Janowski E, Timofeeva O, Chasovskikh S, Goldberg M, Kim A, Banovac F, Pang D, Dritschilo A, Unger K
Department of Radiation Medicine, Georgetown University Hospital, Washington, DC, USA.
Department of Oncology, Georgetown University, Washington, DC, USA.
Oncol Rep. 2017 Jan;37(1):57-65. doi: 10.3892/or.2016.5284. Epub 2016 Nov 29.
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.
不可切除的化疗难治性结直肠癌肝转移（CRCLM）患者的局部治疗选择有限。我们报告了我们机构关于基于树脂的钇-90（90Y）放射性栓塞治疗CRCLM的疗效以及相关循环游离DNA（ccfDNA）研究的结果。在梅斯达乔治敦大学医院，共有58例接受90Y治疗的CRCLM患者在治疗后的中位生存期为6个月[95%置信区间（CI），4.55 - 7.45个月]，12个月生存率为33%。按突变状态分层的治疗后中位生存期，野生型（WT）患者（7个月）比KRAS突变型患者（5个月）长，但未达到统计学意义（p = 0.059）。整个队列90Y治疗后的中位肿瘤局部控制持续时间为2个月（95% CI，0.34 - 3.66个月），WT患者比突变型患者更长（分别为2个月和1个月，p = 0.088）。前瞻性收集了9例单叶治疗前后患者的血浆，并使用定量PCR和原子力显微镜（AFM）测量ccfDNA浓度和片段化指数（FI）。在WT和KRAS突变型患者中，治疗后DNA FI从中位值0.73降至0.65。单叶治疗后DNA FI的降低与总体生存期改善相关（p = 0.046）。对KRAS突变型和WT患者治疗前后配对样本进行AFM分析显示，WT患者片段大小的平均减小幅度更大（p = 0.013）。90Y放射性栓塞可延长CRCLM的局部控制时间，然而，KRAS突变型肿瘤可能对治疗更具放射性抗性。注意到治疗后患者FI的变化，可能需要在更大规模的研究中评估其作为反应生物标志物的相关性。
