Abstract
3066 Background: Circulating tumorigenic cells (CTCs) may be responsible for tumor progression, represent a new source of information of tumor biology, avoiding unnecessary biopsies. Gene-expression analysis (GEA) of CTCs could guide anti-cancer therapies in patients with refractory solid tumors. Methods: Pts >18y ECOG PS 0-2 with advanced refractory solid tumors were recruited. Twelve ml blood samples were collected from each pt and processed for isolation of CTCs using a novel cell adhesion assay (Vita-Cap, Vitatex Inc., Stony Brook, NY) following the manufacturer protocol. Total RNA was extracted with RNeasy Mini Kit (Qiagen Inc.) and GEA was performed with Affymetrix GeneChip Human Genome U133 Plus 2.0 array. The CEL file obtained for each pt sample was used in a gene-set expression analysis (GSEA) to determine the enrichment profile of the pt sample to a pre-determined set of 12 PGx-modeled drugs created from the GI50 data of the NCI-60 cell lines. The drug with the highest Normalized Enrichment Score (NES) obtained from the GSEA was selected as the most sensitive. The NES for each drug was standardized and rank-ordered according to Sensitive/Intermediate/Resistant categories to generate a nominal chemo-sensitivity profile for the pt. This generates a comprehensible report called chemogram (ChG). We assessed preliminary efficacy in pts treated based on ChG. Results: ChG was obtained in 74/75 pts (57% male/43% female, median age 57y [20-81]) Tumor’s type was GI 67% (CRC n=18; pancreatic n=18; gastric n=6; cholangiocarcinoma n=7), NSCLC 14%, breast 8%, sarcoma 8%, others 3%. Median of 2 previous lines of therapy [range 1-12]. ECOG PS was 1 in 56%. Average RNA/pt 2.4 ng/µl (95% CI 1.5-3.4) Median time to obtain the report from blood extraction was 4 wks [range 2-7] Pts treated after the ChG were 37 (49%), of them 25 (69%) based on ChG recommended drug. In patients treated with ChG sensitive drugs, PFSratio ≥ 1.3 (PFS on therapy after ChG/PFS on prior therapy) was 24%, and 3 partial responses (12%) were observed. Conclusions: It is feasible to generate a sensitivity drug profiling on CTCs which shows preliminary activity and merits further studies.
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