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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Sentinel lymph node biopsy alone compared to systematic lymphadenectomy in patients with uterine carcinosarcoma.

OBJECTIVE: To assess survival among patients diagnosed with uterine carcinosarcoma (CS) who underwent sentinel lymph node (SLN) biopsy alone vs. systematic lymph node dissection (LND). METHODS: We identified newly diagnosed CS patients who underwent primary surgical management from January 1996-December 2019. The SLN cohort underwent SLN biopsy alone with bilateral SLNs identified. The systematic LND cohort did not undergo SLN biopsy. RESULTS: Ninety-nine patients underwent SLN biopsy, and 100 patients underwent systematic LND. There was no difference by age, stage, body mass index, myoinvasion (<50%, ≥50%), lymphovascular space invasion, or positive washings. Eighty-five SLN (85.9%) and 15 LND (15%) underwent minimally invasive surgery (P < 0.001). The median total node count was four (range, 1-13) for SLN and 19 (range, 2-50) for LND (P < 0.001). Nodal metastasis occurred in 23 (23.2%) SLN and in 22 (22%) LND (P = 0.4). Postoperative therapy was administered to 85 (85.9%) SLN and 71 (71%) LND (P = 0.02). Median follow-up was 33 months (range, 1-205) for SLN and 55.3 months (range, 1-269) for LND (P = 0.001). The three-year progression-free survival (PFS) was 62.9% (SE 5.2%) for SLN and 52.3% (SE 5.3%) for LND (P = 0.13). The three-year overall survival (OS) was 72.1% (SE 5.1%) for SLN and 71.6% (SE 4.6%) for LND (P = 0.68). An isolated nodal recurrence occurred in two (2%) SLN and four (4%) LND (P = 0.26). CONCLUSIONS: There is no difference in PFS or OS among CS patients who undergo SLN biopsy vs. systematic LND. SLN biopsy detects nodal metastasis without compromising oncologic outcomes.

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.

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.

Risk factors for financial toxicity in patients with gynecologic cancer.

BACKGROUND: The cost of cancer care is high and rising. Evidence of increased patient cost burden is prevalent in the medical literature and has been defined as "financial toxicity," the financial hardship and financial concerns experienced by patients because of a disease and its related treatments. With targeted therapies and growing out-of-pocket costs, patient financial toxicity is a growing concern among patients with gynecologic cancer. OBJECTIVE: This study aimed to determine the prevalence of financial toxicity and identify its risk factors in patients with gynecologic cancer treated at a large cancer center using objective data. STUDY DESIGN: Using institutional databases, we identified patients with gynecologic cancer treated from January 2016 to December 2018. Patients with a preinvasive disease were excluded. Financial toxicity was defined according to institutionally derived metrics as the presence of ≥1 of the following: ≥2 bills sent to collections, application or granting of a payment plan, settlement, bankruptcy, financial assistance program enrollment, or a finance-related social work visit. Clinical characteristics were gathered using a 2-year look-back from the time of the first financial toxicity event or a randomly selected treatment date for those not experiencing toxicity. Risk factors were assessed using chi-squared tests. All significant variables on univariate analysis were included in the logistic regression model. RESULTS: Of the 4655 patients included in the analysis, 1155 (25%) experienced financial toxicity. In the univariate analysis, cervical cancer (35%), stage 3 or 4 disease (24% and 30%, respectively), younger age (35% for age <30 years), nonpartnered marital status (31%), Black (45%) or Hispanic (37%) race and ethnicity, self-pay (48%) or commercial insurance (30%), clinical trial participation (31%), more imaging studies (39% for ≥9), ≥1 emergency department visit (36%), longer inpatient stays (36% for ≥20 days), and more outpatient clinician visits (41% for ≥20 visits) were significantly associated with financial toxicity (P<.01). In multivariate analysis, younger age, nonpartnered marital status, Black and Hispanic race and ethnicity, commercial insurance, more imaging studies, and more outpatient physician visits were significantly associated with financial toxicity. CONCLUSION: Financial toxicity is an increasing problem for patients with gynecologic cancer. Our analysis, using objective measures of financial toxicity, has suggested that demographic factors and healthcare utilization metrics may be used to proactively identify at-risk patients for financial toxicity.

Sentinel lymph node biopsy in patients with endometrial cancer and an indocyanine green or iodinated contrast reaction - A proposed management algorithm.

OBJECTIVE: To describe the incidence of adverse reactions to indocyanine green (ICG) administered during sentinel lymph node (SLN) biopsy for endometrial cancer, and to propose an ICG management algorithm for these patients. METHODS: All patients who underwent surgery for endometrial cancer with SLN biopsy using ICG from 1/2017 to 8/2020 were identified using a single-institution prospective database. Surgical adverse events (SAEs) related to the procedure were identified. A review of the literature was performed. RESULTS: In all, 1414 patients met inclusion criteria and were evaluated. Sixty-seven (4.7%) patients had a history of either an iodine or contrast allergy. No patients had a history of documented ICG allergy. Among patients with an iodine or contrast allergy, 65 (97%) received a corticosteroid with or without diphenhydramine prior to ICG administration. One hundred five patients (7.4%) experienced 116 SAEs. Among these patients, 3 experienced potentially allergic SAEs possibly related to ICG administration. After thorough chart review, however, the likelihood these SAEs were due to ICG appeared low. No patients experienced an anaphylactic response after ICG admission. CONCLUSION: There were no anaphylactic reactions to ICG intracervical administration during 1414 consecutive SLN biopsies, including in patients with a documented iodine or contrast allergy. Intracervical injection of ICG is safe, and premedication using corticosteroids with or without diphenhydramine prior to SLN biopsy is a reasonable strategy in patients with iodinated contrast allergy.

Pelvic exenteration for recurrent or persistent gynecologic malignancies: Clinical and histopathologic factors predicting recurrence and survival in a modern cohort.

OBJECTIVES: To explore pre-operative factors and their impact on overall survival (OS) in a modern cohort of patients who underwent pelvic exenteration (PE) for gynecologic malignancies. METHODS: A retrospective review was performed for all patients who underwent a PE from 1/1/2010 through 12/31/2018 at our institution. Inclusion criteria were exenteration due to recurrent or progressive carcinoma of the uterus, cervix, vagina or vulva, with histologically confirmed complete surgical resection of the malignancy. Exclusion criteria included PE for palliation of symptoms without recurrence, and for ovarian or rare histologic malignancies. Univariable and multivariable analysis were performed to identify factors predicting prolonged survival. RESULTS: Overall, 71 patients met the inclusion criteria. Median age at time of exenteration was 62 years (range, 28-86 years). Vulvar cancer was the most common primary diagnosis (32%); 30% had cervical cancer; 23%, uterine cancer; 15%, vaginal cancer. Median OS was 55.1 months (95% confidence interval (CI): 36-not estimable) with a median follow-up time of 40.8 months (95% CI: 1-116.1). On univariable analysis, age > 62 years (hazard ratio (HR) 2.71, 95% CI 1.27-5.79), American Society of Anesthesia (ASA) 3-4 (HR: 3.41 (95% CI 1.03-11.29), and vulvar cancer (HR 4.19 (95% CI 1.17-14.96) predicted worse OS. Tumor size and prior progression-free interval (PFI) did not meet statistical significance in OS analyses. On multivariable analysis, there were no significant factors associated with worse OS. CONCLUSIONS: PE performed with curative intent may be considered a treatment option in well-counseled, carefully selected patients, irrespective of tumor size and PFI before exenteration.

Surgical ovarian suppression for adjuvant treatment in hormone receptor positive breast cancer in premenopausal patients.

OBJECTIVE: Ovarian suppression is recommended to complement endocrine therapy in premenopausal women with breast cancer and high-risk features. It can be achieved by either medical ovarian suppression or therapeutic bilateral salpingo-oophorectomy. Our objective was to evaluate characteristics of patients with stage I-III hormone receptor positive primary breast cancer who underwent bilateral salpingo-oophorectomy at our institution. MATERIALS AND METHODS: Premenopausal women with stage I-III hormone receptor positive primary breast cancer diagnosed between January 2010 and December 2014 were identified from a database. Patients with confirmed BRCA1/2 mutations were excluded. Distribution of characteristics between treatment groups was assessed using χ2 test and univariate logistic regression. A multivariate model was based on factors significant on univariate analysis. RESULTS: Of 2740 women identified, 2018 (74%) received endocrine treatment without ovarian ablation, 516 (19%) received endocrine treatment plus ovarian ablation, and 206 (7.5%) did not receive endocrine treatment. Among patients undergoing ovarian ablation 282/516 (55%) received medical ovarian suppression, while 234 (45%) underwent bilateral salpingo-oophorectomy. By univariate logistic analyses, predictors for ovarian ablation were younger age (OR 0.97), histology (other vs ductal: OR 0.23), lymph node involvement (OR 1.89), higher International Federation of Gynecology and Obstetrics (FIGO) stage (stage II vs I: OR 1.48; stage III vs I: OR 2.86), higher grade (grade 3 vs 1: OR 3.41; grade 2 vs 1: OR 2.99), chemotherapy (OR 1.52), and more recent year of diagnosis (2014 vs 2010; OR 1.713). Only year of diagnosis, stage, and human epidermal growth factor receptor 2 (HER-2) treatment remained significant in the multivariate model. Within the cohort undergoing ovarian ablation, older age (OR 1.05) was associated with therapeutic bilateral salpingo-oophorectomy. Of 234 undergoing bilateral salpingo-oophorectomy, 12 (5%) mild to moderate adverse surgical events were recorded. CONCLUSIONS: Bilateral salpingo-oophorectomy is used frequently as an endocrine ablation strategy. Older age was associated with bilateral salpingo-oophorectomy. Perioperative morbidity was acceptable. Evaluation of long-term effects and quality of life associated with endocrine ablation will help guide patient/provider decision-making.

Robotic Surgery in the Frail Elderly: Analysis of Perioperative Outcomes.

PURPOSE: The frail are considered at higher risk for unfavorable surgical outcomes (major complications/mortality). We assessed the safety of and outcomes associated with robotic surgery in the frail elderly undergoing gynecologic procedures. METHODS: We identified patients aged ≥ 65 years who underwent a robotic procedure between May 2007 and December 2016. Frailty was defined as the presence of at least three of five frailty factors-more than five comorbidities, low physical activity, weight loss, exhaustion, and fatigue. Perioperative outcomes were recorded. We compared variables among frail and non-frail patients and performed a multivariate logistic regression to detect variables associated with major complications (≥ grade 3) or 90-day mortality. RESULTS: We identified 982 patients: 71 frail and 911 non-frail patients. Median age was 71 years. Median BMI was 29.8 kg/m2. Thirty-four patients (3.5%) had a 30-day readmission. Seventy-seven (7.8%) had a postoperative complication, of which 23 (2.3%) were major. Ninety-day mortality was 0.5%. There were significant differences with regard to age (P < 0.001), body mass index (BMI) (P < 0.001) and performance status (P < 0.001); the frail were more likely to have had surgery for oncologic reasons (P = 0.047). There were differences in hospital stay (P < 0.001), postoperative (P = 0.042) and major complications (P = 0.007), and 90-day mortality (P = 0.05). At multivariable logistic regression, age ≥ 85 was associated with major complications. BMI, performance status, and major complications were associated with 90-day mortality. CONCLUSIONS: The frail elderly have longer hospital stays and more complications after surgery than the general population, consistent with the reported literature. Careful selection of surgical candidates is required.