title: Effect of p16 Status on the Quality-of-Life Experience During Chemoradiation for Locally Advanced Oropharyngeal Cancer: A Substudy of Randomized Trial Trans-Tasman Radiation Oncology Group (TROG) 02.02 (HeadSTART).
abstract: Human papillomavirus-associated oropharyngeal cancer (OPC) has a favorable prognosis. Current research de-escalates treatment, aiming to improve quality of life (QOL). Understanding the QOL experience with current standard treatment (chemoradiation therapy) provides context for emerging data. We report the impact of p16 status on QOL for patients with stage III or IV OPC undergoing chemoradiation therapy in an international phase 3 trial (TROG 02.02 [HeadSTART]).
  
  
  
  A subgroup analysis by p16 status was conducted in patients with OPC treated in a phase 3 randomized trial. The study subset with OPC and known p16 status was mainly from Australasia, Western Europe, and North America. Of 861 participants, 200 had OPC, known p16 status, and baseline QOL data; 82 were p16 negative and 118 were p16 positive. Radiation therapy (70 Gy over a period of 7 weeks) was given concurrently with 3 cycles of either cisplatin (100 mg/m2) or cisplatin (75 mg/m2) plus tirapazamine. QOL was measured with the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) questionnaire at baseline and 2, 6, 12, 23, and 38 months. Because no significant difference in QOL score was observed between arms, results by p16 status are reported with arms combined.
  
  
  
  The p16-positive patients were younger, had a better Eastern Cooperative Oncology Group performance status, and were less often current smokers. Our primary hypothesis that the change in FACT-H&N score from baseline to 6 months would be more favorable in the p16-positive cohort was not met (p16 positive, -6.3; p16 negative, -1.8; P=.14). The mean baseline FACT-H&N score was statistically and clinically significantly better in p16-positive patients (111 vs 102, P<.001); at 2 months, scores declined in both groups but more dramatically for p16-positive patients. By 12 months, p16-positive patients again had superior scores. A higher baseline FACT-H&N score and p16-positive status were independent predictors of overall survival.
  
  
  
  Patients with p16-positive OPC exhibited better baseline QOL but showed a more dramatic QOL drop with concurrent chemoradiation. Given the favorable prognosis of p16-positive OPC, efforts to reduce the QOL burden of treatment are warranted.
authors.affiliation: Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada. Electronic address: Jolie.ringash@rmp.uhn.on.ca.
authors.forename: Jolie
authors.initials: J
authors.lastname: Ringash
authors.affiliation: Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Fisher
authors.affiliation: Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Lester
authors.initials: L
authors.lastname: Peters
authors.affiliation: Moffitt Cancer Center, Tampa, Florida.
authors.forename: Andy
authors.initials: A
authors.lastname: Trotti
authors.affiliation: Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: O'Sullivan
authors.affiliation: Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: June
authors.initials: J
authors.lastname: Corry
authors.affiliation: Royal Brisbane & Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: Lizbeth
authors.initials: L
authors.lastname: Kenny
authors.forename: Sandra
authors.initials: S
authors.lastname: Nuyts
authors.affiliation: Calvary Mater Hospital and University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Chris
authors.initials: C
authors.lastname: Wratten
authors.affiliation: Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Danny
authors.initials: D
authors.lastname: Rischin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D059248:Chemoradiotherapy / Q000401:mortality* / Q000523:psychology* / Q000706:statistics & numerical data; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D006801:Humans; D038622:Internationality; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000401:mortality* / Q000523:psychology / Q000628:therapy*; D015995:Prevalence; D011788:Quality of Life / Q000523:psychology*; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16