Sang Hun Lee

Supplementary Figures and Tables

Purpose:This study aimed to evaluate the prognostic relevance of HER2 positivity and the clinical impact of anti-HER2 therapy in the management of advanced biliary tract cancers using integrated multi-institutional data.Experimental Design:This retrospective analysis included 388 patients with advanced biliary tract cancers and known HER2 status from Yonsei Cancer Center and MD Anderson Cancer Center between 2009 and 2023. HER2 positivity was defined as HER2 IHC 3+, IHC 2+ with in situ hybridization positivity, or ERBB2 amplification by next-generation sequencing. Clinical outcomes, including survival, and genomic profiling with curated oncogenic pathway enrichment were analyzed.Results:HER2 positivity was observed in 25.2% of the epidemiology analysis cohort (n = 309). In the survival analysis (n = 310), HER2-positive biliary tract cancers were associated with shorter overall survival [(OS); 13.7 vs. 17.1 months; HR, 1.25; 95% confidence interval (CI), 0.97–1.60] and significantly shorter first-line progression-free survival (5.1 vs. 7.4 months; HR, 1.91; 95% CI, 1.46–2.48) than HER2-negative biliary tract cancers. Anti-HER2 therapy significantly improved OS among HER2-positive patients (18.2 vs. 8.1 months; HR, 0.39; 95% CI, 0.21–0.62). Genomic analysis showed the strongest enrichment of angiogenesis pathway alterations in HER2-positive patients, whereas KRAS mutations were predominant in HER2-negative biliary tract cancers.Conclusions:HER2 is a clinically meaningful biomarker with prognostic and predictive relevance in advanced biliary tract cancers. Anti-HER2 therapy significantly improves survival in HER2-positive patients. These findings support routine HER2 testing, standardization of HER2 diagnostic criteria, and further prospective evaluation of HER2-targeted strategies for biliary tract cancers.See related commentary by Fitzpatrick and Harding, p. 1603

Purpose: This study aimed to evaluate the prognostic relevance of HER2 positivity and the clinical impact of anti-HER2 therapy in the management of advanced biliary tract cancers using integrated multi-institutional data. Experimental Design: This retrospective analysis included 388 patients with advanced biliary tract cancers and known HER2 status from Yonsei Cancer Center and MD Anderson Cancer Center between 2009 and 2023. HER2 positivity was defined as HER2 IHC 3+, IHC 2+ with in situ hybridization positivity, or ERBB2 amplification by next-generation sequencing. Clinical outcomes, including survival, and genomic profiling with curated oncogenic pathway enrichment were analyzed. Results: HER2 positivity was observed in 25.2% of the epidemiology analysis cohort (n = 309). In the survival analysis (n = 310), HER2-positive biliary tract cancers were associated with shorter overall survival [(OS); 13.7 vs. 17.1 months; HR, 1.25; 95% confidence interval (CI), 0.97–1.60] and significantly shorter first-line progression-free survival (5.1 vs. 7.4 months; HR, 1.91; 95% CI, 1.46–2.48) than HER2-negative biliary tract cancers. Anti-HER2 therapy significantly improved OS among HER2-positive patients (18.2 vs. 8.1 months; HR, 0.39; 95% CI, 0.21–0.62). Genomic analysis showed the strongest enrichment of angiogenesis pathway alterations in HER2-positive patients, whereas KRAS mutations were predominant in HER2-negative biliary tract cancers. Conclusions: HER2 is a clinically meaningful biomarker with prognostic and predictive relevance in advanced biliary tract cancers. Anti-HER2 therapy significantly improves survival in HER2-positive patients. These findings support routine HER2 testing, standardization of HER2 diagnostic criteria, and further prospective evaluation of HER2-targeted strategies for biliary tract cancers.

Gallbladder (GB) cancer is highly prevalent and fatal in South Korea. In operable patients, radical resection with an R0 margin combined with lymphadenectomy is the mainstay of curative-intent therapy. Despite R0 resection, a high recurrence rate has been observed, necessitating the identification of risk factors for recurrence after surgery. This study aimed to identify risk factors strongly related to recurrence after R0 resection of GB cancer. This single-center, retrospective cohort study included 148 patients with GB cancer who underwent R0 resection between January 1, 2014, and December 31, 2019. Variables were analyzed using statistical tools to identify risk factors related to prognosis. Early recurrence, disease progression within 1 year after R0 resection, relapse-free survival, and time from treatment to any event were analyzed with logistic regression and Cox regression analyses. Early recurrence was observed in 15.5% (N = 23) of patients. Based on statistical analysis, the independent risk factors for early recurrence and relapse-free survival were age > 65 years, glycated hemoglobin level > 6.5%, surgical T stage > T3, surgical N stage > N1, moderate or poor pathological differentiation, reversed albumin–globulin ratio, high C-reactive protein level, and high carbohydrate antigen 19-9 level. Advanced pathological stage and high inflammatory marker levels, reflecting high tumor burden, are associated with poor prognosis. High glycated hemoglobin levels were also associated with early recurrence. In conclusion, active screening for early detection, reduction of inflammatory conditions, and management of diabetes may reduce early recurrence after R0 resection of GB cancer.

Sang Hun Lee, Young Jin Choi, Young Mi Seol. Med Biol Sci Eng 2025;8:33-9. https://doi.org/10.30579/mbse.2025.8.1.33

Sang Hun Lee, Do Young Kim, Hyo Jung Kim, Young Mi Seol, Young Jin Choi. Med Biol Sci Eng 2024;7:47-50. https://doi.org/10.30579/mbse.2024.7.1.47