title: E1308: Phase II Trial of Induction Chemotherapy Followed by Reduced-Dose Radiation and Weekly Cetuximab in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx- ECOG-ACRIN Cancer Research Group.
abstract: Purpose Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is treatment-responsive. Definitive chemoradiation results in high cure rates but causes long-term toxicity and may represent overtreatment of some patients. This phase II trial evaluated whether complete clinical response (cCR) to induction chemotherapy (IC) could select patients with HPV-associated OPSCC for reduced radiation dose as a means of sparing late sequelae. Methods Patients with HPV16 and/or p16-positive, stage III-IV OPSCC received three cycles of IC with cisplatin, paclitaxel, and cetuximab. Patients with primary-site cCR to IC received intensity-modulated radiation therapy (IMRT) 54 Gy with weekly cetuximab; those with less than cCR to IC at the primary site or nodes received 69.3 Gy and cetuximab to those regions. The primary end point was 2-year progression-free survival. Results Of the 90 patients enrolled, 80 were evaluable. Their median age was 57 years (range, 35 to 73 years), with the majority having stage T1-3N0-N2b OPSCC and a history of ≤ 10 pack-years of cigarette smoking. Three cycles of IC were delivered to 77 of the 80 patients. Fifty-six patients (70%) achieved a primary-site cCR to IC and 51 patients continued to cetuximab with IMRT 54 Gy. After median follow-up of 35.4 months, 2-year progression-free survival and overall survival rates were 80% and 94%, respectively, for patients with primary-site cCR treated with 54 Gy of radiation (n = 51); 96% and 96%, respectively, for patients with < T4, < N2c, and ≤ 10 pack-year smoking history who were treated with ≤ 54 Gy of radiation (n = 27). At 12 months, significantly fewer patients treated with a radiation dose ≤ 54 Gy had difficulty swallowing solids (40% v 89%; P = .011) or had impaired nutrition (10% v 44%; P = .025). Conclusion For IC responders, reduced-dose IMRT with concurrent cetuximab is worthy of further study in favorable-risk patients with HPV-associated OPSCC. Radiation dose reduction resulted in significantly improved swallowing and nutritional status.
authors.affiliation: Shanthi Marur and William H. Westra, Johns Hopkins University, Baltimore, MD; Shuli Li, Dana Farber Cancer Institute, Boston, MA; Anthony J. Cmelak, Jill Gilbert, and Barbara A. Murphy, Vanderbilt University, Nashville, TN; Maura L. Gillison and Weiqiang J. Zhao, Ohio State University, Columbus, OH; Robert L. Ferris and Julie E. Bauman, University of Pittsburgh, Pittsburgh, PA; Lynne I. Wagner, Wake Forest School of Medicine, Winston-Salem, NC; David R. Trevarthen, Colorado Cancer Research Program, Denver, CO; Jahagirdar Balkrishna, University of Minnesota, St Paul, MN; Nishant Agrawal, University of Chicago Medicine, Chicago, IL; A. Dimitrios Colevas, Stanford University, Stanford, CA; Christine H. Chung, Moffitt Cancer Center, Tampa, FL; and Barbara Burtness, Yale University, New Haven, CT.
authors.forename: Shanthi
authors.initials: S
authors.lastname: Marur
authors.affiliation: Shanthi Marur and William H. Westra, Johns Hopkins University, Baltimore, MD; Shuli Li, Dana Farber Cancer Institute, Boston, MA; Anthony J. Cmelak, Jill Gilbert, and Barbara A. Murphy, Vanderbilt University, Nashville, TN; Maura L. Gillison and Weiqiang J. Zhao, Ohio State University, Columbus, OH; Robert L. Ferris and Julie E. Bauman, University of Pittsburgh, Pittsburgh, PA; Lynne I. Wagner, Wake Forest School of Medicine, Winston-Salem, NC; David R. Trevarthen, Colorado Cancer Research Program, Denver, CO; Jahagirdar Balkrishna, University of Minnesota, St Paul, MN; Nishant Agrawal, University of Chicago Medicine, Chicago, IL; A. Dimitrios Colevas, Stanford University, Stanford, CA; Christine H. Chung, Moffitt Cancer Center, Tampa, FL; and Barbara Burtness, Yale University, New Haven, CT.
authors.forename: Shuli
authors.initials: S
authors.lastname: Li
authors.affiliation: Shanthi Marur and William H. Westra, Johns Hopkins University, Baltimore, MD; Shuli Li, Dana Farber Cancer Institute, Boston, MA; Anthony J. Cmelak, Jill Gilbert, and Barbara A. Murphy, Vanderbilt University, Nashville, TN; Maura L. Gillison and Weiqiang J. Zhao, Ohio State University, Columbus, OH; Robert L. Ferris and Julie E. Bauman, University of Pittsburgh, Pittsburgh, PA; Lynne I. Wagner, Wake Forest School of Medicine, Winston-Salem, NC; David R. Trevarthen, Colorado Cancer Research Program, Denver, CO; Jahagirdar Balkrishna, University of Minnesota, St Paul, MN; Nishant Agrawal, University of Chicago Medicine, Chicago, IL; A. Dimitrios Colevas, Stanford University, Stanford, CA; Christine H. Chung, Moffitt Cancer Center, Tampa, FL; and Barbara Burtness, Yale University, New Haven, CT.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Cmelak
authors.affiliation: Shanthi Marur and William H. Westra, Johns Hopkins University, Baltimore, MD; Shuli Li, Dana Farber Cancer Institute, Boston, MA; Anthony J. Cmelak, Jill Gilbert, and Barbara A. Murphy, Vanderbilt University, Nashville, TN; Maura L. Gillison and Weiqiang J. Zhao, Ohio State University, Columbus, OH; Robert L. Ferris and Julie E. Bauman, University of Pittsburgh, Pittsburgh, PA; Lynne I. Wagner, Wake Forest School of Medicine, Winston-Salem, NC; David R. Trevarthen, Colorado Cancer Research Program, Denver, CO; Jahagirdar Balkrishna, University of Minnesota, St Paul, MN; Nishant Agrawal, University of Chicago Medicine, Chicago, IL; A. Dimitrios Colevas, Stanford University, Stanford, CA; Christine H. Chung, Moffitt Cancer Center, Tampa, FL; and Barbara Burtness, Yale University, New Haven, CT.
authors.forename: Maura L
authors.initials: ML
authors.lastname: Gillison
authors.affiliation: Shanthi Marur and William H. Westra, Johns Hopkins University, Baltimore, MD; Shuli Li, Dana Farber Cancer Institute, Boston, MA; Anthony J. Cmelak, Jill Gilbert, and Barbara A. Murphy, Vanderbilt University, Nashville, TN; Maura L. Gillison and Weiqiang J. Zhao, Ohio State University, Columbus, OH; Robert L. Ferris and Julie E. Bauman, University of Pittsburgh, Pittsburgh, PA; Lynne I. Wagner, Wake Forest School of Medicine, Winston-Salem, NC; David R. Trevarthen, Colorado Cancer Research Program, Denver, CO; Jahagirdar Balkrishna, University of Minnesota, St Paul, MN; Nishant Agrawal, University of Chicago Medicine, Chicago, IL; A. Dimitrios Colevas, Stanford University, Stanford, CA; Christine H. Chung, Moffitt Cancer Center, Tampa, FL; and Barbara Burtness, Yale University, New Haven, CT.
authors.forename: Weiqiang J
authors.initials: WJ
authors.lastname: Zhao
authors.affiliation: Shanthi Marur and William H. Westra, Johns Hopkins University, Baltimore, MD; Shuli Li, Dana Farber Cancer Institute, Boston, MA; Anthony J. Cmelak, Jill Gilbert, and Barbara A. Murphy, Vanderbilt University, Nashville, TN; Maura L. Gillison and Weiqiang J. Zhao, Ohio State University, Columbus, OH; Robert L. Ferris and Julie E. Bauman, University of Pittsburgh, Pittsburgh, PA; Lynne I. Wagner, Wake Forest School of Medicine, Winston-Salem, NC; David R. Trevarthen, Colorado Cancer Research Program, Denver, CO; Jahagirdar Balkrishna, University of Minnesota, St Paul, MN; Nishant Agrawal, University of Chicago Medicine, Chicago, IL; A. Dimitrios Colevas, Stanford University, Stanford, CA; Christine H. Chung, Moffitt Cancer Center, Tampa, FL; and Barbara Burtness, Yale University, New Haven, CT.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ferris
authors.affiliation: Shanthi Marur and William H. Westra, Johns Hopkins University, Baltimore, MD; Shuli Li, Dana Farber Cancer Institute, Boston, MA; Anthony J. Cmelak, Jill Gilbert, and Barbara A. Murphy, Vanderbilt University, Nashville, TN; Maura L. Gillison and Weiqiang J. Zhao, Ohio State University, Columbus, OH; Robert L. Ferris and Julie E. Bauman, University of Pittsburgh, Pittsburgh, PA; Lynne I. Wagner, Wake Forest School of Medicine, Winston-Salem, NC; David R. Trevarthen, Colorado Cancer Research Program, Denver, CO; Jahagirdar Balkrishna, University of Minnesota, St Paul, MN; Nishant Agrawal, University of Chicago Medicine, Chicago, IL; A. Dimitrios Colevas, Stanford University, Stanford, CA; Christine H. Chung, Moffitt Cancer Center, Tampa, FL; and Barbara Burtness, Yale University, New Haven, CT.
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.affiliation: Shanthi Marur and William H. Westra, Johns Hopkins University, Baltimore, MD; Shuli Li, Dana Farber Cancer Institute, Boston, MA; Anthony J. Cmelak, Jill Gilbert, and Barbara A. Murphy, Vanderbilt University, Nashville, TN; Maura L. Gillison and Weiqiang J. Zhao, Ohio State University, Columbus, OH; Robert L. Ferris and Julie E. Bauman, University of Pittsburgh, Pittsburgh, PA; Lynne I. Wagner, Wake Forest School of Medicine, Winston-Salem, NC; David R. Trevarthen, Colorado Cancer Research Program, Denver, CO; Jahagirdar Balkrishna, University of Minnesota, St Paul, MN; Nishant Agrawal, University of Chicago Medicine, Chicago, IL; A. Dimitrios Colevas, Stanford University, Stanford, CA; Christine H. Chung, Moffitt Cancer Center, Tampa, FL; and Barbara Burtness, Yale University, New Haven, CT.
authors.forename: Jill
authors.initials: J
authors.lastname: Gilbert
authors.affiliation: Shanthi Marur and William H. Westra, Johns Hopkins University, Baltimore, MD; Shuli Li, Dana Farber Cancer Institute, Boston, MA; Anthony J. Cmelak, Jill Gilbert, and Barbara A. Murphy, Vanderbilt University, Nashville, TN; Maura L. Gillison and Weiqiang J. Zhao, Ohio State University, Columbus, OH; Robert L. Ferris and Julie E. Bauman, University of Pittsburgh, Pittsburgh, PA; Lynne I. Wagner, Wake Forest School of Medicine, Winston-Salem, NC; David R. Trevarthen, Colorado Cancer Research Program, Denver, CO; Jahagirdar Balkrishna, University of Minnesota, St Paul, MN; Nishant Agrawal, University of Chicago Medicine, Chicago, IL; A. Dimitrios Colevas, Stanford University, Stanford, CA; Christine H. Chung, Moffitt Cancer Center, Tampa, FL; and Barbara Burtness, Yale University, New Haven, CT.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Bauman
authors.affiliation: Shanthi Marur and William H. Westra, Johns Hopkins University, Baltimore, MD; Shuli Li, Dana Farber Cancer Institute, Boston, MA; Anthony J. Cmelak, Jill Gilbert, and Barbara A. Murphy, Vanderbilt University, Nashville, TN; Maura L. Gillison and Weiqiang J. Zhao, Ohio State University, Columbus, OH; Robert L. Ferris and Julie E. Bauman, University of Pittsburgh, Pittsburgh, PA; Lynne I. Wagner, Wake Forest School of Medicine, Winston-Salem, NC; David R. Trevarthen, Colorado Cancer Research Program, Denver, CO; Jahagirdar Balkrishna, University of Minnesota, St Paul, MN; Nishant Agrawal, University of Chicago Medicine, Chicago, IL; A. Dimitrios Colevas, Stanford University, Stanford, CA; Christine H. Chung, Moffitt Cancer Center, Tampa, FL; and Barbara Burtness, Yale University, New Haven, CT.
authors.forename: Lynne I
authors.initials: LI
authors.lastname: Wagner
authors.affiliation: Shanthi Marur and William H. Westra, Johns Hopkins University, Baltimore, MD; Shuli Li, Dana Farber Cancer Institute, Boston, MA; Anthony J. Cmelak, Jill Gilbert, and Barbara A. Murphy, Vanderbilt University, Nashville, TN; Maura L. Gillison and Weiqiang J. Zhao, Ohio State University, Columbus, OH; Robert L. Ferris and Julie E. Bauman, University of Pittsburgh, Pittsburgh, PA; Lynne I. Wagner, Wake Forest School of Medicine, Winston-Salem, NC; David R. Trevarthen, Colorado Cancer Research Program, Denver, CO; Jahagirdar Balkrishna, University of Minnesota, St Paul, MN; Nishant Agrawal, University of Chicago Medicine, Chicago, IL; A. Dimitrios Colevas, Stanford University, Stanford, CA; Christine H. Chung, Moffitt Cancer Center, Tampa, FL; and Barbara Burtness, Yale University, New Haven, CT.
authors.forename: David R
authors.initials: DR
authors.lastname: Trevarthen
authors.affiliation: Shanthi Marur and William H. Westra, Johns Hopkins University, Baltimore, MD; Shuli Li, Dana Farber Cancer Institute, Boston, MA; Anthony J. Cmelak, Jill Gilbert, and Barbara A. Murphy, Vanderbilt University, Nashville, TN; Maura L. Gillison and Weiqiang J. Zhao, Ohio State University, Columbus, OH; Robert L. Ferris and Julie E. Bauman, University of Pittsburgh, Pittsburgh, PA; Lynne I. Wagner, Wake Forest School of Medicine, Winston-Salem, NC; David R. Trevarthen, Colorado Cancer Research Program, Denver, CO; Jahagirdar Balkrishna, University of Minnesota, St Paul, MN; Nishant Agrawal, University of Chicago Medicine, Chicago, IL; A. Dimitrios Colevas, Stanford University, Stanford, CA; Christine H. Chung, Moffitt Cancer Center, Tampa, FL; and Barbara Burtness, Yale University, New Haven, CT.
authors.forename: Jahagirdar
authors.initials: J
authors.lastname: Balkrishna
authors.affiliation: Shanthi Marur and William H. Westra, Johns Hopkins University, Baltimore, MD; Shuli Li, Dana Farber Cancer Institute, Boston, MA; Anthony J. Cmelak, Jill Gilbert, and Barbara A. Murphy, Vanderbilt University, Nashville, TN; Maura L. Gillison and Weiqiang J. Zhao, Ohio State University, Columbus, OH; Robert L. Ferris and Julie E. Bauman, University of Pittsburgh, Pittsburgh, PA; Lynne I. Wagner, Wake Forest School of Medicine, Winston-Salem, NC; David R. Trevarthen, Colorado Cancer Research Program, Denver, CO; Jahagirdar Balkrishna, University of Minnesota, St Paul, MN; Nishant Agrawal, University of Chicago Medicine, Chicago, IL; A. Dimitrios Colevas, Stanford University, Stanford, CA; Christine H. Chung, Moffitt Cancer Center, Tampa, FL; and Barbara Burtness, Yale University, New Haven, CT.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Murphy
authors.affiliation: Shanthi Marur and William H. Westra, Johns Hopkins University, Baltimore, MD; Shuli Li, Dana Farber Cancer Institute, Boston, MA; Anthony J. Cmelak, Jill Gilbert, and Barbara A. Murphy, Vanderbilt University, Nashville, TN; Maura L. Gillison and Weiqiang J. Zhao, Ohio State University, Columbus, OH; Robert L. Ferris and Julie E. Bauman, University of Pittsburgh, Pittsburgh, PA; Lynne I. Wagner, Wake Forest School of Medicine, Winston-Salem, NC; David R. Trevarthen, Colorado Cancer Research Program, Denver, CO; Jahagirdar Balkrishna, University of Minnesota, St Paul, MN; Nishant Agrawal, University of Chicago Medicine, Chicago, IL; A. Dimitrios Colevas, Stanford University, Stanford, CA; Christine H. Chung, Moffitt Cancer Center, Tampa, FL; and Barbara Burtness, Yale University, New Haven, CT.
authors.forename: Nishant
authors.initials: N
authors.lastname: Agrawal
authors.affiliation: Shanthi Marur and William H. Westra, Johns Hopkins University, Baltimore, MD; Shuli Li, Dana Farber Cancer Institute, Boston, MA; Anthony J. Cmelak, Jill Gilbert, and Barbara A. Murphy, Vanderbilt University, Nashville, TN; Maura L. Gillison and Weiqiang J. Zhao, Ohio State University, Columbus, OH; Robert L. Ferris and Julie E. Bauman, University of Pittsburgh, Pittsburgh, PA; Lynne I. Wagner, Wake Forest School of Medicine, Winston-Salem, NC; David R. Trevarthen, Colorado Cancer Research Program, Denver, CO; Jahagirdar Balkrishna, University of Minnesota, St Paul, MN; Nishant Agrawal, University of Chicago Medicine, Chicago, IL; A. Dimitrios Colevas, Stanford University, Stanford, CA; Christine H. Chung, Moffitt Cancer Center, Tampa, FL; and Barbara Burtness, Yale University, New Haven, CT.
authors.forename: A Dimitrios
authors.initials: AD
authors.lastname: Colevas
authors.affiliation: Shanthi Marur and William H. Westra, Johns Hopkins University, Baltimore, MD; Shuli Li, Dana Farber Cancer Institute, Boston, MA; Anthony J. Cmelak, Jill Gilbert, and Barbara A. Murphy, Vanderbilt University, Nashville, TN; Maura L. Gillison and Weiqiang J. Zhao, Ohio State University, Columbus, OH; Robert L. Ferris and Julie E. Bauman, University of Pittsburgh, Pittsburgh, PA; Lynne I. Wagner, Wake Forest School of Medicine, Winston-Salem, NC; David R. Trevarthen, Colorado Cancer Research Program, Denver, CO; Jahagirdar Balkrishna, University of Minnesota, St Paul, MN; Nishant Agrawal, University of Chicago Medicine, Chicago, IL; A. Dimitrios Colevas, Stanford University, Stanford, CA; Christine H. Chung, Moffitt Cancer Center, Tampa, FL; and Barbara Burtness, Yale University, New Haven, CT.
authors.forename: Christine H
authors.initials: CH
authors.lastname: Chung
authors.affiliation: Shanthi Marur and William H. Westra, Johns Hopkins University, Baltimore, MD; Shuli Li, Dana Farber Cancer Institute, Boston, MA; Anthony J. Cmelak, Jill Gilbert, and Barbara A. Murphy, Vanderbilt University, Nashville, TN; Maura L. Gillison and Weiqiang J. Zhao, Ohio State University, Columbus, OH; Robert L. Ferris and Julie E. Bauman, University of Pittsburgh, Pittsburgh, PA; Lynne I. Wagner, Wake Forest School of Medicine, Winston-Salem, NC; David R. Trevarthen, Colorado Cancer Research Program, Denver, CO; Jahagirdar Balkrishna, University of Minnesota, St Paul, MN; Nishant Agrawal, University of Chicago Medicine, Chicago, IL; A. Dimitrios Colevas, Stanford University, Stanford, CA; Christine H. Chung, Moffitt Cancer Center, Tampa, FL; and Barbara Burtness, Yale University, New Haven, CT.
authors.forename: Barbara
authors.initials: B
authors.lastname: Burtness
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000628:therapy*; D000068818:Cetuximab / Q000008:administration & dosage; D059248:Chemoradiotherapy / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005076:Exanthema / Q000209:etiology; D005260:Female; D052162:Human papillomavirus 16 / Q000502:physiology; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology; D009959:Oropharyngeal Neoplasms / Q000150:complications / Q000628:therapy*; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology; D011879:Radiotherapy Dosage; D012074:Remission Induction
chemical_list: D000068818:Cetuximab