Higher Radiation Dose to the Immune Cells Correlates with Worse Tumor Control and Overall Survival in Patients with Stage III NSCLC: A Secondary Analysis of RTOG0617

• Type of Material: Article
• Authors: Jian-Yue Jin, Case Western Reserve University; Chen Hu, NRG Oncology Statistics and Data Management Center; Ying Xiao, University of Pennsylvania; Hong Zhang, University of Maryland; Rebecca Paulus, NRG Oncology Statistics and Data Management Center; Susannah G Ellsworth, University of Pittsburgh; Steven E Schild, Mayo Clinic Hospital; Jeffrey A Bogart, State University of New York Upstate Medical University; Michael C Dobelbower, University of Alabama Birmingham; Vivek S Kavadi, USON-Texas Oncology-Sugar Land; Samir Narayan, Michigan Cancer Research Consortium CCOP; Puneeth Iyengar, University of Texas Southwestern Medical School; Cliff Robinson, Washington University in St. Louis; Joel S Greenberger, University of Pittsburgh; Christopher Koprowski, Christiana Care Health Services, Inc.; Mitchell Machtay, Pennsylvania State University; Walter Curran, Emory University; Hak Choy, University of Texas Southwestern Medical School; Jeffrey Bradley, Emory University; Feng-Ming(Spring) Kong, Hong Kong Univ Shenzhen Hosp
• Language: English
• Date: 2021-12-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/cancers13246193
• Title of Journal or Parent Work: CANCERS
• Volume: 13
• Issue: 24
• Grant/Funding Information: This project was supported in parts by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), UG1CA189867 (NCORP), KQTD20180411185028798, R01CA142840 (PI: Kong) from the National Cancer Institute (NCI) and a grant from Eli Lilly.
• Keywords: Life Sciences & Biomedicine; radiotherapy; IMPACT; TREATMENT-RELATED LYMPHOPENIA; non-small-cell lung cancer; RADIOTHERAPY; radiation-induced immune toxicity; Oncology; CONCURRENT; survival; LUNG-CANCER; OUTCOMES; ESOPHAGEAL CANCER; Science & Technology; HEART
• Research Categories: Health Sciences, Oncology

Abstract

Background: We hypothesized that the Effective radiation Dose to the Immune Cells (EDIC) in circulating blood is a significant factor for the treatment outcome in patients with locally advanced non-small-cell lung cancer (NSCLC). Methods: This is a secondary study of a phase III trial, NRG/RTOG 0617, in patients with stage III NSCLC treated with radiation-based treatment. The EDIC was computed as equivalent uniform dose to the entire blood based on radiation doses to all blood-containing organs, with consideration of blood flow and fractionation effect. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and local progression-free survival (LPFS). The EDIC–survival relationship was analyzed with consideration of clinical significant factors. Results: A total of 456 patients were eligible. The median EDIC values were 5.6 Gy (range, 2.1–12.2 Gy) and 6.3 Gy (2.1–11.6 Gy) for the low-and high-dose groups, respectively. The EDIC was significantly associated with OS (hazard ratio [HR] = 1.12, p = 0.005) and LPFS (HR = 1.09, p = 0.02) but PFS (HR = 1.05, p = 0.17) after adjustment for tumor dose, gross tumor volume and other factors. OS decreased with an increasing EDIC in a non-linear pattern: the two-year OS decreased first with a slope of 8%/Gy when the EDIC < 6 Gy, remained relatively unchanged when the EDIC was 6–8 Gy, and followed by a further reduction with a slope of 12%/Gy when the EDIC > 8 Gy. Conclusions: The EDIC is a significant independent risk factor for poor OS and LPFS in RTOG 0617 patients with stage III NSCLC, suggesting that radiation dose to circulating immune cells is critical for tumor control. Organ at risk for the immune system should be considered during RT plan.