Jean-Charles Nault
@NaultJc
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Soignant dans le service d’hépatologie Hôpital Avicenne 93, Centre de Recherche des Cordeliers
Joined August 2018
📌 Conclusion: The new Atezolizumab–Bevacizumab–Cluster (A-B-C) classification captures biological + prognostic heterogeneity in unresectable HCC. A tool to refine trial design, enrich populations, and personalize expectations.
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Outcomes were strikingly distinct: 🔹 A had best OS (median not reached), lowest progression (25%), longest PFS (~11 mo). 🔸 B OS ~18 mo 🔸 C OS ~14 mo Patterns held across BCLC stages + early hepatic decompensation risk.
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Tumor biology differed: Cluster C showed poorer differentiation and more macrotrabecular-massive subtype → consistent with aggressive disease biology
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Three clusters emerged: 🔹 A (47.5%) – older, higher BMI, good liver function, multiple small tumors. 🔹 B (11%) – VP1/2 PVI, more HBV, fewer metabolic features. 🔹 C (41.2%) – worse liver function, high AFP, VP3/4 PVI or large tumor burden.
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1) We recently published a study in @AGA_CGH
https://t.co/QVjSgZWOZF We analyzed using machine learning an international cohort of 1,399 pts treated with atezo/bev across 12 centers to uncover clinically meaningful subgroups. @GENIAL_project @etrepo @campani_claudia
cghjournal.org
We aimed to identify subgroups of patients with unresectable hepatocellular carcinoma (HCC) using a non‐a priori, data‐driven machine learning approach to uncover subgroups with distinct profiles...
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7/ This work was primarily funded by the #NCI #NIH, with support from the #fibrolamellar cancer foundation (#FCF) and #BMS Thank you to our patients and research teams!
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A therapeutic peptide vaccine for fibrolamellar hepatocellular carcinoma: a phase 1 trial | Nature Medicine
nature.com
Nature Medicine - In this phase 1 trial, treatment of patients with fibrolamellar hepatocellular carcinoma with a therapeutic peptide vaccine targeting the fusion kinase DNAJB1–PRKACA, which...
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6) Immunohistochemistry: PCT is positive in 77% of FLC, but absent in other primary or secondary liver tumors. In conclusion 👉 serum and tumor PCT = sensitive & specific biomarker for fibrolamellar hepatocellular carcinoma.
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5) CALCA (the PCT gene) is strongly overexpressed in FLC and spatial transcriptomics localizes CALCA to tumor cells.
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4) In 4 FLC patients, PCT tracked RECIST response under systemic treatment: ↓ in partial response, ↑ in progression, ↔ in stable disease. A promising dynamic monitoring marker.
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3) Serum PCT is markedly elevated in FLC vs HCC, CCA or cirrhosis, in both EU & US cohorts. 👉 83% high PCT in FLC vs 0 to 3% in HCC or CCA.
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2) Fibrolamellar carcinoma (FLC) affects young patients and lacks reliable biomarkers (AFP/CA19-9 are normals). An unexpectedly high PCT level in one case led us to investigate PCT across two cohorts (Europe and USA)
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1) We recently identified a serum tumor biomarker of fibrolamellar carcinoma, called procalcitonin, with @Zucmanrossi and @MarkYarchoan that you can find in
medrxiv.org
Introduction Fibrolamellar carcinoma (FLC) is a rare primary liver cancer that predominantly affects young patients with normal known serum tumor biomarkers (alpha-fetoprotein (AFP) and CA19-9). An...
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Clinically relevant for hepatobiliary oncologists: ➡️ Procalcitonin is a circulating tumor marker for #fibrolamellar carcinoma (like AFP in HCC & CA19-9 in CCA). Led by @NaultJc and @rossi_zucman. W/ @marinabaretti @_WaqarArif @neumannethan98 Preprint: https://t.co/44pkiWfq63
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Our latest work in J Hep shows the metabolic changes induced by DNAJB1-PRKACA in #FLC, with high glutamine utilization —> immune resistance @marinabaretti and @mnakazawa7 are testing this strategy in pts with FLC https://t.co/fn2dIpUKag
pubmed.ncbi.nlm.nih.gov
The DNAJ-PKAc fusion in fibrolamellar carcinoma (FLC) induces metabolic reprogramming including enhanced glutamine metabolism, which promotes immune evasion. Targeting this metabolic vulnerability...
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Join our #ILCA25 Debates speakers @cw_lab @JulienCaldelaro @DJPinato and our session chairs @NaultJc & @SumeraIlyasMD on November 21 in Hong Kong!
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