Selective internal radiation therapy (SIRT) with yttrium-90 microspheres and peri-procedural FOLFIRI/irinotecan in pre-treated colorectal liver metastases patients: An analysis of outcomes from a UK Cancer Centre between 2009 and 2017
Authors: G. Wilson, D. Bentley, S. Mullamitha, M. Braun, M. Nasralla, J. Bell, D. Mullan, J. Hasan, M. Saunders, F. Marti, C. McBain, N. Alam, H. Laasch, P. Najran, T. Westwood, S. Jeans, J. Tipping, P. Manoharan, J. Lawrance
Journal: Annals of Oncology (2018)

Introduction: Selective Internal Radiation Therapy (SIRT) involves hepatic intra-arterial infusion of β-particle emitting Yttrium-90 labelled microspheres. SIRT increases first line response rates (RR) and hepatic progression free survival (hPFS) in liver predominant metastatic colorectal cancer (mCRC) patients treated with oxaliplatin/5FU/folinic acid (FOLFOX). SIRT is often used in pre-treated mCRC patients with peri-procedural FOLFOX to achieve radio-sensitization and control extra-hepatic disease. Since 2009 we have used FOLFIRI as an alternative peri-procedural regimen with SIRT. Methods: Between 2009 and 2017 we treated 32 mCRC patients with SIRT and peri-procedural irinotecan based chemotherapy followed by further chemotherapy cycles at clinician's discretion. Nine patients also received concurrent cetuximab. Of 32 patients, 20 were KRAS wild type, 12 KRAS mutated. Extra-hepatic disease: 11 patients. Primary in-situ: 7 patients. Average number of metastatic lines of pre-SIRT chemotherapy was 2.1. Not included in the analysis were 4 patients who commenced FOLFIRI up to 2 weeks after SIRT and 11 patients who received FOLFIRI prior to SIRT but not peri-procedurally. 30/32 (94%) patients had prior oxaliplatin+5FU/capecitabine. 28/32 patients (88%) had prior irinotecan, 25 with 5FU/capecitabine. Thirty patients received FOLFIRI (irinotecan 180mg/m2, 5FU 400mg/m2 day 1 and 2400mg/m2 via infuser pump over 46 hrs) and 2 had single agent irinotecan with no 5FU given. In 26 cases SIRT was delivered on FOLFIRI day 2 with 5FU infusion continuing. Eight patients received SIRT within the 2 days prior to chemotherapy. The average number of subsequent cycles of FOLFIRI/irinotecan given after the SIRT+ chemo was 5.2. PET-CT was performed pre-SIRT and 2-3 months later. The median number of subsequent chemotherapy lines was 1 with 4 patients remaining alive at time of censorship. Data was correlated from retrospective case note review using standard statistical techniques to evaluate response, hepatic (h) and extra-hepatic (eh) progression free survival (PFS) and overall survival (OS). Due to the retrospective nature of the analysis, toxicity data was limited but there were no reported cases of neutropenic sepsis or death within 30 days of SIRT, and no cases of Radiation Induced Liver Disease (RILD). Results: In the treated liver, responses were as follows: CT response rates: PR 28% (n = 9), SD 31% (n = 10) and PD 41% (n = 13); PET response rates: PR 34% (n = 11), SD 34% (n = 11), PD 31% (n = 10). Fourteen patients had PD outside the liver at first assessment. Of those 14 patients, 2 had PR and 2 had SD in the liver at that assessment. Median hPFS (n = 31) was 5.62 months (CI 3.22-6.64 m). Median ehPFS in the group with pre-SIRT known extra-hepatic disease (n = 11) was 2.60 months (CI 1.35-5.22 months). Median OS (n = 32) was 12.58 months (CI 9.07-16.30m). Conclusion: SIRT with peri-procedural FOLFIRI in pre-treated mCRC patients produces encouraging response rates and survival. RILD was not observed and the treatment seems to be well tolerated. SIRT with FOLFIRI provides an alternative strategy for patients with pre-treated liver predominant mCRC.