A Systematic Review of the Cost-Effectiveness of Stereotactic Radiation Therapy for Cancer Oligometastases.

It is crucial to economically justify the use of promising therapies such as stereotactic ablative radiotherapy (SABR) for oligometastatic disease (OMD). The goal of this systematic review was to provide a summative evaluation of publications that analyzed the cost-effectiveness (CE) of SABR for OMD. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided methodology, PubMed and Embase were searched for modeling-based CE studies for various forms of limited metastatic disease. Only full publications that specifically compared SABR with a systemic therapy-based approach were included. In total, 9 studies met inclusion criteria; 4 pertained to OMD with mixed histologies, 2 to oligometastatic non-small cell lung cancer, 1 to pulmonary OMD, 1 to liver OMD, and 1 to low-volume oligorecurrent castration-sensitive prostate cancer. All but 1 investigation illustrated that SABR was cost-effective for the studied population (or a subpopulation); of these studies, the incremental CE ratios for SABR (when reported) ranged from $28,000/quality-adjusted life-year (QALY) to $55,000/QALY. Of studies that reported the probability of SABR being cost-effective at common willingness-to-pay values, the median (range) probability of achieving CE was roughly 61% (30%-88%) at a $50,000/QALY threshold and 78% (31%-100%) at a $100,000/QALY threshold. Taken together, the available evidence suggests that SABR appears to be a cost-effective approach for OMD, which has implications for value-based oncologic practice and construction of future health policies. However, reassessment is required in the context of modern systemic therapies (eg, immunotherapy) as well as long-term follow-up of existing and newly reported randomized trials. Prudent patient selection remains the single most important factor influencing the CE of SABR for OMD.

Financial relationships between industry and principal investigators of US cooperative group randomized cancer clinical trials.

Financial conflicts of interest (FCOIs) could bias the potentially practice-changing oncologic randomized clinical trials (RCTs) of tomorrow. This investigation characterized the FCOIs of the principal investigators (PIs) of all currently accruing trials of the four (adult) cooperative groups of the National Clinical Trials Network. For our study, the PI list was first compiled, and each name was then searched in the CMS Open Payments database. For each transaction (general payments (GPs) or research funding (RF)), the amount/number/source of payments was recorded. Results showed that from 2014 to 2019, the 91 PIs collectively accepted nearly one-third of a billion dollars ($10 477 023 GPs and $320 096 233 RF). The mean and median GP was $6505 and $945, respectively, and $301 693 and $49 824 RF, respectively. Multivariable Gamma regression analysis revealed that higher GP sums were associated with RCTs involving any type of systemic therapy, and higher RF sums with medical oncologist PIs, trials with phase III components, and RCTs involving radiotherapy (P < .05 for all). Both higher-volume GPs and RF were predicted by PIs having accepted payment(s) from the manufacturer of the drug utilized in their RCT (P < .001 GP, P = .008 RF). Taken together, the main message of this investigation is that FCOIs may be particularly high in PIs of phase III systemic therapy trials, especially if the PI accepted payments from the manufacturer of the drug utilized in their trial. Such RCTs should be thoroughly scrutinized by medical journals, the FDA, and insurance companies for potential "industry bias" that could influence the integrity of their conclusions.

Association of Medicaid Insurance With Survival Among Patients With Small Cell Lung Cancer.

Importance: Small cell lung cancer (SCLC) is an aggressive neoplasm requiring rapid access to subspecialized multidisciplinary care. For this reason, insurance coverage such as Medicaid may be associated with oncologic outcomes in this disproportionately economically vulnerable population. With Medicaid expansion under the Affordable Care Act, it is important to understand outcomes associated with Medicaid coverage among patients with SCLC. Objective: To determine the association of Medicaid coverage with survival compared with other insurance statuses. Design, Setting, and Participants: This cohort study included adult patients with limited-stage (LS) and extensive-stage (ES) SCLC in the US National Cancer Database from 2004 to 2013. Data were analyzed in January 2019. Main Outcomes and Measures: Patients were analyzed with respect to insurance status. Associations of insurance status with survival were interrogated with univariate analyses, multivariable analyses, and propensity score matching. Results: A total of 181 784 patients with SCLC (93 131 [51.2%] female; median [interquartile range] age; 67 [60-75] years for patients with LS-SCLC and 68 [60-75] years for patients with ES-SCLC) were identified, of whom 70 247 (38.6%) had LS-SCLC and 109 479 (60.2%) had ES-SCLC. On univariate analyses of patients with LS-SCLC, Medicaid coverage was not associated with a survival advantage compared with being uninsured (hazard ratio, 1.02; 95% CI, 0.96-1.08; P = .49). Likewise, on multivariable analyses of patients with ES-SCLC, compared with being uninsured, Medicaid coverage was not associated with a survival advantage (hazard ratio, 1.00; 95% CI, 0.96-1.03; P = .78). After propensity score matching, median survival was similar between the uninsured and Medicaid groups both among patients with LS-SCLC (14.4 vs 14.1 months; hazard ratio, 1.05; 95% CI, 0.98-1.12; P = .17) and those with ES-SCLC (6.3 vs 6.4 months; hazard ratio, 1.00; 95% CI, 0.96-1.04; P = .92). Conclusions and Relevance: Despite of billions of dollars in annual federal and state spending, Medicaid was not associated with improved survival in patients with SCLC compared with being uninsured in the US National Cancer Database. These findings suggest that there are substantial outcome inequalities for SCLC relevant to the policy debate on the Medicaid expansion under the Affordable Care Act.

Commercial Insurance Coverage of Advanced Radiation Therapy Techniques Compared With American Society for Radiation Oncology Model Policies.

PURPOSE: This study aimed to compare and contrast the American Society for Radiation Oncology (ASTRO) model policies (MPs) for intensity modulated radiation therapy (IMRT), stereotactic radiosurgery (SRS), stereotactic ablative radiation therapy (SABR), and proton beam therapy (PBT) with the coverage policies constructed by 5 of the largest publicly available commercial insurers throughout the United States (ie, Aetna, Anthem, Cigna, Humana, and United Healthcare). METHODS AND MATERIALS: Appropriate indications for IMRT, SRS, SABR, and PBT by disease site (and particular clinical setting thereof) were extracted from the most recently published ASTRO MPs and published coverage policies (2019 editions) of the 5 carriers. After tabulation, concordance between ASTRO MPs and insurance policies were calculated for each modality. RESULTS: All 5 insurer policies supported IMRT for neoplasms of the central nervous system, head/neck, hepatopancreaticobiliary, anal, and prostate cancers. The least covered diseases were retroperitoneal tumors (n = 0 carriers) and bladder cancer (n = 1). For SRS, all carriers covered benign brain tumors, brain metastases, arteriovenous malformations, and trigeminal neuralgia. None of the insurance carriers covered SRS for medically refractory epilepsy. For SABR, primary liver, lung, and low- or intermediate-risk prostate cancer were covered by all insurers, and none allowed SABR for primary biliary neoplasms. Only one insurance carrier each covered SABR for primary/metastatic adrenal disease and primary renal cancer. All carriers approved PBT for ocular melanoma, skull base tumors, and pediatric malignancies. The ASTRO MPs listed 4 PBT scenarios (ie, spinal disease, retroperitoneal sarcoma, head/neck neoplasms, and patients with genetic radiosensitivity syndromes) not covered by any insurer. Concordance between insurance carriers and ASTRO MPs was 67.8% for IMRT, 72.0% for SRS, 58.4% for SABR, and 41.8% for PBT (P = .005). CONCLUSIONS: Coverage guidelines for IMRT, SRS, SABR, and PBT vary across 5 major insurance providers and may be substantially discordant compared with ASTRO coverage guidelines. There remain several specific areas where ongoing and future dialogues between ASTRO members, payers, and policymakers remain essential.

Racial and Insurance-related Disparities in Delivery of Immunotherapy-type Compounds in the United States.

Racial and/or socioeconomic factors affect the type of therapies delivered for non-small cell lung cancer (NSCLC). Given the rapid expansion of immunotherapy for NSCLC, it is a crucial public health priority to evaluate disparities in administration thereof. The National Cancer Database (NCDB) was queried for newly diagnosed metastatic NSCLC. Patients were dichotomized based on receipt of immunotherapy-type compounds (ICs) based on NCDB coding. Multivariable logistic regression ascertained factors associated with IC delivery. Subgroup analysis, performed by univariate logistic regression modeling, evaluated the effect of race while stratifying for insurance type. Of 504,447 patients, 11,420 (2.3%) received ICs, and 493,027 (97.7%) did not. From 2004 to 2012, ≤1% of patients received ICs; however, 4.9% did so in 2013, 6.6% in 2014, and 8.7% in 2015. ICs were more likely administered to younger and healthier patients, those living farther from treating facilities, and in more educated areas (P<0.05 for all). ICs were more often delivered to adenocarcinomas, and patients who received chemotherapy but not radiotherapy (P<0.05 for all). In addition to geographic differences, uninsured and Medicaid populations received ICs less often, along with African Americans. On subgroup analysis, African Americans were less likely to receive ICs even when stratified for Medicare, Medicaid, or private insurances. Because IC utilization is expected to amplify even further going forward, these public health and economic issues are essential to identify and address appropriately, and have implications on pharmaceutical/insurance companies, value-based oncology, and public health policy. Methods to address these inequalities are also discussed.

A systematic review of the cost and cost-effectiveness studies of immune checkpoint inhibitors.

BACKGROUND: Escalating healthcare costs are necessitating the practice of value-based oncology. It is crucial to critically evaluate the economic impact of influential but expensive therapies such as immune checkpoint inhibitors (ICIs). To date, no systematic assessment of the cost-effectiveness (CE) of ICIs has been performed. METHODS: PRISMA-guided systematic searches of the PubMed database were conducted. Studies of head/neck (n = 3), lung (n = 5), genitourinary (n = 4), and melanoma (n = 8) malignancies treated with ICIs were evaluated. The reference willingness-to-pay (WTP) threshold was $100,000/QALY. RESULTS: Nivolumab was not cost-effective over chemotherapy for recurrent/metastatic head/neck cancers (HNCs). For non-small cell lung cancer (NSCLC), nivolumab was not cost-effective for a general cohort, but increased PD-L1 cutoffs resulted in CE. Pembrolizumab was cost-effective for both previously treated and newly-diagnosed metastatic NSCLC. For genitourinary cancers (GUCs, renal cell and bladder cancers), nivolumab and pembrolizumab were not cost-effective options. Regarding metastatic/unresected melanoma, ipilimumab monotherapy is less cost-effective than nivolumab, nivolumab/ipilimumab, and pembrolizumab. The addition of ipilimumab to nivolumab monotherapy was not adequately cost-effective. Pembrolizumab or nivolumab monotherapy offered comparable CE profiles. CONCLUSIONS: With limited data and from the reference WTP, nivolumab was not cost-effective for HNCs. Pembrolizumab was cost-effective for NSCLC; although not the case for nivolumab, applying PD-L1 cutoffs resulted in adequate CE. Most data for nivolumab and pembrolizumab in GUCs did not point towards adequate CE. Contrary to ipilimumab, either nivolumab or pembrolizumab is cost-effective for melanoma. Despite these conclusions, it cannot be overstated that careful patient selection is critical for CE. Future publication of CE investigations and clinical trials (along with longer follow-up of existing data) could substantially alter conclusions from this analysis.

Cost Analysis of PET/CT Versus CT as Surveillance for Stage III Non-Small-Cell Lung Cancer After Definitive Radiation Therapy.

INTRODUCTION: A previous study showed that use of positron emission tomography (PET)/computed tomography (CT) for surveillance after treatment of non-small-cell lung cancer (NSCLC) does not yield a detection or survival benefit over the use of chest CT. However, PET/CT remains a common method of follow-up imaging. Here we estimated and compared the costs of PET/CT versus CT for surveillance of patients with stage III NSCLC and identified patient and provider demographic characteristics associated with preference for use of PET/CT. PATIENTS AND METHODS: We reviewed 178 patients with stage III NSCLC who had received ≥ 1 PET/CT scan within 6 months of completing radiotherapy (n = 89) or had received CT after radiotherapy (n = 89) from 2000 to 2011. Costs were measured according to Medicare payments converted from institutional billing records. Total and imaging costs were analyzed at 6, 12, 18, and 24 months after the end of treatment. Patient and provider demographic characteristics were also evaluated for potential associations with PET/CT use. RESULTS: Total costs in the PET/CT group were higher during the first 18 months after treatment (P = .002 at 6 months, P = .019 at 12 months, and P = .018 at 18 months) but was marginally significant (P = .05) at 24 months. In univariate analysis of demographic variables, patients who lived in a state different from the treatment center might have been more likely to receive PET/CT (odds ratio [OR], 1.76; P = .051). In multivariate analysis, patients treated in 2007 to 2010 (OR, 29.9; P < .001) or 2003 to 2006 (OR, 11.6; P = .002) were more likely to receive PET/CT than patients treated in 1999 to 2002. In addition, radiation oncologists with > 10 years of experience were more likely to use PET/CT than those with less experience, although this result might be confounded by the small number of providers. CONCLUSION: Use of PET/CT was associated with higher costs for 18 months after treatment, but the difference was at the borderline of statistical significance at 24 months.

Barriers to Combined-Modality Therapy for Limited-Stage Small Cell Lung Cancer.

Importance: Combined-modality therapy with chemotherapy and radiation therapy plays a crucial role in the upfront treatment of patients with limited-stage small cell lung cancer (SCLC), but there may be barriers to utilization in the United States. Objective: To estimate utilization rates and factors associated with chemotherapy and radiation therapy delivery for limited-stage SCLC using the National Cancer Database. Design, Setting, and Participants: Analysis of initial management of all limited-stage SCLC cases from 2004 through 2013 in the National Cancer Database. Main Outcomes and Measures: Utilization rates of chemotherapy and radiation therapy at time of initial treatment. Multivariable analysis identified independent clinical and socioeconomic factors associated with utilization and overall survival. Results: A total of 70 247 cases met inclusion criteria (55.3% female; median age, 68 y [range, 19-90 y]). Initial treatment was 55.5% chemotherapy and radiation therapy, 20.5% chemotherapy alone, 3.5% radiation therapy alone, and 20.0% neither (0.5% not reported). Median survival was 18.2 (95% CI, 17.9-18.4), 10.5 (95% CI, 10.3-10.7), 8.3 (95% CI, 7.7-8.8), and 3.7 (95% CI, 3.5-3.8) months, respectively. Being uninsured was associated with a lower likelihood of both chemotherapy (odds ratio [OR], 0.65; 95% CI, 0.56-0.75; P < .001) and radiation therapy (OR, 0.75; 95% CI, 0.67-0.85; P < .001) administration on multivariable analysis. Medicare/Medicaid insurance had no impact on chemotherapy use, whereas Medicaid (OR, 0.79; 95% CI, 0.72-0.87; P < .001) and Medicare (OR, 0.86; 95% CI, 0.82-0.91; P < .001) were independently associated with a lower likelihood of radiation therapy delivery. Lack of health insurance (HR, 1.19; 95% CI, 1.13-1.26; P < .001), Medicaid (HR, 1.27; 95% CI, 1.21-1.32; P < .001), and Medicare (HR, 1.12; 95% CI, 1.09-1.15; P < .001) coverage were independently associated with shorter survival on adjusted analysis, while chemotherapy (HR, 0.55; 95% CI, 0.54-0.57; P < .001) and radiation therapy (HR, 0.62; 95% CI, 0.60-0.63; P < .001) were associated with a survival benefit. Conclusions and Relevance: Substantial proportions of patients documented in a major US cancer registry did not receive radiation therapy or chemotherapy as part of initial treatment for limited-stage SCLC, which, in turn, was associated with poor survival. Lack of radiation therapy delivery was uniquely associated with government insurance coverage, suggesting a need for targeted access improvement in this population. Additional work will be necessary to conclusively define exact population patterns, specific treatment deficiencies, and causative factors leading to heterogeneous care delivery.