For patients with unresectable liver-dominant mCRC who meet eligibility criteria for RE, (90)Y-RE microspheres appear to be effective and well-tolerated, regardless of age. Criteria for selecting patients for RE should not include age for exclusion from this potentially beneficial intervention.

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3590 Background: Implantation of radioactive microspheres via the hepatic artery with Yttrium-90 (90Y) is termed “radioembolization, (RE)”. Resin microspheres were FDA cleared for use in colorectal liver metastases (mCRC) in 2002. Rapid worldwide acceptance of this therapy has resulted in greater than 30,000 procedures conducted in the past 10 years. This investigator-initiated study focuses on RE treatment outcomes in US-only patients since 2002. Methods: A retrospective multi-institutional study was designed to analyze the outcome of consecutively treated mCRC patients undergoing RE by experienced treatment centers in the USA using resin 90Y microspheres. IRB approval was obtained by each center with independent data collection and analyses. Primary endpoints: CTC 3.0ae toxicity, RECIST response and survival; baseline treatment parameters, prior chemotherapy, and liver directed therapies. Results: 506 patients at 10 institutions (193 M, 313 F) received 770 RE treatments; median age = 60.4 years (20.8 – 91.9 years); median number of RE treatments per patient = 1.0 (1-5 treatments). Active extrahepatic disease was present at first RE in 34.8% of patients. The majority (90%) of patients received prior chemotherapy, with 30.6% also having undergone prior hepatic surgery/ablative procedures. Median follow up after RE = 8.4 mo. (0.4 – 67.6 mo.) with median survival = 10.1 mo. (95% CI 9.1 – 12.0). For first RE treatment, median tumor volume was 146.0 mL (2.8 – 3228.0 mL). Median radiation activity delivered = 1.18 GBq (0.12 – 2.29 GBq), lung shunt median = 4.8 % (.02 – 45%). Total grade 1-3 events were 32% GI, 44% fatigue and 1% liver failure. Only 2.4% of all treatments required an overnight stay post-procedure. Conclusions: The modern USA experience of 90Y therapy for unresectable, heavily pretreated mCRC liver metastases is encouraging with a median survival of 10.1 months after first RE procedure. Toxicity was mild and of short duration in most patients. RECIST response is being analyzed currently as are data of additional patients.

Background: Patients with liver metastatic colorectal cancer (mCRC) often benefit from receiving 90 Y-microsphere radioembolization (RE) administered via the hepatic arteries. Prior to delivery of liverdirected radiation, standard laboratory tests may assist in improving outcome by identifying correctable preradiation abnormalities. Methods: A database containing retrospective review of consecutively treated patients of mCRC from July 2002 to December 2011 at 11 US institutions was used. Data collected included background characteristics, prior chemotherapy, surgery/ablation, radiotherapy, vascular procedures, 90 Y treatment, subsequent adverse events and survival. Kaplan-Meier estimates compared the survival of patients across lines of chemotherapy. The following values were obtained within 10 days prior to each RE treatment:haemoglobin (HGB), albumin, alkaline phosphatase (Alk phosph), aspartate aminotransferase (AST), alanine transaminase (ALT), total bilirubin and creatinine. Common Terminology Criteria Adverse Events (CTCAEs) 3.0 grade was assigned to each parameter and analysed for impact on survival by line of chemotherapy. Consensus Guidelines were used to categorize the parameter grades as either within or outside guidelines for treatment.Results: A total of 606 patients (370 male; 236 female) were studied with a median follow-up was 8.5 mo.(IQR 4.3-15.6) after RE. Fewer than 11% of patients were treated outside recommended RE guidelines, with albumin being the most common, 10.5% grade 2 (<3-2.0 g/dL) at time of RE. All seven parameters showed statistically significant decreased median survivals with any grade >0 (P<0.001) across all lines of prior chemotherapy. Compared to grade 0, grade 2 albumin decreased overall survival 67%; for grade 2 total bilirubin a 63% drop occurred, and grade 1 HGB resulted in 66% lower median survival. Conclusions: Review of pre-RE laboratory parameters may aid in improving median survivals if correctable grade >0 values are addressed prior to radiation delivery. HGB <10 g/dL is a well-known negative factor in radiation response and is easily corrected. Improving other parameters is more challenging. These efforts are important in optimizing treatment response to liver radiotherapy. IntroductionColorectal cancer is the third most common can¬cer and the second most common cause of cancer death in developed countries (1). The mainstay for the management of metastatic colorectal cancer (mCRC) is chemotherapy ± biologic therapies (2). Drug and regimen advances in systemic therapy (3) have substantially improved median survivals over the last decades and provided a meaningful window for the localized control of liver metastases (a common presentation in mCRC patients), especially whenever the extrahepatic disease appears to have an indolent clinical course. Liver-directed approaches to therapy are used to treat: (I) discrete, visually-targeted tumors using resection, ablation, NanoKnife ® (U/S), irreversible electroporation (IRE), or stereotactic body radiation therapy (SBRT)...

270 Background: Hepatic tumor progression after one or more lines of 5FU-based systemic chemotherapy, with or without biologic agents, is an indication for radioembolization using 90Y microspheres. Methods: An independent imaging review following resin-only 90Y microsphere treated cases of mCRC from July 2002 to December 2011 at 9 US institutions was conducted. A board certified radiologist systematically reviewed hepatic Computed Tomography (CT) images (portal-venous phase) at baseline and 3 months after 90Y treatment. Tumor response was assessed using RECIST 1.0 criteria, based on a maximum of 5 target lesions. Peri-tumoral edema and necrosis; known artifacts which can affect the interpretation of RECIST response, were documented for each lesion. Kaplan Meier analysis compared survival for responders [Partial Response (PR)] vs. non-responders [Stable Disease (SD) or Progressive Disease (PD)]. Results: A total of 184 patients were studied; male (61%) and Caucasians (61%) most common, mean age 62.5 years received a median of 2 (range 1–5) lines of chemotherapy prior to 90Y therapy. Median tumor/liver ratio at 90Y therapy was 15% (IQR 20%). Median 90Y activity administered was 1.18 GBq (IQR 0.55). RECIST response at 3 months was 9.8% PR (n=18), 72.3% SD (133) and 17.9% PD (33); Disease Control Rate = 82.1%. Peri-tumoral edema was documented in 33% (n=60); necrosis in 42% (79); both in 22% (40) of cases, respectively. No significant differences in background characteristics between responders and non-responders were evident (p>0.05). RECIST response at 3 months predicted survival: PR median 13.9 months (95% CI 9.2-30.3) vs. SD 11.0 (8.9-13.5) vs. PD 6.7 (5.5-8.1) [p=0.002]. Conclusions: Radiological lesion response to 90Y therapy at 3 months must be interpreted with caution due to the significant proportions of peri-tumoral edema and necrosis encountered. Both of these artifacts may lead to either the under estimation of PR/SD or the overestimation of PD, respectively. Given these caveats, early (3 month) hepatic radiological response to 90Y therapy appears to predict longer term prognosis.