Locoregional Treatment in Intrahepatic Cholangiocarcinoma: Which Treatment for Which Patient?
Abstract
:Simple Summary
Abstract
1. Introduction
2. Narrative Review about Current Data Regarding LRT of iCC
2.1. Radiofrequency Ablation (RFA) and Microwave Ablation (MWA)
Authors | Methods | Retrospective or Prospective Study | Patients (n) | Tumor (n) | Median Tumor Size (cm) | Number of Lesions | Extrahepatic Disease Patients (n) or % of Patients | Efficacy: Local Tumor Progression | Grade 3–5 Treatment Related Toxicities |
---|---|---|---|---|---|---|---|---|---|
One arm cohort | |||||||||
Butros [16] | RFA | Retrospective study | 7 | 9 | 2.4 (1.3–3.3) | 1–2 | 1/9 (11%) | No major complication | |
Fu [17] | RFA | Retrospective study | 17 | 26 | 4.4 (2.1–6.9) | 1–5 | 7% | 3/17 (17.6%) | 1 major compli- cation occurred (3.6%, 1 of 28 sessions) (pleural effusion) |
Kim [15] | RFA | Retrospective study | 13 | 17 | 0.8–8 | 1–2 | 6/17 (35.3%) | 1 patient died following liver abscess | |
Kim [18] | RFA | Retrospective study | 20 | 29 | 1.5 (0.7–4.4) | 6/29 (20.7%) | 2 major complications occurred (7%) (liver abscess, bile duct stenosis) | ||
Carrafiello [19] | RFA | Retrospective study | 6 | 6 | 3.45 (1.0–5.8) | 3/6 (50%) | No major complication | ||
Chiou [20] | RFA | Prospective cohort | 10 | 10 | 1.9–6.8 | 1 | 2/10 (20%) | No major complication | |
Haidu [21] | RFA | Retrospective study | 11 | 36 | 3 (0.5–10) | 3% | 3/36 (8%) | Major complication rate: 13% (3/23) (bleeding, pseudoaneurysm, pulmonary embolism) | |
Brandi [8] | RFA | Retrospective observational cohort study | 29 | 117 | 1.7 (0.5–4.8) | Local tumor progression-free survival: 9.27 months (7.34–11.15) | Major complication rate: 7% (8/117) (liver abscess, pleural effusion, biloma, intrahepatic hematoma) | ||
Díaz-González [9] | MWA (microwave) and RFA | Retrospective analysis | 27 | 2.1 | 1–2 | 0 | 21/27 (77.8%) | Data not known | |
Ni [11] | MWA | Retrospective study | 78 | 106 | 3.1 (0.8–5.0) | 1–3 | 0 | 3 patients (3.8%) had major complication (liver abscess, pleural effusion) | |
Takahashi [22] | 6 MWA and 44 RFA | Retrospective review | 20 | 50 | 1.8 (0.5–4.7) | 11/50 tumor Or 5/20 patients | No major complication | ||
Zhang [13] | MWA | Retrospective study | 107 | 171 | <5 | 1–3 | 3 patients (2.8%) presented major complication (pleural effusion, liver abscess) | ||
Xu [14] | MWA and RFA | Retrospective study | 18 | 25 | 2.8 (0.7–6.9) | 1–4 | 0 | 12/18 | 1 patient presented major complication (fever) |
Ge [23] | MWA | Retrospective study | 92 (compared to 183 TACE) | 3.3–8.1 | Data not known | ||||
Giorgio [24] | MWA versus RFA | Retrospective study | 71 36 RFA 35 MWA | 98 | 3.6 (2.2–7.2) | 0 | No major complication | ||
Xu [10] | MWA versus surgery | Retrospective study | 121 56 MWA 65 surgery | 2.7 (0.8–5.0) | 11/56 (19.6%) | MWA: rate of major complication was 5.6% (3/56) (hepatic failure, ascites, liver absces) | |||
Zhang [12] | Ablation vs. surgery | Retrospective study | 32 surgery 77 ablation | <5 | 0 | Major complication rate: 3.9% (3/77) (hepatic failure, liver abscesses) |
2.2. External Beam Radiotherapy (EBRT)
2.3. Intra-Arterial Treatment (IAT)
2.3.1. Yttrium-90 Microsphere Selective Internal Radiation Therapy
Authors | Retrospective or Prospective Study | Treatment Dose | Patients (n) | Extrahepatic Disease Patients (n) or % of Patients | Median Tumor Size (cm) | Efficacy | Grade 3–5 Treatment-Related Toxicities |
---|---|---|---|---|---|---|---|
Non-comparative arm | |||||||
Shimizu [25] | Retrospective study | Range: 46.6 Gy in 12 fractions to 74.0 Gy in 37 fractions 16 patients received concomitant CT | 37 | 5.7 (1.5–14) | The 1-year local control rate: 97.3% (95% CI: 92.0–100%) | 3 patients experienced grade 3 biliary tract infections | |
Smart [31] | Retrospective study | Median dose: 58.05 Gy (37.5–67.5) | 66 | 23/66 patients | 5.6 (2.5–16) | Disease recurrence: 42/66 (74%) Local failure: 5/66 | 11% (7/66) patients had grade 3 and 4 toxicities (thrombocytopenia, neutropenia, nausea, anorexia, abdominal pain, dehydration, fever, RILD) |
Kozak [27] | Retrospective study | Median dose: 40 Gy (26–50) Median fractions: 5 (1–5) | 40 | 4.2 (1.0–12.5) | Local failure: 12/40 | 16 patients (40%) experienced grade 3 toxicity (abdominal pain, infection, biliary complication, liver abscess, cholecystitis, elevated liver enzymes) | |
Kasuya [37] | Retrospective study | Carbon-ion radiotherapy Most commonly prescribed dose: 76 Gy in 20 fractions | 56 | 3.7 (1.5–11) | The 1-year local control rate: 79.4% (IC 95%: 62.7–89.2) | 1 patient died of liver failure, 3 patients had liver dysfunction, and 1 patient presented a bile duct stenosis | |
Shen [34] | Retrospective study | Median dose: 45 Gy (36–54) | 28 | The 1-year PFS rate: 50% | 28 patients had at least one grade 3 toxicity (gastrointestinal ulcers elevated liver enzyme, hematological toxicity). | ||
Cho [26] | Retrospective study | Concomitantly with chemotherapy: For IMRT: 45 Gy to the PTV For 3D-CRT: 45 Gy in 25 fractions to the PTV | 64 patients concomitantly with chemotherapy, and 56 underwent surgery | 0/120 patients | The 3-year locoregional failure-free survival: 50% for patients who underwent surgery after radio–chemotherapy | 7.8% (5/64) patients had grade 3 toxicities (nausea, vomiting, epigastric pain, gastric bleeding) | |
Weiner [28] | Prospective trial | Median dose: 55 Gy (40–55) | 26 patients but 12 HCC, 12 iCC and 2 mixed | 5.5 (1.6–12.3) | The 1-year local control rate: 91% 1-year PFS: 50% (95% IC: 29–69%) | 11 patients presented ≥ grade 3 toxicities (hematological toxicity, hepatic failure, abdominal pain, elevated liver enzymes, ascites, vomiting and skin fibrosis) | |
Hong [30] | Prospective trial | 83 patients: 44 HCC 39 iCC | 0 | 5.7 (1.9–12.0) For iCC: 6 (2.2–10.9) | 4 patients (4.8%) presented grade 3 toxicity (thrombocytopenia, liver failure, ascites, gastric ulcer and elevated bilirubin) | ||
Tao [38] | Retrospective study | 58.05 Gy (35–100) | 79 | 7.9 (2.2–17) | The 1-year local control rate: 81% | 4 patients had major complication (cholangitis, gastric bleeding) | |
Ohkawa [29] | Retrospective study | Median total proton dose: 72.6 Gy in 22 fractions for intrahepatic region | 20 12 curative 8 palliative (4 stage IV and 4 stage IIIC for which the irradiation was not sufficient due to a too-wide tumor size | 4/20 patients | 5.0 (1.5–14) | The 1-year local control rate: 88% for the curative group | 5% (1/20) patients had grade 3 toxicities (bone marrow suppression) |
Jung [32] | Retrospective study | 45 Gy in 3 fractions (range: 15 to 60 Gy in 1–5 fractions) SBRT alone or EBRT and SBRT | 58 | The 1-year local control rate: 85% | 6 patients (10%) experienced a toxicity ≥ grade 3 (cholangitis and bile duct stenosis, gastric perforation). | ||
Kim [39] | Retrospective study | In association with chemotherapy: 44 Gy (25–60): 5 fractions of 2–3 Gy | 92:25 in the arm chemo-radiation | 7.6 ± 3.9 | Disease control rate: 56% | Grade 3 neutropenia occurred in 3/25 patients (12%) Grade 3 thrombopenia occurred in 5 (20%) 6/25 (24%) patients had > grade 3 toxicities. | |
Ibarra [40] | Retrospective study | iCC: 30 Gy (22–50) 1–10 fractions | 32:21 HCC 11 iCC | 45.5% | The 1-year disease-free local progression: 50% | 9% (3/32) patients had grade 3 or 4 toxicities | |
Tse [33] | Prospective trial | 36 Gy (24–54) | 41:31 HCC and 10 iCC | 2/10 iCC | Tumor volume: 172 cm3 (10–465) | The 1-year local control rate: 65% (95% IC 44–79%) | 18 events of grade 3 or 4 toxicities were observed (liver toxicity and nausea) |
Yi [41] | Retrospective study | Chemoradiation | 176 | 0 | Response rate: 19.8% | Grade 3 thrombocytopenia occurred in 10.4% of patients |
Authors | Retrospective or Prospective Study | Patients (n) | Localisation | Patients with Extrahepatic Disease n (%) | Previous Treatment | Mean Activity (GBq) | Median Tumor size (cm) | Efficacy mOS or meanOS from the 1st RE | Grade 3–5 Treatment-Related Toxicities |
---|---|---|---|---|---|---|---|---|---|
Helmberger [42] | Prospective observational study | 1050 in the whole cohort 120 iCC | 36/120 (30%) | ICC patients: Chemotherapy: 39.2% received combined regimens based on gemcitabine Locoregional treatments: 34.2% (surgery for 26.7%) | mOS: 14.7 months (95% CI: 10.9–17.9) | Less than 2.5% patients presented grade 3–4 toxicities (gastritis, gastrointestinal ulcerations, radiation cholecystitis and REILD) | |||
Azar [43] | Retrospective review | 96 in whole cohort and 22 iCC | Bilobar: 63.6% Unilobar: 35.4% | 2/22 (9.1%) | 16/22 (72.7%): Surgery: 8/22 (36.4%) Radiotherapy: 5/22 (22.7%) Chemotherapy: 12/22 (54.5%) Locoregional treatment: 1/22 (4.5%) | 1.5 (0.5–2.8) | Data not known | ||
Bargellini [44] | Retrospective study SirSphere | 81 in whole cohort: 35 (42.2%) in group A: first-line treatment at first diagnosis or at recurrence after surgery 19 (23.5%) in group B: SIRT as consolidation treatment after radio-logical disease control following first-line chemotherapy 27 (33.3%) in group C: SIRT because of tumor progression after first-line chemotherapy | Bilobar: 49.4% | 8/81 (10%) | Surgery: 32/81 (39.5%) | 1.46 ± 0.49 | 59.8 ± 32.5 | mOS: 14.5 months (11.1–16.9) | No toxicity grade ≥ 3 was recorded |
Buettner [45] | Retrospective study | 115 92: SIR-Sphere 22: resin microsphere 1: with both | Bilobar: 72% | 27/115 (24%) | Chemotherapy: 91/115 (79%) | Median administered activity measurements were 1.6 GBq (IQR (interquartile range), 1.3–1.9 GBq) for patients who received resin microspheres and 2.6 GBq (IQR, 1.5–3.8 GBq; p = 0.0017) for patients who received glass microspheres. | 7.2 (5.4–10.0) | Median OS after treatment was 11 months (95% CI: 8–13) | 4 patients experienced grade 3 toxicity (4%) (REILD) |
Filippi [46] | Retrospective study | 20 SIR-Sphere | 8/20 (40%) | Chemotherapy: 11 patients Surgery (liver resection): 8 patients Ablation: 1 RT on metastatic site: 1 patient | 1.6 ± 0.4 GBq | meanOS 12.5 ± 1.5 months | Data not known | ||
Köhler [47] | Retrospective study | 46 SIR-Sphere | Bilobar: 63% | 14/46 (30.4%) | 30/46 (65.2%) Chemotherapy: 28 patients Immunotherapy: 1 Radiotherapy: 4 Liver resection: 9 TACE: 1 | Median: 1.74 (0.51–3.26) | mOS: 9.5 months (95% CI: 6.1–12.9) | Data not known | |
Edeline [36] | Phase 2 clinical trial SIRT in association with chemotherapy (GEMCIS) in 1st line | 41 | Unifocal: 34% | 7/41 (17%) (lung metastasis ≤ 1 cm) | Resection: 5 | The median dose delivered to the tumor was 317 Gy (range: 64–1673 Gy) | mOS: 22 months (95% CI: 14–52) | 29 patients (71%) experienced grade 3 or 4 toxicities (gastrointestinal, hematological, hepatobiliary and general toxicities). | |
White [48] | Prospective single-arm observational | 61 SIR-sphere (74%) and therasphere (26%) | Bilobar: 64% | 22/61 (36%) | Chemotherapy: 56/61 (92%) | mOS: 8.7 months (95% CI: 5.3–12.1) | 7 events of grade 3–4 toxicities (fatigue, fever and perturbation of liver function) | ||
Bourien [49] | Retrospective study | 64 | Bilobar: 56% | 10/64 (16%) | Resection: 15/64 (23%) Chemotherapy: 27/64 (42%) | 2.5 (0.6–7.7) | 7.7 (1.4–18.2) | 16.4 months (95% CI: 7.8–25.0) | 10 patients (16%) experienced grade 3 fatigue; 6 patients (9%) experienced grade 3 liver pain; 2 patients (3%) had grade 3 nausea; and 2 patients (3%) had hepatic failure. No grade 4 toxicity was reported |
Gangi [50] | Retrospective study | 85 | Bilobar: 36.5% Solitary tumor: 61.2% | 36/85 (42.4%) | Chemotherapy: 61/85 (71.8%) Liver resection: 14/85 (16.5%) Radiotherapy: 4/85 (4.7%) | Median delivered dose was 136.0 Gy | 12.0 months (95% CI: 8.0–15.2) | 1 patient developed a grade 3 toxicity (liver abscess) | |
Shaker [51] | Retrospective study | 17 9 SIR-sphere 8 therasphere | 5/17 (29.4%) | Chemotherapy: 5/17 patients | The thera-Sphere and SIR-Sphere groups were 158.2 ± 128.1 Gy and 34.5 ± 16.3 Gy, respectively | 7.4 cm ± 3.3 | mOS from the diagnosis 33.6 months (95% CI: 4–64.8) | Data not known | |
Reimer [52] | Retrospective study | 21 | Bilobar: 19% Solitary: 57% | 3/21 (14%) | 0 | Median survival was 15 months | One of the patients had an ulceration of gastric mucosa. | ||
Akinwande [53] | Retrospective study | 25 SIRT 15 TACE | 11/25 (44%) | Chemotherapy: 16/25 (64%) Surgery/ablation: 5/25 (20%) | 1.56 GBq (0.41–5.31) | TACE: 3/33 (9%) grade 3 or more treatment-related toxicities (grade 3 or more treatment related toxicities) SIRT: 4/39 (10%) grade 3 or more treatment-related toxicities (abdominal pain) | |||
Swinburne [54] | Retrospective study | 34, but 5 patients were excluded without histological confirmation of ICC | 11/29 (37.9%) | Surgery: 7 patients Chemotherapy: 15 patients TACE: 1 patient EBRT: 2 patients. | 6.8–4.1 | Median survival: 9.1 months (95% CI: 1.7–16.4) | No major toxicity was observed | ||
Jia [55] | Retrospective study | 24 | 1.6 ± 0.4 GBq. | 9.0 months (5.6–12.4) | Grade 3 toxicities were observed in 20.8% patients (5/24) (abdominal pain and vomiting) | ||||
Soydal [56] | Retrospective study | 16 | 3/16 (19%) | Chemotherapy: 9/16 patients TACE: 1 patient Surgery: 2 patients | Mean 1.7 ± 0.1 GBq | The median overall survival time was calculated as 293 ± 70 days (154–431, 95% CI) | Data not known | ||
Saxena [57] | Retrospective study | 25 | Bilobar: 80% | 12/25 (48%) | Liver resection: 10/25 (40%) Chemotherapy: 18/25 (72%) Ablation: 2/25 (8%) TACE/SIRT: 2/25 (8%) | 1.76 GBq (SD = 0.33; range, 1.0–2.21 GBq | Median survival: 9.3 months | 3/25 patients (12%) developed grade III albumin, alkaline phosphatase and bilirubin toxicity. 1 patient (4%) developed a duodenal ulcer. | |
Manceau [58] | Retrospective study Concomitantly with chemotherapy | 35 | Bilobar: 71.4% | 2.6 ± 1.4GBq | Mean: 7.85 ± 3.47 | Median OS was 28.6 months (95% CI: 21.8 to ∞) | 6/35 (17%) patients presented hepatic dysfunction 1 patient presented with grade 3 cholecystitis. |
2.3.2. Transarterial Chemoembolization (TACE)
Authors | Retrospective or Prospective Study | Chemotherapy | Patients (n) | Median Number of Tumor | Median Tumor Size (cm) | Localisation | Mean Number of Sessions/Patients | Extrahepatic Disease (%) of Patients | Efficacy | Grade 3–5 Toxicities |
---|---|---|---|---|---|---|---|---|---|---|
One arm | ||||||||||
Zhou [66] | Retrospective study | DEB-TACE Epirubicin | 88 | Bilateral 33% | 50% | ORR = 65.9% mOS 9 months | No grade 3–4 toxicity was observed | |||
Luo [67] | Prospective trial | DEB TACE | 37 | 5.7 (3–8.3) | Bilobar 27% Multifocal 67.6% | ORR = 66.7% after DEB-TACE treatment, mean OS of iCC patients was 376 days (95% CI: 341–412 days) | Data not known | |||
Goerg [68] | Retrospective study | 100 mg cisplatin (CDDP), 50 mg doxorubicin and 10 mg mitomycin C | 18 | Bilobar 52% | 3.4 | mOS: 13.3 months (0.95-CI 8.9–17.7 months ORR = 61% | 1 severe toxicity 2 patient deaths due to liver abscess and sudden cardiac arrest. | |||
Aliberti [69] | Prospective cohort | Doxorubicin DEBDOX and LIFDOX | 127 | 0 | Median OS of the LIFDOX group was 14.53 (95% confidence interval = 9.17–15.23) months. | DEBDOX: grade 3 toxicities were nausea/vomiting (24%) and fever (7%) LIFDOX: grade 3 toxicities were pain (7%). No grade 4 toxicity | ||||
Hyder [65] | Retrospective study | Gemcitabine + cisplatin/ Cisplatin + doxorubicin + mitomycin Gemcitabine alone Cisplatin alone | 198 TACE 128 DEB TACE 11 Embolization 13 RE 46 | mOS 13.2 months (95% CI 10.8–15.8) | 16.8% patients developed a major complication (acute renal and hepatic failure, pulmonary embolism and liver abscess). | |||||
Vogl [64] | Retrospective study | Mitomycin C Gemcitabine Mitomycin C and Gemcitabine Mitomycin C, Gemcitabine and Cisplatin | 115 | Bilobar 77.4% 59.6% multiple (>5) | Mean of 7.1 (range, 3–30) | 0 | mOS: 13 months | No major complication was reported. | ||
Kiefer [70] | Retrospective study | Mitomycin-C, doxorubicin and cisplatinum | 62 | Mean, 2.0; range, 1–4 | 19% | Median survival from time of first chemoembolization was 15 months | Major complications occurred following 5 of the 165 procedures (3%) (pulmonary edema and elevated cardiac enzymes post procedure, a pulmonary infarct, postembolization syndrome, acute renal failure and dehydration post procedure.) | |||
Schiffman [60] | Retrospective study | Irinotecan doxorubicin | 24 | 11.5 (4–33.3) | Median number of liver lesions was 3 but ranged from 1 to 25 lesions | 10% | ORR: 79% mOS: 17.5 months | 4 events of grade 3–5 toxicities were observed (hepatorenal syndrome led to death, sepsis from a port infection, hepatic insufficiency) | ||
Shitara [71] | Prospective cohort | Mitomycin | 7.8 (range 3.0–16.0) | Number of tumors 3 (1 × 1010) | ORR: 50.0% mOS: 4.1 months | 5 patients (25%) presented grade 3–4 toxicities (gastroduodenal ulcer, epigastralgia) | ||||
Gusani [72] | Retrospective study | GEMZAR CDDP OXALIPLATIN | 42 | 9.8 cm (range 1.3–17.0) | Median of 3.5 TACE treatments per patient (range 1–16) | 19% | Median overall survival from the date of first TACE treatment was 9.1 months | 2 patients presented grade 4 toxicities (acute myocardial infarction and hepatic abscess) | ||
Comparative arm | ||||||||||
Martin [62] | Prospective trial | IRINOTECAN and GEMCIS (GEMZAR and CISPLATIN) concomitant IV prospective, multicenter, open-label, randomized phase II study | 48 patients: 24 treated with GEMCIS and DEBIRI and 22 with GEMCIS alone | Median OS: 33.7 months (95% CI 13.5–54.5) | Data not known | |||||
Ge [23] | Retrospective study | Epirubicine + 5FU Comparison with MWA | mOS 26.9 months (6.6–44.2) | Data not known | ||||||
Wright [61] | Retrospective study | Surgery vs. IAT GEMCIS (63%) GEMZAR (19.5%) IRINOTECAN (4.9%) CDDP-DOXORUBICIN-MITOMYCIN C 2.1% | 59 patients underwent intra-arterial treatment (IAT) (41 = TACE, 16 = HAIC and 2 = SIRT ) vs. 57 patients who benefited from surgery | IAT: 5 (2–50) HAIC: 7 (2–50) TACE: 4 (2–27) | 10.6 (3.3–25.3) HAIC 9.4 (4.1–19.2) TACE 11.0 (3.3–25.3) | Bilobar: 88% HAIC 81.3% TACE 90.2% | Median of 3 for the whole cohort of IAT (1–15) | mOS for IAT: 16 months (95% CI 13.3–18.7, p = 0.627) For TACE: mOS: 15 months (95% CI 11.4–18.6) HAIC pump = 39 months (95% CI 32.7–51.3) | Data not known | |
Akinwande [53] | Retrospective study | SIRT: 25 TACE: 15 DOXORUBICIN | ORR 6% | TACE: 3/33 (9%) grade 3 or more treatment-related toxicities (fever and abdominal pain) SIRT: 4/39 (10%) grade 3 or more treatment-related toxicities (abdominal pain) | ||||||
Scheuermann [73] | Retrospective study | Surgery vs. TACE | 273 130 surgery 32 TACE 111 palliative | 8.7 (2.0–18.0) | Unilobar 13/32 | Median: 3 (range: 1–18 sessions) | Median survival of TACE patients: 11 months | 1 liver dysfunction (ascites) and 2 vascular complications (dissection or occlusion of the hepatic artery) | ||
Park [63] | Retrospective study | TACE vs. palliative treatment CDDP | 155 72 TACE 83 palliative | Mean 8.1 ± 3.4 | Bilobar 37/72 Multiple or diffuse 41/72 | 2.5 per patient (range: 1–17 sessions) | 12.2 months (95% CI 9.8–14.6) | 11 grade 3 hematological toxicities occurred in 9 patients (13%, 9/72), and 25 grade 3 non-hematological toxicities occurred in 17 patients (24%, 17/72) (elevation of liver enzymes, pain and nausea) |
2.3.3. Hepatic Arterial Infusion Chemotherapy (HAIC)
Authors | Retrospective or Prospective Study | Chemotherapy | Patients (n) | Tumor Size Median (cm) | Extrahepatic Disease (%) of Patients | Number of Sessions per Patient | Efficacy | Grade 3–5 Treatment Related Toxicities |
---|---|---|---|---|---|---|---|---|
Cercek [75] | Phase 2 clinical trial | HAIC floxuridine and systemic gemcitabine and oxaliplatin | 42 included and 38 treated | 8.3 (1.7–24.8) Bilobar: 66% | 18% | The median OS was 25.0 months (95% CI, 20.6-not reached) | The most common grade 3 and 4 adverse events were related to elevated liver enzymes (5% grade 4 elevated bilirubin level, 5% grade 4 elevated AST (aspartate aminotransferase), and 5% grade 4 elevated ALT (alanine aminotransferase)). No grade 4 non-biological toxicities were observed. | |
Marquardt [78] | Retrospective study | Melphalan | 15 | Range: 1–5 | Median OS was 26.9 months from initial diagnosis and 7.6 months from first PHP | 13 patients (50%) presented grade 3–5 toxicities (hematological, pneumonia, acute renal failure, ascites, bleeding, oedema, multi-organ failure, otitis, pseudoaneurysm and stroke) | ||
Higaki [76] | Retrospective study | CDDP + oral S1 | 12 | Multiple (35.7%) | Median survival time = 10.1 months (range, 3.6–23.2) | 1 patient (4.5%) experienced a grade 3 toxicity (anemia) | ||
Konstantinidis [79] | Retrospective study | 5FU pump concomitantly with chemotherapy IV | 167 | 8.5 cm (range: 1.5–16.4 cm) multifocal (63.5%) | mOS: 30.8 months | Data not known | ||
Massani [80] | Retrospective study | 11 | 0 | mOS: 17.6 months (6–40) | 4 patients experienced a major complication (hepatic decompensation and hand–foot syndrome) | |||
Kasai [77] | Retrospective study | Fluorouracil and oxaliplatin after placement of an + HAIC pump + PEG-IFNa-2b SC | 20 | 5% | Mean: 2 cycles (range: 1–8 cycles) | ORR 50% Median survival time: 14.6 months (95 % CI 5.5–16.8) | 6 patients experienced grade 3 hematological toxicity | |
Ghiringhelli [81] | Retrospective study | HAIC GEMOX | 12 | Multifocal 5/62 | ORR 66.6% (95% CI 29–100%) Median OS: 20.3 months (95% CI 13.2–49.7) | 7 grade 3–4 hematological adverse events and 6 grade 3–4 non-hematological adverse events were reported (oxaliplatin-related peripheral neuropathy, infection and oxaliplatin-allergy) | ||
Inaba [74] | Phase I/II clinical trial | HAIC GEMZAR | 11 | 9% | The incidence of adverse events of grade 3–4 was 20% neutropenia, 22% elevated liver enzymes, 4% nausea and 4% fatigue. | |||
Mambrini [82] | Retrospective study | EPIRUBICIN AND CDDP + CAPECITABINE oral | 20 | OS 18 months | One grade 5 toxicity (diarrhea) and one grade 3 toxicity (vomiting). | |||
Vogl [83] | Retrospective study | GEMZAR | 24 | OS 20.2 months | 1 severe adverse event occurred (allergic or toxic lung edema) | |||
Cantore [84] | Retrospective study | EPIRUBICIN + CDPP 5FU IV | 30 | Median 4 (2–8) | ORR 40% mOS 13.2 months | Grade 3 toxicity observed in 11 of 30 patients (37%) (hematological toxicity, stomatitis, nausea, diarrhea, alopecia) | ||
Tanaka [85] | Retrospective study | Epirubicin and cisplatin 5FU | 11 | Mean tumor size: 7.0 ± 2.6 cm (range: 3.8–13.5) | 4% | One severe cholangitis was observed |
2.3.4. Comparisons of the Different Intra-Arterial Therapies
2.4. Existing Guidelines
2.4.1. NCCN (National Comprehensive Cancer Network)
2.4.2. ESMO (European Society for Medical Oncology)
3. Which Treatment for Which Patient?
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Bourien, H.; Pircher, C.C.; Guiu, B.; Lamarca, A.; Valle, J.W.; Niger, M.; Edeline, J. Locoregional Treatment in Intrahepatic Cholangiocarcinoma: Which Treatment for Which Patient? Cancers 2023, 15, 4217. https://doi.org/10.3390/cancers15174217
Bourien H, Pircher CC, Guiu B, Lamarca A, Valle JW, Niger M, Edeline J. Locoregional Treatment in Intrahepatic Cholangiocarcinoma: Which Treatment for Which Patient? Cancers. 2023; 15(17):4217. https://doi.org/10.3390/cancers15174217
Chicago/Turabian StyleBourien, Héloïse, Chiara Carlotta Pircher, Boris Guiu, Angela Lamarca, Juan W Valle, Monica Niger, and Julien Edeline. 2023. "Locoregional Treatment in Intrahepatic Cholangiocarcinoma: Which Treatment for Which Patient?" Cancers 15, no. 17: 4217. https://doi.org/10.3390/cancers15174217