Jul 31

Recent Advances in Radioembolism Therapy for the Treatment of Liver Cancer

Welcome to the first in our new monthly “Recent Advances” blog series, where we bring you the latest developments in the use of NM-related techniques for the diagnosis and/or treatment of common disease. In this inaugural issue we discuss the use of radioembolism therapy for the treatment of liver cancer. Radioembolism involves the injection of radioactive particles (microspheres loaded with 90Y) into the femoral artery, which then travel to the liver where they both occlude the hepatic blood vessels and release the yttrium particles to deliver high-dose radiation to the tumor while sparing normal tumor tissue. Although it is used traditionally for the treatment of unresectable and chemoresistant primary or secondary hepatic malignancies, it is being used increasingly in early-advanced tumors [1,2]. A number of new approaches to and developments in radioembolism therapy have been reported recently, and we discuss some of these below.

Recent studies have assessed the efficacy of personalized approaches to radioembolism treatment, using individualized and intensification regimens [2]. The authors used an initial tumor dose threshold of 205 Gy, and then used 99mTc-macroaggregated albumin SPECT/CT to determine the treatment specificity and sensitivity (90% and 100%m respectively). They calculated the actual tumor dose and healthy injected liver dose, and then used the resulting values to determine which patients received intensified treatment (with the aim of achieving a tumor dose >205 Gy and a healthy injected liver dose <120 Gy by applying an injected liver dose >150 Gy). The use of the intensification regimen achieved a response rate of 85% without increasing liver toxicity compared with patients who did not receive intensification.

An additional recent trial assessed how altering the characteristics of the microspheres themselves affects the safety and potential efficacy of radioembolism therapy [3]. Specifically, the authors used extended-shelf-life 90Y glass microspheres to treat 134 patients, and then assessed the resulting tumor distribution and adverse events. Imaging was performed and laboratory data were collected at baseline and at 3-month intervals post-treatment. The extended-shelf-life microspheres achieved a 103% increase in the number of microspheres delivered to the tumor compared with standard treatment, without increasing toxicity.

Pilot randomized clinical trials have been published that compared the use of 90Y-radioembolism therapy with other treatments, such as such as the monoclonal antibody sorafenib [4] and chemoembolism [5]. Sorafenib and radioembolism achieved comparable patient survival. Compared with chemoembolization, radioembolism achieved a similar tumor control and health-related quality of life. Although the disease control rates were similar, the use of chemoembolization resulted in a better overall response rate.

The final study we decided to highlight assessed the potential of determining tumor heterogeneity using histogram analysis of CT to predict the response of hepatocellular carcinoma patients to transarterial radioembolism [6]. The authors determined arterial perfusion from CT perfusion in the entire tumor volume, and then assessed the response to therapy using follow-up imaging. The results revealed that arterial perfusion was significantly lower in non-responders compared with responders. The authors concluded that the use of voxel-wise histogram analysis of pretreatment CT perfusion to determine tumor heterogeneity could predict the response to treatment.

Overall, research and clinical trials into the use of 90Y-based radioembolism therapy is expanding rapidly, and important new developments are being published. Combining enhanced imaging methods with improved dosing and delivery might lead to the adoption of this important technique more widely and increase the number of potential indications.

What are your thoughts on radioembolism and its future? What developments do you see coming next? As always, we would love to hear your thoughts.

  1. Braat AJAT, Smits MLJ, Braat MNGJA, van den Hoven AF, Prince JF, de Jong HWAM, et al.: Yttrium-90 hepatic radioembolization: an update on current practice and recent developments. J Nucl Med 2015 May 7;56:1079–87.
  2. Garin E, Rolland Y, Edeline J, Icard N, Lenoir L, Laffont S, et al.: Personalized dosimetry with intensification using 90Y-loaded glass microsphere radioembolization induces prolonged overall survival in hepatocellular carcinoma patients with portal vein thrombosis. J Nucl Med 2015 Mar;56:339–46.
  3. Lewandowski RJ, Minocha J, Memon K, Riaz A, Gates VL, Ryu RK, et al.: Sustained safety and efficacy of extended-shelf-life (90)Y glass microspheres: long-term follow-up in a 134-patient cohort. Eur J Nucl Med Mol Imaging 2014 Mar;41:486–93.
  4. Gramenzi A, Golfieri R, Mosconi C, Cappelli A, Granito A, Cucchetti A, et al.: Yttrium-90 radioembolization vs sorafenib for intermediate-locally advanced hepatocellular carcinoma: a cohort study with propensity score analysis. Liver Int 2015 Mar;35:1036–47.
  5. Kolligs FT, Bilbao JI, Jakobs T, Iñarrairaegui M, Nagel JM, Rodriguez M, et al.: Pilot randomized trial of selective internal radiation therapy vs. chemoembolization in unresectable hepatocellular carcinoma. Liver Int 2015 Jul;35:1715–21.
  6. Reiner CS, Gordic S, Puippe G, Morsbach F, Wurnig M, Schaefer N, et al.: Histogram Analysis of CT Perfusion of Hepatocellular Carcinoma for Predicting Response to Transarterial Radioembolization: Value of Tumor Heterogeneity Assessment. Cardiovasc Intervent Radiol 2015 Jul 28; DOI: 10.1007/s00270-015-1185-1