Session Item

Chemoradiotherapy is the standard of care for treating inoperable locally-advanced non-small cell lung cancer (LA-NSCLC). We aim to investigate new models of survival following treatment for LA-NSCLC incorporating the effects of chemotherapy. 

In the baseline tumour control probability (TCP) model, chemotherapy effects had been included via a difference in maximum overall survival (OS_Max_by Treatment) between radiotherapy and any form of chemoradiotherapy, and a radiosensitisation factor for concurrent chemoradiotherapy (cCRT) (RS_cCRT). In our improved model, we separated tumour repopulation parameters (λ, repopulation rate ; T_k, repopulation onset time) by treatment-type to test for differences in repopulation between radiotherapy alone, sequential chemoradiotherapy (sCRT), and cCRT. Model fitting was done using maximum-likelihood estimation, comparing fits using the Akaike Information Criteria and likelihood ratio test. LA-NSCLC dose-response curves for radiotherapy, sCRT, and cCRT were plotted for a fixed treatment duration of 40 days. 

Population data were collated from prospective trials and institutional series with >20 cases published between 2000 – 2016. The data comprised 4866 NSCLC patients receiving radiotherapy (1192 patients), sCRT (1792 patients), or cCRT (1882 patients), with doses varying from 1.26Gy/Fx - 3.00Gy/Fx over 16 - 60 days. In the optimised model, accelerated tumour repopulation began at 16 days for radiotherapy (95% CI: 16 - 26), 25 days for sCRT (95% CI: 16 - 34), and 34 days (95% CI: 16 - 39) for cCRT, and respectively accounted for 0.37Gy (95% CI: 0.20 - 0.49), 0.34Gy (95% CI: 0.24 - 0.58) and 0.92Gy (95% CI: 0.54 - 1.43) radiation dose lost per day of treatment protraction. 

This analysis suggests that cCRT leads to delayed but substantially more rapid accelerated tumour repopulation late in radiotherapy treatments of LA-NSCLC. Consequently, overall treatment time should be carefully considered when designing such cCRT treatments. This analysis partly explains the poorer overall survival seen for protracted dose-escalation schedules such as 74 Gy in 7.5 weeks in the Phase III randomised clinical trial - RTOG-0617. Based on the modelling results, dose-escalation of LA-NSCLC cCRT should be limited to 6 weeks to prevent accelerated tumour repopulation.