Morphologic intratumoral heterogeneity from routine whole-slide histopathology is prognostic for survival in primary central nervous system lymphoma: development in the LOC Network and international external validation
Year: 2026
Type: preprint
Abstract: Background Clinical scores incompletely capture outcomes in primary central nervous system lymphoma (PCNSL). We quantified morphologic heterogeneity in pretreatment hematoxylin and eosin (H&E) whole slides. Patients and methods Three independent cohorts of immunocompetent, HIV- and EBV-negative patients treated recently were analyzed: LOC 2023 (122 slides), phase III BLOCAGE-01 (245 slides; NCT02313389 ), and external Barcelona (BCN; 41 slides). UNI embeddings, prototype learning, spatial metrics, and elastic-net Cox regression defined ITH-C. Results Models achieved bootstrap-corrected concordance of 0.797–0.834. Age-, sex-, and KPS-adjusted ITH-C HRs were 1.29 (95% CI 1.01–1.64), 1.27 (1.07–1.51), and 2.13 (1.35–3.37), respectively. Adding ITH-C increased MSKCC C-index from 0.671 to 0.717, 0.560 to 0.593, and 0.588 to 0.706. Spatial transcriptomics linked ITH-C to immune programs. Conclusions Routine H&E encodes prognostic spatial heterogeneity in PCNSL. ITH-C complements clinical scores, supporting prospective risk stratification.
Authors: Lucas Rincón de la Rosa, Noémie Barillot, Isaias Hernández-Verdin, Roser Velasco, Bertrand Mathon, Sandrine Eimer, Jean Rodolphe Vignes, Audrey Rousseau, Jérôme Paillassa, Guido Ahle, Felix Lerintiu, Emmanuelle Uro-Coste, Lucie Oberic, Emeline Tabouret, Romain Appay, Guillaume Gauchotte, Luc Taillandier, Jean-Pierre Marolleau, Clovis Adam, Renata Ursu, Stefania Cuzzubbo, Anna Schmitt, Lucia Nichelli, Albert Pons-Escoda, Frédéric Charlotte, Frédéric Davi, Magali Le Garff-Tavernier, Sylvain Choquet, Carole Soussain, Noemí Vidal, Eva González-Barca, Fina Climent, Patricia López, Fanny Drieux, Elena-Liana Veresezan, Michael Heming, Gerd Meyer zu Hörste, Oliver Grauer, Fabrice Jardin, Karima Mokhtari, Caroline Houillier, Khê Hoang-Xuan, Agustí Alentorn
Institutions: Centre National de la Recherche Scientifique, Inserm, Sorbonne Université, Institut du Cerveau, Bellvitge University Hospital, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Centre Hospitalier Universitaire de Bordeaux, Hôpital Pellegrin, Centre Hospitalier Universitaire d'Angers, Hopitaux Civils de Colmar, Centre Hospitalier Universitaire de Toulouse, Institut universitaire du cancer de Toulouse Oncopole, Aix-Marseille Université, Institut de Neurophysiopathologie, Hôpital de la Timone, Centre Hospitalier Régional et Universitaire de Nancy, Université de Lorraine, Centre Hospitalier Universitaire Amiens-Picardie, Université Paris Cité, Hôpital Saint-Louis, Institut Bergonié, Institut de Diagnòstic per la Imatge, Institut Curie, Centre Henri Becquerel, University Hospital Münster
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7207614523