Severity and timing of progression predict refractoriness to transarterial chemoembolization in hepatocellular carcinoma

Kim, Hwi Young; Park, Joong-Won; Joo, Jungnam; Jung, Seonghoon; An, Sangbu; Woo, Sang Myung; Kim, Hyun Beom; Lee, Kyung-Hun; Lee, Woojin; Kim, Chang Min

doi:10.1111/j.1440-1746.2011.06963.x

Cited by 62 publications

(76 citation statements)

References 24 publications

(54 reference statements)

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“…In contrast, the JSH definition does not consider the number of TACE procedures, a factor that we believe is appropriate for on-demand TACE. The Asian Expert Panel on Interventions in HCC (EPOIHCC) recommends that TACE refractoriness be defined as no response after >3 TACE procedures within a 6-month period [18,21]. To the best of our knowledge, no information exists about TACE conversion to sorafenib in intermediate-stage HCC patients who are defined as TACE-refractory by the EPOIHCC.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Sorafenib in Intermediate-Stage Hepatocellular Carcinoma Patients Refractory to Transarterial Chemoembolization

Ogasawara

Chiba²,

Ooka³

et al. 2014

Oncology

166

169

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Objective: We compared the benefits of sorafenib therapy with continued transarterial chemoembolization (TACE) in TACE-refractory patients with intermediate-stage hepatocellular carcinoma (HCC). Methods: This retrospective study reviewed intermediate-stage HCC patients who underwent the first TACE. Patients were defined as TACE-refractory and divided into two cohorts: (1) patients who switched from TACE to sorafenib and (2) those who continued TACE. We evaluated the patient overall survival (OS) and time to disease progression (TTDP; the time patients reached Child-Pugh C or developed advanced-stage HCC). Results: A total of 509 patients with HCC underwent TACE. Of 249 intermediate-stage HCC patients undergoing the first TACE, 122 were deemed refractory. At the time they were identified as refractory, 20 patients converted to sorafenib, whereas 36 patients continued TACE. We excluded patients with Child-Pugh scores of ≥8, those with advanced-stage HCC, those who had undergone hepatic arterial infusion chemotherapy or other systemic therapy, and those treated with best supportive care alone. The median TTDP and OS were 22.3 and 25.4 months, respectively, in the conversion group, and 7.7 and 11.5 months, respectively, in the continued group (p = 0.001 and p = 0.003, respectively). Conclusions: It is possible that sorafenib conversion might prolong OS and TTDP in TACE-refractory patients with intermediate-stage HCC.

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Section: Discussionmentioning

confidence: 99%

Efficacy of Sorafenib in Intermediate-Stage Hepatocellular Carcinoma Patients Refractory to Transarterial Chemoembolization

Ogasawara

Chiba²,

Ooka³

et al. 2014

Oncology

166

169

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“…Using vascular invasion and/or extrahepatic metastases as a definition for stage progression, Kim et al [15] noted that the development of stage progression or a requirement of 3 sessions of TACE within 6 months were predictive of TACE refractoriness. Therapeutic response early in the clinical course after starting TACE is thought to be important for predicting TACE-refractory patients.…”

Section: Discussionmentioning

confidence: 99%

Tumor Markers AFP, AFP-L3, and DCP in Hepatocellular Carcinoma Refractory to Transcatheter Arterial Chemoembolization

Hiraoka¹,

Ishimaru²,

Kawasaki

et al. 2015

Oncology

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Background/Aim: We examined tumor marker levels to assess in more detail transcatheter arterial chemoembolization (TACE)-refractory hepatocellular carcinoma (HCC). Materials and Methods: We enrolled patients treated from 2000 to 2011 for HCC beyond the Milan criteria who had good hepatic reserve function (Child-Pugh A) and no portal vein thrombosis or metastases (n = 154). The modified criteria for being TACE-refractory according to the Liver Cancer Study Group of Japan (m-LCSGJ), from which the tumor marker item was excluded, and the Assessment for Retreatment with TACE (ART) score were used for determining whether the HCC was TACE refractory. α-Fetoprotein ≥100 ng/ml, fucosylated α-fetoprotein ≥10%, and des-gamma-carboxy prothrombin ≥100 mAU/ml were used to define whether tumor markers were positive. We added up the number of positive tumor markers as a prognostic score to assess in more detail the evaluation of TACE-refractory HCC. Results: In order to divide the patients into a refractory and nonrefractory group, the m-LCSGJ criteria [mean survival time (MST) 27.1 vs. 49.9 months; p < 0.001] were superior to the ART score (MST 22.0 vs. 35.1 months; p = 0.051). In the refractory group according to the m-LCSGJ criteria, the patients with a low score of positive tumor markers (<2) after 2 sessions of TACE (n = 36) showed a better prognosis than the others (n = 72) (MST 37.7 vs. 23.2 months; p = 0.014). Conclusion: Patients being nonrefractory according to the m-LCSGJ criteria had a better response, and using the number of tumor markers (≥2) is an easy method for predicting the response to TACE and for a more detailed evaluation of TACE-refractory HCC.

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“…The primary outcome is OS, and the secondary outcome variables include the time to progression (TTP), tumor response rate, progression-free survival, and safety. Notably, the inclusion criteria comprise advanced-stage HCC and TACE-refractory HCC, which was defined as either disease progression or the requirement for three sessions of repeated TACE within the first 6 months after the initial TACE treatment, as described earlier [46]. …”

Section: Future Directions For Lrt-mta Combination Strategiesmentioning

confidence: 99%

“…Moreover, the definition of “TACE refractoriness” has not been established. A recent cohort study of 264 TACE-treated patients suggested that disease progression during the first 6 months from the initial TACE treatment or a requirement for three sessions of repeated TACE within the first 6 months might be considered criteria for TACE refractoriness [46]. Because TACE refractoriness is an ill-defined concept, further investigations are urgently warranted to define and overcome this phenomenon in the near future and to verify whether a combined approach of TACE and MTA might be an effective therapeutic option for TACE refractoriness.…”

Section: Future Directions For Lrt-mta Combination Strategiesmentioning

confidence: 99%

Clinical Trials of Combined Molecular Targeted Therapy and Locoregional Therapy in Hepatocellular Carcinoma: Past, Present, and Future

Kim

Park

2014

Liver Cancer

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Background: Sorafenib, a multikinase inhibitor that targets angiogenesis in hepatocellular carcinoma (HCC), has become a standard treatment for advanced-stage HCC and has shown survival benefits in recent clinical trials. Transarterial chemoembolization (TACE) and sorafenib are currently standard treatments for intermediate and advanced-stage HCC, respectively. Combined locoregional therapy, including TACE and molecular targeted therapies such as sorafenib, is an issue under active investigation in an attempt to improve the outcomes of patients with unresectable HCC. Summary: Various clinical trials of these combined strategies have been conducted; however, the designs of these studies are diverse in terms of treatment modalities and schedules; comparisons with controls, baseline tumor stages, and hepatic functional reserves; and outcome measures. Key Messages: This article reviews heterogeneity in the design of recent clinical trials of combined locoregional and molecular targeted therapies and briefly addresses future study directions.

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Severity and timing of progression predict refractoriness to transarterial chemoembolization in hepatocellular carcinoma

Abstract: SP-free survival can be regarded as an end-point for TACE refractoriness. Development of progression or need for three sessions of TACE within the first 6 months could be predictive of TACE refractoriness.

Cited by 62 publications

References 24 publications

Efficacy of Sorafenib in Intermediate-Stage Hepatocellular Carcinoma Patients Refractory to Transarterial Chemoembolization

Efficacy of Sorafenib in Intermediate-Stage Hepatocellular Carcinoma Patients Refractory to Transarterial Chemoembolization

Tumor Markers AFP, AFP-L3, and DCP in Hepatocellular Carcinoma Refractory to Transcatheter Arterial Chemoembolization

Clinical Trials of Combined Molecular Targeted Therapy and Locoregional Therapy in Hepatocellular Carcinoma: Past, Present, and Future

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