Abstract 3962: Circulating tumor DNA (ctDNA) as an alternative to tumor biopsies for precision oncology: The Jules Bordet Institute experience
Authors: Aftimos Philippe G. , Maetens Marion , Rothé Françoise , Brown David , Barèche Yacine , Irrthum Alexandre , Berghmans Thierry , Kerger Joseph , Hendlisz Alain , Ignatiadis Michail , Piccart Martine , Sotiriou Christos , Awada Ahmad 
Published: July 2016

Abstract
Background
In the era of precision medicine, data obtained from sequencing the cancer genome of a patient can be integrated into clinical decision-making. Liquid biopsy using ctDNA is a non-invasive tool, which can circumvent unfeasible or unrepresentative tumor biopsies and allow continuous monitoring of the disease thereby contributing to rational drug delivery.
Experimental procedures
Precision-f is a feasibility molecular screening study that enrolled 34 patients with metastatic melanoma, non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). Results from targeted gene sequencing (TGS) of metastatic biopsies were presented at AACR 2015. The patients had a blood draw concomitantly with the metastatic biopsy for plasma isolation. Similar to biopsies, somatic mutations (substitutions, small insertions and deletions) were assessed using the Ion AmpliSeq™ Cancer Hotspot Panel v2, designed to amplify 207 amplicons covering 2800 COSMIC mutations from the 50 most commonly reported oncogenes and tumor suppressor genes with a sensitivity of 1%. All mutations identified in the biopsy and/or plasma samples using TGS are currently being validated using Droplet Digital PCR (ddPCR) technology.
Results
Evaluable ctDNA-derived sequencing data were available for 32 patients. The sequencing results between biopsies and plasma were fully concordant in 63% (20/32) of the patients. TGS of ctDNA failed to detect clinically relevant mutations (EGFR, PIK3CA, KRAS and BRAF) identified in the metastatic biopsies in 19% (6/32) of the patients. In contrast, biologically relevant mutations (STK11, KRAS, PIK3CA and SMO) not detected in tumor biopsies were found in the ctDNA in 9% (3/32) of the patients. Interestingly, in one CRC patient a KRAS G13D mutation still potentially associated with benefit to anti-EGFR therapy was detected only in the tumor biopsy whereas a KRAS A146T mutation mediating resistance to anti-EGFR therapy was detected solely in ctDNA. Tumor biopsies and plasma are currently being tested using ddPCR to validate the findings. The results of these analyses will be presented at the meeting.
Conclusion
Although technical challenges remain, ctDNA profiling appears to be a promising tool for precision oncology by allowing the identification of genomic alterations associated with drug resistance and tumor progression.
Citation Format: Philippe G. Aftimos, Marion Maetens, Françoise Rothé, David Brown, Yacine Barèche, Alexandre Irrthum, Thierry Berghmans, Joseph Kerger, Alain Hendlisz, Michail Ignatiadis, Martine Piccart, Christos Sotiriou, Ahmad Awada. Circulating tumor DNA (ctDNA) as an alternative to tumor biopsies for precision oncology: The Jules Bordet Institute experience. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3962.