DataSheet1_Tumor budding as a predictor of disease-free survival in patients with cholangiocarcinoma.docx

Background: Tumor budding is considered a prognostic factor in several solid cancer types. However, we lack comprehensive information on the importance of tumor budding in cholangiocarcinoma. Therefore, we aimed to assess the prognostic value of tumor budding in intrahepatic and extrahepatic cholangiocarcinomas and to evaluate its correlations with other clinicopathological parameters.
Methods: We monitored 219 patients who underwent surgery for intrahepatic or extrahepatic cholangiocarcinoma at the Pusan National University Hospital between 2012 and 2021. Tumor budding was evaluated using the International Tumor Budding Consensus Conference scoring system. Tumor budding was classified into low (0–4), intermediate (5–9), and high (≥10). For statistical analysis, tumor budding was divided into two groups based on the cut-off value of 10 (lower: 0–9 vs. higher: ≥10). The correlations between clinicopathological parameters were examined using the chi-square and Fisher’s exact test. The prognostic values of the variables were analyzed using the log-rank test and Cox regression analysis.
Results: Low, intermediate, and high tumor buddings were identified in 135 (61.6%), 63 (28.8), and 21 (9.6%), patients, respectively. Higher tumor budding was related to the presence of lymphatic invasion (p = 0.017), higher tumor grade (p = 0.001), higher N category (p = 0.034). In the univariable and multivariable analyses, higher tumor budding was associated with shorter disease-free survival in 97 (44.3%) patients who underwent R0 resection (p < 0.001 and p = 0.011). Tumor budding did not significantly correlate with disease-specific survival in entire patients.
Conclusion: Tumor budding may serve as a prognostic factor for intrahepatic and extrahepatic cholangiocarcinomas treated with R0 resection.

背景：肿瘤芽变（tumor budding）在多种实体瘤中被视作预后相关因子，但目前针对胆管癌中肿瘤芽变的临床价值仍缺乏全面认知。因此，本研究旨在评估肿瘤芽变对肝内及肝外胆管癌的预后价值，并分析其与其他临床病理参数的相关性。
方法：本研究纳入2012年至2021年间于釜山国立大学医院接受手术治疗的219例肝内或肝外胆管癌患者。采用国际肿瘤芽变共识会议（International Tumor Budding Consensus Conference）评分系统评估肿瘤芽变，将其分为低级别（0~4分）、中级别（5~9分）与高级别（≥10分）三组。为开展统计学分析，以10分为截断值将肿瘤芽变划分为两组：低分组（0~9分）与高分组（≥10分）。采用卡方检验与Fisher确切概率法检验临床病理参数间的相关性；采用对数秩（log-rank）检验及Cox回归分析评估各变量的预后价值。
结果：本研究队列中，135例（61.6%）患者为低级别肿瘤芽变，63例（28.8%）为中级别，21例（9.6%）为高级别。高肿瘤芽变与淋巴管侵犯（p=0.017）、较高肿瘤分级（p=0.001）及更高N分期（p=0.034）显著相关。在单变量及多变量分析中，高肿瘤芽变与接受R0切除术的97例（44.3%）患者更短的无病生存期显著相关（p<0.001及p=0.011）。在全部研究患者中，肿瘤芽变与疾病特异性生存期无显著相关性。
结论：肿瘤芽变可作为接受R0切除术治疗的肝内及肝外胆管癌患者的预后评估因子。