BACKGROUND: Ovarian cancer is associated with delayed diagnosis and poor survival; thus, interest is high in identifying predictive and prognostic biomarkers and novel therapeutic agents. Although the costs of ovarian cancer care are likely to increase as newer, more effective, but more expensive treatment regimens become available, information on the current costs of care for ovarian cancer-across the care continuum from diagnosis to the end of life-are lacking. OBJECTIVE: This study aimed to estimate real-world mean and median costs of ovarian cancer care within the first 5 years after diagnosis by patients' phase of care, age, race/ethnicity, and geographic region. STUDY DESIGN: We performed a retrospective cohort study of ovarian cancer patients diagnosed between January 1, 2015 and December 31, 2020. We used claims data from Optum's deidentified Clinformatics Data Mart database, which includes inpatient, outpatient, and prescription claims for commercial insurance and Medicare beneficiaries nationwide. Cost of ovarian cancer care were calculated for the start of care (ie, the first 6 months), continuing care (ie, period between the initial and end-of-life care), and end-of-life care (ie, the last 6 months) phases and reported in 2021 U.S. dollar amounts. Ovarian cancer care costs were stratified by age, race/ethnicity, and geographic region. Due to the skewed nature of cost data, the mean cost data were log-transformed for modeling. Ordinary least-squares regression was conducted on the log costs, adjusting for patient categorical age, race/ ethnicity, and geographic region. RESULTS: A total of 7913 patients were included in the analysis. The mean cost per year for ovarian cancer care was >$200,000 during the start of care, between $26,000 and $88,000 during the continuing care phase, and >$129,000 during the end-of-life care phase. There were statistically significant associations between age and costs during each phase of care. Compared to younger patients, older patients incurred higher costs during the continuing care phase and lower costs during the end-of-life care phase. Geographic differences in the costs of ovarian cancer care were also noted regardless of the phase of care. There were no associations between cost and race/ethnicity in our cohort. CONCLUSION: Ovarian cancer care costs are substantial and vary by the phase of care, age category, and geographic region. As more effective but expensive treatment options for ovarian cancer become available with potential survival benefit, sustainable interventions to reduce the cost of care for ovarian cancer will be needed throughout the cancer care continuum.

Objectives: Current, real-world healthcare cost information is needed to project future expenditures and inform policy. We estimated the healthcare costs for adults in 2019 in the United States by age, sex, race/ethnicity, geographic region, and comorbidity. Methods: We aggregated and summarized the healthcare costs in 2021 US dollars using claims data derived from Optum's deidentified Clinformatics (R) Data Mart Database, which includes inpatient, outpatient, and prescription claims for commercial and Medicare Advantage beneficiaries nationwide. Results: A total of 9 227 901 adults were included in the analysis. The largest group represented was 71 to 75 years old (13%), female (53%), White (68%), received care in the South (41%), and had commercial health insurance (56%). There was a positive relationship between healthcare cost and age. Females had a 1.3-fold multiplicative increase in costs than males (95% CI 1.33-1.34). There were 92.5% of individuals who had health claims in the Northeast, 89.6% in the Midwest, 88.9% in the South, 77.1% in the West, and 12.7% with unknown geographic region. Patients with severe renal failure, heart failure, or metastatic cancer incurred the highest mean yearly costs ($139 844, $113 031, and $85 299, respectively). Metastatic cancer and severe renal failure were associated with a 5.3-fold multiplicative increase in costs than not having these conditions, after adjusting for potential confounders (95% CI 5.26-5.41 and 4.98-5.16, respectively). Conclusions: We identified patient characteristics and medical conditions that are associated with high healthcare cost burden and could benefit from tailored interventions. We provided detailed cost estimates to aid healthcare modeling, cost projection, and cost-minimizing interventions.

OBJECTIVE:Opportunistic salpingectomy during gynecologic surgeries is associated with a 49% to 77% reduction in ovarian cancer. The impact of the adoption of opportunistic salpingectomy during non-gynecologic abdominopelvic procedures on ovarian cancer-related outcomes is not well-established. We performed cost-effectiveness analyses to assess the impact of opportunistic salpingectomy during 6 common abdominopelvic procedures. METHODS:The cost-effectiveness of opportunistic salpingectomy during laparoscopic hysterectomy, appendectomy, cholecystectomy, gastric bypass, abdominal hernia repair, and colectomy was estimated from the United States single-payer perspective. Markov models were constructed using TreeAge Pro Healthcare software (Version 2023-R1.2) to assess the incremental costs, quality-adjusted life-years, and net monetary benefit associated with opportunistic salpingectomy for each procedure performed for a hypothetical cohort of average-risk United States patients aged 40 years based on the real-world incidence of these procedures within the Merative MarketScan Database. Model inputs were extracted from published literature. Univariate and probabilistic sensitivity analyses were performed. RESULTS:A total of 8633 procedures were identified in MarketScan in 2019 for the hypothetical cohort of 40-year-old patients. Opportunistic salpingectomy during the 6 procedures was incrementally cost-saving ($2176) with more quality-adjusted life-years gained (5.18) from a lifetime perspective, with a net monetary benefit of $520,773. Opportunistic salpingectomy at the time of the 6 procedures for the hypothetical cohort yielded $18.78 million in health care dollars saved, which was derived by multiplying the total number of procedures (8633) by the per-procedure weighted average savings ($2176). Probabilistic sensitivity analyses found that for each procedure, performing opportunistic salpingectomy had less cost and more quality-adjusted life-years gained in over 99% of the 10,000 Monte Carlo simulations. CONCLUSIONS:Widespread adoption of opportunistic salpingectomy during these common abdominopelvic procedures is robustly cost-saving. With no effective general population screening and the high cost and mortality associated with ovarian cancer, performing opportunistic salpingectomy with any of the 6 procedures may be merited.

Abstract Background The Affordable Care Act expanded Medicaid coverage for people with low income in the United States. Expanded insurance coverage could promote more timely access to cancer treatment, which could improve overall survival (OS), yet the long‐term effects of Medicaid expansion (ME) remain unknown. We evaluated whether ME was associated with improved timely treatment initiation (TTI) and 3‐year OS among patients with breast, cervical, colon, and lung cancers who were affected by the policy. Methods Medicaid‐insured or uninsured patients aged 40–64 with stage I–III breast, cervical, colon, or non‐small cell lung cancer within the National Cancer Database (NCDB). A difference‐in‐differences (DID) approach was used to compare changes in TTI (within 60 days) and 3‐year OS between patients in ME states versus nonexpansion (NE) states before (2010–2013) and after (2015–2018) ME. Adjusted DID estimates for TTI and 3‐year OS were calculated using multivariable linear regression and Cox proportional hazards regression models, respectively. Results ME was associated with a relative increase in TTI within 60 days for breast (DID = 4.6; p < 0.001), cervical (DID = 5.0 p = 0.013), and colon (DID = 4.0, p = 0.008), but not lung cancer (p = 0.505). In Cox regression analysis, ME was associated with improved 3‐year OS for breast (DID hazard ratio [HR] = 0.82, p = 0.009), cervical (DID‐HR = 0.81, p = 0.048), and lung (DID‐HR = 0.87, p = 0.003). Changes in 3‐year OS for colon cancer were not statistically different between ME and NE states (DID‐HR, 0.77; p = 0.075). Conclusions Findings suggest that expanded insurance coverage can improve treatment and survival outcomes among low income and uninsured patients with cancer. As the debate surrounding ME continues nationwide, our findings serve as valuable insights to inform the development of policies aimed at fostering accessible and affordable healthcare for all.

e24035 Background: Women with recurrent ovarian cancer (ROC) often must make end-of-life choices involving hospice care. We qualitatively explored patients’ (pt) understanding of hospice, and main decision-making factors. Methods: Pts were recruited by purposive sampling for semi-structured interviews, which were recorded, transcribed, and consensus coded. Results: 40 pts completed interviews. Median age = 63.4 yrs and time since diagnosis = 5.5 yrs. Important facilitators and barriers to hospice emerged. Key facilitators included: 1) desire to reduce care burden on family; 2) desire for a high quality death; and 3) acceptance (not afraid to die). On reducing care burden, one pt noted: “ I would think that the single most important factor would be the relief that it would give my family members. That they would not bear nearly as large a burden if hospice were to pick up part of that...” On desire for a high quality death, and acceptance: “ I’d wanna go out with as much dignity as possible...if it’s my time to go, let me go. I don’t wanna be...connected to all kinds of IVs and tubes and things just to keep my heart beating .”. Key barriers were: 1) lack of knowledge about hospice; 2) equating hospice to ‘giving up’; 3) loss of faith; and 4) letting go of perceived life-extending medical care like hydration or nutrition. Lack of knowledge was a prevalent theme: “ You only do hospice when it’s at the very end of the road. But maybe that’s not true. Maybe you do that to get some special care for a couple of months to get you through a tough...time. I guess I don’t know.” On giving up: “I would not say I'm a fan of it (hospice) at all...I would rather go out fighting....to me it's like giving up...I can't really imagine that I would actually do that.’Regarding loss of faith or letting go of perceived life-extending care: “ Well, my thoughts on how it works is I'm really not sure. They're there to keep you comfortable in your last days, but I don't know because I've heard so many horror stories with hospice...yeah they keep your pain down, but they don't give you faith. They don't give you hydration... it's like, God, pretty much starving you to death. But I don't know if that's true. I mean, that's just what I've heard.” A pivotal decision making factor that could be either a facilitator or barrier was family support for hospice, reinforcing the need for shared decision-making among the pt, family and clinical care team. One pt stated: “ It's an emotional toll, financial toll, it’s a physical toll on the family...and I would just want to talk to my family about all aspects of it, and then they would go from there, what they would want to do, or what I would want to.” Conclusions: Understanding perceived barriers and facilitators to hospice care through elicitation of pt beliefs and values and focusing efforts on educating pts and their support systems about the role of hospice can empower women with ROC to make informed pt-centered decisions about their end-of-life care.

This review aims to synthesize available literature on uterine-conserving treatment options for atypical endometrial hyperplasia and grade 1 endometrial carcinoma while highlighting remaining unanswered questions. The need for uterine-conserving treatment options for atypical endometrial hyperplasia and grade 1 endometrial carcinoma is growing with the increasing number of cases in younger patients or those who cannot undergo surgery. We reviewed the oncological and reproductive outcomes associated with endocrine therapies used for atypical endometrial hyperplasia and grade 1 endometrial carcinoma. The rising prevalence of delayed childbearing, obesity, and diabetes in reproductive-age individuals and of medical comorbidities associated with high surgical risk continues to amplify the demand for uterine-conserving therapies. Appropriate patient selection for such therapies is imperative to maximize likelihood of treatment response. The ideal candidates are patients with atypical endometrial hyperplasia or early-stage, low-grade endometrial cancer with no evidence of myometrial invasion or extrauterine disease. The most accepted conservative therapeutic approach is hormonal therapy with close surveillance, with or without eventual hysterectomy following childbearing or failure of treatment. Further prospective and randomized trials are needed to address optimal patient and treatment selection, as well as the use of molecular profiling for treatment individualization and prognostication.

OBJECTIVE:We assessed real-world trends in the use of maintenance therapy [MT] (i.e., polyADP-ribose polymerase inhibitors (PARPi) and/or bevacizumab following platinum-based chemotherapy), among U.S. patients with ovarian cancer. METHODS:Using Medicare and commercial administrative health claims data from Optum's de-identified Clinformatics® Data Mart Database, we identified patients who had been diagnosed with ovarian cancer between January 1, 2010, and March 31, 2021, and received platinum-based chemotherapy and MT. Multivariable logistic regression and Cox proportional hazards regression were used to evaluate associations between demographic and clinical characteristics and MT use. RESULTS:Our study included 6339 patients, with a median age of 70 years. The majority were White (70.1 %), Medicare-insured (71.9 %), and were treated in the South (42.5 %). Of the 31.5 % who received MT, 18.1 % received bevacizumab alone, 10.2 % PARPi alone, and 3.3 % both. After adjusting for insurance type, PARPi and bevacizumab use increased significantly from 2017 to 2020. Patients with a high Elixhauser comorbidity index were more likely to receive MT than were patients with a low index [OR (95 % CI): 1.46 (1.28-1.67), p < 0.0001]. PARPi use was significantly associated with treatment in the South [1.42 (1.10-1.83), p = 0.01]. Compared to patients who received neither agents, those who received bevacizumab, alone or in combination with PARPi, had a higher risk of death [HR = 2.02 (95 % CI: 1.70-2.28, p < 0.0001) and 1.66 (1.24-2.23), p = 0.001, respectively]. CONCLUSIONS:The majority of patients with ovarian cancer are not utilizing maintenance therapy after platinum-based chemotherapy. Age, comorbidity status, and geographic region of treatment were associated with MT use. Understanding the factors and real-world outcomes associated with MT use is important to support patients in making value concordant and informed decisions.

Abstract Background: A growing proportion of women diagnosed with atypical hyperplasia (AH) and early-stage endometrioid endometrial cancer (EEC) require nonsurgical treatment options. Our previously published phase II clinical trial of the levonorgestrel intrauterine device (LIUD) for AH and grade 1 EEC (G1EEC) demonstrated 83% response rate at 1 year; however, prospective long-term follow-up data and determinants for duration of response to LIUD are limited. Methods: Follow-up data from patients that participated in our prospective phase II trial of LIUD as a nonsurgical approach for AH and G1EEC were collected from medical records. Duration of response and time to relapse were evaluated. Spatial transcriptomic profiling from longitudinal biopsy samples from pre-treatment (n=5), on-treatment (n=5), and disease relapse lesions (n=3) were evaluated using digital spatial profiling (DSP, Nanostring GeoMX Whole Transcriptome Atlas). In silico cell type deconvolution was performed and pathway analyses was conducted using gene set variation analysis enrichment. Results: Of 43 participants exhibiting initial response to LIUD, 41 had follow-up data. Sixteen experienced disease relapse (39%) with a median time to relapse of 17 months after initial response. Clinical factors associated with shorter duration of response included age (HR 0.95, p=0.021), initial diagnosis of G1EEC (HR 3.51, p=0.014), premenopausal status (HR 3.85, p=0.039), and Hispanic ethnicity (HR 3.45, p=0.017). Pre-treatment IGF1 and IGF2 expression levels were positive predictors of duration of response (HR 0.44 and 0.45, respectively, p<0.05). DSP results revealed that LIUD increased NK cells (log2FC=46.13, FDR=0.004), and lymphocyte cytotoxicity signaling markers GZMB (log2FC=1.06, padj=0.023) and PRF1 (log2FC=1.62, padj=0.004), but NK cells were reduced in relapse lesions (log2FC=-55.96, FDR=0.02) as was PRF1 expression (log2FC=-1.87, padj=0.038). Multiple immune-related pathways (IFNα and IFNγ response, TGFβ signaling) were significantly upregulated in relapse lesions compared to matched pre-treatment lesions (FDR<0.05). IDO1 expression, a marker for immune exhaustion, was upregulated in relapse lesions compared to matched pre-treatment and on-treatment lesions (log2FC=2.56, FDR=0.01). Conclusions: While LIUD for treatment of AH or G1EEC has excellent initial response rates, upfront resistance, and relapse after initial response to LIUD impacts nearly half of patients. Our study shows progestin-related immunomodulatory effects, including increased NK cell infiltration and lymphocyte cytotoxicity. Immune mechanisms for relapse are implicated here, including reversal of progestin-related immunomodulatory effects (decreased NK cell infiltration and lymphocyte cytotoxicity) and increased immune exhaustion (prolonged IFNα and IFNγ response and increased IDO1 expression in relapse lesions). Thus, relieving immune exhaustion may increase durability of response to LIUD for treatment of AH or G1EEC. Citation Format: Mikayla B. Bowen, Brenda Melendez, Qian Zhang, Richard Yang, Bryan Fellman, Barrett Lawson, Naomi Adjei, Joseph Celestino, Tri Nguyen, Khalida Wani, Bhavana Singh, Christof Straub, Liang Zhang, Cheryl Tan, Felicia New, Diana Urbauer, Alexander Lazar, Karen Lu, Jennifer Wargo, Shannon N. Westin, Melinda S. Yates. Immune exhaustion and reversal of progestin-related immune modulation in adaptive resistance to levonorgestrel intrauterine device for treatment of atypical hyperplasia and early endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B024.

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.

Supplementary Table S4. Gene set variation analyses of DSP data with FDR<0.05.

Supplementary Figure S1. Digital spatial profiling quality control.

Supplementary Table S1. Representativeness of Study Participants.

AbstractPurpose: Nonsurgical treatment options are increasingly needed for endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC). Despite promising initial response rates, prospective long-term data and determinants for relapse are limited. Materials and Methods: Follow-up data from patients in our prospective phase II trial of levonorgestrel intrauterine device (LIUD) for AH/G1EEC were collected from medical records. Spatial transcriptomics (Nanostring GeoMX digital spatial profiling) with in silico cell type deconvolution and pathway analyses were employed on longitudinal biopsy samples from five patients across pre-treatment, on-treatment, and relapse. Results: Of 43 participants exhibiting initial response to LIUD, 41 had follow-up data. Sixteen (39%) experienced relapse. Clinical factors associated with shorter response duration included younger age, initial diagnosis of G1EEC, lack of response at 6 months, premenopausal status, and Hispanic ethnicity (P < 0.05), but only 6-month response status remained a significant predictor in a multivariate model (P = 0.023). LIUD increased abundance of NK cells (ΔMCP-counter score = 46.13, FDR = 0.004) and cytotoxic lymphocytes (ΔMCP-counter score = 277.67, FDR = 0.004), as well as lymphocyte cytotoxicity markers PRF1 (log2FC = 1.62, FDR = 0.025) and GZMA (log2FC = 2.47, FDR = 0.008). NK cells were reduced at relapse (ΔMCP-counter score = −55.96, FDR = 0.02). Immune-related pathways (IFNα response and TGFβ signaling) were enriched at relapse (FDR < 0.05). IDO1 expression, reflecting immune exhaustion, was upregulated at relapse (FDR < 0.05). Conclusions: Upfront resistance and relapse after initial response to LIUD for AH/G1EEC impacts nearly half of patients, remaining a major hurdle for nonsurgical treatment of AH/G1EEC. Molecular studies evaluating longitudinal biopsies from a small cohort implicate immune mechanisms at relapse, including reversal of progestin-related immunomodulation and increased immune exhaustion. See related commentary by Johannet and Friedman, p. 5001

Supplementary Table S2. Digital spatial profiling metadata.

Supplementary Table S3. Digital spatial profiling log2-normalized gene expression data.

Introduction Ongoing effects of cancer-related financial distress (CRFD) are not well described. We explored the correlation between CRFD and patient-reported outcomes (PROs) in a longitudinal study of individuals with recurrent ovarian cancer (ROC). Methods Participants with ROC completed validated PRO instruments at enrollment and every 3 months thereafter for ≤4 years. Instruments included FACIT-COST (financial distress among people with cancer), MDASI-O (symptom burden), FACT-O (quality of life), CESD-20 (depression), GAD-7 (anxiety), EQ-5D-5L (well-being), and Mini-IPIP (personality). Correlation between FACIT-COST and other PRO was assessed using Spearman correlation (rho). Results Table 1 highlights demographics (N=268; 1974 observations). Table 2 shows correlation between FACIT-COST and other PROs. There were weak positive correlations between the FACIT-COST and the FACT-O subscales and EQ-5D-5L VAS (0.17 $75K had a stronger positive correlation than those with ≤ $75K for social well-being (rho=0.33 and 0.20, <0.001). Lower financial distress was associated with lower anxiety and depression, lower symptom burden, and better overall well-being (p<.01 for all). Conclusion/Implications Patients with lower CRFD were more likely to report lower levels of anxiety, depression, and symptom burden, and higher levels of physical, social, emotional, and functional well-being. Efforts to ameliorate financial toxicity may yield a high return on investment with more sweeping implications on mental, emotional and physical wellbeing.

Cancer-related financial distress (CRFD) is detrimental to patients' quality of life (QOL) and may negatively impact survival. CRFD further impacts patients' social networks and broader society. This qualitative study investigated the financial and social impact of ovarian cancer (OC) care and strategies implemented by patients and their support networks.

e18658 Background: Understanding patient (pt) perspectives on clinical trials is paramount for trial accrual. We qualitatively explored factors pts felt were important when deciding to enroll in clinical trials. Methods: Pts with recurrent ovarian cancer took part in semi-structured interviews which were audio-recorded, transcribed, and consensus coded. Results: 40 pts were interviewed. Median age = 62.4 yrs (41.2, 79.0), 82.5% (33/40) were white, 60% (24/40) were college educated. Median time from diagnosis = 5.5 yrs (0.80, 17.8); 42.5% (17/40) had prior enrollment in a clinical trial. Most pts cited hope for clinical benefit and desire to help others as key motivators for trial participation. Quality of life (QoL) was also an integral factor. Many expressed a willingness to sacrifice QoL for clinical benefit: “I don’t want to, you know, spend the last months suffering…but, if they say ‘Well, we can try this….Maybe you’ll get 6 more months out of it’, which we know that’s hope for 6 more months. So then the suffering might be worth it.” Others would refuse enrollment due to fear of compromised QoL, or poor outcome: “ If I was healthy at the time, I would have difficulty going into a clinical trial. Because my thought would be…“I’m healthy. I feel good. You wanna place me on a clinical trial, and what if it goes bad? What if it doesn’t work?” Another asserted: “I would not participate in a clinical trial if it was going to make me feel worse before it supposedly made me feel better.” A motivator and potential barrier was trust in providers. “I would like to know… this is their…business or work, they're serious about doin' it…and they kind of professional people, someone…that believe in doin' a good job on somethin', not just get up and do it because maybe they gonna get this amount of money for it, but somethin'…at heart that they really believe in…I'll have to know somethin' about the person or the persons that's in charge of that clinical trial.” Another noted: “I would have gone with whatever [my doctor] recommended…at the end of the day, it’s trust. If I didn’t trust my doctor, I’m not so sure I would just jump into this…” Pts cited trial logistics as potential barriers to participation: “Was it something that I would be able to incorporate into my life, both travel-wise and…taking the drug? Was it going to really be a demanding schedule in terms of meals, in terms of sleep…? Those are all things I looked at. ’ Access and affordability were other barriers cited by pts. Conclusions: Pts weigh many factors when considering clinical trials. QoL information is highly desired. Inclusion of patient-reported outcomes in developmental therapeutic trials may inform QoL for future pts. While motivators for participation were apparent, efforts to overcome potential barriers to enrollment by building trust with providers, and increasing education, navigation and decentralized trials may help diversify and improve representation in trial accrual.