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Benjamin H. Kann, Henry S. Park, Skyler B. Johnson, Veronica L. Chiang, and James B. Yu

Background: Management of brain metastases typically includes radiotherapy (RT) with conventional fractionation and/or stereotactic radiosurgery (SRS). However, optimal indications and practice patterns for SRS remain unclear. We sought to evaluate national practice patterns for patients with metastatic disease receiving brain RT. Methods: We queried the National Cancer Data Base (NCDB) for patients diagnosed with metastatic non–small cell lung cancer, breast cancer, colorectal cancer, or melanoma from 2004 to 2014 who received upfront brain RT. Patients were divided into SRS and non-SRS cohorts. Patient and facility-level SRS predictors were analyzed with chi-square tests and logistic regression, and uptake trends were approximated with linear regression. Survival by diagnosis year was analyzed with the Kaplan-Meier method. Results: Of 75,953 patients, 12,250 (16.1%) received SRS and 63,703 (83.9%) received non-SRS. From 2004 to 2014, the proportion of patients receiving SRS annually increased (from 9.8% to 25.6%; P<.001), and the proportion of facilities using SRS annually increased (from 31.2% to 50.4%; P<.001). On multivariable analysis, nonwhite race, nonprivate insurance, and residence in lower-income or less-educated regions predicted lower SRS use (P<.05 for each). During the study period, SRS use increased disproportionally among patients with private insurance or who resided in higher-income or higher-educated regions. From 2004 to 2013, 1-year actuarial survival improved from 24.1% to 49.6% for patients selected for SRS and from 21.0% to 26.3% for non-SRS patients (P<.001). Conclusions: This NCDB analysis demonstrates steadily increasing—although modest overall—brain SRS use for patients with metastatic disease in the United States and identifies several progressively widening sociodemographic disparities in the adoption of SRS. Further research is needed to determine the reasons for these worsening disparities and their clinical implications on intracranial control, neurocognitive toxicities, quality of life, and survival for patients with brain metastases.

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Shane Lloyd, Daniela L. Buscariollo, Cary P. Gross, Danil V. Makarov, and James B. Yu

Whether clinical cancer research currently focuses on gaps in the evidentiary basis for clinical guidelines and/or on cancers that impose greater societal burden is unclear. This study assessed the relationship between cancer research efforts in terms of planned randomized controlled trial (RCT) enrollment, objective measures of evidence quality, and a cancer’s burden on society. The authors calculated the planned RCT enrollment listed on ClinicalTrials.gov for the 17 most prevalent solid cancers. Using cancer type as the unit of analysis, linear regression was used to examine the association between planned enrollment in RCTs and 1) evidence quality, as measured by the absolute number and percent of highest quality category (category 1 [C1]) recommendations in the NCCN Clinical Practice Guidelines in Oncology for each cancer, and 2) measures of burden on society, including prevalence, incidence, person-years of life lost (PYLL), and disability-adjusted life years (DALY). Non-normal distributions were log transformed when appropriate. Overall, 15% of the NCCN recommendations were based on the highest quality evidence. Results produced 1260 RCTs. Planned RCT enrollment ranged from 2270 (testis) to 492,876 (breast) and was correlated neither with absolute number nor percent of C1 recommendations for that cancer. Planned RCT enrollment was positively correlated with a cancer’s prevalence (P=.01), incidence (P<.01), PYLL (P<.01), and DALY (P<0.01). In multivariate analysis, prevalence (P<.01) and PYLL (P<.01) had the strongest association with planned RCT enrollment. Findings showed, therefore, that planned cancer RCT enrollment is associated with higher societal disease burden, not the quality of a cancer’s clinical guidelines.

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Rochelle Payne Ondracek, Michael W. Kattan, Christine Murekeyisoni, Changhong Yu, Eric C. Kauffman, James R. Marshall, and James L. Mohler

Background: The Kattan postoperative radical prostatectomy (RP) nomogram is used to predict biochemical recurrence-free progression (BCRFP) after RP. However, external validation among contemporary patients using modern outcome definitions is limited. Methods: A total of 1,931 patients who underwent RP at Roswell Park Cancer Institute (RPCI) between 1993 and 2014 (median follow-up, 47 months; range, 0–244 months) were assessed for NCCN-defined biochemical failure (BF) and RPCI-defined treatment failure (TF). Actual rates of biochemical failure-free survival (BFS; defined as 1 – BF) and treatment failure-free survival (TFS; defined as 1 – TF) were compared with Kattan BCRFP nomogram predictions. Results: The Kattan BCRFP nomogram predictions at 5 and 10 years were predictive of BFS (area under the receiver operating characteristic curve [AUC], 0.772) and TFS (AUC, 0.774). The Kattan BCRFP nomogram tended to underestimate BFS and TFS compared with actual outcomes. The Kattan 5-year BCRFP predictions consistently overestimated actual 5-year BFS outcomes among subgroups of high- and intermediate-risk patients with at least 5-year outcomes. Conclusions: The Kattan BCRFP nomogram is a robust predictor of NCCN-defined BF in a large sample of patients with RP with substantial follow-up and modern, standardized failure definitions

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Stephen R. Grant, Benjamin D. Smith, Lauren E. Colbert, Qunyh-Nhu Nguyen, James B. Yu, Steven H. Lin, and Aileen B. Chen

Background: There exists wide practice variability in palliative treatment schedules for bone metastases. In an effort to reduce variation and promote high-quality, cost-conscious care, the National Quality Forum (NQF) endorsed measure 1822 in 2012. This measure recommends the use of 30 Gy in 10 fractions, 24 Gy in 6 fractions, 20 Gy in 5 fractions, or 8 Gy in a single fraction for palliative radiation for bone metastases. We report on longitudinal compliance with this measure. Methods: Using the National Cancer Database, patients with metastatic thoracic non–small cell lung cancer diagnosed between 2004 and 2016 who received radiation therapy for bony sites of metastatic disease were identified. Treatment courses fitting 1 of the 4 recommended schedules under NQF 1822 were coded as compliant. Rates of compliance by patient, tumor, and treatment characteristics were analyzed. Results: A total of 42,685 patients met the criteria for inclusion. Among all patients, 60.2% of treatment courses were compliant according to NQF 1822. Compliance increased over time and was highest for treatments to the extremity (69.8%), lowest for treatments to the skull or head (48.8%), and higher for academic practice (67.1%) compared with community (56.0%) or integrated network facilities (61.2%). On multivariable analysis, predictors of NQF 1822 compliance included year of diagnosis after 2011, treatment to an extremity, or treatment at an academic facility. Of noncompliant treatment courses, extended fractionation (≥11 fractions) occurred in 62.6% and was more common before 2012, in community practice, and for treatments of the skull or head. Conclusions: Among patients treated for metastatic non–small cell lung cancer, compliance with NQF 1822 increased over time. Although extended fractionation constituted a majority of noncompliant treatment courses, a substantial proportion also involved shorter courses.