Randomized Phase II study of Physiologic MRI-directed Adaptive Radiation Boost in Poor Prognosis Head and Neck Cancer
Mené sur 81 patients atteints d'un cancer de la tête et du cou de mauvais pronostic, cet essai randomisé multicentrique de phase II évalue l'efficacité, du point de vue de la survie sans maladie, d'une augmentation de la dose de radiothérapie (80 Gy au lieu de 70)
Purpose: We conducted a randomized Phase II multi-center clinical trial to test the hypothesis that physiologic MRI based radiation therapy (RT) dose escalation would improve the outcome of patients with poor prognosis head and neck cancer (HNC). Methods: MRI was acquired at baseline and at RT fraction 10 to create low blood volume (BV)/apparent diffusion coefficient (ADC) maps for RT boost subvolume definition in gross tumor volume (GTV). Patients were randomized to receive 70 Gy (standard RT) or 80 Gy to the boost subvolume (RT boost) with concurrent weekly platinum. The primary endpoint was disease free survival (DFS) with significance defined at a 1-sided 0.1 level, and secondary endpoints included loco-regional failure (LRF), overall survival (OS), comparison of adverse events and patient reported outcomes (PRO)s. Results: Among 81 randomized patients, neither the primary endpoint of DFS (hazard ratio (HR)= 0.849, p=0.31) nor OS (HR =1.19, p=0.66) were significantly improved in the RT Boost arm. However, the incidence of LRF was significantly improved with the addition of the RT boost (HR= 0.43, p=0.047). Two-year estimates (90% CI) of the cumulative incidence of LRF were 40% (27-53%) in the standard RT arm and 18% (10-31%) in the RT boost arm. Two-year estimates (90% CI) for DFS were 48% (34-60%) in the standard RT arm and 57% (43-69%) in the RT boost arm. There were no significant differences in toxicity or longitudinal differences seen in EORTC QLQ30/HN35 subscales between treatment arms in linear mixed effects models. Conclusion: Physiologic MRI based RT boost decreased LRF without a significant increase in grade 3+ toxicity or longitudinal PRO differences, but did not significantly improve DFS or OS. Additional improvements in systemic therapy are likely necessary to realize improvements in DFS and OS.