Results of intensifying radiation treatment in advanced laryngeal, hypopharyngeal (LH) and oropharyngeal cancers (OPC) using metabolic dose escalation strategies: (INTELHOPE).

PURPOSE: Concurrent cisplatin and radiation for high-risk laryngopharyngeal cancers have high failure rates. This Phase II randomized study compares standard radiation dosing with FDG-PET guided escalated dosing in p16-negative oropharyngeal (OP) and locally advanced laryngopharyngeal (LP) cancers. MATERIALS AND METHODS: weekly). The study was designed as a hybrid/seamless Phase 2 study to first exclude excess grade 4 toxicities, followed by an efficacy comparison. Efficacy outcomes included 2-year locoregional recurrence, disease-free survival (DFS), and overall survival (OS). RESULTS: From 2016 to 2021, 102 patients were treated (42 LP, 60 OP), with 51 in each treatment arm. Median age was 59, with 72.5% having T3/4 primaries and 58.8% N2-3 nodal stage. Both arms received a median of 5 cisplatin cycles. Safety assessment showed only a single patient with Grade 4 toxicity, and the trial was allowed to complete accrual. Acute grade 3 toxicities showed no significant differences between the two arms, with mucositis (35.3% in both arms), dermatitis, dysphagia, and feeding tube requirement being similar. With a median follow-up of 40 months, the 2-year locoregional control rate was 85.4%, with no significant difference between the arms (88.6% standard vs 82.2% escalated, p = 0.57). The 2-year DFS and OS rates also showed no significant differences (59.7%, 64.7%, 54.8% for DFS, 67.3%, 68.2%, 66.6% for OS, p = 0.65 and p = 0.99, respectively). CONCLUSION: While feasible, FDG-PET-based dose escalation did not improve local control, DFS, or OS in our patient population.