Left Anterior Descending Coronary Artery Radiation Dose Association With All-Cause Mortality in NRG Oncology Trial RTOG 0617

Elizabeth McKenzie; Samuel Zhang; Roja Zakariaee; Christian V Guthier; Behrooz Hakimian; Amin Mirhadi; Mitchell Kamrava; Sukhmani K Padda; John H Lewis; Andriana Nikolova; Raymond H Mak; Katelyn M Atkins

doi:10.1016/j.ijrobp.2022.11.033

Left Anterior Descending Coronary Artery Radiation Dose Association With All-Cause Mortality in NRG Oncology Trial RTOG 0617

Int J Radiat Oncol Biol Phys. 2023 Apr 1;115(5):1138-1143. doi: 10.1016/j.ijrobp.2022.11.033. Epub 2022 Nov 24.

Affiliations

¹ Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California.
² Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts.
³ Division of Medical Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
⁴ Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, California.
⁵ Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address: katelyn.atkins@cshs.org.

PMID: 36436615
DOI: 10.1016/j.ijrobp.2022.11.033

Abstract

Purpose: A left anterior descending (LAD) coronary artery volume (V) receiving 15 Gy (V15 Gy) ≥10% has been recently observed to be an independent risk factor of major adverse cardiac events and all-cause mortality in patients with locally advanced non-small cell lung cancer treated with radiation therapy. However, this dose constraint has not been validated in independent or prospective data sets.

Methods and materials: The NRG Oncology/Radiation Therapy Oncology Group (RTOG) 0617 data set from the National Clinical Trials Network was used. The LAD coronary artery was manually contoured. Multivariable Cox regression was performed, adjusting for known prognostic factors. Kaplan-Meier estimates of overall survival (OS) were calculated. For assessment of baseline cardiovascular risk, only age, sex, and smoking history were available.

Results: There were 449 patients with LAD dose-volume data and clinical outcomes available after 10 patients were excluded owing to unreliable LAD dose statistics. The median age was 64 years. The median LAD V15 Gy was 38% (interquartile range, 15%-62%), including 94 patients (21%) with LAD V15 Gy <10% and 355 (79%) with LAD V15 Gy ≥10%. Adjusting for prognostic factors, LAD V15 Gy ≥10% versus <10% was associated with an increased risk of all-cause mortality (hazard ratio [HR], 1.43; 95% confidence interval, 1.02-1.99; P = .037), whereas a mean heart dose ≥10 Gy versus <10 Gy was not (adjusted HR, 1.12; 95% confidence interval, 0.88-1.43; P = .36). The median OS for patients with LAD V15 Gy ≥10% versus <10% was 20.2 versus 25.1 months, respectively, with 2-year OS estimates of 47% versus 67% (P = .004), respectively.

Conclusions: In a reanalysis of RTOG 0617, LAD V15 Gy ≥10% was associated with an increased risk of all-cause mortality. These findings underscore the need for improved cardiac risk stratification and aggressive risk mitigation strategies, including implementation of cardiac substructure dose constraints in national guidelines and clinical trials.

Trial registration: ClinicalTrials.gov NCT00533949.

Publication types

Clinical Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Non-Small-Cell Lung* / radiotherapy
Coronary Vessels
Humans
Lung Neoplasms* / radiotherapy
Middle Aged
Prospective Studies
Radiation Dosage
Radiotherapy Dosage

Associated data

ClinicalTrials.gov/NCT00533949