Macarena Rodriguez

Comparison of the survival and tolerability of radioembolization in elderly vs. younger patients with unresectable hepatocellular carcinoma

BACKGROUND & AIMS The European Network on Radioembolization with Yttrium-90 resin microspheres study group (ENRY) conducted a retrospective study to evaluate the outcomes among elderly (≥ 70 years) and younger patients (<70 years) with unresectable hepatocellular carcinoma (HCC) who received radioembolization at 8 European centers. METHODS Patients with confirmed diagnosis of unresectable HCC who either progressed following resection or locoregional treatment and/or who were considered poor candidates for chemoembolization were evaluated by a multidisciplinary team for radioembolization with (90)Y-resin microspheres (SIR-Spheres; Sirtex Medical). The survival outcome and all adverse events were compared between the two age groups. RESULTS Between 2003 and 2009, 128 elderly and 197 younger patients received radioembolization. Patients in both groups had similar demographic characteristics. Many elderly and younger patients alike had multinodular, BCLC stage C disease, invading both lobes (p = 0.648). Elderly patients had a lower tumor burden, a smaller median target liver volume (p = 0.016) and appeared more likely to receive segmental treatment (p = 0.054). Radioembolization was equally well tolerated in both cohorts and common procedure-related adverse events were predominantly grade 1-2 and of short duration. No significant differences in survival between the groups were found (p = 0.942) with similar median survival in patients with early, intermediate or advanced BCLC stage disease. CONCLUSIONS Radioembolization appears to be as well-tolerated and effective for the elderly as it is for younger patients with unresectable HCC. Age alone should not be a discriminating factor for the management of HCC patients.

Analysis of Prognostic Factors After Yttrium-90 Radioembolization of Advanced Hepatocellular Carcinoma

PURPOSE To analyze which patient-, tumor-, and treatment-related factors may influence outcome after (90)Y radioembolization ((90)Y-RE) for hepatocellular carcinoma (HCC). PATIENTS AND METHODS Seventy-two consecutive patients with advanced HCC treated with (90)Y-RE were studied to detect which factors may have influenced response to treatment and survival. RESULTS Median overall survival was 13 months (95% confidence interval, 9.6-16.3 months). In univariate analysis, survival was significantly better in patients with one to five lesions (19 vs. 8 months, p = 0.001) and in patients with alpha-fetoprotein <52 UI/mL (24 vs. 11 months, p = 0.002). The variation in target tumor size and the appearance of new lesions were analyzed among 50 patients with measurable tumors. A decrease in target tumor size was observed in most patients, and the intensity of such decrease was not associated with any of the factors under study. Patients who developed new lesions in the treated liver (and also in the nontargeted liver) at month 3 more frequently had more than five nodules, bilobar disease, and alpha-fetoprotein >52 UI/mL, and their survival in the multivariate analysis was significantly worse (hazard ratio, 4.7; 95% confidence interval, 13-1.73) (p = 0.002). CONCLUSIONS Yttrium-90 radioembolization results in control of target lesions in the majority of patients with HCC but does not prevent the development of new lesions. Survival of patients treated with (90)Y-RE seems to depend largely on factors related to the aggressiveness of the disease (number of nodules, levels of alpha-fetoprotein, and presence of microscopic disease).

Partial liver volume radioembolization induces hypertrophy in the spared hemiliver and no major signs of portal hypertension

BACKGROUND Post-treatment contralateral hemiliver hypertrophy has created an interest in lobar liver radioembolization (RE) as a pre-surgery tool. METHODS Liver and spleen volumes and function were studied in 83 patients submitted to partial liver volume RE at 4-8 weeks (T1), 10-26 weeks (T2), and >26 weeks (T3) after RE. RESULTS More than half of the patients had cirrhosis with hepatocellular carcinoma. The main finding was a progressive increase in the volume of the spared hemiliver (mean absolute increase at T3: 230 ml). The percentage of patients in whom the baseline ratio of spared volume to total liver volume was <40% dropped from 56.6% at baseline to 29.4% at T2 (P < 0.001). A significant and progressive increase in spleen volume but not in portal vein diameter was also observed. A small percentage of patients developed hypersplenism, mostly those without cirrhosis (16.0% at T2). Six patients (five with portal vein thrombosis, cirrhosis or both) developed signs of portal hypertension by T2. CONCLUSIONS The present results warrant further studies to better elucidate the mechanism underlying this phenomenon of spared hemiliver hypertrophy and to investigate its role as an alternative to portal vein embolization in the management of patients with potentially resectable liver tumours.

Pilot randomized trial of selective internal radiation therapy vs. chemoembolization in unresectable hepatocellular carcinoma.

To compare selective internal radiation therapy (SIRT) with transarterial chemoembolization (TACE), the standard‐of‐care for intermediate‐stage unresectable, hepatocellular carcinoma (HCC), as first‐line treatment.

Treatment of Hepatocellular Carcinoma by Radioembolization Using 90Y Microspheres

The use of external beam radiation therapy for primary treatment of hepatocellular carcinoma (HCC) has been limited by the low radiation tolerance of the non-tumoral liver. However, technical advances allowing partial liver volume external irradiation have resulted in consistently high response rates. Internal radiation therapy, also called 90Y radioembolization (90Y-RE), consists in delivering implantable microspheres labeled with 90Y into the arteries that feed liver tumors in order to provide a high dose of radiation to tumor nodules irrespective of their number, size and location, while preserving the non-tumoral liver tissue from receiving a harmful level of radiation. Among patients with HCC, 90Y-RE is used for those that have a preserved liver function and unresectable tumors that cannot be treated with percutaneous ablation. Although 90Y-RE is by and large well tolerated, it may produce relevant toxic effects as a result of radiation of non-target organs including cholecystitis, gastrointestinal ulceration, pneumonitis, and most importantly, liver toxicity. A significant effect on tumor growth in the treated lesions is consistently observed with disease control rates in excess of 80%. Also, 90Y-RE may allow downstaging large or multiple lesions to radical treatments with curative intent. When compared with the survival of HCC patients in advanced stage either not treated or treated with ineffective systemic agents, survival after 90Y-RE is encouraging and warrants future clinical trials. Clinical research in combining the cytotoxic effect of 90Y with the cytostatic mechanism of targeted therapies is currently in progress and will provide valuable safety and toxicity data that may translate into improved clinical outcome and overall survival.

Liver radioembolization using 90Y resin microspheres in elderly patients: tolerance and outcome.

Abstract Purpose: Yttrium 90 (90Y) microsphere radioembolization (90Y-RE) is an emerging locoregional treatment for liver cancer. The most common complications of 90Y-RE arise from excessive irradiation of nontarget organs (eg, gastrointestinal tract, lung, and nontumoral liver). Patients with advanced age may have substantial comorbidities that can affect their life expectancy, and tolerance to radiation in elderly patients may be altered. The purpose of this study is to evaluate the safety and survival of elderly patients treated with 90Y-RE. Materials and Methods: We analyzed 255 patients with liver tumors (primary or metastatic) who were treated with 90Y-RE in our institution from September 2003 to February 2010. We categorized patients as “elderly” if aged ≥ 70 years and “younger” if aged < 70 years. Results: Seventy-three patients (29%) were aged ≥ 70 years. The most frequent liver tumor among elderly patients was hepatocellular carcinoma. Complication rates were similar in both groups: 10.4% of elderly patients and 9.9% of younger patients developed radioembolization-induced liver disease (P = 1.000). Only 1.5% of elderly patients developed gastrointestinal ulceration and no patient in the elderly group developed pneumonitis. The median overall survival of patients with hepatocellular carcinoma was similar in elderly and younger groups (13 months, 95% confidence interval [CI], 10.4–15.5 and 12 months, 95% CI, 4.2–15.7; P = 0.4). In patients with colorectal carcinoma metastatic to the liver, the median overall survival was 10 months (95% CI, 5.2–14.7) for elderly patients and 13 months (95% CI, 7.0–18.9) for younger patients (P = 0.3). The median overall survival of patients with other histologies was 9 months (95% CI, 3.5–14.4) for younger patients and 4 months (95% CI, 2.7–5.2) for elderly patients (P = 0.9). Conclusion: Elderly patients did not have more toxicity than younger patients treated with 90Y-RE, and survival was similar for each histology. Elderly patients should be considered for 90Y-RE if they otherwise meet the inclusion criteria applicable to younger patients.

Factors related to increased resting energy expenditure in men with liver cirrhosis.

Objective Hypermetabolism in cirrhosis is associated with a high risk of complications and mortality. However, studies about underlying mechanisms are usually focussed on isolated potential determinants and specific etiologies, with contradictory results. We aimed at investigating differences in nutrition, metabolic hormones, and hepatic function between hypermetabolic and nonhypermetabolic men with cirrhosis of the liver. Patients and methods We prospectively enrolled 48 male cirrhotic inpatients. We evaluated their resting energy expenditure (REE) and substrate utilization by indirect calorimetry, body composition by dual-energy X-ray absorptiometry, liver function, and levels of major hormones involved in energy metabolism by serum sample tests. Patients with ascites, specific metabolic disturbances, and hepatocellular carcinoma were excluded. Results REE and REE adjusted per fat-free mass (FFM) were significantly increased in cirrhotic patients. Overall, 58.3% of cirrhotic patients were classified as hypermetabolic. Groups did not differ significantly in age, etiology of cirrhosis, liver function, presence of ascites, use of diuretics, &bgr;-blockers, or presence of transjugular intrahepatic portosystemic shunts. Hypermetabolic cirrhotic patients had lower weight, BMI (P<0.05), nonprotein respiratory quotient (P<0.01), leptin (P<0.05), and leptin adjusted per fat mass (FM) (P<0.05), but higher FFM% (P<0.05) and insulin resistance [homeostatic model assessment-insulin resistance (HOMA-IR)] (P<0.05). Only HOMA-IR, leptin/FM, and FFM% were independently related to the presence of hypermetabolism. Conclusion Hypermetabolic cirrhotic men are characterized by lower weight, higher FFM%, insulin resistance, and lower leptin/FM when compared with nonhypermetabolic men. HOMA-IR, FFM%, and leptin/FM were independently associated with hypermetabolism, and may serve as easily detectable markers of this condition in daily clinical practice.

114 SIRTACE: A RANDOMISED MULTICENTRE PILOT TRIAL OF SELECTIVE INTERNAL RADIOEMBOLISATION (SIRT) WITH YTTRIUM-90 MICROSPHERES VERSUS TRANSARTERIAL CHEMO-EMBOLISATION (TACE) IN PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA (HCC)

114 SIRTACE: A RANDOMISED MULTICENTRE PILOT TRIAL OF SELECTIVE INTERNAL RADIOEMBOLISATION (SIRT) WITH YTTRIUM-90 MICROSPHERES VERSUS TRANSARTERIAL CHEMO-EMBOLISATION (TACE) IN PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA (HCC) F.T. Kolligs, J.I. Bilbao, T. Jakobs, M. Inarrairaegui, J. Nagel, M. Rodriguez, A. Haug, D. D’Avola, M. op den Winkel, A. Martinez-Cuesta, C. Trumm, A. Benito, K. Tatsch, C. Zech, R.-T. Hoffmann, B. Sangro. Department of Internal Medicine II, University of Munich (LMU), Munich, Germany; Interventional Radiology, Clinica Universidad de Navarra, Pamplona, Spain; Institute of Radiology, Krankenhaus Barmherzige Bruder, Munich, Germany; Liver Unit, Clinica Universidad de Navarra and CIBEREHD, Nuclear Medicine, Clinica Universidad de Navarra, Pamplona, Spain; Department of Nuclear Medicine, University of Munich (LMU), Munich, Germany; Interventional Radiology, Hospital de Navarra, Pamplona, Spain; Institute of Radiology, University of Munich (LMU), Munich, Germany; Radiology, Clinica Universidad de Navarra, Pamplona, Spain; Institute of Nuclear Medicine, Klinikum Karlsruhe, Karlsruhe, Germany; Institute of Radiology, University of Basel, Basel, Switzerland; Institute of Radiology, University of Dresden, Dresden, Germany E-mail: fkolligs@med.uni-muenchen.de