Long-Term Results of Induction Chemotherapy Followed by 50 Gy Radiation Therapy Alone for Low-Risk HPV-Positive Oropharynx Cancer

Abstract

The standard of care for non-operative management of human papillomavirus-related oropharynx cancer (HPV-OPC) consists of concurrent cisplatin chemotherapy with radiotherapy (RT) to a total dose of 70 Gy. While the oncologic outcomes of this treatment approach have been excellent, there are considerable acute and late toxicities. Here, we report the 5-year survival and toxicity outcomes of 2 prospective HPV-OPC response-adapted de-escalation trials, in which low-risk (LR) patients were treated with dose-reduced RT to 50 Gy, without concurrent chemotherapy. Patients with LR HPV-OPC and ≥50% response to induction by RECIST 1.1 treated per 2 prospective phase II trials as well as on a prospective cohort registry were included for analysis. Patients were considered LR if the following criteria were met: T1-T3, N0-N2b (AJCC 7th edition), and ≤20 pack-year smoking history. Patients were treated with induction chemo- or chemoimmunotherapy followed by RT alone to 50 Gy. In the early trial iteration, patients underwent a planned neck dissection following RT to confirm pathologic clearance of lymph nodes. Clinicodemographic characteristics were summarized using descriptive statistics. Overall survival (OS), progression-free survival (PFS), and local control (LC) were estimated using the Kaplan-Meier method. From January 2015 through March 2020, 73 patients met LR criteria, of which, 54 (74%) had ≥50% response by RECIST and were de-escalated to RT alone. The median follow-up was 58 (range 10-92) months. The median age was 58 (range 38-84) years, and 92.6% were male. 57.4% of patients never smoked, and 42.6% smoked no more than 20 pack-years. The primary site was tonsil for 53.7% and base of tongue for 46.3%. 24.1% were T1, 53.7% were T2, and 22.2% were T3. 1.9% were N0, 5.6% were N1, 11.1% were N2a, and 81.5% were N2b. The 5-year OS, PFS, and LC were 96.3% (95% CI 91.3%-100%), 96.2% (95% CI 91.2%-100%), and 98.1% (95% CI 94.6%-100%), respectively. 2 (3.7%) patients required a G-tube during RT and none at 1 year following completion of RT. Of the 30 patients with a planned neck dissection, 2 (6.7%) had residual pathologic nodal disease. With a median follow-up of 5 years, this analysis demonstrates excellent long-term local control, survival, and swallowing function among patients with low-risk HPV+ oropharynx cancer treated with induction systemic therapy followed by radiotherapy to 50 Gy without concurrent chemotherapy, including a large proportion of patients with N2b disease. Chemo-selection provides a means of identifying a favorable cohort of HPV+ oropharynx cancer patients who can safely receive RT dose de-escalation. Further work is needed to identify this population by other means, including radiographic and genomic factors.