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9 results on '"Lymphoma Study Association (LYSA)"'

1. Bendamustine and rituximab in elderly patients with low-tumour burden follicular lymphoma. Results of the LYSA phase II BRIEF study

Author

Gyan, Emmanuel, Sonet, Anne, Brice, Pauline, Anglaret, Bruno, Laribi, Kamel, Fruchart, Christophe, Tilly, Hervé, Araujo, Carla, Soubeyran, Pierre, Gonzalez, Hugo, Morineau, Nadine, Nicolas-Virelizier, Emmanuelle, Ghesquières, Hervé, Salles, Bruno, Bouabdallah, Réda, Orfeuvre, Hubert, Fahri, Jonathan, Couturier, Olivier, Xerri, Luc, Feugier, Pierre, Lymphoma Study Association (LYSA), Service d'hématologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Catholique de Louvain = Catholic University of Louvain (UCL), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier de Valence (Unité d'Hématologie), Centre hospitalier de Valence, Centre Hospitalier Le Mans (CH Le Mans), Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie (CH de la Côte Basque), Le CHCB, Centre Hospitalier de la Côte Basque, Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Centre Catherine-de-Sienne [Nantes] (CCS), Centre Léon Bérard [Lyon], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier de Bourg en Bresse, Service des maladies du sang [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Design and Application of Innovative Local Treatments in Glioblastoma (CRCINA-ÉQUIPE 17), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Service d'hématologie

Subjects
Bendamustine, Male, medicine.medical_specialty, Efficacy, [SDV]Life Sciences [q-bio], efficacy, Follicular lymphoma, Phases of clinical research, Gastroenterology, Maintenance Chemotherapy, 03 medical and health sciences, 0302 clinical medicine, International Prognostic Index, rituximab, Maintenance therapy, follicular lymphoma, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Bendamustine Hydrochloride, Humans, bendamustine, Lymphoma, Follicular, Aged, Aged, 80 and over, tolerance, business.industry, Remission Induction, Hematology, Middle Aged, medicine.disease, Survival Analysis, 3. Good health, Lymphoma, Tumor Burden, Regimen, Treatment Outcome, 030220 oncology & carcinogenesis, Rituximab, Female, business, Tolerance, 030215 immunology, medicine.drug
Abstract

International audience; The treatment of low-tumour burden follicular lymphoma (LTBFL) remains a challenge. Rituximab-based strategies may be improved by adding chemotherapy. This Lymphoma Study Association multicentre phase II study assessed rituximab and bendamustine in 63 patients with untreated LTBFL who were aged over 60years old and had a follicular lymphoma International Prognostic Index (FLIPI) score ≥2. Induction comprised 4 weekly cycles of rituximab 375mg/m intravenously combined with 2 cycles of bendamustine 90mg/m days 1-2 with a 28-day interval, followed by twelve cycles of 375mg/m rituximab maintenance therapy every 8weeks. The primary endpoint was complete response (CR)/unconfirmed CR (CRu), at 12weeks. Median age was 67·4years and median FLIPI was 3. Ultimately, 18 patients (29%) had high tumour burden according to Groupe d'Etude des Lymphomes Folliculaires criteria. The 12-week CR/CRu rate was 54·0% and the overall response rate was 93·7%. Surprisingly, 3 patients died during maintenance (2 sepsis, 1 neoplasm). Progression-free survival was 85·4% at 24months. In LTBFL patients with FLIPI ≥2, two cycles of rituximab and bendamustine result in a CR rate of 54·0%. However, the treatment-related deaths observed do not allow this regimen to be recommended for LTBFL patients aged over 60years. EudraCT: 2010-020757-14; ClinicalTrials.gov: NCT01313611.

Published
2018

2. Bendamustine and rituximab in elderly patients with low-tumour burden follicular lymphoma. Results of the LYSA phase II BRIEF study.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Gyan, Emmanuel, Sonet, Anne, Brice, Pauline, Anglaret, Bruno, Laribi, Kamel, Fruchart, Christophe, Tilly, Hervé, Araujo, Carla, Soubeyran, Pierre, Gonzalez, Hugo, Morineau, Nadine, Nicolas-Virelizier, Emmanuelle, Ghesquières, Hervé, Salles, Bruno, Bouabdallah, Réda, Orfeuvre, Hubert, Fahri, Jonathan, Couturier, Olivier, Xerri, Luc, Feugier, Pierre, Lymphoma Study Association (LYSA), UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Gyan, Emmanuel, Sonet, Anne, Brice, Pauline, Anglaret, Bruno, Laribi, Kamel, Fruchart, Christophe, Tilly, Hervé, Araujo, Carla, Soubeyran, Pierre, Gonzalez, Hugo, Morineau, Nadine, Nicolas-Virelizier, Emmanuelle, Ghesquières, Hervé, Salles, Bruno, Bouabdallah, Réda, Orfeuvre, Hubert, Fahri, Jonathan, Couturier, Olivier, Xerri, Luc, Feugier, Pierre, and Lymphoma Study Association (LYSA)

Abstract

The treatment of low-tumour burden follicular lymphoma (LTBFL) remains a challenge. Rituximab-based strategies may be improved by adding chemotherapy. This Lymphoma Study Association multicentre phase II study assessed rituximab and bendamustine in 63 patients with untreated LTBFL who were aged over 60 years old and had a follicular lymphoma International Prognostic Index (FLIPI) score ≥2. Induction comprised 4 weekly cycles of rituximab 375 mg/m intravenously combined with 2 cycles of bendamustine 90 mg/m days 1-2 with a 28-day interval, followed by twelve cycles of 375 mg/m rituximab maintenance therapy every 8 weeks. The primary endpoint was complete response (CR)/unconfirmed CR (CRu), at 12 weeks. Median age was 67·4 years and median FLIPI was 3. Ultimately, 18 patients (29%) had high tumour burden according to Groupe d'Etude des Lymphomes Folliculaires criteria. The 12-week CR/CRu rate was 54·0% and the overall response rate was 93·7%. Surprisingly, 3 patients died during maintenance (2 sepsis, 1 neoplasm). Progression-free survival was 85·4% at 24 months. In LTBFL patients with FLIPI ≥2, two cycles of rituximab and bendamustine result in a CR rate of 54·0%. However, the treatment-related deaths observed do not allow this regimen to be recommended for LTBFL patients aged over 60 years. EudraCT: 2010-020757-14; ClinicalTrials.gov: NCT01313611.

Published
2018

3. Soluble programmed death-ligand 1 as a prognostic biomarker for overall survival in patients with diffuse large B-cell lymphoma: a replication study and combined analysis of 508 patients

Author

Karin Tarte, Thomas E. Witzig, Imane Azzaoui, Thomas M. Habermann, Andrew L. Feldman, Céline Pangault, Noel Milpied, Stephen M. Ansell, Thierry Fest, Marie Parrens, Matthew J. Maurer, James R. Cerhan, Delphine Rossille, Mikael Roussel, Susan L. Slager, Thierry Lamy, Gaëlle Labouré, Brian K. Link, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Mayo Clinic [Rochester], CHU Bordeaux [Bordeaux], University of Iowa [Iowa City], This study is supported by the French Health Minister (BMS_LyTrans project, NCT01287923), the National Institute of Cancer (INCa Translational Research 2010), the French Lymphoma Study Association (LYSA), the French National Agency for Research (ANR Carnot/CALYM), the National Cancer Institute (P50 CA97274, R01 CA92153), and the Henry J Predolin Foundation. Concerning the French cohort, we are indebted to the LYSA pathology platform (Hôpital Henri Mondor, Créteil) for immunohistochemical experiments, the Centre de Ressources Biologiques CRB-Santé (BB-0033-00056) of the Rennes hospital for providing high quality samples. This work was partly supported by a French National Cancer Institute post-doctoral fellowship (grant number PDOC-RC-GO/07-003) to the first author (D.R.)., Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Chard-Hutchinson, Xavier

Subjects
Adult, Male, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Cancer Research, medicine.medical_specialty, Adolescent, Programmed Cell Death 1 Receptor, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, Young Adult, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Refractory, immune system diseases, hemic and lymphatic diseases, Internal medicine, Biomarkers, Tumor, Tumor Microenvironment, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Hematology, business.industry, Peripheral tolerance, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, Prognosis, medicine.disease, 3. Good health, Lymphoma, Leukemia, Oncology, Apoptosis, 030220 oncology & carcinogenesis, Immunology, Cancer research, Female, Rituximab, Lymphoma, Large B-Cell, Diffuse, business, Diffuse large B-cell lymphoma, 030215 immunology, medicine.drug
Abstract

Diffuse large B-cell lymphoma (DLBCL) is an aggressive hematologic malignancy with more than two-thirds of the patients cured with first-line rituximab-based treatments. However, relapsing or refractory patients have a very poor survival despite salvage therapies. The PD-1/PD-L1 pathway plays a major role in peripheral tolerance and homeostasis by inhibiting T-cell activation.

Published
2017

4. Total metabolic tumor volume, circulating tumor cells, cell-free DNA: distinct prognostic value in follicular lymphoma

Author

Axel Van Der Gucht, Jehan Dupuis, E. Itti, René-Olivier Casasnovas, Philippine Robert, Alina Berriolo-Riedinger, Salma Hamdane, Jean-Philippe Jais, Asma Beldi-Ferchiou, Gaelle Laboure, Christiane Copie-Bergman, Benjamin Verret, Marie-Hélène Delfau-Larue, Ichrafe Benmaad, Isabelle Nel, Corinne Haioun, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, The lymphoma study association (LYSA), CHU Henri Mondor, Service de Médecine Nucléaire, Centre Georges-François Leclerc [Dijon] (CGFL), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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), Service de médecine nucléaire [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement

Subjects
Adult, Male, 0301 basic medicine, Oncology, endocrine system, medicine.medical_specialty, Follicular lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Polymerase Chain Reaction, Circulating Tumor DNA, law.invention, 03 medical and health sciences, 0302 clinical medicine, Circulating tumor cell, immune system diseases, Predictive Value of Tests, law, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Digital polymerase chain reaction, Lymphoma, Follicular, Polymerase chain reaction, Survival analysis, Aged, Retrospective Studies, Lymphoid Neoplasia, business.industry, Hematology, Middle Aged, Neoplastic Cells, Circulating, Prognosis, medicine.disease, Survival Analysis, Tumor Burden, 3. Good health, Lymphoma, 030104 developmental biology, Cell-free fetal DNA, 030220 oncology & carcinogenesis, Predictive value of tests, Female, business
Abstract

International audience; Outcomes for follicular lymphoma (FL) have greatly improved, but most patients will ultimately relapse. High total metabolic tumor volume (TMTV), computed from baseline 18F-fluorodeoxyglucose-positron emission tomography (PET), is associated with shorter progression-free survival (PFS), but circulating tumor cells (CTCs) and cell-free DNA (cfDNA) may also reflect tumor burden and be of prognostic value. The aim of our study was to correlate CTCs and cfDNA with TMTV in FL at diagnosis and to determine their prognostic values. We retrospectively analyzed 133 patients (with previously untreated FL and a baseline PET) from 2 cohorts with either a baseline plasma sample (n = 61) or a bcl2-JH-informative peripheral blood (PB) sample (n = 68). Quantification of circulating bcl2-JH+ cells and cfDNA was performed by droplet digital polymerase chain reaction. A significant correlation was found between TMTV and both CTCs (P < .0001) and cfDNA (P < .0001). With a median 48-month follow-up, 4-year PFS was lower in patients with TMTV > 510 cm3 (P = .0004), CTCs >0.0018 PB cells (P = .03), or cfDNA >2550 equivalent-genome/mL (P = .04). In comparison with TMTV alone, no additional prognostic information was obtained by measuring CTCs. In contrast, Cox multivariate analysis, including cfDNA and TMTV, showed that both cfDNA and TMTV remained predictive of outcome. In conclusion, CTCs and cfDNA correlate with TMTV in FL, and all 3 influence patient outcome. PFS was shorter for patients with high cfDNA and TMTV, suggesting that these parameters provide relevant information for tumor-tailored therapy.

Published
2018

5. T-cell defect in Diffuse Large B-cell Lymphomas involves expansion of myeloid derived suppressor cells expressing IL-10, PD-L1 and S100A12

Author

Azzaoui, Imane, Uhel, Fabrice, Rossille, Delphine, Pangault, Celine, Dulong, Joelle, Le Priol, Jerome, Lamy, Thierry, Houot, Roch, Le Gouill, Steven, Cartron, Guillaume, Godmer, Pascal, Bouabdallah, Krimo, Milpied, Noel, Damaj, Gandhi, Tarte, Karin, Fest, Thierry, Roussel, Mikael, CHU Pontchaillou [Rennes], Etablissement français du sang [Rennes] (EFS Bretagne), Microenvironnement et cancer (MiCa), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), CHU Bordeaux [Bordeaux], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), This work was supported by a research grant from the National Institute of Cancer (INCa Recherche Translationnelle 2010), the Groupe Ouest-Est des Leucémies et des Autres Maladies du Sang, the Lymphoma Study Association (LYSA) group, and the Ligue Nationale Contre le Cancer (équipe labellisée). M.R. is a recipient of a fellowship from the Nuovo-Soldati Fundation., Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Jonchère, Laurent, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, immune system diseases, hemic and lymphatic diseases, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract

International audience; In diffuse large B-cell lymphoma (DLBCL), the number of circulating monocytes and neutrophils represents an independent prognostic factor. These cell subsets include monocytic and granulocytic myeloid-derived suppressor cells (M- and G-MDSCs) defined by their ability to suppress T-cell responses. MDSCs are a heterogeneous population described in inflammatory and infectious diseases and in numerous tumors including multiple myeloma, chronic lymphocytic leukemia, and DLBCL. However, their mechanisms of action remain unclear. We broadly assessed the presence and mechanisms of suppression of MDSC subsets in DLBCL. First, a myeloid suppressive signature was identified by gene expression profiling in DLBCL peripheral blood. Accordingly, we identified, in a cohort of 66 DLBCL patients, an increase in circulating G-MDSC (LinnegHLA-DRnegCD33posCD11bpos) and M-MDSC (CD14posHLA-DRlow) counts. Interestingly, only M-MDSC number was correlated with the International Prognostic Index, event-free survival, and number of circulating Tregs. Furthermore, T-cell proliferation was restored after monocyte depletion. Myeloid-dependent T-cell suppression was attributed to a release of interleukin-10 and S100A12 and increased PD-L1 expression. In summary, we identified expanded MDSC subsets in DLBCL, as well as new mechanisms of immunosuppression in DLBCL.

Published
2016

6. MYC Rearrangement Prediction From LYSA Whole Slide Images in Large B-Cell Lymphoma: A Multicentric Validation of Self-supervised Deep Learning Models.

Author

Syrykh C, Di Proietto V, Brion E, Copie-Bergman C, Jardin F, Dartigues P, Gaulard P, Molina TJ, Briere J, Oberic L, Haioun C, Tilly H, Maussion C, Morel M, Schiratti JB, and Laurent C

Abstract

Large B-cell lymphoma (LBCL) is a heterogeneous lymphoid malignancy in which MYC gene rearrangement (MYC-R) is associated with a poor prognosis, prompting the recommendation for more intensive treatment. MYC-R detection relies on fluorescence in situ hybridization method which is time consuming, expensive, and not available in all laboratories. Automating MYC-R detection on hematoxylin-and-eosin-stained whole slide images of LBCL would decrease the need for costly molecular testing and improve pathologists' productivity. We developed an interpretable deep learning algorithm to detect MYC-R considering recent advances in self-supervised learning and providing an extensive comparison of 7 feature extractors and 6 multiple instance learning models, themselves. Four different multicentric cohorts, including 1247 patients with LBCL, were used for training and validation. The best deep learning model reached an average area under the receiver operating characteristic curve score of 81.9% during crossvalidation on the largest LBCL cohort, and area under the receiver operating characteristic curve scores ranging from 62.2% to 74.5% when evaluated on other unseen cohorts. In addition, we demonstrated that using this model as a prescreening tool (with a false-negative rate of 0%), fluorescence in situ hybridization testing would be avoided in 35% of cases. This work demonstrates the feasibility of developing a medical device to efficiently detect MYC gene rearrangement on hematoxylin-and-eosin-stained whole slide images in daily practice., (Copyright © 2024. Published by Elsevier Inc.)

Published
2024
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7. Fully automatic segmentation of diffuse large B cell lymphoma lesions on 3D FDG-PET/CT for total metabolic tumour volume prediction using a convolutional neural network.

Author

Blanc-Durand P, Jégou S, Kanoun S, Berriolo-Riedinger A, Bodet-Milin C, Kraeber-Bodéré F, Carlier T, Le Gouill S, Casasnovas RO, Meignan M, and Itti E

Subjects
Humans, Neural Networks, Computer, Positron Emission Tomography Computed Tomography, Prospective Studies, Reproducibility of Results, Retrospective Studies, Tumor Burden, Fluorodeoxyglucose F18, Lymphoma, Large B-Cell, Diffuse diagnostic imaging
Abstract

Purpose: Lymphoma lesion detection and segmentation on whole-body FDG-PET/CT are a challenging task because of the diversity of involved nodes, organs or physiological uptakes. We sought to investigate the performances of a three-dimensional (3D) convolutional neural network (CNN) to automatically segment total metabolic tumour volume (TMTV) in large datasets of patients with diffuse large B cell lymphoma (DLBCL)., Methods: The dataset contained pre-therapy FDG-PET/CT from 733 DLBCL patients of 2 prospective LYmphoma Study Association (LYSA) trials. The first cohort (n = 639) was used for training using a 5-fold cross validation scheme. The second cohort (n = 94) was used for external validation of TMTV predictions. Ground truth masks were manually obtained after a 41% SUVmax adaptive thresholding of lymphoma lesions. A 3D U-net architecture with 2 input channels for PET and CT was trained on patches randomly sampled within PET/CTs with a summed cross entropy and Dice similarity coefficient (DSC) loss. Segmentation performance was assessed by the DSC and Jaccard coefficients. Finally, TMTV predictions were validated on the second independent cohort., Results: Mean DSC and Jaccard coefficients (± standard deviation) in the validations set were 0.73 ± 0.20 and 0.68 ± 0.21, respectively. An underestimation of mean TMTV by - 12 mL (2.8%) ± 263 was found in the validation sets of the first cohort (P = 0.27). In the second cohort, an underestimation of mean TMTV by - 116 mL (20.8%) ± 425 was statistically significant (P = 0.01)., Conclusion: Our CNN is a promising tool for automatic detection and segmentation of lymphoma lesions, despite slight underestimation of TMTV. The fully automatic and open-source features of this CNN will allow to increase both dissemination in routine practice and reproducibility of TMTV assessment in lymphoma patients.

Published
2021
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8. Risk factors and a prognostic score for survival after autologous stem-cell transplantation for relapsed or refractory Hodgkin lymphoma.

Author

Bröckelmann PJ, Müller H, Casasnovas O, Hutchings M, von Tresckow B, Jürgens M, McCall SJ, Morschhauser F, Fuchs M, Borchmann P, Moskowitz CH, and Engert A

Subjects
Adult, Aged, Female, Humans, Male, Middle Aged, Prognosis, Proportional Hazards Models, Recurrence, Risk Factors, Hematopoietic Stem Cell Transplantation, Hodgkin Disease therapy, Survival Analysis
Abstract

Background: Novel agents are changing the treatment of relapsed or refractory Hodgkin lymphoma (HL). Nevertheless, high-dose chemotherapy and autologous stem-cell transplantation (ASCT) are considered standard of care in eligible patients. To identify patients who could benefit most from novel therapeutic approaches, we investigated a comprehensive set of risk factors (RFs) for survival after ASCT., Methods: In this multinational prognostic multivariable modeling study, 23 potential RFs were retrospectively evaluated in HL patients from nine prospective trials with multivariable Cox proportional hazards regression analyses (part I). The resulting prognostic score was then validated in an independent clinical sample (part II)., Results: In part I, we identified 656 patients treated for relapsed/refractory HL between 1993 and 2013 with a median follow-up of 60 months after ASCT. The majority of potential RFs had significant impact on progression-free survival (PFS) with hazard ratios (HR) ranging from 1.39 to 2.22. The multivariable analysis identified stage IV disease, time to relapse ≤3 months, ECOG performance status ≥1, bulk ≥5 cm and inadequate response to salvage chemotherapy [

Published
2017
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9. Rituximab exposure is influenced by baseline metabolic tumor volume and predicts outcome of DLBCL patients: a Lymphoma Study Association report.

Author

Tout M, Casasnovas O, Meignan M, Lamy T, Morschhauser F, Salles G, Gyan E, Haioun C, Mercier M, Feugier P, Boussetta S, Paintaud G, Ternant D, and Cartron G

Subjects
Adult, Aged, Antineoplastic Agents administration & dosage, Antineoplastic Agents metabolism, Antineoplastic Agents pharmacokinetics, Disease-Free Survival, Dose-Response Relationship, Drug, Female, Humans, Kaplan-Meier Estimate, Lymphoma, Large B-Cell, Diffuse metabolism, Lymphoma, Large B-Cell, Diffuse pathology, Male, Middle Aged, Positron-Emission Tomography, Rituximab administration & dosage, Rituximab metabolism, Rituximab pharmacokinetics, Treatment Outcome, Tumor Burden drug effects, Young Adult, Antineoplastic Agents therapeutic use, Lymphoma, Large B-Cell, Diffuse drug therapy, Rituximab therapeutic use
Abstract

High variability in patient outcome after rituximab-based treatment is partly explained by rituximab concentrations, and pharmacokinetic (PK) variability could be influenced by tumor burden. We aimed at quantifying the influence of baseline total metabolic tumor volume (TMTV 0 ) on rituximab PK and of TMTV 0 and rituximab exposure on outcome in patients with diffuse large B-cell lymphoma (DLBCL). TMTV 0 was measured by 18 F-fluorodeoxyglucose-positron emission tomography-computed tomography in 108 previously untreated DLBCL patients who received four 375 mg/m 2 rituximab infusions every 2 weeks in combination with chemotherapy in 2 prospective trials. A 2-compartment population model allowed describing rituximab PK and calculating rituximab exposure (area under the concentration-time curve; AUC). The association of TMTV 0 and AUC with metabolic response after 4 cycles, as well as progression-free survival (PFS) and overall survival (OS), was assessed using logistic regression and Cox models, respectively. Cutoff values for patient outcome were determined using receiver operating characteristic curve analysis. Exposure to rituximab decreased as TMTV 0 increased ( R 2 = 0.41, P < .0001). A high AUC in cycle 1 (≥9400 mg × h per liter) was associated with better response (odds ratio, 5.56; P = .0006) and longer PFS (hazard ratio [HR], 0.38; P = .011) and OS (HR, 0.17; P = .001). A nomogram for rituximab dose needed to obtain optimal AUC according to TMTV 0 was constructed, and the 375 mg/m 2 classical dose would be suitable for patients with TMTV 0 <281 cm 3 In summary, rituximab exposure is influenced by TMTV 0 and correlates with response and outcome of DLBCL patients. Dose individualization according to TMTV 0 should be evaluated in prospective studies. These studies were registered at www.clinicaltrials.gov as #NCT00498043 and #NCT00841945., (© 2017 by The American Society of Hematology.)

Published
2017
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