PMID- 30292852 OWN - NLM STAT- MEDLINE DCOM- 20200408 LR - 20200408 IS - 1556-1380 (Electronic) IS - 1556-0864 (Print) IS - 1556-0864 (Linking) VI - 14 IP - 2 DP - 2019 Feb TI - Toxicity Related to Radiotherapy Dose and Targeting Strategy: A Pooled Analysis of Cooperative Group Trials of Combined Modality Therapy for Locally Advanced Non-Small Cell Lung Cancer. PG - 298-303 LID - S1556-0864(18)33173-3 [pii] LID - 10.1016/j.jtho.2018.09.021 [doi] AB - OBJECTIVE: Concurrent chemoradiotherapy (CRT) was the standard treatment for locally advanced NSCLC (LA-NSCLC). This study was performed to examine thoracic radiotherapy (TRT) parameters and their impact on adverse events (AEs). METHODS: We collected individual patient data from 3600 patients with LA-NSCLC who participated in 16 cooperative group trials of concurrent CRT. The TRT parameters examined included field design strategy (elective nodal irradiation [ENI] versus involved-field [IF] TRT [IF-TRT]) and TRT dose (60 Gy versus >/=60 Gy). The primary end point of this analysis was the occurrence of AEs. ORs for AEs were calculated with univariable and multivariable logistic models. RESULTS: TRT doses ranged from 60 to 74 Gy. ENI was not associated with more grade 3 or higher AEs than IF-TRT was (multivariable OR = 0.77, 95% confidence interval [CI]: 0.543-1.102, p = 0.1545). Doses higher than 60 Gy (high-dose TRT) were associated with significantly more grade 3 or higher AEs (multivariable OR = 1.82, 95% CI: 1.501-2.203, p < 0.0001). In contrast, ENI was associated with significantly more grade 4 or higher AEs (multivariable OR = 1.33, 95% CI: 1.035-1.709, p = 0.0258). Doses higher than 60 Gy were also associated with more grade 4 or higher AEs (multivariate OR = 1.42, 95% CI: 1.191-1.700, p = 0.0001). Grade 5 AEs plus treatment-related deaths were more frequent with higher-dose TRT (p = 0.0012) but not ENI (p = 0.099). CONCLUSIONS: For patients with LA-NSCLC treated with concurrent CRT, IF-TRT was not associated with the overall risk of grade 3 or higher AEs but was associated with significantly fewer grade 4 or higher AEs than ENI TRT. This is likely the result of irradiation of a lesser amount of adjacent critical normal tissue. Higher TRT doses were associated significantly with grade 3 or higher and grade 4 or higher AEs. On the basis of these findings and our prior report on survival, CRT using IF-TRT and 60 Gy (conventionally fractionated) were associated with more favorable patient survival and less toxicity than was the use of ENI or higher radiotherapy doses. CI - Copyright (c) 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. FAU - Schild, Steven E AU - Schild SE AD - Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona. Electronic address: sschild@mayo.edu. FAU - Fan, Wen AU - Fan W AD - Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina. FAU - Stinchcombe, Thomas E AU - Stinchcombe TE AD - Duke Cancer Institute, Durham, North Carolina. FAU - Vokes, Everett E AU - Vokes EE AD - University of Chicago, Department of Medicine and Comprehensive Cancer Center, Chicago, Illinois. FAU - Ramalingam, Suresh S AU - Ramalingam SS AD - Winship Cancer Institute of Emory University, Atlanta, Georgia. FAU - Bradley, Jeffrey D AU - Bradley JD AD - Washington University, Radiation Oncology, St. Louis, Missouri. FAU - Kelly, Karen AU - Kelly K AD - University of California, Medical Oncology, Davis, California. FAU - Pang, Herbert H AU - Pang HH AD - Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina; School of Public Health, HKU Li Ka Shing Faculty of Medicine, Hong Kong Special Autonomous Region, People's Republic of China. FAU - Wang, Xiaofei AU - Wang X AD - Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina; Alliance Statistics and Data Center, Durham, North Carolina. LA - eng GR - R21 AG042894/AG/NIA NIH HHS/United States GR - U10 CA180846/CA/NCI NIH HHS/United States GR - P30 CA014236/CA/NCI NIH HHS/United States GR - P01 CA142538/CA/NCI NIH HHS/United States GR - U10 CA180888/CA/NCI NIH HHS/United States GR - U10 CA180819/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20181004 PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 SB - IM MH - Carcinoma, Non-Small-Cell Lung/*therapy MH - Chemoradiotherapy/*adverse effects MH - Clinical Trials as Topic MH - Female MH - Humans MH - Lung Neoplasms/*therapy MH - Male MH - Middle Aged MH - Radiation Injuries/*etiology MH - Radiotherapy Dosage MH - Radiotherapy Planning, Computer-Assisted PMC - PMC6348032 MID - NIHMS1508844 OTO - NOTNLM OT - Adverse events OT - Combined modality therapy OT - Doses OT - Field design OT - Non-small cell lung cancer OT - Toxicity EDAT- 2018/10/08 06:00 MHDA- 2020/04/09 06:00 PMCR- 2020/02/01 CRDT- 2018/10/08 06:00 PHST- 2018/08/15 00:00 [received] PHST- 2018/09/10 00:00 [revised] PHST- 2018/09/24 00:00 [accepted] PHST- 2018/10/08 06:00 [pubmed] PHST- 2020/04/09 06:00 [medline] PHST- 2018/10/08 06:00 [entrez] PHST- 2020/02/01 00:00 [pmc-release] AID - S1556-0864(18)33173-3 [pii] AID - 10.1016/j.jtho.2018.09.021 [doi] PST - ppublish SO - J Thorac Oncol. 2019 Feb;14(2):298-303. doi: 10.1016/j.jtho.2018.09.021. Epub 2018 Oct 4.