Focus

Abstract

Comparison of the survival and tolerability of radioembolization in elderly vs. younger patients with unresectable hepatocellular carcinomaJournal of HepatologyVol. 59Issue 4PreviewThe 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. Full-Text PDF Treatment of liver disease in the elderly: The case of radioembolization for advanced hepatocellular carcinomaManagement of chronic liver disease and hepatocellular carcinoma (HCC) in older age groups beyond the age of 70 years has been changing in the past decade. The availability of a growing spectrum of anti-viral agents for treatment of chronic viral hepatitis B and C as well the introduction of several non-surgical modalities for loco-regional treatment of advanced HCC have had a major impact on the clinical practice and survival of young and old patients alike [1EASL-EORTC clinical practice guidelines Management of hepatocellular carcinoma.J Hepatol. 2012; 56: 908-943Abstract Full Text Full Text PDF PubMed Scopus (4475) Google Scholar, 2Bruix J. Sherman M. Management of hepatocellular carcinoma: an update.Hepatology. 2011; 53: 1020-1022Crossref PubMed Scopus (6512) Google Scholar, 3Floreani A. Liver diseases in the elderly: an update.Dig Dis. 2007; 25: 138-143Crossref PubMed Scopus (47) Google Scholar]. Cirrhosis of the liver is the most common risk factor for HCC, irrespective of age. The pathophysiology of cirrhosis and consequently also of HCC is driven by several factors including the individual hepatic morbidities associated with HCC (i.e., persistent viral infection, metabolic and/or alcoholic liver disease), which have a variable clinical presentation at older age. The introduction of universal vaccination against hepatitis B virus (HBV) infection in over 170 countries is already leading to a decrease in the incidence of hepatitis B and HCC worldwide. Yet, the incidence of HCC is expected to rise in the next decades due to the current inability to control the progression of hepatitis C virus (HCV) infection on a global scale. In this context, it is important to note that the mean age of diagnosis of HCC, especially in the Western hemisphere varies between 63 and 65 years as compared to 55–59 years in China [[4]El-Serag H.B. Epidemiology of viral hepatitis and hepatocellular carcinoma.Gastroenterology. 2012; 142 ([e1261]): 1264-1273Abstract Full Text Full Text PDF PubMed Scopus (2341) Google Scholar]. The proportion of HCC patients, 70 years and older, seeking treatment has been rising steadily, especially in the US and Europe [4El-Serag H.B. Epidemiology of viral hepatitis and hepatocellular carcinoma.Gastroenterology. 2012; 142 ([e1261]): 1264-1273Abstract Full Text Full Text PDF PubMed Scopus (2341) Google Scholar, 5Altekruse S.F. McGlynn K.A. Reichman M.E. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005.J Clin Oncol. 2009; 27: 1485-1491Crossref PubMed Scopus (1373) Google Scholar, 6Nordenstedt H. White D.L. El-Serag H.B. The changing pattern of epidemiology in hepatocellular carcinoma.Dig Liver Dis. 2010; 42: S206-S214Abstract Full Text PDF PubMed Scopus (413) Google Scholar], although there seems to be a shift of the peak of HCC incidence in some regions to relatively younger age groups [[7]El-Serag H.B. Mason A.C. Rising incidence of hepatocellular carcinoma in the United States.N Engl J Med. 1999; 340: 745-750Crossref PubMed Scopus (2708) Google Scholar]. In the past two decades, major progress has been made in the treatment of HCC including the development of various effective ablation procedures for loco-regional injection, surgical resection and liver transplantation as well as new chemotherapeutic agents [1EASL-EORTC clinical practice guidelines Management of hepatocellular carcinoma.J Hepatol. 2012; 56: 908-943Abstract Full Text Full Text PDF PubMed Scopus (4475) Google Scholar, 2Bruix J. Sherman M. Management of hepatocellular carcinoma: an update.Hepatology. 2011; 53: 1020-1022Crossref PubMed Scopus (6512) Google Scholar]. Yet, clinicians often prefer a conservative approach when considering treatment options for elderly patients with HCC, even in the presence of preserved synthetic liver functions and absence of portal hypertension. The reluctance to offer invasive treatment modalities to the elderly patient is based in part on the notion that molecular pathophysiologic changes of the aging liver predispose to a worse response to treatment, more adverse effects, and less favorable prognosis as compared to younger individuals. There is, however, limited evidence to support such a conservative approach. Indeed, data reported in aging animals and in older humans suggest an increase in hepatocyte size, a rising number of binucleated hepatocytes, a reduction in numbers of mitochondria and oxidative capacity, a loss in hepatic volume and degree of hepatic perfusion as well as a decline in regenerative capacity. However, a recent paper by Sheedfar and co-workers entitled “Liver diseases and aging: friends or foes?” is casting doubt on the practical therapeutic implications of these phenomena and asking: “Is aging an actual risk factor for liver disease or a bystander?” [[8]Sheedfar F. Di Biase S. Koonen D. Vinciguerra M. Liver diseases and aging: friends or foes?.Aging Cell. 2013; https://doi.org/10.1111/acel.12128Crossref PubMed Scopus (137) Google Scholar]. Indeed, current clinical experience suggests that various ablation procedures for HCC including transarterial chemoembolization (TACE), radiofrequency ablation (RFA) and even surgical resection in the elderly patients are not less effective and safe as compared to younger cohorts of <65 years of age [9Biselli M. Forti P. Mucci F. Foschi F.G. Marsigli L. Caputo F. et al.Chemoembolization versus chemotherapy in elderly patients with unresectable hepatocellular carcinoma and contrast uptake as prognostic factor.J Gerontol A Biol Sci Med Sci. 1997; 52: M305-M309Crossref PubMed Scopus (13) Google Scholar, 10Yau T. Yao T.J. Chan P. Epstein R.J. Ng K.K. Chok S.H. et al.The outcomes of elderly patients with hepatocellular carcinoma treated with transarterial chemoembolization.Cancer. 2009; 115: 5507-5515Crossref PubMed Scopus (36) Google Scholar, 11Mirici-Cappa F. Gramenzi A. Santi V. Zambruni A. Di Micoli A. Frigerio M. et al.Treatments for hepatocellular carcinoma in elderly patients are as effective as in younger patients: a 20-year multicentre experience.Gut. 2010; 59: 387-396Crossref PubMed Scopus (136) Google Scholar, 12Lee S.H. Choi H.C. Jeong S.H. Lee K.H. Chung J.I. Park Y.S. et al.Hepatocellular carcinoma in older adults: clinical features, treatments, and survival.J Am Geriatr Soc. 2011; 59: 241-250Crossref PubMed Scopus (27) Google Scholar, 13Cohen M.J. Bloom A.I. Barak O. Klimov A. Nesher T. Shouval D. et al.Trans-arterial chemo-embolization is safe and effective for very elderly patients with hepatocellular carcinoma.World J Gastroenterol. 2013; 19: 2521-2528Crossref PubMed Scopus (38) Google Scholar, 14Lui W.Y. Chau G.Y. Wu C.W. King K.L. Surgical resection of hepatocellular carcinoma in elderly cirrhotic patients.Hepatogastroenterology. 1999; 46: 640-645PubMed Google Scholar, 15Hiraoka A. Michitaka K. Horiike N. Hidaka S. Uehara T. Ichikawa S. et al.Radiofrequency ablation therapy for hepatocellular carcinoma in elderly patients.J Gastroenterol Hepatol. 2010; 25: 403-407Crossref PubMed Scopus (61) Google Scholar].In this context, it is also important to assess the safety and effectiveness of transarterial radioembolization, referred to also as selective internal radiation therapy (SIRS), using 90Ytrium in the elderly population. Early versions of SIRS treatment were already developed in the 1990s [[16]Triller J. Rosler H. Geiger L. Baer H.U. Methods for the superselective radioembolization of liver tumors with 90yttrium-resin particles.Rofo. 1994; 161: 425-431Crossref PubMed Google Scholar]. It took however more than a decade to develop clinically usable compounds containing either 90Y labeled glass or resin microspheres for intra-arterial injection to the liver. SIRS has been evaluated in a number of clinical trials in patients with unresectable HCC, in patients with hepatic metastases of colorectal cancer, neuroendocrine tumors, cholangiocarcinoma and metastatic carcinoma [17Ibrahim S.M. Lewandowski R.J. Sato K.T. Gates V.L. Kulik L. Mulcahy M.F. et al.Radioembolization for the treatment of unresectable hepatocellular carcinoma: a clinical review.World J Gastroenterol. 2008; 14: 1664-1669Crossref PubMed Scopus (83) Google Scholar, 18Woodall C.E. Scoggins C.R. Ellis S.F. Tatum C.M. Hahl M.J. Ravindra K.V. et al.Is selective internal radioembolization safe and effective for patients with inoperable hepatocellular carcinoma and venous thrombosis?.J Am Coll Surg. 2009; 208: 375-382Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar, 19Salem R. Lewandowski R.J. Kulik L. Wang E. Riaz A. Ryu R.K. et al.Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma.Gastroenterology. 2011; 140 (e492): 497-507Abstract Full Text Full Text PDF PubMed Scopus (477) Google Scholar, 20Deleporte A. Flamen P. Hendlisz A. State of the art: radiolabeled microspheres treatment for liver malignancies.Expert Opin Pharmacother. 2010; 11: 579-586Crossref PubMed Scopus (24) Google Scholar, 21Kim Y.H. Kim do Y. Yttrium-90 radioembolization for hepatocellular carcinoma: what we know and what we need to know.Oncology. 2013; 84: 34-39Crossref PubMed Scopus (13) Google Scholar, 22Sangro B. Carpanese L. Cianni R. Golfieri R. Gasparini D. Ezziddin S. et al.Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation.Hepatology. 2011; 54: 868-878Crossref PubMed Scopus (469) Google Scholar, 23Chiesa C. Mira M. Maccauro M. Romito R. Spreafico C. Sposito C. et al.A dosimetric treatment planning strategy in radioembolization of hepatocarcinoma with 90Y glass microspheres.Q J Nucl Med Mol Imaging. 2012; 56: 503-508PubMed Google Scholar, 24Mazzaferro V. Sposito C. Bhoori S. Romito R. Chiesa C. Morosi C. et al.Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study.Hepatology. 2013; 57: 1826-1837Crossref PubMed Scopus (330) Google Scholar]. In a recent retrospective comparative clinical trial, toxicity and survival were evaluated in 245 HCC patients treated by TACE and 123 patients treated by SIRS over a period of 9 years. A statistically non-significant trend for a higher response rate was observed in 49% of SIRS recipients as compared to 36% of TACE treated patients (p = 0.104). Time to tumor progression was longer following SIRS, 13.4 vs. 8.4 months (p = 0.046). Yet, median survival was not statistically different, ranging between 20.5 and 17.4 months following SIRS and TACE respectively [[19]Salem R. Lewandowski R.J. Kulik L. Wang E. Riaz A. Ryu R.K. et al.Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma.Gastroenterology. 2011; 140 (e492): 497-507Abstract Full Text Full Text PDF PubMed Scopus (477) Google Scholar]. Abdominal pain and “transaminitis” were more frequent in TACE recipients (p <0.05). Until recently, limited data were reported regarding safety and effectiveness of SIRS in the elderly HCC patient [[25]Inarrairaegui M. Bilbao J.I. Rodriguez M. Benito A. Sangro B. Liver radioembolization using 90 y resin microspheres in elderly patients: tolerance and outcome.Hosp Pract (1995). 2010; 38: 103-109Crossref PubMed Scopus (7) Google Scholar].In the present issue of the Journal, Dr Golfieri and co-workers report the results of a European multicenter, retrospective study, involving 8 centers, comparing the survival and safety of radioembolization between two cohorts of unresectable HCC patients younger and older than 70 years [[26]Golfieri R, Bilbao JI, Carpanese L, Cianni R, Gasparini D, Ezziddin S, et al. Comparison of the survival and tolerability of radioembolization in elderly versus younger patients with unresectable hepatocellular carcinoma. J Hepatol 2013;59:753–761.Google Scholar]. The main results of this study, performed on 128 elderly patients >70 years old and 197 younger patients <70 years of age, suggest a similar survival by Kaplan-Meier analysis in both groups of 14.5 vs. 12.8 month respectively in early, intermediate or advanced BCLC stage disease, with an overall comparable safety for both procedures. Median survival in BCLC stage A patients was similar, 23.7 vs. 27.4 months in older and younger SIRS recipients, dropping to 16.9 and 18.4 months in BCLC stage B patients and to 10.3 vs. 9.7 months in BCLC stage C patients respectively. Thus, the main conclusion of this study suggests that SIRS treatment is equally effective and safe in elderly patients, 70 years and older as compared to younger patients <70 years of age. This is most probably indeed the case. However, The robustness of this conclusion is limited due to the retrospective design of this study as also acknowledged by the authors. Interestingly, elderly patients had smaller livers, had more selective segmental interventions, and showed delayed tumor growth, as compared to the younger population. This observation is consistent with previous reports in aging experimental animals and in humans, suggesting diminished hepatic perfusion and loss of hepatic volume with advancing age [[8]Sheedfar F. Di Biase S. Koonen D. Vinciguerra M. Liver diseases and aging: friends or foes?.Aging Cell. 2013; https://doi.org/10.1111/acel.12128Crossref PubMed Scopus (137) Google Scholar].Comments: Radioembolization for treatment of advanced HCC has captured the attention of hepatologists, oncologists, and invasive radiologists for more than a decade. SIRS is now available on a commercial basis in many countries. Consequently, relatively large numbers of patients were and are being treated by SIRS although data from large scale prospective randomized trials comparing SIRS to standard of care treatment such as TACE are not yet available. Such trials will require a very large number of patients which will not be easy to recruit in view of the already significant use of SIRS in clinical practice. The BCLC classification provides clear guidelines regarding the treatment options for the various stages of HCC. Yet, so far, the role of SIRS still remains inconclusive.Two recent surveys in Europe, although not comparable by design, provide somewhat conflicting results regarding the use of radioembolization in advanced HCC in Europe. In an Italian survey conducted in 135 centers (with a questionnaire response rate of 64.9%), only 2% of almost 9000 HCC patients were treated by radioembolization [[27]Bargellini I. Florio F. Golfieri R. Grosso M. Lauretti D.L. Cioni R. Trends in Utilization of Transarterial Treatments for Hepatocellular Carcinoma: results of a Survey by the Italian Society of Interventional Radiology.Cardiovasc Intervent Radiol. 2013; (May 30 [Epub ahead of print])Google Scholar]. However, another survey conducted in 45 European centers (with a 62% questionnaire response rate) reports the utilization of radioembolization in 1000 patients in 2009 and 1292 patients in 2010 [[28]Powerski M.J. Scheurig-Munkler C. Banzer J. Schnapauff D. Hamm B. Gebauer B. Clinical practice in radioembolization of hepatic malignancies: a survey among interventional centers in Europe.Eur J Radiol. 2012; 81: e804-e811Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar]. This rising popularity of SIRS is not translated into clinical guidelines as reflected in a quotation from the recent EASL guidelines for management of HCC [[1]EASL-EORTC clinical practice guidelines Management of hepatocellular carcinoma.J Hepatol. 2012; 56: 908-943Abstract Full Text Full Text PDF PubMed Scopus (4475) Google Scholar]: “… Objective response rates (to SIRS) range from 35% to 50%. Around 20% of patients present liver-related toxicity and 3% treatment-related death. Despite the amount of data reported, there are no RCT testing the efficacy of 90Y radioembolization compared with chemoembolization or sorafenib in patients at intermediate or advanced stage, respectively. Further research trials are needed to establish a competitive efficacy role in these populations”. Yet, despite this reservation, the use of SIRS is expanding. Indeed, SIRS is an attractive option for treatment of patients with advanced and multifocal HCC. It is also at present the most promising treatment modality for HCC patients with portal vein thrombosis; it usually requires, in contrast to TACE, a single treatment session (after proper pre-treatment evaluation) and it is effective in downstaging of a large tumor mass. However, the few studies on comparative efficacy of SIRS vs. TACE are retrospective and consequently it is not clear whether SIRS treatment provides a survival advantage over TACE. Finally, SIRS treatment is expensive and requires a specialized infrastructure for handling the intra-arterial injection of 90Y.In summary, the results of the present retrospective study confirm that SIRS is as safe and as effective in older patients and in younger individuals with advanced HCC. Clinical experience suggests that SIRS treatment has the potential to provide palliation to very sick older patients, probably even beyond the age of 75 years with multifocal HCC with or without portal vein thrombosis. However, before translating the already available clinical experience into guideline, it is important to verify if SIRS provides a survival advantage as compared to other standard of care treatment modalities. The variable quality of data obtained in previous retrospective clinical trials, the heterogeneous population studied, and lack of standardization of tumor growth and patient performance do not enable at present a clear cut endorsement of this procedure. Yet, individual response rates to SIRS in patients with advanced HCC are often quite impressive and this treatment modality should remain available in the frame of controlled prospective clinical trials in young and old patients alike.Conflict of interestThe author declared that he does not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. Treatment of liver disease in the elderly: The case of radioembolization for advanced hepatocellular carcinomaManagement of chronic liver disease and hepatocellular carcinoma (HCC) in older age groups beyond the age of 70 years has been changing in the past decade. The availability of a growing spectrum of anti-viral agents for treatment of chronic viral hepatitis B and C as well the introduction of several non-surgical modalities for loco-regional treatment of advanced HCC have had a major impact on the clinical practice and survival of young and old patients alike [1EASL-EORTC clinical practice guidelines Management of hepatocellular carcinoma.J Hepatol. 2012; 56: 908-943Abstract Full Text Full Text PDF PubMed Scopus (4475) Google Scholar, 2Bruix J. Sherman M. Management of hepatocellular carcinoma: an update.Hepatology. 2011; 53: 1020-1022Crossref PubMed Scopus (6512) Google Scholar, 3Floreani A. Liver diseases in the elderly: an update.Dig Dis. 2007; 25: 138-143Crossref PubMed Scopus (47) Google Scholar]. Cirrhosis of the liver is the most common risk factor for HCC, irrespective of age. The pathophysiology of cirrhosis and consequently also of HCC is driven by several factors including the individual hepatic morbidities associated with HCC (i.e., persistent viral infection, metabolic and/or alcoholic liver disease), which have a variable clinical presentation at older age. The introduction of universal vaccination against hepatitis B virus (HBV) infection in over 170 countries is already leading to a decrease in the incidence of hepatitis B and HCC worldwide. Yet, the incidence of HCC is expected to rise in the next decades due to the current inability to control the progression of hepatitis C virus (HCV) infection on a global scale. In this context, it is important to note that the mean age of diagnosis of HCC, especially in the Western hemisphere varies between 63 and 65 years as compared to 55–59 years in China [[4]El-Serag H.B. Epidemiology of viral hepatitis and hepatocellular carcinoma.Gastroenterology. 2012; 142 ([e1261]): 1264-1273Abstract Full Text Full Text PDF PubMed Scopus (2341) Google Scholar]. The proportion of HCC patients, 70 years and older, seeking treatment has been rising steadily, especially in the US and Europe [4El-Serag H.B. Epidemiology of viral hepatitis and hepatocellular carcinoma.Gastroenterology. 2012; 142 ([e1261]): 1264-1273Abstract Full Text Full Text PDF PubMed Scopus (2341) Google Scholar, 5Altekruse S.F. McGlynn K.A. Reichman M.E. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005.J Clin Oncol. 2009; 27: 1485-1491Crossref PubMed Scopus (1373) Google Scholar, 6Nordenstedt H. White D.L. El-Serag H.B. The changing pattern of epidemiology in hepatocellular carcinoma.Dig Liver Dis. 2010; 42: S206-S214Abstract Full Text PDF PubMed Scopus (413) Google Scholar], although there seems to be a shift of the peak of HCC incidence in some regions to relatively younger age groups [[7]El-Serag H.B. Mason A.C. Rising incidence of hepatocellular carcinoma in the United States.N Engl J Med. 1999; 340: 745-750Crossref PubMed Scopus (2708) Google Scholar]. In the past two decades, major progress has been made in the treatment of HCC including the development of various effective ablation procedures for loco-regional injection, surgical resection and liver transplantation as well as new chemotherapeutic agents [1EASL-EORTC clinical practice guidelines Management of hepatocellular carcinoma.J Hepatol. 2012; 56: 908-943Abstract Full Text Full Text PDF PubMed Scopus (4475) Google Scholar, 2Bruix J. Sherman M. Management of hepatocellular carcinoma: an update.Hepatology. 2011; 53: 1020-1022Crossref PubMed Scopus (6512) Google Scholar]. Yet, clinicians often prefer a conservative approach when considering treatment options for elderly patients with HCC, even in the presence of preserved synthetic liver functions and absence of portal hypertension. The reluctance to offer invasive treatment modalities to the elderly patient is based in part on the notion that molecular pathophysiologic changes of the aging liver predispose to a worse response to treatment, more adverse effects, and less favorable prognosis as compared to younger individuals. There is, however, limited evidence to support such a conservative approach. Indeed, data reported in aging animals and in older humans suggest an increase in hepatocyte size, a rising number of binucleated hepatocytes, a reduction in numbers of mitochondria and oxidative capacity, a loss in hepatic volume and degree of hepatic perfusion as well as a decline in regenerative capacity. However, a recent paper by Sheedfar and co-workers entitled “Liver diseases and aging: friends or foes?” is casting doubt on the practical therapeutic implications of these phenomena and asking: “Is aging an actual risk factor for liver disease or a bystander?” [[8]Sheedfar F. Di Biase S. Koonen D. Vinciguerra M. Liver diseases and aging: friends or foes?.Aging Cell. 2013; https://doi.org/10.1111/acel.12128Crossref PubMed Scopus (137) Google Scholar]. Indeed, current clinical experience suggests that various ablation procedures for HCC including transarterial chemoembolization (TACE), radiofrequency ablation (RFA) and even surgical resection in the elderly patients are not less effective and safe as compared to younger cohorts of <65 years of age [9Biselli M. Forti P. Mucci F. Foschi F.G. Marsigli L. Caputo F. et al.Chemoembolization versus chemotherapy in elderly patients with unresectable hepatocellular carcinoma and contrast uptake as prognostic factor.J Gerontol A Biol Sci Med Sci. 1997; 52: M305-M309Crossref PubMed Scopus (13) Google Scholar, 10Yau T. Yao T.J. Chan P. Epstein R.J. Ng K.K. Chok S.H. et al.The outcomes of elderly patients with hepatocellular carcinoma treated with transarterial chemoembolization.Cancer. 2009; 115: 5507-5515Crossref PubMed Scopus (36) Google Scholar, 11Mirici-Cappa F. Gramenzi A. Santi V. Zambruni A. Di Micoli A. Frigerio M. et al.Treatments for hepatocellular carcinoma in elderly patients are as effective as in younger patients: a 20-year multicentre experience.Gut. 2010; 59: 387-396Crossref PubMed Scopus (136) Google Scholar, 12Lee S.H. Choi H.C. Jeong S.H. Lee K.H. Chung J.I. Park Y.S. et al.Hepatocellular carcinoma in older adults: clinical features, treatments, and survival.J Am Geriatr Soc. 2011; 59: 241-250Crossref PubMed Scopus (27) Google Scholar, 13Cohen M.J. Bloom A.I. Barak O. Klimov A. Nesher T. Shouval D. et al.Trans-arterial chemo-embolization is safe and effective for very elderly patients with hepatocellular carcinoma.World J Gastroenterol. 2013; 19: 2521-2528Crossref PubMed Scopus (38) Google Scholar, 14Lui W.Y. Chau G.Y. Wu C.W. King K.L. Surgical resection of hepatocellular carcinoma in elderly cirrhotic patients.Hepatogastroenterology. 1999; 46: 640-645PubMed Google Scholar, 15Hiraoka A. Michitaka K. Horiike N. Hidaka S. Uehara T. Ichikawa S. et al.Radiofrequency ablation therapy for hepatocellular carcinoma in elderly patients.J Gastroenterol Hepatol. 2010; 25: 403-407Crossref PubMed Scopus (61) Google Scholar].In this context, it is also important to assess the safety and effectiveness of transarterial radioembolization, referred to also as selective internal radiation therapy (SIRS), using 90Ytrium in the elderly population. Early versions of SIRS treatment were already developed in the 1990s [[16]Triller J. Rosler H. Geiger L. Baer H.U. Methods for the superselective radioembolization of liver tumors with 90yttrium-resin particles.Rofo. 1994; 161: 425-431Crossref PubMed Google Scholar]. It took however more than a decade to develop clinically usable compounds containing either 90Y labeled glass or resin microspheres for intra-arterial injection to the liver. SIRS has been evaluated in a number of clinical trials in patients with unresectable HCC, in patients with hepatic metastases of colorectal cancer, neuroendocrine tumors, cholangiocarcinoma and metastatic carcinoma [17Ibrahim S.M. Lewandowski R.J. Sato K.T. Gates V.L. Kulik L. Mulcahy M.F. et al.Radioembolization for the treatment of unresectable hepatocellular carcinoma: a clinical review.World J Gastroenterol. 2008; 14: 1664-1669Crossref PubMed Scopus (83) Google Scholar, 18Woodall C.E. Scoggins C.R. Ellis S.F. Tatum C.M. Hahl M.J. Ravindra K.V. et al.Is selective internal radioembolization safe and effective for patients with inoperable hepatocellular carcinoma and venous thrombosis?.J Am Coll Surg. 2009; 208: 375-382Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar, 19Salem R. Lewandowski R.J. Kulik L. Wang E. Riaz A. Ryu R.K. et al.Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma.Gastroenterology. 2011; 140 (e492): 497-507Abstract Full Text Full Text PDF PubMed Scopus (477) Google Scholar, 20Deleporte A. Flamen P. Hendlisz A. State of the art: radiolabeled microspheres treatment for liver malignancies.Expert Opin Pharmacother. 2010; 11: 579-586Crossref PubMed Scopus (24) Google Scholar, 21Kim Y.H. Kim do Y. Yttrium-90 radioembolization for hepatocellular carcinoma: what we know and what we need to know.Oncology. 2013; 84: 34-39Crossref PubMed Scopus (13) Google Scholar, 22Sangro B. Carpanese L. Cianni R. Golfieri R. Gasparini D. Ezziddin S. et al.Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation.Hepatology. 2011; 54: 868-878Crossref PubMed Scopus (469) Google Scholar, 23Chiesa C. Mira M. Maccauro M. Romito R. Spreafico C. Sposito C. et al.A dosimetric treatment planning strategy in radioembolization of hepatocarcinoma with 90Y glass microspheres.Q J Nucl Med Mol Imaging. 2012; 56: 503-508PubMed Google Scholar, 24Mazzaferro V. Sposito C. Bhoori S. Romito R. Chiesa C. Morosi C. et al.Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study.Hepatology. 2013; 57: 1826-1837Crossref PubMed Scopus (330) Google Scholar]. In a recent retrospective comparative clinical trial, toxicity and survival were evaluated in 245 HCC patients treated by TACE and 123 patients treated by SIRS over a period of 9 years. A statistically non-significant trend for a higher response rate was observed in 49% of SIRS recipients as compared to 36% of TACE treated patients (p = 0.104). Time to tumor progression was longer following SIRS, 13.4 vs. 8.4 months (p = 0.046). Yet, median survival was not statistically different, ranging between 20.5 and 17.4 months following SIRS and TACE respectively [[19]Salem R. Lewandowski R.J. Kulik L. Wang E. Riaz A. Ryu R.K. et al.Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma.Gastroenterology. 2011; 140 (e492): 497-507Abstract Full Text Full Text PDF PubMed Scopus (477) Google Scholar]. Abdominal pain and “transaminitis” were more frequent in TACE recipients (p <0.05). Until recently, limited data we