Reduced-Dose Radiation Therapy for HPV-Associated Oropharyngeal Carcinoma (NRG Oncology HN002).

PURPOSE: Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC). Whether reduced-dose radiation produces disease control and QOL equivalent to standard chemoradiation is not proven. PATIENTS AND METHODS: In this randomized, phase II trial, patients with p16-positive, T1-T2 N1-N2b M0, or T3 N0-N2b M0 OPSCC (7th edition staging) with ≤ 10 pack-years of smoking received 60 Gy of intensity-modulated radiation therapy (IMRT) over 6 weeks with concurrent weekly cisplatin (C) or 60 Gy IMRT over 5 weeks. To be considered for a phase III study, an arm had to achieve a 2-year progression-free survival (PFS) rate superior to a historical control rate of 85% and a 1-year mean composite score ≥ 60 on the MD Anderson Dysphagia Inventory (MDADI). RESULTS: Three hundred six patients were randomly assigned and eligible. Two-year PFS for IMRT + C was 90.5% rejecting the null hypothesis of 2-year PFS ≤ 85% (P = .04). For IMRT, 2-year PFS was 87.6% (P = .23). One-year MDADI mean scores were 85.30 and 81.76 for IMRT + C and IMRT, respectively. Two-year overall survival rates were 96.7% for IMRT + C and 97.3% for IMRT. Acute adverse events (AEs) were defined as those occurring within 180 days from the end of treatment. There were more grade 3-4 acute AEs for IMRT + C (79.6% v 52.4%; P < .001). Rates of grade 3-4 late AEs were 21.3% and 18.1% (P = .56). CONCLUSION: The IMRT + C arm met both prespecified end points justifying advancement to a phase III study. Higher rates of grade ≥ 3 acute AEs were reported in the IMRT + C arm.

Impact of Smoking on Outcomes of HPV-related Oropharyngeal Cancer Treated with Primary Radiation or Surgery.

PURPOSE: Tobacco exposure is known to affect the biological behavior of human papilloma virus (HPV)-positive oropharyngeal carcinoma (OPC) with intermediate outcomes relative to tumors that are HPV associated with no smoking exposure and smoking-related HPV-negative tumors. We aim to evaluate the impact of smoking on the outcomes of patients with HPV-associated locally advanced OPC when stratified by treatment modality. METHODS AND MATERIALS: A retrospective chart review was undertaken for 352 patients with known p16-overexpressing locally advanced OPC who were managed with curative-intent therapy from 2006 to 2015. The impact of smoking status on overall survival (OS) and recurrence-free survival were compared using the Kaplan-Meier method. RESULTS: Of the 352 patients, 67.6% (n = 238) were managed with primary chemoradiation therapy (CRT) and 32.4% (n = 114) with primary surgery ± adjuvant therapy. The median smoking pack-year was 15. Twenty-seven percent of patients were active smokers at the time of presentation, with 40.3% identifying as former smokers and 32.7% having never smoked. Median follow-up for surviving patients was 4.2 years. Current smokers had a significantly worse relapse-free survival and OS compared with never and former smokers (P = .03 and P = .0001, respectively), with outcomes significantly worsening with increasing smoking exposure. The 5-year OS for more than 10, 20, and 30 pack-year smoking history was 73.2%, 64.7%, and 59.1%, respectively. Current smokers managed with CRT had a 5-year OS of 64.2% compared with former and never smokers (93.1% and 78.2%, respectively). For current smokers managed primarily by surgery the 5-year OS was 57.6% compared with former and never smokers (69.6% and 73.5%, respectively). CONCLUSIONS: Current smokers and those with higher smoking exposure had poorer outcomes irrespective of their primary modality of treatment. Although not the specific focus of the study, definitive CRT appeared to at least be equivalent to surgery with respect to disease outcomes for patients with HPV-associated oropharyngeal cancer, regardless of smoking status.