Methodological Comparison of Mapping the Expanded Prostate Cancer Index Composite to EuroQoL-5D-3L Using Cross-Sectional and Longitudinal Data: Secondary Analysis of NRG/RTOG 0415.

PURPOSE: To compare the predictive ability of mapping algorithms derived using cross-sectional and longitudinal data. METHODS: This methodological assessment used data from a randomized controlled noninferiority trial of patients with low-risk prostate cancer, conducted by NRG Oncology (ClinicalTrials.gov identifier: NCT00331773), which examined the efficacy of conventional schedule versus hypofractionated radiation therapy (three-dimensional conformal external beam radiation therapy/IMRT). Health-related quality-of-life data were collected using the Expanded Prostate Cancer Index Composite (EPIC), and health utilities were obtained using EuroQOL-5D-3L (EQ-5D) at baseline and 6, 12, 24, and 60 months postintervention. Mapping algorithms were estimated using ordinary least squares regression models through five-fold cross-validation in baseline cross-sectional data and combined longitudinal data from all assessment periods; random effects specifications were also estimated in longitudinal data. Predictive performance was compared using root mean square error. Longitudinal predictive ability of models obtained using baseline data was examined using mean absolute differences in the reported and predicted utilities. RESULTS: A total of 267 (and 199) patients in the estimation sample had complete EQ-5D and EPIC domain (and subdomain) data at baseline and at all subsequent assessments. Ordinary least squares models using combined data showed better predictive ability (lowest root mean square error) in the validation phase for algorithms with EPIC domain/subdomain data alone, whereas models using baseline data outperformed other specifications in the validation phase when patient covariates were also modeled. The mean absolute differences were lower for models using EPIC subdomain data compared with EPIC domain data and generally decreased as the time of assessment increased. CONCLUSION: Overall, mapping algorithms obtained using baseline cross-sectional data showed the best predictive performance. Furthermore, these models demonstrated satisfactory longitudinal predictive ability.

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.

Patterns of Failure Observed in the 2-Step Institution Credentialing Process for NRG Oncology/Radiation Therapy Oncology Group 1005 (NCT01349322) and Lessons Learned.

PURPOSE: To investigate patterns of failure in institutional credentialing submissions to NRG/RTOG 1005 with the aim of improving the quality and consistency for future breast cancer protocols. METHODS AND MATERIALS: NRG/RTOG 1005 allowed the submission of 3-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), and simultaneous integrated boost (SIB) breast plans. Credentialing required institutions to pass a 2-step quality assurance (QA) process: (1) benchmark, requiring institutions to create a plan with no unacceptable deviations and ≤1 acceptable variation among the dose volume (DV) criteria, and (2) rapid review, requiring each institution's first protocol submission to have no unacceptable deviations among the DV criteria or contours. Overall rates, number of resubmissions, and reasons for resubmission were analyzed for each QA step. RESULTS: In total, 352 institutions participated in benchmark QA and 280 patients enrolled had rapid review QA. Benchmark initial failure rates were similar for 3DCRT (18%), IMRT (17%), and SIB (18%) plans. For 3DCRT and IMRT benchmark plans, ipsilateral lung most frequently failed the DV criteria, and SIB DV failures were seen most frequently for the heart. Rapid review contour initial failures (35%) were due to target rather than organs at risk. For 29% of the rapid review initial failures, the planning target volume boost eval volume was deemed an unacceptable deviation. CONCLUSIONS: The review of the benchmark and rapid review QA submissions indicates that acceptable variations or unacceptable deviations for the ipsilateral lung and heart dose constraints were the most commonly observed cause of benchmark QA failure, and unacceptable deviations in target contouring, rather than normal structure contouring, were the most common cause of rapid review QA failure. These findings suggest that a rigorous QA process is necessary for high quality and homogeneity in radiation therapy in multi-institutional trials of breast cancer to ensure that the benefits of radiation therapy far outweigh the risks.

NRG Oncology-Radiation Therapy Oncology Group Study 1014: 1-Year Toxicity Report From a Phase 2 Study of Repeat Breast-Preserving Surgery and 3-Dimensional Conformal Partial-Breast Reirradiation for In-Breast Recurrence.

PURPOSE: To determine the associated toxicity, tolerance, and safety of partial-breast reirradiation. METHODS AND MATERIALS: Eligibility criteria included in-breast recurrence occurring >1 year after whole-breast irradiation, <3 cm, unifocal, and resected with negative margins. Partial-breast reirradiation was targeted to the surgical cavity plus 1.5 cm; a prescription dose of 45 Gy in 1.5 Gy twice daily for 30 treatments was used. The primary objective was to evaluate the rate of grade ≥3 treatment-related skin, fibrosis, and/or breast pain adverse events (AEs), occurring ≤1 year from re-treatment completion. A rate of ≥13% for these AEs in a cohort of 55 patients was determined to be unacceptable (86% power, 1-sided α = 0.07). RESULTS: Between 2010 and 2013, 65 patients were accrued, and the first 55 eligible and with 1 year follow-up were analyzed. Median age was 68 years. Twenty-two patients had ductal carcinoma in situ, and 33 had invasive disease: 19 ≤1 cm, 13 >1 to ≤2 cm, and 1 >2 cm. All patients were clinically node negative. Systemic therapy was delivered in 51%. All treatment plans underwent quality review for contouring accuracy and dosimetric compliance. All treatment plans scored acceptable for tumor volume contouring and tumor volume dose-volume analysis. Only 4 (7%) scored unacceptable for organs at risk contouring and organs at risk dose-volume analysis. Treatment-related skin, fibrosis, and/or breast pain AEs were recorded as grade 1 in 64% and grade 2 in 7%, with only 1 (<2%) grade ≥3 and identified as grade 3 fibrosis of deep connective tissue. CONCLUSION: Partial-breast reirradiation with 3-dimensional conformal radiation therapy after second lumpectomy for patients experiencing in-breast failures after whole-breast irradiation is safe and feasible, with acceptable treatment quality achieved. Skin, fibrosis, and breast pain toxicity was acceptable, and grade 3 toxicity was rare.

Association of Locoregional Control With High Body Mass Index in Women Undergoing Breast Conservation Therapy for Early-Stage Breast Cancer.

PURPOSE: Obesity, as measured by the body mass index (BMI), is a risk factor for distant recurrence and decreased survival in breast cancer. We sought to determine whether the BMI correlated with local recurrence and reduced survival in a cohort of predominantly obese women treated with breast conservation therapy. METHODS AND MATERIALS: From 1998 to 2010, 154 women with early-stage invasive breast cancer and 39 patients with ductal carcinoma in situ underwent prone whole breast irradiation. Cox proportional hazards regression, Kaplan-Meier methods with the log-rank test, and multivariate analysis were used to explore the association of the outcomes with the BMI. RESULTS: The median patient age was 60 years, and the median follow-up duration was 73 months. The median BMI was 33.2 kg/m(2); 91% of the patients were overweight (BMI ≥25 kg/m(2)) and 69% of the patients were clinically obese (BMI ≥30 kg/m(2)). The BMI was significantly associated with the locoregional recurrence-free interval for patients with invasive cancer and ductal carcinoma in situ (hazard ratio [HR], 1.09; P=.047). Also, a trend was seen for increased locoregional recurrence with a higher BMI (P=.09) for patients with invasive disease, which was significant when examining the outcomes with a BMI stratified by the median value of 33.2 kg/m(2) (P=.008). A greater BMI was also significantly associated with decreased distant recurrence-free interval (HR, 1.09; P=.011) and overall survival (HR, 1.09; P=.004); this association remained on multivariate analysis (distant recurrence-free interval, P=.034; overall survival, P=.0007). CONCLUSIONS: These data suggest that the BMI might affect the rate of locoregional recurrence in breast cancer patients. A higher BMI predicted a worse distant recurrence-free interval and overall survival. The present investigation adds to the increasing evidence that BMI is an important prognostic factor in early-stage breast cancer treated with breast conservation therapy.

Reducing the Human Burden of Breast Cancer: Advanced Radiation Therapy Yields Improved Treatment Outcomes.

Radiation therapy is an important modality in the treatment of patients with breast cancer. While its efficacy in the treatment of breast cancer was known shortly after the discovery of x-rays, significant advances in radiation delivery over the past 20 years have resulted in improved patient outcomes. With the development of improved systemic therapy, optimizing local control has become increasingly important and has been shown to improve survival. Better understanding of the magnitude of treatment benefit, as well as patient and biological factors that confer an increased recurrence risk, have allowed radiation oncologists to better tailor treatment decisions to individual patients. Furthermore, significant technological advances have occurred that have reduced the acute and long-term toxicity of radiation treatment. These advances continue to reduce the human burden of breast cancer. It is important for radiation oncologists and nonradiation oncologists to understand these advances, so that patients are appropriately educated about the risks and benefits of this important treatment modality.