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Review

Treatment of head and neck cancer in the elderly

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Pages 1903-1921 | Received 09 Jun 2016, Accepted 01 Aug 2016, Published online: 16 Aug 2016

References

  • Marur S, Forastiere AA. Head and neck cancer: changing epidemiology, diagnosis, and treatment. Mayo Clin Proc. 2008;83(4):489–501.
  • Haddad RI, Shin DM. Recent advances in head and neck cancer. N Engl J Med. 2008;359(11):1143–1154.
  • Seiwert TY, Cohen EE. State-of-the-art management of locally advanced head and neck cancer. Br J Cancer. 2005;92(8):1341–1348.
  • Narayan TV, Revanna GM, Hallikeri U, et al. dental caries and periodontal disease status in patients with oral squamous cell carcinoma: a screening study in urban and semiurban population of Karnataka. J Maxillofac Oral Surg. 2014;13(4):435–443.
  • Tremblay S, Pintor Dos Reis P, Bradley G, et al. Young patients with oral squamous cell carcinoma: study of the involvement of GSTP1 and deregulation of the Fanconi anemia genes. Arch Otolaryngol Head Neck Surg. 2006;132(9):958–966.
  • Grandis JR, Tweardy DJ. Elevated levels of transforming growth factor alpha and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer. Cancer Res. 1993;53(15):3579–3584.
  • Cancer Genome Atlas N. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517(7536):576–582.
  • Stransky N, Egloff AM, Tward AD, et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011;333(6046):1157–1160.
  • Van Allen EM, Lui VW, Egloff AM, et al. Genomic correlate of exceptional erlotinib response in head and neck squamous cell carcinoma. JAMA Oncol. 2015;1(2):238–244.
  • Gillison ML, Broutian T, Pickard RK, et al. Prevalence of oral HPV infection in the United States, 2009–2010. JAMA. 2012;307(7):693–703.
  • Sturgis EM, Cinciripini PM. Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer. 2007;110(7):1429–1435.
  • D’Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356(19):1944–1956.
  • Johansen J, Grau Eriksen J. Academy of Geriatric Cancer R. Trends in cancer of the head and neck in the elderly in Denmark, 1980–2012. Acta Oncol. 2016;55(Suppl 1):13–18.
  • Fakhry C, Westra WH, Li S, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100(4):261–269.
  • Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35.
  • Sano D, Oridate N. The molecular mechanism of human papillomavirus-induced carcinogenesis in head and neck squamous cell carcinoma. Int J Clin Oncol. 2016 Jun 23. [Epub ahead of print].
  • Rampias T, Sasaki C, Weinberger P, et al. E6 and e7 gene silencing and transformed phenotype of human papillomavirus 16-positive oropharyngeal cancer cells. J Natl Cancer Inst. 2009;101(6):412–423.
  • Mirghani H, Amen F, Tao Y, et al. Increased radiosensitivity of HPV-positive head and neck cancers: molecular basis and therapeutic perspectives. Cancer Treat Rev. 2015;41(10):844–852.
  • Egawa N, Egawa K, Griffin H, et al. Human papillomaviruses; epithelial tropisms, and the development of neoplasia. Viruses. 2015;7(7):3863–3890.
  • Markey J, Knott PD, Fritz MA, et al. Recent advances in head and neck free tissue transfer. Curr Opin Otolaryngol Head Neck Surg. 2015;23(4):297–301.
  • Byrd JK, Ferris RL. Is there a role for robotic surgery in the treatment of head and neck cancer? Curr Treat Options Oncol. 2016;17(6):29.
  • Agrawal A, Civantos FJ, Brumund KT, et al. [(99m)Tc]Tilmanocept accurately detects sentinel lymph nodes and predicts node pathology status in patients with oral squamous cell carcinoma of the head and neck: results of a phase III multi-institutional trial. Ann Surg Oncol. 2015;22(11):3708–3715.
  • Porceddu SV, Campbell B, Rischin D, et al. Postoperative chemoradiotherapy for high-risk head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2004;60(2):365–373.
  • Goodwin WJ Jr. Salvage surgery for patients with recurrent squamous cell carcinoma of the upper aerodigestive tract: when do the ends justify the means? The Laryngoscope. 2000;110(3Pt 2 Suppl 93):1–18.
  • Zafereo ME, Hanasono MM, Rosenthal DI, et al. The role of salvage surgery in patients with recurrent squamous cell carcinoma of the oropharynx. Cancer. 2009;115(24):5723–5733.
  • Sanguineti G, Forastiere AA. Determining the survival benefit of adjuvant radiotherapy in patients with node-positive head and neck cancer. Nat Clin Pract Oncol. 2008;5(12):694–695.
  • Grégoire V, Langendijk JA, Nuyts S. Advances in Radiotherapy for Head and Neck Cancer. J Clin Oncol. 2015;33(29):3277–3284.
  • Kao J, Lavaf A, Teng MS, et al. Adjuvant radiotherapy and survival for patients with node-positive head and neck cancer: an analysis by primary site and nodal stage. Int J Radiat Oncol Biol Phys. 2008;71(2):362–370.
  • Pignon JP, Le Maitre A, Maillard E, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009;92(1):4–14.
  • Strojan P, Vermorken JB, Beitler JJ, et al. Cumulative cisplatin dose in concurrent chemoradiotherapy for head and neck cancer: A systematic review. Head Neck. 2016;38(Suppl 1):E2151–2158.
  • Ang KK, Chen A, Curran WJ Jr, et al. Head and neck carcinoma in the United States: first comprehensive report of the Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN). Cancer. 2012;118(23):5783–5792.
  • Bourhis J, Sire C, Graff P, et al. Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial. Lancet Oncol. 2012;13(2):145–153.
  • Denis F, Garaud P, Bardet E, et al. Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clinl Oncol: off J Am Soc Clin Oncol. 2004;22(1):69–76.
  • Hitt R, López-Pousa A, Martínez-Trufero J, et al. Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally advanced head and neck cancer. J Clinl Oncol: off J Am Soc Clin Oncol. 2005;23(34):8636–8645.
  • Pointreau Y, Garaud P, Chapet S, et al. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J Natl Cancer Inst. 2009;101(7):498–506.
  • Posner MR, Hershock DM, Blajman CR, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007;357(17):1705–1715.
  • Gibson MK, Li Y, Murphy B, et al. Randomized phase III evaluation of cisplatin plus fluorouracil versus cisplatin plus paclitaxel in advanced head and neck cancer (E1395): an intergroup trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2005;23(15):3562–3567.
  • Jacobs C, Lyman G, Velez-García E, et al. A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol. 1992;10(2):257–263.
  • Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359(11):1116–1127.
  • Samlowski WE, Moon J, Kuebler JP, et al. Evaluation of the combination of docetaxel/carboplatin in patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN): a Southwest Oncology Group Phase II study. Cancer Invest. 2007;25(3):182–188.
  • Guigay J, Fayette J, Dillies AF, et al. Cetuximab, docetaxel, and cisplatin as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: a multicenter, phase II GORTEC study. Ann oncol: off J Eur Soc Med Oncol /ESMO. 2015;26(9):1941–1947.
  • Machiels JP, Haddad RI, Fayette J, et al. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial. Lancet Oncol. 2015;16(5):583–594.
  • Stewart JS, Cohen EE, Licitra L, et al. Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck [corrected]. J Clin Oncol. 2009;27(11):1864–1871.
  • Mevio N, Bertino G, Occhini A, et al. Electrochemotherapy for the treatment of recurrent head and neck cancers: preliminary results. Tumori. 2012;98(3):308–313.
  • Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354(6):567–578.
  • Rubinstein PG, Lindgren V, Setty S, et al. Durable complete remission induced by cetuximab monotherapy in a patient infected with HIV and diagnosed with recurrent squamous cell carcinoma of the head and neck. J Clin Oncol. 2011;29(9):e222–225.
  • Peddi P, Paryani B, Takalkar A, et al. Exceptional response to cetuximab monotherapy in a patient with metastatic oropharyngeal squamous cell carcinoma: a molecular insight. Onco Targets Ther. 2016;9:705–709.
  • Vermorken JB, Trigo J, Hitt R, et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol. 2007;25(16):2171–2177.
  • Madoz-Gurpide J, Zazo S, Chamizo C, et al. Activation of MET pathway predicts poor outcome to cetuximab in patients with recurrent or metastatic head and neck cancer. J Transl Med. 2015;13:282.
  • Bossi P, Alfieri S. Investigational drugs for head and neck cancer. Expert Opin Investig Drugs. 2016;25(7)797–810.
  • Murthy VH, Krumholz HM, Gross CP. Participation in cancer clinical trials: race-, sex-, and age-based disparities. JAMA. 2004;291(22):2720–2726.
  • Amini A, Jones BL, McDermott JD, et al. Survival outcomes with concurrent chemoradiation for elderly patients with locally advanced head and neck cancer according to the National Cancer Data Base. Cancer. 2016;122(10):1533–1543.
  • Choi YJ, Chung J, Shin HJ, et al. Induction chemotherapy of docetaxel and Cisplatin for the elderly patients with squamous cell carcinoma of the head and neck. Cancer Res Treat. 2007;39(1):1–5.
  • Feinstein AR, Schimpff CR, Andrews JF Jr, et al. Cancer of the larynx: a new staging system and a re-appraisal of prognosis and treatment. J Chronic Dis. 1977;30(5):277–305.
  • Piccirillo JF, Wells CK, Sasaki CT, et al. New clinical severity staging system for cancer of the larynx. Five-year survival rates. Ann Otol Rhinol Laryngol. 1994;103(2):83–92.
  • Paleri V, Wight RG. Applicability of the adult comorbidity evaluation – 27 and the Charlson indexes to assess comorbidity by notes extraction in a cohort of United Kingdom patients with head and neck cancer: a retrospective study. J Laryngol Otol. 2002;116(3):200–205.
  • Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–383.
  • Piccirillo JF, Tierney RM, Costas I, et al. Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA. 2004;291(20):2441–2447.
  • Klabunde CN, Potosky AL, Legler JM, et al. Development of a comorbidity index using physician claims data. J Clin Epidemiol. 2000;53(12):1258–1267.
  • Singh B, Bhaya M, Stern J, et al. Validation of the Charlson comorbidity index in patients with head and neck cancer: a multi-institutional study. Laryngoscope. 1997;107(11 Pt 1):1469–1475.
  • Datema FR, Ferrier MB, van der Schroeff MP, et al. Impact of comorbidity on short-term mortality and overall survival of head and neck cancer patients. Head Neck. 2010;32(6):728–736.
  • Kaplan MH, Feinstein AR. The importance of classifying initial co-morbidity in evaluating the outcome of diabetes mellitus. J Chronic Dis. 1974;27(7–8):387–404.
  • Hall SF, Rochon PA, Streiner DL, et al. Measuring comorbidity in patients with head and neck cancer. Laryngoscope. 2002;112(11):1988–1996.
  • Ribeiro KC, Kowalski LP, Latorre MR. Impact of comorbidity, symptoms, and patients’ characteristics on the prognosis of oral carcinomas. Arch Otolaryngol Head Neck Surg. 2000;126(9):1079–1085.
  • Borggreven PA, Kuik DJ, Langendijk JA, et al. Severe comorbidity negatively influences prognosis in patients with oral and oropharyngeal cancer after surgical treatment with microvascular reconstruction. Oral Oncol. 2005;41(4):358–364.
  • Castro MA, Dedivitis RA, Ribeiro KC. Comorbidity measurement in patients with laryngeal squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec. 2007;69(3):146–152.
  • Kelly CM, Shahrokni A. Moving beyond karnofsky and ECOG performance status assessments with new technologies. J Oncol. 2016;2016:6186543.
  • Schag CC, Heinrich RL, Ganz PA. Karnofsky performance status revisited: reliability, validity, and guidelines. J Clin Oncol. 1984;2(3):187–193.
  • Sadat F, Wienke A, Dunst J, et al. Survival of patients with head and neck cancer. Impact of physical status and comorbidities. Strahlenther Onkol. 2012;188(1):62–70.
  • Taylor AE, Olver IN, Sivanthan T, et al. Observer error in grading performance status in cancer patients. Support Care Cancer. 1999;7(5):332–335.
  • Correa GT, Bandeira GA, Cavalcanti BG, et al. Analysis of ECOG performance status in head and neck squamous cell carcinoma patients: association with sociodemographical and clinical factors, and overall survival. Support Care Cancer. 2012;20(11):2679–2685.
  • Wang JR, Habbous S, Espin-Garcia O, et al. Comorbidity and performance status as independent prognostic factors in patients with head and neck squamous cell carcinoma. Head Neck. 2016;38(5):736–742.
  • Bøje CR, Dalton SO, Grønborg TK, et al. The impact of comorbidity on outcome in 12 623 Danish head and neck cancer patients: a population based study from the DAHANCA database. Acta Oncol. 2013;52(2):285–293.
  • Sanabria A, Carvalho AL, Vartanian JG, et al. Comorbidity is a prognostic factor in elderly patients with head and neck cancer. Ann Surg Oncol. 2007;14(4):1449–1457.
  • Liu CT, Chiu TJ, Huang TL, et al. Impact of comorbidity on survival for locally advanced head and neck cancer patients treated by radiotherapy or radiotherapy plus chemotherapy. Chang Gung Med J. 2010;33(3):283–291.
  • Alho OP, Hannula K, Luokkala A, et al. Differential prognostic impact of comorbidity in head and neck cancer. Head Neck. 2007;29(10):913–918.
  • Derks W, de Leeuw JR, Hordijk GJ, et al. Reasons for non-standard treatment in elderly patients with advanced head and neck cancer. Eur Arch Otorhinolaryngol. 2005;262(1):21–26.
  • Sanabria A, Carvalho AL, Vartanian JG, et al. Factors that influence treatment decision in older patients with resectable head and neck cancer. Laryngoscope. 2007;117(5):835–840.
  • Yang R, Lubek JE, Dyalram D, et al. Head and neck cancer surgery in an elderly patient population: a retrospective review. Int J Oral Maxillofac Surg. 2014;43(12):1413–1417.
  • Shuman AG, Korc-Grodzicki B, Shklar V, et al. A new care paradigm in geriatric head and neck surgical oncology. J Surg Oncol. 2013;108(3):187–191.
  • Clayman GL, Eicher SA, Sicard MW, et al. Surgical outcomes in head and neck cancer patients 80 years of age and older. Head Neck. 1998;20(3):216–223.
  • Peters TT, Post SF, van Dijk BA, et al. Free flap reconstruction for head and neck cancer can be safely performed in both young and elderly patients after careful patient selection. Eur Arch Otorhinolaryngol. 2015;272(10):2999–3005.
  • Nao EE, Dassonville O, Chamorey E, et al. Head and neck free-flap reconstruction in the elderly. Eur Ann Otorhinolaryngol Head Neck Dis. 2011;128(2):47–51.
  • Chen JH, Yen YC, Yang HC, et al. Curative-intent aggressive treatment improves survival in elderly patients with locally advanced head and neck squamous cell carcinoma and high comorbidity index. Medicine (Baltimore). 2016;95(14):e3268.
  • Yoo SH, Roh JL, Choi SH, et al. Incidence and risk factors for morbidity and mortality in elderly head and neck cancer patients undergoing major oncological surgery. J Cancer Res Clin Oncol. 2016;142(6):1343–1351.
  • Geinitz H, Zimmermann FB, Molls M. Radiotherapy of the elderly patient. Radiotherapy tolerance and results in older patients. Strahlenther Onkol. 1999;175(3):119–127.
  • Khor RC, Bressel M, Tedesco J, et al. Tolerability and outcomes of curative radiotherapy in patients aged 85 or more years. Med J Aust. 2015;202(3):153–155.
  • Pignon T, Jc H, van den Bogaert W, et al. No age limit for radical radiotherapy in head and neck tumours. Eur J Cancer. 1996;32A(12):2075–2081.
  • Bøje CR, Dalton SO, Primdahl H, et al. Evaluation of comorbidity in 9388 head and neck cancer patients: a national cohort study from the DAHANCA database. Radiother Oncol. 2014;110(1):91–97.
  • Yancik R, Havlik RJ, Wesley MN, et al. Cancer and comorbidity in older patients: a descriptive profile. Ann Epidemiol. 1996;6(5):399–412.
  • Kimmick GG, Fleming R, Muss HB, et al. Cancer chemotherapy in older adults. A tolerability perspective. Drugs Aging. 1997;10(1):34–49.
  • Balducci L, Corcoran MB. Antineoplastic chemotherapy of the older cancer patient. Hematol Oncol Clin North Am. 2000;14(1):193–212, x–xi.
  • Bahig H, Fortin B, Alizadeh M, et al. Predictive factors of survival and treatment tolerance in older patients treated with chemotherapy and radiotherapy for locally advanced head and neck cancer. Oral Oncol. 2015;51(5):521–528.
  • Argiris A, Li Y, Murphy BA, et al. Outcome of elderly patients with recurrent or metastatic head and neck cancer treated with cisplatin-based chemotherapy. J Clin Oncol. 2004;22(2):262–268.
  • Nguyen NP, Vock J, Chi A, et al. Impact of intensity-modulated and image-guided radiotherapy on elderly patients undergoing chemoradiation for locally advanced head and neck cancer. Strahlenther Onkol. 2012;188(8):677–683.
  • Airoldi M, Cortesina G, Giordano C, et al. Postoperative adjuvant chemoradiotherapy in older patients with head and neck cancer. Arch Otolaryngol Head Neck Surg. 2004;130(2):161–166.
  • Cooper JS, Zhang Q, Pajak TF, et al. Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2012;84(5):1198–1205.
  • Xu B, Boero IJ, Hwang L, et al. Aspiration pneumonia after concurrent chemoradiotherapy for head and neck cancer. Cancer. 2015;121(8):1303–1311.
  • Singh B, Bhaya M, Zimbler M, et al. Impact of comorbidity on outcome of young patients with head and neck squamous cell carcinoma. Head Neck. 1998;20(1):1–7.
  • Paleri V, Wight RG, Davies GR. Impact of comorbidity on the outcome of laryngeal squamous cancer. Head Neck. 2003;25(12):1019–1026.
  • de Cassia Braga Ribeiro K, Kowalski LP, Latorre Mdo R. Perioperative complications, comorbidities, and survival in oral or oropharyngeal cancer. Arch Otolaryngol Head Neck Surg. 2003;129(2):219–228.
  • Hathaway B, Johnson JT, Piccirillo JF, et al. Chemoradiation for metastatic SCCA: role of comorbidity. Laryngoscope. 2001;111(11 Pt 1):1893–1895.
  • Rathod S, Livergant J, Klein J, et al. A systematic review of quality of life in head and neck cancer treated with surgery with or without adjuvant treatment. Oral Oncol. 2015;51(10):888–900.
  • van der Schroeff MP, Derks W, Hordijk GJ, et al. The effect of age on survival and quality of life in elderly head and neck cancer patients: a long-term prospective study. Eur Arch Otorhinolaryngol. 2007;264(4):415–422.
  • Pottel L, Lycke M, Boterberg T, et al. G-8 indicates overall and quality-adjusted survival in older head and neck cancer patients treated with curative radiochemotherapy. BMC Cancer. 2015;15:875.
  • Genther DJ, Gourin CG. Effect of comorbidity on short-term outcomes and cost of care after head and neck cancer surgery in the elderly. Head Neck. 2015;37(5):685–693.
  • Adelstein DJ, Li Y, Adams GL, et al. 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(1):92–98.
  • Hoffmann TK. Systemic therapy strategies for head-neck carcinomas: current status. GMS Curr Top Otorhinolaryngol Head Neck Surg. Laryngorhinootologie. 2012;91(Suppl 1):S123–S143.
  • Schweitzer VG. Cisplatin-induced ototoxicity: the effect of pigmentation and inhibitory agents. Laryngoscope. 1993;103(4 Pt 2):1–52.
  • Ahn MJ, D’Cruz A, Vermorken JB, et al. Clinical recommendations for defining platinum unsuitable head and neck cancer patient populations on chemoradiotherapy: a literature review. Oral Oncol. 2016;53:10–16.
  • Jeremic B, Shibamoto Y, Milicic B, et al. Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. J Clin Oncol. 2000;18(7):1458–1464.
  • Rodriguez CP, Adelstein DJ, Rybicki LA, et al. Randomized phase III study of 2 cisplatin-based chemoradiation regimens in locally advanced head and neck squamous cell carcinoma: impact of changing disease epidemiology on contemporary trial design. Head Neck. 2015;37(11):1583–1589.
  • Blanchard P, Baujat B, Holostenco V, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): a comprehensive analysis by tumour site. Radiother Oncol. 2011;100(1):33–40.
  • Linot B, Augereau P, Breheret R, et al. Efficacy and safety of early G-CSF administration in patients with head and neck cancer treated by docetaxel-cisplatin and 5-fluorouracil (DCF protocol): a retrospective study. Support Care Cancer. 2014;22(10):2831–2837.
  • Wen J, Zeng M, Shu Y, et al. Aging increases the susceptibility of cisplatin-induced nephrotoxicity. Age (Dordr). 2015;37(6):112.
  • Jones R, Ryan M, Friedlander M. Carboplatin hypersensitivity reactions: re-treatment with cisplatin desensitisation. Gynecol Oncol. 2003;89(1):112–115.
  • Tsan DL, Lin CY, Kang CJ, et al. The comparison between weekly and three-weekly cisplatin delivered concurrently with radiotherapy for patients with postoperative high-risk squamous cell carcinoma of the oral cavity. Radiat Oncol. 2012;7:215.
  • Huguenin P, Beer KT, Allal A, et al. Concomitant cisplatin significantly improves locoregional control in advanced head and neck cancers treated with hyperfractionated radiotherapy. J Clin Oncol. 2004;22(23):4665–4673.
  • Ang KK. Concurrent radiation chemotherapy for locally advanced head and neck carcinoma: are we addressing burning subjects? J Clin Oncol. 2004;22(23):4657–4659.
  • Latcha S, Jaimes EA, Patil S, et al. Long-term renal outcomes after cisplatin treatment. Clin J Am Soc Nephrol. 2016;11(7):1173–1179.
  • Gregoire V, Lefebvre JL, Licitra L, et al. Squamous cell carcinoma of the head and neck: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(Suppl 5):v184–186.
  • Bonner JA, Harari PM, Giralt J, et al. 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):21–28.
  • Bhide SA, Nutting CM. Advances in radiotherapy for head and neck cancer. Oral Oncol. 2010;46(6):439–441.
  • Ghosh-Laskar S, Yathiraj PH, Dutta D, et al. Prospective randomized controlled trial to compare 3-dimensional conformal radiotherapy to intensity-modulated radiotherapy in head and neck squamous cell carcinoma: long-term results. Head Neck. 2016;38(Suppl 1):E1481–1487.
  • Ang KK, Zhang Q, Rosenthal DI, et al. Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. J Clin Oncol. 2014;32(27):2940–2950.
  • Abdel-Rahman O, Fouad M. Correlation of cetuximab-induced skin rash and outcomes of solid tumor patients treated with cetuximab: a systematic review and meta-analysis. Crit Rev Oncol Hematol. 2015;93(2):127–135.
  • Lacouture ME, Rodeck U. Skinflammation and drug toxicity–a delicate balance. Sci Transl Med. 2013;5(199):199fs33.
  • Fülöp T, Dupuis G, Witkowski JM, et al. The role of immunosenescence in the development of age-related diseases. Rev Invest Clin. 2016;68(2):84–91.
  • Jehn CF, Böning L, Kröning H, et al. Cetuximab-based therapy in elderly comorbid patients with metastatic colorectal cancer. Br J Cancer. 2012;106(2):274–278.
  • Garrido G, Tikhomirov IA, Rabasa A, et al. Bivalent binding by intermediate affinity of nimotuzumab: a contribution to explain antibody clinical profile. Cancer Biol Ther. 2011;11(4):373–382.
  • Crombet T, Osorio M, Cruz T, et al. Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients. J Clin Oncol. 2004;22(9):1646–1654.
  • Rodríguez MO, Rivero TC, Del Castillo Bahi R, et al. Nimotuzumab plus radiotherapy for unresectable squamous-cell carcinoma of the head and neck. Cancer Biol Ther. 2010;9(5):343–349.
  • Xu S, Ramos Suzarte M, Bai X, et al. Treatment outcome of nimotuzumab plus chemotherapy in advanced cancer patients: a single institute experience. Oncotarget. 2016 Mar 31. doi:10.18632/oncotarget.8516. [Epub ahead of print].
  • Nwizu T, Adelstein D. Pharmacotherapy of head and neck cancer. Expert Opin Pharmacother. 2015;16(16):2409–2422.
  • Hamoir M, Schmitz S, Gregoire V. The role of neck dissection in squamous cell carcinoma of the head and neck. Curr Treat Options Oncol. 2014;15(4):611–624.
  • Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004;350(19):1937–1944.
  • Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004;350(19):1945–1952.
  • Bernier J, Cooper JS, Pajak TF, et al. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck. 2005;27(10):843–850.
  • Forastiere AA, Zhang Q, Weber RS, et al. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013;31(7):845–852.
  • Forastiere AA, Goepfert H, Maor M, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003;349(22):2091–2098.
  • Haddad R, O’Neill A, Rabinowits G, et al. Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol. 2013;14(3):257–264.
  • Cohen EE, Karrison TG, Kocherginsky M, et al. Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer. J Clin Oncol. 2014;32(25):2735–2743.
  • Wong LY, Wei WI, Lam LK, et al. Salvage of recurrent head and neck squamous cell carcinoma after primary curative surgery. Head Neck. 2003;25(11):953–959.
  • Janot F, de Raucourt D, Benhamou E, et al. Randomized trial of postoperative reirradiation combined with chemotherapy after salvage surgery compared with salvage surgery alone in head and neck carcinoma. J Clin Oncol. 2008;26(34):5518–5523.
  • Morton RP, Rugman F, Dorman EB, et al. Cisplatinum and bleomycin for advanced or recurrent squamous cell carcinoma of the head and neck: a randomised factorial phase III controlled trial. Cancer Chemother Pharmacol. 1985;15(3):283–289.
  • The Liverpool Head and Neck Oncology Group. A phase III randomised trial of cistplatinum, methotrextate, cisplatinum + methotrexate and cisplatinum + 5-FU in end stage squamous carcinoma of the head and neck. Liverpool Head and Neck Oncology Group. Br J Cancer. 1990;61(2):311–315.
  • Forastiere AA, Metch B, Schuller DE, et al. Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: a Southwest Oncology Group study. J Clin Oncol. 1992;10(8):1245–1251.
  • Clavel M, Vermorken JB, Cognetti F, et al. Randomized comparison of cisplatin, methotrexate, bleomycin and vincristine (CABO) versus cisplatin and 5-fluorouracil (CF) versus cisplatin (C) in recurrent or metastatic squamous cell carcinoma of the head and neck. A phase III study of the EORTC Head and Neck Cancer Cooperative Group. Ann Oncol. 1994;5(6):521–526.
  • Janinis J, Papadakou M, Xidakis E, et al. Combination chemotherapy with docetaxel, cisplatin, and 5-fluorouracil in previously treated patients with advanced/recurrent head and neck cancer: a phase II feasibility study. Am J Clin Oncol. 2000;23(2):128–131.
  • Baghi M, Hambek M, Wagenblast J, et al. A phase II trial of docetaxel, cisplatin and 5-fluorouracil in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN). Anticancer Res. 2006;26(1B):585–590.
  • Burtness B, Goldwasser MA, Flood W, et al. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol. 2005;23(34):8646–8654.
  • Yang XD, Jia XC, Corvalan JR, et al. Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol. 2001;38(1):17–23.
  • Vermorken JB, Stöhlmacher-Williams J, Davidenko I, et al. Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial. Lancet Oncol. 2013;14(8):697–710.
  • Overdijk MB, Verploegen S, van den Brakel JH, et al. Epidermal growth factor receptor (EGFR) antibody-induced antibody-dependent cellular cytotoxicity plays a prominent role in inhibiting tumorigenesis, even of tumor cells insensitive to EGFR signaling inhibition. J Immunol. 2011;187(6):3383–3390.
  • Bleeker WK, Lammerts Van Bueren JJ, van Ojik HH, et al. Dual mode of action of a human anti-epidermal growth factor receptor monoclonal antibody for cancer therapy. J Immunol. 2004;173(7):4699–4707.
  • Machiels JP, Subramanian S, Ruzsa A, et al. Zalutumumab plus best supportive care versus best supportive care alone in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after failure of platinum-based chemotherapy: an open-label, randomised phase 3 trial. Lancet Oncol. 2011;12(4):333–343.
  • Argiris A, Ghebremichael M, Gilbert J, et al. Phase III randomized, placebo-controlled trial of docetaxel with or without gefitinib in recurrent or metastatic head and neck cancer: an eastern cooperative oncology group trial. J Clin Oncol. 2013;31(11):1405–1414.
  • Solca F, Dahl G, Zoephel A, et al. Target binding properties and cellular activity of afatinib (BIBW 2992), an irreversible ErbB family blocker. J Pharmacol Exp Ther. 2012;343(2):342–350.
  • Clement PM, Gauler T, Machiels JH, et al. Afatinib versus methotrexate in older patients with second-line recurrent and/or metastatic head and neck squamous cell carcinoma: subgroup analysis of the LUX-Head & Neck 1 trial. Ann Oncol. 2016;27(8):1585–1593.
  • Sunaoshi M, Amasaki Y, Hirano-Sakairi S, et al. The effect of age at exposure on the inactivating mechanisms and relative contributions of key tumor suppressor genes in radiation-induced mouse T-cell lymphomas. Mutat Res. 2015;779:58–67.
  • Lui VW, Hedberg ML, Li H, et al. Frequent mutation of the PI3K pathway in head and neck cancer defines predictive biomarkers. Cancer Discov. 2013;3(7):761–769.
  • Wang Z, Martin D, Molinolo AA, et al. mTOR co-targeting in cetuximab resistance in head and neck cancers harboring PIK3CA and RAS mutations. J Natl Cancer Inst. 2014;106:9.
  • Lattanzio L, Tonissi F, Monteverde M, et al. Treatment effect of buparlisib, cetuximab and irradiation in wild-type or PI3KCA-mutated head and neck cancer cell lines. Invest New Drugs. 2015;33(2):310–320.
  • D’Amato V, Rosa R, D’Amato C, et al. The dual PI3K/mTOR inhibitor PKI-587 enhances sensitivity to cetuximab in EGFR-resistant human head and neck cancer models. Br J Cancer. 2014;110(12):2887–2895.
  • Keam B, Kim S, Ahn YO, et al. In vitro anticancer activity of PI3K alpha selective inhibitor BYL719 in head and neck cancer. Anticancer Res. 2015;35(1):175–182.
  • Qian G, Jiang N, Wang D, et al. Heregulin and HER3 are prognostic biomarkers in oropharyngeal squamous cell carcinoma. Cancer. 2015;121(20):3600–3611.
  • Wheeler DL, Huang S, Kruser TJ, et al. Mechanisms of acquired resistance to cetuximab: role of HER (ErbB) family members. Oncogene. 2008;27(28):3944–3956.
  • Jiang N, Wang D, Hu Z, et al. Combination of anti-HER3 antibody MM-121/SAR256212 and cetuximab inhibits tumor growth in preclinical models of head and neck squamous cell carcinoma. Mol Cancer Ther. 2014;13(7):1826–1836.
  • Iida M, Brand TM, Starr MM, et al. Overcoming acquired resistance to cetuximab by dual targeting HER family receptors with antibody-based therapy. Mol Cancer. 2014;13:242.
  • Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol. 2015;33(17):1974–1982.
  • Leibowitz MS, Andrade Filho PA, Ferrone S, et al. Deficiency of activated STAT1 in head and neck cancer cells mediates TAP1-dependent escape from cytotoxic T lymphocytes. Cancer Immunol Immunother. 2011;60(4):525–535.
  • Ferris RL. Immunology and immunotherapy of head and neck cancer. J Clin Oncol. 2015;33(29):3293–3304.
  • Zou W, Chen L. Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol. 2008;8(6):467–477.
  • Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–2526.
  • Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–330.
  • Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803–1813.
  • Jie HB, Schuler PJ, Lee SC, et al. CTLA-4(+) regulatory T cells increased in cetuximab-treated head and neck cancer patients suppress NK cell cytotoxicity and correlate with poor prognosis. Cancer Res. 2015;75(11):2200–2210.
  • Tomihara K, Curiel TJ, Zhang B. Optimization of immunotherapy in elderly cancer patients. Crit Rev Oncog. 2013;18(6):573–583.
  • Nishijima TF, Muss HB, Shachar SS, et al. Comparison of efficacy of immune checkpoint inhibitors (ICIs) between younger and older patients: a systematic review and meta-analysis. Cancer Treat Rev. 2016;45:30–37.
  • Shestak KC, Jones NF, Wu W, et al. Effect of advanced age and medical disease on the outcome of microvascular reconstruction for head and neck defects. Head Neck. 1992;14(1):14–18.
  • Kowalski LP, Alcantara PS, Magrin J, et al. A case-control study on complications and survival in elderly patients undergoing major head and neck surgery. Am J Surg. 1994;168(5):485–490.
  • Allal AS, Maire D, Becker M, et al. Feasibility and early results of accelerated radiotherapy for head and neck carcinoma in the elderly. Cancer. 2000;88(3):648–652.
  • Huang SH, O’Sullivan B, Waldron J, et al. Patterns of care in elderly head-and-neck cancer radiation oncology patients: a single-center cohort study. Int J Radiat Oncol Biol Phys. 2011;79(1):46–51.
  • Michal SA, Adelstein DJ, Rybicki LA, et al. Multi-agent concurrent chemoradiotherapy for locally advanced head and neck squamous cell cancer in the elderly. Head Neck. 2012;34(8):1147–1152.
  • Merlano MC, Monteverde M, Colantonio I, et al. Impact of age on acute toxicity induced by bio- or chemo-radiotherapy in patients with head and neck cancer. Oral Oncol. 2012;48(10):1051–1057.

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