Exploring Radiotherapy Targeting Strategy and Dose: A Pooled Analysis of Cooperative Group Trials of Combined Modality Therapy for Stage III NSCLC

Introduction: Concurrent chemoradiotherapy (CRT) is standard therapy for locally advanced NSCLC (LA-NSCLC) patients. This study was performed to examine thoracic radiotherapy (TRT) parameters and their impact on patient survival.

Methods: We collected individual patient data from 3600 LA-NSCLC patients participating in 16 cooperative group trials of concurrent CRT. The primary TRT parameters examined included field design strategy (elective nodal irradiation [ENI] compared to involved-field TRT (IF-TRT)), total dose, and biologically effective dose (BED). Hazard ratios (HRs) for overall survival were calculated with univariable and multivariable Cox models.

Results: TRT doses ranged from 60 Gy to 74 Gy with most treatments administered once-daily. ENI was associated with poorer survival than IF-TRT (univariable HR = 1.37, 95% confidence interval [CI]: 1.24-1.51, p < 0.0001; multivariable HR = 1.31, 95% CI: 1.08-1.59, p = 0.002). The median survival times of the IF and ENI patients were 24 months and 16 months, respectively. Patients were divided into three dose groups: low total dose (60 Gy), medium total dose (>60 Gy to 66 Gy), and high total dose (>66 Gy to 74 Gy). With reference to the low-dose group, the multivariable HRs were 1.08 for the medium-dose group (95% CI: 0.93-1.25) and 1.12 for the high-dose group (95% CI: 0.97-1.30).The univariate p = 0.054 and multivariable p = 0.17. BED was grouped as follows: low (<55.5 Gy₁₀), medium (55.5 Gy₁₀), or high (>55.5 Gy₁₀). With reference to the low-BED group, the HR was 1.00 (95% CI: 0.85-1.18) for the medium-BED group and 1.10 (95% CI: 0.93-1.31) for the high-BED group. The univariable p = 0.076 and multivariable p = 0.16.

Conclusions: For LA-NSCLC patients treated with concurrent CRT, IF-TRT was associated with significantly better survival than ENI-TRT. TRT total and BED dose levels were not significantly associated with patient survival. Future progress will require research focusing on better systemic therapy and TRT.