ChatGPT accurately performs genetic counseling for gynecologic cancers.

OBJECTIVE: Artificial Intelligence (AI) systems such as ChatGPT can take medical examinations and counsel patients regarding medical diagnosis. We aim to quantify the accuracy of the ChatGPT V3.4 in answering commonly asked questions pertaining to genetic testing and counseling for gynecologic cancers. METHODS: Forty questions were formulated in conjunction with gynecologic oncologists and adapted from professional society guidelines and ChatGPT version 3.5 was queried, the version that is readily available to the public. The two categories of questions were genetic counseling guidelines and questions pertaining to specific genetic disorders. The answers were scored by two attending Gynecologic Oncologists according to the following scale: 1) correct and comprehensive, 2) correct but not comprehensive, 3) some correct, some incorrect, and 4) completely incorrect. Scoring discrepancies were resolved by additional third reviewer. The proportion of responses earning each score were calculated overall and within each question category. RESULTS: ChatGPT provided correct and comprehensive answers to 33/40 (82.5%) questions, correct but not comprehensive answers to 6/40 (15%) questions, partially incorrect answers to 1/40 (2.5%) questions, and completely incorrect answers to 0/40 (0%) questions. The genetic counseling category of questions had the highest proportion of answers that were both correct and comprehensive with ChatGPT answering all 20/20 questions with 100% accuracy and were comprehensive in responses. ChatGPT performed equally in the specific genetic disorders category, with 88.2% (15/17) and 66.6% (2/3) correct and comprehensive answers to questions pertaining to hereditary breast and ovarian cancer and Lynch syndrome questions respectively. CONCLUSION: ChatGPT accurately answers questions about genetic syndromes, genetic testing, and counseling in majority of the studied questions. These data suggest this powerful tool can be utilized as a patient resource for genetic counseling questions, though more data input from gynecologic oncologists would be needed to educate patients on genetic syndromes.

Let's chat about cervical cancer: Assessing the accuracy of ChatGPT responses to cervical cancer questions.

OBJECTIVE: To quantify the accuracy of ChatGPT in answering commonly asked questions pertaining to cervical cancer prevention, diagnosis, treatment, and survivorship/quality-of-life (QOL). METHODS: ChatGPT was queried with 64 questions adapted from professional society websites and the authors' clinical experiences. The answers were scored by two attending Gynecologic Oncologists according to the following scale: 1) correct and comprehensive, 2) correct but not comprehensive, 3) some correct, some incorrect, and 4) completely incorrect. Scoring discrepancies were resolved by additional reviewers as needed. The proportion of responses earning each score were calculated overall and within each question category. RESULTS: ChatGPT provided correct and comprehensive answers to 34 (53.1%) questions, correct but not comprehensive answers to 19 (29.7%) questions, partially incorrect answers to 10 (15.6%) questions, and completely incorrect answers to 1 (1.6%) question. Prevention and survivorship/QOL had the highest proportion of "correct" scores (scores of 1 or 2) at 22/24 (91.7%) and 15/16 (93.8%), respectively. ChatGPT performed less well in the treatment category, with 15/21 (71.4%) correct scores. It performed the worst in the diagnosis category with only 1/3 (33.3%) correct scores. CONCLUSION: ChatGPT accurately answers questions about cervical cancer prevention, survivorship, and QOL. It performs less accurately for cervical cancer diagnosis and treatment. Further development of this immensely popular large language model should include physician input before it can be utilized as a tool for Gynecologists or recommended as a patient resource for information on cervical cancer diagnosis and treatment.

Association of hospital-level factors with utilization of sentinel lymph node biopsy in patients with early-stage vulvar cancer.

OBJECTIVE: To evaluate utilization of sentinel lymph node biopsy (SLNB) for early-stage vulvar cancer at minority-serving hospitals and low-volume facilities. METHODS: Between 2012-2018, individuals with T1b vulvar squamous cell carcinoma were identified using the National Cancer Database. Patient, facility, and disease characteristics were compared between patients undergoing SLNB or inguinofemoral lymph node dissection (IFLD). Multivariable logistic regression, adjusted for patient, facility, and disease characteristics, was used to evaluate factors associated with SLNB. Kaplan-Meier survival analysis using log rank test and Cox regression was performed. RESULTS: Of the 3,532 patients, 2,406 (68.1%) underwent lymph node evaluation, with 1,704 (48.2%) undergoing IFLD and 702 (19.8%) SLNB. In a multivariable analysis, treatment at minority-serving hospitals (OR 0.39, 95% CI 0.19-0.78) and low-volume hospitals (OR 0.44, 95% CI 0.28-0.70) were associated with significantly lower odds of undergoing SLNB compared to receiving care at non-minority-serving and high-volume hospitals, respectively. While SLNB utilization increased over time for the entire cohort and stratified subgroups, use of the procedure did not increase at minority-serving hospitals. After controlling for patient and tumor characteristics, SLNB was not associated with worse OS compared to IFLD in patients with positive (HR 1.02, 95% CI 0.63-1.66) or negative (HR 0.92, 95% CI 0.70-1.21) nodal pathology. CONCLUSIONS: For patients with early-stage vulvar cancer, treatment at minority-serving or low-volume hospitals was associated with significantly decreased odds of undergoing SLNB. Future efforts should be concentrated toward ensuring that all patients have access to advanced surgical techniques regardless of where they receive their care.

Patient-reported outcomes and chemotherapy-related cognitive impairment in gynecologic malignancy.

OBJECTIVE: Chemotherapy has multiple adverse effects, including chemotherapy-related cognitive impairment, the phenomenon colloquially referred to as 'chemobrain'. The objective of this study was to understand patient-reported experiences of this phenomenon in relation to chemotherapy administration among gynecologic oncology patients. METHODS: A prospective patient-reported outcomes program was implemented in the Gynecologic Oncology clinic of a tertiary academic institution in January 2018. Patients with endometrial or ovarian cancer who received chemotherapy were included through September 2019 in this cohort study. Patients completed the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire. Serial responses were compared before, during, and after chemotherapy using a mixed effects linear regression with random effects for repeated measures within patients and a fixed effect for endometrial versus ovarian cancer. RESULTS: Fifty patients were included who completed a total of 152 patient-reported outcome measures. Thirty-five questionnaires were administered before chemotherapy, 59 during treatment, and 58 at a median of 161 days after the final cycle of chemotherapy. Seventy-one percent of patients reported no difficulties with concentration before chemotherapy, which remained stable after chemotherapy (72%). Sixty-six percent reported no difficulty with memory before chemotherapy versus 52% after chemotherapy. There were significant differences in feeling tension (p<0.001), worry (p<0.001), and depression (p=0.02) before and after chemotherapy on mixed effects linear regression, with higher levels of adverse emotional symptoms before chemotherapy administration compared with after. Women reported more interference with their social lives during chemotherapy (mean 1.08) compared with before (mean 0.85) and after chemotherapy (0.75, p=0.04). CONCLUSIONS: While no overt memory issues were discovered with serial administration of patient-reported outcome measures, rates of adverse emotional symptoms such as depression, tension, and worry diminished after chemotherapy administration. Further study is needed about the phenomenon of chemotherapy-related cognitive impairment using a larger cohort.

Disease Distribution at Presentation Impacts Benefit of IP Chemotherapy Among Patients with Advanced-Stage Ovarian Cancer.

BACKGROUND: Ovarian cancer with miliary disease spread is an aggressive phenotype lacking targeted management strategies. We sought to determine whether adjuvant intravenous/intraperitoneal (IV/IP) chemotherapy is beneficial in this disease setting. METHODS: Patient/tumor characteristics and survival data of patients with stage IIIC epithelial ovarian cancer who underwent optimal primary debulking surgery from 01/2010 to 11/2014 were abstracted from records. Chi-square and Mann-Whitney U tests were used to compare categorical and continuous variables. The Kaplan-Meier method was used to estimate survival curves, and outcomes were compared using log-rank tests. Factors significant on univariate analysis were combined into multivariate logistic regression survival models. RESULTS: Among 90 patients with miliary disease spread, 41 (46%) received IV/IP chemotherapy and 49 (54%) received IV chemotherapy. IV/IP chemotherapy, compared with IV chemotherapy, resulted in improved progression-free survival (PFS; 23.0 versus 12.0 months; p = 0.0002) and overall survival (OS; 52 versus 36 months; p = 0.002) in patients with miliary disease. Among 78 patients with nonmiliary disease spread, 23 (29%) underwent IV/IP chemotherapy and 55 (71%) underwent IV chemotherapy. There was no PFS or OS benefit associated with IV/IP chemotherapy over IV chemotherapy in these patients. On multivariate analysis, IV/IP chemotherapy was associated with improved PFS (HR, 0.28; 95% CI 0.15-0.53) and OS (HR, 0.33; 95% CI 0.18-0.61) in patients with miliary disease compared with those with nonmiliary disease (PFS [HR, 1.53; 95% CI 0.74-3.19]; OS [HR, 1.47; 95% CI 0.70-3.09]). CONCLUSIONS: Adjuvant IV/IP chemotherapy was associated with oncologic benefit in miliary disease spread. This survival benefit was not observed in nonmiliary disease.

Lymph node assessment at the time of hysterectomy has limited clinical utility for patients with pre-cancerous endometrial lesions.

OBJECTIVE: The objective of this study was to determine the proportion of patients with a pre-invasive endometrial lesion who meet Mayo criteria for lymph node dissection on final pathology to determine if the use of sentinel lymph node biopsy in patients with pre-invasive lesions would be warranted. METHODS: All women who underwent hysterectomy for a pre-invasive endometrial lesion (atypical hyperplasia or endometrial intra-epithelial neoplasia) between 2009 and 2019 were included for analysis. Relevant statistical tests were utilized to test the associations between patient, operative, and pathologic characteristics. RESULTS: 141 patients met inclusion criteria. 51 patients (36%) had a final diagnosis of cancer, the majority (96%) of which were Stage IA grade 1 endometrioid carcinomas. Seven patients (5%) met Mayo criteria on final pathology (one grade 3, seven size >2 cm, one >50% myoinvasive). Three of these seven patients had lymph nodes assessed of which 0% had metastases. Six of these patients had frozen section performed, and 2 met (33%) Mayo criteria intraoperatively. Of the seven patients in the overall cohort that had lymph node sampling, six had a final diagnosis of cancer and none had positive lymph nodes. Of the 51 patients with cancer, only 10 had cancer diagnosed using frozen section, and only two met intra-operative Mayo criteria. Age > 55 was predictive of meeting Mayo criteria on final pathology (p = 0.007). No patients experienced a cancer recurrence across a median follow up of 24.3 months. CONCLUSIONS: Atypical hyperplasia and endometrial intra-epithelial neoplasia portend low risk disease and universal nodal assessment is of limited value.

Patient reported outcome measures among patients with vulvar cancer at various stages of treatment, recurrence, and survivorship.

OBJECTIVE: Our goal was to pragmatically describe patient reported outcomes (PROs) in a typical clinic population of vulvar cancer patients, as prior studies of vulvar cancer PROs have examined clinical trial participants. METHODS: A prospective PRO program was implemented in the Gynecologic Oncology clinic of a tertiary academic institution in January 2018. Vulvar cancer patients through September 2019 were administered the European Organization for the Research and Treatment of Cancer Quality of life Questionnaire, the Patient Reported Outcome Measurement Information System Instrumental and Emotional Support Scales, and the Functional Assessment of Cancer Therapy-Vulvar questionnaire. Binary logistic regressions were performed to determine adjusted odds ratios for adverse responses to individual questions by insurance, stage, age, time since diagnosis, recurrence, radiation, and surgical radicality. RESULTS: Seventy vulvar cancer patients responded to PROs (85.4% response rate). Seventy-one percent were > 1 year since diagnosis, 61.4% had stage I disease, and 28.6% recurred. Publicly insured women had less support and worse quality of life (QOL, aOR 4.15, 95% CI 1.00-17.32, p = 0.05). Women who recurred noted more interference with social activities (aOR 4.45, 95% CI 1.28-15.41, p = 0.019) and poorer QOL (aOR 5.22 95% CI 1.51-18.10, p = 0.009). There were no major differences by surgical radicality. Those >1 year since diagnosis experienced less worry (aOR 0.17, 95% CI 0.04-0.63, p = 0.008). CONCLUSIONS: Surgical radicality does not affect symptoms or QOL in vulvar cancer patients, whereas insurance, recurrence, and time since diagnosis do. This data can improve counseling and awareness of patient characteristics that would benefit from social services referral.

Impact of residual disease at interval debulking surgery on platinum resistance and patterns of recurrence for advanced-stage ovarian cancer.

OBJECTIVE: To evaluate the impact of size and distribution of residual disease after interval debulking surgery on the timing and patterns of recurrence for patients with advanced-stage epithelial ovarian cancer. METHODS: Patient demographics and data on disease treatment/recurrence were collected from medical records of patients with stage IIIC/IV epithelial ovarian cancer who were managed with neoadjuvant chemotherapy/interval debulking surgery between January 2010 and December 2014. Among patients without complete surgical resection but with ≤1 cm of residual disease, the number of anatomic sites (<1 cm single anatomic location vs <1 cm multiple anatomic locations) was used to describe the size and distribution of residual disease. RESULTS: A total of 224 patients were included. Of these, 70.5% (n=158) had a complete surgical resection, 12.5% (n=28) had <1 cm single anatomic location, and 17.0% (n=38) had <1 cm multiple anatomic locations. Two-year progression-free survival for complete surgical resection, <1 cm single anatomic location, and <1 cm multiple anatomic locations was 22.2%, 17.9% and 7%, respectively (p=0.007). Size and distribution of residual disease after interval debulking surgery did not affect location of recurrence and most patients had recurrence at multiple sites (complete surgical resection: 64.7%, <1 cm single anatomic location: 55.6%, and <1 cm multiple anatomic locations: 71.4%). Controlling for additional factors that may influence platinum resistance and surgical complexity, the rate of platinum-resistant recurrence was similar for patients with complete surgical resection and <1 cm single anatomic location (OR=1.07, 95% CI 0.40 to 2.86; p=0.888), but women with <1 cm multiple anatomic locations had an increased risk of platinum resistance (OR=3.09, 95% CI 1.41 to 6.78 p=0.005). CONCLUSIONS: Despite current classification as 'optimal,' <1 cm multiple anatomic location at the time of interval debulking surgery is associated with a shorter progression-free survival and increased risk of platinum resistance.

Predictive validity of American College of Surgeons: National Surgical Quality Improvement Project risk calculator in patients with ovarian cancer undergoing interval debulking surgery.

INTRODUCTION: In gynecologic patients, few studies describe the accuracy of the American College of Surgeons-National Surgical Quality Improvement Project (ACS-NSQIP) pre-operative risk calculator for women undergoing surgery for ovarian cancer. OBJECTIVE: To determine whether the ACS-NSQIP risk calculator accurately predicts post-operative complications and length of stay in patients undergoing interval debulking surgery for advanced stage epithelial ovarian cancer. METHODS: For this multi-institutional retrospective cohort study, pre-operative risk factors, post-operative complication rates, and Current Procedural Terminology codes were abstracted from records of patients with ovarian cancer managed with open interval debulking surgery from January 2010 to July 2015. A power calculation was done to estimate the minimum number of complications needed to evaluate the accuracy of the ACS-NSQIP risk calculator. Predicted risk compared with observed risk was calculated using logistic regression. The predictive accuracy of the ACS-NSQIP risk calculator in estimating post-operative complications or length of stay was assessed using c-statistics and Briar scores. Complications with a c-statistic of >0.70 and Brier score of <0.01 were considered to have high discriminative ability. RESULTS: A total of 261 patients underwent interval debulking surgery, encompassing 21 unique Current Procedural Terminology codes. Readmission (n=25), surgical site infection (n=35), urinary tract infection (n=12), and serious post-operative complications (n=57) met the minimum event threshold (n>10). All predicted complication rates fell within the IQR of the observed incidence rates. However, the ACS-NSQIP calculator demonstrated neither discriminative ability nor accuracy for any post-operative complications based on c-statistics and Brier scores. The calculator accurately predicted length of stay within 1 day for only 32% of patients and could not accurately predict which patients were likely to have a prolonged length of stay (c-statistic=0.65). CONCLUSION: Among patients undergoing interval debulking surgery, the ACS-NSQIP did not accurately discriminate which patients were at increased risk of complications or extended length of stay. The risk calculator should be considered to have limited utility in informing pre-operative counseling or surgical planning.

Palliative care referral patterns and measures of aggressive care at the end of life in patients with cervical cancer.

INTRODUCTION: Fifteen per cent of women with cervical cancer are diagnosed with advanced disease and carry a 5 year survival rate of only 17%. Cervical cancer may lead to particularly severe symptoms that interfere with quality of life, yet few studies have examined the rate of palliative care referral in this population. This study aims to examine the impact of palliative care referral on women who have died from cervical cancer in two tertiary care centers. METHODS: We conducted a retrospective review of cervical cancer decedents at two tertiary institutions from January 2000 to February 2017. We examined how aggressive measures of care at the end of life, metrics defined by the National Quality Forum, interacted with clinical variables to understand if end-of-life care was affected. Univariate and multivariate parametric and non-parametric testing was used, and linear regression models were generated to determine unadjusted and adjusted associations between aggressive measures of care at the end of life with receipt of palliative care as the main exposure. RESULTS: Of 153 cervical cancer decedents, 73 (47%) received a palliative care referral and the majority (57%) of referrals occurred during an inpatient admission. The median time from palliative care consultation to death was 2.3 months and 34% were referred to palliative care in the last 30 days of life. Palliative care referral was associated with fewer emergency department visits (OR 0.18, 95% CI 0.05 to 0.56), inpatient stays (OR 0.21, 95% CI 0.07 to 0.61), and intensive care unit admissions (OR 0.24, 95% CI 0.06 to 0.93) in the last 30 days of life. Palliative care did not affect chemotherapy or radiation administration within 14 days of death (p=0.36). Women evaluated by palliative care providers were less likely to die in the acute care setting (OR 0.19, 95% CI 0.07 to 0.51). DISCUSSION: In two tertiary care centers, less than half of cervical cancer decedents received palliative care consultations, and those referred to palliative care were often evaluated late in their disease course. Palliative care utilization was also associated with a lower incidence of poor-quality end-of-life care.

Neoadjuvant chemotherapy does not disproportionately influence post-operative complication rates or time to chemotherapy in obese patients with advanced-stage ovarian cancer.

OBJECTIVES: To determine whether neoadjuvant chemotherapy (NACT) disproportionately benefits obese patients. METHODS: Data were collected from stage IIIC-IV ovarian cancer patients treated between 01/2010-07/2015. We performed univariate/multivariate logistic regression analyses with post-operative infection, readmission, any postoperative complication, and time to chemotherapy as outcomes. An interaction term was included in models, to determine if the effect of NACT on post-operative complications was influenced by obesity status. RESULTS: Of 507 patients, 115 (22.6%) were obese and 392 (77.3%) were non-obese (obese defined as BMI ≥30). Among obese patients undergoing primary debulking surgery (PDS) vs. NACT, rates of postoperative infection were 42.9% vs. 30.8% (p = 0.12), 30-day readmission 30.2% vs. 11.5% (p < 0.02), and any post-operative complication were 44.4% vs 30.8% (p = 0.133). Among non-obese patients undergoing PDS vs. NACT, rates of post-operative infection were 20.0% vs. 12.9% (p = 0.057), 30-day readmission 16.9% vs. 9.2% (p = 0.02), and any post-operative complication were 19.4% vs 28% (p = 0.044). Obesity was associated with post-operative infection (OR 2.3; 95%CI 1.22-4.33), 30-day readmission/reoperation (OR 2.27; 95%CI 1.08-3.21) and the development of any post-operative complication (OR 2.1; CI 1.13-3.74). However, there was not a significant interaction between obesity and NACT in any of the models predicting post-operative complications. CONCLUSIONS: The decision to use NACT should not be predicated on obesity alone, as the reduction in post-operative complications in obese patients is similar to non-obese patients.

Clinical trial participation and aggressive care at the end of life in patients with ovarian cancer.

OBJECTIVES: In non-gynecologic cancers, clinical trial participation has been associated with aggressive care at the end of life. The objective of this investigation was to examine how trial participation affects end of life outcomes in patients with ovarian cancer. METHODS: In a retrospective review of women diagnosed with ovarian cancer at our institution between January 2010 and December 2015, we collected variables identified by the National Quality Forum as measures of aggressive end of life care including chemotherapy in the last 14 days of life, intensive care unit (ICU) admission in the last 30 days of life, or death in the acute care setting. Trials investigating medications but not surgical interventions were included. The primary outcome of this study was the association between trial participation and the National Quality Forum measures of aggressive end of life care in ovarian cancer decedents. Data were analyzed with univariable and multivariable parametric and non-parametric testing, and time to event outcomes were analyzed using the Kaplan-Meier method and Cox's proportional hazard models. RESULTS: Among 391 women treated for ovarian cancer, 62 patients (16%) participated in a clinical trial. Patients enrolled in clinical trials were more likely to have chemotherapy administered within 14 days of death; however, no association was found with other metrics of aggressive care at the end of life including the initiation of a new chemotherapy regimen in the last 30 days of life, ICU admissions, and death in an acute care setting. Among patients with recurrent ovarian cancer, median overall survival for trial participants was 57 months compared with only 31 months in non-trial participants (p<0.001). CONCLUSIONS: In patients with ovarian cancer, clinical trial enrollment is associated with chemotherapy administration within 14 days of death, but not other measures of aggressive care at the end of life. Given the importance of clinical trial participation in improving care for women with ovarian cancer, this study suggests that concerns regarding aggressive care prior to death should not limit clinical trial participation.

Factors associated with referral and completion of genetic counseling in women with epithelial ovarian cancer.

OBJECTIVE: The National Comprehensive Cancer Network recommends that all women diagnosed with epithelial ovarian cancer undergo genetic testing, as the diagnosis of pathogenic variants may inform cancer survival and impact treatment options. The objective of this study was to assess factors associated with referral to genetic counseling in women with epithelial ovarian cancer. METHODS: A retrospective cohort study identified women with epithelial ovarian cancer from 2012 to 2017 at Massachusetts General Hospital and North Shore Medical Center, a community hospital affiliated with Massachusetts General Hospital. Multivariate logistic regression evaluated how race, age, stage, year of diagnosis, insurance status, family history of breast or ovarian cancer, and language relates to the receipt of genetic counseling. RESULTS: Of the total 276 women included, 73.9% were referred for genetic screening, of which 90.7% attended a genetic counseling visit. Older women were less likely to undergo genetic counseling (age ≥70 years: OR 0.26, 95% CI 0.07-0.94, p=0.04). Women who died within 365 days of initial oncology consult rarely reached a genetic counselor (OR 0.05, 95% CI 0.01-0.24, p<0.001). Women with a family history of breast or ovarian cancer were more likely to undergo counseling (OR 3.27, 95% CI 1.74-6.15, p<0.001). There was no difference in receipt of genetic counseling by race, stage, year of diagnosis, insurance status, or language. CONCLUSION: Older women with epithelial ovarian cancer and those who died within 1 year of initiation of care were less likely to undergo recommended genetic counseling. Race, insurance status, and language were not identified as predictive factors, although we were limited in this assessment by small sample size.

Use of ablation and ultrasonic aspiration at primary debulking surgery in advanced stage ovarian, fallopian tube, and primary peritoneal cancer.

OBJECTIVES: Ovarian cancer patients with miliary disease have the lowest rates of complete surgical resection and poorest survival. Adjunct surgical techniques may potentially increase rates of complete surgical resection. No studies have evaluated the use of these techniques in primary debulking surgery for ovarian cancer patients with miliary disease. The aim of this study was to examine the use of adjunct surgical techniques during primary debulking surgery for patients with advanced epithelial ovarian, fallopian tube, and primary peritoneal cancer with miliary disease. METHODS: Medical records of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IIIC-IVB epithelial ovarian, fallopian tube, or primary peritoneal cancer with miliary disease undergoing primary debulking surgery from January 2010 to December 2014 were reviewed. Adjunct surgical techniques were defined as ultrasonic surgical aspiration, argon enhanced electrocautery, thermal plasma energy, and traditional electrocautery ablation. Patients undergoing surgery with and without these devices were compared with respect to demographics, operative characteristics, postoperative complications, residual disease, progression free survival and overall survival. RESULTS: A total of 135 patients with miliary disease underwent primary debulking surgery, of which 30 (22.2%) patients used adjunct surgical techniques. The most common devices were ultrasonic surgical aspiration (40%) and argon enhanced electrocautery (36.7%). The most common sites of use were diaphragm (63.3%), pelvic peritoneum (30%), bowel mesentery (20%), and large bowel serosa (20%). There were no differences in age, stage, primary site, histology, operative time, surgical complexity, or postoperative complications for patients operated on with or without these devices. Volume of residual disease was similar (0.1-1 cm: 60% with adjunct techniques versus 68.6% without; complete surgical resection: 16.7% with adjunct techniques versus 13.3% without; p=0.67). For patients with ≤1 cm residual disease, median progression free survival (15 versus 15 months, p=0.65) and median overall survival (40 versus 55 months, p=0.38) were also similar. CONCLUSION: Adjunct surgical techniques may be incorporated during primary debulking surgery for patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer with miliary disease; however, these do not improve the rate of optimal cytoreduction.

Infection, thrombosis, and oncologic outcome after interval debulking surgery: Does perioperative blood transfusion matter?

OBJECTIVES: To determine whether perioperative red blood cell transfusion (PRBCT) affects infection, thrombosis, or survival rates in epithelial ovarian cancer (EOC) patients undergoing neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS). METHODS: Demographics, operative characteristics, and outcome data were abstracted from records of stage IIIC-IV EOC patients managed with NACT-IDS from 01/2010-07/2015. Associations of PRBCT with morbidity and oncologic outcomes were evaluated. RESULTS: Of 270 patients, 136 (50.4%) received PRBCT. Patients with preoperative anemia and higher estimated blood loss (EBL) were more likely to undergo PRBCT (OR,95%CI 1.80, 1.02-3.17) and (OR,95%CI 1.00, 1.002-1.004), respectively. There were no significant differences in PRBCT based on patient age, Charlson Comorbidity Index, or stage. When compared to low complexity operations, patients with moderate and high complexity surgeries were more likely to receive PRBCT (OR,95%CI 1.81, 1.05-3.09) and (OR,95%CI 2.25, 1.13-4.50), respectively. On univariate analysis, PRBCT was associated with intraabdominal infection (OR,95%CI 8.31, 1.03-67.41), but not wound complications (OR,95%CI 1.57, 0.76-3.23) or venous thromboembolism/pulmonary embolism (VTE/PE) (OR,95%CI 2.02, 0.49-8.23). After adjusting for surgical complexity and preoperative anemia, PRBCT was not independently associated with intraabdominal infection (OR,95%CI 7.66, 0.92-63.66), wound complications (OR,95%CI 1.70, 0.80-3.64), or VTE/PE (OR,95%CI 2.15, 0.51-9.09). When comparing patients undergoing PRBCT versus those who did not, there were no significant differences in median progression-free survival (PFS) or median overall survival (OS) on univariate analysis after adjusting for age, stage and residual disease. CONCLUSIONS: Among patients undergoing NACT-IDS, intraabdominal infection, wound complication and VTE/PE rates are similar, regardless of PRBCT. PRBCT does not impact PFS or OS.

Recurrence, death, and secondary malignancy after ovarian conservation for young women with early-stage low-grade endometrial cancer.

OBJECTIVE: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer. METHODS: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy. RESULTS: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged. CONCLUSION: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.

A novel classification of residual disease after interval debulking surgery for advanced-stage ovarian cancer to better distinguish oncologic outcome.

BACKGROUND: Complete surgical resection affords the best prognosis at the time of interval debulking surgery. When complete surgical resection is unachievable, optimal residual disease is considered the next best alternative. Despite contradicting evidence on the survival benefit of interval debulking surgery if macroscopic residual disease remains, the current definition of "optimal" in patients undergoing interval debulking surgery is defined as largest diameter of disease measuring ≤1.0 cm, independent of the total volume of disease. OBJECTIVE: To examine the relationship between volume and anatomic distribution of residual disease and oncologic outcomes among patients with advanced-stage epithelial ovarian/fallopian tube/primary peritoneal carcinoma undergoing neoadjuvant chemotherapy then interval debulking surgery. For patients who did not undergo a complete surgical resection, a surrogate for volume of residual disease was used to assess oncologic outcomes. STUDY DESIGN: Patient demographics, operative characteristics, anatomic site of residual disease, and outcome data were collected from medical records of patients with International Federation of Gynecology and Obstetrics stage IIIC and IV epithelial ovarian cancer undergoing interval debulking surgery from January 2010 to July 2015. Among patients who did not undergo complete surgical resection but had ≤1 cm of residual disease, the number of anatomic sites (single location vs multiple locations) with residual disease was used as a surrogate for volume of residual disease. The effect of residual disease volume on progression-free survival and overall survival was evaluated. RESULTS: Of 270 patients undergoing interval debulking surgery, 173 (64.1%) had complete surgical resection, 34 (12.6%) had ≤1 cm of residual disease in a single anatomic location, 47 (17.4%) had ≤1 cm of residual disease in multiple anatomic locations, and 16 (5.9%) were suboptimally debulked. Median progression-free survival for each group was 14, 12, 10, and 6 months, respectively (P<.001). Median overall survival for each group was: 58, 37, 26, and 33 months, respectively (P<.001). CONCLUSION: Following interval debulking surgery, patients with complete surgical resection have the best prognosis, followed by patients with ≤1 cm single-anatomic location disease. In contrast, despite being considered "optimally debulked," patients with ≤1 cm multiple-anatomic location disease have a survival similar to suboptimally debulked patients.

Patterns of palliative care referral in ovarian cancer: A single institution 5 year retrospective analysis.

BACKGROUND: The American Society of Clinical Oncology recommends that patients with advanced cancer receive dedicated palliative care services early in their disease course. This investigation serves to understand how palliative care services are utilized for ovarian cancer patients in a tertiary referral center. METHODS: We conducted a retrospective review of women treated for ovarian cancer at our institution from 2010 through 2015. Clinical variables included presence and timing of palliative care referral. Data were correlated utilizing univariable and multivariable parametric and non-parametric testing, and survivals were analyzed using the Kaplan-Meier method and cox-proportional hazard models. RESULTS: We identified 391 women treated for ovarian cancer, of whom 68% were diagnosed with stage III or IV disease. Palliative care referral was utilized in 28% in the outpatient (42%) and inpatient (58%) settings. Earlier use of referral was observed in those who never underwent surgical cytoreduction or had interval cytoreductive surgery (p < 0.001). Palliative care referral was independently associated with advanced stage (OR 1.7, p = 0.02), recurrence (OR 2.0, p = 0.002) and hospice referral (OR 6.0, p < 0.001). In 38% of women referral occurred within 30 days of death, and 17% within one week of death. Outpatient initial consultation was associated with an unadjusted 1 year overall survival benefit (p < 0.01) compared to inpatient consultation. CONCLUSIONS: The outcomes in this study suggest a late use of palliative care that is reactionary to patient needs and not a routine component of ovarian cancer care as national guidelines recommend.

Moving beyond "complete surgical resection" and "optimal": Is low-volume residual disease another option for primary debulking surgery?

OBJECTIVES: To examine the relationship between volume of residual disease and oncologic outcomes among patients with advanced-stage epithelial ovarian/fallopian tube/primary peritoneal carcinoma undergoing primary debulking surgery (PDS). For patients that did not undergo a complete surgical resection (CSR), a surrogate for volume of residual disease was used to assess oncologic outcomes. METHODS: Medical records of patients with FIGO stage IIIC and IV epithelial ovarian/fallopian tube/primary peritoneal carcinoma undergoing PDS between January 2010 and November 2014 were reviewed. Patient demographics, operative characteristics, residual disease, anatomic site of residual disease and outcome data were collected. Among patients who did not undergo CSR, but had ≤1 cm of residual disease, the number of anatomic sites (single location vs. multiple locations) with residual disease was utilized as a surrogate for volume of residual disease. The effect of residual disease volume on progression-free survival (PFS) and overall survival (OS) was evaluated. RESULTS: Of 240 patients undergoing PDS, 94 (39.2%) had CSR, 41 (17.1%) had ≤1 cm of residual disease confined to a single anatomic location (≤1 cm-SL), 67 (27.9%) had ≤1 cm of residual disease in multiple anatomic locations (≤1 cm-ML) and 38 (15.8%) were sub-optimally (SO) debulked. Median PFS for CSR, ≤1 cm-SL, ≤1 cm-ML and SO-debulked were: 23, 19, 13 and 10 months, respectively (p < 0.001). Median OS for CSR, ≤1 cm-SL, ≤1 cm-ML and SO-debulked were: Not yet reached, 64, 50 and 49 months, respectively (p = 0.001). CONCLUSIONS: Following PDS, CSR and ≤ 1 cm-SL patients have the best prognosis. In contrast, despite being considered "optimally debulked", ≤1 cm-ML patients have survival similar to those SO-debulked.

Characterization of immune regulatory molecules B7-H4 and PD-L1 in low and high grade endometrial tumors.

BACKGROUND: The objective of this investigation was to characterize the expression landscape of immune regulatory molecules programmed death-ligand-1 (PD-L1, B7-H1) and B7-H4 in a cohort of endometrial tumors across the spectrum of grade and histology. MATERIALS AND METHODS: With institutional review board approval, 70 endometrial tumors from patients with known clinical outcomes were identified representing a spectrum of grade and histology. Immunohistochemistry (IHC) was performed for PD-L1 and B7-H4 and scored. Microsatellite instability (MSI) status was assessed for endometrioid tumors using the institutional IHC assay for expression of the mismatch repair (MMR) genes, MLH1, MSH2, MSH6 and PMS2. RNA sequencing data from the Cancer Genome Atlas was queried for expression levels of CD274 (PD-L1 protein) and VTCN1 (B7-H4) across molecular subtypes of endometrial carcinoma and were correlated with a T cell infiltration index. RESULTS: We identified 40 low grade endometrioid tumors and a cohort of 30 high grade tumors. PD-L1 expression was observed in both high and low grade endometrial tumors (56% vs 35%, p=0.07). In the low grade tumors, PD-L1 expression was associated with MSI status (p<0.01). The high grade cohort had similar rates of PD-L1 expression compared to low grade MSI tumor (56% and 62% respectively), and both were distinct from low grade MSS tumors (22%, p<0.05). High (3+) B7-H4 positive cells were observed in both high and low grade carcinomas (33% and 31% respectively). RNA profiling data from confirmed highest CD274 expression in POLE and MSI tumors that was linearly correlated with T cell infiltration, while VTCN1 expression appeared consistent across molecular subtypes. CONCLUSIONS: While PD-L1 expression correlated with MSI and high grade tumors, B7-H4 expression was independent of grade, histology and immune cell infiltration. The development and testing of multi-agent therapeutics targeting PD-L1 and B7-H4 may be a novel strategy for endometrial tumors.