Long-Term Follow-Up of E3311, an ECOG-ACRIN Cancer Research Group Phase II Trial of Transoral Surgery and Risk-Based Adjuvant Treatment in Human Papillomavirus–Initiated Oropharynx Cancer

B Barbara Burtness (Department of Internal Medicine and Yale Cancer Center, Yale School of Medicine, New Haven, CT) Y Yael Flamand (2Dana-Farber Cancer Institute, Department of Data Science, Boston, United States) H Harry Quon (Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, MD) G Gregory S. Weinstein (University of Pennsylvania, Philadelphia, PA) R Ranee Mehra J Joaquin J. Garcia S Seungwon Kim B Bert W. O'Malley E Enver Ozer (Department of Otolaryngology—Head and Neck Surgery, Ohio State University School of Medicine, Columbus, OH) C Chukwuemeka Ikpeazu (University of Miami/Sylvester Comprehensive Cancer Center, Miami, FL) W Wayne M. Koch (Department of Otolaryngology, Johns Hopkins University School of Medicine, Baltimore, MD) N Neil D. Gross R R. Bryan Bell (Providence Cancer Institute, Earle A. Chiles Research Institute, Portland, OR) M Mihir Patel (Tulane University, New Orleans, Louisiana, United States) M Miriam N. Lango (Department of Head and Neck Surgery, M. D. Anderson Cancer Center, Houston, TX) L Luc G. Morris (Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY) R Russell Smith D Daniel Karakla (Department of Otolaryngology—Head and Neck Surgery, Sentara Norfolk General Hospital, Norfolk, VA) J Jeremy D. Richmon F Floyd C. Holsinger (Department of Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, CA) R Robert L. Ferris (UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA)

Abstract

This phase II trial of transoral surgery (TOS) with deintensified postoperative management in human papillomavirus (HPV)–associated oropharynx cancer (OPC) enrolled patients with resectable cT1-2 stage III/IV American Joint Committee on Cancer (AJCC) seventh edition p16+ OPC without matted neck nodes. Those with clear margins, 0-1 + nodes (LN), and no extranodal extension (ENE) were observed (arm A); those with clear margins, 2-4 + LN, or ENE ≤1 mm were randomly assigned to 50 Gy (arm B) or 60 Gy (arm C); and those with involved margins, >4 + LN, or >1 mm ENE received weekly cisplatin and 60-66 Gy (arm D). Among 359 evaluable patients, the 54-month progression-free (PFS) and overall survival (OS) were 90.6% (90% CI, 87.2% to 93.1%) and 95.3% (93.0% to 96.9%), respectively. The 54-month PFS by arm was A 93.2% (79.6% to 97.8%; all four recurrences among N1 patients), B 94.9% (89.7% to 97.5%), C 90.2% (82.7% to 94.6%), and D 85.5% (77.5% to 90.8%). The 54-month OS by arm was A 97.1% (85.7% to 99.4%), B 97.9% (93.5% to 99.3%), C 95.1% (90.1% to 97.6%), and D 92.5% (86.9% to 95.7%). PFS or OS did not differ by primary site or smoking history. TOS and neck dissection with deintensified postoperative management results in outstanding 54-month PFS and OS. Among patients with favorable pathologic characteristics, those with N1 disease are at risk of late recurrence without radiation.

Article Details

Volume / Issue Vol. 43, Issue 23
Published August 10, 2025
Pages 2559-2565
ISSN 0732-183X
Publisher Lippincott Williams & Wilkins

Journal Info

Journal of Clinical Oncology

Lippincott Williams & Wilkins

ISSN: 0732-183X Health Sciences

Authors (21)

B

Barbara Burtness

Department of Internal Medicine and Yale Cancer Center, Yale School of Medicine, New Haven, CT

Y

Yael Flamand

2Dana-Farber Cancer Institute, Department of Data Science, Boston, United States

H

Harry Quon

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, MD

G

Gregory S. Weinstein

University of Pennsylvania, Philadelphia, PA

R

Ranee Mehra

J

Joaquin J. Garcia

S

Seungwon Kim

B

Bert W. O'Malley

E

Enver Ozer

Department of Otolaryngology—Head and Neck Surgery, Ohio State University School of Medicine, Columbus, OH

C

Chukwuemeka Ikpeazu

University of Miami/Sylvester Comprehensive Cancer Center, Miami, FL

W

Wayne M. Koch

Department of Otolaryngology, Johns Hopkins University School of Medicine, Baltimore, MD

N

Neil D. Gross

R

R. Bryan Bell

Providence Cancer Institute, Earle A. Chiles Research Institute, Portland, OR

M

Mihir Patel

Tulane University, New Orleans, Louisiana, United States

M

Miriam N. Lango

Department of Head and Neck Surgery, M. D. Anderson Cancer Center, Houston, TX

L

Luc G. Morris

Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY

R

Russell Smith

D

Daniel Karakla

Department of Otolaryngology—Head and Neck Surgery, Sentara Norfolk General Hospital, Norfolk, VA

J

Jeremy D. Richmon

F

Floyd C. Holsinger

Department of Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, CA

R

Robert L. Ferris

UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA