Additional Transarterial Chemoembolization Research Articles

Characteristics and Prognosis of Patients with Advanced Hepatocellular Carcinoma Treated with Atezolizumab/Bevacizumab Combination Therapy Who Achieved Complete Response.

To investigate the characteristics and prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Atz/Bev) who achieved a complete response (CR) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). A total of 120 patients with Eastern Cooperative Oncology Group performance status (PS) 0 or 1 and Child-Pugh A at the start of Atz/Bev treatment were included. Barcelona Clinic Liver Cancer stage C was recorded in 59 patients. The CR rate with Atz/Bev alone was 15.0%. The median time to CR was 3.4 months, and the median duration of CR was 15.6 months. A significant factor associated with achieving CR with Atz/Bev alone was an AFP ratio of 0.34 or less at 3 weeks. Adding transarterial chemoembolization (TACE) in the six patients who achieved a partial response increased the overall CR rate to 20%. Among the 24 patients who achieved CR, the median progression-free survival was 19.3 months, the median overall survival was not reached, and 14 patients (58.3%) were able to discontinue Atz/Bev and achieve a drug-free status. Twelve of these patients developed progressive disease (PD), but eleven successfully received post-PD treatments and responded well. Achieving CR by mRECIST using Atz/Bev alone or with additional TACE can be expected to offer an extremely favorable prognosis.

Hepatic arterial infusion chemotherapy for hepatocellular carcinoma refractory to transarterial chemoembolization: exploring the influence of prior transarterial chemoembolization and additional transarterial chemoembolization on survival outcomes.

The selection of an efficacious treatment modality for patients with hepatocellular carcinoma (HCC) diagnosed as refractory to transarterial chemoembolization (TACE) presents numerous challenges. In addition to systemic therapies, hepatic arterial infusion chemotherapy (HAIC) may serve as an alternative option. However, it is imperative to identify patients who are appropriate candidates for HAIC to confer a survival benefit. Our study aimed to evaluate the impact of the number of TACE sessions prior to HAIC treatment and the addition of TACE during HAIC on the survival of HCC patient's refractory to TACE. This retrospective study included 82 patients with HCC refractory to TACE (mean age 60.5 years, 75 males). Survival analysis was conducted using the Kaplan-Meier method, with comparison between two groups via the log-rank test; the Cox regression model was utilized to identify factors influencing survival. The overall response rate (ORR) was observed to be 29.3%, with a disease control rate (DCR) of 56.1%. Patients receiving more than four TACE sessions prior to HAIC exhibited a significantly poorer survival prognosis compared to those receiving fewer than four TACE sessions, with a hazard ratio (HR) of 0.151 (P=0.02). The median overall survival (OS) was markedly different, being 3.4 (range, 0.5-13.6) months for the former group and 14 (range, 8.5-19.5) months for the latter (P=0.01). Furthermore, patients undergoing additional TACE while receiving HAIC treatment demonstrated improved survival outcomes compared to those who did not, with an HR of 0.491 (P=0.02); the respective OS for these groups was 14 (range, 3.6-14.4) and 6.7 (range, 2.8-11) months (P=0.02). HAIC can be a suitable alternative treatment for HCC patient's refractory to TACE. For those with a history of more than 4 TACE sessions, other alternative treatments should be considered. The addition of TACE during HAIC treatment may extend patient OS time, provided it is balanced with maintaining safe liver function.

Significance of Physical Status and Liver Function Reserve for Outcome of Patients with Advanced Hepatocellular Carcinoma Receiving Lenvatinib Treatment.

Tyrosine kinase inhibitors (TKIs) remain the primary therapeutic option for patients with advanced-stage hepatocellular carcinoma (HCC). However, the selection of a suitable TKI is an issue in real-world clinical practice. Thus, this study aimed to identify patients most likely to benefit from lenvatinib treatment. A retrospective review of 143 patients with unresectable advanced-stage HCC treated with lenvatinib between January 2020 and December 2021 was performed. Outcomes related to lenvatinib treatment were measured, and the clinical parameters affecting prognosis were analyzed. Overall, the median time of progression-free survival (PFS) and overall survival (OS) were 7.1 months and 17.7 months, respectively. Prognostic analyses found that Child-Pugh score > 5 (hazard ratio [HR] = 2.43, 95% confidence interval [CI] = 1.55-3.80, p = 0.001) was a significant factor affecting the PFS of HCC after lenvatinib treatment. Child-Pugh score > 5 (HR = 2.12, 95% CI = 1.20-3.74, p = 0.009), body weight ≥ 60 kg (HR = 0.54, 95% CI = 0.32-0.90, p = 0.020), and additional trans-arterial chemoembolization (TACE) treatment (HR = 0.38, 95% CI = 0.21-0.70, p = 0.003) were significant prognostic factors for OS. However, early α-fetoprotein reduction was not significantly correlated with patient outcomes. Additionally, patients with pre-treatment neutrophil-lymphocyte ratio > 4.07 showed a significant worse PFS and OS than other patients. The outcome of patients with advanced-stage HCC remains poor. However, the host condition, including good physical status and better functional liver preservation, largely affected the outcome of patients receiving lenvatinib treatment. Moreover, additional locoregional therapy for intrahepatic HCC, other than TKI treatment, can be considered in certain patients to achieve a favorable outcome.

Comparison of Drug-Eluting Embolics versus Conventional Transarterial Chemoembolization for the Treatment of Patients with Unresectable Hepatocellular Carcinoma: A Cost-Effectiveness Analysis

PurposeTo compare the cost-effectiveness of using doxorubicin-loaded drug-eluting embolic (DEE) transarterial chemoembolization versus that of using conventional transarterial chemoembolization for patients with unresectable hepatocellular carcinoma (HCC). Materials and MethodsA decision-analysis model was constructed over the lifespan of a payer’s perspective. The model simulated the clinical course, including periprocedural complications, additional transarterial chemoembolization or other treatments (ablation, radioembolization, or systemic treatment), palliative care, and death, of patients with unresectable HCC. All clinical parameters were derived from the literature. Base case calculations, probabilistic sensitivity analyses, and multiple two-way sensitivity analyses were performed. ResultsIn the base case calculations for patients with a median age of 67 years (range for conventional transarterial chemoembolization: 28–88 years, range for DEE-transarterial chemoembolization: 16–93 years), conventional transarterial chemoembolization yielded a health benefit of 2.11 quality-adjusted life years (QALY) at a cost of $125,324, whereas DEE-transarterial chemoembolization yielded 1.71 QALY for $144,816. In 10,000 Monte Carlo simulations, conventional transarterial chemoembolization continued to be a more cost-effective strategy. conventional transarterial chemoembolization was cost-effective when the complication risks for both the procedures were simultaneously varied from 0% to 30%. DEE-transarterial chemoembolization became cost-effective if the conventional transarterial chemoembolization mortality exceeded that of DEE-transarterial chemoembolization by 17% in absolute values. The two-way sensitivity analyses demonstrated that conventional transarterial chemoembolization was cost-effective until the risk of disease progression was >0.4% of that for DEE-transarterial chemoembolization in absolute values. Our analysis showed that DEE-transarterial chemoembolization would be more cost-effective if it offered >2.5% higher overall survival benefit than conventional transarterial chemoembolization in absolute values. ConclusionsCompared with DEE-transarterial chemoembolization, conventional transarterial chemoembolization yielded a higher number of QALY at a lower cost, making it the more cost-effective of the 2 modalities.

The Model to Estimate Survival in Ambulatory Hepatocellular Carcinoma Patients Aids in the Decision for TACE Retreatment.

Transarterial chemoembolization (TACE) is a major therapeutic modality for patients with unresectable hepatocellular carcinoma, which needs repeated treatments. Model to Estimate Survival in Ambulatory Hepatocellular carcinoma patients (MESIAH) was recently developed as a model for predicting survival. We aimed to develop a novel index for TACE retreatment using MESIAH scores. From 2005 to 2008, 783 patients with hepatocellular carcinoma who had undergone 1 previous TACE procedure were enrolled. We calculated their pre-TACE and post-TACE-MESIAH and calculated the MESIAH ratio by dividing the post-TACE by pre-TACE score. The discriminatory abilities of the MESIAH ratio and post-TACE-MESIAH were compared with ART and ABCR scores. Among 783 patients, 355 (45.3%) received a second TACE (test set), and 195 (24.9%) patients received a third TACE treatment (validation set). In the test set, patients with a MESIAH ratio <0.9 obtained longer overall survival than patients with a MESIAH ratio ≥0.9 [26.0 vs. 9.0 mo, respectively; hazard ratio 1.66 (1.29-2.14)], and patients with a post-TACE-MESIAH<4.5 showed longer overall survival than patients with a post-TACE-MESIAH≥4.5 [38.0 vs. 7.0 mo, respectively; hazard ratio, 3.17 (2.45-4.09)]. The post-TACE-MESIAH [C-index 0.663 (0.628-0.697)] was better than the ART [C-index 0.596 (0.554-0.638)] and ABCR scores [C-index 0.576 (0.536-0.617)] at estimating prognosis. Our results were confirmed by the validation set. A MESIAH score ≥4.5 after TACE identifies patients with a poor prognosis. Randomized studies are needed to establish whether additional TACE may affect survival.

Transarterial Chemoembolization Followed by Radiotherapy Versus Sandwich Treatment for Unresectable or Ablative Hepatocellular Carcinoma.

Objective:Our objective is to assess whether the outcome of intrahepatic unresectable or ablative hepatocellular carcinoma (HCC) could be improved by supplemental transarterial chemoembolization (TACE) following initial treatment of TACE with 3-dimensional conformal radiotherapy (3DCRT), compared to TACE followed by 3DCRT alone.Methods:We retrospectively analyzed intrahepatic unresectable or ablative HCC patients who underwent TACE, followed by 3DCRT with or without additional TACE, from June 2010 to December 2016 at our institution. Survival was assessed using the Kaplan-Meier method and compared with the log-rank test. Cox regression analyses were used to identify factors that influenced prognosis. Toxicity profiles were evaluated using CTCAE 4.0.Results:27 patients received TACE with 3DCRT (TR group) and 11 received additional TACE following TACE and 3DCRT (sandwich group), respectively. The median intrahepatic progression-free survival (IPFS), progression-free survival (PFS), and overall survival (OS) in the TR group and sandwich group were 5.4 months vs. 17 months (P = 0.018), 5.4 months vs. 17 months (P = 0.008), and 13.5 months vs. 29.2 months (P = 0.011), respectively. Multivariate Cox regression demonstrated that TACE followed by radiotherapy alone had a shorter IPFS (HR: 2.516, 95% CI (1.136-5.570), P = 0.023) and PFS (HR: 2.637, 95% CI (1.182-5.880), P = 0.018) compared with the sandwich treatment. Hepatitis B virus reactivation occurred in 1 patient in the sandwich group. Myleosuppresion was considered a grade 3/4 adverse event.Conclusion:Unresectable or ablative HCC patients possibly benefit from the combination of TACE and 3DCRT followed by additional TACE therapy, compared with TACE followed by 3DCRT alone.

Single-session combined radiofrequency ablation and transarterial chemoembolization in the treatment of hepatocellular carcinoma

Aim of the studyTo evaluate the efficacy of the combined use of both transarterial chemoembolization (TACE) and percutaneous radiofrequency ablation (RFA) in a single session for the treatment of large (≥3 cm in diameter) hepatocellular carcinoma. Patients and methodsThis study was carried out on 30 patients (23 males and 7 females, with age range between 46 and 74 years), with either solitary or multiple hepatocellular carcinomas. Every patient was subjected to a single-session combined RFA with TACE. Targeting the lesion with RFA needle was first done, to secure its access into the lesion, under ultrasound guidance. Super-selective TACE was then performed, followed by the RFA procedure. ResultsOne-month follow-up revealed complete ablation of the tumour in 25 patients (83.3%), while 5 patients (16.7%) showed residual tumour activity, requiring an additional TACE session. No major complications related to the procedure were recorded during the duration of this study. The probability of encountering, both intra- and post-procedural, minor complications was significantly higher with large focal lesion diameters (P = .039 and .003, respectively). ConclusionSingle-session combined TACE and RFA is a safe and effective treatment option for the control of large HCC lesions, with no major procedure-related complications.

Factors affecting survival after concurrent chemoradiation therapy for advanced hepatocellular carcinoma: a retrospective study

BackgroundConcurrent chemoradiation therapy (CCRT) followed by hepatic arterial infusional chemotherapy (HAIC) was reported to be effective for advanced hepatocellular carcinoma (HCC) with portal vein thrombosis. However, transarterial chemoembolization (TACE) is not preferred in this setting. The aim of this study was to assess the factors affecting survival after CCRT, including additional TACE during repeated HAIC.MethodsThirty-eight patients who underwent CCRT as the initial treatment for Barcelona Clinic Liver Cancer stage C HCC with vascular invasion between 2009 and 2016 were reviewed retrospectively. During CCRT, 5-fluorouracil (5-FU) was infused via chemoport during the first and last five days of five weeks of external beam radiation therapy. After CCRT, repeated HAIC with cisplatin and 5-FU was performed monthly. Nineteen patients (50%) underwent additional TACE between repeated HAICs. Factors related to overall survival and progression free survival (PFS) were analyzed.ResultsThe mean age of patients was 55 years (male:female, 33:5). Underlying liver diseases were hepatitis B, hepatitis C and non-B/C in 29, 1 and 8 patients, respectively. The median radiation dose was 4500 cGy. The objective response (OR) rate at one months after CCRT was 36.8%. The median PFS was 7.4 (range, 1.8 − 32.1) months. The median overall survival was 11.6 (range 2.8-65.7) months. Achieving an OR after CCRT (hazard ratio [HR], 0.028; P < 0.001), additional TACE (HR, 0.134, P < 0.001), and further rounds of HAIC (HR, 0.742, P = 0.001) were independent significant factors related to overall survival. The overall survival duration of patients with an OR after CCRT (median 44.2 vs. 6.6 months, P < 0.001) and additional TACE (median 19.8 vs. 9.1 months, P = 0.001) were significantly greater than those without an OR after CCRT or additional TACE.ConclusionPatients who achieved an OR after CCRT, underwent additional TACE, and were subjected to repeated rounds of HAIC following CCRT showed better survival after CCRT for advanced stage of HCC with vascular invasion. A further prospective study is needed to confirm the positive effect of additional TACE after CCRT.

Sorafenib Alone versus Sorafenib Combined with Transarterial Chemoembolization for Advanced-Stage Hepatocellular Carcinoma: Results of Propensity Score Analyses

Purpose To compare the time to progression (TTP) and overall survival (OS) in patients with advanced-stage hepatocellular carcinoma (HCC) who are undergoing sorafenib treatment combined with transarterial chemoembolization (TACE) versus sorafenib monotherapy. Materials and Methods The retrospective analysis of the data was approved by the institutional review board, and the requirement to obtain informed consent was waived. Of 355 patients with advanced-stage HCC (Barcelona Clinic Liver Cancer stage C) who were undergoing sorafenib therapy for at least 5 weeks between April 2007 and July 2011, 164 (46.2%) underwent repeat TACE (or chemolipiodolization if indicated) along with sorafenib therapy (combined group); the remaining 191 patients (53.8%) received sorafenib alone (monotherapy group). The median patient age was 53 years (range, 22–84 years). The median age was 53 years (range, 26–84 years) for men and 56 years (range, 22–75 years) for women. Propensity score–based methods were used to minimize bias when evaluating TTP on the basis of modified Response Evaluation Criteria in Solid Tumors and OS. Statistical analysis was performed with the Kaplan-Meier method by using the log-rank test and Cox regression models. Results In the combined and monotherapy groups, respectively, 64.6% and 49.2% of patients had vascular invasion, 87.8% and 91.1% had extrahepatic metastasis, and 54.3% and 47.1% had both. During follow-up (median duration, 5.5 months), the median TTP and OS in the combined group were longer than those in the monotherapy group (TTP: 2.5 months vs 2.1 months, respectively, P = .008; OS: 8.9 months vs 5.9 months, P = .009). At univariate and subsequent multivariate analyses, additional TACE was an independent predictor of favorable TTP and OS (adjusted hazard ratio: 0.74 and 0.57, respectively; P < .05 for both), consistent with the outcomes of inverse probability of treatment weighting. In the propensity score–matched cohort (96 pairs), the median TTP in the combined group was significantly longer than that in the monotherapy group (2.7 months vs 2.1 months, respectively; P = .011), but median OS was not (9.1 months vs 6.7 months, P = .21). Conclusion In this retrospective study, TACE plus sorafenib was superior to sorafenib alone with respect to TTP in patients with advanced-stage HCC, although it may or may not improve OS. © RSNA, 2013 Supplemental material: S1

Sorafenib Alone versus Sorafenib Combined with Transarterial Chemoembolization for Advanced-Stage Hepatocellular Carcinoma: Results of Propensity Score Analyses

To compare the time to progression (TTP) and overall survival (OS) in patients with advanced-stage hepatocellular carcinoma (HCC) who are undergoing sorafenib treatment combined with transarterial chemoembolization (TACE) versus sorafenib monotherapy. The retrospective analysis of the data was approved by the institutional review board, and the requirement to obtain informed consent was waived. Of 355 patients with advanced-stage HCC (Barcelona Clinic Liver Cancer stage C) who were undergoing sorafenib therapy for at least 5 weeks between April 2007 and July 2011, 164 (46.2%) underwent repeat TACE (or chemolipiodolization if indicated) along with sorafenib therapy (combined group); the remaining 191 patients (53.8%) received sorafenib alone (monotherapy group). The median patient age was 53 years (range, 22-84 years). The median age was 53 years (range, 26-84 years) for men and 56 years (range, 22-75 years) for women. Propensity score-based methods were used to minimize bias when evaluating TTP on the basis of modified Response Evaluation Criteria in Solid Tumors and OS. Statistical analysis was performed with the Kaplan-Meier method by using the log-rank test and Cox regression models. In the combined and monotherapy groups, respectively, 64.6% and 49.2% of patients had vascular invasion, 87.8% and 91.1% had extrahepatic metastasis, and 54.3% and 47.1% had both. During follow-up (median duration, 5.5 months), the median TTP and OS in the combined group were longer than those in the monotherapy group (TTP: 2.5 months vs 2.1 months, respectively, P = .008; OS: 8.9 months vs 5.9 months, P = .009). At univariate and subsequent multivariate analyses, additional TACE was an independent predictor of favorable TTP and OS (adjusted hazard ratio: 0.74 and 0.57, respectively; P < .05 for both), consistent with the outcomes of inverse probability of treatment weighting. In the propensity score-matched cohort (96 pairs), the median TTP in the combined group was significantly longer than that in the monotherapy group (2.7 months vs 2.1 months, respectively; P = .011), but median OS was not (9.1 months vs 6.7 months, P = .21). In this retrospective study, TACE plus sorafenib was superior to sorafenib alone with respect to TTP in patients with advanced-stage HCC, although it may or may not improve OS. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130150/-/DC1.

Therapeutic efficacy of transarterial chemo-embolization with a fine-powder formulation of cisplatin for hepatocellular carcinoma

To evaluate the efficacy of transarterial chemoembolization (TACE) using a suspension of a fine-powder formulation of cisplatin (DDPH) in lipiodol (LPD) in the treatment of hepatocellular carcinoma (HCC). The subjects were 262 HCC patients treated with TACE using a DDPH-LPD suspension. The DDPH-LPD suspension was prepared by mixing 50 mg of DDPH into 10 mL of LPD. TACE was repeated when treated lesions relapsed and/or new hepatic lesions were detected. These patients received additional TACE using the same agent. TACE was repeated until complete regression of the tumor was obtained. The primary efficacy endpoint of the current study was the objective early response rate. Secondary efficacy endpoints were progression-free survival (PFS) and overall survival. The objective early response rate was 43.6%. Cumulative PFS rates were 56.7% at 6 mo, 23.1% at 12 mo, 13.4% at 18 mo, and 10.5% at 24 mo. The median PFS was 6.6 mo. Cumulative survival rates were 90.6% at 6 mo, 81.9% at 12 mo, 70.5% at 24 mo, and 58.8% at 36 mo. Median survival time was 46.6 mo. All adverse reactions were controllable by temporary suspension of treatment. No serious complications or treatment-related deaths were observed. TACE using a suspension of DDPH in LPD may be a useful treatment for HCC.

The cost-effectiveness of transarterial chemoembolization treatments.

e14626 Background: Transarterial chemoembolization (TACE) is often a treatment for patients precluded from surgery. TACE recipients may get ≥1 TACE treatment, yet little is known about the cost-effectiveness of such additional TACEs. Methods: The study population includes 1,095 Medicare patients with a 1st diagnosis of 1ry HCC in 2000-07 who got TACE, or both TACE+ablation (LD) where one occurred prior to any other treatments. Patients were studied through end of 2009, in SEER-Medicare A-B. Stratifying by ablation, Cox proportional hazards models were built to assess the impacts of successive TACEs on all-cause/HCC-mortality, adjusting for clinical (cancer stage, underlying health status, liver conditions) and demographics. Average HCC-related Medicare costs (US$2,011) attributed to additional TACEs was estimated with generalized least squares, obtaining incremental cost effectiveness ratios (ICERs) and 95% confidence intervals, controlling for systemic chemotherapy and radiation therapy in the follow-up period. Results: Cancer stages 1, 2, 3, and 4 represented 34%, 16%, 19%, and 5% of the 1095 patients, respectively: 26% unstaged, 68% male, 71% Caucasian, 6% African American, and 17% Hispanic. 474 non-LD TACE patients had one TACE, 218 two, 93 three, 70 ≥four. Among LD patients, 121 got 1 TACE, 58 two, 34 three, 27 ≥four. In non-LD patients, further reductions in all-cause/HCC mortality were associated with the 2nd (HR .76, p&lt;.01; HR .78, p=.045) and 3rd (HR .68, p&lt;.01; HR .61, p&lt;.01) TACE, but not the 4th; only the 3rd TACE further reduced mortality risk in LD patients (HR .48, p=.01; HR .34, p .01). For non-LD patients, using HCC mortality, the 2nd TACE was attributed to $19,969 per life year (LY) added, 95%CI $8,634, $31,303, the 3rd $10,290/LY ($2,815, $17,764); using all-cause mortality, the 2nd $27,813/LY ($15,943, $39,684), the 3rd ICER was statistically N.S. All ICERs were N.S. for LD patients. Conclusions: Additional TACEs provide survival benefit for HCC Medicare patients in clinical practice. However, that benefit may decrease after the 3rd exposure, which is more cost effective than a 2nd one. Additional TACEs may be confounded if ≥4 TACEs are intended to treat biologically aggressive disease.

Transarterial chemoembolization as salvage therapy after unsuccessful hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma

The prognosis for advanced hepatocellular carcinoma (HCC) remains unsatisfactory. Transarterial chemoembolization (TACE) and/or hepatic arterial infusion chemotherapy (HAIC) have been reported to be useful options. However, there are few reports of salvage therapies for patients without a curative response to initial chemotherapy. The aim of this study was to elucidate the efficacy of additional TACE as salvage therapy in cases of advanced HCC which failed to respond to HAIC. Of 43 patients with advanced HCC who did not show a complete response (CR) to HAIC, 12 were treated with additional TACE as salvage therapy (Group A). The rest were enrolled as disease control subjects (Group B). Response rates and prognosis were compared. For HAIC, cisplatin (10 mg/body on days 1-5) was administered. Subsequent treatment was the infusion of 5-fluorouracil (250 mg/body on days 1-5), which was scheduled for 4 serial courses. For TACE, carboplatin (150 mg/body) or epirubicin (30 mg/body) was administered mixed with 3 ml of ethiodized oil every 4 weeks. A CR or PR, ST and PD were observed in 6, 3, and 3 patients in Group A and 13, 18 and 0 patients in Group B, respectively. The difference in response between the two groups was significant (P=0.0074). The 1-, 2- and 3-year survival rates were 83.3, 75.0 and 44.4% in Group A and 83.9, 41.5 and 11.3% in Group B, respectively. Patients in Group A had a better prognosis than did those in Group B (P=0.018). Median survival was 31.9 months (5.8-41.1) in Group A and 16.2 months (3.3-53.2) in Group B. Consequently, TACE as salvage therapy after HAIC may improve the prognosis for patients with advanced HCC.

Sequential arterial and portal vein embolizations before right hepatectomy in patients with cirrhosis and hepatocellular carcinoma

Selective transarterial chemoembolization (TACE) and portal vein embolization (PVE) could improve the rate of hypertrophy of the future liver remnant (FLR) in patients with chronic liver disease. This study evaluated the feasibility and efficacy of this combined procedure. Between November 1998 and October 2004, 36 patients with cirrhosis and hepatocellular carcinoma underwent right hepatectomy after PVE. Additional TACE preceded PVE by 3-4 weeks in 18 patients (TACE+PVE group) and the remaining 18 patients had PVE alone (PVE group). PVE was well tolerated in all patients. The mean increase in percentage FLR volume was significantly higher in the TACE+PVE group than in the PVE group (mean(s.d.) 12(5) versus 8(4) percent; P=0.022). The rate of hypertrophy was more than 10 percent in 12 patients in the TACE+PVE group and in five who had PVE alone (P=0.044). Duration of surgery, blood loss, incidence of liver failure and mortality (two patients in each group) were similar in the two groups. None of the 17 patients with an increase in FLR volume of more than 10 percent died, whereas there were four deaths among 19 patients with a smaller increase. The incidence of complete tumour necrosis was significantly higher in the TACE+PVE group (15 of 18 versus one of 18; P<0.001), with a higher 5-year disease-free survival rate (37 versus 19 percent; P=0.041). Sequential TACE and PVE before operation increases the rate of hypertrophy of the FLR and leads to a high rate of complete tumour necrosis associated with longer recurrence-free survival.

Initial experience from a combination of systemic and regional chemotherapy in the treatment of patients with nonresectable cholangiocellular carcinoma in the liver

In nonresectable cholangiocellular carcinoma (CCC) therapeutic options are limited. Recently, systemic chemotherapy has shown response rates of up to 30%. Additional regional therapy of the arterially hyper vascularized hepatic tumors might represent a rational approach in an attempt to further improve response and palliation. Hence, a protocol combining transarterial chemoembolization and systemic chemotherapy was applied in patients with CCC limited to the liver. Eight patients (6 women, 2 men, mean age 62 years) with nonresectable CCC received systemic chemotherapy (gemcitabine 1 000 mg/m(2)) and additional transarterial chemoembolization procedures (50 mg/m(2) cisplatin, 50 mg/m(2) doxorubicin, up to 600 mg degradable starch microspheres). Clinical follow-up of patients, tumor markers, CT and ultrasound were performed to evaluate maximum response and toxicity. Both systemic and regional therapies were tolerated well; no severe toxicity (WHO III/IV) was encountered. Nausea and fever were the most commonly observed side effects. A progressive rarefication of the intrahepatic arteries limited the maximum number of chemoembolization procedures in 4 patients. A median of 2 chemoembolization cycles (range, 1-3) and a median of 6.5 gemcitabine cycles (range, 4-11) were administered. Complete responses were not achieved. As maximum response, partial responses were achieved in 3 cases, stable diseases in 5 cases. Two patients died from progressive disease after 9 and 10 mo. Six patients are still alive. The current median survival is 12 mo (range, 9-18); the median time to tumor progression is 7 mo (range, 3-18). Seven patients suffered from tumor-related symptoms prior to therapy, 3 of these experienced a treatment-related clinical relief. In one patient the tumor became resectable under therapy and was successfully removed after 10 mo. The present results indicate that a combination of systemic gemcitabine therapy and repeated regional chemoembolizations is well tolerated and may enhance the effect of palliation in a selected group of patients with intrahepatic nonresectable CCC.

High-Dose proton beam radiotherapy of hepatocellular carcinoma: Preliminary results of a phase II trial

This phase II trial was undertaken to determine the efficacy and toxicity of proton beam radiotherapy for patients with locally unresectable hepatocellular carcinoma. Cirrhotic patients were eligible if they had a Child-Pugh score of 10 or less. Eligible patients included those with T 1 -T 3 hepatocellular carcinoma; selected T 4 patients also were eligible. Patients with lymph node or distant metastases were ineligible. Daily proton beam radiotherapy was directed to the liver tumor with an additional 1-2 cm margin. The total dose was 63 cobalt Gray equivalents, administered in 15 divided fractions over 3 weeks. Thirty-four patients have completed treatment and have been followed up for a minimum of 6 months, with a median follow-up period of 20 months. The mean age was 65 years, and average tumor size was 5.7 cm. Posttreatment toxicity included a small but significant decline in albumin levels and increased total bilirubin; 3 experienced duodenal or colonic bleeding when bowel was immediately adjacent to the treated tumor. Two-year actuarial data showed a 75% local tumor control rate and an overall survival rate of 55%. Of patients with an elevated pretreatment alpha-fetoprotein, 85% were found to have declining alpha-fetoprotein levels from a pretreatment mean of 1405 to 35 at 6 months after treatment. Six patients underwent liver transplantation between 6 and 16 months after completion of radiotherapy with 2 showing no evidence of residual carcinoma within the explanted liver. Overall the majority of patients responded to treatment, and the therapy was well tolerated.

Incidence and risk factors for acute renal failure in patients with hepatocellular carcinoma undergoing transarterial chemoembolization: a prospective study.

Transarterial chemoembolization (TACE) is effective for hepatocellular carcinoma (HCC). Considerable amounts of radiocontrast agent are used for TACE and may induce renal dysfunction. This study prospectively investigated the incidence and risk factors of acute renal failure (ARF), defined as an increase of serum creatinine level >1.5 mg/dl after TACE. ARF developed in 12 (8.6%) of 140 patients after TACE. Univariate analysis showed that number of treatment sessions (2.3 +/- 1.4 vs 1.3 +/- 1.6, P=0.013), Child-Pugh class B (50% vs 21%, P=0.035) and the occurrence of severe postembolization syndrome (75% vs 30%, P=0.020) were significantly associated with the development of ARF. Multivariate logistic regression analysis disclosed that the proportional increased risk of ARF was 65% for each additional TACE therapy (odds ratio [OR]: 1.65, 95% confidence interval [CI]: 1.13-2.41, P=0.010). Other independent risk factors were Child-Pugh class B (OR: 12.82, 95% CI: 2.44-67.29, P=0.003) and severe postembolization syndrome (OR: 6.64, 95% CI: 1.60-27.49, P=0.009). Four (33%) of the patients with ARF developed irreversible renal function impairment, and diabetes mellitus was the only associated factor (P=0.067) in this group. ARF after TACE is closely associated with number of treatment sessions, severity of cirrhosis and development of severe postembolization syndrome. Effective preventive measures should be undertaken especially in high-risk patients.