title: Yttrium-90 radioembolization for colorectal cancer liver metastases in KRAS wild-type and mutant patients: Clinical and ccfDNA studies.
abstract: Patients with unresectable, chemo-refractory colorectal cancer liver metastases (CRCLM) have limited local treatment options. We report our institutional experience on the efficacy of resin-based yttrium-90 (90Y) radioembolization for the treatment of CRCLM and our findings on associated circulating cell-free DNA (ccfDNA) studies. A total of 58 patients treated with 90Y for CRCLM at the Medstar Georgetown University Hospital had a median survival of 6 months [95% confidence interval (CI), 4.55‑7.45 months] after treatment, with a 12-month survival rate of 33%. The median survival from treatment stratified by mutational status was longer in the wild-type (WT) as compared to the KRAS mutant patients at 7 vs. 5 months, but did not achieve statistical significance (p=0.059). Median tumor local control duration after 90Y treatment was 2 months (95% CI, 0.34‑3.66 months) for the entire cohort and was longer in the WT vs. the mutant patients (2 vs. 1 month, respectively, p=0.088). Plasma was prospectively collected from a subset of 9 patients both before and after single lobe treatment, and ccfDNA concentration and fragmentation index (FI) were measured using quantitative PCR and atomic-force microscopy (AFM). In the WT and KRAS mutant patients, DNA FI was reduced from a median of 0.73-0.65 after treatment. A reduction in DNA FI after single lobe treatment was associated with an improved overall survival (p=0.046). Analysis by AFM of paired pre- and post-treatment samples from KRAS mutant and WT patients revealed a larger average decrease in fragment size in the WT patients (p=0.013). 90Y radioembolization extends local control for CRCLM, however, KRAS mutant tumors may be more radio-resistant to treatment. Changes in the FI of patients following treatment were noted and may be evaluated in a larger study for relevance as a biomarker of response.
authors.affiliation: Department of Radiation Medicine, Georgetown University Hospital, Washington, DC, USA.
authors.forename: E
authors.initials: E
authors.lastname: Janowski
authors.affiliation: Department of Oncology, Georgetown University, Washington, DC, USA.
authors.forename: O
authors.initials: O
authors.lastname: Timofeeva
authors.affiliation: Department of Oncology, Georgetown University, Washington, DC, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chasovskikh
authors.affiliation: Department of Oncology, Georgetown University, Washington, DC, USA.
authors.forename: M
authors.initials: M
authors.lastname: Goldberg
authors.affiliation: Department of Interventional Radiology, Georgetown University Hospital, Washington, DC, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kim
authors.affiliation: Department of Interventional Radiology, Vanderbilt University Hospital, Nashville, TN, USA.
authors.forename: F
authors.initials: F
authors.lastname: Banovac
authors.affiliation: Department of Radiation Medicine, Georgetown University Hospital, Washington, DC, USA.
authors.forename: D
authors.initials: D
authors.lastname: Pang
authors.affiliation: Department of Radiation Medicine, Georgetown University Hospital, Washington, DC, USA.
authors.forename: A
authors.initials: A
authors.lastname: Dritschilo
authors.affiliation: Department of Radiation Medicine, Georgetown University Hospital, Washington, DC, USA.
authors.forename: K
authors.initials: K
authors.lastname: Unger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D004247:DNA / Q000097:blood; D004621:Embolization, Therapeutic / Q000379:methods*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D008297:Male; D018625:Microscopy, Atomic Force; D008875:Middle Aged; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
chemical_list: C117307:KRAS protein, human; D015021:Yttrium Radioisotopes; D004247:DNA; D016283:Proto-Oncogene Proteins p21(ras)