Systematic Reviews
Copyright ©The Author(s) 2016.
World J Meta-Anal. Oct 26, 2016; 4(5): 105-117
Published online Oct 26, 2016. doi: 10.13105/wjma.v4.i5.105
Table 1 Summary of data points presented in relevant clinical trials
Ref.YearCountryResearch institutionStudy periodMINORS scoreIHP patients (n)Tumor detailsEligibility and exclusion criteriaIHP details and response rateMorbidity and mortalityComplications and toxicitiesLong-term survivalPrognostic factors
Olofsson et al[55]2014SwedenThe Swedish National Board of Health and WelfareApril 2005 to March 20111834YYYYYYY
Magge et al[56]2014United StatesUniversity of Pittsburgh Cancer InstituteNovember 2003 to February 20121291YNRYYYYY
Fukumoto et al[57]2014JapanThe Kobe University HospitalJanuary 1989 to December 20101268YYYNRYYY
Alexander et al[58]2009United StatesNCIJune 1994 to July 200512120YYYYYYY
van Iersel et al[59]2008NetherlandsLeiden University Medical CenterAugust 1994 to December 200412105YYYYYYY
Rizell et al[60]2008SwedenSahlgrenska University Hospital1985 to 20071127YYYYYYNR
Pingpank et al[61]2005United StatesNCIJuly 2001 to January 20041228YYYYYNRNR
Alexander et al[62]2003United StatesNCIDecember 1997 to August 20021229YYYYYYY
Y: Recorded data available; NR: Not reported; NCI: The National Cancer Institute; MINORS: Methodological index for non-randomized studies.
Table 2 Patient demographics and disease characteristics
Ref.Patients (n)Age(median)Male: FemalePrimary tumorPrimary tumor treatmentn (%)
Liver involvement n (%) or mean percentage (range)
Number of liver metastasesLargest liver metastases diameter (cm), median (range)Extra-hepatic metastases n (%)
ExcisionChemotherapyNo treatment< 5%25%-0%> 0%
Olofsson et al[55]3461 (17-77)15:19Ocular melanoma15 (44%)19 (56%)None31 (91%)3 (9%)None1-100 31 (91%) > 100 3(9%))2.35 (1.0-6.4)None
Magge et al[56]9154.3 (24-77)50:41CRC 54 (59.3%) Ocular melanoma 29 (32%) Others 8 (8.7%)NoneCRC 47 (87%)44 (48%)30% (5%-80%)9 (2-105)NRNR
Fukumoto et al[57]6860 (52-67)61:7HCC68 (100%)NRNoneNRNRNR≥ 48.3 (5.0-12.6)None
Alexander et al[58]12052 (22-74)41:79CRCNRNRNR20% (5%-75%)NR8 (1-50)NR
Iersel et al[59]105 ≤ 7078:27CRC4 (3.8%)51 (48.6%)50 (47.6%)NRNRNR< 10 71 (68%) ≥ 10 34 (32%)NR34 (32.4%)
Rizell et al[60]2753 (36-77)NRMelanomaNRNRNR6 (22%)11 (41%)10 (37%)NRNRNR
Pingpank et al[61]2849 (17-74)14:14Melanoma 13 CRC 2 Others 13NRNRNRNRNRNRNRNR8 (29%)
Alexander et al[62]2949 (26-73)15:14Ocular melanomaNRNRNR20 (69%)8 (28%)1 (3%)25 (4 ≥ 50)5.6 (2-14)NR
Table 3 Isolated hepatic perfusion details and response rate
Ref.Patients evaluable for response (n)IHP/PIHPIHP chemotherapy protocol
Patient response
Overall response (CR + PR, %)
DrugDosePerfusion temperaturePerfusion timeCourses per patient (n)Complete response (%)Partial response (%)Stable disease (%)Progressive disease (%)
Olofsson et al[55]34IHPMelphalan1 mg/kg40 °C60 min14 (12%)19 (56%)6 (18%)5 (15%)68%
Magge et al[56]68IHPMelphalan Oxaliplatin Oxaliplatin + 5FU1.5 mg/kg 40 mg/m2 5FU 200 mg/m240 °C60 min144 (64.7%)24 (35.3%)64.7%
Fukumoto et al[57]67PIHPMitomycin C and/or Doxorubicin20-40 mg/m2 60-120 mg/m2NR30-40 min1.51 (range 1-3)21 (31.3%)27 (40.3%)11 (16.4%)8 (11.9%)71.6%
Alexander et al[58]114IHPMelphalan TNF alone or both1.5 mg/kg 1 mg39.5 °C-40 °C60 min12 (1.8%)67 (58.8%)NRNR60.5%
van Iersel et al[59]97IHPMelphalan200 mg39.5 °C60 min13 (3.1%)49 (50.5%)23 (23.7%)22 (22.7%)53.6%
Rizell et al[60]27IHPMelphalan With or without TNF0.5, 1 and 2 mg/kg 30 μg≥ 40 °C40-60 min12 (7.4%)17 (63.0%)2 (7.4%)6 (22.2%)69.4%
Pingpank et al[61]27PIHPMelphalan2-3.5 mg/kgNR60 min2.642 (7.4%)6 (22.2%)NRNR29.6%
Alexander et al[62]29IHPMelphalan1.5 mg/kgNR60 min13 (10%)15 (52%)NRNR62%
NR: Not reported. IHP: Isolated hepatic perfusion; PIHP: Percutaneous isolated hepatic perfusion.
Table 4 Isolated hepatic perfusion morbidity and mortality
Ref.MortalityToxicity grade 3/4 (%)
Complications grade 3/4 (%)
BilirubinTransaminasesAlkaline phosphataseNeutropeniaPlateletsAnemiaHepatic artery obstructionHepatic failureBleedingHypotensionWound infection
Olofsson et al[55]NoneNRNRNRNRNRNR2.90%NRNRNRNR
Magge et al[56]3.30%20.50%50.00%3.40%2.30%18.20%50.00%NR5.70%NR0%3.40%
Fukumoto et al[57]NRNR77.90%NR44.10%NRNRNRNR1.50%NR8.80%
Alexander et al[58]4%46.70%55.80%4.20%0.80%10.00%NRNR3.30%0.80%5.80%2.50%
van Iersel et al[59]6%18.00%20.00%15.20%2.90%NRNR1.90%NR8.60%NRNR
Rizell et al[60]22%NRNRNRNRNRNRNRNRNRNRNR
Pingpank et al[61]None18.9% (hepatic toxicity)66.20%35.10%17.60%NRNRNRNRNR
Alexander et al[62]None65.5% (hepatic toxicity)NRNRNRNRNRNRNRNR
Pooled P 95%CI5.4% (2.5%-11.2%)10.3 (2%-39%)19.2 (8.7%-37.2%)31.9% (9.3%-68.1%)2.2% (0.7%-6.6%)4.5% (2.3%-8.4%)4.50% (1.8-11.1%)2.7% (0.3%-20.3%)5.7% (3.1%-10.2%)
NR: Not reported.
Table 5 Long-term survival outcomes after isolated hepatic perfusion
Ref.Median follow-up (mo)Median time to local progression (mo)Median time to systemic progression (mo)Median hepatic progression-free survival (mo)Overall survival
Median OS (mo from IHP)1-yr survival (%)2-yr survival (%)3-yr survival (%)4-yr survival (%)5-yr survival (%)
Olofsson et al[55]NR7 (0-31)13 (2-34)NR24NRNRNRNRNR
Magge et al[56]NRNRNRFor CRC group: 12 (10.53-13.47) For CR: 12 For PR: 12 (10.1-13.9) For SD: 12.5 (10.53-13.47)23 (15-28)NRNRNRNRNR
Fukumoto et al[57]20 (3-191)NRNRNR2580.6%NR35.7%NR27.6%
Alexander et al[58]78.1 (52.1-104.2)7.3 (6.5-8.0)NR25 (19.4-30.6)NR53%28%14%NR
van Iersel et al[59]NRNRNR717.4NR34%NRNRNR
Rizell et al[60]IHP I cohort: NR IHP II cohort: NR IHP III cohort: 7 (range 4-18)NRNRNR12.6 (2.5-57)NRNRNRNRNR
Alexander et al[62]11 (3-40)81212.1 (3-39+)NRNRNRNRNR
Median value (range)20 (12.1-25)
OS: Overall survival; NR: Not reported; CRC: Colorectal cancer; CR: Complete response; PR: Partial response; SD: Stable disease.
Table 6 Summary of prognostic factors presented in relevant clinical trials
Ref.YearPrognostic factors for responsePrognostic factors for TTLPPrognostic factors for PFSPrognostic factors for OS
Olofsson et al[55]2014NRYNRY
Magge et al[56]2014YNRNRY
Fukumoto et al[57]2014NRNRNRY
Alexander et al[58]2009YNRYY
van Iersel et al[59]2008YNRYY
Rizell et al[60]2008NRNRNRNR
Pingpank et al[61]2005NRNRNRNR
Alexander et al[62]2003YNRNRY
TTLP: Time to local progression; PFS: Progression free survival; OS: Overall survival; NR: Not reported.