152454-156

Combining Genome Change Index (GCI) and liquid biopsy to predict and monitor therapeutic responses.

Subcategory: 
Category: 
Tumor Biology
Session Type and Session Title: 
This abstract will not be presented at the 2015 ASCO Annual Meeting but has been published in conjunction with the meeting.
Abstract Number: 

e22020

Citation: 
J Clin Oncol 33, 2015 (suppl; abstr e22020)
Author(s): 
Ekkehard Schütz, Julia Beck, Donald Peter Braun, Howard B. Urnovitz, Balazs Dome, Anita Rozsas, Vivek Khemka, Ashish Sangal, Madappa N. Kundranda, Glen J. Weiss; Chronix Biomedical, Göttingen, Germany; Cancer Treatment Centers of America, Zion, IL; National Koranyi Institute for TB and Pulmonology, Budapest, Hungary; Western Regional Medical Center, Cancer Treatment Centers of America, Goodyear, AZ

Abstract Disclosures

Abstract: 

Background: Genomic instability of tumor cells has been associated with a poor prognosis. However, impaired DNA repair pathways leading to genomic instability are also described to increase tumor sensitivity to DNA damaging agents. A comprehensive Genomic Change Index (GCI) as an indicator of defective DNA repair is proposed as a potential predictor of cytotoxic chemotherapy (chemo) response. Cell-free tumor DNA (cftDNA) has the potential to provide minimally invasive patient specific biomarkers to monitor tumor burden (liquid biopsy). Methods: 18 patients (pts) with advanced esophageal cancer (EC; n = 1), pancreatic ductal adenocarcinomas (PDAC; n = 4), small cell (SCLC; n = 6) and non-small cell lung cancer (NSCLC; n = 7) were included. The chemo regimen for PDAC was gemcitabine & nab-paclitaxel. All other pts received carboplatin/cisplatin, with etoposide (SCLC), etoposide, pemetrexed, or paclitaxel (NSCLC; EC). Chemo-resistant cancers (R) were defined as having progressive disease (PD), chemo-sensitive cancers (S) as stable disease (SD) or partial response (PR) on initial therapy. DNA was extracted either from tumor tissue or pre-treatment plasma samples. Copy-numbers were called from shallow shotgun sequencing (~2.5x107reads, Illumina) in genomic windows of 500kbp and converted into a score based on Gaussian transformations. Somatic mutations were called from targeted sequencing and quantified in follow-up plasma DNA by digital PCR. Results: Significantly lower GCI were detected in R vs. S (p = 0.03). Liquid biopsies were obtained for 6 patients with PD, SD, or PR. Decreasing cftDNA levels were detected as early as 2h after starting the first cycle in a pt who received 6 cycles of chemo showing SD. In the one EC pt (PR) < 6 cftDNA copies/mL plasma were detected at end of treatment. Rising cftDNA concentration were detected in 3 PD pts. One NSCLC pt (PD) showed a slight cftDNA decrease from baseline to cycle 2 with still very high concentrations ( > 1000 cp/mL plasma). Conclusions: As shown for other cancers, GCI may serve as predictor of therapy response to DNA-damaging chemo for the investigated cancer types. Liquid biopsy with cftDNA is a highly specific, sensitive and rapid surveillance biomarker.