San-Chi Chen

Background: Small bowel adenocarcinoma (SBA) is a rare gastrointestinal malignancy with limited treatment options and worse outcomes than colorectal cancer. While immune checkpoint inhibitors (ICIs) show impressive results in mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) tumors, microsatellite-stable (MSS) disease is traditionally considered resistant to immunotherapy. Case: We describe a man in his 70s with recurrent duodenal adenocarcinoma who experienced disease progression after multiple systemic therapies, including cetuximab plus FOLFIRI. Molecular profiling by liquid biopsy showed MSS status with low tumor mutational burden (TMB = 1 mutation/Mb). Given the lack of standard alternatives, he was treated with nivolumab, ipilimumab, and cetuximab. Tumor regression was observed within 3 months, followed by a complete radiographic response in October 2022 and a complete metabolic response on PET/CT at 12 months. Immune-related adverse events (irAEs) included grade 2 adrenal insufficiency, vitiligo, and pneumonitis, all of which were manageable. At the latest follow-up in April 2026, the patient had maintained a complete response, approximately 42 months after the first documented radiographic complete response and 27 months after discontinuation of all anticancer therapy. Conclusions: This case describes an exceptional durable complete response to dual immune checkpoint blockade combined with an EGFR inhibitor in MSS duodenal adenocarcinoma. Although the relative contribution of each agent and the presence of pharmacologic synergy cannot be determined from a single case, this observation warrants further investigation in prospective trials with MSS SBA.

Purpose: A well-established prognostic scoring system for unresectable hepatocellular carcinoma (uHCC) receiving systemic therapy is lacking. The Up7-ALBI score has shown prognostic value for lenvatinib. This study aimed to validate its prognostic value in uHCC treated with atezolizumab plus bevacizumab (atezo-bev). Patients and Methods: This retrospective multicenter study included 225 patients with uHCC who received first-line atezo-bev in Taiwan between 2017 and 2025. The Up7-ALBI score (0– 2), combining tumor burden (within vs beyond up-to-7) and ALBI grade (1 vs 2– 3), categorized patients into low-, intermediate-, and high-risk groups. The score was used to stratify progression-free survival (PFS) and overall survival (OS), with multivariate Cox analysis performed. Prognostic performance was compared with previously reported scoring systems. Results: The objective response rate (ORR) and disease control rate were 44.4% and 60.4%, respectively, and the median PFS and OS were 7.0 and 23.8 months. Among the 225 enrolled patients, 178 patients had complete data for Up7-ALBI analysis. The Up7-ALBI score significantly stratified outcomes, with median OS not reached, 36.0 months, and 9.2 months for scores 0, 1, and 2 (p < 0.01); median PFS of 13.4, 7.9, and 5.8 months (p < 0.01); and ORR of 66.7%, 52.2%, and 32.9%, respectively (p < 0.01). Multivariate analysis showed that Up7-ALBI scores 1 and 2, along with macrovascular invasion, were independent risk factors for OS. The Up7-ALBI score demonstrated the lowest Akaike information criterion (484.3) among the previously proposed scores. Conclusion: This study validated the Up7-ALBI score for uHCC receiving atezo-bev. Its consistent prognostic performance across systemic therapies supports its potential as a simple, clinically applicable risk-stratification tool.

Background In CheckMate-9DW, the suboptimal early tumor control of nivolumab–ipilimumab resulted in higher early mortality compared with the sorafenib/lenvatinib arm during the first 12 months. We evaluated whether adding lenvatinib to nivolumab–ipilimumab (NIL) improves outcomes versus nivolumab–ipilimumab (NI). Methods Patients with unresectable HCC treated with NI with or without lenvatinib were retrospectively analyzed. Responses were evaluated by RECIST v1.1, survival outcomes by Kaplan–Meier and inverse probability of treatment weighting (IPTW) adjustment, and multiple sensitivity analyses. Liver function changes were evaluated using the albumin–bilirubin (ALBI) score. Results Among 104 patients, 82 received NI and 22 received NIL. The NIL group demonstrated a higher disease control rate than the NI group (81.8% vs 39.0%; p < 0.01), with similar duration of response (21.4 vs 21.8 months). Median progression-free survival (PFS) was longer with NIL (10.2 vs 3.2 months), but not for overall survival (OS). In the first-line setting, NIL showed a trend toward longer PFS and fewer early deaths within 12 months. After IPTW adjustment and sensitivity analyses, the NIL regimen consistently demonstrated improved PFS (HR 0.44; p < 0.01) without a statistically significant OS benefit. Hypertension, proteinuria and stomatitis were more frequent in the NIL group, while ALBI scores remained stable. Development of immune-related adverse events was associated with improved outcomes. Conclusions This real-world study provides proof-of-concept evidence that incorporating a VEGF inhibitor into dual ICIs therapy is associated with improved tumor control and prolonged PFS, with a potential reduction in early mortality. Prospective studies are warranted to confirm these findings.

Five years after IMbrave150, atezolizumab plus bevacizumab (ate/bev) remains the first-line standard for unresectable hepatocellular carcinoma (uHCC). High response rates allow downstaging and curative conversion, enabling drug-free remission in some patients. Durable responses suggest potential for de-escalation, though discontinuation criteria need validation. In hepatitis B virus-related HCC, ate/bev appears safe across baseline viral loads when administered with concomitant antiviral therapy. Bleeding risk, particularly esophagogastric variceal hemorrhage, warrants baseline endoscopy and proactive management. Hypertension and proteinuria require close surveillance and early control to maintain bevacizumab use. Late bevacizumab interruption is acceptable, whereas early discontinuation is associated with poorer outcomes. After progression on ate/bev, evidence across cohorts favors tyrosine kinase inhibitor strategies such as lenvatinib over sorafenib. Cabozantinib and ramucirumab (for alpha-fetoprotein ≥400 ng/mL) are options and selected patients may benefit from immune checkpoint inhibitor-based combinations. Combining ate/bev with locoregional therapy (LRT) is promising. Phase III data with transarterial chemoembolization show improved progression-related endpoints. Early series suggest potential benefit with Yttrium-90 radioembolization, hepatic arterial infusion chemotherapy and radiotherapy, although high-level evidence is still lacking. Translational markers such as pre-existing immunity and transcriptomic models are promising but unvalidated. Adjuvant ate/bev has not demonstrated durable benefit. The neoadjuvant role and additional combination strategies require further exploration. Although ate/bev has improved outcomes in uHCC, key gaps remain, including biomarkers for regimen selection, de-escalation criteria, optimal sequencing, and integration with LRT or perioperative care. Prospective studies are needed to guide practice.

Introduction: Evidence supporting the combination of immunotherapy with intra-arterial therapy (IAT) for unresectable hepatocellular carcinoma (HCC) remains limited. This study aimed to evaluate whether the addition of IAT to first-line immunotherapy improves survival outcomes. Methods: Using the Taiwan Liver Cancer Association (TLCA) Research Group database, we identified patients with unresectable HCC who initiated first-line immunotherapy between May 2017 and January 2024. Patients with Barcelona Clinic Liver Cancer (BCLC) stage A or D disease, prior liver transplantation, or follow-up of 1 (aHR 1.58, 95% CI: 1.11–2.27; p = 0.012), tumor burden beyond the up-to-7 criteria (aHR 1.67, 95% CI: 1.02–2.74; p = 0.043), and portal vein invasion (aHR 1.67; 95% CI: 1.19–2.35; p = 0.003). Five-year OS was higher in the IAT group than in the control group (28.7% [95% CI: 17.8–46.2] vs. 16.4% [95% CI: 10.7–25.2]; p = 0.007). Landmark and subgroup analyses consistently supported the OS benefit of IAT. Conclusion: In unresectable HCC, the addition of IAT to first-line immunotherapy improves response rates, prolongs the duration of response, and enhances OS.

Background: Advanced sarcomas have limited treatment options. Gemcitabine and docetaxel (GD) regimen showed efficacy in soft tissue sarcomas (STSs) in phase II studies but failed in first‐line phase III trial. Adding cisplatin to GD showed efficacy in other types of cancer. mTOR pathway has been shown to play a role in resistance to these drugs. Inflammatory biomarkers have been identified as potential prognostic indicators in various malignancies, but their role in patients with advanced sarcomas is not clear. Methods: We retrospectively enrolled 77 patients with advanced or metastatic sarcomas (STSs, n = 71; bone sarcomas, n = 6) receiving a novel combination with gemcitabine‐gemcitabine/docetaxel/cisplatin plus everolimus (G‐GDC + E). Primary endpoints included overall survival (OS) and progression‐free survival (PFS). Inflammatory biomarkers were calculated, and their prognostic influence was evaluated. Results: The median OS and PFS were 16.8 months (95% CI, 13.6–23.9) and 5.4 months (95% CI, 4.3–8.3), respectively. Undifferentiated pleomorphic sarcoma/myxofibrosarcoma (UPS/MFS) demonstrated superior PFS compared to round cell sarcoma/translocation‐related sarcoma (7.8 vs. 3.6 months, p = 0.009) and bone sarcoma (7.8 vs. 2.3 months, p < 0.001). Eastern Cooperative Oncology Group Performance Status ≥ 2, unfavorable histology (round cell sarcoma/translocation‐related sarcoma and bone sarcoma), lower albumin level, and lymphocyte‐to‐monocyte ratio < 2.7 were independent predictors of OS. Grade 3–4 toxicities included neutropenia (68.8%), thrombocytopenia (59.7%), anemia (49.4%), diarrhea (18.2%), and skin toxicities (28.6%). Conclusions: G‐GDC + E demonstrates histology‐specific efficacy in advanced/metastatic sarcomas, with substantial hematologic toxicity (Grade 3–4 thrombocytopenia 59.7%, neutropenia 68.8%) and notable non‐hematologic events (Grade 3–4 diarrhea 18.2%, skin reactions 28.6%), all controllable with close monitoring, dose modifications and supportive care. Inflammatory biomarkers provide independent prognostic values.

Introduction: The phase 1/2 CheckMate-040 and the phase 3 CheckMate-9DW trials consistently demonstrated meaningful activity of nivolumab plus ipilimumab (Nivo/Ipi) in previously treated and treatment-naïve patients with advanced HCC. However, patients with ≥50% liver involvement, Vp4 portal vein tumor thrombosis (PVTT), or bile duct invasion were excluded from these trials. We aimed to assess the real-world efficacy and safety of Nivo/Ipi in this high-risk population. Methods: This international, multicenter, retrospective study was conducted in patients with advanced HCC who received Nivo/Ipi at six hospitals in Korea, Hong Kong, Singapore, and Taiwan between 2016 and 2024. Patients with Child-Pugh B/C or ECOG >2 were excluded. Results: Of the 206 patients assessed for eligibility, 145 were included in the final analysis: 44 classified as high risk (Vp4 PVTT, n = 10; ≥50% liver involvement, n = 34; bile duct invasion, n = 7) and 101 as non-high risk. Baseline characteristics were comparable, aside from differences in liver function and high-risk features. Nivo/Ipi was administered as third-line or later-line therapy in 76.6% of patients. The high-risk group exhibited a significantly lower objective response rate (ORR) (12.8% vs. 34.3%) and shorter median progression-free survival (PFS) (1.2 vs. 2.9 months) and overall survival (OS) (3.6 vs. 16.5 months). Among the high-risk features, ≥50% liver involvement was strongly associated with inferior ORR, PFS, and OS, whereas Vp4 PVTT and bile duct invasion alone were not significantly associated with outcomes. A higher intrahepatic tumor burden was also inversely associated with treatment response and survival. Adverse events were more frequent in high-risk patients, particularly hyperbilirubinemia (36.4% vs. 13.9%; grade ≥3: 11.4% vs. 1.0%). On multivariable analysis, ≥50% liver involvement and prior immune-checkpoint inhibitor exposure independently predicted shorter PFS and OS. Conclusion: Extensive liver involvement emerged as the key predictor of poor prognosis, whereas Vp4 PVTT and bile duct invasion were not associated with significantly worse outcomes.

Decision on Final Phase II dose; Guidelines combination dose level adjustments in the phase Ib phase; Schema for dose adjustments if more than 2 patients have DLT; Definitions of DLT

Changes of cell types based on (a) MCP-Counter and (b) Danaher module with post- vs pre-treatment samples. All tests were performed by non-parametric Wilcoxon test.