P1.18-16 Is Tumor Shrinking During Chemoradiation for LA-NSCLC a Biomarker for Outcome?

Abstract

Adaptation of dose distribution to tumor reduction during radiotherapy is an innovative approach. Even if the advantage for lung toxicity is intuitive, some concerns exist about the risk of tumor recurrences in the area of target reduction. Recent data reported no increased local relapse and low pulmonary toxicity so, waiting for the ongoing phase III trial investigating this issue (RTOG 1106-ACRIN 6697), the aims of this study is to compare the long term outcome for patients treated or not with the adaptive approach. LA- NSCLC patients enrolled in a prospective study, where they were treated with concomitant chemoradiation and underwent to replanning in case of tumor shrinkage, have been compared with patients without tumor shrinkage treated with the concurrent treatment in the same period. Toxicity was evaluated with the RTOG/EORTC scale. The differences between groups were compared by Fisher’s exact test (two tail) or χ2 when appropriate. The “time to event” curve was calculated with the Kaplan-Meier method, and log-rank test was used to perform between-group comparisons. Patients in the adaptive group (AG) were more likely to receive a total radiation dose equal or higher than 59.4Gy (58% vs 27%, p=0.003). No statistical differences were reported in local recurrences, even if in non-adaptive (NAG) and AG were 48% and 31%, respectively. Distant recurrences were documented in the 55% and 46% of patients. Acute ≥G2 esophageal and pulmonary toxicity was similar, but G3 acute lung toxicity was lower than a third in AG (2% vs 7%) and G3 chronic lung damage reduced by half (7.5% vs 4%). Median follow up for alive patients was 57.8 months. Median OS were 26,6 and 30,5 months and PFS 7,6 and 8.3 months between NAG and AG, respectively. Survival was affected by the rate of shrinking with better result for patients reducing 25-50% of the initial volume (median not reached) in comparison with no-reduction or until 25% patients (median 25 months) (p=0.016). An apparent contra-intuitive result was the lower survival in case of reduction >50% (median 23 months). PFS reflects the same observation with median values of 7,5 and 7,4 months for patients shrinking 0-25% and >50%, respectively and 13,8 months for patients reporting a tumor reduction in the range of 25-50%. Waiting for randomized phase III results, adaptive approach confirms its role in escalating dose and reducing toxicity without compromise outcome. The worse outcome in patients with >50% reduction could be explained by high proliferating aggressive tumor behavior. The value of the shrinking rate as a biomarker for survival deserves to be investigated in future trials at the aim to intensify treatment in selected population.