90Y radioembolization is an effective treatment for CRCLMs in extending local control for liver-dominant metastatic disease. However, KRAS-mutant tumors may be more radioresistant to treatment.
Einsley Janowski, MD, PhD, Olga Timofeeva, PhD, Sergey Chasovskikh, PhD, Max Goldberg, Alexander Kim, MD, Filip Banovac, MD, Dalong Pang, PhD, Anatoly Dritschilo, MD, Keith Unger, MD; Georgetown University
INTRODUCTION: We report our institutional experience on the efficacy of resin-based yttrium-90 (90Y) radioembolization for the treatment of unresectable, chemorefractory colorectal cancer liver metastases (CRCLMs).
METHODS: From 2011 to 2014, a total of 51 patients underwent 90Y treatment for CRCLMs at our institution. A retrospective review was conducted for clinical outcomes, demographic information, and tumor mutation status. In 38 patients, interval imaging was available for tumor response assessment using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Serum (plasma) was prospectively collected in patients both pretreatment (n = 9) and posttreatment (n = 7), and circulating cell-free DNA (ccfDNA) concentration and integrity index were measured using quantitative PCR. DNA integrity results were validated in two patients using atomic force microscopy (AFM).
RESULTS: Our patient population consisted of 51 patients diagnosed with colon cancer at a median age of 56 years (range: 31–85 yr). Tumor mutation information was available for 41 patients: 24 (58%) patients were KRAS mutant, 15 (37%) were KRAS wild-type, and 2 (5%) had microsatellite instability (MSI). The average survival after 90Y was 5.7 months ± 4.1 (range: 0–21 mo) in the entire cohort, with a 12-month survival of 10%. Average survival stratified by mutation status in KRAS wild-type, KRAS mutant, and MSI patients was 6 months ± 3.5, 5.29 months ± 4.86, and 5 months ± 2.83, respectively. Imaging assessment showed a partial response in 8 patients (21%), stable disease in 16 (42%), and progressive disease in 14 (37%) at a median follow-up of 2 months after treatment. Tumor local control after 90Y treatment averaged 2.17 months ± 2.97 for the entire cohort. Local control response, assessed according to tumor mutation, averaged 2.62 months ± 4.25 for KRAS wild-type, 1.16 months ± 1.43 for KRAS mutant, and 4.5 months ± 3.54 for MSI patients. ccfDNA was detected in 100% of the analyzed samples. Median pretreatment plasma ccfDNA levels of 4.6 ng/mL decreased to 1.8 ng/mL after single-lobe treatment. DNA integrity index was reduced from a median of 0.62 to 0.23 after treatment. Analysis by AFM of paired pre- and posttreatment samples of a KRAS-mutant patient and an MSI patient revealed minimal change in the KRAS sample but a 35% average fragment size drop in the MSI sample.
CONCLUSIONS:90Y radioembolization is an effective treatment for CRCLMs in extending local control for liver-dominant metastatic disease. However, KRAS-mutant tumors may be more radioresistant to treatment.
Proceedings of the 97th Annual Meeting of the American Radium Society- americanradiumsociety.org