTIVE: To determine the relationship between bowel preparation and surgical-site infection (SSI) incidence following colorectal resection during gynecologic oncology surgery. METHODS: This post-hoc analysis used data from a randomized controlled trial of patients enrolled from 03/01/2016-08/20/2019 with presumed gynecologic malignancy investigating negative-pressure wound therapy among those requiring laparotomy. Patients were treated preoperatively without bowel preparation, oral antibiotic bowel preparation (OABP), or OABP plus mechanical bowel preparation (MBP) per surgeon preference. Univariate and multivariable analyses with stepwise model selection for SSI were performed for confirmed gynecologic malignancies requiring colorectal resection. RESULTS: Of 161 cases, 15 (9%) had no preparation, 39 (24%) OABP only, and 107 (66%) OABP+MBP. The overall SSI rate was 19% (n = 31)-53% (n = 8/15) in the no preparation, 21% (n = 8/39) in the OABP alone, and 14% (n = 15/107) in the OABP+MBP groups (P = 0.003). The difference between OABP and OABP+MBP was non-significant (P = 0.44). The median length of stay was 9 (range, 6-12), 6 (range, 5-8), and 7 days (range, 6-10), respectively (P = 0.045). The overall complication rate (34%; n = 54) did not significantly vary by preparation type (P = 0.23). On univariate logistic regression analysis, OABP (OR, 0.23; 95% CI: 0.06-0.80) and OABP+MBP (OR, 0.14; 95% CI: 0.04-0.45) were associated with decreased SSI risk compared to no preparation (P = 0.004). On multivariate analysis, both methods of preparation retained a significant impact on SSI rates (P = 0.004). CONCLUSION: Bowel preparation is associated with reduced SSI incidence and is beneficial for patients undergoing gynecologic oncology surgery with anticipated colorectal resection. Further investigation is needed to determine whether OABP alone is sufficient.

High-Sensitivity Mutation Analysis of Cell-Free DNA for Disease Monitoring in Endometrial Cancer.

PURPOSE: We sought to determine whether sequencing analysis of circulating cell-free DNA (cfDNA) in patients with prospectively accrued endometrial cancer captures the mutational repertoire of the primary lesion and allows for disease monitoring. EXPERIMENTAL DESIGN: Peripheral blood was prospectively collected from 44 newly diagnosed patients with endometrial cancer over a 24-month period (i.e., baseline, postsurgery, every 6 months after). DNA from the primary endometrial cancers was subjected to targeted next-generation sequencing (NGS) of 468 cancer-related genes, and cfDNA to a high-depth NGS assay of 129 genes with molecular barcoding. Sequencing data were analyzed using validated bioinformatics methods. RESULTS: cfDNA levels correlated with surgical stage in endometrial cancers, with higher levels of cfDNA being present in advanced-stage disease. Mutations in cfDNA at baseline were detected preoperatively in 8 of 36 (22%) patients with sequencing data, all of whom were diagnosed with advanced-stage disease, high tumor volume, and/or aggressive histologic type. Of the 38 somatic mutations identified in the primary tumors also present in the cfDNA assay, 35 (92%) and 38 (100%) were detected at baseline and follow-up, respectively. In 6 patients with recurrent disease, changes in circulating tumor DNA (ctDNA) fraction/variant allele fractions in cfDNA during follow-up closely mirrored disease progression and therapy response, with a lead time over clinically detected recurrence in two cases. The presence of ctDNA at baseline (P < 0.001) or postsurgery (P = 0.014) was significantly associated with reduced progression-free survival. CONCLUSIONS: cfDNA sequencing analysis in patients with endometrial cancer at diagnosis has prognostic value, and serial postsurgery cfDNA analysis enables disease and treatment response monitoring. See related commentary by Grant et al., p. 305.

Sentinel lymph node mapping in patients with endometrial hyperplasia: A practice to preserve or abandon?

OBJECTIVES: To compare outcomes of patients with premalignant endometrial pathology undergoing hysterectomy with or without sentinel lymph node (SLN) removal. Outcomes of interest included surgical adverse events (AEs), cancer status on final pathology, postoperative treatment, and The Cancer Genome Atlas (TCGA) molecular risk profiles. METHODS: We retrospectively identified patients with premalignant pathology on preoperative endometrial biopsy who underwent hysterectomy with or without SLN mapping/excision at our institution from 01/01/2017-12/31/2021. Clinical, pathologic, surgical, and TCGA profiling data were abstracted. Appropriate statistical tests were used. RESULTS: Of 221 patients identified, 161 (73%) underwent hysterectomy with SLN excision and 60 (27%) underwent hysterectomy without SLN excision. Median age and body mass index were similar between groups. Median operative time was 130 min for those who underwent SLN mapping/excision versus 136 min for those who did not (p = 0.6). Thirty-day postoperative AE rates were 9% (n = 15/161) and 13% (n = 8/60), respectively (p = 0.9). Ninety-eight (44%) of 221 patients had grade 1-2 endometrioid endometrial cancer on final pathology (4 [4%] were stage IB or higher). Ten (10%) of 98 patients, all within the SLN group, received adjuvant treatment. Among all patients, of 33 (15%) with TCGA molecular classification data, 27 (82%) had copy number-low, 3 (9%) microsatellite instability-high, 2 (6%) POLE-ultramutated, and 1 (3%) copy number-high disease. CONCLUSIONS: SLN assessment appears safe, detects a small number of occult nodal metastases for those upstaged, and provides additional staging information that can guide adjuvant treatment. SLN mapping should be discussed in preoperative counseling and offered using a shared decision-making approach.

Ovarian cancer mutational processes drive site-specific immune evasion.

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.

Gastric-type adenocarcinoma of the cervix: Clinical outcomes and genomic drivers.

OBJECTIVES: Gastric-type endocervical adenocarcinoma (GEA) is a rare form of cervical cancer not associated with human papilloma virus (HPV) infection. We summarize our experience with GEA at a large cancer center. METHODS: Clinical and demographic information on all patients diagnosed with GEA between June 1, 2002 and July 1, 2019 was obtained retrospectively from clinical charts. Kaplan-Meier survival analysis was performed to describe progression-free survival (PFS) and overall survival (OS). Tumors from a subset of patients underwent next generation sequencing (NGS) analysis. RESULTS: A total of 70 women with GEA were identified, including 43 who received initial treatment at our institution: of these 4 (9%) underwent surgery alone, 15 (35%) underwent surgery followed by adjuvant therapy, 10 (23%) were treated with definitive concurrent chemoradiation (CCRT), 7 (16%) with chemotherapy alone, and 3 (7%) with neoadjuvant CCRT and hysterectomy with or without chemotherapy. One-third (n = 14) of patients experienced disease progression, of whom 86% (n = 12) had prior CCRT. The median PFS and OS for patients with stage I GEA were 107 months (95% CI 14.8-199.2 months) and 111 months (95% CI 17-205.1 months) respectively, compared to 17 months (95% CI 5.6-28.4 months) and 33 months (95% CI 28.2-37.8 months) for patients with stages II-IV, respectively. On NGS, 4 patients (14%) had ERBB2 alterations, including 2 patients who received trastuzumab. CONCLUSIONS: GEA is an aggressive form of cervical cancer with poor PFS and OS when diagnosed at stage II or later. Further investigation is needed to identify the optimal management approach for this rare subtype.

A modern-day experience with Brunschwig's operation: Outcomes associated with pelvic exenteration.

OBJECTIVE: To evaluate postoperative and oncologic outcomes associated with pelvic exenteration for non-ovarian gynecologic malignancies. METHODS: This was a retrospective review of patients who underwent pelvic exenteration for non-ovarian gynecologic malignancies at our institution from 1/1/2010-12/31/2019. Palliative exenteration cases were excluded from survival analysis. Postoperative complications were early (≤30 days) or late (31-180 days). Complications were graded using a validated institutional scale. Major complications were considered grade ≥ 3. Categorical variables were compared using the chi-square test, and the Kaplan-Meier method was used for survival analysis. RESULTS: Of 100 patients identified, 89 underwent pelvic exenteration for recurrent disease, 5 for palliation, 5 for primary disease, and 1 for persistent disease. Thirty percent had cervical, 27% vulvar, 24% uterine, and 19% vaginal cancer. Sixty-two percent underwent total, 30% anterior, and 8% posterior exenteration. No deaths occurred intraoperatively or within 30 days of surgery. Six patients died after 30 days. Ninety-seven experienced a perioperative complication-49 early, 1 late, and 47 both. Fifty experienced a major complication-22 (44%) early, 19 (38%) late, and 9 (18%) both. No variables were statistically associated with complication development. The 3-year progression-free survival rate was 61.0%; the 3-year overall survival rate was 61.6%. Of 58 surviving patients, 16 (28%) and 4 (7%) were alive after 5 and 10 years, respectively. CONCLUSION: The overall complication rate for pelvic exenteration remains high. No variables demonstrated association with complication development as the rate was nearly 100%. The low rate of perioperative mortality is likely due to improved perioperative care.

Impact of obesity and white adipose tissue inflammation on the omental microenvironment in endometrial cancer.

BACKGROUND: A complex relationship between adipose tissue and malignancy, involving an inflammatory response, has been reported. The goal of this work was to assess the prevalence of white adipose tissue (WAT) inflammation in patients with endometrial cancer (EC), and the association with circulating inflammation markers. Furthermore, the aim was to characterize the pathways activated in and the cell type composition of adipose tissue in patients with EC. METHODS: Adipose tissue and blood samples were prospectively collected from 101 patients with EC at initial surgery. WAT inflammation was determined based on adipocytes surrounded by macrophages forming crown-like structures. Circulating levels of metabolic syndrome-associated and inflammatory markers were quantified. RNA-sequencing was performed on adipose samples (n = 55); differential gene expression, pathway, and cellular decomposition analyses were performed using state-of-the-art bioinformatics methods. RESULTS: WAT inflammation was identified in 46 (45.5%) of 101 EC patients. Dyslipidemia, hypertension, and diabetes mellitus were significantly associated with WAT inflammation (p < .05). WAT inflammation was associated with greater body mass index (p < .001) and higher circulating levels of leptin, high-sensitivity C-reactive protein, and interleukin-6, as well as lower levels of adiponectin and sex hormone-binding globulin (p < .05). Transcriptomic analysis demonstrated increased levels of proinflammatory and pro-neoplastic-related gene expression in inflamed omental adipose tissue. CONCLUSIONS: WAT inflammation is associated with metabolic syndrome, obesity, and inflammatory markers, as well as increased expression of proinflammatory and proneoplastic genes.

Proliferation of the Fallopian Tube Fimbriae and Cortical Inclusion Cysts: Effects of the Menstrual Cycle and the Levonorgestrel Intrauterine Contraceptive System.

BACKGROUND: The objectives of this study were (i) to explore whether differences in cell proliferation may help explain why most high-grade serous ovarian cancers (HGSOC) arise in the fallopian tube fimbriae (FTF) rather than in ovarian cortical inclusion cysts (CIC); (ii) to compare premenopausal and postmenopausal FTF proliferation as a reason why the age incidence of HGSOC increases at a slower rate after menopause; and (iii) to compare FTF proliferation in cycling women and women using the levonorgestrel intrauterine contraceptive system (Lng-IUS) to see whether proliferation on the Lng-IUS was lower. METHODS: We studied 60 women undergoing a salpingo-oophorectomy. We used Ki67, paired-box gene 8 (PAX8, Müllerian marker), and calretinin (mesothelial marker) to study FTF and CIC proliferation. RESULTS: FTF Ki67%+ was greater in the follicular than in the luteal phase (4.9% vs. 1.5%; P = 0.003); postmenopausal Ki67%+ was 1.7%. Ki67%+ in PAX8 negative (PAX8-) CICs was extremely low. Proliferation in PAX8+ CICs did not vary by menstrual phase or menopausal status. Follicular Ki67%+ was 2.6-fold higher in FTF than PAX8+ CICs. FTF Ki67%+ from 10 women using the Lng-IUS was not lower than in cycling women. CONCLUSIONS: Overall FTF Ki67%+ is greater than overall CIC Ki67%+. Overall FTF Ki67%+ in postmenopausal women is lower than in premenopausal women. The Lng-IUS is not associated with lower FTF Ki67%+. IMPACT: Ki67%+ provides an explanation of the preponderance of FTF-derived HGSOCs, and of the slower increase of HGSOCs after menopause. The Lng-IUS may not be associated with a protective effect against HGSOCs.

Immunotherapy for recurrent or metastatic vulvar carcinoma: A case report and review of current guidelines.

There are limited treatment options for patients with advanced vulvar cancer. However, several immune checkpoint inhibitors (ICIs) are FDA-approved or NCCN-Compendia-listed for qualified patients with advanced disease. In this case report, we present a patient with metastatic vulvar squamous cell carcinoma who was treated with pembrolizumab in the setting of disease progression following prior treatment with radiation and chemotherapy. Best response to immunotherapy was an unconfirmed partial response. We summarize the current role of ICIs in treating advanced vulvar cancer, which is largely extrapolated from the squamous cell skin cancer and cervical cancer guidelines. Additionally, we emphasize the need for more inclusive clinical trials and a better understanding of vulvar cancer molecular biology, as well as the identification of biomarkers to predict response to targeted therapy in patients with advanced vulvar cancer.