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.

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.

Transfusion use and effect on progression-free, overall survival, and quality of life in upfront treatment of advanced epithelial ovarian cancer: evaluation of the European Organization for Research and Treatment EORTC-55971 Cohort.

BACKGROUND: The impact of blood transfusion on ovarian cancer survival is uncertain. OBJECTIVE: To investigate whether peri-operative blood transfusion negatively impacted progression-free survival, overall survival, and quality of life in patients with advanced ovarian cancer. METHODS: We performed an ancillary analysis of the European Organization for Research and Treatment (EORTC) 55971 phase III trial, in which patients were randomized to primary debulking surgery versus neoadjuvant chemotherapy. Patients included in the per-protocol analysis were categorized by receipt of a transfusion. RESULTS: 612 of 632 (97%) of patients had adequate data for analysis. Of those, 323 (53%) received a transfusion. The transfusion cohort was more likely to have had better Word Health Organization (WHO) performance status, serous histology, undergone primary debulking surgery, and received more aggressive surgery, with higher rates of no gross residual disease. Median overall survival was 34.0 vs 35.2 months in the no transfusion and transfusion cohorts (p=0.97). The adjusted HR for death was 1.18 (95% CI 0.94 to 1.48) in favor of the transfusion cohort. Median progression-free survival was 13.6 vs 12.6 months in the no transfusion and transfusion cohorts (p=0.96). The adjusted HR for progression was 1.14 (95% CI 0.91 to 1.43). There were no significant differences in global quality of life, fatigue, dyspnea, or physical functioning between the two cohorts at baseline or at any of the four assessment times. Grade 3 and 4 surgical site infections were more common in the transfusion cohort. CONCLUSION: Transfusion did not negatively impact progression-free survival or overall survival; however, it was associated with increased peri-operative morbidity without improvements in quality of life.

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.

Association between time to diagnosis, time to treatment, and ovarian cancer survival in the United States.

OBJECTIVE: Evaluate the association between time to diagnosis and treatment of advanced ovarian cancer with overall and ovarian cancer specific mortality using a retrospective cross sectional study of a population based cancer registry database. METHODS: The Surveillance, Epidemiology, and End Results-Medicare database was searched from 1992 to 2015 for women aged ≥66 years with epithelial ovarian cancer and abdominal/pelvic pain, bloating, difficulty eating, or urinary symptoms within 1 year of cancer diagnosis. Time from presentation to diagnosis and treatment were evaluated as outcomes and covariables. Cox regression models and adjusted Kaplan-Meier curves evaluated 5 year overall and cancer-specific survival. RESULTS: Among 13 872 women, better survival was associated with longer time from presentation to diagnosis (overall survival hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.94 to 0.95; cancer specific survival HR 0.95, 95% CI 0.94 to 0.96) and diagnosis to treatment (overall survival HR 0.94, 95% CI 0.92 to 0.96; cancer specific survival HR 0.93, 95% CI 0.91 to 0.96). There was longer time from presentation to diagnosis in Hispanic women (relative risk (RR) 1.21, 95% CI 1.12 to 1.32) and from diagnosis to treatment in non-Hispanic black women (RR 1.36, 95% CI 1.21 to 1.54), with lower likelihood of survival at 5 years after adjustment for time to diagnosis and treatment among non-Hispanic black women (HR 1.15, 95% CI 1.05 to 1.26) compared with non-Hispanic white women. Gynecologic oncology visit was associated with improved overall (p<0.001) and cancer specific (p<0.001) survival despite a longer time from presentation to treatment (p<0.001). CONCLUSION: Longer time to diagnosis and treatment were associated with improved survival, suggesting that tumor specific features are more important prognostic factors than the time interval of workup and treatment. Significant sociodemographic disparities indicate social determinants of health influencing workup and care. Gynecologic oncologist visits were associated with improved survival, highlighting the importance of appropriate referral for suspected ovarian cancer.

Contemporary primary treatment of women with stage II-IV low-grade serous ovarian/peritoneal cancer (LGSOC): Determinants of relapse and disease-free survival.

OBJECTIVE: The purpose of the present study is to describe a cohort who received contemporary primary treatment for stage II-IV low-grade serous ovarian/peritoneal cancer (LGSOC), including patient characteristics and determinants of relapse and disease-free survival. METHODS: The study included 99 patients: 1) with pathologically confirmed stage II-IV LGSOC of the ovary or peritoneum, 2) who underwent primary treatment consisting of cytoreductive surgery and either a) platinum/taxane chemotherapy followed by aromatase inhibitor maintenance therapy or b) aromatase inhibitor monotherapy, and 3) for whom there was availability of clinical data. Descriptive statistics were used to characterize clinicodemographic features. Subgroups were compared for PFS and OS. Multivariable Cox regression analyses were performed. RESULTS: Median PFS for the entire cohort was 56.8 months (95% CI, 41.3-NE), and median OS was 130.7 months (95% CI, 115.0-146.4). Forty-nine of 99 (49.5%) patients have relapsed to date. For these 49 patients, median time from diagnosis to relapse was 29.6 months (95% CI, 24.6-33.1) (range, 5.4-69.1 months). Only 1/49 (2%) patients who relapsed did so >5 years from diagnosis. Fifty (50.0%) patients have not experienced disease progression or relapse. Median follow-up time for these 50 patients is 86.2 months (range, 25.3-169.0). Thirty-three of the 50 (66.0%) have been followed for >5 years from diagnosis. On regression analyses, factors associated with improved patient outcomes-either PFS, OS, or both-included no gross residual disease, normal serum CA 125 at diagnosis, primary peritoneal site, and presence of extensive psammomatous calcifications. CONCLUSIONS: This is the first report to describe the clinicopathologic features and outcomes of women with stage II-IV LGSOC who received contemporary primary therapy.

Impacts of Medicaid Expansion on Stage at Cancer Diagnosis by Patient Insurance Type.

INTRODUCTION: The expansion of Medicaid under the Affordable Care Act increased access to health care for millions of low-income Americans. However, the longer-term impacts of the policy on cancer outcomes remain unknown. This study examined the impact of Medicaid expansion on early- and late-stage diagnosis for 4 common cancers (breast, cervical, colorectal, and lung) using 4 full years of postpolicy data. METHODS: Patients aged 40-64 years diagnosed with breast, cervical, colorectal, or lung cancer from 2010 to 2017 were identified using the National Cancer Database. Difference-in-difference analyses compared changes in early-stage and late-stage diagnoses among expansion states with those among nonexpansion states. Subgroup analyses explored potential effect modification by insurance type. Data analysis was performed from June to October 2021. RESULTS: The proportion of early stage diagnosis of breast (difference in difference=1.58, 95% CI=0.89, 2.27), cervical (difference in difference=3.20; 95% CI=0.44, 5.95), colorectal (difference in difference=1.98; 95% CI=1.18, 2.78), and lung (difference in difference=1.74; 95% CI=0.98, 2.50) cancers increased more in expansion states than in nonexpansion states, whereas late-stage diagnosis of colorectal (difference in difference= -2.12; 95% CI= -2.98, -1.27) and lung (difference in difference= -1.87; 95% CI= -2.89, -0.84) cancers decreased more in expansion states following implementation of the Affordable Care Act. In subgroup analyses, difference-in-difference estimates for all sites and stages (except late-stage cervical cancer) were significant and larger in magnitude among Medicaid-insured than among privately insured patients. CONCLUSIONS: Study results highlight the positive impacts of Medicaid expansion on earlier diagnosis of several cancers for which screening and early detection exist, and subgroup analyses revealed greater positive effects among Medicaid-insured patients most targeted by the policy.

Medicaid expansion and 2-year survival in women with gynecologic cancer: a difference-in-difference analysis.

BACKGROUND: The Affordable Care Act implemented optional Medicaid expansion starting in 2014, but the association between Medicaid expansion and gynecologic cancer survival is unknown. OBJECTIVE: To evaluate the impact of Medicaid expansion by comparing 2-year survival among gynecologic cancers before and after 2014 in states that did and did not expand Medicaid using a difference-in-difference analysis. STUDY DESIGN: We searched the National Cancer Database for women aged 40 to 64 years, diagnosed with a primary gynecologic malignancy (endometrial, ovarian, cervical, vulvar, and vaginal) between 2010 and 2016. We used a quasiexperimental difference-in-difference multivariable Cox regression analysis to compare 2-year survival between states that expanded Medicaid in January 2014 and states that did not expand Medicaid as of 2016. We performed univariable subgroup difference-in-difference Cox regression analyses on the basis of stage, income, race, ethnicity, and geographic location. Adjusted linear difference-in-difference regressions evaluated the proportion of uninsured patients on the basis of expansion status after 2014. We evaluated adjusted Kaplan-Meier curves to examine differences on the basis of study period and expansion status. RESULTS: Our sample included 169,731 women, including 78,669 (46.3%) in expansion states and 91,062 (53.7%) in nonexpansion states. There was improved 2-year survival on adjusted difference-in-difference Cox regressions for women with ovarian cancer in expansion than in nonexpansion states after 2014 (hazard ratio, 0.88; 95% confidence interval, 0.82-0.94; P<.001) with no differences in endometrial, cervical, vaginal, vulvar, or combined gynecologic cancer sites on the basis of expansion status. On univariable subgroup difference-in-difference Cox analyses, women with ovarian cancer with stage III-IV disease (P=.008), non-Hispanic ethnicity (P=.042), those in the South (P=.016), and women with vulvar cancer in the Northeast (P=.022), had improved 2-year survival in expansion than in nonexpansion states after 2014. In contrast, women with cervical cancer in the South (P=.018) had worse 2-year survival in expansion than in nonexpansion states after 2014. All cancer sites had lower proportions of uninsured patients in expansion than in nonexpansion states after 2014. CONCLUSION: There was a significant association between Medicaid expansion and improved 2-year survival for women with ovarian cancer in states that expanded Medicaid after 2014. Despite improved insurance coverage, racial, ethnic, and regional survival differences exist between expansion and nonexpansion states.

The genomic landscape of low-grade serous ovarian/peritoneal carcinoma and its impact on clinical outcomes.

OBJECTIVE: Low-grade serous carcinoma (LGSOC) is a rare epithelial ovarian/peritoneal cancer characterized by younger age at diagnosis, relative chemoresistance, prolonged overall survival (OS), and mutations in the mitogen activated protein kinase (MAPK) pathway compared to high-grade serous carcinoma. We describe the genomic profile of LGSOC by next generation sequencing (NGS) and evaluated its potential relationship to clinical outcomes. METHODS: The study included 215 women with LGSOC with: 1) pathologically confirmed LGSOC, 2) availability of NGS data, and 3) adequate clinical data. Clinical subgroups were compared for progression-free survival (PFS) and OS. Multivariable Cox regression analysis was performed. RESULTS: Median age at diagnosis was 46.6 years. The majority had a stage III ovarian primary. One or more mutations were identified in 140 (65.1%) cases; 75 (34.9%) had none. The most common mutations were KRAS (n = 71; 33.0%), NRAS (n = 24; 11.2%), and BRAF (n = 18; 8.4%). Patients with MAPK-mutated tumors (n = 113) (52.6%) had a significantly longer OS compared to those with tumors lacking MAPK pathway mutations (n = 102) (47.4%) [median OS, 147.8 months (95% CI,119.0-176.6) versus 89.5 months (95% CI, 61.4-117.7) (p = 0.01)], respectively. Median OS for patients with MAPK-mutated tumors was also significantly better than for patients whose tumors had no mutations (n = 75) [median OS, 147.8 months (95% CI, 119.0-176.6) versus 78.0 months (95% CI, 57.6-98.3)], respectively (p = 0.001). Median OS for patients with non-MAPK-mutated tumors (n = 27) was 125.1 months (95% CI, 83.9-166.3). In multivariable analysis, having a MAPK mutation was associated with improved OS. CONCLUSIONS: Patients with MAPK-mutated tumors have a significantly improved OS compared to those without MAPK-mutated tumors.

Temporal trends of healthcare system use between symptomatic presentation and ovarian cancer diagnosis in the United States.

OBJECTIVE: To describe trends in healthcare system use over time between onset of classic ovarian cancer symptoms and ovarian cancer diagnosis in the United States. METHODS: A population-based study of the Surveillance, Epidemiology, and End Results-Medicare database was conducted on patients aged ≥66 years with stage II-IV epithelial ovarian cancer between 1992 and 2015 with at least one of the following diagnosis codes: abdominal pain, bloating, difficulty eating, and/or urinary symptoms. The outcomes were frequency of visit type, frequency of diagnostic modality, and Medicare reimbursement between first symptomatic claim and cancer diagnosis. Jonckheere-Terpstra and Cochran-Armitage tests were used to evaluate trends over time. RESULTS: Among 13 872 women, 13 541 (97.6%) had outpatient, 6466 (46.6%) had inpatient, and 4906 (35.4%) had emergency room visits. The frequency of outpatient (p<0.001) and emergency room visits (p<0.001) increased while the frequency of inpatient visits (p<0.001) decreased between 1992 and 2015. The median number of outpatient visits (p<0.001) and physician specialties seen (p<0.001) increased over time. The median hospital length of stay decreased from 10 days in 1992 to 5 days in 2015 (p<0.001). Between 1992 and 2015, the frequency of ultrasound decreased (p<0.001) while the frequency of computed tomography, magnetic resonance imaging, positron emission tomography imaging, and cancer antigen 125 tumor immunoassay increased (p<0.001). Median monthly total (p<0.001), inpatient (p<0.001), and outpatient (p=0.006) reimbursements decreased while emergency room reimbursements increased (p<0.001) over time. CONCLUSION: Healthcare reimbursement between symptomatic presentation and ovarian cancer diagnosis has decreased over time and may reflect the trends in fewer and shorter hospitalizations and increased use of emergency and outpatient management during the evaluation of symptoms of women with ovarian cancer.

Algorithm to Identify Incident Epithelial Ovarian Cancer Cases Using Claims Data.

PURPOSE: To create an algorithm to identify incident epithelial ovarian cancer cases in claims-based data sets and evaluate performance of the algorithm using SEER-Medicare claims data. METHODS: We created a five-step algorithm on the basis of clinical expertise to identify incident epithelial ovarian cancer cases using claims data for (1) ovarian cancer diagnosis, (2) receipt of platinum-based chemotherapy, (3) no claim for platinum-based chemotherapy but claim for tumor debulking surgery, (4) removed cases with nonplatinum chemotherapy, and (5) removed patients with prior claims with personal history of ovarian cancer code to exclude prevalent cases. We evaluated algorithm performance using SEER-Medicare claims data by creating four cohorts: incident epithelial ovarian cancer, a 5% random sample of cancer-free Medicare beneficiaries, a 5% random sample of incident nonovarian cancer, and prevalent ovarian cancer cases. RESULTS: Using SEER tumor registry data as the gold standard, our algorithm correctly classified 89.9% of incident epithelial ovarian cancer cases (cohort n = 572) and almost 100% of cancer-free controls (n = 97,127), nonovarian cancer (n = 714), and prevalent ovarian cancer cases (n = 3,712). The overall algorithm sensitivity was 89.9%, the positive predictive value was 93.8%, and the specificity and negative predictive value were > 99.9%. Patients were more likely to be correctly classified as incident ovarian cancer if they had stage III or IV disease compared with early stage I or II disease (93.5% v 83.7%, P < .01), and grade 1-4 compared with unknown grade tumors (93.8% v 81.4%, P < .01). CONCLUSION: Our algorithm correctly identified most incident epithelial ovarian cancer cases, especially those with advanced disease. This algorithm will facilitate research in other claims-based data sets where cancer registry data are unavailable.

Phase Ib Dose Expansion and Translational Analyses of Olaparib in Combination with Capivasertib in Recurrent Endometrial, Triple-Negative Breast, and Ovarian Cancer.

PURPOSE: On the basis of strong preclinical rationale, we sought to confirm recommended phase II dose (RP2D) for olaparib, a PARP inhibitor, combined with the AKT inhibitor capivasertib and assess molecular markers of response and resistance. PATIENTS AND METHODS: We performed a safety lead-in followed by expansion in endometrial, triple-negative breast, ovarian, fallopian tube, or peritoneal cancer. Olaparib 300 mg orally twice daily and capivasertib orally twice daily on a 4-day on 3-day off schedule was evaluated. Two dose levels (DL) of capivasertib were planned: 400 mg (DL1) and 320 mg (DL-1). Patients underwent biopsies at baseline and 28 days. RESULTS: A total of 38 patients were enrolled. Seven (18%) had germline BRCA1/2 mutations. The first 2 patients on DL1 experienced dose-limiting toxicities (DLT) of diarrhea and vomiting. No DLTs were observed on DL-1 (n = 6); therefore, DL1 was reexplored (n = 6) with no DLTs, confirming DL1 as RP2D. Most common treatment-related grade 3/4 adverse events were anemia (23.7%) and leukopenia (10.5%). Of 32 evaluable subjects, 6 (19%) had partial response (PR); PR rate was 44.4% in endometrial cancer. Seven (22%) additional patients had stable disease greater than 4 months. Tumor analysis demonstrated strong correlations between response and immune activity, cell-cycle alterations, and DNA damage response. Therapy resistance was associated with receptor tyrosine kinase and RAS-MAPK pathway activity, metabolism, and epigenetics. CONCLUSIONS: The combination of olaparib and capivasertib is associated to no serious adverse events and demonstrates durable activity in ovarian, endometrial, and breast cancers, with promising responses in endometrial cancer. Importantly, tumor samples acquired pre- and on-therapy can help predict patient benefit.

Factors impacting the time to ovarian cancer diagnosis based on classic symptom presentation in the United States.

BACKGROUND: Patients with ovarian cancer often present with late-stage disease and nonspecific symptoms, but little is known about factors affecting the time to diagnosis (TTD) in the United States. METHODS: A retrospective, population-based study of the Surveillance, Epidemiology, and End Results-Medicare database was conducted. It included women 66 years old or older with stage II to IV epithelial ovarian cancer with at least 1 code for abdominal/pelvic pain, bloating, difficulty eating, or urinary symptoms within 1 year of the cancer diagnosis. TTD was defined from the first claim with a prespecified symptom to the ovarian cancer diagnosis. Kruskal-Wallis tests were used to assess for differences in TTD by group medians. Univariate and generalized linear models with a log-link function evaluated TTD by covariables. RESULTS: For the 13,872 women analyzed, the mean and median times to diagnosis were 2.9 and 1.1 months, respectively. The median TTD differed significantly by first symptom (P < .001), number of symptoms (P < .001), and first physician specialty seen (P < .001). In a multivariable analysis, TTD differed significantly according to race/ethnicity (P < .001), geographic region (P = .001), urban-rural location (P = .031), emergency room presentation (P < .001), and number of specialties seen (P < .001). A shorter TTD was associated with a diagnosis in 2006-2010 (relative risk [RR], 0.92; 95% confidence interval [CI], 0.87-0.98) or 2011-2015 (RR, 0.87; 95% CI, 0.81-0.93) in comparison with 1992-1999. CONCLUSIONS: The time from a symptomatic presentation to care to a diagnosis of ovarian cancer is influenced by clinical and demographic variables. This study's findings reinforce the importance of educating all physicians on ovarian cancer symptoms to aid in diagnosis. LAY SUMMARY: Ovarian cancer is often diagnosed once disease has spread because the classic symptoms of ovarian cancer-abdominal or pelvic pain, bloating, difficulty eating, and urinary issues-can be mistaken for other problems. This study examined the time between when women with classic ovarian cancer symptoms went to a physician and when they received a cancer diagnosis in a large database population. The authors found that the time to diagnosis differed according to the type and number of symptoms and what type of physician a woman saw as well as factors such as race, geographic location, and year of diagnosis.

Cost-effectiveness of laparoscopic disease assessment in patients with newly diagnosed advanced ovarian cancer.

OBJECTIVE: To determine if laparoscopy is a cost-effective way to assess disease resectability in patients with newly diagnosed advanced ovarian cancer. METHODS: A cost-effectiveness analysis from a health care payer perspective was performed comparing two strategies: (1) a standard evaluation strategy, where a conventional approach to treatment planning was used to assign patients to either primary cytoreduction (PCS) or neoadjuvant chemotherapy with interval cytoreduction (NACT), and (2) a laparoscopy strategy, where patients considered candidates for PCS would undergo laparoscopy to triage between PCS or NACT based on the laparoscopy-predicted likelihood of complete gross resection. A microsimulation model was developed that included diagnostic work-up, surgical and adjuvant treatment, perioperative complications, and progression-free survival (PFS). Model parameters were derived from the literature and our published data. Effectiveness was defined in quality-adjusted PFS years. Results were tested with deterministic and probabilistic sensitivity analysis (PSA). The willingness-to-pay (WTP) threshold was set at $50,000 per year of quality-adjusted PFS. RESULTS: The laparoscopy strategy led to additional costs (average additional cost $7034) but was also more effective (average 4.1 months of additional quality-adjusted PFS). The incremental cost-effectiveness ratio (ICER) of laparoscopy was $20,376 per additional year of quality-adjusted PFS. The laparoscopy strategy remained cost-effective even as the cost added by laparoscopy increased. The benefit of laparoscopy was influenced by mitigation of serious complications and their associated costs. The laparoscopy strategy was cost-effective across a range of WTP thresholds. CONCLUSIONS: Performing laparoscopy is a cost-effective way to improve primary treatment planning for patients with untreated advanced ovarian cancer.

Patient cost sharing during poly(adenosine diphosphate-ribose) polymerase inhibitor treatment in ovarian cancer.

BACKGROUND: More patients with ovarian cancer are being treated with poly(adenosine diphosphate-ribose) polymerase inhibitors because regulatory agencies have granted these drugs new approvals for a variety of treatment indications. However, poly(adenosine diphosphate-ribose) polymerase inhibitors are expensive. When administered as a maintenance therapy, these drugs may be administered for months or years. How much of this cost patients experience as out-of-pocket spending is unknown. OBJECTIVE: This study aimed to estimate the out-of-pocket spending that patients experience during poly(adenosine diphosphate-ribose) polymerase inhibitor treatment and to characterize which healthcare services account for that spending. STUDY DESIGN: A retrospective cohort study was performed with a sample of patients with ovarian cancer treated between 2014 and 2017 with olaparib, niraparib, or rucaparib. Patients were identified using MarketScan, a health insurance claims database. All insurance claims during poly(adenosine diphosphate-ribose) polymerase inhibitor treatment were collected. The primary outcome variable was the patients' out-of-pocket spending (copayment, coinsurance, and deductibles) during poly(adenosine diphosphate-ribose) polymerase inhibitor treatment for the medication itself. Other outcomes of interest included out-of-pocket spending for other healthcare services, the types and frequency of other healthcare services used, health plan spending, the estimated proportion of patients' household income used each month for healthcare, and patients' out-of-pocket spending immediately before poly(adenosine diphosphate-ribose) polymerase inhibitor treatment. RESULTS: We identified 503 patients with ovarian cancer with a median age of 55 years (interquartile range, 50-62 years); 83% of those had out-of-pocket spendings during poly(adenosine diphosphate-ribose) polymerase inhibitor treatment. The median treatment duration was 124 days (interquartile range, 66-240 days). The mean out-of-pocket spending for poly(adenosine diphosphate-ribose) polymerase inhibitors was $305 (standard deviation, $2275) per month. On average, this accounted for 44.8% (standard deviation, 34.8%) of the patients' overall monthly out-of-pocket spending. The mean out-of-pocket spending for other healthcare services was $165 (standard deviation, $769) per month. Health plans spent, on average, $12,661 (standard deviation, $15,668) per month for poly(adenosine diphosphate-ribose) polymerase inhibitors and $7108 (standard deviation, $15,254) per month for all other healthcare services. The cost sharing for office visits, laboratory tests, and imaging studies represented the majority of non-poly(adenosine diphosphate-ribose) polymerase inhibitor treatment out-of-pocket spending. The average amount patients paid for all healthcare services per month during poly(adenosine diphosphate-ribose) polymerase inhibitor treatment was $470 (standard deviation, $2407), which was estimated to be 8.7% of the patients' monthly household income. The mean out-of-pocket spending in the 12 months before poly(adenosine diphosphate-ribose) polymerase inhibitor treatment was $3110 (standard deviation, $6987). CONCLUSION: Patients can face high out-of-pocket costs for poly(adenosine diphosphate-ribose) polymerase inhibitors, although the sum of cost sharing for other healthcare services used during poly(adenosine diphosphate-ribose) polymerase inhibitor treatment is often higher. The spending on healthcare costs consumes a large proportion of these patients' household income. Patients with ovarian cancer experience high out-of-pocket costs for healthcare, both before and during poly(adenosine diphosphate-ribose) polymerase inhibitor treatment.

Prospective phase II trial of levonorgestrel intrauterine device: nonsurgical approach for complex atypical hyperplasia and early-stage endometrial cancer.

BACKGROUND: The incidence of complex atypical hyperplasia and early-stage endometrioid endometrial cancer is increasing, in part owing to the epidemic of obesity, which is a risk factor tightly linked to the development of endometrial hyperplasia and cancer. The standard upfront treatment for complex atypical hyperplasia and early-stage endometrial cancer is hysterectomy. However, nonsurgical treatment of early-stage endometrial neoplasia may be necessary owing to medical comorbidities precluding surgery or desired future fertility. OBJECTIVE: This study aimed to evaluate the efficacy of the levonorgestrel intrauterine device to treat complex atypical hyperplasia and grade 1 endometrioid endometrial carcinoma. STUDY DESIGN: A single-institution, single-arm, phase II study of the levonorgestrel intrauterine device (52 mg levonorgestrel, Mirena) was conducted in patients with complex atypical hyperplasia or grade 1 endometrioid endometrial cancer. The primary endpoint was pathologic response rate at 12 months, including complete or partial response. Quality of life and toxicity were assessed. Molecular analyses for proliferation markers, hormone-regulated genes, and wingless-related integration site pathway activation were performed at baseline and 3 months. RESULTS: A total of 57 patients were treated (21 endometrial cancer, 36 complex atypical hyperplasia). The median age was 48.0 years, and the median body mass index was 45.5 kg/m2. Of the 47 evaluable patients, 12-month response rate was 83% (90% credible interval, 72.7-90.3)-37 were complete responders (8 endometrial cancer; 29 complex atypical hyperplasia), 2 were partial responders (2 endometrial cancer), 3 had stable disease (2 endometrial cancer; 1 complex atypical hyperplasia), and 5 had progressive disease (3 endometrial cancer; 2 complex atypical hyperplasia). After stratification for histology, the response rate was 90.6% for complex atypical hyperplasia and 66.7% for grade 1 endometrioid endometrial cancer. Notably, 4 patients (9.5%) experienced relapse after the initial response. Adverse events were mild, primarily irregular bleeding and cramping. Quality of life was not negatively affected. At 3 months, exogenous progesterone effect was present in 96.9% of responders (31 of 32) vs 25% of nonresponders (2 of 8) (P=.001). Nonresponders had higher baseline proliferation (Ki67) and lower dickkopf homolog 3 gene expression than responders (P=.023 and P=.030). Nonresponders had significantly different changes in secreted frizzled-related protein 1, frizzled class receptor 8, and retinaldehyde dehydrogenase 2 compared with responders. CONCLUSION: The levonorgestrel intrauterine device has a substantial activity in complex atypical hyperplasia and grade 1 endometrioid endometrial cancer, with a modest proportion demonstrating upfront progesterone resistance. Potential biomarkers were identified that may correlate with resistance to therapy; further exploration is warranted.