The association of maintenance hormone therapy with overall survival in advanced-stage low-grade serous ovarian carcinoma: A risk-set matched retrospective study.

OBJECTIVE: We conducted a multi-institutional observational study to investigate whether maintenance hormone therapy following primary treatment of low-grade advanced-stage ovarian cancer (LGSOC) is associated with an overall survival advantage. METHODS: We included patients with histologically confirmed stage III or IV LGSOC diagnosed between Jan 1, 2004, and Dec 31, 2019, treated in Commission on Cancer-accredited cancer programs in the US. Patients who received hormone therapy within six months of diagnosis were matched to controls who did not initiate hormone therapy during this timeframe by risk-set propensity score matching. The primary outcome was the risk of death from any cause within five years of initiation of HT or observation. RESULTS: There were 296 patients who initiated maintenance hormone therapy within six months of diagnosis and 2805 potential controls. Patients who received hormone therapy were more often treated in academic medical centers (55% vs. 44%), diagnosed later in the study period (62% vs. 23% diagnosed in 2018-2019), and frequently received no chemotherapy during initial treatment (45% vs. 17%). After risk set propensity score matching, we identified 225 patients treated with HT and 225 untreated controls who were otherwise similar with respect to measured covariates. In the matched cohort, hormone therapy was associated with a reduction in the risk of death (hazard ratio 0.60; 95% CI 0.38-0.94), corresponding to a 60-month survival of 75% compared with 65%. CONCLUSIONS: Following primary management of LGSOC, maintenance hormone therapy was associated with improved overall survival compared with observation.

Enhanced Recovery After Surgery Patients Are Prescribed Fewer Opioids at Discharge: A Propensity-score Matched Analysis.

OBJECTIVE: We aimed to compare discharge opioid prescriptions pre- and post-ERAS implementation. SUMMARY OF BACKGROUND DATA: ERAS programs decrease inpatient opioid use, but their relationship with postdischarge opioids remains unclear. METHODS: All patients undergoing hysterectomy between October 2016 and November 2020 and pancreatectomy or hepatectomy between April 2017 and November 2020 at 1 tertiary care center were included. For each procedure, ERAS was implemented during the study period. PSM was performed to compare pre - versus post-ERAS patients on discharge opioids (number of pills and oral morphine equivalents). Patients were matched on age, sex, race, payor, American Society of Anesthesiologists score, prior opioid use, and procedure. Sensitivity analyses in open versus minimally invasive surgery cohorts were performed. RESULTS: A total of 3983 patients were included (1929 pre-ERAS; 2054 post-ERAS). Post-ERAS patients were younger (56.0 vs 58.4 years; P < 0.001), more often female (95.8% vs 78.1%; P < 0.001), less often white (77.2% vs 82.0%; P < 0.001), less often had prior opioid use (20.1% vs 28.1%; P < 0.001), and more often underwent hysterectomy (91.1% vs 55.7%; P < 0.001). After PSM, there were no significant differences between cohorts in baseline characteristics. Matched post-ERAS patients were prescribed fewer opioid pills (17.4 pills vs 22.0 pills; P < 0.001) and lower oral morphine equivalents (129.4 mg vs 167.6 mg; P < 0.001) than pre-ERAS patients. Sensitivity analyses confirmed these findings [open (18.8 pills vs 25.4 pills; P < 0.001 \ 138.9 mg vs 198.7 mg; P < 0.001); minimally invasive surgery (17.2 pills vs 21.1 pills; P < 0.001 \ 127.1 mg vs 160.1 mg; P < 0.001). CONCLUSIONS: Post-ERAS patients were prescribed significantly fewer opioids at discharge compared to matched pre-ERAS patients.

A pragmatic clinical trial assessing the effect of a targeted notification and clinical support pathway on the diagnostic evaluation and treatment of individuals with left ventricular hypertrophy (NOTIFY-LVH).

BACKGROUND: Electronic health records contain vast amounts of cardiovascular data, including potential clues suggesting unrecognized conditions. One important example is the identification of left ventricular hypertrophy (LVH) on echocardiography. If the underlying causes are untreated, individuals are at increased risk of developing clinically significant pathology. As the most common cause of LVH, hypertension accounts for more cardiovascular deaths than any other modifiable risk factor. Contemporary healthcare systems have suboptimal mechanisms for detecting and effectively implementing hypertension treatment before downstream consequences develop. Thus, there is an urgent need to validate alternative intervention strategies for individuals with preexisting-but potentially unrecognized-LVH. METHODS: Through a randomized pragmatic trial within a large integrated healthcare system, we will study the impact of a centralized clinical support pathway on the diagnosis and treatment of hypertension and other LVH-associated diseases in individuals with echocardiographic evidence of concentric LVH. Approximately 600 individuals who are not treated for hypertension and who do not have a known cardiomyopathy will be randomized. The intervention will be directed by population health coordinators who will notify longitudinal clinicians and offer to assist with the diagnostic evaluation of LVH. Our hypothesis is that an intervention that alerts clinicians to the presence of LVH will increase the detection and treatment of hypertension and the diagnosis of alternative causes of thickened myocardium. The primary outcome is the initiation of an antihypertensive medication. Secondary outcomes include new hypertension diagnoses and new cardiomyopathy diagnoses. The trial began in March 2023 and outcomes will be assessed 12 months from the start of follow-up. CONCLUSION: The NOTIFY-LVH trial will assess the efficacy of a centralized intervention to improve the detection and treatment of hypertension and LVH-associated diseases. Additionally, it will serve as a proof-of-concept for how to effectively utilize previously collected electronic health data to improve the recognition and management of a broad range of chronic cardiovascular conditions. TRIAL REGISTRATION: NCT05713916.

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.

Trends in the use of neoadjuvant chemotherapy for low-grade serous ovarian cancer in the United States.

OBJECTIVE: To describe trends in neoadjuvant chemotherapy (NACT) use for low-grade serous ovarian carcinoma (LGSOC) and to quantify associations between NACT and extent of cytoreductive surgery. METHODS: We identified women treated for stage III or IV serous ovarian cancer in a Commission on Cancer accredited program between January 2004-December 2020. Regression models were developed to evaluate trends in NACT use for LGSOC, to identify factors associated with receipt of NACT, and to quantify associations between NACT and bowel or urinary resection at the time of surgery. Demographic and clinical factors were used for confounder control. RESULTS: We observed 3350 patients who received treatment for LGSOC during the study period. The proportion of patients who received NACT increased from 9.5% in 2004 to 25.9% in 2020, corresponding to an annual percent change of 7.2% (95% CI 5.6-8.9). Increasing age (rate ratio (RR) 1.15; 95% CI 1.07-1.24), and stage IV disease (RR 2.66; 95% CI 2.31-3.07) were associated with a higher likelihood of receiving NACT. For patients with high-grade disease, NACT was associated with a decrease in likelihood of bowel or urinary surgery (35.3% versus 23.9%; RR 0.68, 95% CI 0.65-0.71). For LGSOC, NACT was associated with a higher likelihood of these procedures (26.6% versus 32.2%; RR 1.24, 95% CI 1.08-1.42). CONCLUSION: NACT use among patients with LGSOC has increased from 2004 to 2020. While NACT was associated with a lower rate of gastrointestinal and urinary surgery among patients with high-grade disease, patients with LGSOC receiving NACT were more likely to undergo these procedures.

Patterns of spread and genetic alterations of primary endometrioid carcinomas of the ovary.

OBJECTIVE: The primary objective was to characterize the rate of lymph node involvement in a cohort of patients with primary ovarian endometrioid adenocarcinoma. Additionally, we sought to quantify the recurrence rate, genetic alterations, and impact of lymphadenectomy on survival in this group of patients. METHODS: Patients diagnosed with primary endometrioid adenocarcinoma of the ovary without synchronous carcinomas of the female genital tract between 2012 and 2021 were identified. Demographic and disease-related data were collected from pathology reports and clinical records. Kaplan-Meier survival analysis using log rank test and Cox regression was performed. RESULTS: Sixty-three patients met inclusion criteria. Median age was 60 (range 22-90) years. Histologic grade was 1 in 20 (32%), 2 in 27 (43%), and 3 in 16 (25%) tumors. International Federation of Gynecology and Obstetrics (FIGO) stage after surgery included IA/B (n=20, 32%), IC (n=23, 37%), II (n=16, 25%), and III (n=4, 6%). Forty-one (65%) patients had pelvic and 33 (52%) had both pelvic and para-aortic lymphadenectomy. All assessed lymph nodes were negative for metastatic carcinoma. No patients with clinically pelvis-confined disease had tumors upstaged by either lymphadenectomy or omentectomy. Twenty-eight patients (44%) had germline mutational status documented; two had a germline BRCA mutation, confirmed to be pathogenic by molecular studies. Complete staging did not significantly impact progression free or overall survival, after adjusting for age and histologic grade in a Cox proportional hazards model. The recurrence rate was 15% for patients with grade 1 endometrioid carcinoma, 7% for grade 2, and 31% for grade 3, respectively. CONCLUSION: There were no lymph node metastases in patients with comprehensively staged primary endometrioid ovarian carcinoma. Staging did not impact survival and may be omitted, regardless of grade. Germline BRCA mutations are rare in ovarian endometrioid carcinoma compared with reported rates in high-grade serous carcinomas.

Black and hispanic women have less support during cancer evaluation and treatment: results from a prospective patient reported outcomes program in gynecologic malignancy.

OBJECTIVE: Race remains a significant predictor of poor outcomes in women with gynecologic cancer and minority patients consistently report worse quality of life during cancer treatment. Disparities between patients in strength of social and emotional supports may contribute to these outcomes. This study's objective was to describe the racial differences in patient reported outcomes of women being evaluated or treated for a gynecologic malignancy at a large tertiary cancer hospital. METHODS: In this prospective cohort study, all patients presenting for care at a tertiary care gynecologic oncology clinic between January 2018 and September 2019 were evaluated for inclusion. All patients were administered validated patient reported outcome measure questionnaires at serial visits. Demographic data was gathered including self-reported race. Patients were characterized as White, Black, Asian, Hispanic/Latino, or Other. Patient reported outcomes were compared between respondents of different races using linear and logistic regression. RESULTS: Between January 2018 to September 2019, 2022 patients with a known race completed questionnaires. Of these patients, 86.7% were White, 4.3% Black, and 4.9% Hispanic/Latino and 58.7% had a known cancer diagnosis. Non-White patients were significantly less likely to complete questionnaires (p<0.001). Non-White patients reported significantly lower levels of emotional support on all questions (Patient-Reported Outcomes Measurement Information System (PROMIS) emotional support: Q1 p<0.001, Q2 p<0.001, Q3 p=0.013, Q4 p=0.002), and lower overall emotional (p=0.005) and instrumental (p=0.005) support scores when compared with White patients. Hispanic/Latino patients reported the lowest levels of emotional and instrumental support and more cognitive (p=0.043) and financial (p=0.040) difficulties associated with treatment. Black women reported having less support with chores while sick (p=0.014) and being less likely to have someone to talk to (p=0.013). CONCLUSIONS: Significant differences exist in patient reported outcomes between women of different racial backgrounds. Hispanic/Latino and Black women have less support during gynecologic cancer evaluation and treatment as compared with White women.

The Surgeon's Perceived Value of Patient-reported Outcome Measures (PROMs): An Exploratory Qualitative Study of 5 Different Surgical Subspecialties.

OBJECTIVE: To understand the surgeon's perceived value of PROMs in 5 different surgical subspecialties. SUMMARY OF BACKGROUND DATA: PROMs are validated questionnaires that assess the symptoms, function, and quality of life from the patient's perspective. Despite the increasing support for use of PROMs in the literature, there is limited uptake amongst surgeons. Furthermore, there is insufficient understanding of the surgeons' perceived value of PROMs. The aim of this study is to understand how surgeons perceive value in PROMs. METHODS: We conducted an exploratory qualitative study to understand the perceived value of PROMs from the perspective of surgeons in various subspecialties. Per convenience sampling, we conducted semi-structured interviews with 30 surgeons from 5 subspecialties across 3 academic medical centers. The surgical subspecialties included bariatric surgery, breast oncologic surgery, orthopedic surgery, plastic and reconstructive surgery, and rhinology. Interviews were transcribed, coded, and evaluated with thematic analysis. RESULTS: Surgeons endorsed that PROMs can be used to enhance clinical management, counsel patients in the preoperative and postoperative settings, and elicit sensitive information from patients that otherwise may go undetected. Obstacles to PROMs use include failure to generate actionable data, implementation obstacles, and inappropriate use of PROMs as a performance metric, with concerns regarding inadequate risk adjustment. CONCLUSIONS: Establishing an effective PROMs program requires an understanding of the surgeon's perspective of PROMs. Despite obstacles, different subspecialty surgeons find PROMs to be valuable in different settings, depending on the specialty and clinical context.

Factors Associated with Physician Tolerance of Uncertainty: an Observational Study.

BACKGROUND: Physicians need to learn and work amidst a plethora of uncertainties, which may drive burnout. Understanding differences in tolerance of uncertainty is an important research area. OBJECTIVE: To examine factors associated with tolerance of uncertainty, including well-being metrics such as burnout. DESIGN: Online confidential survey. SETTING: The Massachusetts General Physicians Organization (MGPO). PARTICIPANTS: All 2172 clinically active faculty in the MGPO. MAIN MEASURES: We examined associations for tolerance of uncertainty with demographic information, personal and professional characteristics, and physician well-being metrics. KEY RESULTS: Two thousand twenty (93%) physicians responded. Multivariable analyses identified significant associations of lower tolerance of uncertainty with female gender (OR, 1.23; 95% CI, 1.03-1.48); primary care practice (OR, 1.56; 95% CI, 1.22-2.00); years since training (OR, 0.99; 95% CI, 0.98-0.995); and lacking a trusted advisor (OR, 1.25; 95% CI, 1.03-1.53). Adjusting for demographic and professional characteristics, physicians with low tolerance of uncertainty had higher likelihood of being burned-out (OR, 3.06; 95% CI, 2.41-3.88), were less likely to be satisfied with career (OR, 0.37; 95% CI, 0.26-0.52), and less likely to be engaged at work (RR, 0.87; 95% CI, 0.84-0.90). CONCLUSION: At a time when concern about physician well-being is high, with much speculation about causes of burnout, we found a strong relationship between tolerance of uncertainty and physician well-being, across specialties. Particular attention likely needs to be paid to those with less experience, those in specialties with high rates of undifferentiated illness and uncertainty, such as primary care, and ensuring all physicians have access to a trusted advisor. These results generate the potential hypothesis that efforts focused in understanding and embracing uncertainty could be potentially effective for reducing burnout. This concept should be tested in prospective trials.

Understanding Physician Work and Well-being Through Social Network Modeling Using Electronic Health Record Data: a Cohort Study.

BACKGROUND: Understanding association between factors related to clinical work environment and well-being can inform strategies to improve physicians' work experience. OBJECTIVE: To model and quantify what drivers of work composition, team structure, and dynamics are associated with well-being. DESIGN: Utilizing social network modeling, this cohort study of physicians in an academic health center examined inbasket messaging data from 2018 to 2019 to identify work composition, team structure, and dynamics features. Indicators from a survey in 2019 were used as dependent variables to identify factors predictive of well-being. PARTICIPANTS: EHR data available for 188 physicians and their care teams from 18 primary care practices; survey data available for 163/188 physicians. MAIN MEASURES: Area under the receiver operating characteristic curve (AUC) of logistic regression models to predict well-being dependent variables was assessed out-of-sample. KEY RESULTS: The mean AUC of the model for the dependent variables of emotional exhaustion, vigor, and professional fulfillment was, respectively, 0.665 (SD 0.085), 0.700 (SD 0.082), and 0.669 (SD 0.082). Predictors associated with decreased well-being included physician centrality within support team (OR 3.90, 95% CI 1.28-11.97, P=0.01) and share of messages related to scheduling (OR 1.10, 95% CI 1.03-1.17, P=0.003). Predictors associated with increased well-being included higher number of medical assistants within close support team (OR 0.91, 95% CI 0.83-0.99, P=0.05), nurse-centered message writing practices (OR 0.89, 95% CI 0.83-0.95, P=0.001), and share of messages related to ambiguous diagnosis (OR 0.92, 95% CI 0.87-0.98, P=0.01). CONCLUSIONS: Through integration of EHR data with social network modeling, the analysis highlights new characteristics of care team structure and dynamics that are associated with physician well-being. This quantitative methodology can be utilized to assess in a refined data-driven way the impact of organizational changes to improve well-being through optimizing team dynamics and work composition.

Initial findings from a prospective, large scale patient reported outcomes program in patients with gynecologic malignancy.

INTRODUCTION: Patient reported outcome measures (PROMs) are associated with improved overall survival in patients with metastatic malignancy; however, routine collection of PROMs is nascent. Little is known about PROs in women with gynecologic malignancy outside of a trial setting, limiting our understanding of how routine populations experience treatment, disease and morbidity. The goal of this study was to prospectively collect and describe disease-specific PROs in a non-trial population of women with gynecologic malignancy. METHODS: PROMs were assigned electronically to all patients presenting for care in our gynecologic oncology clinic. Patients received a general oncology questionnaire (EORTC QLQ C30) a disease specific questionnaire (FACT V, EORTC EN24, EORTC OV28, EORTC Cx 24), and questionnaires assessing support at home. Responses were mapped to relevant clinical variables. Descriptive statistics were performed, and comparisons made with parametric and nonparametric analyses. The association between support at home and perioperative complications was assessed via logistic regression. RESULTS: In the study period, 3239 unique patients were evaluated at new patient visits, post-operative visits, chemotherapy visits and surveillance visits with a PROMs completion rate of 78.1% (n = 2530 women with 4402 completions). There was no difference in completion rates based on age or self-identified race. The EORTC QLQ C-30 questionnaire was able to adequately discern differences between disease sites. Overall, scores were lower than those obtained in trial populations. PROMs responses were not associated with perioperative complications. CONCLUSION: Systematic collection of PROMs is feasible and tech-enabled workflows result in high collection rates. Quality of life scores in our clinic population were lower than published data, indicating caution should be used when extrapolating quality of life data from clinical trials to counseling and decision making around routine patient populations.

Intraoperative Deaths: Who, Why, and Can We Prevent Them?

INTRODUCTION: Intraoperative deaths (IODs) are rare but catastrophic. We systematically analyzed IODs to identify clinical and patient safety patterns. METHODS: IODs in a large academic center between 2015 and 2019 were included. Perioperative details were systematically reviewed, focusing on (1) identifying phenotypes of IOD, (2) describing emerging themes immediately preceding cardiac arrest, and (3) suggesting interventions to mitigate IOD in each phenotype. RESULTS: Forty-one patients were included. Three IOD phenotypes were identified: trauma (T), nontrauma emergency (NT), and elective (EL) surgery patients, each with 2 sub-phenotypes (e.g., ELm and ELv for elective surgery with medical arrests or vascular injury and bleeding, respectively). In phenotype T, cardiopulmonary resuscitation was initiated before incision in 42%, resuscitative thoracotomy was performed in 33%, and transient return of spontaneous circulation was achieved in 30% of patients. In phenotype NT, ruptured aortic aneurysms accounted for half the cases, and median blood product utilization was 2,694 mL. In phenotype ELm, preoperative evaluation did not include electrocardiogram in 12%, cardiac consultation in 62%, stress test in 87%, and chest x-ray in 37% of patients. In phenotype ELv, 83% had a single peripheral intravenous line, and vascular injury was almost always followed by escalation in monitoring (e.g., central/arterial line), alert to the blood bank, and call for surgical backup. CONCLUSIONS: We have created a framework for IOD that can help with intraoperative safety and quality analysis. Focusing on interventions that address appropriateness versus futility in care in phenotypes T and NT, and on prevention and mitigation of intraoperative vessel injury (e.g., intraoperative rescue team) or preoperative optimization in phenotype EL may help prevent IODs.

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.

Losartan treatment enhances chemotherapy efficacy and reduces ascites in ovarian cancer models by normalizing the tumor stroma.

In ovarian cancer patients, tumor fibrosis and angiotensin-driven fibrogenic signaling have been shown to inversely correlate with survival. We sought to enhance drug delivery and therapeutic efficacy by remodeling the dense extracellular matrix in two orthotopic human ovarian carcinoma xenograft models. We hypothesized that targeting the angiotensin signaling axis with losartan, an approved angiotensin system inhibitor, could reduce extracellular matrix content and the associated "solid stress," leading to better anticancer therapeutic effect. We report here four translatable findings: (i) losartan treatment enhances the efficacy of paclitaxel-a drug used for ovarian cancer treatment-via normalizing the tumor microenvironment, resulting in improved vessel perfusion and drug delivery; (ii) losartan depletes matrix via inducing antifibrotic miRNAs that should be tested as candidate biomarkers of response or resistance to chemotherapy; (iii) although losartan therapy alone does not reduce tumor burden, it reduces both the incidence and the amount of ascites formed; and (iv) our retrospective analysis revealed that patients receiving angiotensin system inhibitors concurrently with standard treatment for ovarian cancer exhibited 30 mo longer overall survival compared with patients on other antihypertensives. Our findings provide the rationale and supporting data for a clinical trial on combined losartan and chemotherapy in ovarian cancer patients.

Impact of Gabapentin on PACU Length of Stay and Perioperative Intravenous Opioid Use for ERAS Hysterectomy Patients.

We investigated the impact of preoperative gabapentin on perioperative intravenous opioid requirements and post anesthesia care unit length of stay (PACU LOS) for patients undergoing laparoscopic and vaginal hysterectomies within an Enhanced Recovery After Surgery (ERAS) pathway. A multidisciplinary team retrospectively examined 2,015 patients who underwent laparoscopic or vaginal hysterectomies between October 2016 and January 2020 at a single academic institution. The average PACU LOS was 168 min among patients who did not receive gabapentin vs. 180 min both among patients who received ≤ 300 mg of gabapentin and patients who received > 300 mg of gabapentin. After adjusting for demographics and medical comorbidities, PACU LOS for patients given ≤ 300 mg gabapentin was 6% longer (rate ratio (RR) = 1.06, 95% CI = 1.01-1.11) than for patients who were not given gabapentin, and for patients who received > 300 mg of gabapentin was 7% longer (RR = 1.07, 95%CI = 1.01-1.13) than for those who did not receive gabapentin. Patients who received ≤ 300 mg gabapentin received 9% less perioperative intravenous hydromorphone than patients who did not receive gabapentin (RR = 0.91, 95% CI = 0.86 - 0.97); patients who received > 300 mg of gabapentin received 12% less perioperative intravenous hydromorphone than patients who did not receive gabapentin (RR = 0.88, 95% CI = 0.82 - 0.95). These findings represent an absolute difference of 0.09 mg intravenous hydromorphone. There were no statistically significant differences in total intravenous fentanyl received. Preoperative gabapentin given as part of an ERAS pathway is associated with statistically but not clinically significant increases in PACU LOS and decreases in total perioperative intravenous opioid use.

Survival after Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer.

BACKGROUND: Minimally invasive surgery was adopted as an alternative to laparotomy (open surgery) for radical hysterectomy in patients with early-stage cervical cancer before high-quality evidence regarding its effect on survival was available. We sought to determine the effect of minimally invasive surgery on all-cause mortality among women undergoing radical hysterectomy for cervical cancer. METHODS: We performed a cohort study involving women who underwent radical hysterectomy for stage IA2 or IB1 cervical cancer during the 2010-2013 period at Commission on Cancer-accredited hospitals in the United States. The study used inverse probability of treatment propensity-score weighting. We also conducted an interrupted time-series analysis involving women who underwent radical hysterectomy for cervical cancer during the 2000-2010 period, using the Surveillance, Epidemiology, and End Results program database. RESULTS: In the primary analysis, 1225 of 2461 women (49.8%) underwent minimally invasive surgery. Women treated with minimally invasive surgery were more often white, privately insured, and from ZIP Codes with higher socioeconomic status, had smaller, lower-grade tumors, and were more likely to have received a diagnosis later in the study period than women who underwent open surgery. Over a median follow-up of 45 months, the 4-year mortality was 9.1% among women who underwent minimally invasive surgery and 5.3% among those who underwent open surgery (hazard ratio, 1.65; 95% confidence interval [CI], 1.22 to 2.22; P=0.002 by the log-rank test). Before the adoption of minimally invasive radical hysterectomy (i.e., in the 2000-2006 period), the 4-year relative survival rate among women who underwent radical hysterectomy for cervical cancer remained stable (annual percentage change, 0.3%; 95% CI, -0.1 to 0.6). The adoption of minimally invasive surgery coincided with a decline in the 4-year relative survival rate of 0.8% (95% CI, 0.3 to 1.4) per year after 2006 (P=0.01 for change of trend). CONCLUSIONS: In an epidemiologic study, minimally invasive radical hysterectomy was associated with shorter overall survival than open surgery among women with stage IA2 or IB1 cervical carcinoma. (Funded by the National Cancer Institute and others.).

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.

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.

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.

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.