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J Thorac Oncol. 2019 Feb;14(2):298-303. doi: 10.1016/j.jtho.2018.09.021. Epub 2018 Oct 4.

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.

Author information

1
Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona. Electronic address: sschild@mayo.edu.
2
Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina.
3
Duke Cancer Institute, Durham, North Carolina.
4
University of Chicago, Department of Medicine and Comprehensive Cancer Center, Chicago, Illinois.
5
Winship Cancer Institute of Emory University, Atlanta, Georgia.
6
Washington University, Radiation Oncology, St. Louis, Missouri.
7
University of California, Medical Oncology, Davis, California.
8
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.
9
Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina; Alliance Statistics and Data Center, Durham, North Carolina.

Abstract

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.

KEYWORDS:

Adverse events; Combined modality therapy; Doses; Field design; Non-small cell lung cancer; Toxicity

PMID:
30292852
PMCID:
PMC6348032
[Available on 2020-02-01]
DOI:
10.1016/j.jtho.2018.09.021

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