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

被引:14
作者
Janowski, E. [1 ,2 ]
Timofeeva, O. [3 ,4 ]
Chasovskikh, S. [3 ]
Goldberg, M. [3 ]
Kim, A. [5 ]
Banovac, F. [6 ]
Pang, D. [1 ]
Dritschilo, A. [1 ]
Unger, K. [1 ]
机构
[1] Georgetown Univ Hosp, Dept Radiat Med, Washington, DC 20007 USA
[2] Univ Virginia, Dept Radiat Oncol, POB 800383, Charlottesville, VA 22908 USA
[3] Georgetown Univ, Dept Oncol, Washington, DC USA
[4] Temple Univ, Dept Pathol, Philadelphia, PA 19122 USA
[5] Georgetown Univ Hosp, Dept Intervent Radiol, Washington, DC 20007 USA
[6] Vanderbilt Univ Sch Med, Dept Intervent Radiol, Nashville, TN USA
关键词
yttrium-90; radioembolization; KRAS; colorectal cancer; liver metastases; atomic-force microscopy; ccfDNA; PCR; KIRSTEN RAS MUTATIONS; CELL-FREE DNA; TUMOR PROGRESSION; CIRCULATING DNA; SURVIVAL; MICROSPHERES; BIOMARKERS; MANAGEMENT; CETUXIMAB; THERAPY;
D O I
10.3892/or.2016.5284
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 (Y-90) radioembolization for the treatment of CRCLM and our findings on associated circulating cell-free DNA (ccfDNA) studies. A total of 58 patients treated with Y-90 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 Y-90 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). Y-90 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.
引用
收藏
页码:57 / 65
页数:9
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