241 - A Phase II Randomized Study of Proton vs. Intensity-Modulated Radiation Therapy in the Treatment of Unilateral Head and Neck Cancer
Presenter(s)
N. Y. Lee1, N. S. Kalman2, D. J. Ma3, S. C. Lester3, Z. Zhang4, D. Gelblum1, Y. Yu1, L. Chen5, S. McBride1, N. Riaz1, B. A. Mueller1, A. Shamseddine6, K. Zakeri1, J. J. Kang7, C. J. Tsai8, Y. Wu6, A. Ho9, R. J. Wong10, P. B. Romesser1, C. A. Barker5, and E. C. Dee1; 1Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 2Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 3Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 4Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, 5Memorial Sloan Kettering Cancer Center, New York, NY, 6Memorial Sloan-Kettering Cancer Center, New York, NY, 7Yale University, New Haven, CT, 8Princess Margaret Cancer Centre, Toronto, ON, Canada, 9Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
Purpose/Objective(s): To report the results of a multi-center Phase II randomized trial comparing proton therapy and IMRT in the treatment of unilateral head/neck or skin cancer.
Materials/Methods: Eligible patients were those with salivary gland tumors, skin cancer, melanoma, and tonsil cancer, where post-operative unilateral radiation is the standard. The high-risk region received 60–66Gy, while the lower-risk region received 50–54Gy. Chemotherapy was given when indicated. The primary endpoint was to determine whether proton therapy reduces acute grade = 2 mucositis (CTCAE v4.03) versus IMRT, assessed from the start of radiation until three months post-treatment. Secondary endpoints: other acute and late toxicities, local and regional control, distant metastasis-free, progression-free survival (PFS), overall survival (OS), and patient-reported outcomes (PRO). Median follow-up was calculated using the reverse Kaplan-Meier method. An intention-to-treat (ITT) analysis was performed for the primary endpoint.
Results: Between 3/17 - 9/24, 108 patients were enrolled, 98 analyzable. Of these, 60 had parotid/salivary gland tumors, 27 had skin cancers, and 11 had tonsil cancers. Patients were randomized to receive proton (n=53) or IMRT (n=45); as treated proton (n=52) and IMRT (n=46). The most common histologies were squamous cell carcinoma, mucoepidermoid carcinoma, and adenoid cystic carcinoma. 5 patients also received platinum-based chemotherapy. Median follow-up for all patients was 26.3 months. There was a significantly lower rate of acute grade = 2 mucositis in the proton group (7.5%) versus IMRT group (22.2%), p = 0.0376 (ITT analysis). Similar results were observed in the as-treated analysis: 7.7% (proton) vs. 21.7%(IMRT), p = 0.045. Proton therapy compared to IMRT also had lower incidence of acute grade = 2 dysgeusia (7.7% vs. 33%, p = 0.002). There were no significant differences between proton vs. IMRT for local control, regional control, distant metastasis-free survival, acute dermatitis, acute dysphagia, or late toxicities. The 3-year PFS, OS rates were 92.3% (95% CI: 77.5%–97.5%), 97.4% (95% CI: 83.2%–99.6%) for proton versus 94.1% (95% CI: 77.9%–98.5%) and 97.6% (95% CI: 83.9%–99.7%) for IMRT, respectively. PRO will be presented at the meeting.
Conclusion: This multi-center Phase II randomized trial demonstrates that proton therapy significantly reduces the incidence of acute = 2 mucositis and dysgeusia versus IMRT in patients receiving unilateral radiation for head/neck or skin cancer. Tumor control and survival outcomes were comparable between the two arms. Skin toxicity was not significantly increased with proton therapy. Based on these findings, proton therapy should be considered for patients undergoing unilateral head/neck radiation.