Clinical Outcomes after Re-irradiation in Recurrent Head and Neck Cancers treated with Intensity Modulated Proton and Photon Therapies

Abstract

Loco-regional recurrence remains a challenge regardless of primary treatment modality in head and neck cancer (HNC). Re-irradiation (RR) is a potential option for local control in previously irradiated patients. We report our institutional experience comparing clinical outcomes in recurrent HNC treated curatively with intensity modulated proton (IMPT) and photon (IMRT) therapy. This is an IRB approved retrospective analysis of prospectively collected outcomes for loco-regionally recurrent or second primary HNC. All patients were treated with radiation to head and neck region at least once previously. Local recurrence (LR), overall survival (OS), disease-free survival (DFS) and acute toxicities occurring within 3 months of RR were analyzed. Statistical tools included Chi-square, Wilcoxon Rank Sum, Fischer Exact, and Unequal Variance T-Tests. We evaluated 44 patients with loco-regional recurrence treated with RR to the head and neck between April 2013 and December 2018. It included 26 patients (59%) treated with IMPT and 18 (41%) with IMRT. Median follow-up was 1.7 years in all patients with at least one year follow-up in both arms. All patients were treated with curative intent. Overall median RR dose was 63 Gy (IMPT=61.5 Gy, IMRT=69.6 Gy) whereas the overall median total dose was same in both arms, 130 Gy. IMPT used conventional fractionation in 17 (65%), SBRT in 8 (31%), and hyperfractionation in 1 (4%) patients. IMRT utilized hyperfractionation in 14 (78%), conventional in 3 (17%) and 1 (6%) SBRT. IMPT was found to have significantly lower rates of physician-reported overall grade 3 (G3) acute toxicities 31% vs 73% in IMRT (p=0.01). This included dysphagia (4% vs 39%, p=0.01), mucositis (8% vs 39%, p=0.001), and dermatitis (12% vs 33%, p=0.03). Commonly treated sites were 52% mucosal (n=23), 14% neck/nodal sites (n=6), and 32% both mucosal and neck sites (n=14), and 2% (n=1) cutaneous only treatment. IMPT patients with mucosal site RR had lower chances of G3 dysphagia (5% vs 40%, p=0.01) and lower G3 mucositis (9% vs 47%, p=0.02); and those with neck nodal/neck RR had lower chances of G3 dermatitis (18% vs 56%, p=0.16). OS at 2-year was 69% with IMPT compared to 58% with IMRT cohort (p=0.26). 2-year LR was 9.5% with IMPT vs 6.5% with IMRT (p=0.66). 2-year DFS was 54% with IMRT compared to 46% with IMPT, respectively (p=0.94). RR is a safe and effective treatment option in the management of recurrent HNC. IMPT RR was found to carry reduced rates of grade 3 toxicity compared to IMRT. IMPT appears to confer a similar rate of OS, DFS and LR compared to IMRT, although these results warrant further exploration in the form of larger prospective studies with longer follow up.