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Session: ePoster: Colon and Colorectal Cancer 13 (Mon1015)

EP704 - Comprehensive genetic analysis of locally advanced colorectal cancer patients receiving neoadjuvant chemotherapy

Monday, May 12, 2025
10:31 AM - 10:36 AM PT
Location: Monitor 4, Sails Pavilion, Upper Level

    ePoster Presenter(s)

  • HB

    HyungJoo Baik

    Assistant Professor
    Inje University Busan Paik Hospital
    Busan, Pusan-jikhalsi, Republic of Korea

    All of the relevant financial relationships listed below have been mitigated.
    This individual has no financial relationships with ineligible companies.

    View ePoster

    • Author(s)

  • KB

    Ki Beom Bae, MD PhD.

    Professor
    Inje University Busan Paik Hospital
    Busan, Pusan-jikhalsi, Republic of Korea

    Disclosure information not submitted.

All of the relevant financial relationships listed below have been mitigated.
HyungJoo Baik: This individual has no financial relationships with ineligible companies.
Purpose/Background: Neoadjuvant chemotherapy (NAC) in locally advanced colorectal cancer (LACC) has become one of the effective treatments, especially for those who may require multiorgan resection due to local invasiveness. However, little is known regarding which patients may benefit the most from NAC. Hence, we aimed to investigate whether different response rates were due to mutation differences, and the possible genetic alterations caused by NAC.

Methods/Interventions: 53 patients with LACC were enrolled in this study. All patients were clinically T3 or above, and received either FOLFOX or CapeOx chemotherapy before surgery. Cycles varied depending on patients’ condition but this study aimed for the administration of 3 to 5 cycles of FOLFOX chemotherapy. Patients with rectal cancer also received preoperative concurrent chemoradiotherapy. Clinical and pathologic stages were compared, and T or N stage regression was considered a good responder. 2-year recurrence rate and mutation analysis using Next Generation Sequencing (NGS) were investigated in all patients. For those with recurrence, we performed NGS with specimens before and after NAC and compared the possible differences.

Results/Outcomes: 41 out of 53 patients (77.4%) were good responders in our study. Pathologic complete regression was achieved in 5 patients (9.4%). Good responders tended to have APC, TP53, and KRAS mutations (n=23, 19, and 9 respectively). 4 out of 5 MSI-H patients and all of 3 POLE mutant patients were good responders. However, there was no significant difference in tumor mutational burden (TMB) between good and poor responders (median TMB 4.74 vs. 6.63). Notably, 3 out of 12 poor responders had SOX9 mutations. 10 out of 53 patients (18.9%) had recurrence within 2 years. 7 of 10 patients had a concurrent TP53 and KRAS mutation. NGS analysis before and after NAC showed a decrease in TMB after NAC, but gene variation was not frequently observed in our study.

Conclusion/Discussion: Oxaliplatin-based NAC resulted in a high rate of downstaging in LACC. We have found frequent mutation of APC, TP53, and KRAS mutations, as well as MSI-H and POLE mutations in the good responders. Furthermore, all SOX9 mutant patients were poor responders, but due to small sample size, further studies are required to validate this. Lastly, due to a tendency of decrease in TMB after NAC, we suggest that NGS may be performed using pre-NAC tumor samples for a more accurate analysis of tumor mutations.

Tumor response to NAC
77.4% of all patients were good responders to NAC.

Gene mutations in good responders.
APC, TP53, KRAS were most frequent mutations in good responders.