Vaccination of Adults With Cancer: ASCO Guideline.

PURPOSE: To guide the vaccination of adults with solid tumors or hematologic malignancies. METHODS: A systematic literature review identified systematic reviews, randomized controlled trials (RCTs), and nonrandomized studies on the efficacy and safety of vaccines used by adults with cancer or their household contacts. This review builds on a 2013 guideline by the Infectious Disease Society of America. PubMed and the Cochrane Library were searched from January 1, 2013, to February 16, 2023. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS: A total of 102 publications were included in the systematic review: 24 systematic reviews, 14 RCTs, and 64 nonrandomized studies. The largest body of evidence addressed COVID-19 vaccines. RECOMMENDATIONS: The goal of vaccination is to limit the severity of infection and prevent infection where feasible. Optimizing vaccination status should be considered a key element in the care of patients with cancer. This approach includes the documentation of vaccination status at the time of the first patient visit; timely provision of recommended vaccines; and appropriate revaccination after hematopoietic stem-cell transplantation, chimeric antigen receptor T-cell therapy, or B-cell-depleting therapy. Active interaction and coordination among healthcare providers, including primary care practitioners, pharmacists, and nursing team members, are needed. Vaccination of household contacts will enhance protection for patients with cancer. Some vaccination and revaccination plans for patients with cancer may be affected by the underlying immune status and the anticancer therapy received. As a result, vaccine strategies may differ from the vaccine recommendations for the general healthy adult population vaccine.Additional information is available at www.asco.org/supportive-care-guidelines.

Dietary Magnesium Replacement for Prevention of Hypomagnesemia in Patients With Ovarian Cancer Receiving Carboplatin-Based Chemotherapy.

PURPOSE: Hypomagnesemia is a common side effect of platinum-based chemotherapy and predicts poor overall survival in some cancers. Standard magnesium replacement strategies are often inadequate for maintaining magnesium levels. We hypothesized that a daily dietary magnesium replacement approach through magnesium-rich foods would help maintain adequate magnesium levels during platinum-based treatment. MATERIALS AND METHODS: We conducted a prospective feasibility study of magnesium-rich diets in patients 18 years and older with previously untreated ovarian cancer scheduled to receive carboplatin-containing chemotherapy of at least six consecutive cycles. Education about magnesium-rich diets was provided at enrollment and then weekly during chemotherapy. Feasibility was defined as ≥60% completion of dietary recalls and ≥280 mg average daily dietary magnesium intake across all patients. RESULTS: Twenty-one of 26 patients enrolled completed at least five chemotherapy cycles and were included in the analysis. Adherence to the study diet was 76%. Daily dietary magnesium intake was 100.5 mg at baseline and increased throughout each cycle: 6% of patients at baseline, 24% after the first cycle, and 67% after the fifth cycle reached ≥280-mg/day magnesium intake. Seven (33%) of 21 had at least one incident of hypomagnesemia. Patients who were adherent had significantly lower incidence of hypomagnesemia (19% v 80%, P = .03) and less need for intravenous magnesium (6% v 60%, P = .03) than those who were nonadherent. CONCLUSION: The study achieved primary feasibility objectives of retention and adherence to the study intervention. Weekly education about magnesium-rich diets was effective in increasing dietary magnesium intake. Adequate dietary magnesium appeared to be protective against hypomagnesemia.

Efficacy, safety, and feasibility of Apixaban for postoperative venous thromboembolism prophylaxis following open gynecologic cancer surgery at a comprehensive cancer center.

OBJECTIVES: To evaluate safety, efficacy, and feasibility of apixaban for postoperative venous thromboembolism (VTE) prophylaxis following open gynecologic cancer surgery at a comprehensive cancer center. METHODS: This retrospective, cohort study included patients with gynecologic cancer who underwent open surgery between 3/2021 and 3/2023 and received 28-day postoperative VTE prophylaxis. Patients on therapeutic anticoagulation preoperatively were excluded. Predictors of 90- and 30-day VTE and 30-day bleeding events were determined using multivariable logistic regression, adjusting for known confounders. RESULTS: 452 patients were included in the cohort: 348 received apixaban and 104 received enoxaparin. Those who received enoxaparin were more likely to be American Society of Anesthesiologists class III/IV (compared to I/II) (p = 0.033), current or former smokers (p = 0.012) and have a higher BMI (p < 0.001), Charlson Comorbidity Index (p = 0.005), and age (p = 0.046). 30-day VTE rate was significantly lower in the apixaban group (0.6%) compared to the enoxaparin group (6.2%) (adjusted OR 0.13, 95% CI 0.03-0.56; p = 0.006). 90-day VTE rate was 2.7% and 6.2% in the apixaban and enoxaparin groups, respectively (adjusted OR 0.85, 95% CI 0.38-1.92; p = 0.704). Major bleeding complications (2.4% vs. 2.0%) and minor bleeding complications (0.9% vs. 3.0%) were similar in the apixaban and enoxaparin groups, respectively, on multivariate analyses. The median patient out of pocket cost was $10 (IQR 0.0-40.0) for apixaban and $20 (IQR 3.7-67.7) for enoxaparin (p = 0.001). CONCLUSIONS: Our findings along with previously published data suggest that apixaban should be considered the standard of care for VTE prophylaxis in patients undergoing open surgery for gynecologic malignancies.

Determination of quality of life-related health utilities for surgical complications in ovarian cancer.

OBJECTIVE: To assess the health state utilities of ovarian cancer patients, clinicians, and non-cancer controls regarding surgical complications in ovarian cancer. METHODS: Utilities for 14 surgical complications were assessed from patients with recently diagnosed or recurrent ovarian cancer, clinicians, and non-cancer controls using the visual analog scale (VAS) and time trade-off (TTO) methods. Health state utilities were converted to a 0-to-1 scale, where 0 represents the least favorable outcome and 1 represents the most favorable outcome. RESULTS: Fifty patients, 50 clinicians, and 50 controls participated. Median VAS scores were lower than TTO scores across all groups (p < 0.01). Patients viewed 'bleeding requiring transfusion' most favorably (VAS utility 0.75), followed in order by less favorable utility scores for hernia, thromboembolism, pleural effusion, abscess, ileus/bowel obstruction, wound infection, bowel obstruction requiring surgery, anastomotic leak requiring drain, temporary ostomy, anastomotic leak requiring surgery, genito-urinary fistula, permanent ostomy, and genito-intestinal fistula (VAS utility 0.2). Overall, clinicians perceived complications more favorably than patients by VAS (overall utility score 0.49 vs 0.43, p < 0.01), but not by the TTO. There were no differences in overall utility scores between patients and controls. Patients who had not experienced certain surgical complications had less favorable scores than patients who did (utility score for ostomy = 0.2 for patients without ostomy vs. 0.7 for patients with ostomy, p = 0.02). CONCLUSIONS: This study establishes health state utilities for surgical complications associated with ovarian cancer. These utilities can be used in future cost-effectiveness evaluations to determine quality-adjusted outcomes and may help in counseling patients during the shared decision-making process.

Randomized phase 2 trial of tremelimumab and durvalumab in combination versus sequentially in recurrent platinum-resistant ovarian cancer.

BACKGROUND: Single-agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%-40% of patients achieve stable disease. The primary objective was to estimate progression-free survival (PFS) after sequential versus combination cytotoxic T-lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum-resistant high-grade serous ovarian cancer (HGSOC). METHODS: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm. The primary end point was immune-related PFS (irPFS). RESULTS: Sixty-one subjects were randomized to sequential (n = 38) or combination therapy (n = 23). Thirteen patients (34.2%) in the sequential arm received durvalumab. There was no difference in PFS in the sequential arm (1.84 months; 95% CI, 1.77-2.17 months) compared with the combination arm (1.87 months; 95% CI, 1.77-2.43 months) (p = .402). In the sequential arm, no responses were observed, although 12 patients (31.6%) demonstrated stable disease. In the combination arm, two patients (8.7%) had partial response, whereas one patient (4.4%) had stable disease. Adverse events were consistent with those previously reported for ICIs. Patient-reported outcomes were similar in both arms. CONCLUSIONS: There was no difference in irPFS for combination tremelimumab plus durvalumab compared to tremelimumab alone (administered as part of a sequential treatment strategy) in a heavily pretreated population of patients with platinum-resistant HGSOC. Response rates were comparable to prior reports, although the combination regimen did not add significant benefit, as has been previously described.

Proteometabolomics of initial and recurrent glioblastoma highlights an increased immune cell signature with altered lipid metabolism.

BACKGROUND: There is an urgent need to better understand the mechanisms associated with the development, progression, and onset of recurrence after initial surgery in glioblastoma (GBM). The use of integrative phenotype-focused -omics technologies such as proteomics and lipidomics provides an unbiased approach to explore the molecular evolution of the tumor and its associated environment. METHODS: We assembled a cohort of patient-matched initial (iGBM) and recurrent (rGBM) specimens of resected GBM. Proteome and metabolome composition were determined by mass spectrometry-based techniques. We performed neutrophil-GBM cell coculture experiments to evaluate the behavior of rGBM-enriched proteins in the tumor microenvironment. ELISA-based quantitation of candidate proteins was performed to test the association of their plasma concentrations in iGBM with the onset of recurrence. RESULTS: Proteomic profiles reflect increased immune cell infiltration and extracellular matrix reorganization in rGBM. ASAH1, SYMN, and GPNMB were highly enriched proteins in rGBM. Lipidomics indicates the downregulation of ceramides in rGBM. Cell analyses suggest a role for ASAH1 in neutrophils and its localization in extracellular traps. Plasma concentrations of ASAH1 and SYNM show an association with time to recurrence. CONCLUSIONS: We describe the potential importance of ASAH1 in tumor progression and development of rGBM via metabolic rearrangement and showcase the feedback from the tumor microenvironment to plasma proteome profiles. We report the potential of ASAH1 and SYNM as plasma markers of rGBM progression. The published datasets can be considered as a resource for further functional and biomarker studies involving additional -omics technologies.

Longitudinal perioperative patient-reported outcomes in open compared with minimally invasive hysterectomy.

BACKGROUND: There are few prospective studies in the gynecologic surgical literature that compared patient-reported outcomes between open and minimally invasive hysterectomies within enhanced recovery after surgery pathways. OBJECTIVE: This study aimed to compare prospectively collected perioperative patient-reported symptom burden and interference measures in open compared with minimally invasive hysterectomy cohorts within enhanced recovery after surgery pathways. STUDY DESIGN: We compared patient-reported symptom burden and functional interference in 646 patients who underwent a hysterectomy (254 underwent open surgery and 392 underwent minimally invasive surgery) for benign and malignant indications under enhanced recovery after surgery protocols. Outcomes were prospectively measured using the validated MD Anderson Symptom Inventory, which was administered perioperatively up to 8 weeks after surgery. Cohorts were compared using Fisher exact and chi-squared tests, adjusted longitudinal generalized linear mixed modeling, and Kaplan Meier curves to model return to no or mild symptoms. RESULTS: The open cohort had significantly worse preoperative physical functional interference (P=.001). At the time of hospital discharge postoperatively, the open cohort reported significantly higher mean symptom severity scores and more moderate or severe scores for overall (P<.001) and abdominal pain (P<.001), fatigue (P=.001), lack of appetite (P<.001), bloating (P=.041), and constipation (P<.001) when compared with the minimally invasive cohort. The open cohort also had significantly higher interference in physical functioning (score 5.0 vs 2.7; P<.001) than the minimally invasive cohort at the time of discharge with no differences in affective interference between the 2 groups. In mixed modeling analysis of the first 7 postoperative days, both cohorts reported improved symptom burden and functional interference over time with generally slower recovery in the open cohort. From 1 to 8 postoperative weeks, the open cohort had worse mean scores for all evaluated symptoms and interference measures except for pain with urination, although scores indicated mild symptomatic burden and interference in both cohorts. The time to return to no or mild symptoms was significantly longer in the open cohort for overall pain (14 vs 4 days; P<.001), fatigue (8 vs 4 days; P<.001), disturbed sleep (2 vs 2 days; P<.001), and appetite (1.5 vs 1 days; P<.001) but was significantly longer in the minimally invasive cohort for abdominal pain (42 vs 28 days; P<.001) and bloating (42 vs 8 days; P<.001). The median time to return to no or mild functional interference was longer in the open than in the minimally invasive hysterectomy cohort for physical functioning (36 vs 32 days; P<.001) with no difference in compositive affective functioning (5 vs 5 days; P=.07) between the groups. CONCLUSION: Open hysterectomy was associated with increased symptom burden in the immediate postoperative period and longer time to return to no or mild symptom burden and interference with physical functioning. However, all patient-reported measures improved within days to weeks of both open and minimally invasive surgery and differences were not always clinically significant.

Experiences of patients with peritoneal carcinomatosis-related complex care needs and their caregivers.

BACKGROUND: Patients with peritoneal carcinomatosis (PC) frequently undergo palliative procedures, yet these patients and their caregivers report being unprepared to manage ostomies, drains, and other complex care needs at home. The purpose of this study was to characterize the unique needs of these patients and their caregivers during care transitions. METHODS: Patients completed measures of health status and advance care planning, caregivers completed measures of preparedness and burden, and all participants completed measures of depression and anxiety. Participants detailed their experiences in individual, semi-structured interviews. We analyzed data using descriptive statistics and conventional content analysis. RESULTS: Sixty-one patients and 39 caregivers completed baseline measures. Twenty-four (39.3%) patients acknowledged their terminal illness and seven (11.5%) had discussed end-of-life care preferences with clinicians. Most (26/39, 66.7%) caregivers provided daily care. Among caregivers who managed symptoms, few were taught how to do so (6/20, 30%). Seven patients (11.5%) and seven caregivers (17.9%) met case criteria for anxiety, while 15 patients (24.6%) and two caregivers (5.1%) met case criteria for depression. Interview participants described a diagnosis of PC as a turning point for which there is no road map and identified the need for health systems change to minimize suffering. CONCLUSION: Patients with PC and their caregivers are highly burdened by symptoms and care needs. Patients' prognostic understanding and advance care planning are suboptimal. Interventions that train patients with PC and their caregivers to perform clinical care tasks, facilitate serious illness conversations, and provide psychosocial support are needed.

Evaluation of a tiered opioid prescription algorithm in an ERAS pathway: exploring opportunities for further refinement.

BACKGROUND: Opioid over-prescription is wasteful and contributes to the opioid crisis. We implemented a personalized tiered discharge opioid protocol and education on opioid disposal to minimize over-prescription. OBJECTIVE: To evaluate the intervention by investigating opioid use post-discharge for women undergoing abdomino-pelvic surgery, and patient adherence to opioid disposal education. METHODS: We analyzed post-discharge opioid consumption among 558 patients. Eligible patients included those who underwent elective gynecologic surgery, were not taking scheduled opioids pre-operatively, and received discharge opioids according to a tiered prescribing algorithm. A survey assessing discharge opioid consumption and disposal safety knowledge was distributed on post-discharge day 21. Over-prescription was defined as >20% of the original prescription left over. Descriptive statistics were used for analysis. RESULTS: The survey response rate was 61% and 59% in the minimally invasive surgery and open surgery cohorts, respectively. Overall, 42.8% of patients reported using no opioids after hospital discharge, 45.2% in the minimally invasive surgery and 38.6% in the open surgery cohort. Furthermore, 74.9% of respondents were over-prescribed, with median age being statistically significant for this group (p=0.004). Finally, 46.4% of respondents expressed no knowledge regarding safe disposal practices, with no statistically significant difference between groups (p>0.99). CONCLUSION: Despite implementation of the tiered discharge opioid algorithm aimed to personalize opioid prescriptions to estimated need, we still over-prescribed opioids. Additionally, despite targeted education, nearly half of all patients who completed the survey did not know how to dispose of their opioid tablets. Additional efforts are needed to further refine the algorithm to reduce over-prescription of opioids and improve disposal education.

Assisted reproductive technology in France: The reproductive rights of LGBT people.

BACKGROUND: In 2021, France authorized ART with sperm donor for female couples and single women. OBJECTIVES: We summarize here the possibilities of ART among LGBT people in France to date, pointing out the main restrictions for LGBT reproductive rights, requiring future legislative changes. RESULTS: Despite the latest modification of the French bioethics laws which notably opens ART to female couples, French legislation still excludes most LGBT people from parenthood through ART, especially gay men and transgender people in most cases. Surrogacy, ROPA, co-parenting and directed sperm donation are banned. CONCLUSIONS: Legalize ROPA and overcome gender issues for trans people are necessary. A French model of surrogacy is to be considered.

Rate of venous thromboembolism on an enhanced recovery program after gynecologic surgery.

BACKGROUND: Venous thromboembolism is a life-threatening complication of surgery. An Enhanced Recovery After Surgery program is a multimodal care pathway that facilitates faster recovery from surgery. The rate of venous thromboembolism after gynecologic surgery on an Enhanced Recovery After Surgery program is unknown. OBJECTIVE: This study aimed to evaluate the rate of venous thromboembolism within 30 days of gynecologic surgery on an Enhanced Recovery After Surgery pathway performed at a cancer center. STUDY DESIGN: Data were collected prospectively on Enhanced Recovery After Surgery pathway gynecologic patients undergoing open surgery (November 3, 2014, to March 31, 2021) and minimally invasive surgery (February 1, 2017, to March 31, 2021). Care was delivered at a tertiary cancer care center located in a large urban area. Patients undergoing emergency surgery or multispecialty surgeries were excluded. Patients undergoing open surgery were to receive heparin prophylaxis before surgery, sequential compression devices during surgery and admission, and low-molecular-weight heparin prophylaxis during admission. If diagnosed with malignancy, patients were to receive extended venous thromboembolism prophylaxis for 28 days after surgery. For minimally invasive surgery, patients received only sequential compression devices during surgery and no heparin prophylaxis before or after surgery. Venous thromboembolism events were included if detected on imaging obtained for symptoms or other indications. Descriptive statistics and bivariate statistical analyses were performed. RESULTS: Of 3329 patients, 1519 (45.6%) underwent laparotomy, 1452 (43.6%) underwent laparoscopy, and 358 (10.8%) underwent robotic surgery. The incidence rates of venous thromboembolism were 0.6% (n=21; 95% confidence interval, 0.4%-0.9%) overall, 1.1% (n=16, 95% confidence interval, 0.6%-1.7%) in the open approach, and 0.3% (n=5; 95% confidence interval, 0.3%-0.6%) in the minimally invasive approach (P=.02). The incidence rates of venous thromboembolism among the 1999 patients with malignancy were 0.9% (n=18; 95% confidence interval, 0.5%-1.4%) overall, 1.4% (n=15; 95% confidence interval, 0.7%-2.2%) in the open approach, and 0.3% (n=3; 95% confidence interval, 0.1%-0.9%) in the minimally invasive approach. The incidence rates of venous thromboembolism among the 1165 patients with benign disease were 0.3% (n=3; 95% confidence interval, 0.1%-0.7%) overall, 0.3% (n=1; 95% confidence interval, 0.0%-1.7%) in the open approach, and 0.2% (n=2; 95% confidence interval, 0.0%-0.9%) in the minimally invasive approach. CONCLUSION: The rate of venous thromboembolism among patients undergoing laparotomy and minimally invasive surgery on an Enhanced Recovery After Surgery pathway was ≤1%. This study established a benchmark for the rate of venous thromboembolism after gynecologic surgery on an Enhanced Recovery After Surgery pathway performed at a cancer center.

Secondary validation of an ovarian cancer-specific comorbidity index in a US population.

OBJECTIVES: The Ovarian Cancer Comorbidity Index (OCCI) is an age-specific index developed and previously found to be more predictive of overall and cancer-specific survival than the Charlson Comorbidity Index (CCI). The objective was to perform secondary validation of the OCCI in a US population. METHODS: A cohort of ovarian cancer patients undergoing primary or interval cytoreductive surgery from January 2005 to January 2012 was identified in SEER-Medicare. OCCI scores were calculated with the regression coefficients determined from the original developmental cohort for five comorbidities. Cox regression analyses were used to calculate associations between the OCCI risk groups and 5-year overall survival and 5-year cancer-specific survival in comparison to the CCI. RESULTS: A total of 5052 patients were included. Median age was 74 (range 66-82) years. 47% (n=2375) had stage III and 24% (n=1197) had stage IV disease at diagnosis. 67% had a serous histology subtype (n=3403). All patients were categorized as moderate (48.4%) or high risk (51.6%). The prevalence of the five predictive comorbidities were: coronary artery disease 3.7%, hypertension 67.5%, chronic obstructive pulmonary disease 16.7%, diabetes 21.8%, and dementia 1.2%. Controlling for histology, grade, and age-stratification, worse overall survival was associated with both a higher OCCI (hazard ratio (HR) 1.57; 95% confidence interval (CI) 1.46 to 1.69) and CCI (HR 1.96; 95% CI 1.66 to 2.32). Cancer-specific survival was associated with the OCCI (HR 1.33; 95% CI 1.22 to 1.44) but was not associated with the CCI (HR 1.15; 95% CI 0.93 to 1.43). CONCLUSIONS: This internationally developed comorbidity score for ovarian cancer patients is predictive for both overall and cancer-specific survival in a US population. CCI was not predictive for cancer-specific survival. This score may have research applications when utilizing large administrative datasets.

Association between COVID-19 and Postoperative Neurological Complications and Antipsychotic Medication Use after Cancer Surgery: A Retrospective Study.

INTRODUCTION: Millions of Americans infected with the severe acute respiratory syndrome-associated coronavirus-19 (COVID-19) need oncologic surgery. Patients with acute or resolved COVID-19 illness complain of neuropsychiatric symptoms. How surgery affects postoperative neuropsychiatric outcomes such as delirium is unknown. We hypothesize that patients with a history of COVID-19 could have an exaggerated risk of developing postoperative delirium after undergoing major elective oncologic surgery. METHODS: We conducted a retrospective study to determine the association between COVID-19 status and antipsychotic drugs during postsurgical hospitalization as a surrogate of delirium. Secondary outcomes included 30 days of postoperative complications, length of stay, and mortality. Patients were grouped into pre-pandemic non-COVID-19 and COVID-19-positive groups. A 1:2 propensity score matching was used to minimize bias. A multivariable logistic regression model estimated the effects of important covariates on the use of postoperative psychotic medication. RESULTS: A total of 6003 patients were included in the study. Pre- and post-propensity score matching demonstrated that a history of preoperative COVID-19 did not increase the risk of antipsychotic medications postoperatively. However, respiratory and overall 30-day complications were higher in COVID-19 individuals than in pre-pandemic non-COVID-19 patients. The multivariate analysis showed that the odds of using postoperative antipsychotic medication use for the patients who had COVID-19 compared to those who did not have the infection were not significantly different. CONCLUSION: A preoperative diagnosis of COVID-19 did not increase the risk of postoperative antipsychotic medication use or neurological complications. More studies are needed to reproduce our results due to the increased concern of neurological events post-COVID-19 infection.

Financial toxicity: A practical review for gynecologic oncology teams to understand and address patient-level financial burdens.

Financial toxicity describes the adverse impact patients experience from the monetary and time costs of cancer care. The financial burden patients experience comes from substantially increased out-of-pocket spending that often occurs concurrent with reduced income due to sick leave from work. Financial toxicity is common affecting approximately half of patients with a gynecological cancer depending on the validated instrument used for measurement. Financial toxicity is experienced by patients in three domains: economic hardship affecting patients' material conditions (i.e., medical debt), psychological response (i.e., distress), and health-related coping behaviors that patients adopt (i.e., foregoing care due to costs). Higher financial toxicity among cancer patients has been associated with decreased quality of life, impaired adherence to recommended care, and worse overall survival. In this review, we describe the current literature on financial toxicity, including how it can be assessed with validated tools, the downstream impact on patients, risk factors, and employment concerns of survivors. Whenever possible, we highlight data from research featuring patients with gynecologic cancer specifically. We also review studies with interventions aimed to mitigate financial toxicity and offer the reader real world examples of interventions currently being used. Lastly, we provide an overview of health policy developments relevant to financial toxicity and advocate for innovation in the development and implementation of strategies to decrease the financial toxicity patients experience following a diagnosis of gynecologic cancer.

Patient-reported symptoms at discharge and risk of complications after gynecologic surgery.

OBJECTIVE: Current gaps in knowledge limit clinicians from fully implementing patient-reported outcomes in routine post-operative care. METHODS: This prospective study assessed symptoms via the gynecologic module of the MD Anderson Symptom Inventory (MDASI-PeriOp-GYN) in patients who underwent open laparotomy. RESULTS: At discharge, patient-reported moderate to severe (≥4 on a 0-10 scale) abdominal bloating or abdominal cramping, combined with length of stay of ≥4 days, were found to be associated with a higher risk of 30-day post-operative grade II-IV complications by the Clavien-Dindo system (all p values <0.01). Also, length of stay of ≥4 days and moderate to severe urinary urgency at discharge were found to be associated with the need for re-admission (all p values <0.01). CONCLUSION: This study defined the clinically meaningful symptoms that related to the risk of developing important complications after discharge from major open gynecological surgery.These findings support the integration of assessment of patient-reported outcomes into patient-centered post-operative care.

Medicaid Expansion and Postoperative Mortality in Women with Gynecologic Cancer: A Difference-in-Difference Analysis.

BACKGROUND: The association between Medicaid expansion and postoperative mortality after surgery for gynecologic cancer is unknown. Our objective was to compare 30- and 90-day postoperative mortality after gynecologic cancer surgery before and after 2014 in states that did and did not expand Medicaid. METHODS: We searched the National Cancer Database for women aged 40-64 years old between 2010 and 2016 who underwent surgery for a primary gynecologic malignancy. We used pre/post and quasi-experimental difference-in-difference (DID) multivariable logistic regressions to evaluate mortality pre-2014 (2010-2013) and post-2014 (2014-2016) for states that did and did not expand Medicaid in January 2014. We completed univariable logistic regressions for covariates of interest. RESULTS: Among 169,731 women, 30-day postoperative mortality in expansion states after 2014 significantly decreased for endometrial cancer (odds ratio [OR] 0.42, 95% confidence interval [CI] 0.26-0.67) and ovarian cancer (OR 0.67, 95% CI 0.46-0.99) and increased for cervical cancer (OR 3.82, 95% CI 1.12-13.01). Compared with non-expansion states, expansion states had improved 30-day postoperative mortality for endometrial cancer after 2014 (DID OR 0.54, 95% CI 0.31-0.96). Univariable analysis demonstrated improved 30-day postoperative mortality for Black women with endometrial cancer in expansion states (DID OR 0.22, 95% CI 0.05-0.95). There was improved 90-day postoperative mortality for endometrial cancer in expansion states (OR 0.66, 95% CI 0.50-0.85), and improved 90-day postoperative mortality for Midwestern women with ovarian cancer in expansion states on univariable analysis (DID OR 0.48, 95% CI 0.26-0.91). CONCLUSIONS: State Medicaid legislation was associated with improved postoperative survival in women with endometrial cancer and subgroups of women with endometrial and ovarian cancer.

Predicting 180-day mortality for women with ovarian cancer using machine learning and patient-reported outcome data.

Contrary to national guidelines, women with ovarian cancer often receive treatment at the end of life, potentially due to the difficulty in accurately estimating prognosis. We trained machine learning algorithms to guide prognosis by predicting 180-day mortality for women with ovarian cancer using patient-reported outcomes (PRO) data. We collected data from a single academic cancer institution in the United States. Women completed biopsychosocial PRO measures every 90 days. We randomly partitioned our dataset into training and testing samples. We used synthetic minority oversampling to reduce class imbalance in the training dataset. We fitted training data to six machine learning algorithms and combined their classifications on the testing dataset into an unweighted voting ensemble. We assessed each algorithm's accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) using testing data. We recruited 245 patients who completed 1319 PRO assessments. The final voting ensemble produced state-of-the-art results on the task of predicting 180-day mortality for ovarian cancer paitents (Accuracy = 0.79, Sensitivity = 0.71, Specificity = 0.80, AUROC = 0.76). The algorithm correctly identified 25 of the 35 women in the testing dataset who died within 180 days of assessment. Machine learning algorithms trained using PRO data offer encouraging performance in predicting whether a woman with ovarian cancer will die within 180 days. This model could be used to drive data-driven end-of-life care and address current shortcomings in care delivery. Our model demonstrates the potential of biopsychosocial PROM information to make substantial contributions to oncology prediction modeling. This model could inform clinical decision-making Future research is needed to validate these findings in a larger, more diverse sample.

Neoadjuvant checkpoint inhibitor immunotherapy for resectable mucosal melanoma.

Background: Neoadjuvant checkpoint inhibition (CPI) has recently demonstrated impressive outcomes in patients with stage 3 cutaneous melanoma. However, the safety, efficacy, and outcome of neoadjuvant CPI in patients with mucosal melanoma (MM) are not well studied as MM is a rare melanoma subtype. CPI such as combination nivolumab and ipilimumab achieves response rates of 37-43% in unresectable or metastatic MM but there is limited data regarding the efficacy of these agents in the preoperative setting. We hypothesize that neoadjuvant CPI is a safe and feasible approach for patients with resectable MM. Method: Under an institutionally approved protocol, we identified adult MM patients with resectable disease who received neoadjuvant anti-PD1 +/- anti-CTLA4 between 2015 to 2019 at our institution. Clinical information include age, gender, presence of nodal involvement or satellitosis, functional status, pre-treatment LDH, tumor mutation status, and treatment data was collected. Outcomes include event free survival (EFS), overall survival (OS), objective response rate (ORR), pathologic response rate (PRR), and grade ≥3 toxicities. Results: We identified 36 patients. Median age was 62; 58% were female. Seventy-eight percent of patients received anti-PD1 + anti-CTLA4. Node positive disease or satellite lesions was present at the time of treatment initiation in 47% of patients. Primary sites of disease were anorectal (53%), urogenital (25%), head and neck (17%), and esophageal (6%). A minority of patients did not undergo surgery due to complete response (n=3, 8%) and disease progression (n=6, 17%), respectively. With a median follow up of 37.9 months, the median EFS was 9.2 months with 3-year EFS rate of 29%. Median OS had not been reached and 3-year OS rate was 55%. ORR was 47% and PRR was 35%. EFS was significantly higher for patients with objective response and for patients with pathologic response. OS was significantly higher for patients with pathologic response. Grade 3 toxicities were reported in 39% of patients. Conclusion: Neoadjuvant CPI for resectable MM is a feasible approach with signs of efficacy and an acceptable safety profile. As there is currently no standard approach for resectable MM, this study supports further investigations using neoadjuvant therapy for these patients.

Opioid-sparing anesthesia and patient-reported outcomes after open gynecologic surgery: a historical cohort study.

PURPOSE: Dexmedetomidine and ketamine may be administered intraoperatively as continuous infusions to provide opioid-sparing anesthesia. Recent evidence has yielded controversial results regarding the impact of opioid-free anesthesia on postoperative complications, and there is a gap in knowledge regarding patient-reported outcomes (PROs). This study aimed to determine the impact of opioid-sparing anesthesia and opioid-based anesthesia on PROs among gynecologic patients within an enhanced recovery after surgery (ERAS) program. METHODS: We formed a single-center historical cohort from patients enrolled in another study who underwent open gynecologic surgery on an ERAS program from November 2014 to December 2020 (n = 2,095). We identified two cohorts based on the type of balanced anesthesia administered: 1) opioid-sparing anesthesia defined as the continuous infusion of dexmedetomidine and ketamine (adjuvants) during surgery or 2) opioid-based anesthesia (no adjuvants). We measured the quality of postoperative recovery using the MD Anderson Symptom Inventory (MDASI), a 29-item validated tool that was administered preoperatively, daily while admitted, and weekly after discharge until week 6. The primary outcome was interference with walking. We matched both cohorts and used a multilevel linear mixed-effect model to evaluate the effect of opioid-sparing anesthesia on the primary outcome. RESULTS: In total, 498 patients were eligible (159 in the opioid-sparing anesthesia cohort and 339 in the opioid-based anesthesia cohort), of whom 149 matched pairs were included in the final analysis. Longitudinal assessment showed no significant or clinically important difference in interference with walking (P = 0.99), general activity (P = 0.99), or other PROs between cohorts. Median [interquartile range (IQR)] intraoperative opioid administration (expressed as morphine milligram equivalents [MME]) among matched patients in the opioid-sparing anesthesia cohort was 30 [25-55] mg vs 58 [8-70] mg in the opioid-based anesthesia cohort (P < 0.01). Patients in the opioid-sparing anesthesia cohort had a lower opioid consumption in the postanesthesia care unit than those in the opioid-based anesthesia cohort (MME, 3 [0-10] mg vs 5 [0-15] mg; P < 0.01), but there was no significant difference between cohorts in total postoperative opioid consumption (MME, 23 [0-94] mg vs 35 [13-95] mg P = 0.053). CONCLUSIONS: In this single-center historical cohort study, opioid-sparing anesthesia had no significant or clinically important effects on interference with walking or other PROs in patients undergoing gynecologic surgery compared with opioid-based anesthesia. Opioid-sparing anesthesia was associated with less short-term opioid consumption than opioid-based anesthesia.

RéSUMé: OBJECTIF: La dexmédétomidine et la kétamine peuvent être administrées en peropératoire sous forme de perfusions continues pour fournir une anesthésie avec épargne opioïde. Des données probantes récentes ont présenté des résultats controversés concernant l'impact d'une anesthésie sans opioïdes sur les complications postopératoires, et il existe une lacune dans les connaissances concernant les issues rapportées par les patients (IRP). Cette étude visait à déterminer l'impact d'une anesthésie avec épargne opioïde et d'une anesthésie à base d'opioïdes sur les IRP chez les patientes de chirurgie gynécologique dans le cadre d'un programme de Récupération rapide après la chirurgie (ERAS ­ Enhanced Recovery After Surgery). MéTHODE: Nous avons formé une cohorte historique monocentrique composée de patientes inscrites à une autre étude qui ont bénéficié d'une chirurgie gynécologique avec laparotomie dans le cadre d'un programme d'ERAS entre novembre 2014 et décembre 2020 (n = 2095). Nous avons identifié deux cohortes en fonction du type d'anesthésie équilibrée administrée : 1) anesthésie avec épargne opioïde, définie comme une perfusion continue de dexmédétomidine et de kétamine (adjuvants) pendant la chirurgie, ou 2) anesthésie à base d'opioïdes (sans adjuvants). Nous avons mesuré la qualité de la récupération postopératoire à l'aide de l'inventaire des symptômes MDASI, un outil validé comportant 29 éléments qui a été administré avant l'opération, quotidiennement pendant l'admission et chaque semaine après le congé jusqu'à la semaine 6. Le critère d'évaluation principal était l'interférence avec la marche. Nous avons apparié les deux cohortes et utilisé un modèle linéaire à effets mixtes à plusieurs niveaux pour évaluer l'effet de l'anesthésie avec épargne opioïde sur le critère d'évaluation principal. RéSULTATS: Au total, 498 patientes étaient éligibles (159 dans la cohorte d'anesthésie avec épargne opioïde et 339 dans la cohorte d'anesthésie à base d'opioïdes), dont 149 paires appariées ont été incluses dans l'analyse finale. L'évaluation longitudinale n'a révélé aucune différence significative ou cliniquement importante dans l'interférence avec la marche (P = 0,99), l'activité générale (P = 0,99), ou d'autres IRP entre les deux cohortes. L'administration médiane d'opioïdes peropératoires [écart interquartile (ÉIQ)] (exprimée en équivalents de morphine en milligrammes [EMM]) chez les patientes appariées de la cohorte d'anesthésie avec épargne opioïde était de 30 [25-55] mg vs 58 [8­70] mg dans la cohorte d'anesthésie à base d'opioïdes (P < 0,01). Les patientes de la cohorte d'anesthésie avec épargne opioïde avaient une consommation d'opioïdes plus faible en salle de réveil que celles de la cohorte d'anesthésie à base d'opioïdes (EMM, 3 [0-10] mg vs 5 [0­15] mg; P < 0,01), mais il n'y avait pas de différence significative entre les cohortes dans la consommation totale d'opioïdes postopératoires (EMM, 23 [0-94] mg vs 35 [13­95] mg; P = 0,053). CONCLUSION: Dans cette étude de cohorte historique monocentrique, l'anesthésie avec épargne opioïde n'a eu aucun effet significatif ou cliniquement important sur l'interférence avec la marche ou d'autres IRP chez les patientes bénéficiant d'une chirurgie gynécologique par rapport à l'anesthésie à base d'opioïdes. L'anesthésie avec épargne opioïde était associée à une consommation d'opioïdes moindre à court terme que l'anesthésie à base d'opioïdes.