Treatment of early and locoregionally advanced nasopharyngeal carcinoma
- Edwin P Hui, MD
Edwin P Hui, MD
- Clinical Associate Professor (Honorary)
- Department of Clinical Oncology
- Prince of Wales Hospital
- The Chinese University of Hong Kong
- Anthony TC Chan, MD
Anthony TC Chan, MD
- Professor of Clinical Oncology
- Prince of Wales Hospital
- The Chinese University of Hong Kong
- Quynh-Thu Le, MD
Quynh-Thu Le, MD
- Professor and Chair
- Stanford University
- 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
Nasopharyngeal carcinoma arises from the lining of the nasopharynx, the narrow tubular passage behind the nasal cavity. Worldwide, there are approximately 80,000 incident cases and 50,000 deaths annually, but there is remarkable variation in racial and geographic distribution . (See "Epidemiology, etiology, and diagnosis of nasopharyngeal carcinoma", section on 'Epidemiology'.)
The treatment of locoregional nasopharyngeal cancer is presented here. The treatment of recurrent and metastatic disease is discussed separately. (See "Treatment of recurrent and metastatic nasopharyngeal carcinoma".)
PATHOLOGY AND STAGING
The World Health Organization (WHO) classifies nasopharyngeal carcinoma into three histopathologic types  (see "Epidemiology, etiology, and diagnosis of nasopharyngeal carcinoma", section on 'Histology'):
●Keratinizing squamous cell carcinoma (formerly WHO type I)
●Nonkeratinizing carcinoma, which includes differentiated carcinoma (formerly WHO type II) and undifferentiated carcinoma (formerly WHO type III)
- Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127:2893.
- Pathology and genetics of head and neck tumors. In: World Health Organization Classification of Tumours, Barnes, L, Eveson, JW, Reichart, P, Sidransky, D (Eds), IARC Press, Lyon 2005.
- AJCC (American Joint Committee on Cancer) Staging Manual, 7th, Edge, SB, Byrd, DR, Compton, CC, et al (Eds), Springer, New York 2010.
- Pan JJ, Ng WT, Zong JF, et al. Proposal for the 8th edition of the AJCC/UICC staging system for nasopharyngeal cancer in the era of intensity-modulated radiotherapy. Cancer 2016; 122:546.
- Chua ML, Wee JT, Hui EP, Chan AT. Nasopharyngeal carcinoma. Lancet 2016; 387:1012.
- Peng G, Wang T, Yang KY, et al. A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs. conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma. Radiother Oncol 2012; 104:286.
- Lee AW, Ng WT, Chan LL, et al. Evolution of treatment for nasopharyngeal cancer--success and setback in the intensity-modulated radiotherapy era. Radiother Oncol 2014; 110:377.
- Pow EH, Kwong DL, McMillan AS, et al. Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial. Int J Radiat Oncol Biol Phys 2006; 66:981.
- 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.
- Taheri-Kadkhoda Z, Björk-Eriksson T, Nill S, et al. Intensity-modulated radiotherapy of nasopharyngeal carcinoma: a comparative treatment planning study of photons and protons. Radiat Oncol 2008; 3:4.
- Widesott L, Pierelli A, Fiorino C, et al. Intensity-modulated proton therapy versus helical tomotherapy in nasopharynx cancer: planning comparison and NTCP evaluation. Int J Radiat Oncol Biol Phys 2008; 72:589.
- Wei WI, Sham JS. Nasopharyngeal carcinoma. Lancet 2005; 365:2041.
- Altun M, Fandi A, Dupuis O, et al. Undifferentiated nasopharyngeal cancer (UCNT): current diagnostic and therapeutic aspects. Int J Radiat Oncol Biol Phys 1995; 32:859.
- Lee AW, Sze H, Ng WT. Is selective neck irradiation safe for node-negative nasopharyngeal carcinoma? Int J Radiat Oncol Biol Phys 2013; 85:902.
- Lee AW, Tung SY, Chan AT, et al. A randomized trial on addition of concurrent-adjuvant chemotherapy and/or accelerated fractionation for locally-advanced nasopharyngeal carcinoma. Radiother Oncol 2011; 98:15.
- Lee AW, Ngan RK, Tung SY, et al. Preliminary results of trial NPC-0501 evaluating the therapeutic gain by changing from concurrent-adjuvant to induction-concurrent chemoradiotherapy, changing from fluorouracil to capecitabine, and changing from conventional to accelerated radiotherapy fractionation in patients with locoregionally advanced nasopharyngeal carcinoma. Cancer 2015; 121:1328.
- Teo PM, Leung SF, Chan AT, et al. Final report of a randomized trial on altered-fractionated radiotherapy in nasopharyngeal carcinoma prematurely terminated by significant increase in neurologic complications. Int J Radiat Oncol Biol Phys 2000; 48:1311.
- Daoud J, Toumi N, Siala W, et al. Results of a prospective randomised trial comparing conventional radiotherapy to split course bifractionated radiation therapy in patients with nasopharyngeal carcinoma. Radiother Oncol 2007; 85:17.
- Lee AW, Poon YF, Foo W, et al. Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976-1985: overall survival and patterns of failure. Int J Radiat Oncol Biol Phys 1992; 23:261.
- Hsu MM, Tu SM. Nasopharyngeal carcinoma in Taiwan. Clinical manifestations and results of therapy. Cancer 1983; 52:362.
- Li JG, Yuan X, Zhang LL, et al. A randomized clinical trial comparing prophylactic upper versus whole-neck irradiation in the treatment of patients with node-negative nasopharyngeal carcinoma. Cancer 2013; 119:3170.
- Geara FB, Sanguineti G, Tucker SL, et al. Carcinoma of the nasopharynx treated by radiotherapy alone: determinants of distant metastasis and survival. Radiother Oncol 1997; 43:53.
- Sun LM, Li CI, Huang EY, Vaughan TL. Survival differences by race in nasopharyngeal carcinoma. Am J Epidemiol 2007; 165:271.
- Lee AW, Sze WM, Au JS, et al. Treatment results for nasopharyngeal carcinoma in the modern era: the Hong Kong experience. Int J Radiat Oncol Biol Phys 2005; 61:1107.
- Chua DT, Sham JS, Kwong DL, Au GK. Treatment outcome after radiotherapy alone for patients with Stage I-II nasopharyngeal carcinoma. Cancer 2003; 98:74.
- Chua DT, Ma J, Sham JS, et al. Improvement of survival after addition of induction chemotherapy to radiotherapy in patients with early-stage nasopharyngeal carcinoma: Subgroup analysis of two Phase III trials. Int J Radiat Oncol Biol Phys 2006; 65:1300.
- Cheng SH, Tsai SY, Yen KL, et al. Concomitant radiotherapy and chemotherapy for early-stage nasopharyngeal carcinoma. J Clin Oncol 2000; 18:2040.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on February 27, 2016).
- Chan AT, Grégoire V, Lefebvre JL, et al. Nasopharyngeal cancer: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012; 23 Suppl 7:vii83.
- Chen QY, Wen YF, Guo L, et al. Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial. J Natl Cancer Inst 2011; 103:1761.
- Blanchard P, Lee A, Marguet S, et al. Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis. Lancet Oncol 2015; 16:645.
- Ribassin-Majed L, Marguet S, Lee AW, et al. What Is the Best Treatment of Locally Advanced Nasopharyngeal Carcinoma? An Individual Patient Data Network Meta-Analysis. J Clin Oncol 2016.
- Al-Sarraf M, LeBlanc M, Giri PG, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 1998; 16:1310.
- Rossi A, Molinari R, Boracchi P, et al. Adjuvant chemotherapy with vincristine, cyclophosphamide, and doxorubicin after radiotherapy in local-regional nasopharyngeal cancer: results of a 4-year multicenter randomized study. J Clin Oncol 1988; 6:1401.
- Chi KH, Chang YC, Guo WY, et al. A phase III study of adjuvant chemotherapy in advanced nasopharyngeal carcinoma patients. Int J Radiat Oncol Biol Phys 2002; 52:1238.
- Chen L, Hu CS, Chen XZ, et al. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol 2012; 13:163.
- Chen L, Hu CS, Chen XZ, et al. Adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicentre randomised controlled trial. Eur J Cancer 2017; 75:150.
- Lee AW, Tung SY, Chua DT, et al. Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst 2010; 102:1188.
- Hui EP, Ma BB, Chan KC, et al. Clinical utility of plasma Epstein-Barr virus DNA and ERCC1 single nucleotide polymorphism in nasopharyngeal carcinoma. Cancer 2015; 121:2720.
- Chan ATC, Hui EP, Ngan RKC, et al. A multicenter randomized controlled trial of adjuvant chemotherapy in NPC with residual plasma EBV DNA following primary radiotherapy or chemoradiation (abstract 6002). 2017 American Society of Clinical Oncology annual meeting.
- Sun Y, Li WF, Chen NY, et al. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol 2016; 17:1509.
- 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.
- 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.
- Cao SM, Yang Q, Guo L, et al. Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: A phase III multicentre randomised controlled trial. Eur J Cancer 2017; 75:14.
- Lee JY, Sun JM, Oh DR, et al. Comparison of weekly versus triweekly cisplatin delivered concurrently with radiation therapy in patients with locally advanced nasopharyngeal cancer: A multicenter randomized phase II trial (KCSG-HN10-02). Radiother Oncol 2016; 118:244.
- Lee AW, Tung SY, Ngan RK, et al. Factors contributing to the efficacy of concurrent-adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma: combined analyses of NPC-9901 and NPC-9902 Trials. Eur J Cancer 2011; 47:656.
- Loong HH, Ma BB, Leung SF, et al. Prognostic significance of the total dose of cisplatin administered during concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. Radiother Oncol 2012; 104:300.
- Zhang L, Zhao C, Peng PJ, et al. Phase III study comparing standard radiotherapy with or without weekly oxaliplatin in treatment of locoregionally advanced nasopharyngeal carcinoma: preliminary results. J Clin Oncol 2005; 23:8461.
- Wu X, Huang PY, Peng PJ, et al. Long-term follow-up of a phase III study comparing radiotherapy with or without weekly oxaliplatin for locoregionally advanced nasopharyngeal carcinoma. Ann Oncol 2013; 24:2131.
- Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, et al. Chemoradiation comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial. Eur J Cancer 2007; 43:1399.
- Ma BB, Kam MK, Leung SF, et al. A phase II study of concurrent cetuximab-cisplatin and intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma. Ann Oncol 2012; 23:1287.
- 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.
- Liu T, Xu W, Yan WL, et al. FDG-PET, CT, MRI for diagnosis of local residual or recurrent nasopharyngeal carcinoma, which one is the best? A systematic review. Radiother Oncol 2007; 85:327.
- Comoretto M, Balestreri L, Borsatti E, et al. Detection and restaging of residual and/or recurrent nasopharyngeal carcinoma after chemotherapy and radiation therapy: comparison of MR imaging and FDG PET/CT. Radiology 2008; 249:203.
- Hui EP, Leung SF, Au JS, et al. Lung metastasis alone in nasopharyngeal carcinoma: a relatively favorable prognostic group. A study by the Hong Kong Nasopharyngeal Carcinoma Study Group. Cancer 2004; 101:300.
- Chao SS, Loh KS, Tan LK. Modalities of surveillance in treated nasopharyngeal cancer. Otolaryngol Head Neck Surg 2003; 129:61.
- Sun X, Su S, Chen C, et al. Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities. Radiother Oncol 2014; 110:398.
- Le QT, Jones CD, Yau TK, et al. A comparison study of different PCR assays in measuring circulating plasma epstein-barr virus DNA levels in patients with nasopharyngeal carcinoma. Clin Cancer Res 2005; 11:5700.
- Lin JC, Wang WY, Chen KY, et al. Quantification of plasma Epstein-Barr virus DNA in patients with advanced nasopharyngeal carcinoma. N Engl J Med 2004; 350:2461.
- Leung SF, Zee B, Ma BB, et al. Plasma Epstein-Barr viral deoxyribonucleic acid quantitation complements tumor-node-metastasis staging prognostication in nasopharyngeal carcinoma. J Clin Oncol 2006; 24:5414.
- Chen Y, Liu MZ, Liang SB, et al. Preliminary results of a prospective randomized trial comparing concurrent chemoradiotherapy plus adjuvant chemotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma in endemic regions of china. Int J Radiat Oncol Biol Phys 2008; 71:1356.
- Hui EP, Ma BB, Leung SF, et al. Randomized phase II trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma. J Clin Oncol 2009; 27:242.
- 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.
- Yeh SA, Tang Y, Lui CC, et al. Treatment outcomes and late complications of 849 patients with nasopharyngeal carcinoma treated with radiotherapy alone. Int J Radiat Oncol Biol Phys 2005; 62:672.
- Chen WC, Jackson A, Budnick AS, et al. Sensorineural hearing loss in combined modality treatment of nasopharyngeal carcinoma. Cancer 2006; 106:820.
- Teo PM, Chan AT, Leung SF, et al. Increased incidence of tongue cancer after primary radiotherapy for nasopharyngeal carcinoma--the possibility of radiation carcinogenesis. Eur J Cancer 1999; 35:219.
- Goh YH, Chong VF, Low WK. Temporal bone tumours in patients irradiated for nasopharyngeal neoplasm. J Laryngol Otol 1999; 113:222.
- Lin YS, Jen YM, Lin JC. Radiation-related cranial nerve palsy in patients with nasopharyngeal carcinoma. Cancer 2002; 95:404.
- Chew NK, Sim BF, Tan CT, et al. Delayed post-irradiation bulbar palsy in nasopharyngeal carcinoma. Neurology 2001; 57:529.
- Aiken RD. Neurologic complications of head and neck cancers. Semin Oncol 2006; 33:348.
- Bhandare N, Kennedy L, Malyapa RS, et al. Hypopituitarism after radiotherapy for extracranial head and neck cancers. Head Neck 2008; 30:1182.
- Lee AW, Kwong DL, Leung SF, et al. Factors affecting risk of symptomatic temporal lobe necrosis: significance of fractional dose and treatment time. Int J Radiat Oncol Biol Phys 2002; 53:75.
- Lam HC, Abdullah VJ, Wormald PJ, Van Hasselt CA. Internal carotid artery hemorrhage after irradiation and osteoradionecrosis of the skull base. Otolaryngol Head Neck Surg 2001; 125:522.
- Siala W, Mnejja W, Abid M, et al. Thyroid toxicity after radiotherapy of nasopharyngeal carcinoma. Ann Endocrinol (Paris) 2011; 72:19.
- Lam TC, Wong FC, Leung TW, et al. Clinical outcomes of 174 nasopharyngeal carcinoma patients with radiation-induced temporal lobe necrosis. Int J Radiat Oncol Biol Phys 2012; 82:e57.
- Hsiao KY, Yeh SA, Chang CC, et al. Cognitive function before and after intensity-modulated radiation therapy in patients with nasopharyngeal carcinoma: a prospective study. Int J Radiat Oncol Biol Phys 2010; 77:722.
- PATHOLOGY AND STAGING
- GENERAL TREATMENT PRINCIPLES
- Radiation therapy
- - Intensity-modulated RT
- - Radiation dose
- - Alternative RT schedules
- Management of the neck
- Endemic versus nonendemic disease
- EARLY (STAGE I) DISEASE
- INTERMEDIATE (STAGE II) DISEASE
- ADVANCED (STAGE III, IVA, AND IVB) DISEASE
- Concurrent chemoradiotherapy
- Adjuvant chemotherapy
- Sequential chemotherapy
- Chemotherapy regimen
- POSTTREATMENT FOLLOW-UP
- Documentation of remission
- Surveillance for recurrence
- Posttreatment EBV DNA levels
- TREATMENT-RELATED COMPLICATIONS
- SUMMARY AND RECOMMENDATIONS