Yttrium-90 radioembolization for colorectal cancer liver metastases in KRAS wild-type and mutant patients: Clinical and ccfDNA studies

Janowski,E.; Timofeeva,O.; Chasovskikh,S.; Goldberg,M.; Kim,A.; Banovac,F.; Pang,D.; Dritschilo,A.; Unger,K.

doi:10.3892/or.2016.5284

Yttrium-90 radioembolization for colorectal cancer liver metastases in KRAS wild-type and mutant patients: Clinical and ccfDNA studies

Authors:
- E. Janowski
- O. Timofeeva
- S. Chasovskikh
- M. Goldberg
- A. Kim
- F. Banovac
- D. Pang
- A. Dritschilo
- K. Unger
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Affiliations: Department of Radiation Medicine, Georgetown University Hospital, Washington, DC, USA, Department of Oncology, Georgetown University, Washington, DC, USA, Department of Interventional Radiology, Georgetown University Hospital, Washington, DC, USA, Department of Interventional Radiology, Vanderbilt University Hospital, Nashville, TN, USA
Published online on: November 29, 2016 https://doi.org/10.3892/or.2016.5284
Pages: 57-65
Copyright: © Janowski et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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