Combined transcatheter arterial chemoembolization and local radiotherapy of unresectable hepatocellular carcinoma

Seong, Jinsil; Keum, Ki Chang; Han, Kwang Hyub; Lee, Do Yun; Lee, Jong Tae; Chon, Chae Yoon; Moon, Young Myoung; Suh, Chang‐Ok; Kim, Gwi Eon

doi:10.1016/s0360-3016(98)00415-5

Cited by 141 publications

(71 citation statements)

References 31 publications

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“…Although percutaneous ethanol injection, radiofrequency ablation, and TACE are generally effective for patients with one to three lesions <4 cm in diameter, they are not considered as a curative treatment and have achieved very limited success in eradicating larger hepatocellular carcinomas, and repeated treatments are often necessary until there is tumor progression to extensive disease (9)(10)(11)(12). With the development of three-dimensional conformal radiotherapy techniques, radiotherapy can be more safely given to patients with larger tumor-bearing parts of liver for whom percutaneous ethanol injection, radiofrequency ablation, and TACE are no longer possible (13)(14)(15)(16).…”

mentioning

confidence: 99%

Sublethal Irradiation Induces Vascular Endothelial Growth Factor and Promotes Growth of Hepatoma Cells: Implications for Radiotherapy of Hepatocellular Carcinoma

Chung

Jian²,

Cheng³

et al. 2006

Clinical Cancer Research

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Purpose: To investigate the clinical benefit of additional radiotherapy to patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoembolization (TACE) and the molecular effects of radiation on gene expression in hepatoma cells. Experimental Design: Between August 1996 and August 2003, 276 and 64 patients with American Joint Committee on Cancer stage T 3 N 0 M 0 hepatocellular carcinoma receiving TACE alone andTACE followed by three-dimensional conformal radiotherapy, respectively, at our institution were studied. Clinical outcome and pattern of failure were analyzed for the association of survival benefit with radiotherapy. The molecular effects of radiotherapy were studied in vitro and in vivo using human hepatoma cells with different p53 mutation and hepatitis B virus infection status. Results: Median follow-up and survival time in theTACE alone and TACE + radiotherapy groups were 39 and 19 months, and 51and 17 months, respectively. Additional radiotherapy toTACE did not improve overall survival (P = 0.65). However, different failure patterns were noted afterTACE and after radiotherapy. Although all irradiated tumors regressed substantially, radiotherapy rapidly enhanced both intrahepatic and extrahepatic tumor progression outside the radiotherapy treatment field in a significant portion of patients, which offset the benefit of radiotherapy on overall survival. In molecular analysis of the radiation effects on human hepatoma cells, radiotherapy rapidly induced p53-independent transcriptional up-regulation of vascular endothelial growth factor (VEGF), increased VEGF secretion in a dose-, time-, and cell type^dependent manner, and promoted hepatoma cell growth in vivo with enhanced intratumor angiogenesis, which correlated well with elevated levels of serumVEGF. Conclusions: Radiotherapy to eradicate a primary hepatocellular carcinoma might result in the outgrowth of previously dormant microtumors not included in the radiotherapy treatment field. Radiotherapy-inducedVEGF could be a paracrine proliferative stimulus.Therapeutic implications of the study justify the combination of three-dimensional conformal radiotherapy with anti-VEGF angiogenic modalities for the treatment of unresectable hepatocellular carcinoma to reduce relapses.

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confidence: 99%

Sublethal Irradiation Induces Vascular Endothelial Growth Factor and Promotes Growth of Hepatoma Cells: Implications for Radiotherapy of Hepatocellular Carcinoma

Chung

Jian²,

Cheng³

et al. 2006

Clinical Cancer Research

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“…To improve the therapeutic effect, RT was added after TACE in the TACE group based on previous reports (Seong et al 1999;Shim et al 2005), which showed better outcomes than with TACE alone. Compared to single TACE, these reports showed a good therapeutic result by adding RT after TACE.…”

Section: Discussionmentioning

confidence: 99%

Radiation Therapy Is a Reasonable Option for Improving the Prognosis in Hepatocellular Carcinoma

Kondo

Kimura

Kogure

et al. 2015

Tohoku J. Exp. Med.

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Radiation therapy (RT) may be suitable for treating patients with hepatocellular carcinoma (HCC) who are difficult to treat with any other option. However, it remains unclear whether RT extends survival in these patients. Among the 957 HCC patients treated at Tohoku University Hospital from January 2007 to December 2013, only 49 patients received RT. We therefore retrospectively analyzed the outcomes of these patients; they were divided into three groups based on the reasons for choosing RT: 27 patients at Stage IV A (67.1 ± 1.6 years, 50.5 ± 2.1 Gy), 9 patients with alternative therapy (72.2 ± 2.4 years, 58.9 ± 1.1 Gy), and 13 patients who received RT after transarterial chemoembolization (TACE) (75.6 ± 2.1 years, 56.5 ± 1.5 Gy). RT was employed to ensure the local control of the lesion. The patients at Stage IV A were treated with radical RT (n = 16) or with palliative RT (n = 11). In radical RT group, the response rate was 37.5% and the complete response rate was 25%. The survival rate was 12.5 ± 2.6 months after radical RT. This is considered relatively good for Stage IV A. The disease-free survival rate was 13.0 ± 2.8 months after RT. This excellent disease-free survival indicates that RT is an alternative to other treatments. In the TACE group, patients who received the RT had the significantly long disease-free survival rate than only-TACE (18.0 ± 3.8 months vs. 11.2 ± 0.58 months). We propose that RT is effective and safe for HCC.

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“…The objective response rate was 63.3%, and survival reached 67% and 22.2% at one and 3-years, with 17 months overall survival. 11 Although achieved in uncontrolled settings, subsequent studies compared TACE+3D-HDCRT to TACE monotherapy, and clearly isolated irradiation as an independent positive predictor of survival. The combination therapy gave higher response rates than TACE monotherapy (47.4% vs. 28.1%, P < .05), and additionally prolonged survival (19 vs. 10 months, P = .0001).…”

Section: Discussionmentioning

confidence: 99%

“…Of interest, toxicities were reduced, including only transient elevation of liver function tests in all patients, but without treatment-related death. 11,12 Subsequent studies compared TACE + 3D-HDCRT combination to TACE alone in retrospective analysis, and clearly isolated irradiation as an independent predictor of tumour response and prolonged survival. [13][14][15] In the present study, we showed that, for uninodular HCC developed in noncirrhotics or Child-Pugh A cirrhotics, the combination of TACE and 3D-HDCRT led to high complete response rates, low risk of local recurrence and acceptable toxicity.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of transarterial chemoembolization combined to conformal radiotherapy for uninodular hepatocellular carcinoma

Merle

Rode

Benlaredj

et al. 2014

Int J Cancer Ther Oncol

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Original ArticleAbstract Purpose: A proportion of patients with uninodular hepatocellular carcinoma (HCC) cannot benefit from potential curative therapies such as liver transplantation, surgical resection or radiofrequency ablation. Thus, they are prone to receive transarterial chemoembolization (TACE) that is a palliative option with low probability of both complete response and prolonged local control. Herein, we assessed the combination of TACE and 3D-high dose conformal radiotherapy (3D-HDCRT) for efficacy and safety in HCC. Methods: We retrospectively analyzed the outcome of 35 consecutive patients with uninodular HCC ≤ 100 mm, treated by one course of TACE combined to 3D-HDCRT. The follow-up consisted on clinics, biology, hepatic CT-scan or MRI at month-1 and -3, and thereafter every 3 months. Results: Complete response was obtained in 80% of patients following mRE-CIST criteria (95% in HCC ≤ 50 mm, and 60% in HCC > 50 mm) with uncommon local recurrence (11%), overall survival rates of 79%, 59% and 44% at respectively 1, 2 and 3 years (median, 37.3 months), and 11.4% grade-3/4 toxicities. Pre-therapeutic α-fetoprotein level ≥ 200 ng/mL was found as a strong predictor of poorer outcome. Conclusion: We showed that TACE combined to 3D-HDCRT can be highly efficient to reach local control and interesting overall survival rates for uninodular HCC, with limited severe toxicities for Child-Pugh A patients. Subsequent prospective controlled trials are warranted for comparison with therapeutic standards.

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Combined transcatheter arterial chemoembolization and local radiotherapy of unresectable hepatocellular carcinoma

Cited by 141 publications

References 31 publications

Sublethal Irradiation Induces Vascular Endothelial Growth Factor and Promotes Growth of Hepatoma Cells: Implications for Radiotherapy of Hepatocellular Carcinoma

Sublethal Irradiation Induces Vascular Endothelial Growth Factor and Promotes Growth of Hepatoma Cells: Implications for Radiotherapy of Hepatocellular Carcinoma

Radiation Therapy Is a Reasonable Option for Improving the Prognosis in Hepatocellular Carcinoma

Efficacy and safety of transarterial chemoembolization combined to conformal radiotherapy for uninodular hepatocellular carcinoma

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