Table 7.
Studies examining hepatic arterial infusion (HAI) for intrahepatic cholangiocarcinoma.
| HAI | |||||
|---|---|---|---|---|---|
| Author (Year) | Study Type and Time Period | Patient Population | Technique | Outcomes | Complications |
| Single Cohorts | |||||
| Huang (2022) [107] | Retrospective Study 12/2020–05/2021 |
N = 9 Mean age 55.3 y/o ChT and immunotherapy refractory, unresectable ICC Tumor size 3.3–13 cm |
HAI = FOLFIRI Mean # HAI cycles = 2.9 |
6 mo OS: 22.2% Median PFS = 5 mo |
Grade 3–4: 22% |
| Pietge (2021) [112] | Prospective Study 06/2012–01/2016 |
N = 12 ICC, Hilar CC and gallbladder cancer Median age 63.5 y/o |
HAI = FUDR + Systemic ChT = GC | Median OS = 23.9 mo Median PFS = 10.1 mo |
Serious adverse event N = 16 |
| Cercek (2020) [113] | Phase II Clinical Trial 05/2013–05/2019 |
N = 38 Median age 64 y/o Unresectable ICCTumor size 1.7–24.8 cm |
HAI = FUDR + Systemic ChT = GEMOX | Median OS = 25.0 mo Median PFS = 11.8 mo |
Grade 4 requiring removal from study: 11% |
| Kasai (2014) [118] | Retrospective Study 10/2008–07/2013 |
N = 20 Mean age 62.45 y/o Advanced ICC Tumor size 5.8–19 cm |
HAI = 5-fluorouracil + SubQ PEG-IFNα-2b | Median OS = 14.6 mo Median PFS = 8.0 mo |
Grade 4: 0% |
| Inaba (2011) [119] | Phase I/II Clinical Trial 05/2004–11/2006 |
N = 25 Median 58 y/o Unresectable ICC |
HAI = gemcitabine | Median OS = 340 days | Grade 4: 4% |
| Kemeny (2011) [120] | Retrospective Study | ICC N = 18 HCC N = 4 Unresectable ICC or HCC Tumor size 1.1–16.4 cm |
HAI = FUDR + dexamethasone + Systemic Bev | Median OS = 31.1 mo Median PFS = 8.45 mo |
Grade 3–4 events N = 32 |
| Jarnagin (2009) [121] | Phase II Clinical Trial 08/2003–03/2007 |
ICC N = 26 HCC N = 8 Mean age 56.5 y/o Unresectable ICC or HCC Tumor size 2.7–18.1 cm |
HAI = FUDR + dexamethasone | Median OS = 29.5 mo Median PFS = 7.4 mo |
Grade 3–4: 14.7% |
| Comparative Cohorts | |||||
| Franssen (2022) [106] | Retrospective Cohort Study 01/2001–12/2018 |
HAI N = 141 SR N = 178 Median age HAI 62 y/o Median age SR 60 y/o Multifocal ICC Median tumor size HAI, SR = 8.4 cm, 7.0 cm |
HAI = FUDR vs. SR Median # HAI cycles = 8 |
Median OS HAI = 20.3 mo Median OS SR = 18.9 mo (p = 0.32) |
HAI Grade 3A+: 6.4% SR Grade 3A+: 25.3% (p = 0.04) |
| Ishii (2022) [108] | Retrospective Cohort Study 04/2014–12/2020 |
HAI N = 18 ChT N = 24 Mean age 64 y/o Advanced ICC Tumor size 1–12.1 cm |
HAI = GEM-FP vs. Systemic ChT = GC |
Median OS HAI = 19.7 mo Median OS ChT = 10.8 mo (p = 0.006) |
HAI vs. ChT = ND except leukopenia > in ChT group |
| Zhang (2022) [109] | Retrospective Cohort Study 01/2021–03/2022 |
HAI N = 39 TACE N = 19 Unresectable ICC Included tumors >7 cm |
HAI = GEMOX vs. TACE |
Median PFS HAI = not reached by end of study Median PFS TACE = 11 mo |
HAI vs. TACE = ND |
| Cai (2021) [110] | Retrospective Cohort Study 03/2011–10/2019 |
HAI N = 57 TACE N = 69 Unresectable ICC Included tumors >5 cm |
HAI = mFOLFOX vs. TACE |
Median OS HAI = 19.6 mo Median OS TACE = 10.8 mo Median PFS HAI vs. TACE = ND |
Total HAI N = 26 Total TACE N = 9 |
| Jolissaint (2021) [111] | Retrospective Cohort Study 2008–2018 |
HAI N = 196 SR N = 237 ChT N = 140 ICC with LN metastasis Included tumors >10 cm |
HAI = FUDR vs. SR vs. Systemic ChT | LN (-) median OS: SR = 59.9 mo, HAI = 24.9 mo, ChT = 13.7 mo (p < 0.001) LN (+) median OS: SR vs. HAI = ND |
|
| Higaki (2018) [114] | Retrospective Cohort Study 2007–2011 |
HAI + ChT N = 12 Other N = 16 Unresectable ICC Median age HAI + ChT = 76 y/o Median age Other = 67 y/o Included tumors > 5 cm |
HAI + Systemic ChT vs Other treatment (radiation, TACE or systemic ChT alone) |
Median OS HAI + ChT = 10.1 mo Median OS Other = 4.0 mo |
Grade 3–4: 4.54% |
| Wright (2018) [115] | Retrospective Cohort Study 01/2004–06/2016 |
IAT N = 59 SR N = 57 Mean age IAT 61.9 y/o Mean age SR 64.9 y/o Multifocal ICC Included tumors > 10 cm |
IAT = HAI, TACE or TARE vs. SR | Median OS IAT = 16 mo (HA = 39 mo, TACE = 15 mo) Median OS SR = 20 mo |
|
| Konstantinidis (2016) [116] | Retrospective Cohort Study 01/2000–08/2012 |
HAI + ChT N = 78 ChT alone N = 26 Median age 62 y/o Unresectable ICC Tumor size 1.5–16.4 cm |
HAI = FUDR + Systemic ChT vs. Systemic ChT alone | Median OS HAI + ChT = 30.8 mo Median OS ChT alone = 18.4 mo |
|
| Konstantinidis (2014) [117] | Retrospective Cohort Study 08/2003–09/2009 |
N = 44 Mean 59 y/o Unresectable ICC Mean tumor size = 9.3 cm |
HAI = FUDR vs. FUDR + Bev | Median OS FUDR = 29.3 mo Median OS FUDR + Bev = 28.5 mo |
Grade 3–4: 22.7% |
Abbreviations: Bev = bevacizumab; CC = cholangiocarcinoma; ChT = chemotherapy; FOLFIRI = 5-fluorouracil + irinotecan; FUDR = floxuridine; GC = gemcitabine + cisplatin; GEM-FP = gemcitabine + cisplatin + 5-fluorouracil; GEMOX = gemcitabine + oxaliplatin; HAI = hepatic arterial infusion; HCC = hepatocellular carcinoma; IAT = intra-arterial therapy; ICC = intrahepatic cholangiocarcinoma; LN = lymph node; mFOLFOX = leucovorin + fluorouracil + oxaliplatin; mo = month; ND = no difference; OS = overall survival; PFS = progression-free survival; SR = surgical resection; SubQ = subcutaneous; TACE = transarterial chemoembolization; TARE = transarterial radioembolization; yr = year; y/o = years old.