Abstract A33: The use of personalized biomarkers for accessing tumor regression and defining surgical approach in rectal cancer patients treated with neoadjuvant chemoradiation.

Abstract

Abstract Neoadjuvant chemoradiation (nCRT) is the preferred initial treatment for locally advanced rectal cancer due to improved local disease control, lower toxicity and significant tumor regression. Response to nCRT varies substantially among patients and complete tumor regression can be observed in up to 42% of the patients. To avoid unnecessary postoperative morbidity associated with radical surgery, patients exhibiting significant tumor regression have been referred for conservative surgical approaches or even no immediate surgery with strict follow-up (Wait and Watch approach). However, assessment of treatment response remains a significant challenge due to the subjectivity of the clinical assessment and limitations of available radiological studies. In this context, identification of biomarkers capable of accessing tumor regression and complete response to nCRT would allow accurate selection of patients for alternative treatment strategies without immediate radical surgery after nCRT. Circulating DNA carrying tumor-specific genetic alterations can be found in the cell-free fraction of the blood (circulating tumor DNA - ctDNA) and has been successfully used to monitor tumor dynamics in both hematological and solid tumors. Recent advances in sequencing technologies have enabled the rapid and cost effective identification of genetic alterations in individual tumors. These alterations, in special tumor-specific chromosomal rearrangements, can then be used as personalized biomarkers to monitor treatment response and detect minimal residual disease, overcoming the problem imposed by the absence of a universally recurrent genetic alteration in solid tumors. In the present work, we sequenced the whole genome of 6 rectal tumors using mate-pair reads and identified tumor-specific chromosomal rearrangements (TSCR) that were subsequently validated by Sanger sequencing. Personalized assays were then designed to monitor these TSCR in serum samples collected at different time points during nCRT. TSCRs were detected in all pre-treatment serum samples and in post-treatment serum samples from patients presenting marginal tumor regression after nCRT. Post-treatment samples from patients with significant or complete tumor regression were mainly negative for the presence of TSCR. Our preliminary results suggest that personalized biomarkers can be used in the clinics for accessing tumor regression and defining the best surgical approach in rectal cancer patients treated with neoadjuvant chemoradiation. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A33. Citation Format: Paola Carpinetti, Elisa Donnard, Paula Asprino, Fabiana Bettoni, Fernanda Koyama, Angelita Habr-Gama, Raphael Parmigiani, Pedro Galante, Rodrigo Perez, Anamaria A. Camargo. The use of personalized biomarkers for accessing tumor regression and defining surgical approach in rectal cancer patients treated with neoadjuvant chemoradiation. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A33.