Faculty Collaboration Database

Modeling the Impact of Cardiopulmonary Irradiation on Overall Survival in NRG Oncology Trial RTOG 0617. Clin Cancer Res 2020 Sep 01;26(17):4643-4650

Date

05/14/2020

Pubmed ID

32398326

Pubmed Central ID

PMC7877447

DOI

10.1158/1078-0432.CCR-19-2627

Scopus ID

2-s2.0-85086172648 (requires institutional sign-in at Scopus site)   46 Citations

Abstract

PURPOSE: To quantitatively predict the impact of cardiopulmonary dose on overall survival (OS) after radiotherapy for locally advanced non-small cell lung cancer.

EXPERIMENTAL DESIGN: We used the NRG Oncology/RTOG 0617 dataset. The model building procedure was preregistered on a public website. Patients were split between a training and a set-aside validation subset (N = 306/131). The 191 candidate variables covered disease, patient, treatment, and dose-volume characteristics from multiple cardiopulmonary substructures (atria, lung, pericardium, and ventricles), including the minimum dose to the hottest x% volume (Dx%[Gy]), mean dose of the hottest x% (MOHx%[Gy]), and minimum, mean (Mean[Gy]), and maximum dose. The model building was based on Cox regression and given 191 candidate variables; a Bonferroni-corrected P value threshold of 0.0003 was used to identify predictors. To reduce overreliance on the most highly correlated variables, stepwise multivariable analysis (MVA) was repeated on 1000 bootstrapped replicates. Multivariate sets selected in ≥10% of replicates were fit to the training subset and then averaged to generate a final model. In the validation subset, discrimination was assessed using Harrell c-index, and calibration was tested using risk group stratification.

RESULTS: Four MVA models were identified on bootstrap. The averaged model included atria D45%[Gy], lung Mean[Gy], pericardium MOH55%[Gy], and ventricles MOH5%[Gy]. This model had excellent performance predicting OS in the validation subset (c = 0.89).

CONCLUSIONS: The risk of death due to cardiopulmonary irradiation was accurately modeled, as demonstrated by predictions on the validation subset, and provides guidance on the delivery of safe thoracic radiotherapy.

Author List

Thor M, Deasy JO, Hu C, Gore E, Bar-Ad V, Robinson C, Wheatley M, Oh JH, Bogart J, Garces YI, Kavadi VS, Narayan S, Iyengar P, Witt JS, Welsh JW, Koprowski CD, Larner JM, Xiao Y, Bradley J

Author

Elizabeth M. Gore MD Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Carcinoma, Non-Small-Cell Lung
Chemoradiotherapy
Datasets as Topic
Dose-Response Relationship, Radiation
Female
Heart
Humans
Lung
Lung Neoplasms
Male
Middle Aged
Models, Biological
Organs at Risk
Radiotherapy Dosage
Radiotherapy Planning, Computer-Assisted
Risk Assessment
Survival Analysis
Treatment Outcome