Complete tumor regression in rectal cancer patients after neoadjuvant chemoradiation: molecular prediction of tumor response based on intratumoral heterogeneity and assessment of response by circulating tumoral DNA

• Grant number: 18/15582-9
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• Start date: May 01, 2019
• End date: April 30, 2025
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Rodrigo Oliva Perez
• Grantee: Rodrigo Oliva Perez
• Host Institution: Hospital de Beneficência Portuguesa de São Paulo. Real e Benemérita Associação Portuguesa de Beneficência de São Paulo (RBAPB). São Paulo , SP, Brazil
• Associated researchers: Anamaria Aranha Camargo ; Cibele Masotti ; Ramon Torreglosa Do Carmo
• Associated research grant: 11/51130-6 - Genetic heterogeneity of rectal cancer: identification of sub populations of tumor cells resistant to neoadjuvant CRT, AP.JP
• Associated scholarship(s): 22/03631-0 - Characterization of intratumoral genetic heterogeneity as a predictive biomarker of response to neoadjuvant chemoradiotherapy in patients with Rectal Cancer, BP.PD; 20/11204-0 - Intratumoral genetic heterogeneity and defective DNA repair mutational signatures as predictive biomarkers of response to nCRT in Rectal Cancer patients, BP.PD

Abstract

Neoadjuvant chemoradiation (nCRT) is the preferred initial treatment strategy for Distal Rectal Cancer. nCRT may lead to significant primary tumor regression in these patients and eventually to complete pathological response (pCR). Clinical, endoscopic and radiological features have been used to identify patients with pCR to avoid potentially unnecessary radical surgery and its associated morbidity, mortality and functional consequences (urinary, sexual and anorectal). These patients could be enrolled in organ-preserving strategies without immediate surgical resection of the rectum. However, this organ-preserving approach has 2 main limitations: the absence of predictive tests for the response to nCRT and significant subjectivity/inaccuracy in clinical, endoscopic and radiological assessment of response. Rectal Cancers exhibit significant intratumoral heterogeneity (ITGH). There is a direct association between the levels of ITGH and primary disease stage. The present study aims to establish a correlation between ITGH and response to nCRT. In addition, Rectal Cancer patients have variable levels of circulating tumor DNA (ctDNA). In this setting, the present study will also address the accuracy of ctDNA and response to nCRT. (AU)