山本 智支

BACKGROUND/AIM: Atezolizumab plus bevacizumab (Ate+Bev) is widely used as first-line therapy for unresectable hepatocellular carcinoma (HCC). However, a subset of patients experience early disease progression, often detected at the first radiologic assessment around 6 weeks. Evidence guiding second-line therapy in this subgroup is limited, and the clinical value of lenvatinib after early progressive disease (PD) remains unclear. PATIENTS AND METHODS: We retrospectively analyzed 36 patients with unresectable HCC who received lenvatinib after failure of first-line Ate+Bev. Patients were stratified by early PD, defined as radiologic progression at the scheduled 6-week assessment after starting Ate+Bev. Outcomes included antitumor response, progression-free survival (PFS), and overall survival (OS). RESULTS: Objective response rate (ORR) and disease control rate (DCR) assessed by RECIST 1.1 were comparable between patients with and without early PD (ORR: 28.6% vs. 13.8%; DCR: 85.7% vs. 86.2%; p=0.342). Median PFS was also similar between groups [5.2 months (95% confidence interval=1.9-NA) vs. 6.1 months (3.7-7.5); p=0.307]. In multivariate analyses adjusting for Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage, and reduced starting dose, early PD was not significantly associated with either PFS or OS, whereas Child-Pugh class A was independently associated with improved OS. Correlation between first- and second-line PFS was weak and non-significant (r=0.077, p=0.682). CONCLUSION: Lenvatinib demonstrated comparable antitumor activity and survival outcomes even in patients with early PD on first-line Ate+Bev, indicating that early radiologic progression does not necessarily signify refractoriness to subsequent systemic therapy. These findings support lenvatinib as a viable second-line option regardless of early Ate+Bev response, particularly in patients with preserved liver function. Larger prospective studies are needed to confirm these observations.

OBJECTIVES: This retrospective multicenter study aimed to clarify the clinical impact of endotherapy for painless pancreatic duct (PD) stones compared with that in patients who received conservative treatment without endotherapy. METHODS: We enrolled 268 patients suffering from chronic pancreatitis with painless PD stones (145 with endotherapy and 123 without endotherapy) and evaluated the impact of endotherapy for painless PD stones on clinical and radiological outcomes. RESULTS: When conservative treatment without endotherapy was set as a reference, complete clearance of the targeted PD stones decreased the relative risk for atrophy of pancreatic parenchyma after inclusion (hazard ratio [HR] 0.42; 95% confidence interval [CI] 0.21-0.84). Incomplete clearance of the targeted PD stones was identified as a risk factor for new-onset or worsening of diabetes (HR 2.08; 95% CI 1.10-3.91) and inducement of pain attack (HR 4.03; 95% CI 1.45-11.19), although complete clearance was not correlated with these outcomes. CONCLUSION: In chronic pancreatitis patients with painless PD stones, endotherapy with complete stone clearance allows the maintenance of pancreatic parenchymal volume. However, if complete clearance fails, endotherapy could lead to aggravation of glucose tolerance and pain attacks during follow-up.