Clinical Medicine Journal
Articles Information
Clinical Medicine Journal, Vol.2, No.2, Apr. 2016, Pub. Date: Mar. 4, 2016
Prognostic Impact of p16 Alterations and Pretreatment Anemia in Head and Neck Cancer Patients Undergoing Definitive Radiochemotherapy
Pages: 13-19 Views: 1437 Downloads: 459
Authors
[01] Martina E. Becker-Schiebe, Department of Radiotherapy and Radio-Oncology, Klinikum Braunschweig, Hannover Medical School, Braunschweig, Germany; Radiation Oncology, Hannover Medical School, Hannover, Germany.
[02] Matthias Sperling, Department of Pathology, Klinikum Braunschweig, Hannover Medical School, Braunschweig, Germany.
[03] Fabian l Wetze, Department of Radiotherapy and Radio-Oncology, Klinikum Braunschweig, Hannover Medical School, Braunschweig, Germany.
[04] Uwe Pinkert, Department of Radiotherapy and Radio-Oncology, Klinikum Braunschweig, Hannover Medical School, Braunschweig, Germany.
[05] Wolfgang Hoffmann, Department of Radiotherapy and Radio-Oncology, Klinikum Braunschweig, Hannover Medical School, Braunschweig, Germany.
Abstract
Aim: Up to now, the incidence of HPV-associated oropharyngeal cancer is rising, indicating the increased impact of the viral etiology, but prognostic significance of HPV/p16 in other pharyngeal sites remains unclear. In addition, hypoxia might be important for carcinogenesis of head and neck cancer (HNSCC) and treatment response as well. This evaluation was carried out to explore, whether there is any correlation between pretreatment factors like pre-RT anemia and p16 expression and to determine the prognostic value of these factors in advanced HNSCC pts. Methods: A total of 79 locally advanced HNSCC patients (pts.) who underwent definitive RCT- or RT-antibody-therapy were retrospectively analysed. p16 (INK4A) expression was detected by immunohistochemical analysis. Factors predisposing for treatment response were examined and survival curves were compared. Results: The follow-up period ranged from 16 to 48 months, with a median of 25.3 months. Pretreatment anemia was apparent in one third of pts..P16 overexpression was detected in 32 cases. A significant correlation was found between p16 expression and pretreatment hemoglobin level. Only 3 pts. were characterized by both pre-RT anemia and p16 overexpression. Two-year locoregional control, progression-free survival (PFS) and overall survival (OS) were 75%, 62% and 70%, respectively. The prognostic value of p16 in the entire HNSCC patient cohort was confirmed; Kaplan-Meier analysis proved significant differences in progression-free survival (PFS) depending on p16 overexpression and PFS was significantly improved in the non-anemic patient group (p=0.023). In conclusion, this study demonstrated that p16 expression and pretreatment anemia are related to HNSCC subgroups. The prognostic value of this variables was confirmed for a patient cohort consisting of advanced naso-/oro-and hypopharyngeal carcinomas undergoing definitive RCT.
Keywords
Anemia, p16, Head and Neck Cancer, Radiochemotherapy
References
[01] Becker-Schiebe M, Hoffmann W, Pinkert U, Ochel J, Gademann G: Prognostic impact of p53 mutations and loss of heterozygosity at 9p21 and 11p15 in head and neck cancer. Trends in Cancer Research 2008; 4: 19-24.
[02] Deng Z, Hasegawa M, Aoki K, Matayoshi S, Kiyuna A, Yamashita Y, Uehara T, Agena S, Maeda H, Xie M, Suzuki M: A comprehensive evaluation of human papilloma virus positive status and p16INK4a overexpression as a prognostic biomarker in head and neck squamous cell carcinoma Int J Oncol 2014; 45: 67-76.
[03] Chung CH, Guthrie VB, Masica DL, Tokheim C, Kang H, Richmon J, Agrawal N, Fakhry C, Quon H, Subramaniam RM, Zuo Z, Seiwert T, Chalmers ZR, Frampton GM, Ali SM, Yelensky R, Stephens PJ, Miller VA, Karchin R, Bishop JA: Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing. Ann Oncol 2015; 26(6): 1216-23.
[04] Tong C, Lau K, Rivera M, Cannan D, Aguirre-Ghiso J, Sikora AG, Gupta V, Forsythe K, Ko EC, Misiukiewicz K, Gurudutt V, Teng MS, Packer SH, Genden EM, Kao J: Prognostic significance in locoregionally advanced head and neck cancer treated with concurrent 5-fluorouracil, hydroxyurea, cetuximab and intensity-modulated radiation therapy. Oncol Reports 2012; 27: 1580-86.
[05] Chung C, Guthrie V, Masica D, Tokheim C, Kang H, Richmon J, Agrawal N, Fakhry C, Quon H, Subramaniam R, Zuo Z, Seiwert T, Chalmers Z, Frampton G, Ali S, Yelensky R, Stephens P, Miller V, Karchin R, Bishop J: Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing. Ann Oncol 2015; 26(6): 1216-23.
[06] Henneman R, VAN Monsjou H, Verhagen C, VAN Velthuysen M, Haar N, Osse E, Lopez-Yurda M, Balm A, VAN DEN Brekel M: Incidence Changes of Human Papillomavirus in Oropharyngeal Squamous Cell Carcinoma and Effects on Survival in the Netherlands Cancer Institute, 1980-2009. Anticancer Res 2015; 35(7): 4015-22.
[07] Masunaga S, Uto Y, Nagasawa H, Hori H, Nagata K, Suzuki M, Kinashi Y, Ono K: Evaluation of hypoxic cell radio-sensitizers in terms of radio-sensitizing and repair-inhibiting potential. Dependency on p53 status of tumor cells and the effects on intratumor quiescent cells. Anticancer Res 2006; 26(2A): 1261-70.
[08] Nguyen-Tan P, Zhang Q, Ang K, Weber R, Rosenthal D, Soulieres D, Kim H, Silverman C, Raben A, Galloway T, Fortin A, Gore E, Westra W, Chung C, Jordan R, Gillison M, List M, Le Q: Randomized Phase III Trial to Test Accelerated Versus Standard Fractionation in Combination With Concurrent Cisplatin for Head and Neck Carcinomas in the Radiation Therapy Oncology Group 0129 Trial: Long-Term Report of Efficacy and Toxicity. J Clin Oncol 2014; 32(34): 3858-66.
[09] Tehrany N, Kitz J, Rave-Fränk M, Lorenzen S, Li L, Küffer S, Hess C, Burfeind P, Reichardt H, Canis M, Beißbarth T, Wolff H: High grade acute organ toxicity and p16INK4a expression as positive prognostic factors in primary radio (chemo) therapy for patients with head and neck squamous cell carcinoma. Strahlenther Onkol 2015; 191: 566-572.
[10] Strigari L, Pedicini P, D'Andrea M, Pinnarò P, Marucci L, Giordano C, Benassi M: A new model for predicting acute mucosal toxicity in head-and-neck cancer patients undergoing radiotherapy with altered schedules. Int J Radiat Oncol Biol Phys 2012; 83(5): e697-702.
[11] Bonner J, Harari P, Giralt J, Cohen R, Jones CU, Sur R, Raben D, Baselga J, Spencer S, Zhu J, Youssoufian H, Rowinsky E, Ang: Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 2010; 11(1): 21-8.
[12] Trotti A, Colevas A, Setser A, Rusch V, Jaques D, Budach V, Langer C, Murphy B, Cumberlin R, Coleman C, Rubin P: CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 2003; 13(3): 176-81.
[13] Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF: An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol 2003; 21: 92–98.
[14] Castro G, Snitcovsky IML, Gebrim EM, Leitao GM, Nadalin W, Ferraz AR: High-dose cisplatin concurrent to conventionally delivered radiotherapy is associated with unacceptable toxicity in unresectable, non-metastatic stage IV head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol 2007; 264(12): 1475–1482.
[15] Rades D, Fehlauer F, Sheikh-Sarraf M, Kazic N, Basic H, Poorter R: Toxicity of two cisplatin-based radiochemotherapy regimes for the treatment of patients with stage III/IV head and neck cancer. Head Neck 2008; 30(2): 235–241.
[16] Chandarana S, Lee J, Chanowski E, Sacco A, Bradford C, Wolf G, Prince M, Moyer J, Eisbruch A, Worden F, Giordano T, Kumar B, Cordell K, Carey T, Chepeha D: The Prevalence and Predictive Role of p16 and EGFR in Surgically Treated Oropharyngeal and Oral Cavity Cancer. Head Neck. 2013; 35(8): 1083–1090.
[17] Lassen P, Eriksen J, Hamilton-Dutoit S, Tramm T, Alsner J, Overgaard J; Danish Head and Neck Cancer Group (DAHANCA): Effect of HPV associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol 2009; 27:1992-98.
[18] Hanasoge S, Magliocca K, Switchenko J, Saba N, Wadsworth J, El-Deiry M, Shin D, Khuri F, Beitler J, Higgins K. J: Clinical outcome in elderly patients with human papilloma virus positive squamous cell carcinoma of the oropharynx treated with definitive chemoradiation therapy. Head Neck 2015 doi: 10.1002/hed.24073.
[19] Rosenthal D, Trotti A. Strategies for Managing Radiation-Induced Mucositis in Head and Neck Cancer. Sem Radiat Oncol 2007; 19(1):29-34.
[20] Hafkamp H, Manni J, Haesevoets A, Voogd A, Schepers M, Bot F, Hopman A, Ramaekers F, Speel E A: Marked differences in survival rate between smokers and nonsmokers with HPV 16-associated tonsillar carcinomas. Int J Cancer 2008; 122: 2656-2664.
[21] Ang K, Harris J, Wheeler R, Weber R, Rosenthal D, Nguyen-Tân P, Westra W, Chung C, Jordan R, Lu C, Kim H, Axelrod R, Silverman C, Redmond K, Gillison M: Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010; 363(1): 24-35.
[22] Fazekas J, Scott C, Marcial V, Davis L, Wasserman T, Cooper J: The role of hemoglobin concentration in the outcome of misonidazole- sensitized radiotherapy of head and neck cancers: Based on RTOG trial #79-15. Int J Radiat Oncol Biol Phys 1989; 17: 1177-1181.
[23] Bar-Ad V, Wang Z, Leiby B, Tuluc M: Combination of p16 levels and pre-radiotherapy factors predicts outcome in patients treated for oropharyngeal carcinoma. JBUON 2013; 18(4): 982-988.
[24] Lee W, Berkey B, Marcial V, Fu K, Cooper J, Vikram B, Coia L, Rotman M, Ortiz H: Anemia is associated with decreased survival and increased locoregional failure in patients with locally advanced head and neck carcinoma: A secondary analysis of RTOG 85-27. Int J Radiat Oncol Biol Phys 1998; 42: 1069-1075.
[25] Obermair A, Handisurya A, Kaider A, Sevelda P, Kolbl H, Gitsch G. The relationship of pretreatment serum hemoglobin level to the survival of epithelial ovarian carcinoma patients. Cancer 1998; 83: 726-731.
[26] Driessen C, Janssen G, Van der Graaf W, et al. Toxicity and efficacy of accelerated radiotherapy with concurrent weekly cisplatin for locally advanced head and neck carcinoma. Head Neck 2015. doi: 10.1002/hed.24039.
[27] Rosenthal DI, Harari PM, Giralt J, et al. Association of Human Papillomavirus and p16 Status With Outcomes in the IMCL-9815 Phase III Registration Trial for Patients With Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma of the Head and Neck Treated With Radiotherapy With or Without Cetuximab. J Clin Oncol. 2015 Dec 28. pii: JCO625970. [Epub ahead of print]
[28] Wilson DD, Crandley EF, Sim A, et al Prognostic significance of p16 and its relationship with human papillomavirus in pharyngeal squamous cell carcinomas. JAMA Otolaryngol Head Neck Surg. 2014 Jul; 140(7): 647-53. doi: 10.1001/jamaoto.2014.821.
[29] O'Sullivan B, Huang S, Siu L, Waldron J, Zhao H, Perez-Ordonez B, Weinreb I, Kim J, Ringash J, Bayley A, Dawson L, Hope A, Cho J, Irish J, Gilbert R, Gullane P, Hui A, Liu F, Chen E, Xu W: Deintensification Candidate Subgroups in Human Papillomavirus–Related Oropharyngeal Cancer According to Minimal Risk of Distant Metastasis. J Clin Oncol 2013; 31: 543-550.
600 ATLANTIC AVE, BOSTON,
MA 02210, USA
+001-6179630233
AIS is an academia-oriented and non-commercial institute aiming at providing users with a way to quickly and easily get the academic and scientific information.
Copyright © 2014 - 2017 American Institute of Science except certain content provided by third parties.