Randomized Phase II Study of DCE-MRI-Based Dose Escalation for Poor-Prognosis Head and Neck Cancer

PURPOSE/OBJECTIVE(S) Loco-regional failure accounts for the majority of failures in loco-regionally advanced head and neck cancer (HNC). We have previously shown that poor perfusion on DCE-MRI in HNC was associated with worse LRC and OS. A prospective randomized multi-center clinical trial was designed to evaluate the role of DCE-MRI based RT dose escalation in poor prognosis HNC. MATERIALS/METHODS Eligibility included 1) AJCC 8 stage III p16+ OPSCC or 2) T3-4 or N3 p16- oropharynx/non-oropharynx HNSCC planned for definitive chemoradiation, ECOG 0-2, with concurrent weekly cisplatin 40mg/m2 or carboplatin (AUC = 2) for cisplatin ineligibility. FDG-PET and DCE-MRI were acquired at baseline and at fraction 10. BV was derived from DCE-MRI 1cc low BV/ADC persistent tumor subvolume (GTVboost) at fraction 10 were randomized to total dose of 70Gy (arm A) or 80Gy (86Gy EQD2) total dose to GTVboost subvolume (arm B). The primary endpoint of DFS and secondary endpoints including LRC and OS were compared between treatment arms using stratified log-rank tests. Acute and late toxicities were compared with Chi-squared test. EORTC QLQ30/HN35 PROs, VFSS endpoints, HPV DNA kinetics were also analyzed. RESULTS All patients included in this analysis (N = 91) completed definitive therapy with min 12 mo and mean 32 mo follow-up. Treatment arms were balanced with respect to sex, p16+ status, smoking status, ECOG status, and chemotherapy. Mean age was higher in arm B (P = 0.01). Disease sites included 62% p16(+) AJCC 8 stage 3 oropharynx cancer. Randomization was stratified by GTVtotal (≥ 56cc) and GTV boost (> 10cc). Mean GTVtotal was 91cc in p16+ OPSCC and 67 cc in p16- OPSCC/non-OPSCC. Mean GTVboost was 15cc. 12 pts (7 p16+ OPSCC) were not randomized due to < 1cc persistent boostable tumor subvolume and were treated on an observation arm with LRC 83% and OS of 83% at 2 years. Treatment outcomes for randomized patients listed in Table 1. In a subgroup analysis of p16+ OPSCC patients, LRC was improved in the boost arm 93% vs 73% (2-sided P = 0.088). All local failures occurred within the 70Gy isodose line. Grade 3+ toxicities occurred in 53% (arm A) vs 64% (arm B) (P = 0.33). Feeding tube (FT) rate at 3 months was 15% (arm A) vs 27% (arm B) (P = .17) with no FT at 12 months post RT. There were 2 early deaths in arm B related to lingual arterial bleeding, 1 at 3 months and 1 at 12 mo post RT. CONCLUSION LRC improvement was numerically but not significantly improved with DCE-MRI directed boost for all randomized patients and p16+ oropharynx subgroup; DFS was not improved. Boost volume < 1cc was associated with good prognosis. Grade 3+ toxicities and 3 mo FT use were non-significantly higher in Arm B. Table 1. Outcomes according to treatment arm for randomized patients.