Baseline SUVmax is related to tumor cell proliferation and patient outcome in follicular lymphoma
Cédric Rossi
(1, 2, 3, 4, 5)
,
Marie Tosolini
(1, 3, 3)
,
Pauline Gravelle
(1, 3, 3, 2, 4)
,
Sarah Pericart
(1, 3)
,
Salim Kanoun
(3)
,
Solene Evrard
(3)
,
Julia Gilhodes
(3)
,
Don-Marc Franchini
(1, 2, 3, 4)
,
Nadia Amara
(3)
,
Charlotte Syrykh
(3, 6)
,
Pierre Bories
(3, 6)
,
Lucie Oberic
(3)
,
Loïc Ysebaert
(1, 2, 3, 4)
,
Laurent Martin
(5, 7, 8)
,
Selim Ramla
(5, 7, 8)
,
Philippine Robert
(5, 7, 8)
,
Claire Tabouret-Viaud
(9)
,
René-Olivier Casasnovas
(5, 7, 8)
,
Jean-Jacques Fournié
(1, 2, 3, 4)
,
Christine Bezombes
(1, 2, 3, 4)
,
Camille Laurent
(1, 2, 3, 4, 3)
1
CRCT -
Centre de Recherches en Cancérologie de Toulouse
2 Laboratoire d’Excellence ‘TOUCAN’ [Toulouse]
3 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
4 CALYM - Institut Carnot Lymphome
5 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
6 Réseau régional de cancérologie Onco-Occitanie
7 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
8 UFR SVTE - UFR Sciences de la Vie, de la Terre et de l'Environnement (Université de Bourgogne)
9 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
2 Laboratoire d’Excellence ‘TOUCAN’ [Toulouse]
3 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
4 CALYM - Institut Carnot Lymphome
5 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
6 Réseau régional de cancérologie Onco-Occitanie
7 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
8 UFR SVTE - UFR Sciences de la Vie, de la Terre et de l'Environnement (Université de Bourgogne)
9 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
Marie Tosolini
- Fonction : Auteur
- PersonId : 768352
- ORCID : 0000-0001-5278-5952
- IdRef : 146550811
Pauline Gravelle
- Fonction : Auteur
- PersonId : 948576
- ORCID : 0000-0002-0462-5652
- IdRef : 176934472
Sarah Pericart
- Fonction : Auteur
- PersonId : 1224109
- IdRef : 234024925
Salim Kanoun
- Fonction : Auteur
- PersonId : 770462
- ORCID : 0000-0002-8592-3773
- IdRef : 177841451
Don-Marc Franchini
- Fonction : Auteur
- PersonId : 1222157
- ORCID : 0000-0002-2562-5643
- IdRef : 119199610
Pierre Bories
- Fonction : Auteur
- PersonId : 768478
- ORCID : 0000-0002-2252-0395
Loïc Ysebaert
- Fonction : Auteur
- PersonId : 806931
- ORCID : 0000-0001-8478-5623
- IdRef : 06931151X
Jean-Jacques Fournié
- Fonction : Auteur
- PersonId : 178841
- IdHAL : jean-jacques-fournie
- ORCID : 0000-0001-6542-6908
- IdRef : 031095887
Christine Bezombes
- Fonction : Auteur
- PersonId : 870021
- ORCID : 0000-0003-4079-4872
- IdRef : 157707199
Camille Laurent
- Fonction : Auteur
- PersonId : 948580
- ORCID : 0000-0002-5375-7512
Résumé
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 PET 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 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 (HR=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, 4 out of 5 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 R-chemotherapy.