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 Table of Contents  
EDITORIAL
Year : 2018  |  Volume : 2  |  Issue : 1  |  Page : 1-3

Transarterial embolization of intermediate hepatocellular carcinoma in elderly patients: Which technique should be first-line?


1 Department of Medical Imaging, King Abdulaziz Medical City, Jeddah, Saudi Arabia
2 Department of Oncology, King Abdulaziz Medical City, Riyadh, Saudi Arabia

Date of Web Publication6-Feb-2018

Correspondence Address:
Azzam Khankan
Department of Medical Imaging, King Abdulaziz Medical City, Jeddah
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AJIR.AJIR_4_18

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How to cite this article:
Khankan A, Jazieh AR. Transarterial embolization of intermediate hepatocellular carcinoma in elderly patients: Which technique should be first-line?. Arab J Intervent Radiol 2018;2:1-3

How to cite this URL:
Khankan A, Jazieh AR. Transarterial embolization of intermediate hepatocellular carcinoma in elderly patients: Which technique should be first-line?. Arab J Intervent Radiol [serial online] 2018 [cited 2018 Aug 14];2:1-3. Available from: http://www.arabjir.com/text.asp?2018/2/1/1/224830

In the last few decades, the treatment of hepatocellular carcinoma (HCC) has significantly improved with established efficacy of many interventional radiologic therapies. As per current international guidelines, the choice of optimal therapy is based on clinical, biological, and radiological factors such as performance status, tumor characteristics, liver functions, and comorbidities. However, age is not quoted in any treatment strategies.[1] The management of HCC in elderly patients is significantly more complicated than that of younger patients due to the comorbidities and fear of potential toxicity that may be related to any given therapy, which may result in poor adherence to guidelines recommendations. Thus, elderly patients did not receive optimal therapy.[2] This article discusses several questions that surround treatment of elderly patients with HCC:

  • What does palliative treatment really mean to the physician and the patient?
  • How does the overall patient's condition impact treatment decisions to ensure that the selected therapy has a safe and speedy recovery?
  • How does the technical complexity, clinical effectiveness, and cost-effectiveness impact treatment decisions in elderly patients with the availability of all treatments options?
  • How does quality-of-life (QoL) impact treatment decisions in elderly patients with limited survival time?
  • How should these priorities be weighed when choosing the treatment?


Hepatobiliary cancers have been associated with a poor prognosis and diminished health-related QoL, with pain, jaundice, anorexia, and depression as common symptoms.[3]

Majority of patients with HCC are treated with palliative intent due to the late-stage presentation, comorbidities, and limited donor availability. Many locoregional therapies are available as palliative therapies to treat those patients with differences regarding patient and disease characterizations, indications, side effects, and cost but may have similar survival rate. That is clear when comparing two transarterial emblotherapies; transarterial chemoembolization (TACE) to radioembolization with Y-90 (RE). Both TACE and RE have been shown to improve overall survival in HCC patients with equivalent survival rate.[4],[5],[6],[7],[8],[9] Although no randomized prospective trials comparing TACE to RE, it has been reported that RE may have better profile in terms of adverse events, clinical toxicities, response rate, and time-to-progression compared with TACE.[10],[11] Moreover, RE performed better than TACE in downstaging to transplantation, time-to-progression [12] and in safe use for advanced patient population such as vascular invasion without the risk of ischemic hepatitis.[13]

Postembolization syndrome is the most common adverse effect of TACE. It manifests by pain, nausea, vomiting, and fever and it usually managed during the hospitalization (1–3 days). Other complications may include biliary duct injury, liver abscesses in patients after biliary interventions, duodenal, or gastric ulcers from the inadvertent deposition of the chemotherapeutic agents, vascular injuries such as spasm/dissection from repeated chemotherapy injection in the arterial system, tumor rupture, and hepatic failure.[14],[15],[16] Adverse effects of RE are distinctly different from those related to TACE. Fatigue and nausea are the dominant adverse effects. Others adverse include duodenal or gastric ulcer from nontarget deposition of microspheres, fibrosis/scarring of the liver parenchyma, cholecystitis, and radioembolization-induced liver disease.[17],[18]

In general, TACE is associated with higher rates of clinical toxicities including abdominal pain, nausea, and hospitalization compare to RE.[10],[19]

In elderly patients (>70 years), RE appeared to be well tolerated and effective with no more toxicity compared to younger patients with unresectable HCC.[20],[21] Elderly patients should be considered for RE if they otherwise meet the inclusion criteria applicable to younger patients and age alone should not be a discriminating factor for the management of HCC patients.


  Quality of Life Top


Although in oncology outcomes are generally measured in terms of toxicities and survival, it has been reported that up to 95% of patients with advanced cancer state that their QoL was at least as important as the length of life.[22] For HCC with reduced life expectancy and unavailable curative treatment, the goal of treatment is to relieve the symptoms and maintain the patients' functional status. Therefore, health-related QoL has emerged as both clinically significant and biologically meaningful in HCC patients outcome analysis. It is as relevant as the disease progression and response to treatment.[23] A recent prospective study has compared health-related QoL in HCC patients receiving TACE or 90Y RE using Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep), a validated tool for hepatobiliary malignancies.[24],[25]

It used an embolotherapy-specific score (ESS) that reflects the summation of embolization specific toxicities most commonly experienced by patients after TACE or RE. The score was created from the FACT-Hep items, capturing QoL parameters most relevant to embolization procedures including the following items: pain, bothered by treatment side effects, able to work, diarrhea, and good appetite. The study concluded that patients who received RE had significant increase in several features of QoL, whereas patients who received TACE had decrease in QoL scores. The increase was greatest in the ESS representing that RE is better in maintaining health-related QoL when compared with TACE.


  Cost Top


The cost of interventional radiology (IR) procedures in the treatment of HCC is a factor that may impact treatment decision. A cost analysis from the payer perspective was performed to determine whether there is a cost advantage for one of the commonly performed IR procedures in the treatment of HCC using decision-tree analysis and taking into consideration repeat procedure rate.[14] The study uses Monte Carlo Simulation for randomizing the distribution of the value for each variable in the models. The variables included allowable reimbursements of each procedure type, the probability of the need for repeat procedures, and the underlying mortality rate (which was determined by the age and sex of any potential subject). The direct cost comparison between TACE and TARE showed that although TACE is less costly on a per procedure basis, it is typically repeated far more frequently than TARE which makes it potentially more costly and the Monte Carlo simulation showed a preference for RE in more than one-third of all scenarios. Sensitivity analyses showed that the most important variables assessed were the need for repeat procedures.


  Palliative Therapy Top


The World Health Organization defined palliative care as “an approach that improves the QoL of patients and their families facing the problem associated with life-threatening illness, through the prevention, and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial, and spiritual.”[26] The goal of palliative treatment then is to prevent and relieve suffering and to improve the QoL for people facing serious, complex illness. To be successful, palliative care requires attention to all aspects of a patient's suffering.

The choice of IR procedure in treating patients with HCC should be evidence based to ensure optimal outcome. However, the therapeutic decisions have to be personalized and based on the individual circumstances taking into consideration the patient's overall condition and the QoL before proceeding with any intervention. Although there are needs for randomized prospective trials comparing TACE and RE that incorporate QoL and econometrics in addition to other oncologic variables such as time-to-progression and combination with systemic therapy, the aforementioned seminal studies in this manuscript should be taken into consideration and QoL should be considered as important as overall survival and the goal of all palliative measures should include QoL as endpoints in HCC patients with reduced life expectancy. As patients grow increasingly knowledgeable about available treatment options, their concerns about QoL emerge as leading factors in decision-making. The Belmont Principles of medical ethics require both respect for patient's autonomy and beneficence, that is, acting in the best interest of the patient.[27] It is reasonable and ethical to provide the patients with detailed information on the available therapies weighing benefits versus risks. Since TACE and TARE are medically equivalent in benefit and risk in intermediate-advanced HCC, it is appropriate to let the patients decide which form of embolotherapy to have at the first-line rather than to take decision on their behalf.

In summary, when considering an intervention for patients with intermediate HCC, a decision should not be based on the sole cost of the procedure but should take into account more comprehensive view about risk-benefit assessment, input on QoL, and patient preference. The role of multidisciplinary teams and institutional experience cannot be overemphasized.

 
  References Top

1.
Brunot A, Le Sourd S, Pracht M, Edeline J. Hepatocellular carcinoma in elderly patients: Challenges and solutions. J Hepatocell Carcinoma 2016;3:9-18.  Back to cited text no. 1
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2.
Mirici-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;59:387-96.  Back to cited text no. 2
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Heffernan N, Cella D, Webster K, Odom L, Martone M, Passik S, et al. Measuring health-related quality of life in patients with hepatobiliary cancers: The functional assessment of cancer therapy-hepatobiliary questionnaire. J Clin Oncol 2002;20:2229-39.  Back to cited text no. 3
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4.
Salem R, Lewandowski RJ, Mulcahy MF, Riaz A, Ryu RK, Ibrahim S, et al. Radioembolization for hepatocellular carcinoma using yttrium-90 microspheres: A comprehensive report of long-term outcomes. Gastroenterology 2010;138:52-64.  Back to cited text no. 4
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Lewandowski RJ, Mulcahy MF, Kulik LM, Riaz A, Ryu RK, Baker TB, et al. Chemoembolization for hepatocellular carcinoma: Comprehensive imaging and survival analysis in a 172-patient cohort. Radiology 2010;255:955-65.  Back to cited text no. 5
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European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: Management of hepatocellular carcinoma. J Hepatol 2012;56:908-43.  Back to cited text no. 6
    
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Hilgard P, Hamami M, Fouly AE, Scherag A, Müller S, Ertle J, et al. Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival. Hepatology 2010;52:1741-9.  Back to cited text no. 7
    
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Sangro 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;54:868-78.  Back to cited text no. 8
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Salem R, Mazzaferro V, Sangro B. Yttrium 90 radioembolization for the treatment of hepatocellular carcinoma: Biological lessons, current challenges, and clinical perspectives. Hepatology 2013;58:2188-97.  Back to cited text no. 9
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Salem R, Lewandowski RJ, Kulik L, Wang E, Riaz A, Ryu RK, et al. Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology 2011;140:497-507.e2.  Back to cited text no. 10
    
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Salem R, Lewandowski RJ. Chemoembolization and radioembolization for hepatocellular carcinoma. Clin Gastroenterol Hepatol 2013;11:604-11.  Back to cited text no. 11
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12.
Lewandowski RJ, Kulik LM, Riaz A, Senthilnathan S, Mulcahy MF, Ryu RK, et al. A comparative analysis of transarterial downstaging for hepatocellular carcinoma: Chemoembolization versus radioembolization. Am J Transplant 2009;9:1920-8.  Back to cited text no. 12
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13.
Memon K, Kulik L, Lewandowski RJ, Mulcahy MF, Benson AB, Ganger D, et al. Radioembolization for hepatocellular carcinoma with portal vein thrombosis: Impact of liver function on systemic treatment options at disease progression. J Hepatol 2013;58:73-80.  Back to cited text no. 13
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14.
Ray CE Jr., Battaglia C, Libby AM, Prochazka A, Xu S, Funaki B, et al. Interventional radiologic treatment of hepatocellular carcinoma – A cost analysis from the payer perspective. J Vasc Interv Radiol 2012;23:306-14.  Back to cited text no. 14
    
15.
Belli L, Magistretti G, Puricelli GP, Damiani G, Colombo E, Cornalba GP, et al. Arteritis following intra-arterial chemotherapy for liver tumors. Eur Radiol 1997;7:323-6.  Back to cited text no. 15
    
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Malagari K, Pomoni M, Spyridopoulos TN, Moschouris H, Kelekis A, Dourakis S, et al. Safety profile of sequential transcatheter chemoembolization with DC bead™: Results of 237 hepatocellular carcinoma (HCC) patients. Cardiovasc Intervent Radiol 2011;34:774-85.  Back to cited text no. 16
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17.
Riaz A, Lewandowski RJ, Kulik LM, Mulcahy MF, Sato KT, Ryu RK, et al. Complications following radioembolization with yttrium-90 microspheres: A comprehensive literature review. J Vasc Interv Radiol 2009;20:1121-30.  Back to cited text no. 17
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18.
Gil-Alzugaray B, Chopitea A, Iñarrairaegui M, Bilbao JI, Rodriguez-Fraile M, Rodriguez J, et al. Prognostic factors and prevention of radioembolization-induced liver disease. Hepatology 2013;57:1078-87.  Back to cited text no. 18
    
19.
Kooby DA, Egnatashvili V, Srinivasan S, Chamsuddin A, Delman KA, Kauh J, et al. Comparison of yttrium-90 radioembolization and transcatheter arterial chemoembolization for the treatment of unresectable hepatocellular carcinoma. J Vasc Interv Radiol 2010;21:224-30.  Back to cited text no. 19
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20.
Golfieri R, Bilbao JI, Carpanese L, Cianni R, Gasparini D, Ezziddin S, et al. Comparison of the survival and tolerability of radioembolization in elderly vs. Younger patients with unresectable hepatocellular carcinoma. J Hepatol 2013;59:753-61.  Back to cited text no. 20
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21.
Iñarrairaegui M, Bilbao JI, Rodríguez M, Benito A, Sangro B. Liver radioembolization using 90Y resin microspheres in elderly patients: Tolerance and outcome. Hosp Pract (1995) 2010;38:103-9.  Back to cited text no. 21
    
22.
Meropol NJ, Weinfurt KP, Burnett CB, Balshem A, Benson AB 3rd, Castel L, et al. Perceptions of patients and physicians regarding phase I cancer clinical trials: Implications for physician-patient communication. J Clin Oncol 2003;21:2589-96.  Back to cited text no. 22
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23.
Steel JL, Eton DT, Cella D, Olek MC, Carr BI. Clinically meaningful changes in health-related quality of life in patients diagnosed with hepatobiliary carcinoma. Ann Oncol 2006;17:304-12.  Back to cited text no. 23
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24.
Salem R, Gilbertsen M, Butt Z, Memon K, Vouche M, Hickey R, et al. Increased quality of life among hepatocellular carcinoma patients treated with radioembolization, compared with chemoembolization. Clin Gastroenterol Hepatol 2013;11:1358-650.  Back to cited text no. 24
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25.
Steel J, Baum A, Carr B. Quality of life in patients diagnosed with primary hepatocellular carcinoma: Hepatic arterial infusion of cisplatin versus 90-yttrium microspheres (Therasphere). Psychooncology 2004;13:73-9.  Back to cited text no. 25
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26.
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27.
Sims JM. A brief review of the belmont report. Dimens Crit Care Nurs 2010;29:173-4.  Back to cited text no. 27
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