S2163 Understanding Prolonged Survival in Advanced Colorectal Cancer Using Genomics: A Case Series

Abstract

Introduction: Recent progress in molecular biology and cancer genome research had opened a new venue for clinical research and changed treatment paradigm for metastatic colorectal cancer. Case Description/Methods: Case 1: A 61-year -old Hispanic male underwent colonoscopy which revealed an mass in the proximal ascending colon with biopsy showing moderately differentiated adenocarcinoma. The patient underwent a right hemicolectomy in 2012. He subsequently completed chemotherapy with mFOLFOX-6. Further treatment was declined by patient. Follow up chest CT scan in April 2018, uncovered progression of pulmonary nodules (Figure, Panel 1). Patient was put on FOLFIRI/bevacizumab chemotherapy. NGS study showed following results; MS stable; TMB 4 mutations/Mb (low); APCR1450, BRAF D594N, FAM 123B K761, SOX9 G225fs, and TP53 R175H.The patient has stable disease on follow up. Case 2: A 73-year-old Hispanic male underwent colonoscopy showing a obstructing mass in the sigmoid colon. Biopsy showed moderately differentiated adenocarcinoma in December 2013. Patient underwent sigmoidectomy. Liver masses were found on repeat CT abdomen. The NGS reported as follows; MS-Stable, TMB 1 muts/Mb(low), APC T282fs*12/P1453fs*20, CDK8 amplification, fms like tyrosine kinase 3 (FLT3) amplification, KRAS amplification and TP53 V147D. It also detected wild type KRAS mutations in exons 2, 3 and 4. The patient was started on chemotherapy with mFOLFOX. Follow- up studies show stable disease. Case 3: A 73-year-old Hispanic male underwent colonoscopy showed a completely obstructing mass in the sigmoid colon. Biopsy showed moderately differentiated adenocarcinoma in June 2012. The tumor cells have KRAS G12D mutation in in codon 12 of KRAS. He underwent a left hemicolectomy. He completed mFOLFOX6.PET scan was done and showed a right upper lobe mass consistent with metastatic cancer. He was started on FOLFIRI/ bevacizumab. NGS reported as follows; MS-Stable, TMB 1 muts/Mb(low), APC V1452fs*21, and ATM S47fs*11. Bone Scan intense uptake in the right distal tibia (Figure, Panel 2). MRI of the right lower extremity showed a lesion in the distal tibia. He was then switched to irinotecan and bevacizumab regimen. He has stable disease. Discussion: Identification of genomic signature is key to understanding the molecular mechanism of CRC and the development of novel therapeutics.Figure 1.: Panel 1 (left) shows CT Chest for Case 1 with multiple pulmonary nodules few with cavitation, largest 9mm. Panel 2 (right) shows Bone Scan for Case 3 in February 2021 with intense uptake in the right distal tibia.