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.

The Evolution of Care of Cancers of the Head and Neck Region: State of the Science in 2020

“…In the adjuvant setting, the reduction of RT dosing (to 30-36 Gy) with concurrent docetaxel resulted in comparable LRC and survival, with significant reductions of acute and late toxicities compared to reported standard therapy outcomes [70]. Similarly, sparing of RT to the primary site during adjuvant treatment found reassuring survival (100% OS, 98% 2-year recurrence-free survival [RFS]) and quality of life outcomes [71].…”

Human papillomavirus oropharynx carcinoma: Aggressive de‐escalation of adjuvant therapy

“…We recently reported the first prospective phase II trial of aggressive dose de-escalation of adjuvant therapy as a single institutional trial (MC1273) in an effort to rapidly investigate the efficacy of aggressive dose de-escalation. 16 Perhaps the most impactful finding from MC1273 and this comparison to standard of care adjuvant therapy is that intermediate risk patients (completely resected disease (R0), 1-4 nodes (pN1), without ENE) have a very low incidence of recurrence with both de-escalation and standard adjuvant therapy. The most important risk factors for progression were higher T stage, pN2 disease, and the presence of ENE.…”

Systematic review of postoperative therapy for resected squamous cell carcinoma of the head and neck: Executive summary of the American Radium Society appropriate use criteria

“…An additional five eligible studies were added, including four that were published after the cut-off date of 01/10/2019 [15][16][17][18] and one randomized trial that was not identified through the literature search. 19 Studies with primary oncologic endpoints are shown in Table S1 and included 11 systematic reviews, [20][21][22][23][24][25][26][27][28][29][30] 24 randomized trials with four long-term updates, 19,31-57 29 nonrandomized clinical trials, [15][16][17][18] and nine post hoc analyses of randomized trials. [83][84][85][86][87][88][89][90][91] The randomized trials are presented in Table 4.…”

“…16,18 A recent phase II study of 80 patients with HPV-mediated oropharynx SCC showed a 2-year PFS and LRC of 91.1% and 96.2%, respectively, with a postoperative regimen of 30 Gy given at 1.5 Gy twice daily with a simultaneous integrated boost of 1.8 Gy BID to areas of ENE (total dose 36 Gy) and concurrent weekly docetaxel 15 mg/m 2 . 16 The ECOG 3311 phase II clinical trial has completed followup and will determine the efficacy of reduced-dose PORT (50 Gy) compared to standard PORT (60 Gy) for patients with intermediate-risk cancers, negative margins, and ≤1 mm extranodal extension (NCT01898494). At the time of this publication, ECOG 3311 is published in abstract form 123 with a median follow-up of 31.8 months and suggests that 50 Gy may be sufficient for such patients.…”