Faculty Bibliography

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/CONCLUSIONS: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.

Radiation Recall encompasses an array of inflammatory reactions, most commonly dermatitis, that occurs in response to a systemic medication with distribution in a previously irradiated field. While historically cytotoxic chemotherapy was a major culprit, this case report describes radiation recall dermatitis in response to pembrolizumab and lenvatinib in a 62-year old female with ongoing advanced endometrial cancer and history of breast cancer. Discontinuation of lenvatinib alone lead to complete resolution of the dermatitis, and she ultimately resumed her previous lenvatinib dose without recurrent symptoms. This case represents an important possible adverse effect of a commonly used targeted therapy, particularly in a population likely to have a history of prior radiation exposure.

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.

OBJECTIVE:To describe the use of National Comprehensive Cancer Network guideline-concordant inguinofemoral lymph node (LN) evaluation in individuals with early-stage vulvar cancer. METHODS:This retrospective cohort study identified patients with T1b and T2 vulvar squamous cell carcinoma diagnosed between 2012 and 2018 using the National Cancer Database. Factors associated with LN evaluation were examined using logistic regression analyses, adjusting for patient, disease, and facility-level characteristics. Kaplan-Meier survival analysis using log rank test and Cox regression was performed for the entire cohort and a subgroup of older patients, defined as individuals aged 80 years or older. RESULTS:Of the 5,685 patients with vulvar cancer, 3,756 (66.1%) underwent guideline-concordant LN evaluation. In our adjusted model, age 80 years or older (odds ratio [OR], 0.30; 95% CI 0.22-0.42) and Black race (OR 0.72; 95% CI 0.54-0.95) were associated with lower odds of LN evaluation. High-volume hospitals were associated with increased odds of LN evaluation compared with low-volume hospitals (OR 1.62; 95% CI 1.28-2.05). Older individuals who did not undergo LN evaluation had significantly worse overall survival than those with pathologically negative LNs (hazard ratio [HR] 0.45; 95% CI 0.37-0.55) and similar overall survival as those with pathologically positive LNs (HR 1.05; 95% CI 0.77-1.43). CONCLUSION/CONCLUSIONS:Guideline-concordant LN evaluation for early-stage vulvar squamous cell carcinoma is low. Lower utilization is associated with older age, Black race, and care at a low-volume hospital.

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.

INTRODUCTION/BACKGROUND: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/CONCLUSIONS: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.

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.

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.

Uterine carcinoma (UC) is the most common gynecologic malignancy in the United States. TP53 mutant UCs cause a disproportionate number of deaths due to limited therapies for these tumors and the lack of mechanistic understanding of their fundamental vulnerabilities. Here we sought to understand the functional and therapeutic relevance of TP53 mutations in UC. We functionally profiled targetable TP53 dependent DNA damage repair and cell cycle control pathways in a panel of TP53 mutant UC cell lines and patient-derived organoids. There were no consistent defects in DNA damage repair pathways. Rather, most models demonstrated dependence on defective G2/M cell cycle checkpoints and subsequent upregulation of Aurora kinase-LKB1-p53-AKT signaling in the setting of baseline mitotic defects. This combination makes them sensitive to Aurora kinase inhibition. Resistant lines demonstrated an intact G2/M checkpoint, and combining Aurora kinase and WEE1 inhibitors, which then push these cells through mitosis with Aurora kinase inhibitor-induced spindle defects, led to apoptosis in these cases. Overall, this work presents Aurora kinase inhibitors alone or in combination with WEE1 inhibitors as relevant mechanism driven therapies for TP53 mutant UCs. Context specific functional assessment of the G2/M checkpoint may serve as a biomarker in identifying Aurora kinase inhibitor sensitive tumors.

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.