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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) (p¼0.016). 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%. Conclusion: 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.

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