Adaptive Chemoradiation Therapy for Head and Neck Cancer Based on Multiparametric MRI: Interim Results of a Prospective Randomized Trial

Abstract

Tumor regions characterized by hypoperfusion (HP) and restricted diffusion (RD) by multiparametric MRI have been reported to harbor aggressive disease. We report interim results of a randomized trial assessing boost to these subvolumes in poor-prognosis head and neck cancer (HNC). Patients with HPV-positive, T4/N3 oropharyngeal cancer (OPC); HPV (-), T3-4/N2-N3 OPC; EBV (-), T3-4/N3 nasopharyngeal cancer; locally-advanced, bulky, or unresectable T3-4 laryngeal or hypopharyngeal cancer; or stage III-IV oral cavity or paranasal sinus cancer who refuse or are unfit for surgery undergo MRI at baseline and 2-weeks midtreatment. Patients with stable HP or RD subvolumes are randomized to boost to these areas to 80 Gy versus standard dose (70 Gy). Cox regression and Kaplan-Meier were used to compare rates of failure. CTCAE v4, and EORTC QLQ-C30 and H&N35 are used to assess toxicity and quality of life (QOL). At time of analysis, 31 of the planned 80 patients have completed treatment: 15 randomized to boost and 16 to standard therapy. At a median follow-up of 13.3 months, there were 7 (22.6%) locoregional failures (LRFs) in all patients: 5 (31.2%) in the 70-Gy arm and 2 (13.3%) in the 80-Gy arm (HR 0.36, P = .218 ). There were 6 (19.4%) distant failures (DFs): 4 (25%) in the 70-Gy arm and 2 (13.3%) in the 80-Gy arm (HR 0.46, P = .365). Rates of HPV positivity were 56.2% and 66.7% in the 70-Gy and 80-Gy arms, respectively (P = .567). In HPV (+) patients, there were 2 (10.5%) LRFs: 2 (22.2%) in the 70-Gy arm and 0 in the 80-Gy arm (HR 0.19, P = .211). There were 3 (15.8%) DFs: 2 (22.2%) in the 70-Gy arm and 1 (10%) in the 80-Gy arm (HR 0.41, P = .463). In HPV (-) patients, there were 5 (41.7%) LRFs: 3 (42.8%) in the 70-Gy arm and 2 (40%) in the 80-Gy arm (HR 0.60, P = .586). There were 3 (15.8%) DFs: 2 (22.2%) in the 70-Gy arm and 1 (20%) in the 80-Gy arm (HR 0.59, P = .670). On univariate analysis, HPV positivity (HR 0.22, P = .073), as well as pretreatment hypermetabolic (HFDG) (HR 1.57, P = .079) and union of HP, RD, and HFDG (HR 2.15, P =.046) volumes were significant or marginally significant correlates of LRF. There were no significant differences in acute toxicity between arms. “Lost-Weight” QOL scores were worse in the boost arm at baseline and at 4 weeks posttreatment, although the difference at 4 weeks was of lesser magnitude than at baseline. At 72 weeks, “Cough” scores were worse in the boost arm at 2 versus 1.2 on a 4-point scale (P = .010). In this interim analysis of MRI-guided boost in poor-prognosis HNC, there were not yet significant differences in outcomes between arms. However, the HR for LRF was encouraging as it was consistent with the value used to calculate power for the study. Boost was associated with no increased acute toxicity and minimal difference in QOL.