TY - JOUR
TI - Comparative effectiveness of different transarterial embolization
therapies alone or in combination with local ablative or adjuvant
systemic treatments for unresectable hepatocellular carcinoma: A network
meta-analysis of randomized controlled trials
AU - Katsanos, Konstantinos
AU - Kitrou, Panagiotis
AU - Spiliopoulos, Stavros
AU - and Maroulis, Ioannis
AU - Petsas, Theodore
AU - Karnabatidis, Dimitris
JO - PLOS ONE
PY - 2017
VL - 12
TODO - 9
SP - null
PB - Public Library of Science
SN - null
TODO - 10.1371/journal.pone.0184597
TODO - null
TODO - Background
The optimal transcatheter embolization strategy for patients with
unresectable hepatocellular carcinoma (HCC) remains elusive. We
conducted a systematic review and network meta-analysis (NMA) of
different embolization options for unresectable HCC.
Methods
Medical databases were searched for randomized controlled trials
evaluating bland transarterial embolization (TAE), conventional TACE,
drug-eluting bead chemoembolization (DEB-TACE), or transarterial
radioembolization (TARE), either alone or combined with adjuvant
chemotherapy, or local liver ablation, or external radiotherapy for
unresectable HCC up to June 2017. Random effects Bayesian models with a
binomial and normal likelihood were fitted (WinBUGS). Primary endpoint
was patient survival expressed as hazard ratios (HR) and 95% credible
intervals. An exponential model was used to fit patient survival curves.
Safety and objective response were calculated as odds ratios (OR) and
accompanying 95% credible intervals. Competing treatments were ranked
with the SUCRA statistic. Heterogeneity-adjusted effective sample sizes
were calculated to evaluate information size for each comparison.
Quality of evidence (QoE) was assessed with the GRADE system adapted for
NMA reports. All analyses complied with the ISPOR-AMCP-NCP Task Force
Report for good practice in NMA.
Findings
The network of evidence included 55 RCTs (12 direct comparisons) with
5,763 patients with preserved liver function and unresectable HCC
(intermediate to advanced stage). All embolization strategies achieved a
significant survival gain over control treatment (HR range, 0.42-0.76;
very low-to-moderate QoE). However, TACE, DEB-TACE, TARE and adjuvant
systemic agents did not confer any survival benefit over bland TAE alone
(moderate QoE, except low in case of TARE). There was moderate QoE that
TACE combined with external radiation or liver ablation achieved the
best patient survival (SUCRA 86% and 96%, respectively). Estimated
median survival was 13.9 months in control, 18.1 months in TACE, 20.6
months with DEB-TACE, 20.8 months with bland TAE, 30.1 months in TACE
plus external radiotherapy, and 33.3 months in TACE plus liver ablation.
TARE was the safest treatment (SUCRA 77%), however, all examined
therapies were associated with a significantly higher risk of toxicity
over control (OR range, 6.35 to 68.5). TACE, DEB-TACE, TARE and adjuvant
systemic agents did not improve objective response over bland
embolization alone (OR range, 0.85 to 1.65). There was clinical
diversity among included randomized controlled trials, but statistical
heterogeneity was low.
Conclusions
Chemo-and radio-embolization for unresectable hepatocellular carcinoma
may improve tumour objective response and patient survival, but are not
more effective than bland particle embolization. Chemoembolization
combined with external radiotherapy or local liver ablation may
significantly improve tumour response and patient survival rates over
embolization monotherapies. Quality of evidence remains mostly low to
moderate because of clinical diversity.
ER -