📌 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 treatments.

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.

Tumor biology differed: Cluster C showed poorer differentiation and more macrotrabecular-massive subtype → consistent with aggressive disease biology.

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.

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.

5) CALCA (the PCT gene) is strongly overexpressed in FLC and spatial transcriptomics localizes CALCA to tumor cells.

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.

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.

2) Fibrolamellar carcinoma (FLC) affects young patients and lacks reliable biomarkers (AFP/CA19-9 usually normal). An unexpectedly high PCT level in one case led us to investigate PCT across two cohorts (Europe and USA)

Yes sure !

7/ In conclusion,
Systematic biopsies during RFA = safe + informative.
They can sharpen diagnosis, guide therapy & predict prognosis in newly diagnosed HCC. #HCC #LiverCancer #Biopsy