Proton Therapy for Locally Advanced Oropharyngeal Cancer: Initial Clinical Experience at the University of Washington

Abstract

Purpose: Proton therapy can potentially improve the therapeutic ratio over conventional radiation therapy for oropharyngeal squamous cell cancer (OPSCC) by decreasing acute and late toxicity. We report our early clinical experience with intensity-modulated proton therapy (IMPT).

Materials and methods: We retrospectively reviewed patients with OPSCC treated with IMPT at our center. Endpoints include local regional control (LRC), progression-free survival (PFS), overall survival (OS), tumor response, and toxicity outcomes. Toxicity was graded as per the Common Terminology Criteria for Adverse Events v4.03. Descriptive statistics and Kaplan-Meier method were used.

Results: We treated 46 patients from March 2015 to August 2017. Median age was 58 years, 93.5% were male, 67% were nonsmokers, 98% had stage III-IVB disease per the 7th edition of the AJCC [American Joint Committee on Cancer] Cancer Staging Manual, and 89% were p16 positive. Twenty-eight patients received definitive IMPT to total dose of 70 to 74.4 Gy(RBE), and 18 patients received postoperative IMPT to 60 to 66 Gy(RBE) following transoral robotic surgery (TORS). Sixty-four percent of patients received concurrent systemic therapy. There were no treatment interruptions or observed acute grade 4 or 5 toxicities. Eighteen patients had percutaneous endoscopic gastrostomy (PEG) tube placement; the majority (14) were placed prophylactically. The most common grade 3 acute toxicities were dermatitis (76%) and mucositis (72%). The most common late toxicity was grade 2 xerostomia (30%). At a median follow-up time of 19.2 months (interquartile range [IQR], 11.2-28.4), primary complete response was 100% and nodal complete response was 92%. One patient required a salvage neck dissection owing to an incomplete response at 4 months. There were no recorded local regional or marginal recurrences, PFS was 93.5%, and OS was 95.7%.

Conclusion: Our early results for IMPT in OPSCC are promising with no local regional or marginal recurrences and a favorable toxicity profile. Our data add to a body of evidence that supports the clinical use of IMPT. Randomized comparative trials are encouraged.

Keywords: HPV/p16 positive; proton beam therapy; squamous cell cancer; tongue base cancer; tonsil cancer.

Figure 1.

Kaplan-Meier curves (median follow-up, 19.2 months).

Figure 2.

IMPT plans for a bilateral neck irradiation case (top panel) and a unilateral radiation case (bottom panel). Contours = PTV70 (orange, color-wash), PTV63 (blue, color-wash), PTV54 (green, color-wash), right parotid (sky blue), left parotid (teal), submandibular gland (purple). Iso-dose lines = 70 Gy (red), 63 Gy (blue), 54 Gy (green), 30 Gy (black). A custom dental stent is seen. Abbreviations: IMPT, intensity-modulated proton therapy; PTV, planning target volume.