Targeting Radiotherapy in the Liver: SIR-Spheres®

Andrew S. Kennedy, MD, FACRO

The liver is a common site of metastatic recurrence for many tumors, including colorectal cancers (CRCs).¹For a minority of patients, surgical resection may be an option; however, most patients will not qualify for surgery due to insufficient liver functional reserve or other contraindications.¹Locoregional interventions, such as radiofrequency or microwave ablation may be an option for palliative care or, in some cases, curative intent, although the prognosis for such patients is poor.¹Radiation therapy plays an increasingly important role in the treatment of both primary hepatocellular carcinoma and metastatic liver disease.¹Evidence supporting the use and safety of more advanced targeted RT techniques, including stereotactic body radiotherapy and proton beam therapy, has been recently reviewed.¹Of note, both retrospective and prospective data supporting the use of Selective Internal Radiation or SIRT within liver tumors, using microspheres containing yttrium-90 (SIR-Spheres® microspheres) continue to accumulate.^1-3

According to Andrew S. Kennedy, MD, FACRO, physician in chief of radiation oncology and director of radiation oncology research at Sarah Cannon Research Institute in Nashville, Tennessee, SIR-Spheres® microspheres are essentially radiation-containing microparticles that are delivered directly to tumors in the liver.

“Yttrium 90 has a half-life of 64 hours, so almost all of the radiation is delivered over the first 11 days, so while the microspheres are a permanent implant, it’s a very safe way of giving radiation,” Kennedy said.

During an interview at the ASCO Annual Meeting, he described the overall process, whereby a microcatheter inserted into the common hepatic artery or left or right hepatic artery is utilized to deliver approximately 15 to 20 million of the radioactive microspheres in the tumors. The size of the microspheres is important (≈20 to 60 microns in diameter). “They’re small enough to get into the tumor, but too large to get out of the tumor,” Kennedy noted. This enables them to become permanently embedded in the tumor which is then killed by the radiation, with normal tissue being spared.²

Radiation is emitted to treat the tumor in much the same way as a battery would expend its energy until it has been completely depleted, according to Kennedy. Yttrium-90 is a pure beta emitter and, in therapeutic use, 94% of the radiation is delivered within 11 days.²

Kennedy emphasized the low toxicity of the technique, citing his experience with patients who have virtually no side effects from the treatment (≈90%). “[For] those that do have side effects, it is generally fatigue, lasting 3 to 5 days after the procedure; a few will have pain, and a few will have some nausea,” he said. “Very rarely do those symptoms last more than 5 days,” he added, noting that if symptoms do occur, they can be readily managed with medications.

SIR-Spheres® microspheres were first approved by the US Food and Drug Administration for use in hepatic metastases in CRC in 2002. A retrospective analysis of patients in the United States found mild and transient toxicity and an encouraging median survival of 10.1 months in heavily pretreated metastatic CRC patients.⁴Additional and extensive experience with SIR-Spheres® in the treatment of liver metastases in CRC across a broad clinical platform has been summarized elsewhere.³

“The indications for radioactive microspheres are only in the liver, and only in tumors that can’t be removed by surgery. So, regardless of the tumor type, if it’s in the liver, and it’s not responding to chemotherapy, or even if it’s partially responding, those patients should all be considered for this approach,” Kennedy stated.

“I’ve been fortunate to use radioactive microspheres since 1999, and over the last decade or so, I’ve seen tremendous improvement in the acceptability of this modality,” Kennedy noted. “I know it works wonderfully for a lot of patients.” He added, however, that one frustration has been that patients who most need this type of therapy often are not being cared for by physicians that have sufficient knowledge or understanding of the procedure.

“I am very excited that it’s getting more and more accessibility,” Kennedy said. “The frustration over the years has been that patients I know would benefit weren’t being offered this treatment.” He also stressed that it is important for patients with hepatic tumors to ask their medical oncologist about treatment with SIR-Spheres®.

Kennedy noted that some emerging data on SIRSpheres ® are expected in the near future. In particular, results from a study previously presented in part at the American Society for Clinical Oncology (ASCO) Annual Meeting in 2012⁴are to be published this year. He also said that results from the SIRFLOX study (NCT00724503) are expected to be available early next year, and presented at the next ASCO Annual Meeting in 2015.

References

1. Kennedy AS. Radiation oncology approaches in liver malignancies.Am Soc Clin Oncol Educ Book. 2014;34:e150-e155. doi:10.14694/EdBook_ AM.2014.34.e150.
2. SIR-Spheres® microspheres (yttrium-90 microspheres) [package insert]. North Sydney, Australia: Sirtex Medical Limited; 2013.
3. Sirtex Medical Limited. SIR-Spheres® in Colorectal Cancer. http://www .sirspheresmicrospheres.com/media/34437/summary_of_sir-spheres_ in_mcrc_638-u-1112.pdf. Accessed: June 16, 2014.
4. Kennedy AS, Ball D, Cohen SJ, et al. US patients receiving resin 90Y microspheres for unresectable colorectal liver metastases: a multicenter study of 506 patients. Poster presented at the Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2012. Abstract 3590.