BACKGROUND: HPV/p16-positive head and neck cancers (HNSCC) show superior response to radiotherapy, compared with virus-negative tumours. Tumour hypoxia induces radioresistance and the randomised DAHANCA 5 trial found that the hypoxic cell radiosensitiser nimorazole significantly improved the outcome in HNSCC. Using p16-status as a retrospective stratification parameter, we aimed to assess the influence of p16-expression on the response to nimorazole in HNSCC. MATERIALS AND METHODS: Pre-treatment tumour blocks were available from 331 of the 414 patients in the DAHANCA 5 trial and evaluated by immunohistochemistry for p16-expression. The influence of p16-expression on outcome was analysed as a function of treatment group (nimorazole/placebo) 5 years after radiotherapy. RESULTS: Overall, patients treated with nimorazole had significantly better loco-regional control than did those given placebo: hazard ratio (HR) 0.70 [95% CI 0.52-0.93]. Positive expression of p16 also significantly improved outcome after radiotherapy (0.41 [0.28-0.61]). In the subgroup of patients with p16-negative tumours, loco-regional failure was more frequent in the placebo group than in the nimorazole group (0.69 [0.50-0.95]). However, in the p16-positive group, patients treated with nimorazole had a loco-regional control rate similar to patients given placebo (0.93 [0.45-1.91]). CONCLUSIONS: HPV/p16-expression significantly improved outcome after radiotherapy in HNSCC. Hypoxic modification improved outcome in HPV/p16-negative tumours but was of no significant benefit in HPV/p16-positive tumours, suggesting that hypoxic radioresistance may not be clinically relevant in these tumours. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
RCT Entities:
BACKGROUND: HPV/p16-positive head and neck cancers (HNSCC) show superior response to radiotherapy, compared with virus-negative tumours. Tumour hypoxia induces radioresistance and the randomised DAHANCA 5 trial found that the hypoxic cell radiosensitiser nimorazole significantly improved the outcome in HNSCC. Using p16-status as a retrospective stratification parameter, we aimed to assess the influence of p16-expression on the response to nimorazole in HNSCC. MATERIALS AND METHODS: Pre-treatment tumour blocks were available from 331 of the 414 patients in the DAHANCA 5 trial and evaluated by immunohistochemistry for p16-expression. The influence of p16-expression on outcome was analysed as a function of treatment group (nimorazole/placebo) 5 years after radiotherapy. RESULTS: Overall, patients treated with nimorazole had significantly better loco-regional control than did those given placebo: hazard ratio (HR) 0.70 [95% CI 0.52-0.93]. Positive expression of p16 also significantly improved outcome after radiotherapy (0.41 [0.28-0.61]). In the subgroup of patients with p16-negative tumours, loco-regional failure was more frequent in the placebo group than in the nimorazole group (0.69 [0.50-0.95]). However, in the p16-positive group, patients treated with nimorazole had a loco-regional control rate similar to patients given placebo (0.93 [0.45-1.91]). CONCLUSIONS: HPV/p16-expression significantly improved outcome after radiotherapy in HNSCC. Hypoxic modification improved outcome in HPV/p16-negative tumours but was of no significant benefit in HPV/p16-positive tumours, suggesting that hypoxic radioresistance may not be clinically relevant in these tumours. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
Authors: Fei-Fei Liu; Paul Okunieff; Eric J Bernhard; Helen B Stone; Stephen Yoo; C Norman Coleman; Bhadrasain Vikram; Martin Brown; John Buatti; Chandan Guha Journal: Clin Cancer Res Date: 2013-09-16 Impact factor: 12.531
Authors: C Cleary; J E Leeman; D S Higginson; N Katabi; E Sherman; L Morris; S McBride; N Lee; N Riaz Journal: Clin Oncol (R Coll Radiol) Date: 2016-04-01 Impact factor: 4.126
Authors: Quynh-Thu Le; Richard Fisher; Kelly S Oliner; Richard J Young; Hongbin Cao; Christina Kong; Edward Graves; Rodney J Hicks; Grant A McArthur; Lester Peters; Brian O'Sullivan; Amato Giaccia; Danny Rischin Journal: Clin Cancer Res Date: 2012-03-01 Impact factor: 12.531
Authors: Stephen Mf Jamieson; Peter Tsai; Maria K Kondratyev; Pratha Budhani; Arthur Liu; Neil N Senzer; E Gabriela Chiorean; Shadia I Jalal; John J Nemunaitis; Dennis Kee; Avik Shome; Way W Wong; Dan Li; Nooriyah Poonawala-Lohani; Purvi M Kakadia; Nicholas S Knowlton; Courtney Rh Lynch; Cho R Hong; Tet Woo Lee; Reidar A Grénman; Laura Caporiccio; Trevor D McKee; Mark Zaidi; Sehrish Butt; Andrew Mj Macann; Nicholas P McIvor; John M Chaplin; Kevin O Hicks; Stefan K Bohlander; Bradly G Wouters; Charles P Hart; Cristin G Print; William R Wilson; Michael A Curran; Francis W Hunter Journal: JCI Insight Date: 2018-08-23
Authors: Grace C Blitzer; Molly A Smith; Stephen L Harris; Randall J Kimple Journal: Int J Radiat Oncol Biol Phys Date: 2014-03-15 Impact factor: 7.038
Authors: Nadine C Olthof; Christian U Huebbers; Jutta Kolligs; Mieke Henfling; Frans C S Ramaekers; Iris Cornet; Josefa A van Lent-Albrechts; Alexander P A Stegmann; Steffi Silling; Ulrike Wieland; Thomas E Carey; Heather M Walline; Susanne M Gollin; Thomas K Hoffmann; Johan de Winter; Bernd Kremer; Jens P Klussmann; Ernst-Jan M Speel Journal: Int J Cancer Date: 2014-08-14 Impact factor: 7.396