High serum LDH and liver metastases are the dominant predictors of primary cancer resistance to anti-PD(L)1 immunotherapy
| العنوان: | High serum LDH and liver metastases are the dominant predictors of primary cancer resistance to anti-PD(L)1 immunotherapy |
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| المؤلفون: | Laurent Dercle, Samy Ammari, Elvire Roblin, Amelie Bigorgne, Stéphane Champiat, Lokmane Taihi, Athèna Plaian, Sophie Hans, Sara Lakiss, Lambros Tselikas, Mathieu Rouanne, Eric Deutsch, Lawrence H. Schwartz, Mithat Gönen, Jessica Flynn, Christophe Massard, Jean-Charles Soria, Caroline Robert, Aurélien Marabelle |
| المساهمون: | Institut Gustave Roussy (IGR), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Département de radiologie, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Hôpital Foch [Suresnes], Département de médecine oncologique [Gustave Roussy], Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO) |
| المصدر: | European Journal of Cancer European Journal of Cancer, 2022, 177, pp.80-93. ⟨10.1016/j.ejca.2022.08.034⟩ |
| بيانات النشر: | Elsevier BV, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Hyperprogression, Cancer Research, Survival, Liver Neoplasms, Lactate dehydrogenase, Cancer immunotherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Prognosis, Liver metastases, Treatment Outcome, Oncology, Machine learning, Humans, Immunologic Factors, Prospective Studies, Immunotherapy, Melanoma, Retrospective Studies |
| الوصف: | International audience; Aim: Anti-PD-(L)1 immunotherapies improve survival in multiple cancers but remain ineffective for most patients. We applied machine-learning algorithms and multivariate analyses on baseline medical data to estimate their relative impact on overall survival (OS) upon anti-PD-(L)1 monotherapies. Method: This prognostic/predictive study retrospectively analysed 33 baseline routine medical variables derived from computed tomography (CT) images, clinical and biological meta-data. 695 patients with a diagnosis of advanced cancer were treated in prospective clinical trials in a single tertiary cancer centre in 3 cohorts including systemic anti-PD-(L)1 (251, 235 patients) versus other systemic therapies (209 patients). A random forest model combined variables to identify the combination (signature) which best estimated OS in patients treated with immunotherapy. The performance for estimating OS [95%CI] was measured using Kaplan–Meier Analysis and Log–Rank test. Results: Elevated serum lactate dehydrogenase (LDHhi) and presence of liver metastases (LM+) were dominant and independent predictors of short OS in independent cohorts of melanoma and non-melanoma solid tumours. Overall, LDHhiLM+ patients treated with anti-PD-(L)1 monotherapy had a poorer outcome (median OS: 3.1[2.4–7.8] months]) compared to LDHlowLM-patients (median OS: 15.3[8.9-NA] months; P < 0.0001). The OS of LDHlowLM-patients treated with immunotherapy was 28.8[17.9-NA] months (vs 13.1[10.8–18.5], P = 0.02) in the overall population and 30.3[19.93-NA] months (vs 14.1[8.69-NA], P = 0.0013) in patients with melanoma. Conclusion: LDHhiLM+ status identifies patients who shall not benefit from anti-PD-(L)1 monotherapy. It could be used in clinical trials to stratify patients and eventually address this specific medical need. |
| تدمد: | 0959-8049 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4af139afb11127f7db519d45c75cb5e2Test https://doi.org/10.1016/j.ejca.2022.08.034Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....4af139afb11127f7db519d45c75cb5e2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 09598049 |
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