Basic Research - Cancer(구연) (E-006)

Pilot study for evaluating the role circulating tumor DNA as an early predictor of response to immune check point inhibitors in patients with metastatic renal cell carcinoma
Urology, Samsung Medical Center, Samsung Genome Institute, Samsung Medical Center, Urology, Samsung Medical Center, Urology, Samsung Medical Center, Urology, Samsung Medical Center, Urology, Samsung Medical Center, Urology, Samsung Medical Center, Urology, Samsung Medical Center, Genius, Seoul, Genius, Seoul, Urology, Samsung Medical Center
Taejin Kim, Yeon Jeong Kim, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Donghyun Park, Minyong Kang
Background: Although Circulating tumor DNA (ctDNA) is emerging as a potential alternative method for predicting disease recurrence and treatment responsiveness in RCC, there is little published study evaluating the role of ctDNA in RCC. / Objectives: To evaluate the predictive role of ctDNA detection by targeted deep sequencing in patients with metastatic renal cell carcinoma (mRCC) who treated by immune check point blockades (ICB) / Materials and Methods: To determine the feasibility of ctDNA panel encompassing 40 genes (LiquidSCAN RCC panel, 115 kb), we prospectively collected 10 ml blood from 20 patients with RCC at the time of radical nephrectomy at our institution. Using capture-based targeted deep sequencing, we analyzed somatic tumor mutations in primary tumors and ctDNA samples from these patients. After confirming the feasibility of ctDNA detection using this method, we also prospectively collected 10 ml blood before and after one month of treatment, respectively, from four patients with mRCC receiving ICB. / Results and Conclusion: Results: Among a total of 20 patients, variants were detected in primary tumors of 15 patients (75%) and ctDNA were detected in plasma of 9 patients (45%). Most common variants detected in ctDNA were VHL (25%), PBRM1 (20%) and KDM5C (15%). Genomic alterations were concordantly detected between tissue and plasma in 53.3% (n=8/15). Of note, in 71.4% of patients with mRCC (n=5/7), mutations present in primary tumors were concordantly detected in plasma. Then, we examined the predictive role of ctDNA in four patients with mRCC receiving ICB. Notably, ctDNA were detected in three patients (75%) who received first-line ipilimumab and nivolumab. In two patients showing partial responses, ctDNA level decreased at the time of one month after ICB (Figure A). One patient had TP53 mutation and other patient had MTOR and ARID1A mutations, respectively. However, one patient showing progression disease, ctDNA level increased at the time of one month after ICB, with variants of TP53, VHL and PIK3CA genes (Figure B).   Conclusions: In sum, our data showed that ctDNA detection in plasma by targeted deep sequencing were feasible in patients with RCC. Moreover, the level of ctDNA can predict the treatment response in patients with mRCC who were received ICB.       
keywords : : circulating tumor DNA, renal cell carcinoma, immune checkpoint blockade

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