Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus-Associated Oropharynx Squamous Cell Carcinoma

Abstract

Purpose: The purpose of this study was to determine if dose de-escalation from 60 to 66 Gy to 30 to 36 Gy of adjuvant radiotherapy (RT) for selected patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma could maintain historical rates for disease control while reducing toxicity and preserving swallow function and quality of life (QOL).

Patients and methods: MC1273 was a single-arm phase II trial testing an aggressive course of RT de-escalation after surgery. Eligibility criteria included patients with p16-positive oropharyngeal squamous cell carcinoma, smoking history of 10 pack-years or less, and negative margins. Cohort A (intermediate risk) received 30 Gy delivered in 1.5-Gy fractions twice per day over 2 weeks along with 15 mg/m² docetaxel once per week. Cohort B included patients with extranodal extension who received the same treatment plus a simultaneous integrated boost to nodal levels with extranodal extension to 36 Gy in 1.8-Gy fractions twice per day. The primary end point was locoregional tumor control at 2 years. Secondary end points included 2-year progression-free survival, overall survival, toxicity, swallow function, and patient-reported QOL.

Results: Accrual was from September 2013 to June 2016 (N = 80; cohort A, n = 37; cohort B, n = 43). Median follow-up was 36 months, with a minimum follow-up of 25 months. The 2-year locoregional tumor control rate was 96.2%, with progression-free survival of 91.1% and overall survival of 98.7%. Rates of grade 3 or worse toxicity at pre-RT and 1 and 2 years post-RT were 2.5%, 0%, and 0%. Swallowing function improved slightly between pre-RT and 12 months post-RT, with one patient requiring temporary feeding tube placement.

Conclusion: Aggressive RT de-escalation resulted in locoregional tumor control rates comparable to historical controls, low toxicity, and little decrement in swallowing function or QOL.

Trial registration: ClinicalTrials.gov NCT01932697.

FIG 1.

Protocol schema. OPSCC, oropharyngeal squamous cell carcinoma; QOL, quality of life; RT, radiotherapy.

FIG 2.

(A) Locoregional control, (B) distant metastasis–free survival, (C) progression-free survival, and (D) overall survival for patients in MC1273. Red line indicates cohort A (extranodal extension [ENE] negative), green line indicates cohort B (ENE positive), and blue line indicates total cohort. Crosses indicate censored observations. Error bars represent 95% CIs for given time points.

FIG 3.

Patient reported outcome for quality of life as measured by (A) Functional Assessment of Cancer Therapy–Head and Neck Cancer (FACT-HN; version 4), (B) European Organisation for Research and Treatment of Cancer QOL Questionnaire for Head and Neck Cancer Module 35 (EORTC-QLQ HN35), (C) three-level version of the EuroQol five-dimensional instrument (EQ-5D-3L), and (D) University of Michigan Xerostomia QOL Scale (XeQoLS). Error bars represent 95% CIs for given time points.

FIG A1.

Representative isodose lines for (A) patient in cohort A (well-lateralized tonsil cancer) and (B) patient in cohort B (tongue base cancer). PTV3000 in cyan, and PTV3600 (for cohort B) in pink; parotids in yellow.