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Non Hodgkin-Lymphoma
Baseline SUVmax is related to tumor cell proliferation and patient outcome in follicular lymphoma
Cédric Rossi,1-5 Marie Tosolini,1,3,6,7 Pauline Gravelle,1-4,6 Sarah Pericart,1,6 Salim Kanoun,8 Solene Evrard,6 Julia Gilhodes,9 Don-Marc Franchini,1-4 Nadia Amara,6 Charlotte Syrykh,6, 10,11 Pierre Bories,10,11 Lucie Oberic,11 Loïc Ysebaert,1-4,11 Laurent Martin,12,13 Selim Ramla,12,13 Philippine Robert,5,13 Claire Tabouret-Viaud,14 René-Olivier Casasnovas,5,13 Jean-Jacques Fournié,1-4 Christine Bezombes1-4# and Camille Laurent1-4,6#
1Centre de Recherches en Cancérologie de Toulouse (CRCT), UMR1037 INSERM, Université Toulouse III Paul-Sabatier, ERL5294 CNRS, Toulouse; 2Laboratoire d’Excellence TOUCAN, Toulouse; 3Programme Hospitalo-Universitaire en Cancérologie CAPTOR, Université Toulouse, Toulouse; 4CALYM Carnot Institute, Pierre-Bénite; 5CHU Dijon, Hématologie Clinique, Hôpital François Mitterrand, Dijon; 6Département de Pathologie, Institut Universitaire du Cancer de Toulouse, Université Toulouse, Toulouse; 7Pôle Technologique du Centre de Recherches en Cancérologie de Toulouse, Toulouse; 8Médecine Nucléaire, Institut Universitaire du Cancer Toulouse- Oncopole, Université Toulouse, Toulouse; 9Bureau des Essais Cliniques, Institut Universitaire du Cancer Toulouse-Oncopole, Université Toulouse, Toulouse; 10Réseau Régional de Cancérologie, Onco-Occitanie, Institut Universitaire du Cancer, Université Toulouse, Toulouse-Oncopole; 11Service d’Hématologie, Institut Universitaire du Cancer de Toulouse, Université Toulouse Toulouse; 12Département de Pathologie, CHU Hôpital François Mitterrand, Dijon; 13INSERM UMR 1231 UFR, Bourgogne and 14Département de Médecine Nucléaire, Centre Georges-François Leclerc, Dijon, France
#CB and CL contributed equally as co-senior authors.
ABSTRACT
Follicular lymphoma (FL) is the most common indolent lymphoma. Despite the clear benefit of CD20-based therapy, a subset of FL patients still progress to aggressive lymphoma. Thus, identifying early biomarkers that incorporate positron emission tomography met- rics could be helpful to identify patients with a high risk of treatment failure with rituximab. We retrospectively included a total of 132 untreated FL patients separated into training and validation cohorts. Optimal threshold of baseline whole-body maximum standardized uptake (SUVmax) was first determined in the training cohort (n=48) to predict progression-free survival (PFS). The PET results were investi- gated along with the tumor and immune microenvironment, which were determined by immunochemistry and transcriptome studies involving gene set enrichment analyses and immune cell deconvolu- tion, together with the tumor mutation profile. We report that base- line SUVm a x >14.5 was associated with poorer PFS than baseline SUVmax≤14.5 (hazard ratio =0.28; P=0.00046). Neither immune T-cell infiltration nor immune checkpoint expression were associated with baseline PET metrics. By contrast, FL samples with Ki-67 staining ≥10% showed enrichment of cell cycle/DNA genes (P=0.013) and sig- nificantly higher SUVmax values (P=0.007). Despite similar oncogenic pathway alterations in both SUVmax groups of FL samples, four out of five cases harboring the infrequent FOXO1 transcription factor muta- tion were seen in FL patients with SUVmax>14.5. Thus, high baseline SUVmax reflects FL tumor proliferation and, together with Ki-67 prolifer- ative index, can be used to identify patients at risk of early relapse with rituximab chemotherapy.
Ferrata Storti Foundation
Haematologica 2022 Volume 107(1):221-230
Correspondence:
CHRISTINE BEZOMBES
christine.bezombes@inserm.fr
CAMILLE LAURENT laurent.camille@iuct-oncopole.fr
CÉDRIC ROSSI cedric.rossi@chu-dijon.fr
Received: June 24, 2020. Accepted: December 11, 2020. Pre-published: December 17, 2020.
https://doi.org/10.3324/haematol.2020.263194 ©2022 Ferrata Storti Foundation
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