Treatment of locoregionally advanced (stage III and IV) head and neck cancer: The larynx and hypopharynx
- 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
- Kerstin M Stenson, MD, FACS
Kerstin M Stenson, MD, FACS
- Professor of Otolaryngology
- Chief, Head and Neck Cancer Program, Rush University Medical Center
- Department of Otolaryngology/Head and Neck Surgery
- David J Sher, MD, MPH
David J Sher, MD, MPH
- Associate Professor of Radiation Oncology
- UT Southwestern Medical Center
- Section Editors
- 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
- Marvin P Fried, MD, FACS
Marvin P Fried, MD, FACS
- Section Editor — Head and Neck Surgery
- Professor and University Chairman, Department of Otorhinolaryngology - Head and Neck Surgery
- Montefiore Medical Center, Albert Einstein College of Medicine
Worldwide, there are approximately 238,000 new laryngeal cancer cases and 106,000 deaths annually . In the United States, there are approximately 13,000 cases and 3660 deaths due to laryngeal cancer annually . Glottic, supraglottic, and subglottic cancers represent approximately two-thirds, one-third, and 2 percent of laryngeal cancers, respectively. Hypopharyngeal cancer is less common than laryngeal cancer, with approximately one-fourth as many cases.
Tumors of the glottic larynx commonly present with hoarseness and are most often diagnosed at an early stage. However, patients with supraglottic and subglottic laryngeal cancers, as well as hypopharyngeal cancers, usually present with advanced disease due to a paucity of symptoms, propensity for local extension (subglottis), and rich lymphatics resulting in a high incidence of lymph node metastases (supraglottis).
The management of locoregionally advanced laryngeal and hypopharyngeal cancer is presented here. The treatment of early stage laryngeal and hypopharyngeal cancers is discussed separately.
- Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Allen C, et al. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol 2016.
- Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017.
- American Joint Committee on Cancer Staging Manual, 7th ed, Edge SB, Byrd DR, Compton CC, et al (Eds), Springer, New York 2010.
- Kelly SL, Jackson JE, Hickey BE, et al. Multidisciplinary clinic care improves adherence to best practice in head and neck cancer. Am J Otolaryngol 2013; 34:57.
- Wheless SA, McKinney KA, Zanation AM. A prospective study of the clinical impact of a multidisciplinary head and neck tumor board. Otolaryngol Head Neck Surg 2010; 143:650.
- Wuthrick EJ, Zhang Q, Machtay M, et al. Institutional clinical trial accrual volume and survival of patients with head and neck cancer. J Clin Oncol 2015; 33:156.
- Gourin CG, Conger BT, Sheils WC, et al. The effect of treatment on survival in patients with advanced laryngeal carcinoma. Laryngoscope 2009; 119:1312.
- American Society of Clinical Oncology, Pfister DG, Laurie SA, et al. American Society of Clinical Oncology clinical practice guideline for the use of larynx-preservation strategies in the treatment of laryngeal cancer. J Clin Oncol 2006; 24:3693.
- Lefebvre JL, Ang KK, Larynx Preservation Consensus Panel. Larynx preservation clinical trial design: key issues and recommendations--a consensus panel summary. Head Neck 2009; 31:429.
- Lefebvre JL, Ang KK, Larynx Preservation Consensus Panel. Larynx preservation clinical trial design: key issues and recommendations-a consensus panel summary. Int J Radiat Oncol Biol Phys 2009; 73:1293.
- 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.
- Browman GP, Mohide EA, Willan A, et al. Association between smoking during radiotherapy and prognosis in head and neck cancer: a follow-up study. Head Neck 2002; 24:1031.
- Silver CE, Beitler JJ, Shaha AR, et al. Current trends in initial management of laryngeal cancer: the declining use of open surgery. Eur Arch Otorhinolaryngol 2009; 266:1333.
- Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group. N Engl J Med 1991; 324:1685.
- Becker M. Neoplastic invasion of laryngeal cartilage: radiologic diagnosis and therapeutic implications. Eur J Radiol 2000; 33:216.
- Rodriguez CP, Adelstein DJ, Rybicki LA, et al. Clinical predictors of larynx preservation after multiagent concurrent chemoradiotherapy. Head Neck 2008; 30:1535.
- Knab BR, Salama JK, Solanki A, et al. Functional organ preservation with definitive chemoradiotherapy for T4 laryngeal squamous cell carcinoma. Ann Oncol 2008; 19:1650.
- Stenson KM, Maccracken E, Kunnavakkam R, et al. Chemoradiation for patients with large-volume laryngeal cancers. Head Neck 2012; 34:1162.
- Hong WK, Lippman SM, Wolf GT. Recent advances in head and neck cancer--larynx preservation and cancer chemoprevention: the Seventeenth Annual Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res 1993; 53:5113.
- Lefebvre JL, Chevalier D, Luboinski B, et al. Larynx preservation in pyriform sinus cancer: preliminary results of a European Organization for Research and Treatment of Cancer phase III trial. EORTC Head and Neck Cancer Cooperative Group. J Natl Cancer Inst 1996; 88:890.
- Lefebvre JL, Andry G, Chevalier D, et al. Laryngeal preservation with induction chemotherapy for hypopharyngeal squamous cell carcinoma: 10-year results of EORTC trial 24891. Ann Oncol 2012; 23:2708.
- Vokes EE. Competing roads to larynx preservation. J Clin Oncol 2013; 31:833.
- 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; 100:33.
- 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; 31:845.
- Pignon JP, Bourhis J, Domenge C, Designé L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 2000; 355:949.
- Vermorken JB, Remenar E, van Herpen C, et al. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med 2007; 357:1695.
- 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.
- Lefebvre JL, Pointreau Y, Rolland F, et al. Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study. J Clin Oncol 2013; 31:853.
- Forastiere AA, Goepfert H, Maor M, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 2003; 349:2091.
- Holsinger FC, Nussenbaum B, Nakayama M, et al. Current concepts and new horizons in conservation laryngeal surgery: an important part of multidisciplinary care. Head Neck 2010; 32:656.
- Chu EA, Kim YJ. Laryngeal cancer: diagnosis and preoperative work-up. Otolaryngol Clin North Am 2008; 41:673.
- Barbera L, Groome PA, Mackillop WJ, et al. The role of computed tomography in the T classification of laryngeal carcinoma. Cancer 2001; 91:394.
- Beitler JJ, Muller S, Grist WJ, et al. Prognostic accuracy of computed tomography findings for patients with laryngeal cancer undergoing laryngectomy. J Clin Oncol 2010; 28:2318.
- Akbas Y, Demireller A. Oncologic and functional results of supracricoid partial laryngectomy with cricohyoidopexy. Otolaryngol Head Neck Surg 2005; 132:783.
- Paleri V, Thomas L, Basavaiah N, et al. Oncologic outcomes of open conservation laryngectomy for radiorecurrent laryngeal carcinoma: a systematic review and meta-analysis of English-language literature. Cancer 2011; 117:2668.
- Steiner W, Ambrosch P, Hess CF, Kron M. Organ preservation by transoral laser microsurgery in piriform sinus carcinoma. Otolaryngol Head Neck Surg 2001; 124:58.
- Vilaseca I, Blanch JL, Bernal-Sprekelsen M, Moragas M. CO2 laser surgery: a larynx preservation alternative for selected hypopharyngeal carcinomas. Head Neck 2004; 26:953.
- Suárez C, Rodrigo JP. Transoral microsurgery for treatment of laryngeal and pharyngeal cancers. Curr Oncol Rep 2013; 15:134.
- Leong SC, Kathan C, Mortimore S. Early outcomes after transoral CO2 laser resection of laryngeal and hypopharyngeal squamous cell carcinoma: one centre's experience. J Laryngol Otol 2010; 124:185.
- Kutter J, Lang F, Monnier P, Pasche P. Transoral laser surgery for pharyngeal and pharyngolaryngeal carcinomas. Arch Otolaryngol Head Neck Surg 2007; 133:139.
- Cabanillas R, Rodrigo JP, Llorente JL, Suárez C. Oncologic outcomes of transoral laser surgery of supraglottic carcinoma compared with a transcervical approach. Head Neck 2008; 30:750.
- Hinni ML, Salassa JR, Grant DG, et al. Transoral laser microsurgery for advanced laryngeal cancer. Arch Otolaryngol Head Neck Surg 2007; 133:1198.
- Peretti G, Piazza C, Ansarin M, et al. Transoral CO2 laser microsurgery for Tis-T3 supraglottic squamous cell carcinomas. Eur Arch Otorhinolaryngol 2010; 267:1735.
- Peretti G, Piazza C, Cocco D, et al. Transoral CO(2) laser treatment for T(is)-T(3) glottic cancer: the University of Brescia experience on 595 patients. Head Neck 2010; 32:977.
- Blanch JL, Vilaseca I, Caballero M, et al. Outcome of transoral laser microsurgery for T2-T3 tumors growing in the laryngeal anterior commissure. Head Neck 2011; 33:1252.
- Preuss SF, Cramer K, Klussmann JP, et al. Transoral laser surgery for laryngeal cancer: outcome, complications and prognostic factors in 275 patients. Eur J Surg Oncol 2009; 35:235.
- Olthoff A, Ewen A, Wolff HA, et al. Organ function and quality of life after transoral laser microsurgery and adjuvant radiotherapy for locally advanced laryngeal cancer. Strahlenther Onkol 2009; 185:303.
- Remacle M, Lawson G, Hantzakos A, Jamart J. Endoscopic partial supraglottic laryngectomies: techniques and results. Otolaryngol Head Neck Surg 2009; 141:374.
- Bernal-Sprekelsen M, Blanch JL, Caballero-Borrego M, Vilaseca I. The learning curve in transoral laser microsurgery for malignant tumors of the larynx and hypopharynx: parameters for a levelled surgical approach. Eur Arch Otorhinolaryngol 2013; 270:623.
- Lango MN. Multimodal treatment for head and neck cancer. Surg Clin North Am 2009; 89:43.
- Agrawal N, Goldenberg D. Primary and salvage total laryngectomy. Otolaryngol Clin North Am 2008; 41:771.
- Chen AY, Halpern M. Factors predictive of survival in advanced laryngeal cancer. Arch Otolaryngol Head Neck Surg 2007; 133:1270.
- Grover S, Swisher-McClure S, Mitra N, et al. Total Laryngectomy Versus Larynx Preservation for T4a Larynx Cancer: Patterns of Care and Survival Outcomes. Int J Radiat Oncol Biol Phys 2015; 92:594.
- Timme DW, Jonnalagadda S, Patel R, et al. Treatment Selection for T3/T4a Laryngeal Cancer: Chemoradiation Versus Primary Surgery. Ann Otol Rhinol Laryngol 2015; 124:845.
- O'Neill CB, O'Neill JP, Atoria CL, et al. Treatment complications and survival in advanced laryngeal cancer: a population-based analysis. Laryngoscope 2014; 124:2707.
- Layland MK, Sessions DG, Lenox J. The influence of lymph node metastasis in the treatment of squamous cell carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx: N0 versus N+. Laryngoscope 2005; 115:629.
- Ljumanovic R, Langendijk JA, Hoekstra OS, et al. Pre- and post-radiotherapy MRI results as a predictive model for response in laryngeal carcinoma. Eur Radiol 2008; 18:2231.
- ANATOMY AND STAGING
- OVERVIEW OF MANAGEMENT
- COMBINED MODALITY THERAPY
- Functional organ preservation (chemoradiotherapy) versus surgery
- Concurrent chemoradiotherapy
- Induction chemotherapy
- Sequential chemoradiotherapy
- Comparison of combined chemotherapy and radiation therapy approaches
- Larynx preservation surgery
- - Preoperative evaluation
- Conservation surgery
- - Postoperative radiation therapy
- Total laryngectomy
- MANAGEMENT OF THE NECK
- Patients treated with chemoradiotherapy
- Patients managed with primary surgery
- OLDER AND POOR PERFORMANCE STATUS PATIENTS
- COMPLICATIONS OF TREATMENT
- POSTTREATMENT EVALUATION AND SURVEILLANCE
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS