Predictive value of baseline metabolic tumor volume in early-stage favorable Hodgkin Lymphoma - Data from the prospective, multicenter phase III HD16 trial

Lutz van Heek, Colin Stuka, Helen Kaul, Horst Müller, Jasmin Mettler, Felicitas Hitz, Christian Baues, Michael Fuchs, Peter Borchmann, Andreas Engert, Markus Dietlein, Conrad-Amadeus Voltin, Carsten Kobe, Lutz van Heek, Colin Stuka, Helen Kaul, Horst Müller, Jasmin Mettler, Felicitas Hitz, Christian Baues, Michael Fuchs, Peter Borchmann, Andreas Engert, Markus Dietlein, Conrad-Amadeus Voltin, Carsten Kobe

Abstract

Background: 18F -fluorodeoxyglucose (FDG) positron emission tomography (PET) plays an important role in the staging and response assessment of lymphoma patients. Our aim was to explore the predictive relevance of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients with early stage Hodgkin lymphoma treated within the German Hodgkin Study Group HD16 trial.

Methods: 18F-FDG PET/CT images were available for MTV and TLG analysis in 107 cases from the HD16 trial. We calculated MTV and TLG using three different threshold methods (SUV4.0, SUV41% and SUV140%L), and then performed receiver-operating-characteristic analysis to assess the predictive impact of these parameters in predicting an adequate therapy response with PET negativity after 2 cycles of chemotherapy.

Results: All three threshold methods analyzed for MTV and TLG calculation showed a positive correlation with the PET response after 2 cycles chemotherapy. The largest area under the curve (AUC) was observed using the fixed threshold of SUV4.0 for MTV- calculation (AUC 0.69 [95% CI 0.55-0.83]) and for TLG-calculation (AUC 0.69 [0.55-0.82]). The calculations for MTV and TLG with a relative threshold showed a lower AUC: using SUV140%L AUCs of 0.66 [0.53-0.80] for MTV and 0.67 for TLG [0.54-0.81]) were observed, while with SUV41% an AUC of 0.61 [0.45-0.76] for MTV, and an AUC 0.64 [0.49-0.80]) for TLG were seen.

Conclusions: MTV and TLG do have a predictive value after two cycles ABVD in early stage Hodgkin lymphoma, particularly when using the fixed threshold of SUV4.0 for MTV and TLG calculation.

Trial registration: ClinicalTrials.gov NCT00736320 .

Keywords: FDG PET; Hodgkin lymphoma; Metabolic tumor volume; Response prediction.

Conflict of interest statement

All authors declare that they have no conflict of interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Flow chart. 1150 patients included in the HD16 trial. Baseline 18F-FDG PET was centrally reviewed in 107 patients with quantitative analyses. Abbreviations: ITT, intention to treat. HL, Hodgkin lymphoma. MTV, metabolic tumor volume. TLG, total lesion glycolysis
Fig. 2
Fig. 2
Histograms of MTV distribution assessed by different thresholding methods. MTV was obtained using the following thresholds: 41% of the SUVmax within the respective lymphoma site (MTV41%), a fixed SUV of 4.0 (MTV4.0), and 140% of the SUVmax of liver background MTV140%L. Abbreviations: MTV, metabolic tumor volume
Fig. 3
Fig. 3
Histograms of TLG distribution assessed by different thresholding methods. TLG was obtained using the following thresholds: 41% of the SUVmax within the respective lymphoma site (TLG41%), a fixed SUV of 4.0 (TLG4.0), and 140% of the SUVmax of liver background (TLG140%L). Abbreviations: TLG, total lesion glycolysis
Fig. 4
Fig. 4
ROC curves of MTV distribution assessed by different thresholding methods for PET response after two cycles of ABVD (16/107 = 15% PET-2-positive patients with Deauville score 4). MTV was obtained using the following thresholds: 41% of the SUVmax within the respective lymphoma site (MTV41%) a fixed SUV of 4.0 (MTV4.0) and 140% of liver background (MTV140%L). Abbreviations: MTV, metabolic tumor volume. AUC, area under the curve
Fig. 5
Fig. 5
ROC curves of TLG distribution assessed by different thresholding methods for PET response after two cycles of ABVD (16/107 = 15% PET-2-positive patients with Deauville score 4). TLG was obtained using the following thresholds: 41% of the SUVmax within the respective lymphoma site (TLG41%) a fixed SUV of 4.0 (TLG4.0) and 140% of the SUVmax of liver background (TLG140%L). Abbreviations: TLG, total lesion glycolysis. AUC, area under the curve

References

    1. Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, et al. SEER Cancer Statistics Review. 1975–2016. . Accessed 7 Nov 2021.
    1. Fermé C, Eghbali H, Meerwaldt JH, et al. Chemotherapy plus involved-field radiation in early-stage Hodgkin’s disease. N Engl J Med. 2007;357:1916–1927. doi: 10.1056/NEJMoa064601.
    1. Engert A, Plütschow A, Eich HT, et al. Reduced treatment intensity in patients with early-stage Hodgkin’s lymphoma. N Engl J Med. 2010;363:640–652. doi: 10.1056/NEJMoa1000067.
    1. Connors JM. State-of-the-art therapeutics: Hodgkin´s lymphoma. J Clin Oncol. 2005;23:6400–6408. doi: 10.1200/JCO.2005.05.016.
    1. Engert A, Horning S, editors. Hodgkin Lymphoma. Heidelberg: Springer; 2011.
    1. Fuchs M, Goergen H, Kobe C, et al. Positron emission tomography-guided treatment in early-stage favorable Hodgkin Lymphoma: final results of the international, radomized phase II HD16 trial by the German Hodgkin Study Group. J Clin Oncol. 2019;37(31):2835–2845. doi: 10.1200/JCO.19.00964.
    1. Eichenauer DA, André M, Johnson P, et al. Controversies in the treatment of classical Hodgkin Lymphoma. Hemasphere. 2008;2(5):e149. doi: 10.1097/HS9.0000000000000149.
    1. Engert A, Younges A (eds): Principles of radiation therapy for Hodgkin Lymphoma in Hodgkin Lymphoma: a comprehensive overview. Basel: Springer International Publishing; 2015. p. 157–77.
    1. Kobe C, Dietlein M, Franklin J, et al. Positron emission tomography has a high negative predictive value for progression or early relapse for patients with residual disease after first-line chemotherapy in advanced stage Hodgkin lymphoma. Blood. 2008;112:3989–3994. doi: 10.1182/blood-2008-06-155820.
    1. Weihrauch MR, Re D, Bischoff S, et al. Whole-body positron emission tomography using 18F-fluorodeoxyglucose for initial staging of patients with Hodgkin´s disease. Ann Hematol. 2002;81:20–25. doi: 10.1007/s00277-001-0390-y.
    1. Gallamini A, Rigacci L, Merli F, et al. The predictive value of positron emission tomography scanning performed after two courses of standard therapy on treatment outcome in advanced stage Hodgkin´s disease. Haematologica. 2006;91:475–481.
    1. Gallamini A, Hutchings M, Rigacci L, 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;25:3746–3752. doi: 10.1200/JCO.2007.11.6525.
    1. Engert A, Haverkamp H, Kobe C, et al. Reduced-intensity chemotherapy and-guided radiptheray in patients with advanced stage Hodgkin´s lymphoma (HD15 trial): a randomized, open label phase 3 non-inferiority trial. Lancet. 2012;379:1791–1799. doi: 10.1016/S0140-6736(11)61940-5.
    1. Borchmann P, Goergen H, Kobe C, et al. PET-guided treatment in patients with advanced-stage Hodgkin´s lymphoma (HD18): final results of an open-label, international, randomized phase 3 trial by the German Hodgkin Study Group. Lancet. 2017;390:2790–2802. doi: 10.1016/S0140-6736(17)32134-7.
    1. Borchman P, Plütschow A, Kobe C, et al. PET-guided omission of radiotherapy in early-stage unfavourable Hodgkin lymphoma (GHSG HD17): a multicenter, open-label, randomized, phase 3 trial. Lancet Oncol. 2021;22(2):223–234. doi: 10.1016/S1470-2045(20)30601-X.
    1. Raemaekers JMM, André MPE, Federico M, et al. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relaps: clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 Trial. J Clin Oncol. 2014;32(12):1188–1194. doi: 10.1200/JCO.2013.51.9298.
    1. Radford J, Illidge T, Counsell N, et al. Results of trial of PET-directed therapy for early-stage Hodgkin´s lymphoma. N Engl J Med. 2015;372:1598–1607. doi: 10.1056/NEJMoa1408648.
    1. Meignan M, Cottereau AS, Versari A, et al. Baseline metabolic tumor volume predicts outcome in high-tumor-burden follicular lymphoma: apooled analysis of three multicentre studies. J Clin Oncol. 2016;34:3618–3626. doi: 10.1200/JCO.2016.66.9440.
    1. Gallamini A, Barrington SF, Biggi A, et al. The predictive role of interim positron emission tomography for Hodgkin lymphoma treatment outcome is confirmed using the interpretation criteria of the Deauville five point scale. Haematologica. 2014;99:1107–1113. doi: 10.3324/haematol.2013.103218.
    1. Akhtari M, Milgrom SA, Pinnix CC, et al. Reclassifying patients with early-stage Hodgkin lymphoma based on functional radiographic markers at presentation. Blood. 2018;131:84–94. doi: 10.1182/blood-2017-04-773838.
    1. Kanoun S, Rossi C, Berriolo-Riedinger A, et al. Baseline metabolic tumour volume is an independent prognostic factor in Hodgkin lymphoma. Eur J Nucl Med Mol Imaging. 2014;41:1735–1743. doi: 10.1007/s00259-014-2783-x.
    1. Cottereau AS, Versari A, Loft A, et al. Prognostic value of baseline metabolic tumor volume in early-stage Hodgkin lymphoma in the standard arm of the H10 trial. Blood. 2018;131:1456–1463. doi: 10.1182/blood-2017-07-795476.
    1. Song MK, Chung JS, Lee JJ, 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;104:1656–1661. doi: 10.1111/cas.12282.
    1. Moskowitz AJ, Schoder H, Gavane S, et al. Prognostic significance of baseline metabolic tumor volume in relapsed and refractory Hodgkin lymphoma. Leuk Lymphoma. 2009;50:1257–1260. doi: 10.1080/10428190903040048.
    1. Mettler J, Müller H, Voltin CA, et al. Metabolic tumor volume for response prediction in advance-stage Hodgkin Lymphoma. J Nucl Med. 2019;60:207–211. doi: 10.2967/jnumed.118.210047.
    1. Kim TM, Paeng JC, Chun IK, et al. Total lesion glycolysis in positron emission tomography is a better predictor of outcome than the international prognostic index for patients with diffus lage B Cell lymphoma. Cancer. 2013;119(6):1195–1202. doi: 10.1002/cncr.27855.
    1. Meignan M, Sasanelli M, Casasnovas RO, et al. Metabolic tumour volumes measured at staging in lymphoma: Methodological evaluation on phantom experiments and patients. Eur J Nucl Med Mol Imaging. 2014;41:1113–1122. doi: 10.1007/s00259-014-2705-y.
    1. Carlier T, Bailly C. State-of-theart and recent advances in quantification for therapeutic follow-up in oncology using PET. Front Med. 2015;2:18. doi: 10.3389/fmed.2015.00018.
    1. Tutino F, Puccini G, Linguanti F, et al. Baseline metabolic tumor volume calculation using different SUV thresholding methods in Hodgkin Lymphoma patients: interobserver argreement and reproducibility across software platforms. Nuc Med Com. 2021;42(3):284–291. doi: 10.1097/MNM.0000000000001324.
    1. Borchmann S. Liquid biopsy in Hodgkin lymphoma – moving beyond the proof of principle. Br J Haematol. 2021;195(4):493–494. doi: 10.1111/bjh.17796.

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