Guidelines Summary

Guidelines for the treatment of nasopharyngeal carcinoma (NPC), issued by the American College of Radiology (ACR) in 2015, include the following recommendations^[74]:

Nasopharyngectomy, stereotactic radiation therapy (SRT), intensity-modulated radiation therapy (IMRT), or IMRT with concurrent chemotherapy are all acceptable treatments for locally recurrent NPC in the absence of distant disease
Patients who had poor tolerance to initial concurrent therapy for locally advanced NPC may omit or receive adjuvant chemotherapy, provided that it is administered in a timely manner and there is good recovery from the toxicity
Patients with locally advanced and bulky, invasive NPC are typically treated with concurrent chemoradiation, although sequential or adjuvant approaches are also acceptable
Patients with an isolated bone focus of metastatic disease may achieve lengthy progression-free survival when treated with definitive concurrent chemoradiation to the primary site, as well as definitive radiation or stereotactic body radiation therapy to the metastatic bone disease
A platinum doublet is the standard systemic regimen for recurrent or metastatic NPC

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Axial T2-weighted image shows a left-sided cervical nodal metastasis resulting from nasopharyngeal cancer.

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Table 1. Diagnostic profiles of IgA to EA and IgA to VCA ^[14]

Serology Status	Sensitivity	Specificity	PPV			NPV
IgA to EA	80.2%	100%	100%		83.5%
IgA to VCA	97.3%	46.8%	64.7%	94.5%

Table 2. Predictive Value of Epstein-Barr Virus Serology Combinations

IgA Antibody to EA	IgA Antibody to VCA	Probability of NPC
+	+	100%
+	—	100%
—	—	5.5%
—	+	37.8%

Table 3. Diagnostic Values of the 4 EBV Antibodies ^[15]

Serology Status	Sensitivity	Specificity	Area Under ROC Curve (95% CI)
IgA to EA	89.1%	98.5%	0.94 (0.92-0.96)
IgA to VCA	98.1%	82.8%	0.98 (0.96-0.99)
IgG to Rta	90.5%	85.2%	0.92 (0.89-0.95)
IgA to EBNA1	87.2%	84.2%	0.92 (0.89-0.95)

Table 4. Diagnostic Accuracy based on Different Combination of the 4 EBV Antibodies

Combination	Sensitivity	Specificity	Area Under ROC Curve (95% CI)
IgG to Rta + IgA to EBNA1	93.4%	90.6%	0.97 (0.95-0.98)
IgA to VCA + IgA to EA	92.4%	98.5%	0.98 (0.96-0.99)
IgA to VCA + IgA to EBNA1	94.3%	98.0%	0.98 (0.97-0.99)
IgA to VCA + IgG to Rta	94.8%	98.0%	0.99 (0.98-1.00)
IgA to VCA + IgA to EA + IgA to EBNA1	97.2%	95.6%	0.98 (0.97-0.99)
IgA to VCA + IgA to EA + IgG to Rta	92.9%	99.5%	0.99 (0.98-1.00)
IgA to VCA + IgG to Rta + IgA to EBNA1	94.8%	98.5%	0.99 (0.98-1.00)
IgA to VCA + IgA to EA + IgG to Rta + IgA to EBNA1	96.7%	97.0%	0.99 (0.98-1.00)

Table 5. Prospective Randomized Clinical Trials of Chemoradiation Versus Radiation Alone in the Treatment of Locally Advanced NPC

Author, Year	Stage	Number of Patients	Treatment Arms	Survival Rate	P Value
Neoadjuvant Chemotherapy Followed by Radiation
VUMCA, 1996^[52]	IV	n=171	Bleomycin/epirubicin/cisplatin X 3 Radiation	60% (3 yr OS)	P > .05
		n=168	Radiation alone	54% (3 y OS)
Hareyama, 2002^[53]	I-IV	n=40	Cisplatin/5-FU X 2 Radiation	60% (5 y OS)	P > .05
		n=40	Radiation alone	45% (5 y OS)
Chua, 1998^[37]	T3 N2-3	n=167	Cisplatin/epirubicin X 2-3 Radiation	78% (3 y OS)	P = .57
		n=167	Radiation alone	71% (3 y OS)
Ma, 2001^[38]	III-IV	n=224	Cisplatin/bleomycin/5-FU X 2-3 Radiation	63% (5 y OS)	P = .11
		n=225	Radiation alone	56% (5 y OS)
Concurrent Chemotherapy and Radiation
Lin, 2003^[40]	III-IV	n=141	Cisplatin/5-FU X 2 + Radiation	72.3% (5 y OS)	P = .002
		n=143	Radiation alone	54.2% (5 y OS)
Chan, 2005^[39]	II-IV	n=174	Cisplatin weekly and Radiation	70.3% (5 y OS)	P = .048
		n=176	Radiation alone	58.6% (5 y OS)
Radiation Followed by Adjuvant Chemotherapy
Rossi, 1988^[54]	I-IV	n=113	Radiation Vincristine/cyclophosphamide/Adriamycin X 6	59% (4 y OS)	P > .05
		n=116	Radiation alone	67% (4 y OS)
Chi, 2002^[35]	IV	n=77	Radiation Cisplatin/5-FU/leucovorin X 9	61% (5 y OS)	P = .5
		n=77	Radiation alone	55% (5 y OS)
Neoadjuvant Chemotherapy Followed by Radiation Followed by Adjuvant Chemotherapy
Chan, 1995^[39]		n=34	Cisplatin/5-FU X 2 Radiation Cisplatin/5-FU X 4	80% (5 y OS)	P = .1
		n=40	Radiation alone	81% (5 y OS)
Concurrent Chemotherapy and Radiation Followed by Adjuvant Chemotherapy
Al-Sarraf, 1998^[32]	III-IV	n=93	Cisplatin X 3 + Radiation Cisplatin/5-FU X 3	78% (3 y OS)	P< 0.001
		n=92	Radiation alone	47% (3 y OS)
Al-Sarraf, 2002^[34]; 2001^[55]	III-IV	n=93	Cisplatin X 3 + Radiation Cisplatin/5-FU X 3	67% (5 y OS)	P< 0.001
		n=92	Radiation alone	37% (5 y OS)
Wee, 2004^{[41, 42]}	III-IV	n=111	Cisplatin X 3 + Radiation Cisplatin/5-FU X 3	67% (5 y OS)	P = 0.008
		n=110	Radiation alone	49% (5 y OS)
Lee, 2005^[43]; 2010^[44]	T1-4 N2-3	n=172	Cisplatin X 3 + Radiation Cisplatin/5-FU X 3	68% (5 y OS)	P = 0.22
		n=176	Radiation alone	64% (5 y OS)
Chen, 2013^[46]	III-IV	n=158	1) Cisplatin weekly + radiation 2) Cisplatin/5-FU X 3	72% (5 y OS)	P = 0.043
		n=158	Radiation alone
				62% (5 y OS)

Table 6. Intergroup Study 0099. Subgroup Analysis of 5-Year Overall Survival Based on WHO Types ^[32]

Treatment

WHO I, II, III

(n=147) OS, %

WHO II and III

(n=111, 75) OS, %

WHO I

(n=36, 25%) OS, %

Radiation

Chemoradiation

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Author

Ho-Sheng Lin, MD, FACS Professor and Interim Chair, Department of Otolaryngology-Head and Neck Surgery, Faculty, Sleep Fellowship Program, Divison of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Wayne State University School of Medicine; Chief, Section of Otolaryngology, Department of Surgery, John D Dingell Veterans Affairs Medical Center

Ho-Sheng Lin, MD, FACS is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Association of University Professors, American College of Surgeons, American Head and Neck Society, Association of VA Surgeons, Chinese American Medical Society, SWOG, American Academy of Sleep Medicine, Triological Society

Disclosure: Received consulting fee from Intuitive Surgical for proctoring; consultant for Checkpoint Surgical.

Coauthor(s)

Willard E Fee, Jr, MD Edward C and Amy H Sewall Professor Emeritus, Chairman Emeritus, Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine

Willard E Fee, Jr, MD is a member of the following medical societies: American College of Surgeons, American Laryngological Association, American Medical Association, California Medical Association, The Triological Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Nader Sadeghi, MD, FRCSC Professor and Chairman, Department of Otolaryngology-Head and Neck Surgery, McGill University Faculty of Medicine; Chief Otolaryngologist, MUHC; Director, McGill Head and Neck Cancer Program, Royal Victoria Hospital, Canada

Nader Sadeghi, MD, FRCSC is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society, American Thyroid Association, Royal College of Physicians and Surgeons of Canada

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Merck.

Chief Editor

Arlen D Meyers, MD, MBA Professor of Otolaryngology, Dentistry, and Engineering, University of Colorado School of Medicine

Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cerescan; Ryte; Neosoma; MI10<br/>Received income in an amount equal to or greater than $250 from: Neosoma; Cyberionix (CYBX)<br/>Received ownership interest from Cerescan for consulting for: Neosoma, MI10.

Additional Contributors

Benoit J Gosselin, MD, FRCSC Associate Professor of Surgery, Dartmouth Medical School; Director, Comprehensive Head and Neck Oncology Program, Norris Cotton Cancer Center; Staff Otolaryngologist, Division of Otolaryngology-Head and Neck Surgery, Dartmouth-Hitchcock Medical Center

Benoit J Gosselin, MD, FRCSC is a member of the following medical societies: American Head and Neck Society, American Academy of Facial Plastic and Reconstructive Surgery, North American Skull Base Society, American Academy of Otolaryngology-Head and Neck Surgery, American Medical Association, American Rhinologic Society, Canadian Medical Association, Canadian Society of Otolaryngology-Head & Neck Surgery, College of Physicians and Surgeons of Ontario, New Hampshire Medical Society, Ontario Medical Association

Disclosure: Nothing to disclose.