Ryoji Miyahara

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.

Background Foveolar‐type gastric adenomas with a raspberry‐like appearance in the stomach have recently been identified. However, their etiology and mechanisms of development and growth remain unknown. Case Presentation We observed a foveolar‐type gastric adenoma with a raspberry‐like appearance that underwent rapid morphological changes. The first esophagogastroduodenoscopy revealed multiple reddish polyps on the cardia and fundus of the stomach, without Helicobacter pylori infection. The second‐largest polyp on the fundus had a red glove appearance and measured 5 mm in diameter. We diagnosed all of them as hyperplastic polyps on the basis of their shape. Given that the patient had received 10 mg of vonoprazan for a long time to treat reflux esophagitis, 20 mg of famotidine was prescribed instead. Eight months later, the largest polyp on the cardia had disappeared. However, a reddish raspberry‐like lesion was observed at the site of a previously identified polyp on the fundus and was diagnosed as foveolar‐type gastric adenoma by forceps biopsy. The pathological diagnosis was foveolar‐type gastric adenoma with high‐grade dysplasia as determined by tissue resection with endoscopic mucosal resection (EMR). Conclusion This is a valuable case report of a lesion evolving from a hyperplastic‐like polyp morphology to a raspberry‐like lesion within eight months.

AIM: This study evaluated the relationship between longitudinal dosing patterns and clinical outcomes of cabozantinib used as third- or later-line therapy in advanced hepatocellular carcinoma (HCC) previously treated with immune checkpoint inhibitors (ICIs), focusing on disease control (DC). METHODS: We retrospectively analyzed 33 patients with unresectable HCC who had received atezolizumab plus bevacizumab and lenvatinib, followed by cabozantinib. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors v1.1, and patients were classified into DC (complete response/partial response/stable disease) or non-DC (progressive disease/not evaluable) groups. Initial dose, longitudinal dosing, and treatment outcomes were compared. RESULTS: Most patients (90.9%) started at reduced doses (40 mg/day: n = 18; 20 mg/day: n = 12), with only three starting at 60 mg/day. Objective response rate was 3.0%, and DC rate was 51.5%. Compared with the non-DC group, the DC group had significantly longer median progression-free survival (4.4 vs. 1.2 months; p < 0.0001), overall survival (10.7 vs. 3.0 months; p = 0.0456), and treatment duration (134 vs. 22 days; p < 0.0001). Time to first dose reduction and average daily dose over the first 6 weeks did not differ significantly between groups. Child-Pugh class A was independently associated with DC and survival. CONCLUSIONS: In real-world practice, cabozantinib is often initiated at reduced doses, yet DC can be achieved even at ∼20 mg/day. For patients with preserved liver function, long-term stable disease is attainable, and individualized dose-reduction strategies represent an effective and feasible approach in later-line HCC treatment after ICIs.

OBJECTIVES: Since the efficacy of salvage photodynamic therapy (PDT) for locally recurrent esophageal cancer after definitive chemoradiotherapy (CRT) was proven for the first time in an investigator-initiated clinical trial, various reports have supported the clinical utility of PDT for these lesions. However, the clinical trial had limited indications, including a luminal circumference of ≤1/2, maximum longitudinal lesion length of 3 cm, and no invasion into the cervical esophagus, and there have been few reports of treatment outcomes for lesions exceeding the indications used in the investigator-initiated clinical trial. Therefore, this study was performed to assess the outcomes of treating lesions exceeding the above indications. METHODS: We retrospectively enrolled 34 consecutive esophageal cancer patients with 38 lesions who underwent PDT with talaporfin sodium. Lesions were classified as meeting (within-indications group; 23 patients, 25 lesions) or exceeding (beyond-indications group; 11 patients, 13 lesions) the indications in the investigator-initiated clinical trial. The local complete response rate (L-CR), overall survival (OS), progression-free survival (PFS), and incidence of PDT-related adverse events were compared between the groups. RESULTS: The L-CR rate was 88.0 and 92.3% in the within- and beyond-indications groups, respectively. The 2-year OS rate was 69.5% and 90.0% and the 2-year PFS rate was 43.3 and 56.6% in the within- and beyond-indications groups, respectively. In terms of adverse events, there were no serious adverse events in either group. CONCLUSION: Salvage PDT might be effective for local recurrence after CRT for lesions exceeding the indications in the investigator-initiated clinical trial.