De-Intensified (DI) IMPT vs. IMRT(Chemo) for HPV-Associated Oropharynx Cancer (HPV-OPC): Initial Quality of Life (QOL) Results From a Prospective, Multi-Institutional Trial

Abstract

To compare patient-reported QOL/symptoms between DI IMPT(chemo) and IMRT(chemo) for HPV-OPC.LCCC1612 is a multi-institutional phase II trial of DI RT(chemo) using 60 Gy/30 fx in 6 wk with weekly concurrent cisplatin, 30 mg/m2 for HPV-OPC. Eligible patients (AJCC 8 ed, T0-3, N0-2, M0, p16+, regardless of smoking history) received IMPT at one participating center. T0-2, N1 (single node, < 3 cm) received RT alone. ≥10 pk-y smokers underwent p53 mutation analysis, and only those with wild-type p53 received DI RT(chemo). The IMPT cohort (initial 25 patients with 1y f/u) were matched (2:1) to a randomly selected IMRT cohort using the following: T-class, N-class, and uni- vs. bi-lateral neck RT. QOL/symptoms assessed by EORTC QLQ30, HN35, and EAT-10 were compared at baseline, endRT, 3, 6, and 12 mo. Differences of ≥10 in QLQ30 and HN35 (range, 0-100) and ≥3 in EAT-10 (range, 0-40) were considered clinically relevant.The IMRT cohort consisted of 46 matches (only 1:1 available for 4 IMPT pts). There were no significant differences between non-matched variables (RT dose, chemo, age, gender, smoking history, or primary site). 1-yr PFS was comparable (IMPT, 92%; IMRT, 93%). Only 2/25 (8%) IMPT and 18/46 (39%) IMRT patients required short-term feeding tubes. Both cohorts reported excellent QOL/symptom scores with worse mean scores at end of RT, which returned to baseline by 3 mo for most patients with some exceptions such as dry mouth, sticky saliva, and sensory changes. IMPT resulted in higher (better) mean scores for QLQ30 Global QOL at endRT (55.8/45.8), and role function at endRT (60.1/43.6) and 3 mo (91.7/80.4). Several HN35 mean symptom scores were lower (better) after IMPT including fatigue at endRT (49.3/60.4) and 3 mo (17.2/31.6); appetite loss at 3 mo (16.7/34.8), 6 mo (13.9/27.8), and 12 mo (5.8/16.7); impaired social eating at 3 mo (14.0/30.2) and 6 mo (11.1/22.8); coughing at endRT (29.0/43.2) and 6 mo (15.3/25.6); and feeding tube use at endRT (4.3/34.1) and 3 mo (4.5/15.6). IMPT patients reported less dysphagia with lower mean EAT-10 scores at 3 mo (5.8/10.0) and 6 mo (4.5/8). Narcotic use was higher with IMPT than IMRT at end RT and 3 mo without a difference in pain scores. There was no difference in financial difficulties despite the added costs with proton therapy.DI IMPT(chemo) and IMRT(chemo) resulted in favorable patient-reported QOL/symptoms with most patients reporting return to baseline QOL/symptom scores by 3 mo with some exceptions. DI IMPT(chemo) resulted in very low rate of feeding tube use and less swallowing/eating-related symptoms compared with IMRT(chemo) using independently validated instruments. Additional data and long-term follow-up will be needed to validate these findings and confirm the long-term safety/efficacy of DI RT(chemo).