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Reprinted by permission of Otolaryngol Head Neck Surg. 2016; 154(3):421-432.

Systematic Review/Meta-analysis

Otolaryngology– Head and Neck Surgery 2016, Vol. 154(3) 421–432 American Academy of Otolaryngology—Head and Neck

Detecting Residual/Recurrent Head Neck Squamous Cell Carcinomas Using PETor PET/CT: Systematic Review and Meta- analysis

Surgery Foundation 2015 Reprints and permission:

sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599815621742 http://otojournal.org

Phylannie K. F. Cheung, BVSc, MBBS 1 , Ronald Y. Chin, FRACS, MBBS 2 , and Guy D. Eslick, DrPH, PhD 3

S quamous cell carcinomas (SCCs) account for more than 90% of head and neck cancers. 1,2 Early-stage disease is typically treated with unimodality treatment (surgery or radiotherapy ) , while locally advanced tumors require a multimodality approach consisting of a combina- tion of surgery and radiotherapy with or without chemother- apy. 3 Despite treatment, up to 40% patients with advanced tumors will have a locoregional recurrence, 4,5 and up to 25% will have distant metastases, 6,7 with most of these locoregional recurrences occurring in the first 2 years post- treatment. 8 Patients with early-stage recurrences have a better prognosis compared with those with advanced-stage disease. 9 Those with residual or recurrent disease confined to the head and neck may be candidates for salvage surgery and reirradiation. However, palliative measures may be more appropriate for those in whom distant metastases are present at the time of recurrence. Furthermore, the recogni- tion of patients with a complete response postchemora- diotherapy can reduce the need for unnecessary tissue biopsies and neck dissections following treatment. Thus, from a clinical perspective, the ability to accurately detect residual or recurrent locoregional disease and exclude dis- tant metastases is important as it can help guide ongoing management of patients after chemoradiotherapy. Functional imaging using 18F-fluorodeoxyglucose posi- tron emission tomography (FDG PET) and integrated FDG PET/computed tomography (CT) is now widely used in the assessment of residual or recurrent disease in patients with head and neck squamous cell carcinoma (HNSCC). As 1 Sydney Medical School, The University of Sydney, New South Wales, Australia 2 Department of Otolaryngology Head and Neck Surgery, The University of Sydney, Nepean Hospital, Penrith, New South Wales, Australia 3 The Whiteley-Martin Research Centre, Discipline of Surgery, The University of Sydney, Nepean Hospital, Penrith, New South Wales, Australia Corresponding Author: Ronald Y. Chin, Department of Otolaryngology Head and Neck Surgery, The University of Sydney, Nepean Hospital,1 Hope St, Penrith, NSW 2750, Australia. Email: drronaldchin@gmail.com

No sponsorships or competing interests have been disclosed for this article.

Abstract Objective. To evaluate the diagnostic accuracy of positron emission tomography (PET) and PET/computed tomography (CT) for detecting residual and/or recurrent local and regional disease and distant metastases in patients with head and neck squamous cell carcinomas (HNSCCs) following radiotherapy with or without chemotherapy. Data Sources. A systematic review with no language restric- tions was conducted using PREMEDLINE, MEDLINE, EMBASE, and Google Scholar. Review Methods. Only prospective studies with histopatholo- gical and/or clinical follow-up that assessed the diagnostic accuracy of PET and PET/CT in detecting residual and/or recurrent disease following radiotherapy with or without chemotherapy in patients with HNSCCs were included. Results. Twenty-seven studies were identified. The pooled sen- sitivity and specificity of PET and PET/CT for detecting residual or recurrent disease at the primary site was 86.2% and 82.3%, respectively. For residual and recurrent neck disease, the sensi- tivity and specificity were 72.3% and 88.3%, while for distant metastases, the values were 84.6% and 94.9%. Conclusions. PET and PET/CT are highly accurate in detecting residual and/or recurrent HNSCC. PET/CT is more specific than PET alone. Specificity is also greater for scans per- formed more than 12 weeks after radiotherapy with or without chemotherapy. The authors support the use of PET/CT after 12 weeks posttreatment for the assessment of residual or recurrent disease. Keywords squamous cell carcinoma of the head and neck, locoregional neoplasm recurrence, systematic review, meta-analysis, posi- tron emission tomography

Received September 2, 2015; revised October 29, 2015; accepted November 19, 2015.

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