Management and prevention of complications during initial treatment of head and neck cancer
- Thomas Galloway, MD
Thomas Galloway, MD
- Assistant Professor
- Department of Radiation Oncology
- Fox Chase Cancer Center
- Robert J Amdur, MD
Robert J Amdur, MD
- Department of Radiation Oncology
- University of Florida College of Medicine
- Section Editors
- Marshall R Posner, MD
Marshall R Posner, MD
- Section Editor — Cancer of the Head and Neck
- Professor of Gene and Cell Medicine
- The Tisch Cancer Institute
- Icahn School of Medicine at Mount Sinai
- Bruce E Brockstein, MD
Bruce E Brockstein, MD
- Section Editor — Cancer of the Head and Neck
- Clinical Professor of Medicine
- University of Chicago Pritzker School of Medicine
- David M Brizel, MD
David M Brizel, MD
- Section Editor — Radiation Therapy
- Leonard R Prosnitz Professor of Radiation Oncology
- Professor of Otolaryngology Head & Neck Surgery
- Duke University Cancer Institute
- Daniel G Deschler, MD, FACS
Daniel G Deschler, MD, FACS
- Section Editor — Otorhinolaryngology
- Professor of Otology and Laryngology
- Harvard Medical School
Toxicity from cancer therapy is classified as acute or late based upon its temporal relationship to treatment. Acute toxicity develops during or shortly after the completion of treatment and is usually temporary. Late toxicity presents months to years after the completion of treatment and is often permanent. The term "complication" is used for a treatment toxicity that causes an important medical problem.
This topic will review the care of patients with head and neck cancer during their initial therapy, both to treat acute toxicity and to prevent late complications. The management of late complications is discussed separately. (See "Management of late complications of head and neck cancer and its treatment".)
Spectrum of issues — Cancers of the upper aerodigestive tract are in close proximity to organs vital to a patient's quality of life (eg, tongue, larynx, mandible), and they often emanate from such organs. The involvement of these structures with cancer and the steps needed to eradicate the malignancy can cause a wide spectrum of toxicities.
The most basic toxicities are the impairment in the ability to breathe, communicate, and maintain an adequate oral intake. Oral intake is compromised by swallowing problems (dysphagia and odynophagia), poor taste (dysgeusia), trismus, xerostomia, and mucositis. Respiration and communication can be compromised by bulky tumors, neuromuscular impairment secondary to tumor growth, or an edematous pharynx and/or larynx. In addition to toxicity limiting the ability to speak, eat, and breathe, patients can experience cutaneous toxicity from both radiation and targeted therapy (cetuximab), neurotoxicity from both commonly used chemotherapy agents (cisplatin) and radiation, and dental complications from the effects of radiation dose to the mandible/maxilla and salivary glands.
The treatment of these tumors is complex and best handled by a coordinated team involving surgeons, radiation oncologists, medical oncologists, dentists, oral surgeons, speech pathologists, physical/occupational therapists, nutritionists, and skilled nurses.
- Valero V, Holmes FA, Walters RS, et al. Phase II trial of docetaxel: a new, highly effective antineoplastic agent in the management of patients with anthracycline-resistant metastatic breast cancer. J Clin Oncol 1995; 13:2886.
- Piccart MJ, Klijn J, Paridaens R, et al. Corticosteroids significantly delay the onset of docetaxel-induced fluid retention: final results of a randomized study of the European Organization for Research and Treatment of Cancer Investigational Drug Branch for Breast Cancer. J Clin Oncol 1997; 15:3149.
- Ang KK, et AL. A randomized phase III trial (RTOG 0522) of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III-IV head and neck squamous cell carcinomas (abstract #5500). J Clin Oncol 2011.
- Rugg T, Saunders MI, Dische S. Smoking and mucosal reactions to radiotherapy. Br J Radiol 1990; 63:554.
- Browman GP, Wong G, Hodson I, et al. Influence of cigarette smoking on the efficacy of radiation therapy in head and neck cancer. N Engl J Med 1993; 328:159.
- Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010; 363:24.
- Burlage FR, Coppes RP, Meertens H, et al. Parotid and submandibular/sublingual salivary flow during high dose radiotherapy. Radiother Oncol 2001; 61:271.
- Avila JL, Grundmann O, Burd R, Limesand KH. Radiation-induced salivary gland dysfunction results from p53-dependent apoptosis. Int J Radiat Oncol Biol Phys 2009; 73:523.
- Abok K, Brunk U, Jung B, Ericsson J. Morphologic and histochemical studies on the differing radiosensitivity of ductular and acinar cells of the rat submandibular gland. Virchows Arch B Cell Pathol Incl Mol Pathol 1984; 45:443.
- Nagler R, Marmary Y, Fox PC, et al. Irradiation-induced damage to the salivary glands: the role of redox-active iron and copper. Radiat Res 1997; 147:468.
- Deasy JO, Moiseenko V, Marks L, et al. Radiotherapy dose-volume effects on salivary gland function. Int J Radiat Oncol Biol Phys 2010; 76:S58.
- Chao KS, Deasy JO, Markman J, et al. A prospective study of salivary function sparing in patients with head-and-neck cancers receiving intensity-modulated or three-dimensional radiation therapy: initial results. Int J Radiat Oncol Biol Phys 2001; 49:907.
- Blanco AI, Chao KS, El Naqa I, et al. Dose-volume modeling of salivary function in patients with head-and-neck cancer receiving radiotherapy. Int J Radiat Oncol Biol Phys 2005; 62:1055.
- Eisbruch A, Kim HM, Terrell JE, et al. Xerostomia and its predictors following parotid-sparing irradiation of head-and-neck cancer. Int J Radiat Oncol Biol Phys 2001; 50:695.
- Murdoch-Kinch CA, Kim HM, Vineberg KA, et al. Dose-effect relationships for the submandibular salivary glands and implications for their sparing by intensity modulated radiotherapy. Int J Radiat Oncol Biol Phys 2008; 72:373.
- Nutting CM, Morden JP, Harrington KJ, et al. Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol 2011; 12:127.
- Kam MK, Leung SF, Zee B, et al. Prospective randomized study of intensity-modulated radiotherapy on salivary gland function in early-stage nasopharyngeal carcinoma patients. J Clin Oncol 2007; 25:4873.
- Brizel DM, Wasserman TH, Henke M, et al. Phase III randomized trial of amifostine as a radioprotector in head and neck cancer. J Clin Oncol 2000; 18:3339.
- Wasserman TH, Brizel DM, Henke M, et al. Influence of intravenous amifostine on xerostomia, tumor control, and survival after radiotherapy for head-and- neck cancer: 2-year follow-up of a prospective, randomized, phase III trial. Int J Radiat Oncol Biol Phys 2005; 63:985.
- Bourhis J, Blanchard P, Maillard E, et al. Effect of amifostine on survival among patients treated with radiotherapy: a meta-analysis of individual patient data. J Clin Oncol 2011; 29:2590.
- Antonadou D, Pepelassi M, Synodinou M, et al. Prophylactic use of amifostine to prevent radiochemotherapy-induced mucositis and xerostomia in head-and-neck cancer. Int J Radiat Oncol Biol Phys 2002; 52:739.
- Büntzel J, Küttner K, Fröhlich D, Glatzel M. Selective cytoprotection with amifostine in concurrent radiochemotherapy for head and neck cancer. Ann Oncol 1998; 9:505.
- Vacha P, Fehlauer F, Mahlmann B, et al. Randomized phase III trial of postoperative radiochemotherapy +/- amifostine in head and neck cancer. Is there evidence for radioprotection? Strahlenther Onkol 2003; 179:385.
- Buentzel J, Micke O, Adamietz IA, et al. Intravenous amifostine during chemoradiotherapy for head-and-neck cancer: a randomized placebo-controlled phase III study. Int J Radiat Oncol Biol Phys 2006; 64:684.
- Bardet E, Martin L, Calais G, et al. Subcutaneous compared with intravenous administration of amifostine in patients with head and neck cancer receiving radiotherapy: final results of the GORTEC2000-02 phase III randomized trial. J Clin Oncol 2011; 29:127.
- Hensley ML, Hagerty KL, Kewalramani T, et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol 2009; 27:127.
- Liu XK, Su Y, Jha N, et al. Submandibular salivary gland transfer for the prevention of radiation-induced xerostomia in patients with nasopharyngeal carcinoma: 5-Year outcomes. Head Neck 2011; 33:389.
- Jha N, Seikaly H, Harris J, et al. Phase III randomized study: oral pilocarpine versus submandibular salivary gland transfer protocol for the management of radiation-induced xerostomia. Head Neck 2009; 31:234.
- Jha N, Harris J, Seikaly H, et al. A phase II study of submandibular gland transfer prior to radiation for prevention of radiation-induced xerostomia in head-and-neck cancer (RTOG 0244). Int J Radiat Oncol Biol Phys 2012; 84:437.
- Rieger JM, Jha N, Lam Tang JA, et al. Functional outcomes related to the prevention of radiation-induced xerostomia: oral pilocarpine versus submandibular salivary gland transfer. Head Neck 2012; 34:168.
- Epstein JB, Epstein JD, Epstein MS, et al. Oral doxepin rinse: the analgesic effect and duration of pain reduction in patients with oral mucositis due to cancer therapy. Anesth Analg 2006; 103:465.
- Leenstra JL, Miller RC, Qin R, et al. Doxepin rinse versus placebo in the treatment of acute oral mucositis pain in patients receiving head and neck radiotherapy with or without chemotherapy: a phase III, randomized, double-blind trial (NCCTG-N09C6 [Alliance]). J Clin Oncol 2014; 32:1571.
- Jensen SB, Pedersen AM, Vissink A, et al. A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact. Support Care Cancer 2010; 18:1061.
- Epstein JB, Burchell JL, Emerton S, et al. A clinical trial of bethanechol in patients with xerostomia after radiation therapy. A pilot study. Oral Surg Oral Med Oral Pathol 1994; 77:610.
- Scarantino C, LeVeque F, Swann RS, et al. Effect of pilocarpine during radiation therapy: results of RTOG 97-09, a phase III randomized study in head and neck cancer patients. J Support Oncol 2006; 4:252.
- Warde P, O'Sullivan B, Aslanidis J, et al. A Phase III placebo-controlled trial of oral pilocarpine in patients undergoing radiotherapy for head-and-neck cancer. Int J Radiat Oncol Biol Phys 2002; 54:9.
- Jham BC, Teixeira IV, Aboud CG, et al. A randomized phase III prospective trial of bethanechol to prevent radiotherapy-induced salivary gland damage in patients with head and neck cancer. Oral Oncol 2007; 43:137.
- Jaguar GC, Lima EN, Kowalski LP, et al. Double blind randomized prospective trial of bethanechol in the prevention of radiation-induced salivary gland dysfunction in head and neck cancer patients. Radiother Oncol 2015; 115:253.
- Forner L, Hyldegaard O, von Brockdorff AS, et al. Does hyperbaric oxygen treatment have the potential to increase salivary flow rate and reduce xerostomia in previously irradiated head and neck cancer patients? A pilot study. Oral Oncol 2011; 47:546.
- Teguh DN, Levendag PC, Noever I, et al. Early hyperbaric oxygen therapy for reducing radiotherapy side effects: early results of a randomized trial in oropharyngeal and nasopharyngeal cancer. Int J Radiat Oncol Biol Phys 2009; 75:711.
- Meng Z, Garcia MK, Hu C, et al. Randomized controlled trial of acupuncture for prevention of radiation-induced xerostomia among patients with nasopharyngeal carcinoma. Cancer 2012; 118:3337.
- Meng Z, Kay Garcia M, Hu C, et al. Sham-controlled, randomised, feasibility trial of acupuncture for prevention of radiation-induced xerostomia among patients with nasopharyngeal carcinoma. Eur J Cancer 2012; 48:1692.
- Elting LS, Cooksley CD, Chambers MS, Garden AS. Risk, outcomes, and costs of radiation-induced oral mucositis among patients with head-and-neck malignancies. Int J Radiat Oncol Biol Phys 2007; 68:1110.
- 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; 357:1705.
- Nguyen-Tan PF, Zhang Q, Ang KK, et al. 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; 32:3858.
- Allison RR, Ambrad AA, Arshoun Y, et al. Multi-institutional, randomized, double-blind, placebo-controlled trial to assess the efficacy of a mucoadhesive hydrogel (MuGard) in mitigating oral mucositis symptoms in patients being treated with chemoradiation therapy for cancers of the head and neck. Cancer 2014; 120:1433.
- Epstein JB, Silverman S Jr, Paggiarino DA, et al. Benzydamine HCl for prophylaxis of radiation-induced oral mucositis: results from a multicenter, randomized, double-blind, placebo-controlled clinical trial. Cancer 2001; 92:875.
- McNeil Consumer and Specialty Pharmaceuticals study report
- Le QT, Kim HE, Schneider CJ, et al. Palifermin reduces severe mucositis in definitive chemoradiotherapy of locally advanced head and neck cancer: a randomized, placebo-controlled study. J Clin Oncol 2011; 29:2808.
- Henke M, Alfonsi M, Foa P, et al. Palifermin decreases severe oral mucositis of patients undergoing postoperative radiochemotherapy for head and neck cancer: a randomized, placebo-controlled trial. J Clin Oncol 2011; 29:2815.
- Bensadoun RJ, Franquin JC, Ciais G, et al. Low-energy He/Ne laser in the prevention of radiation-induced mucositis. A multicenter phase III randomized study in patients with head and neck cancer. Support Care Cancer 1999; 7:244.
- Arun Maiya G, Sagar MS, Fernandes D. Effect of low level helium-neon (He-Ne) laser therapy in the prevention & treatment of radiation induced mucositis in head & neck cancer patients. Indian J Med Res 2006; 124:399.
- Gouvêa de Lima A, Villar RC, de Castro G Jr, et al. Oral mucositis prevention by low-level laser therapy in head-and-neck cancer patients undergoing concurrent chemoradiotherapy: a phase III randomized study. Int J Radiat Oncol Biol Phys 2012; 82:270.
- Bensadoun RJ, Nair RG. Low-level laser therapy in the prevention and treatment of cancer therapy-induced mucositis: 2012 state of the art based on literature review and meta-analysis. Curr Opin Oncol 2012; 24:363.
- Gautam AP, Fernandes DJ, Vidyasagar MS, et al. Low level laser therapy for concurrent chemoradiotherapy induced oral mucositis in head and neck cancer patients - a triple blinded randomized controlled trial. Radiother Oncol 2012; 104:349.
- Keefe DM, Schubert MM, Elting LS, et al. Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer 2007; 109:820.
- Stokman MA, Spijkervet FK, Burlage FR, et al. Oral mucositis and selective elimination of oral flora in head and neck cancer patients receiving radiotherapy: a double-blind randomised clinical trial. Br J Cancer 2003; 88:1012.
- El-Sayed S, Nabid A, Shelley W, et al. Prophylaxis of radiation-associated mucositis in conventionally treated patients with head and neck cancer: a double-blind, phase III, randomized, controlled trial evaluating the clinical efficacy of an antimicrobial lozenge using a validated mucositis scoring system. J Clin Oncol 2002; 20:3956.
- Trotti A, Garden A, Warde P, et al. A multinational, randomized phase III trial of iseganan HCl oral solution for reducing the severity of oral mucositis in patients receiving radiotherapy for head-and-neck malignancy. Int J Radiat Oncol Biol Phys 2004; 58:674.
- Yen SH, Wang LW, Lin YH, et al. Phenylbutyrate mouthwash mitigates oral mucositis during radiotherapy or chemoradiotherapy in patients with head-and-neck cancer. Int J Radiat Oncol Biol Phys 2012; 82:1463.
- Huang EY, Leung SW, Wang CJ, et al. Oral glutamine to alleviate radiation-induced oral mucositis: a pilot randomized trial. Int J Radiat Oncol Biol Phys 2000; 46:535.
- Cerchietti LC, Navigante AH, Lutteral MA, et al. Double-blinded, placebo-controlled trial on intravenous L-alanyl-L-glutamine in the incidence of oral mucositis following chemoradiotherapy in patients with head-and-neck cancer. Int J Radiat Oncol Biol Phys 2006; 65:1330.
- Wagner W, Alfrink M, Haus U, Matt J. Treatment of irradiation-induced mucositis with growth factors (rhGM-CSF) in patients with head and neck cancer. Anticancer Res 1999; 19:799.
- Nicolatou O, Sotiropoulou-Lontou A, Skarlatos J, et al. A pilot study of the effect of granulocyte-macrophage colony-stimulating factor on oral mucositis in head and neck cancer patients during X-radiation therapy: a preliminary report. Int J Radiat Oncol Biol Phys 1998; 42:551.
- Ryu JK, Swann S, LeVeque F, et al. The impact of concurrent granulocyte macrophage-colony stimulating factor on radiation-induced mucositis in head and neck cancer patients: a double-blind placebo-controlled prospective phase III study by Radiation Therapy Oncology Group 9901. Int J Radiat Oncol Biol Phys 2007; 67:643.
- Makkonen TA, Minn H, Jekunen A, et al. Granulocyte macrophage-colony stimulating factor (GM-CSF) and sucralfate in prevention of radiation-induced mucositis: a prospective randomized study. Int J Radiat Oncol Biol Phys 2000; 46:525.
- Sprinzl GM, Galvan O, de Vries A, et al. Local application of granulocyte-macrophage colony stimulating factor (GM-CSF) for the treatment of oral mucositis. Eur J Cancer 2001; 37:2003.
- Su YB, Vickers AJ, Zelefsky MJ, et al. Double-blind, placebo-controlled, randomized trial of granulocyte-colony stimulating factor during postoperative radiotherapy for squamous head and neck cancer. Cancer J 2006; 12:182.
- Staar S, Rudat V, Stuetzer H, et al. Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys 2001; 50:1161.
- Ertekin MV, Koç M, Karslioglu I, Sezen O. Zinc sulfate in the prevention of radiation-induced oropharyngeal mucositis: a prospective, placebo-controlled, randomized study. Int J Radiat Oncol Biol Phys 2004; 58:167.
- Lin LC, Que J, Lin KL, et al. Effects of zinc supplementation on clinical outcomes in patients receiving radiotherapy for head and neck cancers: a double-blinded randomized study. Int J Radiat Oncol Biol Phys 2008; 70:368.
- Lin LC, Que J, Lin LK, Lin FC. Zinc supplementation to improve mucositis and dermatitis in patients after radiotherapy for head-and-neck cancers: a double-blind, randomized study. Int J Radiat Oncol Biol Phys 2006; 65:745.
- Rashad UM, Al-Gezawy SM, El-Gezawy E, Azzaz AN. Honey as topical prophylaxis against radiochemotherapy-induced mucositis in head and neck cancer. J Laryngol Otol 2009; 123:223.
- Bardy J, Molassiotis A, Ryder WD, et al. A double-blind, placebo-controlled, randomised trial of active manuka honey and standard oral care for radiation-induced oral mucositis. Br J Oral Maxillofac Surg 2012; 50:221.
- Duke RL, Campbell BH, Indresano AT, et al. Dental status and quality of life in long-term head and neck cancer survivors. Laryngoscope 2005; 115:678.
- Hong CH, Napeñas JJ, Hodgson BD, et al. A systematic review of dental disease in patients undergoing cancer therapy. Support Care Cancer 2010; 18:1007.
- Chang DT, Sandow PR, Morris CG, et al. Do pre-irradiation dental extractions reduce the risk of osteoradionecrosis of the mandible? Head Neck 2007; 29:528.
- 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; 354:567.
- Hovan AJ, Williams PM, Stevenson-Moore P, et al. A systematic review of dysgeusia induced by cancer therapies. Support Care Cancer 2010; 18:1081.
- Epstein JB, Hong C, Logan RM, et al. A systematic review of orofacial pain in patients receiving cancer therapy. Support Care Cancer 2010; 18:1023.
- Cohen EG, Deschler DG, Walsh K, Hayden RE. Early use of a mechanical stretching device to improve mandibular mobility after composite resection: a pilot study. Arch Phys Med Rehabil 2005; 86:1416.
- Hammerlid E, Ahlner-Elmqvist M, Bjordal K, et al. A prospective multicentre study in Sweden and Norway of mental distress and psychiatric morbidity in head and neck cancer patients. Br J Cancer 1999; 80:766.
- Lydiatt WM, Bessette D, Schmid KK, et al. Prevention of depression with escitalopram in patients undergoing treatment for head and neck cancer: randomized, double-blind, placebo-controlled clinical trial. JAMA Otolaryngol Head Neck Surg 2013; 139:678.
- GENERAL PRINCIPLES
- Spectrum of issues
- - Surgery
- - Radiation therapy
- - Chemotherapy
- Smoking cessation
- SALIVARY GLAND DAMAGE AND XEROSTOMIA
- Acute injury
- - Highly conformal RT technique
- - Amifostine
- - Submandibular gland transfer
- - Doxepin rinse
- - Pilocarpine
- - Bethanechol
- - Hyperbaric oxygen
- - Acupuncture
- Management and prevention
- - Mucoadhesive hydrogel
- - Benzydamine
- - "Miracle" mouthwashes
- - Palifermin
- Laser therapy
- Other approaches
- DENTAL ISSUES
- RADIATION DERMATITIS
- OROFACIAL PAIN
- WEIGHT LOSS AND MALNUTRITION
- ANXIETY AND DEPRESSION
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS