Metabolic tumor burden on baseline 18F-FDG PET/CT improves risk stratification in pediatric patients with mature B-cell lymphoma

  • Suyun Chen
  • Kejun He
  • Fang Feng
  • Shaoyan Wang
  • Yafu Yin
  • Hongliang Fu
  • Hui WangEmail author
Original Article



In order to better identify patients most at risk of treatment failure and disease progression in pediatric mature B-cell non-Hodgkin lymphoma (B-NHL), the prognostic role of metabolic tumor burden measured on baseline 18F-FDG PET/CT scan, including total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG), was investigated.


Pretreatment 18F-FDG PET/CT scans from 46 consecutive pediatric patients (median age 7 years; range 2–18 years) with newly diagnosed B-NHL were retrospectively analyzed. Clinicopathological parameters and imaging characteristics, including TMTV, TLG, and bone marrow (BM) involvement detected by PET/CT were compared to predict progression-free survival (PFS) and overall survival (OS).


The median follow-up time was 31 months. Areas under the curve of TMTV and TLG to predict events were 0.820 and 0.816, respectively. The 2-year PFS and OS were 29% and 43% in 7 patients with high TLG (> 5797 g) vs. 93% and 96% in those with low TLG (P < 0.001). High TMTV (> 524 cm3) was present in ten patients and predicted a significantly inferior outcome (PFS: 50% vs. 92%, P = 0.001; OS: 60% vs. 96%, P = 0.002). In multivariate analysis, TMTV and TLG outperformed other clinicopathological factors, including serum lactate dehydrogenase and BM involvement on biopsy, and remained the most robust predictors of survival. Furthermore, TLG sub-stratified patients with distinct outcomes efficiently within high- or intermediate-risk groups, with the negative predictive value of 100% and 92% and the positive predictive value of 100% and 50% for high-risk and intermediate-risk patients, respectively. On the other hand, BM involvement identified only by PET demonstrated an inferior prognostic value in comparison with BM biopsy.


Baseline TMTV and TLG are both strong independent prognostic factors for pediatric B-NHL and provide a potential approach to aid in risk sub-stratification, especially in patients with high-risk disease.


18F-FDG PET/CT TMTV TLG Pediatric Mature B-cell non-Hodgkin lymphoma Survival 



This study has received funding by the National Natural Science Fund (81801731, 51673116 and 11775143).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This retrospective study was approved by the Institutional Review Board (Ethics Committee of Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, XHEC-D-2019-012, 2019). All procedures performed in this study involving human participants were in accordance with the ethical standards of the institution and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study, the requirement for informed consent is waived.

Supplementary material

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  1. 1.
    Reiter A, Schrappe M, Tiemann M, Ludwig WD, Yakisan E, Zimmermann M, et al. Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy: a report of the Berlin-Frankfurt-Munster group trial NHL-BFM 90. Blood. 1999;94:3294–306.PubMedGoogle Scholar
  2. 2.
    Patte C, Auperin A, Gerrard M, Michon J, Pinkerton R, Sposto R, et al. Results of the randomized international FAB/LMB96 trial for intermediate risk B-cell non-Hodgkin lymphoma in children and adolescents: it is possible to reduce treatment for the early responding patients. Blood. 2007;109:2773–80.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Jourdain A, Auperin A, Minard-Colin V, Aladjidi N, Zsiros J, Coze C, et al. Outcome of and prognostic factors for relapse in children and adolescents with mature B-cell lymphoma and leukemia treated in three consecutive prospective "Lymphomes Malins B" protocols. A Societe Francaise des cancers de l'Enfant study. Haematologica. 2015;100:810–7.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Cairo M, Auperin A, Perkins SL, Pinkerton R, Harrison L, Goldman S, et al. Overall survival of children and adolescents with mature B cell non-Hodgkin lymphoma who had refractory or relapsed disease during or after treatment with FAB/LMB 96: a report from the FAB/LMB 96 study group. Br J Haematol. 2018;182:859–69.CrossRefPubMedGoogle Scholar
  5. 5.
    Chen S, Wang S, He K, Ma C, Fu H, Wang H. PET/CT predicts bone marrow involvement in paediatric non-Hodgkin lymphoma and may preclude the need for bone marrow biopsy in selected patients. Eur Radiol. 2018;28:2942–50.CrossRefPubMedGoogle Scholar
  6. 6.
    Weiler-Sagie M, Bushelev O, Epelbaum R, Dann EJ, Haim N, Avivi I, et al. (18)F-FDG avidity in lymphoma readdressed: a study of 766 patients. J Nucl Med. 2010;51:25–30.CrossRefPubMedGoogle Scholar
  7. 7.
    Minard-Colin V, Brugieres L, Reiter A, Cairo MS, Gross TG, Woessmann W, et al. Non-Hodgkin lymphoma in children and adolescents: progress through effective collaboration, current knowledge, and challenges ahead. J Clin Oncol. 2015;33:2963–74.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Rosolen A, Perkins SL, Pinkerton CR, Guillerman RP, Sandlund JT, Patte C, et al. Revised international pediatric non-Hodgkin lymphoma staging system. J Clin Oncol. 2015;33:2112–8.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Cottereau AS, Lanic H, Mareschal S, Meignan M, Vera P, Tilly H, et al. Molecular profile and FDG-PET/CT total metabolic tumor volume improve risk classification at diagnosis for patients with diffuse large B-cell lymphoma. Clin Cancer Res. 2016;22:3801–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Meignan M, Cottereau AS, Versari A, Chartier L, Dupuis J, Boussetta S, et al. Baseline metabolic tumor volume predicts outcome in high-tumor-burden follicular lymphoma: a pooled analysis of three multicenter studies. J Clin Oncol. 2016;34:3618–26.CrossRefPubMedGoogle Scholar
  11. 11.
    Cottereau AS, Becker S, Broussais F, Casasnovas O, Kanoun S, Roques M, et al. Prognostic value of baseline total metabolic tumor volume (TMTV0) measured on FDG-PET/CT in patients with peripheral T-cell lymphoma (PTCL). Ann Oncol. 2016;27:719–24.CrossRefPubMedGoogle Scholar
  12. 12.
    Kanoun S, Rossi C, Berriolo-Riedinger A, Dygai-Cochet I, Cochet A, Humbert O, et al. Baseline metabolic tumour volume is an independent prognostic factor in Hodgkin lymphoma. Eur J Nucl Med Mol Imaging. 2014;41:1735–43.CrossRefPubMedGoogle Scholar
  13. 13.
    Sandlund JT, Guillerman RP, Perkins SL, Pinkerton CR, Rosolen A, Patte C, et al. International pediatric non-Hodgkin lymphoma response criteria. J Clin Oncol. 2015;33:2106–11.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Purz S, Mauz-Korholz C, Korholz D, Hasenclever D, Krausse A, Sorge I, et al. [18F]Fluorodeoxyglucose positron emission tomography for detection of bone marrow involvement in children and adolescents with Hodgkin's lymphoma. J Clin Oncol. 2011;29:3523–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Berthet L, Cochet A, Kanoun S, Berriolo-Riedinger A, Humbert O, Toubeau M, et al. In newly diagnosed diffuse large B-cell lymphoma, determination of bone marrow involvement with 18F-FDG PET/CT provides better diagnostic performance and prognostic stratification than does biopsy. J Nucl Med. 2013;54:1244–50.CrossRefPubMedGoogle Scholar
  16. 16.
    Boellaard R, Delgado-Bolton R, Oyen WJ, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42:328–54.CrossRefPubMedGoogle Scholar
  17. 17.
    Meignan M, Sasanelli M, Casasnovas RO, Luminari S, Fioroni F, Coriani C, et al. Metabolic tumour volumes measured at staging in lymphoma: methodological evaluation on phantom experiments and patients. Eur J Nucl Med Mol Imaging. 2014;41:1113–22.CrossRefPubMedGoogle Scholar
  18. 18.
    Cottereau A-S, Versari A, Loft A, Casasnovas O, Bellei M, Ricci R, et al. Prognostic value of baseline metabolic tumor volume in early-stage Hodgkin lymphoma in the standard arm of the H10 trial. Blood. 2018;131:1456–63.CrossRefPubMedGoogle Scholar
  19. 19.
    Rogasch JMM, Hundsdoerfer P, Hofheinz F, Wedel F, Schatka I, Amthauer H, et al. Pretherapeutic FDG-PET total metabolic tumor volume predicts response to induction therapy in pediatric Hodgkin’s lymphoma. BMC Cancer. 2018;18:521.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Tout M, Casasnovas O, Meignan M, Lamy T, Morschhauser F, Salles G, et al. Rituximab exposure is influenced by baseline metabolic tumor volume and predicts outcome of DLBCL patients: a lymphoma study association report. Blood. 2017;129:2616–23.CrossRefPubMedGoogle Scholar
  21. 21.
    Mikhaeel NG, Smith D, Dunn JT, Phillips M, Moller H, Fields PA, et al. Combination of baseline metabolic tumour volume and early response on PET/CT improves progression-free survival prediction in DLBCL. Eur J Nucl Med Mol Imaging. 2016;43:1209–19.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Sasanelli M, Meignan M, Haioun C, Berriolo-Riedinger A, Casasnovas RO, Biggi A, et al. Pretherapy metabolic tumour volume is an independent predictor of outcome in patients with diffuse large B-cell lymphoma. Eur J Nucl Med Mol Imaging. 2014;41:2017–22.CrossRefPubMedGoogle Scholar
  23. 23.
    Albano D, Bosio G, Pagani C, Re A, Tucci A, Giubbini R, et al. Prognostic role of baseline 18F-FDG PET/CT metabolic parameters in Burkitt lymphoma. Eur J Nucl Med Mol Imaging. 2018;46(1):87–96.
  24. 24.
    Dunleavy K, Gross TG. Management of aggressive B-cell NHLs in the AYA population: an adult vs pediatric perspective. Blood. 2018;132:369–75.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Badr S, Kotb M, Elahmadawy MA, Moustafa H. Predictive value of FDG PET/CT versus bone marrow biopsy in pediatric lymphoma. Clin Nucl Med. 2018;43:e428–e38.PubMedGoogle Scholar
  26. 26.
    Khan AB, Barrington SF, Mikhaeel NG, Hunt AA, Cameron L, Morris T, et al. PET-CT staging of DLBCL accurately identifies and provides new insight into the clinical significance of bone marrow involvement. Blood. 2013;122:61–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Adams HJ, Kwee TC, Fijnheer R, Dubois SV, Nievelstein RA, de Klerk JM. Bone marrow 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography cannot replace bone marrow biopsy in diffuse large B-cell lymphoma. Am J Hematol. 2014;89:726–31.CrossRefPubMedGoogle Scholar
  28. 28.
    Hong J, Lee Y, Park Y, Kim SG, Hwang KH, Park SH, et al. Role of FDG-PET/CT in detecting lymphomatous bone marrow involvement in patients with newly diagnosed diffuse large B-cell lymphoma. Ann Hematol. 2012;91:687–95.CrossRefPubMedGoogle Scholar
  29. 29.
    Cerci JJ, Gyorke T, Fanti S, Paez D, Meneghetti JC, Redondo F, et al. Combined PET and biopsy evidence of marrow involvement improves prognostic prediction in diffuse large B-cell lymphoma. J Nucl Med. 2014;55:1591–7.CrossRefPubMedGoogle Scholar
  30. 30.
    Kanoun S, Tal I, Berriolo-Riedinger A, Rossi C, Riedinger JM, Vrigneaud JM, et al. Influence of software tool and methodological aspects of total metabolic tumor volume calculation on baseline [18F]FDG PET to predict survival in Hodgkin lymphoma. PLoS One. 2015;10:e0140830.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Suyun Chen
    • 1
  • Kejun He
    • 2
  • Fang Feng
    • 1
  • Shaoyan Wang
    • 1
  • Yafu Yin
    • 1
  • Hongliang Fu
    • 1
  • Hui Wang
    • 1
    Email author
  1. 1.Department of Nuclear Medicine, Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
  2. 2.Department of Pediatric Hematology/Oncology, Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

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