Jeffrey M Vainshtein1, Matthew E Spector2, Jonathan B McHugh3, Ka Kit Wong4, Heather M Walline5, Serena A Byrd6, Christine M Komarck7, Mohannad Ibrahim8, Matthew H Stenmark1, Mark E Prince2, Carol R Bradford2, Gregory T Wolf2, Scott McLean2, Francis P Worden9, Douglas B Chepeha2, Thomas Carey2, Avraham Eisbruch10. 1. Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States. 2. Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, MI, United States. 3. Department of Pathology, University of Michigan, Ann Arbor, MI, United States. 4. Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, MI, United States. 5. Doctoral Program in Cancer Biology, University of Michigan, Ann Arbor, MI, United States. 6. University of Michigan School of Medicine, Ann Arbor, MI, United States. 7. Department of Otolaryngology, University of Michigan, Ann Arbor, MI, United States. 8. Department of Radiology, University of Michigan, Ann Arbor, MI, United States. 9. Division of Hematology Oncology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, United States. 10. Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States. Electronic address: eisbruch@umich.edu.
Abstract
BACKGROUND: To determine whether the addition of molecular and imaging biomarkers to established clinical risk factors could help predict locoregional failure (LRF) after chemoradiation in human papillomavirus (HPV)-related (+) oropharyngeal cancer (OPC) and improve patient selection for locoregional treatment de-intensification. METHODS: HPV status was determined for 198 consecutive patients with stage III/IV OPC treated with definitive chemoradiation from 5/2003 to 10/2010. The impact of pre-therapy epidermal growth factor receptor (EGFR) overexpression; imaging biomarkers including primary tumor and nodal maximum standardized uptake values on FDG-PET, gross tumor volumes, and matted nodes; and clinical factors on LRF (including residual disease at adjuvant neck dissection) was assessed. RESULTS: Primary tumors were HPV+ in 184 patients and HPV-negative in 14. EGFR overexpression was related to HPV-negative status and was univariately associated with LRF in the overall population, but was neither retained in the multivariate model after adjustment for HPV status, nor associated with LRF in HPV+ patients. Similarly, imaging biomarkers were univariately associated with LRF, but correlated with T-stage and/or N-stage and did not remain predictive in HPV+ patients after adjustment for T4- and N3-stages, which were the only significant predictors of LRF on multivariate analysis. Among HPV+ patients with non-T4- or N3-stages, only minimal smoking was associated with decreased LRF. CONCLUSIONS: The prognostic impact of EGFR overexpression and imaging biomarkers on LRF was predominantly related to their association with HPV-negative status and T- or N-stage, respectively. Among HPV+ OPC patients treated with uniform chemoradiation, only T4-stage, N3-stage, and smoking contributed to risk-stratification for LRF.
BACKGROUND: To determine whether the addition of molecular and imaging biomarkers to established clinical risk factors could help predict locoregional failure (LRF) after chemoradiation in human papillomavirus (HPV)-related (+) oropharyngeal cancer (OPC) and improve patient selection for locoregional treatment de-intensification. METHODS:HPV status was determined for 198 consecutive patients with stage III/IV OPC treated with definitive chemoradiation from 5/2003 to 10/2010. The impact of pre-therapy epidermal growth factor receptor (EGFR) overexpression; imaging biomarkers including primary tumor and nodal maximum standardized uptake values on FDG-PET, gross tumor volumes, and matted nodes; and clinical factors on LRF (including residual disease at adjuvant neck dissection) was assessed. RESULTS:Primary tumors were HPV+ in 184 patients and HPV-negative in 14. EGFR overexpression was related to HPV-negative status and was univariately associated with LRF in the overall population, but was neither retained in the multivariate model after adjustment for HPV status, nor associated with LRF in HPV+ patients. Similarly, imaging biomarkers were univariately associated with LRF, but correlated with T-stage and/or N-stage and did not remain predictive in HPV+ patients after adjustment for T4- and N3-stages, which were the only significant predictors of LRF on multivariate analysis. Among HPV+ patients with non-T4- or N3-stages, only minimal smoking was associated with decreased LRF. CONCLUSIONS: The prognostic impact of EGFR overexpression and imaging biomarkers on LRF was predominantly related to their association with HPV-negative status and T- or N-stage, respectively. Among HPV+ OPC patients treated with uniform chemoradiation, only T4-stage, N3-stage, and smoking contributed to risk-stratification for LRF.
Authors: David L Schwartz; Joseph Rajendran; Bevan Yueh; Marc D Coltrera; Michael Leblanc; Janet Eary; Kenneth Krohn Journal: Arch Otolaryngol Head Neck Surg Date: 2004-12
Authors: Mitchell Machtay; Mona Natwa; Jocelyn Andrel; Terry Hyslop; P Rani Anne; Jororsali Lavarino; Charles M Intenzo; William Keane Journal: Head Neck Date: 2009-02 Impact factor: 3.147
Authors: Matthew E Spector; K Kelly Gallagher; Emily Light; Mohannad Ibrahim; Eric J Chanowski; Jeffrey S Moyer; Mark E Prince; Gregory T Wolf; Carol R Bradford; Kitrina Cordell; Jonathan B McHugh; Thomas Carey; Francis P Worden; Avraham Eisbruch; Douglas B Chepeha Journal: Head Neck Date: 2012-01-13 Impact factor: 3.147
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: Avraham Eisbruch; Hyungjin M Kim; Felix Y Feng; Teresa H Lyden; Marc J Haxer; Mary Feng; Frank P Worden; Carol R Bradford; Mark E Prince; Jeffrey S Moyer; Gregory T Wolf; Douglas B Chepeha; Randall K Ten Haken Journal: Int J Radiat Oncol Biol Phys Date: 2011-05-17 Impact factor: 7.038
Authors: Niklas Reimers; Hans U Kasper; Soenke J Weissenborn; Hartmut Stützer; Simon F Preuss; Thomas K Hoffmann; Ernst Jan M Speel; Hans P Dienes; Herbert J Pfister; Orlando Guntinas-Lichius; Jens P Klussmann Journal: Int J Cancer Date: 2007-04-15 Impact factor: 7.396
Authors: Jeffrey M Vainshtein; Dominic H Moon; Felix Y Feng; Douglas B Chepeha; Avraham Eisbruch; Matthew H Stenmark Journal: Int J Radiat Oncol Biol Phys Date: 2015-04-01 Impact factor: 7.038
Authors: Kyle K VanKoevering; Emily Marchiano; Heather M Walline; Thomas E Carey; Jonathan B McHugh; J Chad Brenner; Christine M Goudsmit; Emily Belille; Matthew E Spector; Andrew G Shuman Journal: Otolaryngol Head Neck Surg Date: 2017-09-26 Impact factor: 3.497
Authors: Stuart E Samuels; Jeffrey Vainshtein; Matthew E Spector; Mohannad Ibrahim; Jonathan B McHugh; Yebin Tao; Matthew Schipper; Francis Worden; Avraham Eisbruch Journal: Radiother Oncol Date: 2015-06-17 Impact factor: 6.280
Authors: Jeffrey M Vainshtein; Matthew E Spector; Mohannad Ibrahim; Carol R Bradford; Gregory T Wolf; Matthew H Stenmark; Francis P Worden; Jonathan B McHugh; Mark E Prince; Thomas Carey; Douglas B Chepeha; Avraham Eisbruch Journal: Head Neck Date: 2015-07-15 Impact factor: 3.147
Authors: Stuart E Samuels; Yebin Tao; Teresa Lyden; Marc Haxer; Matthew Spector; Kelly M Malloy; Mark E Prince; Carol R Bradford; Francis P Worden; Matthew Schipper; Avraham Eisbruch Journal: Oral Oncol Date: 2016-01-06 Impact factor: 5.337
Authors: Lauren J Beesley; Peter G Hawkins; Lahin M Amlani; Emily L Bellile; Keith A Casper; Steven B Chinn; Avraham Eisbruch; Michelle L Mierzwa; Matthew E Spector; Gregory T Wolf; Andrew G Shuman; Jeremy M G Taylor Journal: Cancer Date: 2018-10-06 Impact factor: 6.860
Authors: H Kuno; M M Qureshi; M N Chapman; B Li; V C Andreu-Arasa; K Onoue; M T Truong; O Sakai Journal: AJNR Am J Neuroradiol Date: 2017-10-12 Impact factor: 3.825
Authors: Linda X Yin; Gypsyamber D'Souza; William H Westra; Steven J Wang; Annemieke van Zante; Yuehan Zhang; Eleni M Rettig; William R Ryan; Patrick K Ha; Alicia Wentz; Wayne Koch; David W Eisele; Carole Fakhry Journal: Laryngoscope Date: 2018-03-14 Impact factor: 3.325