Treatment of locoregionally advanced (stage III and IV) head and neck cancer: The oropharynx
- Francis P Worden, MD
Francis P Worden, MD
- Department of Internal Medicine
- Division of Hematology and Oncology
- University of Michigan
- Carol R Bradford, MD, FACS
Carol R Bradford, MD, FACS
- Professor and Chair
- Department of Otolaryngology-Head and Neck Surgery
- University of Michigan
- Avraham Eisbruch, MD
Avraham Eisbruch, MD
- Professor and Associate Chair for Clinical Research
- Department of Radiation Oncology
- University of Michigan
- 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
- 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
Oropharyngeal squamous cell carcinomas originate in the soft palate, tonsils, base of tongue, pharyngeal wall, or the vallecula, the fold located between the base of tongue and the epiglottis (figure 1) . Oropharyngeal cancer is a relatively uncommon malignancy, with approximately 100,000 cases of oropharyngeal cancer diagnosed worldwide each year, which cause death in at least half of cases .
The tumor, node, metastasis (TNM) staging system of the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) is used to stage oropharyngeal cancer. In the eighth edition of the AJCC TNM staging system, separate staging systems have been established for HPV associated oropharyngeal carcinoma (figure 2 and table 1A and table 1B) and for HPV negative oropharyngeal cancer (table 2 and table 3) [3,4] (see "Overview of the diagnosis and staging of head and neck cancer"). The eighth edition AJCC staging system will go into effect in the United States in 2018, and this section will be updated. Comments in this section still apply to seventh edition AJCC unless otherwise noted.
The treatment of locally advanced, stage III to IVB cancers of the oropharynx will be reviewed here. The treatment of early stage oropharyngeal cancer is discussed separately, as is the management of patients with distant metastases (stage IVC).To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- American Joint Committee on Cancer Staging Manual, 7th ed, Edge SB, Byrd DR, Compton CC, et al (Eds), Springer, New York 2010.
- Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55:74.
- O'Sullivan B, Lydiatt WM, Haughey BH, et al. HPV-Mediated (p16+) Oropharyngeal Cancer. In: AJCC Cancer Staging Manual, 8th, Amin MB (Ed), Springer, New York 2017. p.113.
- Lydiatt WM, Ridge JA, Patel SG, et al. Oropharynx (p16-) and Hypopharynx. In: AJCC Cancer Staging Manual, 8th, Amin MB (Ed), Springer, New York 2017. p.123.
- Sturgis EM, Ang KK. The epidemic of HPV-associated oropharyngeal cancer is here: is it time to change our treatment paradigms? J Natl Compr Canc Netw 2011; 9:665.
- O'Sullivan B, Huang SH, Su J, et al. Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study. Lancet Oncol 2016; 17:440.
- NCCN Clinical Practice Guidelines, Head and Neck Cancers http://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf.
- Pignon JP, le Maître 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; 92:4.
- 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.
- 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.
- Domenge C, Hill C, Lefebvre JL, et al. Randomized trial of neoadjuvant chemotherapy in oropharyngeal carcinoma. French Groupe d'Etude des Tumeurs de la Tête et du Cou (GETTEC). Br J Cancer 2000; 83:1594.
- 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.
- Rosenthal DI, Harari PM, Giralt J, et al. Association of Human Papillomavirus and p16 Status With Outcomes in the IMCL-9815 Phase III Registration Trial for Patients With Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma of the Head and Neck Treated With Radiotherapy With or Without Cetuximab. J Clin Oncol 2016; 34:1300.
- Magrini SM, Buglione M, Corvò R, 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.
- 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; 32:2940.
- Bourhis J, Overgaard J, Audry H, et al. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet 2006; 368:843.
- 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.
- Feng FY, Kim HM, Lyden TH, et al. Intensity-modulated chemoradiotherapy aiming to reduce dysphagia in patients with oropharyngeal cancer: clinical and functional results. J Clin Oncol 2010; 28:2732.
- Haughey BH, Hinni ML, Salassa JR, et al. Transoral laser microsurgery as primary treatment for advanced-stage oropharyngeal cancer: a United States multicenter study. Head Neck 2011; 33:1683.
- Moore EJ, Olsen SM, Laborde RR, et al. Long-term functional and oncologic results of transoral robotic surgery for oropharyngeal squamous cell carcinoma. Mayo Clin Proc 2012; 87:219.
- Smith RV, Schiff BA, Garg M, Haigentz M. The impact of transoral robotic surgery on the overall treatment of oropharyngeal cancer patients. Laryngoscope 2015; 125 Suppl 10:S1.
- Kish JA, Zhang Q, Langer CJ, 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; (abstr 6003).
- Paccagnella A, Buffoli A, Koussis H, et al. Concomitant chemoradiotherapy versus neoadjuvant chemotherapy with docetaxel, cisplatin, 5-fluorouracil (TPF) followed by chemoradiotherapy in locally advanced head and neck cancer. J Clin Oncol 2008; 26:6000.
- Leemans CR, Tiwari R, van der Waal I, et al. The efficacy of comprehensive neck dissection with or without postoperative radiotherapy in nodal metastases of squamous cell carcinoma of the upper respiratory and digestive tracts. Laryngoscope 1990; 100:1194.
- Ries LG, Melbert D, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2005, National Cancer Institute. Bethesda, MD http://seer.cancer.gov/csr/1975_2005/ (Accessed on March 14, 2011).
- Carvalho AL, Nishimoto IN, Califano JA, Kowalski LP. Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. Int J Cancer 2005; 114:806.
- Licitra L, Perrone F, Bossi P, et al. High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma. J Clin Oncol 2006; 24:5630.
- 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; 100:261.
- Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010; 363:24.
- Rischin D, Young RJ, Fisher R, et al. Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol 2010; 28:4142.
- Lorch JH, Goloubeva O, Haddad RI, et al. Induction chemotherapy with cisplatin and fluorouracil alone or in combination with docetaxel in locally advanced squamous-cell cancer of the head and neck: long-term results of the TAX 324 randomised phase 3 trial. Lancet Oncol 2011; 12:153.
- Posner MR, Lorch JH, Goloubeva O, et al. Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial. Ann Oncol 2011; 22:1071.
- Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 2011; 29:4294.
- Trosman SJ, Koyfman SA, Ward MC, et al. Effect of human papillomavirus on patterns of distant metastatic failure in oropharyngeal squamous cell carcinoma treated with chemoradiotherapy. JAMA Otolaryngol Head Neck Surg 2015; 141:457.
- 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.
- EFFECT OF HPV INFECTION
- NONSURGICAL VERSUS SURGICAL APPROACHES
- FUNCTIONAL ORGAN PRESERVATION APPROACHES
- Chemotherapy plus RT versus RT alone
- Contemporary trials
- Induction chemotherapy
- - Induction chemotherapy followed by radiation with or without surgery (locoregional therapy) versus definitive locoregional therapy alone
- - Sequential induction chemotherapy followed by radiation with or without surgery (locoregional therapy) versus definitive locoregional therapy alone
- - Concurrent chemotherapy regimen
- Cetuximab versus a platinum regimen
- Radiation schedule and technique
- OLDER AND POOR PERFORMANCE STATUS PATIENTS
- MANAGEMENT OF THE NECK
- After definitive chemoradiotherapy
- After primary surgery
- POSTTREATMENT EVALUATION AND SURVEILLANCE
- SUMMARY AND RECOMMENDATIONS