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Random survival forest to predict transplant-eligible newly diagnosed multiple myeloma outcome including FDG-PET radiomics: a combined analysis of two independent prospective European trials

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Abstract

Purpose

Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is included in the International Myeloma Working Group (IMWG) imaging guidelines for the work-up at diagnosis and the follow-up of multiple myeloma (MM) notably because it is a reliable tool as a predictor of prognosis. Nevertheless, none of the published studies focusing on the prognostic value of PET-derived features at baseline consider tumor heterogeneity, which could be of high importance in MM. The aim of this study was to evaluate the prognostic value of baseline PET-derived features in transplant-eligible newly diagnosed (TEND) MM patients enrolled in two prospective independent European randomized phase III trials using an innovative statistical random survival forest (RSF) approach.

Methods

Imaging ancillary studies of IFM/DFCI2009 and EMN02/HO95 trials formed part of the present analysis (IMAJEM and EMN02/HO95, respectively). Among all patients initially enrolled in these studies, those with a positive baseline FDG-PET/CT imaging and focal bone lesions (FLs) and/or extramedullary disease (EMD) were included in the present analysis. A total of 17 image features (visual and quantitative, reflecting whole imaging characteristics) and 5 clinical/histopathological parameters were collected. The statistical analysis was conducted using two RSF approaches (train/validation + test and additional nested cross-validation) to predict progression-free survival (PFS).

Results

One hundred thirty-nine patients were considered for this study. The final model based on the first RSF (train/validation + test) approach selected 3 features (treatment arm, hemoglobin, and SUVmaxBone Marrow (BM)) among the 22 involved initially, and two risk groups of patients (good and poor prognosis) could be defined with a mean hazard ratio of 4.3 ± 1.5 and a mean log-rank p value of 0.01 ± 0.01. The additional RSF (nested cross-validation) analysis highlighted the robustness of the proposed model across different splits of the dataset. Indeed, the first features selected using the train/validation + test approach remained the first ones over the folds with the nested approach.

Conclusion

We proposed a new prognosis model for TEND MM patients at diagnosis based on two RSF approaches.

Trial registration

IMAJEM: NCT01309334 and EMN02/HO95: NCT01134484

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Notes

  1. The scalar output of an RSF, known as “ensemble mortality,” provides an estimator of “the number of deaths expected under the null hypothesis of similar survival behavior” [13]. In this paper, the RSF mortality does not refer to deaths but to progression events.

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Funding

This work has been supported in part by grants from the French National Agency for Research called “Investissements d’Avenir” IRON Labex no. ANR-11-LABX-0018-01, INCa-DGOS-Inserm_12558 (SIRIC ILIAD), and the European Regional Development Fund, the Pays de la Loire region on the Connect Talent scheme MILCOM, Nantes Métropole (Convention 2017-10470).

Author information

Author notes

  1. Bastien Jamet, Ludivine Morvan, Diana Mateus and Thomas Carlier contributed equally to this work.

Authors and Affiliations

  1. Nuclear Medicine Department, University Hospital, 1 place Ricordeau, 44093, Nantes, France

    Bastien Jamet, Anne-Victoire Michaud, Clément Bailly, Caroline Bodet-Milin, Françoise Kraeber-Bodéré & Thomas Carlier

  2. CRCINA, INSERM, CNRS, Université d’Angers, Université de Nantes, Nantes, France

    Ludivine Morvan, Clément Bailly, Caroline Bodet-Milin, Françoise Kraeber-Bodéré & Thomas Carlier

  3. LS2N, CNRS UMR 6004, Ecole Centrale de Nantes, Nantes, France

    Ludivine Morvan & Diana Mateus

  4. Nuclear Medicine, AOU Policlinico S. Orsola-Malpighi, Bologna, Italy

    Cristina Nanni

  5. Medical Physics Division, Santa Croce e Carle Hospital, Cuneo, Italy

    Stéphane Chauvie

  6. Haematology Department, University Hospital, Nantes, France

    Philippe Moreau & Cyrille Touzeau

  7. Seragnoli Institute of Hematology, Bologna University School of Medicine, Bologna, Italy

    Elena Zamagni

  8. Nuclear Medicine, ICO Cancer Center, Saint-Herblain, France

    Françoise Kraeber-Bodéré

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  1. Bastien Jamet
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Correspondence to Thomas Carlier.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Jamet, B., Morvan, L., Nanni, C. et al. Random survival forest to predict transplant-eligible newly diagnosed multiple myeloma outcome including FDG-PET radiomics: a combined analysis of two independent prospective European trials. Eur J Nucl Med Mol Imaging 48, 1005–1015 (2021). https://doi.org/10.1007/s00259-020-05049-6

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