Skip to main content
SpringerLink
Log in

Nodal parameters of FDG PET/CT performed during radiotherapy for locally advanced mucosal primary head and neck squamous cell carcinoma can predict treatment outcomes: SUVmean and response rate are useful imaging biomarkers

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the prognostic utility of nodal metabolic parameters derived from FDG PET/CT performed before radiotherapy (prePET) and during the third week of radiotherapy (iPET) in patients with mucosal primary head and neck squamous cell carcinoma (MPHNSCC).

Methods

This analysis included 75 patients with newly diagnosed locally advanced node-positive MPHNSCC treated with radical radiotherapy and concurrent systemic therapy who underwent prePET and iPET: N1 11 patients, N2a 38, N2b 12, N2c 9, N3 5. The median follow-up was 28 months (9 – 70 months). The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of the index lymph node (node with the highest TLG) and the combined total lymph nodes, and their percentage reductions on iPET were determined, and the results were correlated with 3-year Kaplan-Meier locoregional, regional and distant metastatic failure-free survival (FFS), disease-free survival (DFS) and overall survival (OS). Optimal cut-off values were derived from receiver operating characteristic curves. Cox regression univariate and multivariate analyses with clinical covariates were performed.

Results

Based on assessment of residual nodal metabolic burden during treatment, the iPET index node SUVmean (optimal cut-off value 2.95 g/ml) and the total node SUVmean (optimal cut-off value 3.25) were the best independent predictors of outcome in the multivariate analysis: index node SUVmean for DFS and OS p = 0.033 and 0.003, respectively, and the total node SUVmean for locoregional FFS, DFS and OS p = 0.028, 0.025 and 0.014, respectively. Based on the assessment of response rates during treatment, a reduction of more than 50 % in the total node TLG was the best biomarker for locoregional and regional FFS, DFS and OS in the multivariate analysis (p = 0.001, 0.016, 0.001 and 0.004, respectively), and reduction in the total node MTV for locoregional FFS, DFS and OS (p = 0.026, 0.003 and 0.014, respectively). There were no significant correlations between oncological outcomes and prePET nodal parameters.

Conclusion

We demonstrated that the index node and total node SUVmean on iPET and a reduction of more than 50 % in MTV and TLG are useful imaging biomarkers, and can potentially identify those patients with MPHNSCC who have a high risk of locoregional metastatic failure and death.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Marta GN, Silva V, de Andrade Carvalho H, de Arruda FF, Hanna SA, Gadia R, et al. Intensity-modulated radiation therapy for head and neck cancer: systematic review and meta-analysis. Radiother Oncol. 2014;110(1):9–15.

    Article  PubMed  Google Scholar 

  2. Corry J, Peters LJ, Rischin D. Optimising the therapeutic ratio in head and neck cancer. Lancet Oncol. 2010;11(3):287–291.

    Article  PubMed  Google Scholar 

  3. Gregoire V, Jeraj R, Lee JA, O’Sullivan B. Radiotherapy for head and neck tumours in 2012 and beyond: conformal, tailored, and adaptive? Lancet Oncol. 2012;13(7):e292–e300.

    Article  PubMed  Google Scholar 

  4. Chao KS, Ozyigit G, Tran BN, Cengiz M, Dempsey JF, Low DA. Patterns of failure in patients receiving definitive and postoperative IMRT for head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2003;55(2):312–321.

    Article  PubMed  Google Scholar 

  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;38(11):2083–2095.

    Article  PubMed  Google Scholar 

  6. Ceulemans G, Voordeckers M, Farrag A, Verdries D, Storme G, Everaert H. Can 18-FDG-PET during radiotherapy replace post-therapy scanning for detection/demonstration of tumor response in head-and-neck cancer? Int J Radiat Oncol Biol Phys. 2011;81(4):938–942.

    Article  PubMed  Google Scholar 

  7. Castaldi P, Rufini V, Bussu F, Micciche F, Dinapoli N, Autorino R, et al. Can “early” and “late”18F-FDG PET-CT be used as prognostic factors for the clinical outcome of patients with locally advanced head and neck cancer treated with radio-chemotherapy? Radiother Oncol. 2012;103(1):63–8.

    Article  PubMed  Google Scholar 

  8. Brun E, Kjellen E, Tennvall J, Ohlsson T, Sandell A, Perfekt R, et al. FDG PET studies during treatment: prediction of therapy outcome in head and neck squamous cell carcinoma. Head Neck. 2002;24(2):127–135.

    Article  PubMed  Google Scholar 

  9. Hentschel M, Appold S, Schreiber A, Abolmaali N, Abramyuk A, Dorr W, et al. Early FDG PET at 10 or 20 Gy under chemoradiotherapy is prognostic for locoregional control and overall survival in patients with head and neck cancer. Eur J Nucl Med Mol Imaging. 2011;38(7):1203–1211.

    Article  PubMed  Google Scholar 

  10. Min M, Lin P, Lee MT, Shon IH, Lin M, Forstner D, et al. Prognostic role of metabolic parameters of 18F-FDG PET-CT scan performed during radiation therapy in locally advanced head and neck squamous cell carcinoma. Eur J Nucl Med Mol Imaging. 2015;42(13):1984–1994.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Min M, Lin P, Lee M, Shon IH, Lin M, Forstner D, et al. 18F-FDG PET-CT performed before and during radiation therapy of head and neck squamous cell carcinoma: are they independent or complementary to each other? J Med Imaging Radiat Oncol. 2016;60(3):433–440.

    Article  PubMed  Google Scholar 

  12. Min M, Lin P, Liney G, Lee M, Forstner D, Fowler A, et al. A review of the predictive role of functional imaging in patients with mucosal primary head and neck cancer treated with radiation therapy. J Med Imaging Radiat Oncol. 2016. doi:10.1111/1754-9485.12496.

    Google Scholar 

  13. Lin P, Min M, Lee M, Holloway L, Forstner D, Bray V, et al. Prognostic utility of 18F-FDG PET-CT performed prior to and during primary radiotherapy for nasopharyngeal carcinoma: index node is a useful prognostic imaging biomarker site. Radiother Oncol. 2016;120(1):87–91.

    Article  CAS  PubMed  Google Scholar 

  14. 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(12):1675–1682.

    Article  PubMed  Google Scholar 

  15. 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(15):1444–1454.

    Article  CAS  PubMed  Google Scholar 

  16. 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(4):609–616.

    Article  PubMed  Google Scholar 

  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(9):1411–1416.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Min M, Lin P, Lee M, Ho Shon I, Lin M, Forstner D, et al. Prognostic value of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography scan carried out during and after radiation therapy for head and neck cancer using visual therapy response interpretation criteria. Clin Oncol. 2016;28(6):393–401.

    Article  CAS  Google Scholar 

  19. Chung MK, Jeong HS, Son YI, So YK, Park GY, Choi JY, et al. Metabolic tumor volumes by [18F]-fluorodeoxyglucose PET/CT correlate with occult metastasis in oral squamous cell carcinoma of the tongue. Ann Surg Oncol. 2009;16(11):3111–3117.

    Article  PubMed  Google Scholar 

  20. La TH, Filion EJ, Turnbull BB, Chu JN, Lee P, Nguyen K, et al. Metabolic tumor volume predicts for recurrence and death in head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2009;74(5):1335–1341.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Kim G, Kim YS, Han EJ, Yoo Ie R, Song JH, Lee SN, et al. FDG-PET/CT as prognostic factor and surveillance tool for postoperative radiation recurrence in locally advanced head and neck cancer. Radiat Oncol J. 2011;29(4):243–251.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Higgins KA, Hoang JK, Roach MC, Chino J, Yoo DS, Turkington TG, et al. Analysis of pretreatment FDG-PET SUV parameters in head-and-neck cancer: tumor SUVmean has superior prognostic value. Int J Radiat Oncol Biol Phys. 2012;82(2):548–553.

    Article  PubMed  Google Scholar 

  23. Pak K, Cheon GJ, Kang KW, Chung J-K, Kim EE, Lee DS. Prognostic value of SUVmean in oropharyngeal and hypopharyngeal cancers: comparison with SUVmax and other volumetric parameters of 18F-FDG PET. Clin Nucl Med. 2015;40(1):9–13.

    Article  PubMed  Google Scholar 

  24. Tang C, Murphy JD, Khong B, La TH, Kong C, Fischbein NJ, et al. Validation that metabolic tumor volume predicts outcome in head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2012;83(5):1514–1520.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Pak K, Cheon GJ, Nam HY, Kim SJ, Kang KW, Chung JK, et al. Prognostic value of metabolic tumor volume and total lesion glycolysis in head and neck cancer: a systematic review and meta-analysis. J Nucl Med. 2014;55(6):884–890.

    Article  CAS  PubMed  Google Scholar 

  26. Van de Wiele C, Kruse V, Smeets P, Sathekge M, Maes A. Predictive and prognostic value of metabolic tumour volume and total lesion glycolysis in solid tumours. Eur J Nucl Med Mol Imaging. 2013;40(2):290–301.

    Article  CAS  PubMed  Google Scholar 

  27. Busk M, Horsman MR, Kristjansen PE, van der Kogel AJ, Bussink J, Overgaard J. Aerobic glycolysis in cancers: implications for the usability of oxygen‐responsive genes and fluorodeoxyglucose‐PET as markers of tissue hypoxia. Int J Cancer. 2008;122(12):2726–2734.

    Article  CAS  PubMed  Google Scholar 

  28. Grégoire V, Langendijk JA, Nuyts S. Advances in radiotherapy for head and neck cancer. J Clin Oncol. 2015;33(29):3277–3284.

    Article  PubMed  Google Scholar 

  29. Jeong J, Setton JS, Lee NY, Oh JH, Deasy JO. Estimate of the impact of FDG-avidity on the dose required for head and neck radiotherapy local control. Radiother Oncol. 2014;111(3):340–347.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Nyflot MJ, Harari PM, Yip S, Perlman SB, Jeraj R. Correlation of PET images of metabolism, proliferation and hypoxia to characterize tumor phenotype in patients with cancer of the oropharynx. Radiother Oncol. 2012;105(1):36–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Dierckx RA, Van de Wiele C. FDG uptake, a surrogate of tumour hypoxia? Eur J Nucl Med Mol Imaging. 2008;35(8):1544–1549.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Busk M, Horsman MR, Jakobsen S, Bussink J, Van der Kogel A, Overgaard J. Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage. Eur J Nucl Med Mol Imaging. 2008;35(12):2294–2303.

    Article  CAS  PubMed  Google Scholar 

  33. van Baardwijk A, Dooms C, van Suylen RJ, Verbeken E, Hochstenbag M, Dehing-Oberije C, et al. The maximum uptake of 18F-deoxyglucose on positron emission tomography scan correlates with survival, hypoxia inducible factor-1α and GLUT-1 in non-small cell lung cancer. Eur J Cancer. 2007;43(9):1392–1398.

    Article  PubMed  Google Scholar 

  34. Han MW, Lee HJ, Cho KJ, Kim JS, Roh JL, Choi SH, et al. Role of FDG‐PET as a biological marker for predicting the hypoxic status of tongue cancer. Head Neck. 2012;34(10):1395–1402.

    Article  PubMed  Google Scholar 

  35. Hajian-Tilaki K. Receiver operating characteristic (ROC) curve analysis for medical diagnostic test evaluation. Caspian J Intern Med. 2013;4(2):627–635.

    PubMed  PubMed Central  Google Scholar 

  36. Hilsenbeck SG, Clark GM, McGuire WL. Why do so many prognostic factors fail to pan out? Breast Cancer Res Treat. 1992;22(3):197–206.

    Article  CAS  PubMed  Google Scholar 

  37. Brown E, Owen R, Harden F, Mengersen K, Oestreich K, Houghton W, et al. Predicting the need for adaptive radiotherapy in head and neck cancer. Radiother Oncol. 2015;116(1):57–63.

    Article  PubMed  Google Scholar 

  38. Brouwer CL, Steenbakkers RJ, Langendijk JA, Sijtsema NM. Identifying patients who may benefit from adaptive radiotherapy: does the literature on anatomic and dosimetric changes in head and neck organs at risk during radiotherapy provide information to help? Radiother Oncol. 2015;115(3):285–294.

    Article  PubMed  Google Scholar 

  39. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Min M, Lee MT, Lin P, Holloway L, Wijesekera D, Gooneratne D, et al. Assessment of serial multi-parametric functional MRI (diffusion-weighted imaging and R 2*) with 18F-FDG-PET in patients with head and neck cancer treated with radiation therapy. Br J Radiol. 2016;89(1058), 20150530.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine and PET, Liverpool Hospital, Locked Bag 7103, Liverpool BC, NSW, Australia

    Peter Lin

  2. South Western Sydney Clinical School, University of New South Wales, Sydney, NSW, Australia

    Peter Lin, Myo Min, Mark Lee, Lois Holloway & Dion Forstner

  3. Western Sydney University, Sydney, NSW, Australia

    Peter Lin & Lois Holloway

  4. Cancer Therapy Centre, Liverpool Hospital, Liverpool, NSW, Australia

    Myo Min, Mark Lee, Lois Holloway, Dion Forstner, Victoria Bray & Allan Fowler

  5. Ingham Institute of Applied Medical Research, Liverpool, NSW, Australia

    Myo Min, Lois Holloway & Dion Forstner

Authors
  1. Peter Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Myo Min
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mark Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lois Holloway
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dion Forstner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Victoria Bray
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Allan Fowler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Lin.

Ethics declarations

Funding

None.

Conflicts of interest

None.

Ethical approval

This study was approved by the local research ethics committee (Sydney South West Area Health Service Human Research Ethics Committee). For this type of study, formal consent is not required.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOCX 30 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lin, P., Min, M., Lee, M. et al. Nodal parameters of FDG PET/CT performed during radiotherapy for locally advanced mucosal primary head and neck squamous cell carcinoma can predict treatment outcomes: SUVmean and response rate are useful imaging biomarkers. Eur J Nucl Med Mol Imaging 44, 801–811 (2017). https://doi.org/10.1007/s00259-016-3584-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-016-3584-1

Keywords

Search

Navigation