Supplementary Material for: Adjuvant Radiotherapy for Extrahepatic Cholangiocarcinoma: A Quality Assessment-Based Meta-Analysis

<b><i>Introduction:</i></b> The benefits of adjuvant radiotherapy (ART) for extrahepatic cholangiocarcinoma are uncertain largely because existing publications lack clear comparisons between ART and non-ART arms. <b><i>Methods:</i></b> PubMed, Medline, Embase, and the Cochrane library were systematically searched until December 2020. The primary endpoint was overall survival (OS). Sensitivity analysis was performed for studies with reliable comparability (i.e., no favorable prognosticators in the ART arm that could skew the data). <b><i>Results:</i></b> Twenty-three studies involving 1,731 patients with extrahepatic cholangiocarcinoma were reviewed. The overall median of all median prescribed doses was 50.4 Gy; brachytherapy or an intraoperative boost of 10–21 Gy was applied in 5 studies. The pooled 1-, 3-, and 5-year OS rates in the non-ART and ART arms were 69.2% versus 81.0%, <i>p</i> = 0.035; 34.3% versus 44.7%, <i>p</i> = 0.025; 25.6% versus 31.7%, <i>p</i> = 0.115, respectively. The corresponding pooled locoregional recurrence rates were 52.1% versus 34.9% (<i>p</i> = 0.014). The pooled rate of grade ≥3 gastrointestinal complications was 9.8%. Sensitivity analysis performed on 14 eligible studies showed that the ART arms had a lower pooled R0 rate (36.8% vs. 63.2%, <i>p</i> = 0.02) and a higher rate of positive lymph nodes (47.4% vs. 34.9%, <i>p</i> = 0.08). The pooled 1-, 3-, and 5-year OS rates in the non-ART versus ART arms of the selected studies were 78.2% versus 84.9%, <i>p</i> = 0.143; 38.5% versus 49.2%, <i>p</i> = 0.026; and 27.8% versus 34.5%, <i>p</i> = 0.11, respectively. <b><i>Conclusions:</i></b> ART was shown to improve OS in all studies and in those selected for their reliable comparability.

<b><i>引言：</i></b> 辅助放疗（adjuvant radiotherapy, ART）用于肝外胆管癌的获益尚不明确，这主要是因为现有文献缺乏辅助放疗组与非辅助放疗组之间的清晰对照。<b><i>方法：</i></b> 本研究系统检索了PubMed、Medline、Embase及Cochrane图书馆数据库，检索时限截至2020年12月。本研究的主要终点为总生存期（overall survival, OS）。针对可比性可靠的研究（即辅助放疗组未存在可导致数据偏倚的有利预后因素）开展了敏感性分析。<b><i>结果：</i></b> 本研究共纳入23项研究，涉及1731例肝外胆管癌患者。所有研究的中位处方放疗剂量的总体中位数为50.4 Gy；其中5项研究采用了近距离放疗（brachytherapy）或术中推量10~21 Gy的放疗方案。非辅助放疗组与辅助放疗组合并后的1年、3年、5年总生存率分别为69.2% vs 81.0%，<i>p</i>=0.035；34.3% vs 44.7%，<i>p</i>=0.025；25.6% vs 31.7%，<i>p</i>=0.115。两组合并后的局部区域复发率分别为52.1% vs 34.9%（<i>p</i>=0.014）。合并的≥3级胃肠道并发症发生率为9.8%。对14项符合入组标准的研究进行敏感性分析显示，辅助放疗组的合并R0切除率更低（36.8% vs 63.2%，<i>p</i>=0.02），淋巴结阳性率更高（47.4% vs 34.9%，<i>p</i>=0.08）。在该亚组分析中，非辅助放疗组与辅助放疗组的1年、3年、5年总生存率分别为78.2% vs 84.9%，<i>p</i>=0.143；38.5% vs 49.2%，<i>p</i>=0.026；27.8% vs 34.5%，<i>p</i>=0.11。<b><i>结论：</i></b> 本研究结果表明，无论是在所有纳入研究还是在符合可靠可比性标准的亚组研究中，辅助放疗（ART）均可改善肝外胆管癌患者的总生存期。