Skip to main content
SpringerLink
Log in

Metabolic tumour volumes measured at staging in lymphoma: methodological evaluation on phantom experiments and patients

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

Abstract

Purpose

The presence of a bulky tumour at staging on CT is an independent prognostic factor in malignant lymphomas. However, its prognostic value is limited in diffuse disease. Total metabolic tumour volume (TMTV) determined on 18F-FDG PET/CT could give a better evaluation of the total tumour burden and may help patient stratification. Different methods of TMTV measurement established in phantoms simulating lymphoma tumours were investigated and validated in 40 patients with Hodgkin lymphoma and diffuse large B-cell lymphoma.

Methods

Data were processed by two nuclear medicine physicians in Reggio Emilia and Créteil. Nineteen phantoms filled with 18F-saline were scanned; these comprised spherical or irregular volumes from 0.5 to 650 cm3 with tumour-to-background ratios from 1.65 to 40. Volumes were measured with different SUVmax thresholds. In patients, TMTV was measured on PET at staging by two methods: volumes of individual lesions were measured using a fixed 41 % SUVmax threshold (TMTV41) and a variable visually adjusted SUVmax threshold (TMTVvar).

Results

In phantoms, the 41 % threshold gave the best concordance between measured and actual volumes. Interobserver agreement was almost perfect. In patients, the agreement between the reviewers for TMTV41 measurement was substantial (ρ c = 0.986, CI 0.97 – 0.99) and the difference between the means was not significant (212 ± 218 cm3 for Créteil vs. 206 ± 219 cm3 for Reggio Emilia, P = 0.65). By contrast the agreement was poor for TMTVvar. There was a significant direct correlation between TMTV41 and normalized LDH (r = 0.652, CI 0.42 – 0.8, P <0.001). Higher disease stages and bulky tumour were associated with higher TMTV41, but high TMTV41 could be found in patients with stage 1/2 or nonbulky tumour.

Conclusion

Measurement of baseline TMTV in lymphoma using a fixed 41% SUVmax threshold is reproducible and correlates with the other parameters for tumour mass evaluation. It should be evaluated in prospective studies.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Eichenauer DA, Engert A, Dreyling M. Hodgkin’s lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2011;22 Suppl 6:vi55–8.

    PubMed  Google Scholar 

  2. Pfreundschuh M, Ho AD, Cavallin-Stahl E, Wolf M, Pettengell R, Vasova I, et al. Prognostic significance of maximum tumour (bulk) diameter in young patients with good-prognosis diffuse large-B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: an exploratory analysis of the MabThera International Trial Group (MInT) study. Lancet Oncol. 2008;9:435–44.

    Article  PubMed  Google Scholar 

  3. Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, et al. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011;12:1013–22.

    Article  CAS  PubMed  Google Scholar 

  4. Hasenclever D, Diehl V. A prognostic score for advanced Hodgkin’s disease. International prognostic factors project on advanced Hodgkin’s disease. N Engl J Med. 1998;339:1506–14.

    Article  CAS  PubMed  Google Scholar 

  5. Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235–42.

    Article  CAS  PubMed  Google Scholar 

  6. Gobbi PG, Bassi E, Bergonzi M, Merli F, Coriani C, Iannitto E, et al. Tumour burden predicts treatment resistance in patients with early unfavourable or advanced stage Hodgkin lymphoma treated with ABVD and radiotherapy. Hematol Oncol. 2012;30:194–9.

    Article  PubMed  Google Scholar 

  7. 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. 2012;40:290–301.

    Article  PubMed  Google Scholar 

  8. Berkowitz A, Basu S, Srinivas S, Sankaran S, Schuster S, Alavi A. Determination of whole-body metabolic burden as a quantitative measure of disease activity in lymphoma: a novel approach with fluorodeoxyglucose-PET. Nucl Med Commun. 2008;29:521–6.

    Article  CAS  PubMed  Google Scholar 

  9. Song MK, Chung JS, Shin HJ, Moon JH, Lee JO, Lee HS, et al. Prognostic value of metabolic tumor volume on PET/CT in primary gastrointestinal diffuse large B cell lymphoma. Cancer Sci. 2012;103:477–82.

    Article  CAS  PubMed  Google Scholar 

  10. Song MK, Chung JS, Shin HJ, Lee SM, Lee SE, Lee HS, et al. Clinical significance of metabolic tumor volume by PET/CT in stages II and III of diffuse large B cell lymphoma without extranodal site involvement. Ann Hematol. 2012;91:697–703.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Mikhaeel NG, Smith D, Philips MM, Dunn JT, Fields PA, Moller H, et al. Does quantitative PET-CT predict prognosis in diffuse large B cell lymphoma. Hematol Oncol. 2013;31 Suppl 1:96–150.

    Google Scholar 

  12. Song MK, Chung JS, Lee JJ, Jeong SY, Lee SM, Hong JS, et al. Metabolic tumor volume by positron emission tomography/computed tomography as a clinical parameter to determine therapeutic modality for early stage Hodgkin's lymphoma. Cancer Sci. 2013;104:1656–61.

    Article  CAS  PubMed  Google Scholar 

  13. Luminari S, Cesaretti M, Tomasello C, Guida A, Bagni B, Merli F, et al. Use of 2-[18 F]fluoro-2-deoxy-D-glucose positron emission tomography in patients with Hodgkin lymphoma in daily practice: a population-based study from Northern Italy. Leuk Lymphoma. 2011;52:1689–96.

    Article  PubMed  Google Scholar 

  14. Casasnovas RO, Meignan M, Berriolo-Riedinger A, Bardet S, Julian A, Thieblemont C, et al. SUVmax reduction improves early prognosis value of interim positron emission tomography scans in diffuse large B-cell lymphoma. Blood. 2011;118:37–43.

    Article  CAS  PubMed  Google Scholar 

  15. Juweid ME, Stroobants S, Hoekstra OS, Mottaghy FM, Dietlein M, Guermazi A, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol. 2007;25:571–8.

    Article  PubMed  Google Scholar 

  16. Boellaard R, O’Doherty MJ, Weber WA, Mottaghy FM, Lonsdale MN, Stroobants SG, et al. FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2010;37:181–200.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Lin LI. A concordance correlation coefficient to evaluate reproducibility. Biometrics. 1989;45:255–68.

    Article  CAS  PubMed  Google Scholar 

  18. Barnhart HX, Haber MJ, Lin LI. An overview on assessing agreement with continuous measurements. J Biopharm Stat. 2007;17:529–69.

    Article  PubMed  Google Scholar 

  19. McBride GB. A proposal for strength of agreement criteria for Lin’s concordance correlation coefficient. NIWA Client Report HAM2005-062. Hamilton, New Zealand: National Institute of Water & Atmospheric Research Ltd; 2005.

  20. Erdi YE, Mawlawi O, Larson SM, Imbriaco M, Yeung H, Finn R, et al. Segmentation of lung lesion volume by adaptive positron emission tomography image thresholding. Cancer. 1997;80:2505–9.

    Article  CAS  PubMed  Google Scholar 

  21. Ford EC, Kinahan PE, Hanlon L, Alessio A, Rajendran J, Schwartz DL, et al. Tumor delineation using PET in head and neck cancers: threshold contouring and lesion volumes. Med Phys. 2006;33:4280–8.

    Article  PubMed  Google Scholar 

  22. van Dalen JA, Hoffmann AL, Dicken V, Vogel WV, Wiering B, Ruers TJ, et al. A novel iterative method for lesion delineation and volumetric quantification with FDG PET. Nucl Med Commun. 2007;28:485–93.

    Article  PubMed  Google Scholar 

  23. Schinagl DA, Vogel WV, Hoffmann AL, van Dalen JA, Oyen WJ, Kaanders JH. Comparison of five segmentation tools for 18F-fluoro-deoxy-glucose-positron emission tomography-based target volume definition in head and neck cancer. Int J Radiat Oncol Biol Phys. 2007;69:1282–9.

    Article  CAS  PubMed  Google Scholar 

  24. Frings V, de Langen AJ, Smit EF, van Velden FH, Hoekstra OS, van Tinteren H, et al. Repeatability of metabolically active volume measurements with 18F-FDG and 18F-FLT PET in non-small cell lung cancer. J Nucl Med. 2010;51:1870–7.

    Article  PubMed  Google Scholar 

  25. Sasanelli M, Itti E, Biggi A, Berriolo-Riedinger A, Cashen A, Tilly H, et al. Prognostic value of pretherapy metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients with diffuse large B-cell lymphoma (DLBCL). J Nucl Med. 2012;53:170P.

    Google Scholar 

  26. Casasnovas RO, Sasanelli M, Berriolo-Riedinger A, Morschhauser F, Itti E, Huglo D, et al. Baseline metabolic tumor volume is predictive of patient outcome in diffuse large B cell lymphoma. Blood. 2012;120:1598.

    Google Scholar 

  27. Bodet-Milin C, Kraeber-Bodere F, Moreau P, Campion L, Dupas B, Le Gouill S. Investigation of FDG-PET/CT imaging to guide biopsies in the detection of histological transformation of indolent lymphoma. Haematologica. 2008;93:471–2.

    Article  PubMed  Google Scholar 

  28. Schöder H, Noy A, Gönen M, Weng L, Green D, Erdi YE, et al. Intensity of 18fluorodeoxyglucose uptake in positron emission tomography distinguishes between indolent and aggressive non-Hodgkin’s lymphoma. J Clin Oncol. 2005;23:4643–51.

    Article  PubMed  Google Scholar 

  29. Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50 Suppl 1:122S–50S.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Kanoun SRC, Berriolo-Riedinger A, Humbert O, Dygay-Cochet I, Chretien ML, Legouge C, et al. Metabolic tumor volume is an independent prognosis factor predicting patient’s outcome in Hodgkin lymphoma. Blood. 2012;120:3631.

    Google Scholar 

  31. Nestle U, Kremp S, Schaefer-Schuler A, Sebastian-Welsch C, Hellwig D, Rübe C, et al. Comparison of different methods for delineation of 18F-FDG PET-positive tissue for target volume definition in radiotherapy of patients with non-small cell lung cancer. J Nucl Med. 2005;46:1342–8.

    PubMed  Google Scholar 

  32. Jentzen W, Freudenberg L, Eising EG, Heinze M, Brandau W, Bockisch A. Segmentation of PET volumes by iterative image thresholding. J Nucl Med. 2007;48:108–14.

    CAS  PubMed  Google Scholar 

  33. Tylski P, Stute S, Grotus N, Doyeux K, Hapdey S, Gardin I, et al. Comparative assessment of methods for estimating tumor volume and standardized uptake value in (18)F-FDG PET. J Nucl Med. 2010;51:268–76.

    Article  PubMed  Google Scholar 

Download references

Author contributions

Conception and design

Michel Meignan, Annibale Versari, Stefano Luminari, Francesco Merli, Paolo G. Gobbi, Olivier Casasnovas.

Collection and assembly of data

All authors.

Data analysis and interpretation

Myriam Sasanelli, Annibale Versari, Michel Meignan, Federica Fioroni, Chiara Coriani, Olivier Casasnovas, Emmanuel Itti.

Manuscript writing

Michel Meignan, Annibale Versari, Olivier Casasnovas.

Final approval of manuscript

All authors.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, Hôpital Henri Mondor and Paris-Est University, Créteil, France

    Michel Meignan, Myriam Sasanelli & Emmanuel Itti

  2. Department of Hematology, CHU Le Bocage, Dijon, France

    René Olivier Casasnovas

  3. Department of Diagnostic, Clinic and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy

    Stefano Luminari

  4. Department of Medical Physics, Santa Maria Nuova Hospital-IRCCS, Reggio Emilia, Italy

    Federica Fioroni

  5. Department of Radiology, Santa Maria Nuova Hospital-IRCCS, Reggio Emilia, Italy

    Chiara Coriani

  6. Department of Radiophysics, Henri Mondor Hospital, Créteil, France

    Helene Masset

  7. Department of Internal Medicine and Gastroenterology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy

    Paolo G. Gobbi

  8. Department of Hematology, Santa Maria Nuova Hospital-IRCCS, Reggio Emilia, Italy

    Francesco Merli

  9. Department of Nuclear Medicine, Santa Maria Nuova Hospital-IRCCS, Reggio Emilia, Italy

    Annibale Versari

  10. Service de Médecine Nucléaire, EAC CNRS 7054, Hôpital Henri Mondor AP-HP, Paris-Est University, 51 Ave. du Mal de Lattre de Tassigny, 94010, Créteil, France

    Michel Meignan

Authors
  1. Michel Meignan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Myriam Sasanelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. René Olivier Casasnovas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stefano Luminari
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Federica Fioroni
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chiara Coriani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Helene Masset
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Emmanuel Itti
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Paolo G. Gobbi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Francesco Merli
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Annibale Versari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michel Meignan.

Additional information

This study was presented in part at the 4th International Workshop on PET in Lymphoma, Menton 2012.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meignan, M., Sasanelli, M., Casasnovas, R.O. et al. Metabolic tumour volumes measured at staging in lymphoma: methodological evaluation on phantom experiments and patients. Eur J Nucl Med Mol Imaging 41, 1113–1122 (2014). https://doi.org/10.1007/s00259-014-2705-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-014-2705-y

Keywords

Search

Navigation