Mapping expanded prostate cancer index composite to EQ5D utilities to inform economic evaluations in prostate cancer: Secondary analysis of NRG/RTOG 0415.

PURPOSE: The Expanded Prostate Cancer Index Composite (EPIC) is the most commonly used patient reported outcome (PRO) tool in prostate cancer (PC) clinical trials, but health utilities associated with the different health states assessed with this tool are unknown, limiting our ability to perform cost-utility analyses. This study aimed to map EPIC tool to EuroQoL-5D-3L (EQ5D) to generate EQ5D health utilities. METHODS AND MATERIALS: This is a secondary analysis of a prospective, randomized non-inferiority clinical trial, conducted between 04/2006 and 12/2009 at cancer centers across the United States, Canada, and Switzerland. Eligible patients included men >18 years with a known diagnosis of low-risk PC. Patient HRQoL data were collected using EPIC and health utilities were obtained using EQ5D. Data were divided into an estimation sample (n = 765, 70%) and a validation sample (n = 327, 30%). The mapping algorithms that capture the relationship between the instruments were estimated using ordinary least squares (OLS), Tobit, and two-part models. Five-fold cross-validation (in-sample) was used to compare the predictive performance of the estimated models. Final models were selected based on root mean square error (RMSE). RESULTS: A total of 565 patients in the estimation sample had complete information on both EPIC and EQ5D questionnaires at baseline. Mean observed EQ5D utility was 0.90±0.13 (range: 0.28-1) with 55% of patients in full health. OLS models outperformed their counterpart Tobit and two-part models for all pre-determined model specifications. The best model fit was: "EQ5D utility = 0.248541 + 0.000748*(Urinary Function) + 0.001134*(Urinary Bother) + 0.000968*(Hormonal Function) + 0.004404*(Hormonal Bother)- 0.376487*(Zubrod) + 0.003562*(Urinary Function*Zubrod)"; RMSE was 0.10462. CONCLUSIONS: This is the first study to identify a comprehensive set of mapping algorithms to generate EQ5D utilities from EPIC domain/ sub-domain scores. The study results will help estimate quality-adjusted life-years in PC economic evaluations.

Patient Prioritization for Proton Beam Therapy in a Cost-neutral Payer Environment: Use of the Clinical Benefit Score for Resource Allocation.

Objectives There has been a rapid increase in the number of one- and two-room proton beam therapy (PBT) centers, which may be limited in the number of patients they can treat. The objective of this study was to analyze the impact of the 'clinical benefit score' (CBS), utilized as a method for treatment prioritization for PBT operating in a 'cost-neutral' proton-photon payer environment. Materials & methods This study includes patients considered for PBT at a center that initially had only one or two treatment rooms available for clinical use. Patients were prospectively scored using the CBS, and higher scores were prioritized. The outcome was receipt of PBT and the independent variable was CBS. Crude and adjusted analyses were performed using logistic regression. Results There were 2163 patients evaluated. A total of 205 patients (9.5%) were deemed candidates for PBT, which was received by 122 (5.6%) patients. In patients considered for PBT, the mean CBS was 18.7. Patients who were <21 years old, female, non-Caucasian, receiving re-irradiation, and those with Medicare had a higher CBS. Multivariate analysis adjusting for insurance status revealed both CBS and insurance to be significant predictors for receiving PBT. A unit increase in CBS was associated with 1.04 times increased odds of receiving PBT (OR=1.04, 95%CI: 1.01-1.07, p=0.0145) and having Medicare was associated with 3.13 times increased odds of receiving PBT (OR=3.13, 95%CI: 1.57-6.26, p=0.0012). Subgroup analysis, which only included patients enrolled prior to opening the second gantry, showed 1.05 times increased odds of receiving PBT per unit increase in CBS (OR=1.05, 95%CI: 1.00-1.10, p=0.03) and 2.87 times increased odds of receiving PBT in patients with Medicare (OR=2.87, 95%CI: 1.04-7.92, p=0.04). Conclusion  The CBS utilized was significantly associated with the receipt of PBT in a cost-neutral payer setting. Physicians may consider the use of CBS as a resource allocation tool.

Evaluating the Cost-Effectiveness of Hydrogel Rectal Spacer in Prostate Cancer Radiation Therapy.

PURPOSE: A hydrogel rectal spacer (HRS) is a medical device that is approved by the U.S. Food and Drug Administration to increase the separation between the prostate and rectum. We conducted a cost-effectiveness analysis of HRS use for reduction in radiation therapy (RT) toxicities in patients with prostate cancer (PC) undergoing external beam RT (EBRT). METHODS AND MATERIALS: A multistate Markov model was constructed from the U.S. payer perspective to examine the cost-effectiveness of HRS in men with localized PC receiving EBRT (EBRT alone vs EBRT + HRS). The subgroups analyzed included site of HRS placement (hospital outpatient, physician office, ambulatory surgery center) and proportion of patients with good baseline erectile function (EF). Data on EF, gastrointestinal and genitourinary toxicities incidence, and potential risks associated with HRS implantation were obtained from a recently published randomized clinical trial. Health utilities and costs were derived from the literature and the 2018 Physician Fee Schedule and were discounted 3% annually. Quality-adjusted life years (QALYs) and costs were modeled for a 5-year period from receipt of RT. Probabilistic sensitivity analysis and value-based threshold analyses were conducted. RESULTS: The per-patient 5-year incremental cost for spacers administered in a hospital outpatient setting was $3578, and the incremental effectiveness was 0.0371 QALYs. The incremental cost-effectiveness ratio was $96,440/QALY for patients with PC undergoing HRS insertion in a hospital and $39,286/QALY for patients undergoing HRS insertion in an ambulatory facility. For men with good baseline EF, the incremental cost-effectiveness ratio was $35,548/QALY and $9627/QALY in hospital outpatient and ambulatory facility settings, respectively. CONCLUSIONS: Based on the current Medicare Physician Fee Schedule, HRS is cost-effective at a willingness to pay threshold of $100,000. These results contain substantial uncertainty, suggesting more evidence is needed to refine future decision-making.

Establishing Evidence-Based Indications for Proton Therapy: An Overview of Current Clinical Trials.

PURPOSE: To review and assess ongoing proton beam therapy (PBT) clinical trials and to identify major gaps. METHODS AND MATERIALS: Active PBT clinical trials were identified from clinicaltrials.gov and the World Health Organization International Clinical Trials Platform Registry. Data on clinical trial disease site, age group, projected patient enrollment, expected start and end dates, study type, and funding source were extracted. RESULTS: A total of 122 active PBT clinical trials were identified, with target enrollment of >42,000 patients worldwide. Ninety-six trials (79%), with a median planned sample size of 68, were classified as interventional studies. Observational studies accounted for 21% of trials but 71% (n=29,852) of planned patient enrollment. The most common PBT clinical trials focus on gastrointestinal tract tumors (21%, n=26), tumors of the central nervous system (15%, n=18), and prostate cancer (12%, n=15). Five active studies (lung, esophagus, head and neck, prostate, breast) will randomize patients between protons and photons, and 3 will randomize patients between protons and carbon ion therapy. CONCLUSIONS: The PBT clinical trial portfolio is expanding rapidly. Although the majority of ongoing studies are interventional, the majority of patients will be accrued to observational studies. Future efforts should focus on strategies to encourage optimal patient enrollment and retention, with an emphasis on randomized, controlled trials, which will require support from third-party payers. Results of ongoing PBT studies should be evaluated in terms of comparative effectiveness, as well as incremental effectiveness and value offered by PBT in comparison with conventional radiation modalities.

Cost-effectiveness of prophylactic cranial irradiation with hippocampal avoidance in limited stage small cell lung cancer.

BACKGROUND AND PURPOSE: Prophylactic cranial irradiation (PCI) in limited stage small cell lung cancer (LS-SCLC) prevents brain metastases and improves survival, with the potential for neurocognitive toxicity. RTOG0933 demonstrated that hippocampal avoidance (HA) during whole brain radiotherapy preserves neurocognition. This study's objective was to evaluate the cost-effectiveness of HA-PCI in LS-SCLC through decision analysis. MATERIALS AND METHODS: A Markov model was developed to simulate the clinical course of LS-SCLC who received HA-PCI or conventional PCI (C-PCI). A willingness-to-pay threshold of $100,000/QALY was used. Incremental cost effectiveness ratio was calculated (ICER). Sensitivity analyses were performed to determine the parameter thresholds and to assess the robustness of the model. RESULTS: In the base case scenario, HA-PCI is more cost-effective than C-PCI, with an ICER of $47,107/QALY. HA-PCI was preferred over C-PCI provided that the risk of developing brain metastases was not increased by at least 14%, or if neurocognitive dysfunction rates were reduced by at least 40%. HA-PCI was the cost-effective strategy in 68% of tested iterations in probabilistic sensitivity analysis. CONCLUSION: This study demonstrates that HA-PCI is more cost-effective than C-PCI in LS-SCLC. Our results support the use of HA-PCI in this patient population, should results from RTOG0933 be confirmed by the ongoing NRGCC003 trial.

Improving Outcomes for Esophageal Cancer using Proton Beam Therapy.

Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with proton beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT.

A systematic review of the cost and cost-effectiveness studies of proton radiotherapy.

BACKGROUND: Economic analyses of new technologies, such as proton-beam radiotherapy (PBT), are a public health priority. To date, no systematic review of the cost-effectiveness of PBT has been performed. METHODS: Systematic searches of PubMed, EMBASE, abstracts from American Society for Radiation Oncology and American Society of Clinical Oncology meetings, and the Cost-Effectiveness Analysis Registry were conducted (2000-2015) along with abstracts from the Particle Therapy Co-Operative Group of North America for both years of existence (2014-2015). Eighteen original investigations were analyzed. RESULTS: The cost-effectiveness for prostate cancer-the single most common diagnosis currently treated with PBT-was suboptimal. PBT was the most cost-effective option for several pediatric brain tumors. PBT costs for breast cancer were increased but were favorable for appropriately selected patients with left-sided cancers at high risk of cardiac toxicity and compared with brachytherapy for accelerated partial breast irradiation. For non-small cell lung cancer (NSCLC), the greatest cost-effectiveness benefits using PBT were observed for locoregionally advanced-but not early stage-tumors. PBT offered superior cost-effectiveness in selected head/neck cancer patients at higher risk of acute mucosal toxicities. Similar cost-effectiveness was observed for PBT, enucleation, and plaque brachytherapy in patients with uveal melanoma. CONCLUSIONS: With greatly limited amounts of data, PBT offers promising cost-effectiveness for pediatric brain tumors, well-selected breast cancers, locoregionally advanced NSCLC, and high-risk head/neck cancers. Heretofore, it has not been demonstrated that PBT is cost-effective for prostate cancer or early stage NSCLC. Careful patient selection is absolutely critical to assess cost-effectiveness. Together with increasing PBT availability, clinical trial evidence, and ongoing major technological improvements, cost-effectiveness data and conclusions from this analysis could change rapidly. Cancer 2016;122:1483-501. © 2016 American Cancer Society.

Evaluation of Health Economics in Radiation Oncology: A Systematic Review.

PURPOSE: Despite the rising costs in radiation oncology, the impact of health economics research on radiation therapy practice analysis patterns is unclear. We performed a systematic review of cost-effectiveness analyses (CEAs) and cost-utility analyses (CUAs) to identify trends in reporting quality in the radiation oncology literature over time. METHODS AND MATERIALS: A systematic review of radiation oncology economic evaluations up to 2014 was performed, using MEDLINE and EMBASE databases. The Consolidated Health Economic Evaluation Reporting Standards guideline informed data abstraction variables including study demographics, economic parameters, and methodological details. Tufts Medical Center CEA registry quality scores provided a basis for qualitative assessment of included studies. Studies were stratified by 3 time periods (1995-2004, 2005-2009, and 2010-2014). The Cochran-Armitage trend test and linear trend test were used to identify trends over time. RESULTS: In total, 102 articles were selected for final review. Most studies were in the context of a model (61%) or clinical trial (28%). Many studies lacked a conflict of interest (COI) statement (67%), a sponsorship statement (48%), a reported study time horizon (35%), and the use of discounting (29%). There was a significant increase over time in the reporting of a COI statement (P<.001), health care payer perspective (P=.019), sensitivity analyses using multivariate (P=.043) or probabilistic methods (P=.011), incremental cost-effectiveness threshold (P<.001), secondary source utility weights (P=.010), and cost effectiveness acceptability curves (P=.049). There was a trend toward improvement in Tuft scores over time (P=.065). CONCLUSIONS: Recent reports demonstrate improved reporting rates in economic evaluations; however, there remains significant room for improvement as reporting rates are still suboptimal. As fiscal pressures rise, we will rely on economic assessments to guide our practice decisions and policies. We recommend improved adherence to published guidelines and further research to determine the clinical implications of our findings.

Radiation oncology services in the modern era: evolving patterns of usage and payments in the office setting for medicare patients from 2000 to 2010.

PURPOSE: We evaluated long-term changes in the volume and payments for radiation oncology services in the intensity-modulated radiation therapy (IMRT) era from 2000 to 2010 using a database of Medicare claims. METHODS: We used the Medicare Physician/Supplier Procedure Summary Master File (PSPSMF) for each year from 2000 to 2010 to tabulate the volume and payments for radiation oncology services. This database provides a summary of each billing code submitted to Medicare part B. We identified all codes used in radiation oncology services and categorized billing codes by treatment modality and place of service. RESULTS: We focused our analysis on office-based practices. Total office-based patient volume increased 8.2% from 2000 to 2010, whereas total payments increased 217%. Increase in overall payments increased dramatically from 2000 to 2007, but subsequently plateaued from 2008 to 2010. Increases in complexity of care, and image guidance in particular, have also resulted in higher payments. CONCLUSION: The cost of radiation oncology services increased from 2000 to 2010, mostly due to IMRT, but also with significant contribution from increased overall complexity of care. A cost adjustment occurred after 2007, limiting further growth of payments. Future health policy studies should explore the potential for further cost containment, including differences in use between freestanding and hospital outpatient facilities.

Comparative effectiveness research for prostate cancer radiation therapy: current status and future directions.

Comparative effectiveness research aims to help clinicians, patients and policymakers make informed treatment decisions under real-world conditions. Prostate cancer patients have multiple treatment options, including active surveillance, androgen deprivation therapy, surgery and multiple modalities of radiation therapy. Technological innovations in radiation therapy for prostate cancer have been rapidly adopted into clinical practice despite relatively limited evidence for effectiveness showing the benefit for one modality over another. Comparative effectiveness research has become an essential component of prostate cancer research to help define the benefits, risks and effectiveness of the different radiation therapy modalities currently in use for prostate cancer treatment.

Postprostatectomy radiation therapy: an evidence-based review.

While the majority of men with localized prostate cancer who undergo a radical prostatectomy will remain disease free, men with certain clinical and pathological features are known to be at an increased risk for developing a biochemical recurrence and, ultimately, distant metastatic disease. The optimal management of these patients continues to be a source of controversy. To date, three randomized Phase III trials have demonstrated that adjuvant radiation therapy (ART) for patients with certain adverse pathological features results in an improvement in several clinically-relevant end points, including biochemical recurrence-free survival and overall survival. Despite the evidence from these trials showing a benefit for ART, many believe that ART results in overtreatment and unwarranted treatment morbidity for a significant number of patients. Many physicians, therefore, instead advocate for close observation followed by early salvage radiation therapy (SRT) at the time of a biochemical recurrence. The purpose of this review is to evaluate the evidence for and to distinguish between ART and early SRT. We will also highlight current and future areas of research for this patient population, including radiation treatment dose escalation, hypofractionation and androgen deprivation therapy. We will also discuss the cost-effectiveness of ART and early SRT.