Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Quantification of 18F-fluorodeoxyglucose uptake to detect residual nodal disease in locally advanced head and neck squamous cell carcinoma after chemoradiotherapy: results from the ECLYPS study

Abstract

Background

The Hopkins criteria were introduced for nodal response evaluation after therapy in head and neck cancer, but its superiority over quantification is not yet confirmed.

Methods

SUVbody weight thresholds and lesion-to-background ratios were explored in a prospective multicenter study of standardized FDG-PET/CT 12 weeks after CRT in newly diagnosed locally advanced head and neck squamous cell carcinoma (LAHNSCC) patients (ECLYPS). Reference standard was histology, negative FDG-PET/CT at 12 months after treatment or ≥ 2 years of negative follow-up. Area under the receiver operator characteristics curves (AUROC) were estimated and obtained thresholds were validated in an independent cohort of HNSCC patients (n = 127).

Results

In ECLYPS, 124 patients were available for quantification. With a median follow-up of 20.4 months, 23 (18.5%) nodal neck recurrences were observed. A SUV70 threshold of 2.2 (AUROC = 0.89; sensitivity = 79.7%; specificity = 80.8%) was identified as optimal metric to identify nodal recurrence within 1 year after therapy. For lesion-to-background ratios, an SUV50/SUVliver threshold of 0.96 (AUROC = 0.89; sensitivity = 79.7%; specificity = 82.8%) had the best performance. Compared with Hopkins criteria (AUROC = 0.81), SUV70 and SUV50/SUVliver provided a borderline significant (p = 0.040 and p = 0.094, respectively) improvement. Validation of thresholds yielded similar AUROC values (SUV70 = 0.93, SUV50/SUVliver = 0.95), and were comparable to the Hopkins score (AUROC = 0.91; not statistically significant).

Conclusion

FDG quantification detects nodal relapse in LAHNSCC patients. When using EARL standardized PET acquisitions and reconstruction, absolute SUV metrics (SUV70 threshold 2.2) prove robust, yet ratios (SUV50/SUVliver, threshold 0.96) may be more useful in routine clinical care. In this setting, the diagnostic value of quantification is comparable to the Hopkins criteria.

Trial registration

US National Library for Medicine, NCT01179360. Registered 11 August 2010, https://clinicaltrials.gov/ct2/show/NCT01179360

This is a preview of subscription content, log in to check access.

Fig. 1

References

  1. 1.

    Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JWW, Comber H, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49:1374–403. https://doi.org/10.1016/j.ejca.2012.12.027.

  2. 2.

    Clayman G, Johnson C 2nd, Morrison W, Ginsberg L, Lippman S. The role of neck dissection after chemoradiotherapy for oropharyngeal cancer with advanced nodal disease. Arch Otolaryngol Head Neck Surg. 2001;127:135–9.

  3. 3.

    Frank D, Hu K, Culliney B, Persky M, Nussbaum M, Schantz S, et al. Planned neck dissection after concomitant radiochemotherapy for advanced head and neck cancer. Laryngoscope. 2005;115:1015–20.

  4. 4.

    Brizel D, Prosnitz R, Hunter S, Fisher S, Clough R, Downe M, et al. Necessity for adjuvant neck dissection in setting of concurrent chemoradiation for advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2004;58.

  5. 5.

    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. 2011:2083–95.

  6. 6.

    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.

  7. 7.

    Helsen N, Van den Wyngaert T, Carp L, Stroobants S. 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. Germany; 2018;

  8. 8.

    Rodrigues RS, Bozza FA, Christian PE, Hoffman JM, Butterfield RI, Christensen CR, et al. Comparison of whole-body PET/CT, dedicated high-resolution head and neck PET/CT, and contrast-enhanced CT in preoperative staging of clinically M0 squamous cell carcinoma of the head and neck. J Nucl Med. 2009;50:1205–13.

  9. 9.

    Yamamoto Y, Wong TZ, Turkington TG, Hawk TC, Coleman RE. Head and neck cancer: dedicated FDG PET/CT protocol for detection--phantom and initial clinical studies. Radiology. 2007;244:263–72.

  10. 10.

    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.

  11. 11.

    Porceddu SV, Jarmolowski E, Hicks RJ, Ware R, Weih L, Rischin D, et al. Utility of positron emission tomography for the detection of disease in residual neck nodes after (chemo) radiotherapy in head and neck cancer. Head Neck. 2005;27:175–81.

  12. 12.

    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.

  13. 13.

    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.

  14. 14.

    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.

  15. 15.

    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.

  16. 16.

    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.

  17. 17.

    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.

  18. 18.

    Boellaard R, Krak NC, Hoekstra OS, Lammertsma AA. Effects of noise, image resolution, and ROI definition on the accuracy of standard uptake values: a simulation study. J Nucl Med. 2004;45:1519–27.

  19. 19.

    Van Den Wyngaert T, Helsen N, Carp L, Hakim S, Martens MJ, Hutsebaut I, et al. Fluorodeoxyglucose-positron emission tomography/computed tomography after concurrent chemoradiotherapy in locally advanced head-and-neck squamous cell cancer: the ECLYPS study. J Clin Oncol. 2017;35.

  20. 20.

    Boellaard R, Willemsen AT, Arends B, Visser EP. EARL procedure for assessing P ET/CT system specific patient FDG activity preparations for q uantitative FDG PET/CT studies 2010;1–3. Available from: http://earl.eanm.org/html/img/pool/EARL-procedure-for-optimizing-FDG-activity-for-quantitative-FDG-PET-studies_version_1_1.pdf. Accessed 9 February 2020.

  21. 21.

    Boellaard R, Oyen WJG, Hoekstra CJ, Hoekstra OS, Visser EP, Willemsen AT, et al. The Netherlands protocol for standardisation and quantification of FDG whole body PET studies in multi-Centre trials. Eur J Nucl Med Mol Imaging. 2008;35:2320–33.

  22. 22.

    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.

  23. 23.

    Blanche P, Dartiques J, Jacqmin-Gadda H. Estimating and comparing time-dependent areas under receiver operating characteristic curves for censored event times with competing risks. Stat Med. 2013;32:5381–97.

  24. 24.

    Heagerty P, Lumley T, Pepe M. Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics. 2000;56:337–44.

  25. 25.

    Lapela M, Eigtved A, Jyrkkiö S, Grénman R, Kurki T, Lindholm P, et al. Experience in qualitative and quantitative FDG PET in follow-up of patients with suspected recurrence from head and neck cancer. Eur J Cancer. 2000;36:858–67.

  26. 26.

    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.

  27. 27.

    Ly J, Minarik D, Edenbrandt L, Wollmer P, Trägårdh E. The use of a proposed updated EARL harmonization of 18F-FDG PET-CT in patients with lymphoma yields significant differences in Deauville score compared with current EARL recommendations. EJNMMI Res. 2019.

  28. 28.

    Hamberg LM, Hunter GJ, Alpert NM, Choi NC, Babich JW, Fischman AJ. The dose uptake ratio as an index of glucose metabolism: useful parameter or oversimplification? J Nucl med. 1994;35:1308–12 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8046485 . Accessed 9 February 2020.

Download references

Funding

This study was supported by Grant No. IWT-90867 from the Flemish Agency for Innovation by Science and Technology.

Author information

NH, TVdW, LC, OMV, OSH, DVdW and SS participated in the study design. The collection and assembly of the data was performed by NH, TVdW, LC, OMV, SH, MM, OSH, RdB, FDG, AM, JPC, KS, LB, and DVdW. NH, TVdW, NH, LC, OSH, DVdW contributed to the data analysis and interpretation. All authors read and approved the final manuscript.

Correspondence to Nils Helsen.

Ethics declarations

Competing interests

The authors declare that they have no competing interests.

Ethics approval and consent to participate

This study and the informed consent was approved by our Ethics Committee (B30020109153). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Consent for publication

All authors approved the final manuscript and consent for publication.

Availability of data and material

The datasets used in this study are available from the corresponding author on reasonable request.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Oncology - Head and Neck

Electronic supplementary material

ESM 1

(PDF 467 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Helsen, N., Van den Wyngaert, T., Carp, L. et al. Quantification of 18F-fluorodeoxyglucose uptake to detect residual nodal disease in locally advanced head and neck squamous cell carcinoma after chemoradiotherapy: results from the ECLYPS study. Eur J Nucl Med Mol Imaging (2020). https://doi.org/10.1007/s00259-020-04710-4

Download citation

Keywords

  • Chemoradiotherapy
  • Standard uptake value (SUV)
  • 18F-fluorodeoxyglucose