Abstract 2694: DNA copy number aberrant profiles predict complete pathologic tumor response to preoperative chemoradiation therapy in locally advanced rectal cancer

Abstract

Abstract Purpose: The treatment of locally advanced rectal cancer includes chemoradiation (CRT) followed by surgical resection. The response of rectal cancers to the CRT is variable. The finding that up to 25% of tumor seem to be totally eradicated by the CRT has raised the question as to whether surgery can be avoided in these patients. Findings predictors or response or resistance to CRT could potentially change the treatment paradigm of rectal cancer patients. In this study we explored DNA copy number alterations as predictors of rectal cancer response to preoperative CRT. Patients and Methods: High-density oligonucleotide-based comparative genomic hybridization (human 244k aCGH kit, Agilent Cor.) was employed to identify the DNA copy number alterations in 89 pretreatment tumor biopsy specimens and paired normal surgical specimens collected from stage II and III rectal cancer patients treated in a prospective multi-institutional study. Data analysis was performed using Nexus Copy Number and Ingenuity Pathway Analysis. A pathologic complete response (pCR), defined as absence of cancer cells in the surgical specimen, was used as clinical end-point. Results: A total of 25 (28%) patients had a pCR. The pCR rate was higher among tumors with low fractional genomic alterations (FGA, ≤21%) (12/26 or 46.1%) compared to tumors with high FGA (>21%) (13/63 or 20.6%) (p<0.02). Gain or losses of individual chromosome segments containing individual candidate genes and miRNAs in tumors with or without pCR are presented in table 1.Chrom. LocationCandidate GeneChangepCRNon- pCRp-valuechr18q21.2SMAD4loss52%82.8%0.0059chr.8p12EIF4EBP1loss8%35.9%0.0085chr.17q12ERBB2gain4%29.7%0.0098chr.16p12.1PRKCBgain4%29.7%0.0098chr.7p15.2hsa-mir-148again32%58.7%0.0352 Conclusion: This study shows that DNA copy number aberrations, measured as a FGA and individual chromosome regions gain and loses, may be predictors of rectal cancer resistance to CRT. This information could be used to select patients that may not benefit from a non-surgical treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2694.