The demographics of squamous cell carcinoma of the head and neck (SCCHN) is marked by a growing number of patients aged 65 and over, which is in line with global projections for other cancer types. In developed countries, more than half of new SCCHN cases are diagnosed in older people, and in 15 years from now, the proportion is expected to rise by more than 10%. Still, a high-level evidence-based consensus to guide the clinical decision process is strikingly lacking. The available data from retrospective studies and subset analyses of prospective trials suffer from a considerable underrepresentation of senior participants. The situation is even more challenging in the recurrent and/or metastatic setting, where usually only palliative measures are employed. Nevertheless, it is becoming clear that, if treated irrespective of chronological age, fit elderly patients in a good general condition and with a low burden of comorbidities may derive a similar survival advantage as their younger counterparts. Despite that, undertreatment represents a widespread phenomenon and, together with competing non-cancer mortality, is suggested to be an important cause of the worse treatment outcomes observed in this population. Due to physiological changes in drug metabolism occurring with advancing age, the major concerns relate to chemotherapy administration. In locally advanced SCCHN, concurrent chemoradiotherapy in patients over 70 years remains a point of controversy owing to its possibly higher toxicity and questionable benefit. However, accumulating evidence suggests that it should, indeed, be considered in selected cases when biological age is taken into account. Results from a randomized trial conducted in lung cancer showed that treatment selection based on a comprehensive geriatric assessment (CGA) significantly reduced toxicity. However, a CGA is time-consuming and not necessary for all patients. To overcome this hurdle, geriatric screening tools have been introduced to decide who needs such a full evaluation. Among the various screening instruments, G8 and Flemish version of the Triage Risk Screening Tool were prospectively verified and found to have prognostic value. We, therefore, conclude that also in SCCHN, the application of elderly specific prospective trials and integration of clinical practice-oriented assessment tools and predictive models should be promoted.

Department of Internal Medicine Hematology and Oncology University Hospital Brno Brno Czech Republic; School of Medicine Masaryk University Brno Czech Republic

Department of Medical Oncology Antwerp University Hospital Edegem Belgium; Faculty of Medicine and Health Sciences University of Antwerp Antwerp Belgium

Zobrazit více v PubMed

Vokes EE, Weichselbaum RR, Lippman SM, Hong WK. Head and neck cancer. N Engl J Med (1993) 328:184–94.10.1056/NEJM199301213280306 PubMed DOI

National Cancer Institute. Head and Neck Cancers. (2013). Available from: http://www.cancer.gov/types/head-and-neck/head-neck-fact-sheet

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin (2015) 65:87–108.10.3322/caac.21262 PubMed DOI

Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Altekruse SF, et al. SEER Cancer Statistics Review, 1975-2013. Bethesda, MD: National Cancer Institute; (2016). Available from: http://seer.cancer.gov/csr/1975_2013/, based on November 2015 SEER data submission, posted to the SEER web site

Vermorken JB, Specenier P. Optimal treatment for recurrent/metastatic head and neck cancer. Ann Oncol (2010) 21(Suppl 7):vii252–61.10.1093/annonc/mdq453 PubMed DOI

Omran AR. The epidemiologic transition. A theory of the epidemiology of population change. Milbank Mem Fund Q (1971) 49:509–38.10.2307/3349375 PubMed DOI

Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008-2030): a population-based study. Lancet Oncol (2012) 13:790–801.10.1016/S1470-2045(12)70211-5 PubMed DOI

Sivasithamparam J, Visk CA, Cohen EE, King AC. Modifiable risk behaviors in patients with head and neck cancer. Cancer (2013) 119:2419–26.10.1002/cncr.27993 PubMed DOI PMC

Chaturvedi AK, Anderson WF, Lortet-Tieulent J, Curado MP, Ferlay J, Franceschi S, et al. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol (2013) 31:4550–9.10.1200/JCO.2013.50.3870 PubMed DOI PMC

Simard EP, Torre LA, Jemal A. International trends in head and neck cancer incidence rates: differences by country, sex and anatomic site. Oral Oncol (2014) 50:387–403.10.1016/j.oraloncology.2014.01.016 PubMed DOI

Kemeny MM, Peterson BL, Kornblith AB, Muss HB, Wheeler J, Levine E, et al. Barriers to clinical trial participation by older women with breast cancer. J Clin Oncol (2003) 21:2268–75.10.1200/JCO.2003.09.124 PubMed DOI

Decoster L. Geriatric oncology and supportive care: a global approach to advance the science. Belg J Med Oncol (2016) 10:108–9. PubMed

de Magalhães JP. How ageing processes influence cancer. Nat Rev Cancer (2013) 13:357–65.10.1038/nrc3497 PubMed DOI

Buchow H, Cayotte E, Agafitei L. Circulatory Diseases – Main Causes of Death for Persons Aged 65 and More in Europe, 2009. Statistics in Focus: Population and Social Conditions, 7/2012. Luxembourg: Eurostat; (2012). 12 p.

Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. International Agency for Research on Cancer. (2013). Available from: http://globocan.iarc.fr

Harding C, Pompei F, Wilson R. Peak and decline in cancer incidence, mortality, and prevalence at old ages. Cancer (2012) 118:1371–86.10.1002/cncr.26376 PubMed DOI

Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA. Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol (2009) 27:2758–65.10.1200/JCO.2008.20.8983 PubMed DOI

Gugić J, Strojan P. Squamous cell carcinoma of the head and neck in the elderly. Rep Pract Oncol Radiother (2012) 18:16–25.10.1016/j.rpor.2012.07.014 PubMed DOI PMC

Balducci L. Management of cancer in the elderly. Oncology (Williston Park) (2006) 20:135–43. PubMed

Argiris A, Li Y, Murphy BA, Langer CJ, Forastiere AA. Outcome of elderly patients with recurrent or metastatic head and neck cancer treated with cisplatin-based chemotherapy. J Clin Oncol (2004) 22:262–8.10.1200/JCO.2004.08.039 PubMed DOI

Hervás Morón A. Cancer in the elderly. Clin Transl Oncol (2007) 9:611–3.10.1007/s12094-007-0112-6 PubMed DOI

Kahana E, Kahana B. Baby boomers’ expectations of health and medicine. Virtual Mentor (2014) 16:380–4.10.1001/virtualmentor.2014.16.05.msoc2-1405 PubMed DOI PMC

Grénman R, Chevalier D, Gregoire V, Myers E, Rogers S. Treatment of head and neck cancer in the elderly: European consensus (panel 6) at the EUFOS congress in Vienna 2007. Eur Arch Otorhinolaryngol (2010) 267:1619–21.10.1007/s00405-010-1263-6 PubMed DOI

Moye VA, Chandramouleeswaran S, Zhao N, Muss HB, Weissler MC, Hayes DN, et al. Elderly patients with squamous cell carcinoma of the head and neck and the benefit of multimodality therapy. Oncologist (2015) 20:159–65.10.1634/theoncologist.2013-0325 PubMed DOI PMC

Derks W, de Leeuw RJ, Hordijk GJ, Winnubst JA. Quality of life in elderly patients with head and neck cancer one year after diagnosis. Head Neck (2004) 26:1045–52.10.1002/hed.20113 PubMed DOI

Derks W, Leeuw JR, Hordijk GJ, Winnubst JA. Differences in coping style and locus of control between older and younger patients with head and neck cancer. Clin Otolaryngol (2005) 30:186–92.10.1111/j.1365-2273.2004.00938.x PubMed DOI

Camilon PR, Stokes WA, Nguyen SA, Lentsch EJ. Are the elderly with oropharyngeal carcinoma undertreated? Laryngoscope (2014) 124:2057–63.10.1002/lary.24660 PubMed DOI

Sarris EG, Harrington KJ, Saif MW, Syrigos KN. Multimodal treatment strategies for elderly patients with head and neck cancer. Cancer Treat Rev (2014) 40:465–75.10.1016/j.ctrv.2013.10.007 PubMed DOI

Brugel L, Laurent M, Caillet P, Radenne A, Durand-Zaleski I, Martin M, et al. Impact of comprehensive geriatric assessment on survival, function, and nutritional status in elderly patients with head and neck cancer: protocol for a multicentre randomised controlled trial (EGeSOR). BMC Cancer (2014) 14:427.10.1186/1471-2407-14-427 PubMed DOI PMC

van der Schroeff MP, Derks W, Hordijk GJ, de Leeuw RJ. 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) 264:415–22.10.1007/s00405-006-0203-y PubMed DOI

Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol (2007) 25:1824–31.10.1200/JCO.2007.10.6559 PubMed DOI

Extermann M. Evaluation of the senior cancer patient: comprehensive geriatric assessment and screening tools for the elderly. In: Schrijvers D, Aapro M, Zakotnik B, Audisio R, van Halteren H, Hurria A, editors. ESMO handbook of cancer in the senior patient. London: Informa Healthcare; (2010). p. 13–21.

Mohile SG, Magnuson A. Comprehensive geriatric assessment in oncology. Interdiscip Top Gerontol (2013) 38:85–103.10.1159/000343608 PubMed DOI

Extermann M, Overcash J, Lyman GH, Parr J, Balducci L. Comorbidity and functional status are independent in older cancer patients. J Clin Oncol (1998) 16:1582–7. PubMed

Horiot JC, Aapro MS. Treatment of the elderly head and neck cancer patient. In: Bernier J, editor. Head and Neck Cancer: Multimodality Management. New York: Springer; (2011). p. 581–8.

Sanabria A, Carvalho AL, Vartanian JG, Magrin J, Ikeda MK, Kowalski LP. Comorbidity is a prognostic factor in elderly patients with head and neck cancer. Ann Surg Oncol (2007) 14:1449–57.10.1245/s10434-006-9296-1 PubMed DOI

Paleri V, Wight RG, Silver CE, Haigentz M, Jr, Takes RP, Bradley PJ, et al. Comorbidity in head and neck cancer: a critical appraisal and recommendations for practice. Oral Oncol (2010) 46:712–9.10.1016/j.oraloncology.2010.07.008 PubMed DOI

Piccirillo JF, Tierney RM, Costas I, Grove L, Spitznagel EL, Jr. Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA (2004) 291:2441–7.10.1001/jama.291.20.2441 PubMed DOI

Tanvetyanon T, Padhya T, McCaffrey J, Zhu W, Boulware D, Deconti R, et al. Prognostic factors for survival after salvage reirradiation of head and neck cancer. J Clin Oncol (2009) 27:1983–91.10.1200/JCO.2008.20.0691 PubMed DOI

Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med (2010) 363:24–35.10.1056/NEJMoa0912217 PubMed DOI PMC

Rietbergen MM, Brakenhoff RH, Bloemena E, Witte BI, Snijders PJ, Heideman DA, et al. Human papillomavirus detection and comorbidity: critical issues in selection of patients with oropharyngeal cancer for treatment De-escalation trials. Ann Oncol (2013) 24:2740–5.10.1093/annonc/mdt319 PubMed DOI

Locher JL, Bonner JA, Carroll WR, Caudell JJ, Keith JN, Kilgore ML, et al. Prophylactic percutaneous endoscopic gastrostomy tube placement in treatment of head and neck cancer: a comprehensive review and call for evidence-based medicine. JPEN J Parenter Enteral Nutr (2011) 35:365–74.10.1177/0148607110377097 PubMed DOI

Kenis C, Decoster L, Van Puyvelde K, De Grève J, Conings G, Milisen K, et al. Performance of two geriatric screening tools in older patients with cancer. J Clin Oncol (2014) 32:19–26.10.1200/JCO.2013.51.1345 PubMed DOI

PACE participants. Audisio RA, Pope D, Ramesh HS, Gennari R, van Leeuwen BL, et al. Shall we operate? Preoperative assessment in elderly cancer patients (PACE) can help. A SIOG surgical task force prospective study. Crit Rev Oncol Hematol (2008) 65:156–63.10.1016/j.critrevonc.2007.11.001 PubMed DOI

Girre V, Falcou MC, Gisselbrecht M, Gridel G, Mosseri V, Bouleuc C, et al. Does a geriatric oncology consultation modify the cancer treatment plan for elderly patients? J Gerontol A Biol Sci Med Sci (2008) 63:724–30.10.1093/gerona/63.7.724 PubMed DOI

Chaïbi P, Magné N, Breton S, Chebib A, Watson S, Duron JJ, et al. Influence of geriatric consultation with comprehensive geriatric assessment on final therapeutic decision in elderly cancer patients. Crit Rev Oncol Hematol (2011) 79:302–7.10.1016/j.critrevonc.2010.08.004 PubMed DOI

National Comprehensive Cancer Network. Older Adult Oncology (Version 1.2016). (2016). Available from: https://www.nccn.org/professionals/physician_gls/pdf/senior.pdf

Wildiers H, Brain E, Penninckx B, Ring A, Repetto L, Soubeyran P, et al. The EORTC cancer in the elderly task force, a protostar for EORTC’s future. Eur J Cancer Suppl (2012) 10:34–8.10.1016/S1359-6349(12)70008-3 DOI

Extermann M, Aapro M, Bernabei R, Cohen HJ, Droz JP, Lichtman S, et al. Use of comprehensive geriatric assessment in older cancer patients: recommendations from the task force on CGA of the International Society of Geriatric Oncology (SIOG). Crit Rev Oncol Hematol (2005) 55:241–52.10.1016/j.critrevonc.2005.06.003 PubMed DOI

Corre R, Greillier L, Le Caër H, Audigier-Valette C, Baize N, Bérard H, et al. Use of a comprehensive geriatric assessment for the management of elderly patients with advanced non-small-cell lung cancer: the phase III randomized ESOGIA-GFPC-GECP 08-02 study. J Clin Oncol (2016) 34:1476–83.10.1200/JCO.2015.63.5839 PubMed DOI

Presley CJ, Gross CP, Lilenbaum RC. Optimizing treatment risk and benefit for elderly patients with advanced non-small-cell lung cancer: the right treatment for the right patient. J Clin Oncol (2016) 34:1438–42.10.1200/JCO.2015.65.9599 PubMed DOI

Decoster L, Van Puyvelde K, Mohile S, Wedding U, Basso U, Colloca G, et al. Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations†. Ann Oncol (2015) 26:288–300.10.1093/annonc/mdu210 PubMed DOI

Perri F, Ionna F, Pavone E, Longo F, Caponigro F. Treatment approaches in elderly patients with head and neck cancer. Anticancer Agents Med Chem (2013) 13:1383–90.10.2174/18715206113136660355 PubMed DOI

National Comprehensive Cancer Network. Head and Neck Cancers (Version 1.2016). (2016). Available from: https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf PubMed PMC

Grégoire V, Lefebvre JL, Licitra L, Felip E. EHNS-ESMO-ESTRO guidelines working group. 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):v184–6.10.1093/annonc/mdq185 PubMed DOI

Carmona R, Zakeri K, Green G, Hwang L, Gulaya S, Xu B, et al. Improved method to stratify elderly patients with cancer at risk for competing events. J Clin Oncol (2016) 34:1270–7.10.1200/JCO.2015.65.0739 PubMed DOI PMC

McGuirt WF, Loevy S, McCabe BF, Krause CJ. The risks of major head and neck surgery in the aged population. Laryngoscope (1977) 87:1378–82.10.1288/00005537-197708000-00017 PubMed DOI

Morgan RF, Hirata RM, Jaques DA, Hoopes JE. Head and neck surgery in the aged. Am J Surg (1982) 144:449–51.10.1016/0002-9610(82)90420-2 PubMed DOI

Clayman GL, Eicher SA, Sicard MW, Razmpa E, Goepfert H. Surgical outcomes in head and neck cancer patients 80 years of age and older. Head Neck (1998) 20:216–23.10.1002/(SICI)1097-0347(199805)20:3<216::AID-HED6>3.0.CO;2-3 PubMed DOI

Ferrier MB, Spuesens EB, Le Cessie S, Baatenburg de Jong RJ. Comorbidity as a major risk factor for mortality and complications in head and neck surgery. Arch Otolaryngol Head Neck Surg (2005) 131:27–32.10.1001/archotol.131.1.27 PubMed DOI

Sanabria A, Carvalho AL, Melo RL, Magrin J, Ikeda MK, Vartanian JG, et al. Predictive factors for complications in elderly patients who underwent head and neck oncologic surgery. Head Neck (2008) 30:170–7.10.1002/hed.20671 PubMed DOI

Pignon T, Horiot JC, Van den Bogaert W, Van Glabbeke M, Scalliet P. No age limit for radical radiotherapy in head and neck tumours. Eur J Cancer (1996) 32A:2075–81.10.1016/S0959-8049(96)00265-1 PubMed DOI

Lusinchi A, Bourhis J, Wibault P, Le Ridant AM, Eschwege F. Radiation therapy for head and neck cancers in the elderly. Int J Radiat Oncol Biol Phys (1990) 18:819–23.10.1016/0360-3016(90)90403-7 PubMed DOI

Ortholan C, Lusinchi A, Italiano A, Bensadoun RJ, Auperin A, Poissonnet G, et al. Oral cavity squamous cell carcinoma in 260 patients aged 80years or more. Radiother Oncol (2009) 93:516–23.10.1016/j.radonc.2009.07.015 PubMed DOI

Bourhis J, Overgaard J, Audry H, Ang KK, Saunders M, Bernier J, et al. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet (2006) 368:843–54.10.1016/S0140-6736(06)69121-6 PubMed DOI

Corry J, Peters LJ, Costa ID, Milner AD, Fawns H, Rischin D, et al. The ‘QUAD SHOT’ – a phase II study of palliative radiotherapy for incurable head and neck cancer. Radiother Oncol (2005) 77:137–42.10.1016/j.radonc.2005.10.008 PubMed DOI

Porceddu SV, Rosser B, Burmeister BH, Jones M, Hickey B, Baumann K, et al. Hypofractionated radiotherapy for the palliation of advanced head and neck cancer in patients unsuitable for curative treatment – “Hypo Trial”. Radiother Oncol (2007) 85:456–62.10.1016/j.radonc.2007.10.020 PubMed DOI

Al-mamgani A, Tans L, Van rooij PH, Noever I, Baatenburg de jong RJ, Levendag PC. Hypofractionated radiotherapy denoted as the “Christie scheme”: an effective means of palliating patients with head and neck cancers not suitable for curative treatment. Acta Oncol (2009) 48:562–70.10.1080/02841860902740899 PubMed DOI

Nguyen NT, Doerwald-Munoz L, Zhang H, Kim DH, Sagar S, Wright JR, et al. 0-7-21 Hypofractionated palliative radiotherapy: an effective treatment for advanced head and neck cancers. Br J Radiol (2015) 88:20140646.10.1259/bjr.20140646 PubMed DOI PMC

van Beek KM, Kaanders JH, Janssens GO, Takes RP, Span PN, Verhoef CG. Effectiveness and toxicity of hypofractionated high-dose intensity-modulated radiotherapy versus 2- and 3-dimensional radiotherapy in incurable head and neck cancer. Head Neck (2016) 38(Suppl 1):E1264–70.10.1002/hed.24203 PubMed DOI

Bledsoe TJ, Noble AR, Reddy CA, Burkey BB, Greskovich JF, Nwizu T, et al. Split-course accelerated hypofractionated radiotherapy (SCAHRT): a safe and effective option for head and neck cancer in the elderly or infirm. Anticancer Res (2016) 36:933–9. PubMed

Amini A, McDermott JD, Gan G, Bhatia S, Sumner W, Fisher CM, et al. Stereotactic body radiotherapy as primary therapy for head and neck cancer in the elderly or patients with poor performance. Front Oncol (2014) 4:274.10.3389/fonc.2014.00274 PubMed DOI PMC

Vargo JA, Ferris RL, Clump DA, Heron DE. Stereotactic body radiotherapy as primary treatment for elderly patients with medically inoperable head and neck cancer. Front Oncol (2014) 4:214.10.3389/fonc.2014.00214 PubMed DOI PMC

Pignon JP, le Maître A, Maillard E, Bourhis J, MACH-NC Collaborative Group . Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol (2009) 92:4–14.10.1016/j.radonc.2009.04.014 PubMed DOI

Machtay M, Moughan J, Trotti A, Garden AS, Weber RS, Cooper JS, et al. Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol (2008) 26:3582–9.10.1200/JCO.2007.14.8841 PubMed DOI PMC

Kish JA, Zhang Q, Langer CJ, Nguyen-Tan F, Rosenthal DI, Weber RS, et al. The effect of age on outcome in prospective, phase III NRG oncology/RTOG trials of radiotherapy (XRT) +/− chemotherapy in locally advanced (LA) head and neck cancer (HNC). J Clin Oncol (2015) 33(Suppl; abstr 6003).

Amini A, Jones BL, McDermott JD, Serracino HS, Jimeno A, Raben D, 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) 122:1533–43.10.1002/cncr.29956 PubMed DOI

VanderWalde NA, Meyer AM, Deal AM, Layton JB, Liu H, Carpenter WR, et al. Effectiveness of chemoradiation for head and neck cancer in an older patient population. Int J Radiat Oncol Biol Phys (2014) 89:30–7.10.1016/j.ijrobp.2014.01.053 PubMed DOI

Naeim A, Aapro M, Subbarao R, Balducci L. Supportive care considerations for older adults with cancer. J Clin Oncol (2014) 32:2627–34.10.1200/JCO.2014.55.3065 PubMed DOI

Chang PH, Yeh KY, Huang JS, Chen EY, Yang SW, Wang CH. Chemoradiotherapy in elderly patients with advanced head and neck cancer under intensive nutritional support. Asia Pac J Clin Oncol (2015) 11:228–35.10.1111/ajco.12323 PubMed DOI

Calvert AH, Newell DR, Gumbrell LA, O’Reilly S, Burnell M, Boxall FE, et al. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol (1989) 7:1748–56. PubMed

Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol (2011) 29:3457–65.10.1200/JCO.2011.34.7625 PubMed DOI PMC

Hurria A, Mohile S, Gajra A, Klepin H, Muss H, Chapman A, et al. Validation of a prediction tool for chemotherapy toxicity in older adults with cancer. J Clin Oncol (2016) 34:2366–71.10.1200/JCO.2015.65.4327 PubMed DOI PMC

Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med (2006) 354:567–78.10.1056/NEJMoa053422 PubMed DOI

Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med (2008) 359:1116–27.10.1056/NEJMoa0802656 PubMed DOI

Giro C, Berger B, Bölke E, Ciernik IF, Duprez F, Locati L, et al. High rate of severe radiation dermatitis during radiation therapy with concurrent cetuximab in head and neck cancer: results of a survey in EORTC institutes. Radiother Oncol (2009) 90:166–71.10.1016/j.radonc.2008.09.007 PubMed DOI

Pryor DI, Porceddu SV, Burmeister BH, Guminski A, Thomson DB, Shepherdson K, et al. Enhanced toxicity with concurrent cetuximab and radiotherapy in head and neck cancer. Radiother Oncol (2009) 90:172–6.10.1016/j.radonc.2008.09.018 PubMed DOI

Petrelli F, Coinu A, Riboldi V, Borgonovo K, Ghilardi M, Cabiddu M, et al. Concomitant platinum-based chemotherapy or cetuximab with radiotherapy for locally advanced head and neck cancer: a systematic review and meta-analysis of published studies. Oral Oncol (2014) 50:1041–8.10.1016/j.oraloncology.2014.08.005 PubMed DOI

Magrini SM, Buglione M, Corvò R, Pirtoli L, Paiar F, Ponticelli P, et al. Cetuximab and radiotherapy versus cisplatin and radiotherapy for locally advanced head and neck cancer: a randomized phase II trial. J Clin Oncol (2016) 34:427–35.10.1200/JCO.2015.63.1671 PubMed DOI

Husain ZA, Burtness BA, Decker RH. Cisplatin versus cetuximab with radiotherapy in locally advanced squamous cell carcinoma of the head and neck. J Clin Oncol (2016) 34:396–8.10.1200/JCO.2015.64.7586 PubMed DOI

Specenier P, Vermorken JB. Locoregionally advanced squamous cell carcinoma of the head and neck: chemoradiation or bioradiation. Transl Cancer Res (2016) 5:223–8.10.21037/tcr.2016.06.29 DOI

Curran D, Giralt J, Harari PM, Ang KK, Cohen RB, Kies MS, et al. Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab. J Clin Oncol (2007) 25:2191–7.10.1200/JCO.2006.08.8005 PubMed DOI

Ahn MJ, D’Cruz A, Vermorken JB, Chen JP, Chitapanarux I, Dang HQ, et al. Clinical recommendations for defining platinum unsuitable head and neck cancer patient populations on chemoradiotherapy: a literature review. Oral Oncol (2016) 53:10–6.10.1016/j.oraloncology.2015.11.019 PubMed DOI

Ferris RL. Immunology and immunotherapy of head and neck cancer. J Clin Oncol (2015) 33:3293–304.10.1200/JCO.2015.61.1509 PubMed DOI PMC

Casares N, Pequignot MO, Tesniere A, Ghiringhelli F, Roux S, Chaput N, et al. Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death. J Exp Med (2005) 202:1691–701.10.1084/jem.20050915 PubMed DOI PMC

Kepp O, Senovilla L, Vitale I, Vacchelli E, Adjemian S, Agostinis P, et al. Consensus guidelines for the detection of immunogenic cell death. Oncoimmunology (2014) 3:e955691.10.4161/21624011.2014.955691 PubMed DOI PMC

Derer A, Frey B, Fietkau R, Gaipl US. Immune-modulating properties of ionizing radiation: rationale for the treatment of cancer by combination radiotherapy and immune checkpoint inhibitors. Cancer Immunol Immunother (2016) 65:779–86.10.1007/s00262-015-1771-8 PubMed DOI PMC

Teng F, Kong L, Meng X, Yang J, Yu J. Radiotherapy combined with immune checkpoint blockade immunotherapy: achievements and challenges. Cancer Lett (2015) 365:23–9.10.1016/j.canlet.2015.05.012 PubMed DOI

Vermorken JB. Systemic treatment of recurrent/metastatic squamous cell carcinoma of the head and neck. In: Bernier J, editor. Head and Neck Cancer: Multimodality Management. New York: Springer; (2011). p. 651–64.

Young ER, Diakos E, Khalid-Raja M, Mehanna H. Resection of subsequent pulmonary metastases from treated head and neck squamous cell carcinoma: systematic review and meta-analysis. Clin Otolaryngol (2015) 40:208–18.10.1111/coa.12348 PubMed DOI

Buglione M, Maddalo M, Mazzeo E, Bonomo P, Spiazzi L, Bruni A, et al. Reirradiation in head and neck recurrent or second primary tumor: efficacy, safety, and prognostic factors. Tumori (2015) 101:585–92.10.5301/tj.5000368 PubMed DOI

Machiels JP, Haddad RI, Fayette J, Licitra LF, Tahara M, Vermorken JB, 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) 16:583–94.10.1016/S1470-2045(15)70124-5 PubMed DOI

Clement PM, Gauler T, Machiels JH, Haddad RI, Fayette J, Licitra LF, 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) 27:1585–93.10.1093/annonc/mdw151 PubMed DOI PMC

Gillison ML, Blumenschein G, Jr, Fayette J, Guigay J, Colevas AD, Licitra L, et al. Nivolumab Versus Investigator’s Choice (IC) for Recurrent or Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (SCCHN): CheckMate-141. New Orleans, LA: American Association for Cancer Research; (2016).

Seiwert TY, Burtness B, Weiss J, Gluck I, Eder JP, Pai SI, et al. A phase Ib study of MK-3475 in patients with human papillomavirus (HPV)-associated and non-HPV-associated head and neck (H/N) cancer. J Clin Oncol (2014) 32(Suppl; abstr 6011).

Fury M, Ou SI, Balmanoukian A, Hansen A, Massarelli E, Blake-Haskins A, et al. Clinical activity and safety of MEDI4736, an anti-PD-L1 antibody, in patients with head and neck cancer. Ann Oncol (2014) 25(Suppl 4):iv341.

Guigay J, Le Caer H, Mertens C, Ortholan C, Blot E, Tao Y, et al. Elderly head and neck cancer (ELAN) study: personalized treatment according to geriatric assessment in patients age 70 or older: first prospective trials in patients with squamous cell cancer of the head and neck (SCCHN) unsuitable for surgery. J Clin Oncol (2014) 32(Suppl; abstr TPS6099).

Giant locally advanced and metastatic squamous cell skin carcinoma of head and neck region: case report