Definitive radiation therapy alone for advanced (stage III and IV) head and neck cancer: Dose and fractionation schedule
- Shlomo A Koyfman, MD
Shlomo A Koyfman, MD
- Assistant Professor of Medicine
- Departments of Radiation Oncology and Bioethics
- Cleveland Clinic
- Wendy Hara, MD
Wendy Hara, MD
- Clinical Assistant Professor, Department of Radiation Oncology
- Stanford University
- Section Editors
- 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
- 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
Patients with locoregionally advanced, stage III or IV, head and neck squamous cell carcinoma are usually managed with a combined modality approach that includes surgery, radiation therapy (RT), and/or chemotherapy. Traditionally, these tumors were managed with a combination of surgery and RT, if operable. In the last several decades, definitive RT plus chemotherapy is being used for patients where organ function preservation is appropriate, for those with surgically unresectable disease, and for those who are medically inoperable.
Issues regarding the optimal dose and schedule for patients receiving definitive RT are reviewed here. The principles of RT as applied to patients with head and neck cancer are presented separately. (See "General principles of radiation therapy for head and neck cancer".)
PATIENT SELECTION FOR DEFINITIVE RADIATION
Definitive RT alone remains an appropriate option for selected patients with stage III/IV disease. These include:
●Patients with a contraindication to platinum-based chemotherapy (eg, hearing loss, renal insufficiency, neuropathy, bone marrow disease). The use of RT plus cetuximab in this setting is discussed elsewhere. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Cetuximab alone plus RT'.)
●Patients who refuse chemotherapy but still desire the locoregional control and possible survival benefits of RT.
- 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; 13:145.
- Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010; 363:24.
- Fu KK, Pajak TF, Trotti A, et al. A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys 2000; 48:7.
- Beitler JJ, Zhang Q, Fu KK, et al. Final results of local-regional control and late toxicity of RTOG 9003: a randomized trial of altered fractionation radiation for locally advanced head and neck cancer. Int J Radiat Oncol Biol Phys 2014; 89:13.
- Bourhis J, Overgaard J, Audry H, et al. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet 2006; 368:843.
- Pignon JP, le Maître A, Bourhis J, MACH-NC Collaborative Group. Meta-Analyses of Chemotherapy in Head and Neck Cancer (MACH-NC): an update. Int J Radiat Oncol Biol Phys 2007; 69:S112.
- Cox JD, Pajak TF, Marcial VA, et al. ASTRO plenary: interfraction interval is a major determinant of late effects, with hyperfractionated radiation therapy of carcinomas of upper respiratory and digestive tracts: results from Radiation Therapy Oncology Group protocol 8313. Int J Radiat Oncol Biol Phys 1991; 20:1191.
- Fu KK, Pajak TF, Marcial VA, et al. Late effects of hyperfractionated radiotherapy for advanced head and neck cancer: long-term follow-up results of RTOG 83-13. Int J Radiat Oncol Biol Phys 1995; 32:577.
- Brizel DM, Albers ME, Fisher SR, et al. Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med 1998; 338:1798.
- Budach V, Stuschke M, Budach W, et al. Hyperfractionated accelerated chemoradiation with concurrent fluorouracil-mitomycin is more effective than dose-escalated hyperfractionated accelerated radiation therapy alone in locally advanced head and neck cancer: final results of the radiotherapy cooperative clinical trials group of the German Cancer Society 95-06 Prospective Randomized Trial. J Clin Oncol 2005; 23:1125.
- Jeremić B, Miličić B. Pretreatment prognostic factors influencing distant metastasis-free survival in locally advanced squamous cell carcinoma of the head and neck treated with radiation therapy with or without concurrent chemotherapy. Am J Clin Oncol 2009; 32:483.
- Bensadoun RJ, Bénézery K, Dassonville O, et al. French multicenter phase III randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy (BiRCF) in unresectable pharyngeal carcinoma: Results at 2 years (FNCLCC-GORTEC). Int J Radiat Oncol Biol Phys 2006; 64:983.
- 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 Clin Oncol 2004; 22:69.
- Bourhis J, Lapeyre M, Tortochaux J, et al. Phase III randomized trial of very accelerated radiation therapy compared with conventional radiation therapy in squamous cell head and neck cancer: a GORTEC trial. J Clin Oncol 2006; 24:2873.
- Horiot JC, Bontemps P, van den Bogaert W, et al. Accelerated fractionation (AF) compared to conventional fractionation (CF) improves loco-regional control in the radiotherapy of advanced head and neck cancers: results of the EORTC 22851 randomized trial. Radiother Oncol 1997; 44:111.
- Marcial VA, Pajak TF, Chang C, et al. Hyperfractionated photon radiation therapy in the treatment of advanced squamous cell carcinoma of the oral cavity, pharynx, larynx, and sinuses, using radiation therapy as the only planned modality: (preliminary report) by the Radiation Therapy Oncology Group (RTOG). Int J Radiat Oncol Biol Phys 1987; 13:41.
- Beck-Bornholdt HP, Dubben HH, Liertz-Petersen C, Willers H. Hyperfractionation: where do we stand? Radiother Oncol 1997; 43:1.
- Dische S, Saunders M, Barrett A, et al. A randomised multicentre trial of CHART versus conventional radiotherapy in head and neck cancer. Radiother Oncol 1997; 44:123.
- Dobrowsky W, Naudé J. Continuous hyperfractionated accelerated radiotherapy with/without mitomycin C in head and neck cancers. Radiother Oncol 2000; 57:119.
- Overgaard J, Hansen HS, Specht L, et al. Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomised controlled trial. Lancet 2003; 362:933.
- Skladowski K, Maciejewski B, Golen M, et al. Continuous accelerated 7-days-a-week radiotherapy for head-and-neck cancer: long-term results of phase III clinical trial. Int J Radiat Oncol Biol Phys 2006; 66:706.
- Lyhne NM, Primdahl H, Kristensen CA, et al. The DAHANCA 6 randomized trial: Effect of 6 vs 5 weekly fractions of radiotherapy in patients with glottic squamous cell carcinoma. Radiother Oncol 2015; 117:91.
- Skladowski K, Hutnik M, Wygoda A, et al. Radiation-free weekend rescued! Continuous accelerated irradiation of 7-days per week is equal to accelerated fractionation with concomitant boost of 7 fractions in 5-days per week: report on phase 3 clinical trial in head-and-neck cancer patients. Int J Radiat Oncol Biol Phys 2013; 85:741.
- 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.
- Mortensen HR, Overgaard J, Specht L, et al. Prevalence and peak incidence of acute and late normal tissue morbidity in the DAHANCA 6&7 randomised trial with accelerated radiotherapy for head and neck cancer. Radiother Oncol 2012; 103:69.
- Xiao C, Hanlon A, Zhang Q, et al. Risk factors for clinician-reported symptom clusters in patients with advanced head and neck cancer in a phase 3 randomized clinical trial: RTOG 0129. Cancer 2014; 120:848.
- Mortensen HR, Jensen K, Aksglæde K, et al. Late dysphagia after IMRT for head and neck cancer and correlation with dose-volume parameters. Radiother Oncol 2013; 107:288.
- Lee NY, Zhang Q, Pfister DG, et al. Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): a phase 2 multi-institutional trial. Lancet Oncol 2012; 13:172.
- PATIENT SELECTION FOR DEFINITIVE RADIATION
- PARADIGMS OF DOSE AND FRACTIONATION MODIFICATION
- Clinical trial results
- - RTOG 9003
- - MARCH meta-analysis
- Optimal hyperfractionation: Dose and schedule
- Concurrent chemoradiotherapy using hyperfractionated RT
- ACCELERATED FRACTIONATION RT
- Clinical trial results
- Concurrent chemoradiotherapy using accelerated RT
- TOXICITY OF HYPERFRACTIONATED AND ACCELERATED RT
- COST AND CONVENIENCE
- SIMULTANEOUS INTEGRATED BOOST TECHNIQUE WITH IMRT
- MANAGEMENT OF THE NECK AFTER RT
- SUMMARY AND RECOMMENDATIONS