1. Baseline SUVmax is related to tumor cell proliferation and patient outcome in follicular lymphoma
- Author
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Rossi, Cédric, Tosolini, Marie, Gravelle, Pauline, Pericart, Sarah, Kanoun, Salim, Evrard, Solene, Gilhodes, Julia, Franchini, Don-Marc, Amara, Nadia, Syrykh, Charlotte, Bories, Pierre, Oberic, Lucie, Ysebaert, Loïc, Martin, Laurent, Ramla, Selim, Robert, Philippine, Tabouret-Viaud, Claire, Casasnovas, René-Olivier, Fournié, Jean-Jacques, Bezombes, Christine, Laurent, Camille, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d’Excellence ‘TOUCAN’ [Toulouse], Programme Hospitalo-Universitaire en Cancérologie CAPTOR [Cancer Pharmacology of Toulouse and Region] (IUCT Oncopole), IUCT Oncopole - Institut Universitaire du Cancer de Toulouse, Institut Carnot CALYM [Pierre-Benite], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Réseau régional de cancérologie Onco-Occitanie, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), UFR Sciences de la Vie, de la Terre et de l'Environnement (Université de Bourgogne) (UFR SVTE), Université de Bourgogne (UB), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), and UNICANCER
- Subjects
Lymphoma, Non-Hodgkin ,[SDV]Life Sciences [q-bio] ,Tumor Microenvironment ,Humans ,Rituximab ,Lymphoma, Follicular ,Article ,Cell Proliferation ,Retrospective Studies - 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 metrics 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 investigated along with the tumor and immune microenvironment, which were determined by immunochemistry and transcriptome studies involving gene set enrichment analyses and immune cell deconvolution, together with the tumor mutation profile. We report that baseline SUVmax>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 significantly 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 mutation were seen in FL patients with SUVmax>14.5. Thus, high baseline SUVmax reflects FL tumor proliferation and, together with Ki-67 proliferative index, can be used to identify patients at risk of early relapse with rituximab chemotherapy.
- Published
- 2020