SRT//Yttrium-90: Have We Found Its Place?

Many valid points. The conclusion is a little -ve.
Note some peripheral funding by Bayer.

http://jco.ascopubs.org/content/early/2016/09/07/JCO.2016.68.6782?ct

We read with interest the recent article in Journal of Clinical Oncology by van Hazel et al,¹ which examines the addition of selective internal radiation therapy (SIRT) to a standard regimen of mFOLFOX6 (plus or minus bevacizumab). This trial represents an important milestone in assessing the utility of this technique. It also raises a number of points of interest that should be highlighted.
First, given the local control of liver metastases provided by SIRT, one could postulate that the inclusion of patients with extrahepatic disease (40% of patients in this trial) will distort analysis of efficacy of this technique, given that previous studies suggest lack of extrahepatic disease to be an independent predictor of better survival outcomes.^2,3 Equally we wonder if repeat SIRT sessions in the setting of liver-confined disease would help translate the improved median hepatic progression-free survival into an overall survival benefit. This could be done in a manner analogous to the way in which repeat transarterial chemotherapy sessions are used for effective tumor control in surgically unresectable cases of hepatocellular carcinoma.⁴ It has been shown that repeat sessions of SIRT can be performed with an acceptable safety profile.⁵
Second, we have noted in our own practice a wide variety of treatment responses to a single SIRT administration, ranging from progressive disease to a significant partial response (unpublished data). This varied response may reflect genetic heterogeneity in the tumor target in the liver. It is probable that in the future, molecular profiling of the tumor will allow greater patient selection and more targeted use of SIRT. Indeed, molecular characterization of colorectal cancer dictates use of different biologic agents, which in previous studies has been shown to have a significant impact on efficacy of SIRT administration.⁶ We wonder if the authors looked at microsatellite instability or assessed the patients for RAS/RAF mutations, and whether this had any correlation with treatment outcomes.
Third, observed toxicities in the SIRT patient cohort were comparable to those reported elsewhere.^7,8 However, it has also been reported that the use of bevacizumab is likely to increase toxicity of liver-directed therapy and has not been shown to improve outcome.⁹ In addition, a trend toward improved outcomes in patients receiving SIRT, who did not receive prior bevacizumab, has been seen in other studies.² Although the SIRFLOX trial is not intended to assess the utility of bevacizumab, we would be interested in the authors’ opinion on its use combined with SIRT, as well as with oxaliplatin-based therapy rather than irinotecan-based therapy. In our opinion, many questions need to be answered before establishing SIRT as a therapy for unresectable colorectal liver metastases. Results of the FOXFIRE trial are awaited, as is the combined overall survival data from SIRFLOX, FOXFIRE, and FOXFIRE Global.
Previous SectionNext Section
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Previous SectionNext Section
Selective Internal Radiation Therapy/Yttrium-90: Have We Found Its Place?

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer towww.asco.org/rwc orjco.ascopubs.org/site/ifc.
Previous SectionNext Section
Emily C. Harrold

Travel, Accommodations, Expenses: Bayer