Skip to main content

Advertisement

SpringerLink
Log in

FDG PET in response evaluation of bulky masses in paediatric Hodgkin’s lymphoma (HL) patients enrolled in the Italian AIEOP-LH2004 trial

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

Abstract

Purpose

We present the results of an investigation of the role of FDG PET in response evaluation of bulky masses in paediatric patients with Hodgkin’s lymphoma (HL) enrolled in the Italian AIEOP-LH2004 trial.

Methods

We analysed data derived from 703 patients (388 male, 315 female; mean age 13 years) with HL and enrolled in 41 different Italian centres from March 2004 to September 2012, all treated with the AIEOP-LH2004 protocol. The cohort comprised 309 patients with a bulky mass, of whom 263 were evaluated with FDG PET at baseline and after four cycles of chemotherapy. Responses were determined according to combined functional and morphological criteria. Patients were followed up for a mean period of 43 months and for each child we calculated time-to-progression (TTP) and relapse rates considering clinical monitoring, and instrumental and histological data as the reference standard. Statistical analyses were performed for FDG PET and morphological responses with respect to TTP. Multivariate analysis was used to define independent predictive factors.

Results

Overall, response evaluation revealed 238 PET-negative patients (90.5%) and 25 PET-positive patients (9.5%), with a significant difference in TTP between these groups (mean TTP: 32.67 months for negative scans, 23.8 months for positive scans; p < 0.0001, log-rank test). In the same cohort, computed tomography showed a complete response (CR) in 85 patients (32.3%), progressive disease (PD) in 6 patients (2.3%), and a partial response (PR) in 165 patients (62.7%), with a significant difference in TTP between patients with CR and patients with PD (31.1 months and 7.9 months, respectively; p < 0.001, log-rank test). Similarly, there was a significant difference in relapse rates between PET-positive and PET-negative patients (p = 0000). In patients with PR, there was also a significant difference in TTP between PET-positive and PET-negative patients (24.6 months and 34.9 months, respectively; p < 0.0001). In the multivariate analysis with correction for multiple testing, only the PET result was an independent predictive factor in both the entire cohort of patients and the subgroup showing PR on CT (p < 0.01).

Conclusion

After four cycles of chemotherapy, FDG PET response assessment in paediatric HL patients with a bulky mass is a good predictor of TTP and disease outcome. Moreover, in patients with a PR on CT, PET was able to differentiate those with a longer TTP. In paediatric HL patients with a bulky mass and in patients with a PR on CT, response on FDG PET was an independent predictive factor.

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
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Bar-Sever Z, Keidar Z, Ben-Barak A, Bar-Shalom R, Postovsky S, Guralnik L, et al. The incremental value of 18F-FDG PET/CT in paediatric malignancies. Eur J Nucl Med Mol Imaging. 2007;34:630–7.

    Article  Google Scholar 

  2. Tatsumi M, Miller JH, Wahl RL. 18F-FDG PET/CT in evaluating non-CNS pediatric malignancies. J Nucl Med. 2007;48:1923–31.

    Article  Google Scholar 

  3. Jadvar H, Connolly LP, Fahey FH, Shulkin BL. PET and PET/CT in pediatric oncology. Semin Nucl Med. 2007;37:316–31.

    Article  Google Scholar 

  4. Meany HJ, Gidvani VK, Minniti CP. Utility of PET scans to predict disease relapse in pediatric patients with Hodgkin lymphoma. Pediatr Blood Cancer. 2007;48:399–402.

    Article  Google Scholar 

  5. Lopci E, Burnelli R, Ambrosini V, Nanni C, Castellucci P, Biassoni L, et al. (18)F-FDG PET in pediatric lymphomas: a comparison with conventional imaging. Cancer Biother Radiopharm. 2008;23(6):681–90.

    Article  CAS  Google Scholar 

  6. Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M. Report of the Committee on Hodgkin’s Disease Staging Classification. Cancer Res. 1971;31:1860–1.

    CAS  PubMed  Google Scholar 

  7. Oberlin O. Hodgkin’s disease. In: Voûte PA, Kalifa C, Barrett A, editors. Cancer in children. Clinical management. 4th ed. New York: Oxford University; 1998. p. 137–53.

    Google Scholar 

  8. Lanzkowski P. Hodgkin’s disease. In: Lanzkowski P, editor. Manual of pediatric hematology and oncology. 3rd ed. San Diego: Academic; 1999. p. 413–43.

    Google Scholar 

  9. Hudson MM, Donaldson SS. Treatment of pediatric Hodgkin’s lymphoma. Semin Hematol. 1999;36:313–23.

    CAS  PubMed  Google Scholar 

  10. Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, et al. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children’s Oncology Group Study AHOD0031. J Clin Oncol. 2014;32:3651–8.

    Article  Google Scholar 

  11. Furth C, Steffen IG, Amthauer H, Ruf J, Misch D, Schönberger S, et al. Early and late therapy response assessment with [18F] fluorodeoxyglucose positron emission tomography in pediatric Hodgkin’s lymphoma: analysis of a prospective multicenter trial. J Clin Oncol. 2009;27(26):4385–91.

    Article  Google Scholar 

  12. Bakhshi S, Bhethanabhotla S, Kumar R, Agarwal K, Sharma P, Thulkar S, et al. Posttreatment PET/CT rather than interim PET/CT using Deauville criteria predicts outcome in pediatric Hodgkin lymphoma: a prospective study comparing PET/CT with conventional imaging. J Nucl Med. 2017;58(4):577–83.

    Article  CAS  Google Scholar 

  13. Kostakoglu L, Goldsmith SJ. Fluorine-18 fluorodeoxyglucose positron emission tomography in the staging and follow-up of lymphoma: is it time to shift gears? Eur J Nucl Med. 2000;27:1564–78.

    Article  CAS  Google Scholar 

  14. Schöder H, Meta J, Yap C, Ariannejad M, Rao J, Phelps ME, et al. Effect of whole-body (18)FFDG PET imaging on clinical staging and management of patients with malignant lymphoma. J Nucl Med. 2001;42:1139–43.

    PubMed  Google Scholar 

  15. Hoh CK, Glaspy J, Rosen P, Dahlbom M, Lee SJ, Kunkel L, et al. Whole-body FDG-PET imaging for staging of Hodgkin’s disease and lymphoma. J Nucl Med. 1997;38:343–8.

    CAS  PubMed  Google Scholar 

  16. Talbot JN, Haioun C, Rain JD, Meignan M, Wioland M, Misset JL, et al. [18F]-FDG positron imaging in clinical management of lymphoma patients. Crit Rev Oncol Hematol. 2001;38:193–221.

    Article  CAS  Google Scholar 

  17. Hueltenschmidt B, Sautter-Bihl ML, Lang O, Maul FD, Fischer J, Mergenthaler HG, et al. Whole body positron emission tomography in the treatment of Hodgkin disease. Cancer. 2001;91:302–10.

    Article  CAS  Google Scholar 

  18. Buchmann I, Reinhardt M, Elsner K, Bunjes D, Altehoefer C, Finke J, et al. 2-(Fluorine-18)fluoro- 2-deoxy-D-glucose positron emission tomography in the detection and staging of malignant lymphoma. A bicenter trial. Cancer. 2001;91:889–99.

    Article  CAS  Google Scholar 

  19. Moog F, Bangerter M, Diederichs CG, Guhlmann A, Kotzerke J, Merkle E, et al. Lymphoma: role of whole-body 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) PET in nodal staging. Radiology. 1997;203:795–800.

    Article  CAS  Google Scholar 

  20. Spaepen K, Stroobants S, Dupont P, Van Steenweghen S, Thomas J, Vandenberghe P, et al. Prognostic value of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose ([18F]FDG) after first-line chemotherapy in non- Hodgkin’s lymphoma: is [18F]FDG-PET a valid alternative to conventional diagnostic methods? J Clin Oncol. 2001;19:414–9.

    Article  CAS  Google Scholar 

  21. Tatsumi M, Kitayama H, Sugahara H, Tokita N, Nakamura H, Kanakura Y, et al. Whole-body hybrid PET with 18F-FDG in the staging of non-Hodgkin’s lymphoma. J Nucl Med. 2001;42:601–8.

    CAS  PubMed  Google Scholar 

  22. Canellos GP. Residual mass in lymphoma may not be residual disease. J Clin Oncol. 1988;6:931–3.

    Article  CAS  Google Scholar 

  23. Hill M, Cunningham D, MacVicar D, Roldan A, Husband J, McCready R, et al. Role of magnetic resonance imaging in predicting relapse in residual masses after treatment of lymphoma. J Clin Oncol. 1993;11:2273–8.

    Article  CAS  Google Scholar 

  24. Shankar A, Fiumara F, Pinkerton R. Role of FDG PET in the management of childhood lymphomas – case proven or is the jury still out? Eur J Cancer. 2008;44:663–73.

    Article  Google Scholar 

  25. Reinhardt MJ, Herkel C, Altehoefer C, Finke J, Moser E. Computer tomography and 18F-FDG positron emission tomography for therapy control of Hodgkin’s and non-Hodgkin’s lymphoma patients: when do we really need FDG-PET? Ann Oncol. 2005;16:1524–9.

    Article  CAS  Google Scholar 

  26. Schwartz CL, Chen L, McCarten K, Wolden S, Constine LS, Hutchison RE, et al. Childhood Hodgkin International Prognostic Score (CHIPS) predicts event-free survival in Hodgkin lymphoma: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2017;64(4):10.1002/pbc.26278.

    Article  Google Scholar 

  27. Weihrauch MR, Re D, Scheidhauer K, Ansén S, Dietlein M, Bischoff S, et al. Thoracic positron emission tomography using 18F-fluorodeoxyglucose for the evaluation of residual mediastinal Hodgkin disease. Blood. 2001;98:2930–4.

    Article  CAS  Google Scholar 

  28. Burnelli R, Rinieri S, Todesco A, Locatelli F, Sala A, BuffardiS, et al. Protocollo AIEOP-LH 2004 per la terapia del linfoma di Hodgkin in età pediatrica: analisi ad interim. XXXV Congresso Nazionale AIEOP, Ancona, 26–28 October 2008. Aricó M, editor. Abstract book, P044. Haematologica 2008;93 Suppl 4:S27.

  29. Lopci E, Burnelli R, Guerra L, Cistaro A, Piccardo A, Zucchetta P, et al. Postchemotherapy PET evaluation correlates with patient outcome in paediatric Hodgkin’s disease. Eur J Nucl Med Mol Imaging. 2011;38(9):1620–7.

    Article  Google Scholar 

  30. Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579–86.

    Article  Google Scholar 

  31. 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(5):571–8.

    Article  Google Scholar 

  32. Kaplan E, Meier P. Nonparametric estimation for incomplete observations. J Am Stat Assoc. 1958;53:456–81.

    Article  Google Scholar 

  33. Cox DR. Regression models and life tables (with discussion). J R Stat Soc Ser B. 1972;34:187–220.

    Google Scholar 

  34. Sarrazin R, Dyon JF. Mediastinoscopy. Rev Mal Respir. 1992;9:99–110.

    CAS  PubMed  Google Scholar 

  35. Oki Y, Chuang H, Chasen B, Jessop A, Pan T, Fanale M, et al. The prognostic value of interim positron emission tomography scan in patients with classical Hodgkin lymphoma. Br J Haematol. 2014;165(1):112–6.

    Article  CAS  Google Scholar 

  36. Gallamini A, Hutchings M, Rigacci L, Specht L, Merli F, Hansen M, et al. Early interim 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin’s lymphoma: A report from a joint Italian-Danish study. J Clin Oncol. 2007;25:3746–52.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) is acknowledged for its support of the current research. AIRC (Associazione Italiana per la Ricerca sul Cancro) is acknowledged for the fellowship support provided to Angelo Castello with the grant no. 18923.

Author information

Authors and Affiliations

  1. Nuclear Medicine Department, Humanitas Clinical and Research Hospital, Via Manzoni 56, 20089, Rozzano, MI, Italy

    Egesta Lopci & Angelo Castello

  2. AYA and Pediatric Radiotherapy, IRCCS Centro di Riferimento Oncologico, Aviano, PN, Italy

    Maurizio Mascarin & Caterina Elia

  3. Nuclear Medicine, Galliera Hospital, Genoa, Italy

    Arnoldo Piccardo

  4. Nuclear Medicine, Hospital San Gerardo, Monza, Italy

    Luca Guerra

  5. Nuclear Medicine, Centro di Riferimento Oncologico, Aviano, Pordenone, Italy

    Eugenio Borsatti

  6. Pediatric Division, Hospital San Gerardo, Monza, Italy

    Alessandra Sala

  7. Pediatric Division, University Hospital, Padova, Italy

    Alessandra Todesco

  8. Nuclear Medicine Department, University Hospital, Padova, Italy

    Pietro Zucchetta

  9. Pediatric Division, Ospedale dei Bambini, Palermo, Italy

    Piero Farruggia

  10. Positron Emission Tomography Centre IRMET S.p.A. Affidea, Turin, Italy

    Angelina Cistaro

  11. Department of Oncology, Hospital Santobono-Pausilipon, Naples, Italy

    Salvatore Buffardi

  12. Hematology and Pediatric Oncology, Azienda Ospedaliera, Parma, Italy

    Patrizia Bertolini

  13. Oncohematology, Regina Margherita Hospital, Torino, Italy

    Maurizio Bianchi & Franca Fagioli

  14. Pediatric Oncohematology, Hospital Umberto I, University La Sapienza, Rome, Italy

    Maria Luisa Moleti

  15. Radiotherapy, Hospital San Salvatore, Pesaro, Italy

    Feisal Bunkheila

  16. Department of Pediatrics, II University Hospital, Naples, Italy

    Paolo Indolfi

  17. Hematology and Pediatric Oncology, Gaslini Hospital, Genoa, Italy

    Alberto Garaventa

  18. Pediatric Onco-hematologic Unit, University Hospital S. Anna, Ferrara, Italy

    Roberta Burnelli

Authors
  1. Egesta Lopci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maurizio Mascarin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Arnoldo Piccardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Angelo Castello
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Caterina Elia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luca Guerra
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Eugenio Borsatti
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alessandra Sala
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alessandra Todesco
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Pietro Zucchetta
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Piero Farruggia
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Angelina Cistaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Salvatore Buffardi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Patrizia Bertolini
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Maurizio Bianchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Maria Luisa Moleti
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Feisal Bunkheila
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Paolo Indolfi
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Franca Fagioli
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Alberto Garaventa
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Roberta Burnelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

AIEOP Hodgkin Lymphoma Study Group, Italy

Corresponding author

Correspondence to Egesta Lopci.

Ethics declarations

Ethical approval

All procedures performed in the AIEOP-LH 2004 protocol involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lopci, E., Mascarin, M., Piccardo, A. et al. FDG PET in response evaluation of bulky masses in paediatric Hodgkin’s lymphoma (HL) patients enrolled in the Italian AIEOP-LH2004 trial. Eur J Nucl Med Mol Imaging 46, 97–106 (2019). https://doi.org/10.1007/s00259-018-4155-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-018-4155-4

Keywords

Search

Navigation