Sialyl-Tn serves as a potential therapeutic target for ovarian cancer.

BACKGROUND: Ovarian cancer remains the deadliest of the gynecologic cancers in the United States. There have been limited advances in treatment strategies that have seen marked increases in overall survival. Thus, it is essential to continue developing and validating new treatment strategies and markers to identify patients who would benefit from the new strategy. In this report, we sought to further validate applications for a novel humanized anti-Sialyl Tn antibody-drug conjugate (anti-STn-ADC) in ovarian cancer. METHODS: We aimed to further test a humanized anti-STn-ADC in sialyl-Tn (STn) positive and negative ovarian cancer cell line, patient-derived organoid (PDO), and patient-derived xenograft (PDX) models. Furthermore, we sought to determine whether serum STn levels would reflect STn positivity in the tumor samples enabling us to identify patients that an anti-STn-ADC strategy would best serve. We developed a custom ELISA with high specificity and sensitivity, that was used to assess whether circulating STn levels would correlate with stage, progression-free survival, overall survival, and its value in augmenting CA-125 as a diagnostic. Lastly, we assessed whether the serum levels reflected what was observed via immunohistochemical analysis in a subset of tumor samples. RESULTS: Our in vitro experiments further define the specificity of the anti-STn-ADC. The ovarian cancer PDO, and PDX models provide additional support for an anti-STn-ADC-based strategy for targeting ovarian cancer. The custom serum ELISA was informative in potential triaging of patients with elevated levels of STn. However, it was not sensitive enough to add value to existing CA-125 levels for a diagnostic. While the ELISA identified non-serous ovarian tumors with low CA-125 levels, the sample numbers were too small to provide any confidence the STn ELISA would meaningfully add to CA-125 for diagnosis. CONCLUSIONS: Our preclinical data support the concept that an anti-STn-ADC may be a viable option for treating patients with elevated STn levels. Moreover, our STn-based ELISA could complement IHC in identifying patients with whom an anti-STn-based strategy might be more effective.

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.

Guideline-Discordant Care in Early-Stage Vulvar Cancer.

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: 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.

The Loop Electrosurgical Excision Procedure and Cone Conundrum: The Role of Cumulative Excised Depth in Predicting Preterm Birth.

Objective The objective was to determine factors associated with spontaneous preterm birth at less than 37 weeks in a cohort of patients who underwent a loop electrosurgical excision procedure (LEEP) or cone prior to pregnancy. Study Design This was a nested case-control study within a cohort of patients who underwent at least one LEEP or cone and had care for the next singleton pregnancy at either of two institutions between 1994 and 2014. Cases had spontaneous preterm birth at less than 37 weeks. Exposures included potential risk factors for preterm birth such as cumulative depth of excised cervix and time since excision. Reverse stepwise selection was used to identify the covariates for multivariable logistic regression. Results A total of 134 patients were included. Eighteen (13%) had a spontaneous preterm birth at less than 37 weeks. Median second-trimester cervical lengths were similar between those who delivered preterm and term (3.9-cm preterm and 3.6-cm term, p = 0.69). Patients who delivered preterm had a significantly greater median total excised depth of cervix (1.2 vs. 0.8 cm, p = 0.04). After adjustment for confounders, total excised depth remained significantly associated with preterm birth (adjusted odds ratio [aOR] = 2.2, 95% confidence interval [CI]: 1.3-3.8). Conclusion Total excised depth should be considered in addition to cervical length screening when managing subsequent pregnancies. Key Points A history of a LEEP or cone excision has been associated with spontaneous preterm birth.A two-fold increase in spontaneous preterm birth was seen per cumulative centimeter excised.There was no difference in second-trimester cervical length between the term and preterm groups.

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.

Effect of Mismatch Repair Status on Outcome of Early-Stage Grade 1 to 2 Endometrial Cancer Treated With Vaginal Brachytherapy.

OBJECTIVES: The objective of this study was to determine if deficiency of mismatch repair (dMMR) proteins in patients with early-stage favorable endometrial cancer treated with vaginal brachytherapy (VB) is associated with increased recurrence. MATERIALS AND METHODS: A multi-institutional retrospective cohort study of 141 patients with stage I to II grade 1 and 2 endometrioid adenocarcinoma treated with surgery and adjuvant VB was performed to compare recurrence risk in dMMR (n=41) versus MMR-preserved (pMMR) (n=100). Additional clinical and pathologic risk factors were also collected. Univariate analysis and multivariable analysis Cox regression analysis was performed to identify factors associated with any recurrence. Kaplan-Meier method and log rank test were used to compare recurrence free survival and overall survival (OS). RESULTS: Median follow up was 42 months. Forty-one patients (29%) were dMMR. There were 7 recurrences (17%) in dMMR versus 4 recurrences (4%) in pMMR (P=0.009). On univariate analysis of any recurrence, both dMMR (hazard ratio: 5.3, P=0.008) and stage (hazard ratio: 3.8, P=0.05) were statistically significantly associated with time to first recurrence. The 5-year recurrence free survival was 90% (95% CI: 73%-96%) in pMMR versus 61.0% (95% CI: 19%-86%) in dMMR (P=0.003). Five-year OS was 96% (95% CI: 76%-99%) in pMMR versus 86% (95% CI: 62%-95%) in dMMR (P=0.03). CONCLUSIONS: MMR deficiency in stage I to II grade 1 to 2 endometrial cancer patients treated with adjuvant VB alone was associated with statistically significant increased risk for any recurrence and worse OS. MMR status may be an important prognosticator in this cohort of patients warranting adjuvant treatment intensification in the clinical trial setting.

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.

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.

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.

Enhanced Efficacy of Aurora Kinase Inhibitors in G2/M Checkpoint Deficient TP53 Mutant Uterine Carcinomas Is Linked to the Summation of LKB1-AKT-p53 Interactions.

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.

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.

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.

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.

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.

Prognostic Value of Preoperative Imaging: Comparing 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography to Computed Tomography Alone for Preoperative Planning in High-risk Histology Endometrial Carcinoma.

OBJECTIVE: 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) increases the sensitivity for preoperative detection of lymph nodes and distant metastases in endometrial cancer. The objective of this investigation was to determine the prognostic value of preoperative PET-CT compared with computed tomography (CT) alone for high-risk endometrial carcinoma. MATERIALS AND METHODS: We performed a retrospective review of high-risk histology endometrial cancer from 2008 to 2015. Clinical variables including surgical procedure, preoperative imaging modality, and outcome were collected. Survival analysis was performed utilizing the Kaplan-Meier and Cox proportional hazards methodologies. RESULTS: Of the 555 women treated for high-risk histology endometrial cancer, 88 (16%) had preoperative PET-CT, and 97 (17%) CT without PET available. PET-CT demonstrated positive findings in 37 women (42%) compared with 33 (30%) with preoperative CT alone. PET-CT had a positive predictive value of 96% for nodal metastasis compared with 60% for CT alone. The median follow-up time for the entire cohort was 59 months (range, 12 to 96 mo). Patients with a negative preoperative PET-CT (n=54) had a median progression-free survival (PFS) that was not reached, whereas the median PFS in the PET-CT positive group was 13 months (n=34). Women with a negative PET-CT had a longer median overall survival (OS) not yet reached compared with 34 months in the PET-CT positive cohort (hazard ratio, 2.4; P<0.001). CT findings did not associate with PFS or OS. CONCLUSIONS: PET-CT demonstrated superior sensitivity for lymph node metastasis and detecting distant disease compared with CT. Preoperative PET-CT, whether positive or negative, offered OS and PFS prognostic value not observed with CT alone.

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.

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.

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.