Carole Fakhry1, Qiang Zhang2, Phuc Felix Nguyen-Tan2, David Rosenthal2, Adel El-Naggar2, Adam S Garden2, Denis Soulieres2, Andy Trotti2, Vilija Avizonis2, John Andrew Ridge2, Jonathan Harris2, Quynh-Thu Le2, Maura Gillison2. 1. Carole Fakhry, Johns Hopkins Medical Institutions; Milton J. Dance Jr Head and Neck Center, Baltimore, MD; Qiang Zhang, Jonathan Harris, Radiation Therapy Oncology Group Statistical Center; John Andrew Ridge, Fox Chase Cancer Center, Philadelphia, PA; David Rosenthal, Adel El-Naggar, Adam S. Garden, The University of Texas MD Anderson Cancer Center, Houston, TX; Andy Trotti, H. Lee Moffitt Cancer Center, Tampa, FL; Vilija Avizonis, Intermountain Medical Center, Murray, UT; Quynh-Thu Le, Stanford University Medical Center, Stanford, CA; Maura Gillison, Ohio State University Medical Center, Columbus, OH; Phuc Felix Nguyen-Tan, Denis Soulieres, Centre Hospitalier de l'Université de Montréal Hospital Notre Dame, Montreal, Canada. cfakhry@jhmi.edu. 2. Carole Fakhry, Johns Hopkins Medical Institutions; Milton J. Dance Jr Head and Neck Center, Baltimore, MD; Qiang Zhang, Jonathan Harris, Radiation Therapy Oncology Group Statistical Center; John Andrew Ridge, Fox Chase Cancer Center, Philadelphia, PA; David Rosenthal, Adel El-Naggar, Adam S. Garden, The University of Texas MD Anderson Cancer Center, Houston, TX; Andy Trotti, H. Lee Moffitt Cancer Center, Tampa, FL; Vilija Avizonis, Intermountain Medical Center, Murray, UT; Quynh-Thu Le, Stanford University Medical Center, Stanford, CA; Maura Gillison, Ohio State University Medical Center, Columbus, OH; Phuc Felix Nguyen-Tan, Denis Soulieres, Centre Hospitalier de l'Université de Montréal Hospital Notre Dame, Montreal, Canada.
Abstract
PURPOSE: Risk of cancer progression is reduced for patients with human papillomavirus (HPV) -positive oropharynx cancer (OPC) relative to HPV-negative OPC, but it is unknown whether risk of death after progression is similarly reduced. PATIENTS AND METHODS: Patients with stageIII-IV OPC enrolled onto Radiation Therapy Oncology Group trials 0129 or RTOG 0522 who had known tumor p16 status plus local, regional, and/or distant progression after receivingplatinum-based chemoradiotherapy were eligible for a retrospective analysis of the association between tumor p16 status and overall survival (OS) after disease progression. Rates were estimated by Kaplan-Meier method and compared by log-rank; hazard ratios (HRs) were estimated by Cox models. Tests and models were stratified by treatment protocol. RESULTS: A total of 181 patients with p16-positive (n = 105) or p16-negative (n = 76) OPC were included in the analysis. Patterns of failure and median time to progression (8.2 v 7.3 months; P = .67) were similar for patients with p16-positive and p16-negative tumors. After a median follow-up period of 4.0 years after disease progression, patients with p16-positiveOPC had significantly improved survival rates compared with p16-negative patients (2-year OS, 54.6% v 27.6%; median, 2.6 v 0.8 years; P < .001). p16-positive tumor status (HR, 0.48; 95% CI, 0.31 to 0.74) and receipt of salvage surgery (HR, 0.48; 95% CI; 0.27 to 0.84) reduced risk of death after disease progression whereas distant versus locoregional progression (HR, 1.99; 95% CI, 1.28 to 3.09) increased risk, after adjustment for tumor stage and cigarette pack-years at enrollment. CONCLUSION: Tumor HPV status is a strong and independent predictor of OS after disease progression and should be a stratification factor for clinical trials for patients with recurrent or metastatic OPC.
RCT Entities:
PURPOSE: Risk of cancer progression is reduced for patients with human papillomavirus (HPV) -positive oropharynx cancer (OPC) relative to HPV-negative OPC, but it is unknown whether risk of death after progression is similarly reduced. PATIENTS AND METHODS: Patients with stage III-IV OPC enrolled onto Radiation Therapy Oncology Group trials 0129 or RTOG 0522 who had known tumorp16 status plus local, regional, and/or distant progression after receiving platinum-based chemoradiotherapy were eligible for a retrospective analysis of the association between tumorp16 status and overall survival (OS) after disease progression. Rates were estimated by Kaplan-Meier method and compared by log-rank; hazard ratios (HRs) were estimated by Cox models. Tests and models were stratified by treatment protocol. RESULTS: A total of 181 patients with p16-positive (n = 105) or p16-negative (n = 76) OPC were included in the analysis. Patterns of failure and median time to progression (8.2 v 7.3 months; P = .67) were similar for patients with p16-positive and p16-negative tumors. After a median follow-up period of 4.0 years after disease progression, patients with p16-positive OPC had significantly improved survival rates compared with p16-negative patients (2-year OS, 54.6% v 27.6%; median, 2.6 v 0.8 years; P < .001). p16-positive tumor status (HR, 0.48; 95% CI, 0.31 to 0.74) and receipt of salvage surgery (HR, 0.48; 95% CI; 0.27 to 0.84) reduced risk of death after disease progression whereas distant versus locoregional progression (HR, 1.99; 95% CI, 1.28 to 3.09) increased risk, after adjustment for tumor stage and cigarette pack-years at enrollment. CONCLUSION:TumorHPV status is a strong and independent predictor of OS after disease progression and should be a stratification factor for clinical trials for patients with recurrent or metastatic OPC.
Authors: Olcay Cem Bulut; Katja Lindel; Henrik Hauswald; Regine Brandt; Frederick Klauschen; Janina Wolf; Thomas Wolf; Peter K Plinkert; Christian Simon; Wilko Weichert; Albrecht Stenzinger Journal: Eur Arch Otorhinolaryngol Date: 2013-08-29 Impact factor: 2.503
Authors: Brian O'Sullivan; Shao Hui Huang; Lillian L Siu; John Waldron; Helen Zhao; Bayardo Perez-Ordonez; Ilan Weinreb; John Kim; Jolie Ringash; Andrew Bayley; Laura A Dawson; Andrew Hope; John Cho; Jonathan Irish; Ralph Gilbert; Patrick Gullane; Angela Hui; Fei-Fei Liu; Eric Chen; Wei Xu Journal: J Clin Oncol Date: 2013-01-07 Impact factor: 44.544
Authors: Anil K Chaturvedi; Eric A Engels; Ruth M Pfeiffer; Brenda Y Hernandez; Weihong Xiao; Esther Kim; Bo Jiang; Marc T Goodman; Maria Sibug-Saber; Wendy Cozen; Lihua Liu; Charles F Lynch; Nicolas Wentzensen; Richard C Jordan; Sean Altekruse; William F Anderson; Philip S Rosenberg; Maura L Gillison Journal: J Clin Oncol Date: 2011-10-03 Impact factor: 44.544
Authors: Randall J Kimple; Molly A Smith; Grace C Blitzer; Alexandra D Torres; Joshua A Martin; Robert Z Yang; Chimera R Peet; Laurel D Lorenz; Kwangok P Nickel; Aloysius J Klingelhutz; Paul F Lambert; Paul M Harari Journal: Cancer Res Date: 2013-06-07 Impact factor: 12.701
Authors: Jan B Vermorken; Jan Stöhlmacher-Williams; Irina Davidenko; Lisa Licitra; Eric Winquist; Cristian Villanueva; Paolo Foa; Sylvie Rottey; Krzysztof Skladowski; Makoto Tahara; Vasant R Pai; Sandrine Faivre; Cesar R Blajman; Arlene A Forastiere; Brian N Stein; Kelly S Oliner; Zhiying Pan; Bruce A Bach Journal: Lancet Oncol Date: 2013-06-06 Impact factor: 41.316
Authors: Paul M Weinberger; Ziwei Yu; Bruce G Haffty; Diane Kowalski; Malini Harigopal; Janet Brandsma; Clarence Sasaki; John Joe; Robert L Camp; David L Rimm; Amanda Psyrri Journal: J Clin Oncol Date: 2006-01-09 Impact factor: 44.544
Authors: Shao Hui Huang; Bayardo Perez-Ordonez; Fei-Fei Liu; John Waldron; Jolie Ringash; Jonathan Irish; Bernard Cummings; Lillian L Siu; John Kim; Ilan Weinreb; Andrew Hope; Patrick Gullane; Dale Brown; Willa Shi; Brian O'Sullivan Journal: Int J Radiat Oncol Biol Phys Date: 2010-10-13 Impact factor: 7.038
Authors: Carole Fakhry; William H Westra; Sigui Li; Anthony Cmelak; John A Ridge; Harlan Pinto; Arlene Forastiere; Maura L Gillison Journal: J Natl Cancer Inst Date: 2008-02-12 Impact factor: 13.506
Authors: Stefan Michiels; Aurélie Le Maître; Marc Buyse; Tomasz Burzykowski; Emilie Maillard; Jan Bogaerts; Jan B Vermorken; Wilfried Budach; Thomas F Pajak; Kian K Ang; Jean Bourhis; Jean-Pierre Pignon Journal: Lancet Oncol Date: 2009-02-24 Impact factor: 41.316
Authors: Marci L Nilsen; Lingyun Lyu; Michael A Belsky; Leila J Mady; Dan P Zandberg; David A Clump; Heath D Skinner; Shyamal Das Peddada; Susan George; Jonas T Johnson Journal: Otolaryngol Head Neck Surg Date: 2019-10-15 Impact factor: 3.497
Authors: Julia M L Brotherton; Mark Jit; Patti E Gravitt; Marc Brisson; Aimée R Kreimer; Sara I Pai; Carole Fakhry; Joseph Monsonego; Silvia Franceschi Journal: Int J Cancer Date: 2016-03-22 Impact factor: 7.396
Authors: Theresa Guo; Akihiro Sakai; Bahman Afsari; Michael Considine; Ludmila Danilova; Alexander V Favorov; Srinivasan Yegnasubramanian; Dylan Z Kelley; Emily Flam; Patrick K Ha; Zubair Khan; Sarah J Wheelan; J Silvio Gutkind; Elana J Fertig; Daria A Gaykalova; Joseph Califano Journal: Cancer Res Date: 2017-07-21 Impact factor: 12.701
Authors: Glenn J Hanna; Alec Kacew; Nicole G Chau; Priyanka Shivdasani; Jochen H Lorch; Ravindra Uppaluri; Robert I Haddad; Laura E MacConaill Journal: JCI Insight Date: 2018-09-06
Authors: Adam D Swick; Prashanth J Prabakaran; Margot C Miller; Amal M Javaid; Michael M Fisher; Emmanuel Sampene; Irene M Ong; Rong Hu; Mari Iida; Kwangok P Nickel; Justine Y Bruce; Deric L Wheeler; Randall J Kimple Journal: Mol Cancer Ther Date: 2017-04-26 Impact factor: 6.261
Authors: Huaising C Ko; Paul M Harari; Ryan M Sacotte; Shuai Chen; Aaron M Wieland; Menggang Yu; Andrew M Baschnagel; Justine Y Bruce; Randall J Kimple; Matthew E Witek Journal: J Cancer Res Clin Oncol Date: 2017-07-27 Impact factor: 4.553
Authors: Melina J Windon; Gypsyamber D'Souza; Farhoud Faraji; Tanya Troy; Wayne M Koch; Christine G Gourin; Ana P Kiess; Karen T Pitman; David W Eisele; Carole Fakhry Journal: Cancer Date: 2019-01-15 Impact factor: 6.860