Molecular Profile and Treatment Response in Locally Advanced Rectal Cancer
Posted: Wednesday, March 18, 2020
Response to chemotherapy and radiation therapy in patients with rectal cancer may be associated with specific molecular determinants, potentially helping “to select those who can avoid surgery and benefit from watch-and-wait strategies,” according to Julio Garcia-Aguilar, MD, PhD, and colleagues, of the Memorial Sloan Kettering Cancer Center. Findings from the study were presented at the 2020 Gastrointestinal (GI) Cancers Symposium in San Francisco (Abstract 192).
In this study, the researchers used targeted-exome sequencing, whole-exome sequencing, and RNA sequencing to profile 371 untreated tumors from patients with locally advanced rectal cancer. Of them, 62 primary tumors were located in the lower rectum, 115 were located in the middle rectum, and 107 were located in the upper rectum. Molecular determinants of complete response and relapse-free survival were examined for patients treated with chemoradiotherapy alone, induction therapy and chemoradiotherapy, or consolidation chemotherapy after chemoradiotherapy.
The overall 5-year complete response and relapse-free survival rates of patients in the study were 24% and 75%, respectively. Those who had microsatellite-instable tumors did not relapse and had a higher rate of complete response than did patients who had microsatellite-stable tumors (50% vs. 23%, respectively). Relapse-free survival rates were worse for those with microsatellite-stable tumors that had altered KRAS signaling and were treated with consolidation chemotherapy after chemoradiotherapy.
Alterations to the WNT signaling pathway due to APC mutations were characteristic of tumors in the upper rectum, as was enrichment of genes coding for mTOR signaling, G2M checkpoint, EMT transition, and DNA repair. Alterations to RTK/RAS signaling were characteristic of tumors in the lower rectum.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.