Supplementary Material for: Multidisciplinary clinic approach improves immunotherapy treatment outcomes in unresectable hepatocellular carcinoma: a multicentre retrospective study.

Introduction Given the complexity of managing unresectable hepatocellular carcinoma (HCC), few Italian centres have implemented integrated multidisciplinary clinics (MDTc), where hepatologists and oncologists jointly assess patients. This study aimed to evaluate whether this model improves survival outcomes in patients treated with Atezolizumab and Bevacizumab (A+B). Methods In this multicentre retrospective study, 146 patients with cirrhosis and unresectable HCC treated with A+B were included. Based on the outpatient care model, centres were categorised into two groups: those with MDTc and those with standard oncology clinics, where hepatologists were consulted on demand. Primary outcomes were overall survival (OS) and progression-free survival (PFS); secondary outcomes included disease control rate (DCR) and objective response rate (ORR). An inverse probability weighting (IPW) analysis was performed to adjust for baseline imbalances between groups. Results Seventy-seven patients (53%) were managed in MDTc settings, and 69 (47%) in oncology clinics. Median treatment duration was 6.0 months (IQR 2.0–11.0). Median OS did not significantly differ between groups [19.7 months (95%CI: 16.6–23.1) vs 13.4 months (95%CI: 10.7–19.5); p=0.07], whereas median PFS was significantly longer in the MDTc group [13.6 months (95%CI: 8.9–NA) vs 7.7 months (95%CI: 4.9–13.0); p=0.02]. While ORR was similar, DCR was higher in the MDTc group (70.1% vs 60.3%; p=0.05). Patients followed in MDTc remained on first-line therapy significantly longer [8 months (IQR 3–12) vs 4 months (IQR 1–8); p=0.009]. Although the overall treatment discontinuation rate did not differ between the two groups, liver-related events were more frequent and accounted for a greater proportion of discontinuations in oncology clinics (40.6% vs 10.4%; p=0.04). Furthermore, treatment duration was shorter in patients discontinuing A+B due to liver-related events than other causes [2.5 months (IQR 1.8–6.3) vs 7.1 months (IQR 3.9–11.2); p<0.001]. However, in the IPW analysis, the association between MDTc management and clinical outcomes was no longer significant. Conclusions In patients with unresectable HCC treated with A+B, MDTc management did not significantly improved OS, but was associated with better PFS and DCR. These benefits were likely driven by longer treatment duration and lower rates of liver-related decompensation, underscoring the value of integrated hepatologic-oncologic management in this complex population.