Table 2. Selected studies of adjuvant chemotherapy/radiotherapy/chemoradiotherapy for intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma.
| Category | Reference | Regimen | Study type | Patients, n* intervention/observation | ICC | ECC |
|---|---|---|---|---|---|---|
| Adjuvant CT | (i) Sur et al. (2015)76; (ii) Miura et al. (2015)45; (iii) Reames et al. (2017)80; (iv) Schweitzer et al. (2017)81; (v) Lee et al. (2019)77; (vi) Altman et al. (2020)78 | (i) CT; (ii) CT; (iii) CIS/GEM/5-FU; (iv) GEM-based CT; (v) CT; (vi) CT | (i) Retrospective; (ii) Retrospective; (iii) Retrospective; (iv) Retrospective; (v) Retrospective; (vi) Retrospective | (i) 75/416; (ii) 985/1,766; (iii) 347/807; (iv) 39/171; (v) 1,189/1,624; (vi) 470/753 | (i) Positive LN subgroup OS: HR=0.54, p=0.037; positive margin subgroup: HR=0.44, p=0.002. (ii) T3/T4 subgroup mOS: 21.3 vs. 15.6 months, p<0.001; N1 subgroup mOS: 19.8 vs. 10.7 months, p<0.001; R1/R2 subgroup mOS: 19.5 vs. 11.6 months, p=0.006. (iii) T3/T4 subgroup OS: HR=0.44, p<0.01; N1 subgroup: HR=0.24, p<0.001. (iv) PSM cohort OS: HR=0.33, p=0.002. (v) high-risk subgroup OS: HR=0.66, p<0.001. (vi) N1 subgroup OS: HR=0.46, p=0.001 | (a) PCC; OS: HR=0.25, p=0.035. (b) ECC; positive LN subgroup OS: HR=0.85, p<0.05. (c) DCC; OS: HR=0.21, p=0.001; DFS: HR=0.34, p=0.002. (d) ECC; OS: HR=0.62, p=0.008; PFS, HR=0.62, p=0.007. (e) PCC; PSM cohort 5-year OS: 43.2% vs. 15.6%, p=0.001; 3-year RFS: 46.9% vs. 15.9, p=0.01. (f) ECC; OS: HR not reported, p=0.114; DFS: HR=1.64, p=0.035. (g) ECC; OS: HR=1.01, p=0.964; RFS: HR=0.9, p=0.693. (h) DCC; PSM cohort mOS: 26.3 vs. 43.3 months, p=0.340; mDFS: 15.5 vs. 14.7 months, p=0.790. (i) ECC; 5-year OS: 40.8% vs 44.6%, p=0.916; RFS, 30.9% vs. 38.4%, p=0.794. (j) PCC; early recurrence subgroup OS: HR=0.38, p=0.039. (k) PCC; OS: HR=0.47, p=0.001; DFS: HR=0.69, p=0.068 |
| (a) Murakami et al. (2009)97; (b) Hoehn et al. (2015)98; (c) Kim et al. (2016)92; (d) Im et al. (2016)95; (e) Mizuno et al. (2017)99; (f) Yin et al. (2018)100; (g) Ebata et al. (2018)101; (h) Bergeat et al. (2018)102; (i) Morino et al. (2019)103; (j) Zhao et al. (2020)104; (k) Im et al. (2021)94; | (a) GEM-based CT; (b) CT; (c) 5-FU/DOX/GEM; (d) 5-FU/CIS/GEM; (e) GEM monotherapy; (f) GEM/CIS/OXA/S-1/CAP; (g) GEM monotherapy; (h) GEM-based CT; (i) GEM/S-1; (j) GEM/S-1; (k) 5-FU/GEM-based CT | (a) Retrospective; (b) Retrospective; (c) Retrospective; (d) Retrospective; (e) Retrospective; (f) Retrospective; (g) RCT; (h) Retrospective; (i) Retrospective; (j) Retrospective; (k) Retrospective | (a) 18/20; (b) 444/5,739; (c) 27/102; (d) 90/168; (e) 67/113; (f) 40/40; (g) 117/108; (h) 56/122; (i) 57/49; (j) 25/310; (k) 67/90 | |||
| Adjuvant RT | (i) Shinohara et al. (2008)83; (ii) Jiang et al. (2010)84; (iii) Hammad et al. (2016)86; (iv) Zheng et al. (2018)85 | (i) RT; (ii) EBRT; (iii) RT; (iv) IMRT/VMAT | (i) Retrospective; (ii) Retrospective; (iii) Retrospective; (iv) Retrospective | (i) 286/948; (ii) 24/66; (iii) 525/2,372; (iv) 26/23 | (i) mOS: 11 vs. 6 months, p=0.014. (ii) OS: HR=0.48, p=0.013.(iii) PSM cohort OS: HR=1.01, p=0.923. (iv) OS: HR=0.27, p=0.011 | (a) ECC; OS: HR=0.89, p=0.074. (b) ECC; OS: HR=0.59, p=0.078; PFS, HR=0.57, p=0.045. (c) DCC; OS: HR=2.38, p=0.040; RFS: HR=1.42, p=0.361. (d) PCC; mOS: 22 vs. 23 months, p=0.978; mCSS, 17 vs 18 months, p=0.554. (e) ECC; OS: HR=0.49, p=0.085; LRFS, HR=0.31, p=0.043. (f) PCC; OS: HR=0.81, p=0.538; DFS: HR=1.32, p=0.368 |
| (a) Vern-Gross et al. (2011)91; (b) Im et al. (2016)95; (c) Kim et al. (2016)92; (d) Leng et al. (2017)93; (e) Kim et al. (2017)96; (f) Im et al. (2021)94 | (a) RT; (b) 3D-CRT; (c) EBRT; (d) RT; (e) RT; (f) EBRT/IMRT | (a) Retrospective; (b) Retrospective; (c) Retrospective; (d) Retrospective; (e) Retrospective; (f) Retrospective | (a) 473/1,018; (b) 29/168; (c) 9/102; (d) 762/1,155; (e) 23/36; (f) 18/90 | |||
| Adjuvant CRT | (i) Sur et al. (2015)76 | (i) CRT | (i) Retrospective | (i) 147/416 | (i) positive LN subgroup OS: HR=0.50, p=0.005; positive margin subgroup: HR=0.57, p=0.004 | (a) ECC; OS: HR=0.53, p=0.005; DFS: HR=0.55 p=0.005. (b) ECC; OS: HR=0.82, p<0.001. (c) DCC; OS: HR=0.25, p=0.024; DFS: HR=0.33, p=0.004. (d) PCC; OS: HR=0.46, p=0.003; PFS, HR=0.41, p=0.001. (e) PCC; OS: HR=0.26, p<0.001; DFS: HR=0.31, p<0.001 |
| (a) Kim et al. (2011)105; (b) Hoehn et al. (2015)98; (c) Kim et al. (2016)92; (d) Im et al. (2016)95; (e) Im et al. (2021)94 | (a) 5-FU-based CT+EBRT; (b) CRT; (c) 5-FU/CAP/GEM+EBRT; (d) 5-FU/CIS/GEM+3D-CRT; (e) 5-FU/GEM-based CT+EBRT/IMRT | (a) Retrospective; (b) Retrospective; (c) Retrospective; (d) Retrospective; (e) Retrospective | (a) 115/53; (b) 1,902/5,739; (c) 20/102; (d) 49/168; (e) 21/90 |
*Numbers of patients in the intervention/observation groups. i–vi are studies of adjuvant CT/RT/CRT in ICC; a–k are studies of adjuvant CT/RT/CRT in ECC. 3D-CRT, three-dimensional conformal radiotherapy; 5-FU, 5-Fluoropyrimidine; CAP, capecitabine; CIS, cisplatin; CRT, chemoradiotherapy; CSS, cancer-specific survival; CT, chemotherapy; DCC, distal cholangiocarcinoma; DFS, disease-free survival; DOX, doxorubicin; EBRT, external beam radiotherapy; ECC, extrahepatic cholangiocarcinoma; GEM, gemcitabine; HR, hazard ratio; ICC, intrahepatic cholangiocarcinoma; IMRT, intensity-modulated radiotherapy; LN, lymph nodes; LRFS, local recurrence-free survival; mOS, median OS; OS, overall survival; OXA, oxaliplatin; PCC, perihilar cholangiocarcinoma; PFS, progression-free survival; PSM, propensity score matching; RCT, randomized controlled trial; RFS, recurrence-free survival; RT, radiotherapy; VMAT, volumetric modulated arc therapy.