BACKGROUND:The use of artificial intelligence (AI) in medicine has surged. Given the sensitive nature of palliative care, it is crucial to apply AI tools in a patient-centered and ethical manner. AIM:We sought to understand the ethical implications of implementing AI-based tools in palliative care from various stakeholders. DESIGN:Using a framework of ethics of care, we conducted thematic analysis to identify emerging themes. SETTING/PARTICIPANTS:We recruited and interviewed 22 participants: six patients, four care-partners, five clinicians, three bioethicists, and four clinician-bioethicists, recruited through a single hospital clinic for patients and care-partners and purposeful snowball sampling for clinicians and bioethicists based on their knowledge and interest in AI-based tools. The mean age of participants was 48 years old; 64% were male. Clinician participants had practiced for a mean of 11 years, and ethicists for 15 years. We aimed to recruit clinicians and bioethicists from multiple states and specialties. RESULTS:From the interviews we extracted five main themes: (1) Primacy of the doctor-patient relationship over AI performance; (2) Humans have intuition and nuance that AI lacks; (3) Agreement about the importance of oversight of AI tools; (4) New AI technologies should include a process for patient education; and (5) AI increases efficiency, scalability, and a more unified approach to serious illness. CONCLUSIONS:When building and implementing AI-based tools, we recommend: establishing oversight committees; reflecting on the unique contributions of humans to care; proactively educating patients and contextualizing the tools; and ensuring data use is restricted to clinical care.

Objective: Maintenance therapy with poly(ADP-ribose) polymerase inhibitors (PARPi) improves survival in patients with advanced epithelial ovarian cancer (EOC), a benefit most pronounced in patients with homologous recombination deficient (HRD) tumors. We estimated the survival benefits of increasing universal germline and somatic testing among patients with advanced EOC. Methods: We developed a simulation model to estimate the survival of patients with newly diagnosed stage III or IV EOC, using data from the National Cancer Database (NCDB). In our model, we applied hazard ratios from clinical trials to survival data from the NCDB, in order to reflect the differential effects of maintenance PARPi in patients who are germline BRCA1/2+; somatic BRCA1/2+ (or other HRD mutation+); or homologous recombination proficient (HRP). We simulated a "current practice" strategy, in which only half of patients received HRD testing, and a "universal testing" strategy, in which all patients were tested. In the primary analysis, we compared the predicted median survival. In sensitivity analyses, we explored effects of 100% uptake of PARPi among eligible patients. Results: In the “current practice” strategy, median survival was 49 months. With “universal testing”, median survival increased to 51 months, a 2-month benefit compared to current practice. In a sensitivity analysis, the median survival associated with universal testing and 100% uptake of PARPi was 53 months, a 4-month benefit compared to “current practice.” Conclusions: Universal HRD testing may improve median survival by 2 months for patients diagnosed with advanced EOC. Increased PARPi uptake may extend this benefit by an additional 2 months.

PURPOSE:To understand from patients, care partners (P/CPs), and physicians the ideal timing of specialty palliative care (SPC) involvement. METHODS:Using a framework of phenomenology and care ethics, we analyzed interviews through a thematic analysis approach. Two investigators independently coded transcripts of recorded interviews. P/CPs were recruited from a single hospital clinic from multiple different oncologists. Physicians were recruited via purposeful snowball sampling based on their knowledge and expertise. RESULTS:Thirty-one participants were recruited: 14 (45%) P/CPs and 17 (55%) clinicians. The mean age of P/CP was 49 years, whereas clinicians' mean age was 44 years. Half of P/CPs were female, and a similar portion of clinicians (53%) were female. More than half of patients had gliomas (57%), and all clinicians were physicians who had practiced neuro-oncology for a mean of 12 years. We identified four themes: (1) Participants felt patients would have benefited from earlier SPC, but there were slight differences in timing based on brain tumor type and grade; (2) neuro-oncology patients have unique supportive care needs compared to other cancers; (3) specialty knowledge of neuro-oncology is important to P/CP for advance care planning, prognostication, and anticipatory guidance; and (4) the broadly intensive role played by care partners in neuro-oncology means they have equally heavy supportive needs. CONCLUSION:This is one of the first studies to explore timing of SPC for patients with CNS tumors. P/CPs and clinicians agreed that early, time-based SPC is beneficial for management of high-grade tumors. Increasing knowledge of neuro-oncology among SPC clinicians working with this population is an area for further study.

Background Oncology practices increasingly collect electronic patient-reported outcomes (ePROs). While ePROs provide valuable insights, it is unknown whether electronically-reported symptoms are addressed during clinic visits. Large language models (LLMs) present a novel opportunity to systematically compare ePROs to symptoms documented by clinicians. Objectives To assess LLM performance identifying symptoms in visit notes and evaluate concordance between clinician-documented symptoms and ePROs. Methods In this retrospective study, we analyzed records of adults with an estimated prognosis < 1 year (1) evaluated in gastrointestinal and gynecologic oncology clinics from January 2022-July 2023. We manually annotated 12 symptoms in a training dataset of 500 notes (gold standard), then prompted a HIPAA-compliant LLM (GPT4DFCI 4o) to identify these symptoms. To assess LLM performance compared to the gold standard, we calculated model F1 scores (goal ≥0.70) for each symptom. We then used the LLM to identify symptoms in notes written within four days of an ePRO submission and calculated sensitivity and specificity of notes to ePRO symptoms by severity. Results Of 772 eligible patients, 552 submitted an ePRO during the study period. Notes from 5,049 visits were included in the analysis. Model F1 scores ranged from 0.60 (trouble drinking) to 0.90 (numbness/tingling); scores were 0.70-0.79 for four symptoms and ≥0.80 for six symptoms. Among the 10 accurately identified symptoms, visit note sensitivity compared to ePROs ranged from 0.31 (anxiety) to 0.71 (pain); specificity ranged from 0.65 (fatigue) to 0.95 (dyspnea). When only severe symptoms were considered, sensitivity ranged from 0.57 (anxiety) to 0.94 (pain). Conclusions The LLM accurately identified most symptoms. Notes reliably reflected ePRO reports of pain and absence of dyspnea; more severe symptoms were more often documented. There is a gap between patient reports and clinician documentation of anxiety, highlighting a potentially unmet need and underscoring the importance of ePROs when characterizing symptoms.

Importance The longitudinal patterns of patient-reported outcomes and their association with mortality in routine oncology care are largely unexplored. Objectives To characterize the longitudinal patient-reported outcomes among patients undergoing chemotherapy and evaluate their association with mortality. Design, Setting, and Participants This secondary analysis assessed patients in the intervention arm of a cluster randomized clinical trial conducted by the Symptom Management Implementation of Patient Reported Outcomes in Oncology (SIMPRO) consortium. Patients with gastrointestinal, gynecologic, or thoracic cancer who started a new chemotherapy regimen and completed at least 1 symptom questionnaire within 180 days at medical oncology clinics at 6 hospitals (Northeast and Southern US) were assessed from September 1, 2019, to August 31, 2023. Data analysis was performed from March to September 2025. Exposure Electronic health record–integrated symptom questionnaires along with patient education, decision support alerts, and clinical reports to facilitate symptom management. Main Outcomes and Measures Outcomes were patient-reported symptoms, physical function, overall well-being, and mortality. Multivariable regression identified factors associated with mortality during the 180-day follow-up period with symptoms included as time-varying covariates. Results Overall, 3735 patients (median [IQR] age, 67 [59-74] years; 2196 [59%] female) submitted 35 059 symptom questionnaires; 1710 (46%) were diagnosed with gastrointestinal, 1163 (31%) with thoracic, and 852 (23%) with gynecologic cancer. On multivariable analysis, moderate (hazard ratio [HR], 2.07; 95% CI, 1.34-3.20; P < .001) and severe (HR, 3.39; 95% CI, 2.20-5.22; P < .001) physical function deficits were associated with a higher hazard of death. Fatigue was the most common symptom reported (29 138 [83%]) followed by pain (19 959 [57%]). The prevalence of severe symptom reports decreased from 1440 of 30 660 reported symptoms (5%) in week 1 to 40 of 3528 reported symptoms (1%) in week 26, whereas moderate symptom reports decreased from 3522 of 30 660 symptoms (11%) to 265 of 3528 (8%). Other time-varying factors associated with higher hazard of death were moderate pain (HR, 1.43; 95%, CI 1.08-1.90; P = .01), severe pain (HR, 1.66; 94% CI, 1.21-2.26; P = .001), moderate dyspnea (HR, 1.31; 95% CI, 1.02-1.69; P = .04), severe dyspnea (HR, 1.62; 95% CI, 1.17-2.24; P = .004), moderate loss in appetite (HR, 1.40; 95% CI, 1.02-1.92; P = .04), and severe loss in appetite (HR, 2.27; 95% CI, 1.55-3.33; P < .001). Conclusions and Relevance This secondary analysis of a cluster randomized clinical trial of patients with cancer characterized the burden of cancer-related symptoms and described normative experiences for patients receiving chemotherapy for 3 common types of cancer and found that mortality was associated with patients’ evolving health status. These findings may help inform programs to monitor and manage symptoms and to deliver targeted interventions that enhance outcomes. Trial Registration ClinicalTrials.gov Identifier: NCT03850912

Abstract Immune checkpoint inhibitors (ICI) synergize preclinically with antibody drug conjugates (ADC), harboring anti-tubulin maytansinoid payloads. We conducted an investigator-initiated, single-arm, phase 2 trial of mirvetuximab soravtansine (MIRV), a folate receptor alpha (FOLR1/FRα)-targeting ADC with the maytansinoid payload, DM4, combined with pembrolizumab in female patients with recurrent FOLR1-expressing serous endometrial cancer (EC, NCT03835819). Co-primary objectives include objective response rate (ORR) and rate of progression-free survival at 6 months (PFS6); secondary objectives include PFS, overall survival, duration of response and safety. Exploratory objectives include correlation of tumor genomics and immunoprofiling with clinical activity. Eighteen patients initiated protocol therapy [MIRV 6 mg/kg adjusted ideal body weight IV and pembrolizumab 200 mg IV every 3 weeks]. Confirmed ORR is 28% (1 complete and 4 partial responses, 95% CI:10-53%), Kaplan Meier estimate of PFS6 is 24.4% (95% CI:7.7-46.1%) with 4 patients progression free at 6 months; trial was closed early for feasibility (planned sample size of 35 patients not reached) and hence these results are considered preliminary. G3 treatment-related adverse effects were rare with no grade ≥4 toxicities. We report a population of high FOLR1-expressing tumor-associated macrophages (CD163 + FOLR1 + ), suggesting potential on-target, off-tumor immune editing by MIRV. A composite biomarker score derived in this cohort correlates with objective response to MIRV and pembrolizumab.

IntroductionPain is among the most prevalent and distressing symptoms in advanced cancer, impairing physical, emotional, and social well-being. Management often requires support from family caregivers, whose own health and psychological well-being may also be adversely affected. This study examined the potential utility of digital phenotyping-moment-to-moment quantification of individual-level human behavior-to assess pain and physical quality of life (QOL) in patients with advanced cancer and their family caregivers.MethodsPatients with advanced cancer (n = 14) and their caregivers (n = 32) installed the Beiwe smartphone application, which enabled passive GPS data collection over 24 weeks. Raw GPS data were processed into daily mobility features and aggregated using biweekly moving averages and variability measures. Participants completed PROMIS measures of pain (intensity and interference) and physical QOL every 6 weeks. Within-person regression models were used to examine associations between changes in passive mobility features and changes in outcomes, with adjusted R² interpreted as effect size (small = 0.02, medium = 0.13, large = 0.26).ResultsCaregiver GPS-derived mobility features predicted a large proportion of variance in patient pain intensity (R² = 0.31) and pain interference (R² = 0.32). Combined caregiver and patient mobility data predicted large variance in caregiver physical QOL (R² = 0.43) and medium-to-large variance in patient pain intensity (R² = 0.16) and pain interference (R² = 0.33). Patient mobility features alone predicted small variance in caregiver physical QOL (R² = 0.02). When examining patient data predicting patient outcomes, mobility features were associated with small variance in physical QOL (R² = 0.03), pain intensity (R² = 0.05), and pain interference (R² = 0.08).DiscussionThese findings suggest that digital phenotyping may be a useful approach for predicting pain and physical QOL in advanced cancer, particularly when incorporating both patient and caregiver data. Further research is warranted to evaluate digital phenotyping as a novel method for monitoring symptoms and functional outcomes in advanced cancer care.

BACKGROUND:Opioid receipt differs by race and ethnicity across multiple settings, yet few studies have examined disparities after cancer-directed surgery. METHODS:Using fee-for-service Medicare claims, we identified cancer-directed surgeries between 2012 to 2021. Multivariable linear regression models estimated racial and ethnic differences in postoperative opioid fills and doses within 30-days, adjusting for demographic and clinical factors. We ran separate models among older (age ≥ 65) and younger (age < 65) Medicare beneficiaries (who typically qualify based on disability), and further models by preoperative opioid use (opioid-naïve vs not). RESULTS:We identified 958,593 surgical episodes. Overall 84.9% were non-Hispanic White (White), 8.1% non-Hispanic Black (Black), 4.4% Hispanic, and 2.2% Asian. Among older beneficiaries, Black and Hispanic patients were 4.7 [95%CI : 4.3,5.1] and 3.1 [95%CI : 2.6,3.6] percentage points more likely to fill ≥1 opioid than White patients. Mean 30day doses were similar between Black and White patients; whereas Hispanic and Asian patients filled modestly lower doses (-22 MME [95%CI:-27,-16], -53 MME [95%CI:-61,-46]). Among younger beneficiaries, opioid fill rates were relatively similar across racial and ethnic groups. However, mean 30-day doses were substantially lower among Black (-135 MME [95%CI:-154,-115]), Hispanic (-167 MME [95%CI:-198,-136]), and Asian (-259 MME [95%CI:-327,-191]) vs White patients, particularly those with prior opioid use. CONCLUSIONS:We observed modest racial and ethnic differences in opioid fills following cancer-directed surgeries among older Medicare beneficiaries. However, among younger beneficiaries, Black, Hispanic, and Asian patients filled substantially lower 30-day doses than White patients, primarily among those with prior opioid use. Cancer pain equity efforts should target populations experiencing meaningful disparities.

Abstract Background In the era of precision oncology, patients with advanced cancer are often living longer but are enduring years of fatiguing treatment. Fatigue is among the most common, chronic, and under-addressed side effects of advanced cancer treatment, and can lead to dose reductions, treatment interruptions, and discontinuation. Oral PolyADP-ribose polymerase (PARP) inhibitors have revolutionized the treatment of advanced ovarian cancer but are often accompanied by clinically-significant fatigue, and evidence-based treatments to cope with this side effect remain limited. A pilot trial suggests that telehealth acceptance and commitment therapy (ACT), a variant of cognitive behavioral therapy based on acceptance, mindfulness, and personal values, has potential to improve fatigue interference (i.e. disrupting activity and quality of life) among ovarian cancer patients on maintenance PARP inhibitors. This study protocol describes a fully-powered randomized controlled trial (RCT) of an innovative, remotely-delivered ACT intervention (‘REVITALIZE’) that aims to improve fatigue outcomes and PARP inhibitor adherence. Methods This two-armed, prospective RCT randomizes 240 adults with advanced ovarian cancer who report moderate to severe fatigue while on PARP inhibitors 1:1 to either REVITALIZE or education-enhanced usual care. The REVITALIZE intervention includes eight weekly one-hour individual sessions delivered via videoconference, plus two booster sessions at one- and two-month intervals thereafter. Participants, recruited from both academic and community cancer care sites across three U.S. regions, will complete assessments at baseline, mid-intervention, post-intervention, and 20 and 28-week follow-up (FU). The primary patient-reported outcome is change in fatigue interference from baseline to week 20 (FU1). Secondary patient-reported outcomes include fatigue severity, catastrophizing, self-efficacy, and quality of life. The primary behavioral outcome is monthly PARP inhibitor adherence, assessed by wireless medication adherence monitors; dose interruptions, reductions, and persistence will also be evaluated using adherence monitors and medical chart review. Discussion This paper describes a RCT that will evaluate the efficacy of the telehealth REVITALIZE intervention for improving fatigue-related outcomes and medication adherence among adults with advanced ovarian cancer taking PARP inhibitors. Findings will inform clinical practice and supportive care for adults with advanced ovarian cancer receiving treatments that cause fatigue. Trial registration Clinicaltrials.gov NCT06710548 on November 29, 2024.

BACKGROUND:Ovarian cancer debulking is associated with improved survival but carries significant morbidity, and data on meaningful outcomes among older adults remain limited. This study evaluated the association between frailty and days at home (DAH) at 1 year after surgery and identified modifiable factors. PATIENTS AND METHODS:This is a population-based study of Medicare fee-for-service beneficiaries (2014-2019) undergoing surgery for ovarian cancer. The primary exposure was a claims-based frailty index (CFI). The primary outcome was DAH at 1 year after surgery, calculated by subtracting hospital (inpatient, emergency department, and observation), nursing home (long-term hospital, skilled nursing, and rehabilitation facility), and death (days not alive) days from 365. Outcomes were stratified by frailty and age, and a multivariate linear regression model identified significant predictors of DAH. RESULTS:Among 7,348 patients (mean [SD] age, 74.3 [6.0] years), 44.0% were robust, 49.8% prefrail, and 6.2% frail. Mean [SD] DAH for all patients was 323 [89]; frail patients had significantly fewer DAH (269 [126]), as did prefrail patients (315 [96]), compared with robust patients (330 [68]) (P<.001). Robust older (age ≥80 years) patients had higher DAH than their frail younger (aged <70 years) counterparts (330 [79] vs 275 [117]). After 90 days, long-term mortality contributed to more loss in DAH through death days (26 [73]) than through hospital (3 [8]) or nursing home (2 [11]) days. Before 90 days, DAH were lost to hospital (6 [8)] and nursing home (3 [9]) rather than death (2 [10]) days. Frailty was the strongest predictor of fewer DAH (-52; 95% CI, -61 to -43) followed by high-risk surgical procedures (-30; 95% CI, -35 to -25). Minimally invasive surgery (MIS) was associated with higher DAH (+28 days; 95% CI, 24 to 33; P<.001). CONCLUSIONS:Frailty is the strongest predictor of DAH at 1 year after ovarian cancer surgery. Including frailty in surgical risk stratification, minimizing high-risk procedures, and utilizing MIS may improve patient-centered care for older adults with ovarian cancer.

Importance:The longitudinal patterns of patient-reported outcomes and their association with mortality in routine oncology care are largely unexplored. Objectives:To characterize the longitudinal patient-reported outcomes among patients undergoing chemotherapy and evaluate their association with mortality. Design, Setting, and Participants:This secondary analysis assessed patients in the intervention arm of a cluster randomized clinical trial conducted by the Symptom Management Implementation of Patient Reported Outcomes in Oncology (SIMPRO) consortium. Patients with gastrointestinal, gynecologic, or thoracic cancer who started a new chemotherapy regimen and completed at least 1 symptom questionnaire within 180 days at medical oncology clinics at 6 hospitals (Northeast and Southern US) were assessed from September 1, 2019, to August 31, 2023. Data analysis was performed from March to September 2025. Exposure:Electronic health record-integrated symptom questionnaires along with patient education, decision support alerts, and clinical reports to facilitate symptom management. Main Outcomes and Measures:Outcomes were patient-reported symptoms, physical function, overall well-being, and mortality. Multivariable regression identified factors associated with mortality during the 180-day follow-up period with symptoms included as time-varying covariates. Results:Overall, 3735 patients (median [IQR] age, 67 [59-74] years; 2196 [59%] female) submitted 35 059 symptom questionnaires; 1710 (46%) were diagnosed with gastrointestinal, 1163 (31%) with thoracic, and 852 (23%) with gynecologic cancer. On multivariable analysis, moderate (hazard ratio [HR], 2.07; 95% CI, 1.34-3.20; P < .001) and severe (HR, 3.39; 95% CI, 2.20-5.22; P < .001) physical function deficits were associated with a higher hazard of death. Fatigue was the most common symptom reported (29 138 [83%]) followed by pain (19 959 [57%]). The prevalence of severe symptom reports decreased from 1440 of 30 660 reported symptoms (5%) in week 1 to 40 of 3528 reported symptoms (1%) in week 26, whereas moderate symptom reports decreased from 3522 of 30 660 symptoms (11%) to 265 of 3528 (8%). Other time-varying factors associated with higher hazard of death were moderate pain (HR, 1.43; 95%, CI 1.08-1.90; P = .01), severe pain (HR, 1.66; 94% CI, 1.21-2.26; P = .001), moderate dyspnea (HR, 1.31; 95% CI, 1.02-1.69; P = .04), severe dyspnea (HR, 1.62; 95% CI, 1.17-2.24; P = .004), moderate loss in appetite (HR, 1.40; 95% CI, 1.02-1.92; P = .04), and severe loss in appetite (HR, 2.27; 95% CI, 1.55-3.33; P < .001). Conclusions and Relevance:This secondary analysis of a cluster randomized clinical trial of patients with cancer characterized the burden of cancer-related symptoms and described normative experiences for patients receiving chemotherapy for 3 common types of cancer and found that mortality was associated with patients' evolving health status. These findings may help inform programs to monitor and manage symptoms and to deliver targeted interventions that enhance outcomes. Trial Registration:ClinicalTrials.gov Identifier: NCT03850912.

BACKGROUND:Serious illness conversations (SICs) aim to elicit patient preferences and are associated with improved quality of life and reduced care utilization, but they occur infrequently. Sustainable interventions that encourage SICs are needed. PATIENTS AND METHODS:This pragmatic 4-arm randomized controlled trial enrolled adult patients at 5 disease-based oncology clinics at 2 sites of an academic cancer center between December 4, 2022, and July 31, 2024. All patients had pathways data indicating they were starting a treatment associated with a poor prognosis without documentation of an SIC in the Advance Care Planning module of the electronic health record (ACP-SICs) in the prior 6 months. Patients were randomized to 1 of 4 groups: (1) a nudge consisting of a mailed letter and questionnaire encouraging SICs; (2) a clinician nudge comprising an email reminder sent the day prior to the clinic visit to prompt an SIC; (3) both nudges; or (4) no nudges. The primary outcome was the proportion of patients with ACP-SICs within 60 days of randomization comparing the control (no-nudge) and combined-nudge arms; a prespecified alternate primary outcome included SICs identified in the free text of clinician notes using natural language processing (ACP + NLP-SIC). RESULTS:A total of 1,051 patients (median age, 65 years; 60% female; 79% White) were randomized to the control (n=261), clinician-nudge (n=240), patient-nudge (n=273), and combined-nudge arms (n=277). The ACP-SIC rates were 10.7%, 16.7%, 10.6%, and 17.3% for the control, clinician-nudge, patient-nudge, and combined-nudge arms, respectively, and the ACP + NLP-SIC rates were 22.6%, 28.8%, 22.3%, and 32.5%, respectively. Patients in the combined-nudge group had significantly higher ACP-SIC and ACP + NLP-SIC rates than the control group (P=.045 and P=.01, respectively), whereas the clinician-nudge and patient-nudge groups did not. CONCLUSIONS:Combined clinician- and patient-directed nudges resulted in higher SIC rates in 60 days, driven largely by the clinician nudge. NLP increased detection of SICs, demonstrating the importance of evaluating SICs in free-text notes.

Although there have been significant advances in the management of gynecologic malignancies in recent years, individuals with advanced disease continue to have high rates of recurrence. Strategies to decrease rates of recurrence and increase time to recurrence are urgently needed. Historically, prolonged chemotherapy treatment and consolidation therapy were unsuccessful. However, continuation of maintenance therapy after initial chemotherapy may offer improved progression-free survival (PFS) and overall survival (OS) in select circumstances. In recent years, maintenance agents including VEGF and poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors have improved PFS and sometimes even OS among women with ovarian cancer when used as monotherapy or in combination. PARP inhibitors demonstrate particularly robust results in patients with BRCA-mutated disease or other homologous recombination-deficient cancers. In endometrial and cervical cancers, immune checkpoint inhibitors combined with chemotherapy and used as maintenance thereafter have improved PFS and OS, with particular benefits noted in mismatch repair-deficient endometrial cancer and PD-L1-positive cervical cancer. Beyond currently available therapies, ongoing trials are exploring additional options for maintenance therapy, including antibody-drug conjugates, hormone-directed therapies, and novel targeted therapies such as XPO-1 inhibitors. Maintenance therapy can be accompanied by increased toxicity and cost; as such, careful consideration must be made about the relative benefit of any given maintenance strategy weighed against potential impacts on quality of life or financial toxicity. This review focuses on current maintenance therapy practices, emerging areas of research, and challenges in this area of study.

Objective : To examine the impact of comorbidity on overall survival in ovarian cancer patients and determine whether guideline-concordant care (GCC) mitigates the adverse effects of comorbidity. Design : Retrospective cohort study. Setting : United States. Population : Ovarian cancer patients in the National Cancer Database (2004-2021). Methods : Patients with comorbidities were identified using the Charlson-Deyo Comorbidity index (0, 1, and ≥2) and a GCC metric was developed with patients classified as receiving concordant care if they received all eligible treatments, and discordant care otherwise. We generated Kaplan-Meier curves and Cox proportional hazards models to examine the association between comorbidity, GCC, and overall survival. Multiplicative and additive interactions were examined between comorbidity and GCC. Results : We identified 165,944 ovarian cancer patients. Overall survival decreased with increasing comorbidity score (p<0.001) and was worse for patients receiving discordant vs. concordant care. Patients who received discordant care had worse survival across comorbidity levels compared with those who received concordant care (p<0.001). We observed additive and multiplicative interactions between comorbidity and GCC. Patients with 1 and ≥2 comorbidities with discordant care had a 27% and 65% increased hazard of death (adjusted hazard ratio [aHR]=1.27, 95% CI: 1.23 – 1.32 and aHR=1.65, 95% CI: 1.59 – 1.72), respectively, while those with concordant care had an 11% and 27% increased hazard of death (aHR=1.11, 95% CI: 1.08 – 1.14 and aHR=1.27, 95% CI: 1.22 – 1.33), respectively. Conclusion : Ovarian cancer patients with pre-existing comorbidities have worse survival than patients without comorbidities. Increasing adherence to guideline-directed treatment for all patients may improve outcomes.

Importance:The Centers for Medicare & Medicaid Services Oncology Care Model (OCM) was an episode payment model for patients with cancer; episodes were triggered by receipt of systemic cancer therapy. OCM provided monthly care management payments, and all practices were engaged in 1-sided risk in its early years. A concern about episode payment models triggered by use of a particular service is that they may prompt increases in episode volume. Objective:To assess if OCM is associated with an increase in the likelihood of initiating systemic therapy for cancer. Design, Setting, and Participants:This quasi-experimental study used matched difference-in-differences analysis of serial cross sections of Medicare beneficiaries with an index visit for cancer from January 2010 to December 2019 who were treated at OCM practices or matched practices not participating in the OCM and followed up for 1 year, comparing changes in outcomes before vs after OCM began in July 2016. Data were analyzed from October 2021 to November 2025. Main Outcomes and Measures:Systemic therapy initiation in the year after an index visit for newly diagnosed (incident) or poor-prognosis cancer; a secondary outcome examined total Medicare payments in the year after the index visit. Results:The study included 754 182 patient episodes (750 483 patients; mean [SD] age, 74.1 [9.0] years; 467 071 female [62.2%]) in the incident population and 517 858 patients (mean [SD] age, 72.4 [9.7] years; 270 416 female [52.2%]) in the poor prognosis cohort treated at 197 intervention and 197 comparison practices. There was no statistically significant differential change in the initiation of systemic therapy in the incident population (-0.9 percentage point difference; 95% CI, -2.2 to 0.3 percentage points; P = .14). Among patients with poor-prognosis cancers, there was a statistically significant differential decrease in the likelihood of systemic therapy initiation (1.5 percentage points, 95% CI, -2.8 to -0.2 percentage points; P = .03). Following OCM, there was a non-statistically significant relative decrease in spending (-$898.26; 95% CI, -$1890.31 to $93.80; P = .08) in the year after the index incident diagnosis and a statistically significant relative decrease (-$2192.15; 95% CI, -3559.66 to -833.63; P = .002) in the poor prognosis cohort. Conclusions and Relevance:Despite concerns about greater use of systemic therapy for patients with cancer under 1-sided risk, this study found that the OCM was not associated with an increase in the likelihood of initiating systemic therapy episodes among patients with incident cancers but was associated with less chemotherapy initiation and lower spending among patients with poor-prognosis cancers. By not examining changes in chemotherapy initiation, the OCM evaluation may have underestimated savings related to the model.

OBJECTIVE:While bevacizumab may benefit patients with recurrent, platinum-sensitive epithelial ovarian cancer (EOC), its use is inconsistent. In part, this may be due to its cost. To assess whether a lower-cost biosimilar (bevacizumab-awwb) could be cost-effective, we evaluated the cost-effectiveness of bevacizumab-awwb in combination with platinum-based chemotherapy versus chemotherapy alone in this setting. METHODS:We evaluated the incremental cost-effectiveness of 1) bevacizumab-awwb and 2) brand-name bevacizumab, when used with standard, platinum-based chemotherapy. Lifetime costs and median overall survival were compared to those with chemotherapy alone. Treatment regimens and survival estimates were based on the GOG-0213 trial. Costs were obtained from Centers for Medicare & Medicaid Services data. We assumed brand-name bevacizumab and bevacizumab-awwb, the lowest-price biosimilar, were differentiated by cost only ($74 vs $24 per 10 mg). In threshold analysis, we identified bevacizumab and biosimilar costs that would achieve cost-effectiveness at a willingness-to-pay (WTP) threshold of $150,000 per life-year gained (LYG). RESULTS:Total costs of treatment with platinum-based chemotherapy alone were $198,440; median survival was 3.11 years. Adding brand-name bevacizumab increased total costs and median survival ($362,206, 3.52 years), resulting in an ICER of $399,400/LYG. Substituting bevacizumab-awwb for brand-name bevacizumab reduced total costs and the ICER ($252,512, ICER = $131,900/LYG vs. chemotherapy alone). For bevacizumab (or a biosimilar) to be cost-effective within the above-specified WTP threshold, its price would need to be under $27/10 mg; bevacizumab-awwb is within this range. CONCLUSION:Bevacizumab has the potential to be cost-effective in treating recurrent, platinum-sensitive EOC, provided its cost is similar to current, lowest-cost biosimilars.

Based on preclinical studies showing synergism with simultaneous inhibition of the estrogen receptor (ER), CDK4/6 and PI3K pathways and based on window of opportunity studies showing that metformin suppresses PI3K/mTOR signaling in endometrial cancer (EC), we conduct a non-randomized phase 2 study of letrozole/abemaciclib/metformin in ER positive endometrioid EC (NCT03675893). Primary objectives include objective response rate (ORR) and rate of progression-free survival (PFS) at 6 months (PFS6) while secondary objectives include PFS, overall survival, duration of response and toxicity. Twenty-five patients initiate protocol therapy [letrozole 2.5 mg orally (PO) once a day (qd), abemaciclib 150 mg PO twice a day (bid) and metformin 500 mg PO qd]. ORR is 32

e13843 Background: Ovarian cancer debulking surgery is associated with improved survival but also with significant perioperative morbidity. Days at home (DAH) is a novel measure that reflects what many older adults value: being alive, returning home, and limiting facility stays, and is associated with self-rated quality of life. We evaluated the association between frailty and DAH one year after ovarian cancer surgery and determined modifiable predictors of low DAH to guide surgical decision-making in older adults with ovarian cancer. Methods: This population-based cohort study of fee-for-service Medicare beneficiaries receiving surgery for ovarian cancer between 2014-2019 examined associations between a frailty and DAH in the year after surgery. Frailty was identified using a validated claims-based frailty index (CFI) and patients were categorized as robust (CFI < 0.15), pre-frail (CFI 0.15 to < 0.25), and frail (CFI > = 0.25). DAH were calculated by subtracting hospital (inpatient, emergency department, and observation days), nursing home (long-term hospital, skilled nursing, and rehab facility days), and death days (days not alive in the year after surgery) from 365. Outcomes were stratified by frailty and age. A multivariate linear regression of DAH with patient and surgical covariates was performed. Results: Among 7,348 patients (mean [SD] age 74.1 [6.0] years), 44.0% were robust, 49.8% pre-frail, and 6.2% frail. The mean [SD] DAH for all patients was 322.6 [89.4] days; frail patients had significantly fewer DAH (269.0 [126.0]) as did pre-frail (314.5 [96.3]), compared with robust patients (330.4 [68.2]) (p < 0.001). Stratification by age and frailty indicated robust oldest (> = 80 years old) patients had more DAH than frail younger (< 70 years old) counterparts (329.6 [78.7] vs 274.5 [117.4]). Long-term mortality after 90 days contributed to loss in DAH in death days (25.7 [73.1]) rather than hospital (3.2 [7.9]) and nursing home days (1.7 [10.7]). Before 90-days, most DAH were lost to hospital (6.5 [8.0)] and nursing home (2.7 [9.2]) days rather than death (2.5 [12.4]). One year mortality rates were highest in frail patients (27.8%) and lowest in robust patients (8.8%). In adjusted models, frailty was the strongest predictor of fewer DAH (-51.8), followed by high-risk procedures (-29.9), and surgery without chemotherapy (-23.2); minimally invasive surgery was associated with an increase in DAH (+28.4 days, p < 0.001 all). Conclusions: Cancer-directed surgery in older adults is a high-stakes decision with limited data to guide surgical decision-making. In this study, frailty was the greatest predictor of fewer DAH, suggesting that frailty, above usual metrics of age and comorbidities, should be incorporated into surgical decision-making. Future studies should examine whether counseling older adults about outcomes beyond 90-days and tailoring surgical approaches to minimize surgical stress results in more personalized patient-centered surgical care.