title: Phase 2 Trial of De-intensified Chemoradiation Therapy for Favorable-Risk Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.
abstract: OBJECTIVE
  To perform a prospective, multi-institutional, phase 2 study of a substantial decrease in concurrent chemoradiation therapy (CRT) intensity as primary treatment for favorable-risk, human papillomavirus-associated oropharyngeal squamous cell carcinoma.
  
  
  METHODS
  The major inclusion criteria were: (1) T0 to T3, N0 to N2c, M0; (2) human papillomavirus or p16 positive; and (3) minimal/remote smoking history. Treatment was limited to 60 Gy intensity modulated radiation therapy with concurrent weekly intravenous cisplatinum (30 mg/m(2)). The primary study endpoint was pathologic complete response (pCR) rate based on required biopsy of the primary site and dissection of pretreatment positive lymph node regions, regardless of radiographic response. Power computations were performed for the null hypothesis that the pCR rate is 87% and n=40, resulting in a type 1 error of 14.2%. Secondary endpoint measures included physician-reported toxicity (Common Toxicity Terminology for Adverse Events, CTCAE), patient-reported symptoms (PRO-CTCAE), and modified barium swallow studies.
  
  
  RESULTS
  The study population was 43 patients. The pCR rate was 86% (37 of 43). The incidence of CTCAE grade 3/4 toxicity and PRO-CTCAE severe/very severe symptoms was as follows: mucositis 34%/45%, general pain 5%/48%, nausea 18%/52%, vomiting 5%/34%, dysphagia 39%/55%, and xerostomia 2%/75%. Grade 3/4 hematologic toxicities were 11%. Thirty-nine percent of patients required a feeding tube for a median of 15 weeks (range, 5-22 weeks). There were no significant differences in modified barium swallow studies before and after CRT.
  
  
  CONCLUSIONS
  The pCR rate with decreased intensity of therapy with 60 Gy of IMRT and weekly low-dose cisplatinum is very high in favorable-risk oropharyngeal squamous cell carcinoma, with evidence of decreased toxicity compared with standard therapies. ClinicalTrials.gov ID: NCT01530997.
authors.affiliation: Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina. Electronic address: bchera@med.unc.edu.
authors.forename: Bhishamjit S
authors.initials: BS
authors.lastname: Chera
authors.affiliation: Department of Radiation Oncology, University of Florida School of Medicine, Gainesville, Florida; Shands Cancer Center, University of Florida School of Medicine, Gainesville, Florida.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Amdur
authors.affiliation: Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Joel
authors.initials: J
authors.lastname: Tepper
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Bahjat
authors.initials: B
authors.lastname: Qaqish
authors.affiliation: Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Green
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Aumer
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Division of Hematology Oncology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Neil
authors.initials: N
authors.lastname: Hayes
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Division of Hematology Oncology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Jared
authors.initials: J
authors.lastname: Weiss
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Division of Hematology Oncology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Juneko
authors.initials: J
authors.lastname: Grilley-Olson
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Adam
authors.initials: A
authors.lastname: Zanation
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Trevor
authors.initials: T
authors.lastname: Hackman
authors.affiliation: Department of Pathology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: William
authors.initials: W
authors.lastname: Funkhouser
authors.affiliation: Rex UNC Healthcare, Raleigh, North Carolina.
authors.forename: Nathan
authors.initials: N
authors.lastname: Sheets
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Mark
authors.initials: M
authors.lastname: Weissler
authors.affiliation: Department of Radiation Oncology, University of Florida School of Medicine, Gainesville, Florida; Shands Cancer Center, University of Florida School of Medicine, Gainesville, Florida.
authors.forename: William
authors.initials: W
authors.lastname: Mendenhall
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000473:pathology / Q000628:therapy* / Q000821:virology; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D006801:Humans; D008197:Lymph Node Excision; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D009959:Oropharyngeal Neoplasms / Q000737:chemistry / Q000473:pathology / Q000628:therapy* / Q000821:virology; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications*; D010349:Patient Compliance; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods*; D012907:Smoking / Q000453:epidemiology; D013280:Stomatitis / Q000209:etiology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D002945:Cisplatin