Jethwa Krishan R, Sannapaneni Shilpa, Mullikin Trey C, Harmsen William S, Petersen Molly M, Antharam Phanindra, Laughlin Brady, Mahipal Amit, Halfdanarson Thorvardur R, Merrell Kenneth W, Neben-Wittich Michelle, Sio Terence T, Haddock Michael G, Hallemeier Christopher L
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA.
Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
J Gastrointest Oncol. 2020 Dec;11(6):1408-1420. doi: 10.21037/jgo-20-245.
Although surgical resection is the preferred curative-intent treatment option for patients with non-metastatic, extra-hepatic biliary cancer (EBC), radiotherapy (RT) or chemoradiotherapy (CRT) may be utilized in select cases when surgical resection is not feasible. The purpose of this study is to report the efficacy and adverse events (AEs) associated with CRT for patients with locally advanced and unresectable EBC.
This was a retrospective cohort study of patients with EBC, including extra-hepatic cholangiocarcinoma or gallbladder cancer, deemed inoperable who received RT between 1998 and 2018. The median RT dose was 50.4 Gy in 28 fractions and 94% received concurrent 5-fluorouracil. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS) from the start of RT. The cumulative incidence of local progression (LP), locoregional progression (LRP), and distant metastasis (DM) were reported with death as a competing risk. Cox proportional hazards regression models were used to assess for correlation between patient and treatment characteristics and outcomes.
Forty-eight patients were included for analysis. The median OS was 12.0 months [95% confidence interval (CI): 2.3-73.2 months]. The 2-, 3-, and 5-year OS were 33% (95% CI: 22-50%), 20% (95% CI: 11-36%), and 7% (95% CI: 2-20%), respectively. The 2-year PFS, LP, LRP, and DM were 21% (95% CI: 12-36%), 27% (95% CI: 17-44%), 31% (95% CI: 20-48%), and 33% (95% CI: 22-50%), respectively. On univariate analysis, biologically effective dose (BED) >59.5 Gy was associated with improved OS [hazard ratio (HR): 0.40, 95% CI: 0.18-0.92, P=0.03] and PFS (HR: 0.37, 95% CI: 0.16-0.84, P=0.02) and primary tumor size (per 1 cm increase) was associated with worsened PFS (HR: 1.29, 95% CI: 1.02-1.63, P=0.04). BED >59.5 Gy remained associated with PFS on multivariate analysis (HR: 0.34, 95% CI: 0.15-0.78, P=0.01). Treatment-related grade 3+ acute and late gastrointestinal AEs occurred in 13% and 17% of patients, respectively.
RT is associated with 3- and 5-year survival in a subset of patients with unresectable EBC. Further exploration of the role of RT as part of a multi-modality curative treatment strategy is warranted.
尽管手术切除是无转移的肝外胆管癌（EBC）患者首选的根治性治疗方案，但在手术切除不可行的特定情况下，可采用放射治疗（RT）或放化疗（CRT）。本研究的目的是报告CRT治疗局部晚期和不可切除EBC患者的疗效和不良事件（AE）。
这是一项对EBC患者（包括肝外胆管癌或胆囊癌）的回顾性队列研究，这些患者被认为无法手术，并于1998年至2018年期间接受了RT。中位放疗剂量为50.4 Gy，分28次给予，94%的患者同时接受5-氟尿嘧啶治疗。采用Kaplan-Meier方法从放疗开始估计总生存期（OS）和无进展生存期（PFS）。报告局部进展（LP）、局部区域进展（LRP）和远处转移（DM）的累积发生率，并将死亡作为竞争风险。采用Cox比例风险回归模型评估患者和治疗特征与结局之间的相关性。
48例患者纳入分析。中位OS为12.0个月[95%置信区间（CI）：2.3 - 73.2个月]。2年、3年和5年OS分别为33%（95% CI：22 - 50%）、20%（95% CI：11 - 36%）和7%（95% CI：2 - 20%）。2年PFS、LP、LRP和DM分别为21%（95% CI：12 - 36%）、27%（95% CI：17 - 44%）、31%（95% CI：20 - 48%）和33%（95% CI：22 - 50%）。单因素分析中，生物等效剂量（BED）>59.5 Gy与OS改善相关[风险比（HR）：0.40，95% CI：0.18 - 0.92，P = 0.03]和PFS（HR：0.37，95% CI：0.16 - 0.84，P = 0.02），且原发肿瘤大小（每增加1 cm）与PFS恶化相关（HR：1.29，95% CI：1.02 - 1.63，P = 0.04）。多因素分析中，BED >59.5 Gy仍与PFS相关（HR：0.34，95% CI：0.15 - 0.78，P = 0.01）。治疗相关的3级及以上急性和晚期胃肠道AE分别发生在13%和17%的患者中。
RT与部分不可切除EBC患者的3年和5年生存率相关。有必要进一步探索RT作为多模式根治性治疗策略一部分的作用。
