PURPOSE: To prospectively identify markers of response to therapy and outcome in an organ-sparing trial for advanced oropharyngeal cancer. PATIENTS AND METHODS: Pretreatment biopsies were examined for expression of epidermal growth factor receptor (EGFR), p16, Bcl-xL, and p53 as well as for p53 mutation. These markers were assessed for association with high-risk human papillomavirus (HPV), response to therapy, and survival. Patient variables included smoking history, sex, age, primary site, tumor stage, and nodal status. RESULTS: EGFR expression was inversely associated with response to induction chemotherapy (IC) (P = .01), chemotherapy/radiotherapy (CRT; P = .055), overall survival (OS; P = .001), and disease-specific survival (DSS; P = .002) and was directly associated with current smoking (P = .04), female sex (P = .053), and lower HPV titer (P = .03). HPV titer was significantly associated with p16 expression (P < .0001); p16 was significantly associated with response to IC (P = .008), CRT (P = .009), OS (P = .001), and DSS (P = .003). As combined markers, lower HPV titer and high EGFR expression were associated with worse OS (rho(EGFR) = 0.008; rho(HPV) = 0.03) and DSS (rho(EGFR) = 0.01; rho(HPV) = 0.016). In 36 of 42 biopsies, p53 was wild-type, and only one HPV-positive tumor had mutant p53. The combination of low p53 and high Bcl-xL expression was associated with poor OS (P = .005) and DSS (P = .002). CONCLUSION: Low EGFR and high p16 (or higher HPV titer) expression are markers of good response to organ-sparing therapy and outcome, whereas high EGFR expression, combined low p53/high Bcl-xL expression, female sex, and smoking are associated with a poor outcome. Smoking cessation and strategies to target EGFR and Bcl-xL are important adjuncts to the treatment of oropharyngeal cancer.
PURPOSE: To prospectively identify markers of response to therapy and outcome in an organ-sparing trial for advanced oropharyngeal cancer. PATIENTS AND METHODS: Pretreatment biopsies were examined for expression of epidermal growth factor receptor (EGFR), p16, Bcl-xL, and p53 as well as for p53 mutation. These markers were assessed for association with high-risk human papillomavirus (HPV), response to therapy, and survival. Patient variables included smoking history, sex, age, primary site, tumor stage, and nodal status. RESULTS:EGFR expression was inversely associated with response to induction chemotherapy (IC) (P = .01), chemotherapy/radiotherapy (CRT; P = .055), overall survival (OS; P = .001), and disease-specific survival (DSS; P = .002) and was directly associated with current smoking (P = .04), female sex (P = .053), and lower HPV titer (P = .03). HPV titer was significantly associated with p16 expression (P < .0001); p16 was significantly associated with response to IC (P = .008), CRT (P = .009), OS (P = .001), and DSS (P = .003). As combined markers, lower HPV titer and high EGFR expression were associated with worse OS (rho(EGFR) = 0.008; rho(HPV) = 0.03) and DSS (rho(EGFR) = 0.01; rho(HPV) = 0.016). In 36 of 42 biopsies, p53 was wild-type, and only one HPV-positive tumor had mutant p53. The combination of low p53 and high Bcl-xL expression was associated with poor OS (P = .005) and DSS (P = .002). CONCLUSION: Low EGFR and high p16 (or higher HPV titer) expression are markers of good response to organ-sparing therapy and outcome, whereas high EGFR expression, combined low p53/high Bcl-xL expression, female sex, and smoking are associated with a poor outcome. Smoking cessation and strategies to target EGFR and Bcl-xL are important adjuncts to the treatment of oropharyngeal cancer.
Authors: G Almadori; G Cadoni; P Cattani; J Galli; F Bussu; G Ferrandina; G Scambia; G Fadda; M Maurizi Journal: Clin Cancer Res Date: 2001-12 Impact factor: 12.531
Authors: J P Klussmann; S J Weissenborn; U Wieland; V Dries; J Kolligs; M Jungehuelsing; H E Eckel; H P Dienes; H J Pfister; P G Fuchs Journal: Cancer Date: 2001-12-01 Impact factor: 6.860
Authors: Scott E Strome; Athanasia Savva; Anthony E Brissett; Bobbie S Gostout; Jean Lewis; Amy C Clayton; Renee McGovern; Amy L Weaver; David Persing; Jan L Kasperbauer Journal: Clin Cancer Res Date: 2002-04 Impact factor: 12.531
Authors: Bijan Khademi; Farzaneh Mohammadalizadeh Shirazi; Mohammad Vasei; Mehrnoosh Doroudchi; Behrouz Gandomi; Helmout Modjtahedi; Abdul Mohammad Pezeshki; Abbas Ghaderi Journal: Cancer Lett Date: 2002-10-28 Impact factor: 8.679
Authors: Matti J Pukkila; Eero J Kumpulainen; Jukka A Virtaniemi; Risto T Johansson; Pirjo M Halonen; Jari K Kellokoski; Ari S T Kosunen; Juhani Nuutinen; Veli-Matti Kosma Journal: Head Neck Date: 2002-08 Impact factor: 3.147
Authors: Daniel M Aebersold; Susanne C Froehlich; Maciej Jonczy; Karl T Beer; Jean Laissue; Richard H Greiner; Valentin Djonov Journal: Radiother Oncol Date: 2002-06 Impact factor: 6.280
Authors: Alice L Tang; Samantha J Hauff; John H Owen; Martin P Graham; Michael J Czerwinski; Jung Je Park; Heather Walline; Silvana Papagerakis; Jay Stoerker; Jonathan B McHugh; Douglas B Chepeha; Carol R Bradford; Thomas E Carey; Mark E Prince Journal: Head Neck Date: 2011-12-13 Impact factor: 3.147
Authors: K Kian Ang; Jonathan Harris; Richard Wheeler; Randal Weber; David I Rosenthal; Phuc Felix Nguyen-Tân; William H Westra; Christine H Chung; Richard C Jordan; Charles Lu; Harold Kim; Rita Axelrod; C Craig Silverman; Kevin P Redmond; Maura L Gillison Journal: N Engl J Med Date: 2010-06-07 Impact factor: 91.245
Authors: James S Lewis; Wade L Thorstad; Rebecca D Chernock; Bruce H Haughey; James H Yip; Qin Zhang; Samir K El-Mofty Journal: Am J Surg Pathol Date: 2010-08 Impact factor: 6.394
Authors: Moonef Alotaibi; Valeria Valova; Toni HÄnsel; Carmen Stromberger; Grzegorz Kofla; Heidi Olze; Iris Piwonski; Andreas Albers; Sebastian Ochsenreither; Annekatrin Coordes Journal: In Vivo Date: 2021 Mar-Apr Impact factor: 2.155
Authors: Randall J Kimple; Paul M Harari; Alexandra D Torres; Robert Z Yang; Benjamin J Soriano; Menggang Yu; Eric A Armstrong; Grace C Blitzer; Molly A Smith; Laurel D Lorenz; Denis Lee; David T Yang; Timothy M McCulloch; Gregory K Hartig; Paul F Lambert Journal: Clin Cancer Res Date: 2012-12-18 Impact factor: 12.531