Abstract
Purpose
18-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) is increasingly used to evaluate treatment response in head and neck squamous cell carcinoma (HNSCC). This analysis assessed the diagnostic value of FDG-PET/CT in detecting nodal disease within 6 months after treatment, considering patient and disease characteristics.
Methods
A systematic review was performed using the MEDLINE and Web of Knowledge databases. The results were pooled using a bivariate random effects model of the sensitivity and specificity.
Results
Out of 22 identified studies, a meta-analysis of 20 studies (1293 patients) was performed. The pooled estimates of sensitivity, specificity and diagnostic odds ratio (with 95% CI) were 85% (76–91%), 93% (89–96%) and 76 (35–165), respectively. With the prevalence set at 10%, the positive and negative predictive values were 58% and 98%. There was significant heterogeneity between the trials (p < 0.001). HPV positive tumors were associated with lower sensitivity (75% vs 89%; p = 0.01) and specificity (87% vs 95%; p < 0.005).
Conclusion
FDG-PET/CT within 6 months after (chemo)radiotherapy in HNSCC patients is a reliable method for ruling out residual/recurrent nodal disease and obviates the need for therapeutic intervention. However, FDG-PET/CT may be less reliable in HPV positive tumors and the optimal surveillance strategy remains to be determined.
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References
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.
Marur S, Forastiere AA. Head and neck cancer: changing epidemiology, diagnosis, and treatment. Mayo Clin Proc. 2008;83:489–501.
Petrelli F, Coinu A, Riboldi V, Borgonovo K, Ghilardi M, Cabiddu M, et al. Concomitant platinum-based chemotherapy or cetuximab with radiotherapy for locally advanced head and neck cancer: a systematic review and meta-analysis of published studies. Oral Oncol. 2014;50:1041–8.
Barkley HT, Fletcher GH, Jesse RH, Lindberg RD. Management of cervical lymph node metastases in squamous cell carcinoma of the tonsillar fossa, base of tongue, supraglottic larynx, and hypopharynx. Am J Surg. 1972;124:462–7.
Hamoir M, Ferlito A, Schmitz S, Hanin FX, Thariat J, Weynand B, et al. The role of neck dissection in the setting of chemoradiation therapy for head and neck squamous cell carcinoma with advanced neck disease. Oral Oncol. 2012;48:203–10.
Posner M, Hershock D, Blajman C, Mickiewicz E, Winquist E, Gorbounova V, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007;357:1705–15.
Lavertu P, Adelstein D, Saxton J, Secic M, Wanamaker J, Eliachar I, et al. Management of the neck in a randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer. Head Neck. 1997;19:559–66.
McHam SA, Adelstein DJ, Rybicki LA, Lavertu P, Esclamado RM, Wood BG, et al. Who merits a neck dissection after definitive chemoradiotherapy for N2-N3 squamous cell head and neck cancer? Head Neck. 2003;25:791–8.
Isles MG, McConkey C, Mehanna HM. A systematic review and meta-analysis of the role of positron emission tomography in the follow up of head and neck squamous cell carcinoma following radiotherapy or chemoradiotherapy. Clin Otolaryngol. 2008;33:210–22.
Gupta T, Master Z, Kannan S, Agarwal JP, Ghsoh-Laskar S, Rangarajan V, et al. Diagnostic performance of post-treatment FDG PET or FDG PET/CT imaging in head and neck cancer: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging. 2011;38:2083–95.
Gourin CG, Boyce BJ, Williams HT, Herdman AV, Bilodeau PA, Coleman TA. Revisiting the role of positron-emission tomography/computed tomography in determining the need for planned neck dissection following chemoradiation for advanced head and neck cancer. Laryngoscope. 2009;119:2150–5.
Moeller BJ, Rana V, Cannon BA, Williams MD, Sturgis EM, Ginsberg LE, et al. Prospective risk-adjusted [18F]fluorodeoxyglucose positron emission tomography and computed tomography assessment of radiation response in head and neck cancer. J Clin Oncol. 2009;27:2509–15.
Fakhry N, Barberet M, Paris J, Jacob T, Deveze A, Mundler O, et al. Intérêt de la TEP au 18FDG couplée à la TDM dans la surveillance post-thérapeutiquedes carcinomes épidermoïdesdes voies aérodigestives supérieures. Ann Otolaryngol Chir Cervicofac. 2006;123:167–74.
Ito K, Yokoyama J, Kubota K, Morooka M, Shiibashi M, Matsuda H. 18F-FDG versus 11C-choline PET/CT for the imaging of advanced head and neck cancer after combined intra-arterial chemotherapy and radiotherapy: the time period during which PET/CT can reliably detect non-recurrence. Eur J Nucl Med Mol Imaging. 2010;37:1318–27.
Nayak JV, Walvekar RR, Andrade RS, Daamen N, Lai SY, Argiris A, et al. Deferring planned neck dissection following chemoradiation for stage IV head and neck cancer: the utility of PET-CT. Laryngoscope. 2007;117:2129–34.
Cho AH, Shah S, Ampil F, Bhartur S, Nathan C-AO. N2 disease in patients with head and neck squamous cell cancer treated with chemoradiotherapy: is there a role for posttreatment neck dissection? Arch Otolaryngol Head Neck Surg. 2009;135:1112–8.
Chan JYK, Sanguineti G, Richmon JD, Marur S, Gourin CG, Koch W, et al. Retrospective review of positron emission tomography with contrast-enhanced computed tomography in the posttreatment setting in human papillomavirus-associated oropharyngeal carcinoma. Arch Otolaryngol Head Neck Surg. 2012;138:1040–6.
Ng SH, Chan SC, Yen TC, Liao CT, Lin CY, Tung-Chieh Chang J, et al. PET/CT and 3-T whole-body MRI in the detection of malignancy in treated oropharyngeal and hypopharyngeal carcinoma. Eur J Nucl Med Mol Imaging. 2011;38:996–1008.
Chen AY, Vilaseca I, Hudgins PA, Schuster D, Halkar R. PET-CT vs contrast-enhanced CT: what is the role for each after chemoradiation for advanced oropharyngeal cancer? Head Neck. 2006;28:487–95.
Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14.
Stein AP, Saha S, Kraninger JL, Swick AD, Yu M, Lambert PF, et al. Prevalence of human papillomavirus in oropharyngeal cancer: a systematic review. Cancer J. 2015;21:138–46.
Whiting P, Rutjes A, Westwood M, Mallett S, Deeks J, Reitsma J, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155:529–36.
Jüni P, Witschi A, Bloch R, Egger M. The hazards of scoring the quality of clinical trials for meta-analysis. JAMA. 1999;282:1054–60.
Møller B, Weedon-Fekjaer H, Haldorsen T. Empirical evaluation of prediction intervals for cancer incidence. BMC Med Res Methodol. 2005;5:21.
Harbord RM, Deeks JJ, Egger M, Whiting P, Sterne JA. A unification of models for meta-analysis of diagnostic accuracy studies. Biostatistics. 2007;8:239–51.
Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol. 2005;58:982–90.
Helsen N, Roothans D, Van Den Heuvel B, Van den Wyngaert T, van den Weyngaert D, Carp L, et al. 18F-FDG-PET/CT for the detection of disease in patients with head and neck cancer treated with radiotherapy. PLoS One. 2017;12:e0182350.
Bird T, Barrington S, Thavaraj S, Jeannon JP, Lyons A, Oakley R, et al. 18F-FDG PET/CT to assess response and guide risk-stratified follow-up after chemoradiotherapy for oropharyngeal squamous cell carcinoma. Eur J Nucl Med Mol Imaging. 2016;43:1239–47.
Connell CA, Corry J, Milner AD, Hogg A, Hicks RJ, Rischin D, et al. Clinical impact of, and prognostic stratification by, F-18 FDG PET/CT in head and neck mucosal squamous cell carcinoma. Head Neck. 2007;29:986–95.
Gupta T, Jain S, Agarwal JP, Rangarajan V, Purandare N, Ghosh-Laskar S, et al. Diagnostic performance of response assessment FDG-PET/CT in patients with head and neck squamous cell carcinoma treated with high-precision definitive (chemo)radiation. Radiother Oncol. 2010;97:194–9.
Keski-Säntti H, Mustonen T, Schildt J, Saarilahti K, Mäkitie A. FDG-PET/CT in the assessment of treatment response after oncologic treatment of head and neck squamous cell carcinoma. Clin. Med. Insights ear. Nose Throat. 2014;19:25–9.
Loo SW, Geropantas K, Beadsmoore C, Montgomery PQ, Martin WM, Roques TW. Neck dissection can be avoided after sequential chemoradiotherapy and negative post-treatment positron emission tomography-computed tomography in N2 head and neck squamous cell carcinoma. Clin Oncol. 2011;23:512–7.
Malone JP, Gerberi MA, Vasireddy S, Hughes LF, Rao K, Shevlin B, et al. Early prediction of response to chemoradiotherapy for head and neck cancer: reliability of restaging with combined positron emission tomography and computed tomography. Arch Otolaryngol Head Neck Surg. 2009;135:1119–25.
Porceddu SV, Pryor DI, Burmeister E, Burmeister BH, Poulsen MG, Foote MC, et al. Results of a prospective study of positron emission tomography-directed management of residual nodal abnormalities in node-positive head and neck cancer after definitive radiotherapy with or without systemic therapy. Head Neck. 2011;33:1675–82.
Prestwich RJ, Subesinghe M, Gilbert A, Chowdhury FU, Sen M, Scarsbrook AF. Delayed response assessment with FDG-PET-CT following (chemo)radiotherapy for locally advanced head and neck squamous cell carcinoma. Clin Radiol. 2012;67:966–75.
Rabalais AG, Walvekar R, Nuss D, McWhorter A, Wood C, Fields R, et al. Positron emission tomography-computed tomography surveillance for the node-positive neck after chemoradiotherapy. Laryngoscope. 2009;119:1120–4.
Schouten CS, de Graaf P, Alberts FM, Hoekstra OS, Comans EF, Bloemena E, et al. Response evaluation after chemoradiotherapy for advanced nodal disease in head and neck cancer using diffusion-weighted MRI and 18F-FDG-PET-CT. Oral Oncol. 2015;51:541–7.
Sjövall J, Bitzén U, Kjellén E, Nilsson P, Wahlberg P, Brun E. Qualitative interpretation of PET scans using a Likert scale to assess neck node response to radiotherapy in head and neck cancer. Eur J Nucl Med Mol Imaging. 2016;43:609–16.
Slevin F, Subesinghe M, Ramasamy S, Sen M, Scarsbrook AF, Prestwich RJD. Assessment of outcomes with delayed 18F-FDG PET-CT response assessment in head and neck squamous cell carcinoma. Br J Radiol. 2015;88:20140592.
Vainshtein JM, Spector ME, Stenmark MH, Bradford CR, Wolf GT, Worden FP, et al. Reliability of post-chemoradiotherapy F-18-FDG PET/CT for prediction of locoregional failure in human papillomavirus-associated oropharyngeal cancer. Oral Oncol. 2014;50:234–9.
Zundel MT, Michel MA, Schultz CJ, Maheshwari M, Wong SJ, Campbell BH, et al. Comparison of physical examination and fluorodeoxyglucose positron emission tomography/computed tomography 4-6 months after radiotherapy to assess residual head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2011;81:825–32.
Mehanna H, Wong W-L, McConkey CC, Rahman JK, Robinson M, Hartley AG, et al. PET-CT surveillance versus neck dissection in advanced head and neck cancer. N Engl J Med. 2016;374:1444–54.
Fakhry N, Lussato D, Jacob T, Giorgi R, Giovanni A, Zanaret M. Comparison between PET and PET/CT in recurrent head and neck cancer and clinical implications. Eur Arch Otorhinolaryngol. 2007;264:531–8.
Goshen E, Davidson T, Yahalom R, Talmi YP, Zwas ST. PET/CT in the evaluation of patients with squamous cell cancer of the head and neck. Int J Oral Maxillofac Surg. 2006;35:332–6.
Krupar R, Robold K, Gaag D, Spanier G, Kreutz M, Renner K, et al. Immunologic and metabolic characteristics of HPV-negative and HPV-positive head and neck squamous cell carcinomas are strikingly different. Virchows Arch. 2014;465:299–312.
Tahari AK, Alluri KC, Quon H, Koch W, Wahl RL, Subramaniam RM. FDG PET/CT imaging of oropharyngeal squamous cell carcinoma: characteristics of human papillomavirus-positive and -negative tumors. Clin Nucl Med. 2014;39:225–31.
Clark J, Jeffery CC, Zhang H, Cooper T, O’Connell DA, Harris J, et al. Correlation of PET-CT nodal SUVmax with p16 positivity in oropharyngeal squamous cell carcinoma. J Otolaryngol Head Neck Surg. 2015;44.
Ang K, Harris J, Wheeler R, Weber R, Rosenthal D, Nguyen-Tân P, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24–35.
Mirghani H, Amen F, Tao Y, Deutsch E, Levy A. Increased radiosensitivity of HPV-positive head and neck cancers: molecular basis and therapeutic perspectives. Cancer Treat Rev. 2015;41:844–52.
Huang SH, O’Sullivan BO, Xu W, Zhao H, Chen D, Ringash J, et al. Temporal nodal regression and regional control after primary radiation therapy for N2-N3 head-and-neck cancer stratified by HPV status. Radiat Oncol Biol Elsevier Inc. 2013;87:1078–85.
Marcus C, Ciarallo A, Tahari AK, Mena E, Koch W, Wahl RL, et al. Head and neck PET/CT: therapy response interpretation criteria (Hopkins criteria)-interreader reliability, accuracy, and survival outcomes. J Nucl Med. 2014;55:1411–6.
Aide N, Lasnon C, Veit-Haibach P, Sera T, Sattler B, Boellaard R. EANM/EARL harmonization strategies in PET quantification: from daily practice to multicentre oncological studies. Eur J Nucl Med Mol Imaging. 2017;44:17–31.
Acknowledgements
We would like to thank the corresponding authors of the selected studies who provided additional information that contributed significantly to this meta-analysis.
This study was supported by a grant by the Flemish agency for innovation by science and technology (IWT-90867).
Funding
This study was supported by a grant by the Flemish agency for innovation by science and technology (IWT-90867).
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Helsen, N., Van den Wyngaert, T., Carp, L. et al. FDG-PET/CT for treatment response assessment in head and neck squamous cell carcinoma: a systematic review and meta-analysis of diagnostic performance. Eur J Nucl Med Mol Imaging 45, 1063–1071 (2018). https://doi.org/10.1007/s00259-018-3978-3
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DOI: https://doi.org/10.1007/s00259-018-3978-3