EP934 - Discordance of Radiologic and Pathologic Outcomes in Patients with dMMR Colorectal Cancer Undergoing Surgery after Immune-checkpoint Inhibitor Therapy.

Tuesday, May 13, 2025

8:16 AM – 8:21 AM PT

Location: Monitor 5, Sails Pavilion, Upper Level

ePoster Presenter(s)

Maysoon Gamaleldin, MD

Colorectal Fellow
Cleveland Clinic Foundation
Cleveland Clinic Foundation
Beachwood, OH, United States

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

Author(s)

IK

Imran Khan, MD

Research Fellow
Cleveland Clinic
Cleveland, Ohio, United States

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

Associate Professor, Chair
Department of Colorectal Surgery, Cleveland Clinic
Cleveland Clinic, Cleveland, Ohio
Cleveland, Ohio, United States

Disclosure information not submitted.
EG

Emre Gorgun, MD, MBA

Vice Chair, Department of Colorectal Surgery
Cleveland Clinic Foundation-Main Campus
Cleveland, Ohio, United States

All of the relevant financial relationships listed below have been mitigated.
This individual has no relevant relationships with ineligible companies.
Hermann Kessler, MD, PhD, Professor of Surgery (he/him/his)

Staff
Cleveland Clinic Foundation-Main Campus
Cleveland, OH, United States

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

Satish E. Viswanath, PhD

Associate Professor
Case Western Reserve University
Cleveland, Ohio, United States

Disclosure information not submitted.
SK

Smitha Krishnamurthi, MD

Staff
Cleveland Clinic Foundation-Main Campus
Cleveland, Ohio, United States

Disclosure information not submitted.
JM

Jacob G. Mansell, BS

Clinical Research Coordinator
Cleveland Clinic Department of Colorectal Surgery
North Ridgeville, Ohio, United States

Disclosure information not submitted.

Senior Author(s)

Jonathan B. Mitchem, MD (he/him/his)

Cleveland Clinic Foundation
Cleveland Clinic Foundation
Cleveland, OH, US

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

All of the relevant financial relationships listed below have been mitigated.

Maysoon Gamaleldin, MD: This individual has no financial relationships with ineligible companies.

Imran Khan, MD: This individual has no financial relationships with ineligible companies.

Emre Gorgun, MD, MBA: This individual has no relevant relationships with ineligible companies.

Hermann Kessler, MD, PhD, Professor of Surgery: This individual has no financial relationships with ineligible companies.

Jonathan B. Mitchem, MD: This individual has no financial relationships with ineligible companies.

Image or Table (Do Not add text here):

Purpose/Background: Immune checkpoint inhibitor (ICI) therapy has significantly improved survival in mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC). While initially used only in the setting of metastatic disease, recent clinical trials utilizing ICI therapy in the neoadjuvant setting for the treatment of dMMR locally advanced colon cancer (LACC) have shown substantial efficacy. However, despite high pathologic response rates, few patients demonstrate significant radiologic response. Therefore, in this study, we sought to determine factors associated with imaging and pathologic response, as well as surgical and long-term outcomes in patients with dMMR CRC.

Methods/Interventions: We conducted a retrospective study using a multi-institutional dataset to identify patients with dMMR colorectal cancer treated with immune checkpoint inhibitors (ICI).Patients were excluded if they received ICI therapy for non-colorectal malignancy or had incomplete data. Statistical analysis was completed using R version 4.3.1. Summary statistics were performed, and Fisher's exact test was used to determine whether radiologic response was associated with any baseline or tumor-related characteristics.

Results/Outcomes: A total of 34 patients met inclusion criteria, with a median age of 71.5 years (IQR: 61.25-77-ZZ), and 14 (41.1%) were female. Seven patients had lynch syndrome and 5 had BRAFV600E mutation. (Table 1) Radiologic response was evaluated in 28 patients using iRECIST criteria, with 3 patients achieving a complete response CR), 20 with partial response (PR), 1 with stable disease, and 4 with disease progression, for an overall response rate (ORR) of 75%. Ten patients with a median age of 61.5 years (IQR: 49-73.25) underwent surgery at a median of 1 month (range 1-23) after last dose of ICI therapy and after receiving a median of 5 doses (range 2-17) of ICI. The most common indication for surgery was residual disease (9, 90%). Six patients underwent hemicolectomy, 1 debulking, 1 total proctocolectomy, 1 total abdominal colectomy, and 1 abdominoperineal resection. Surgical complications with Clavien-Dindo score ≥2 were observed in 3 patients (30%), No patients experienced anastomotic leak, readmission, or underwent reoperation. The complete pathologic response rate was 50%. Eight of 10 patients had imaging after ICI treatment prior to surgery, 7 with PR and 1 with no response. The patient with no radiologic response also had residual disease on pathology. Of the 7 patients with PR on imaging, 3 had CR, 1 had CR in the primary with positive lymph nodes, and 3 had residual disease on pathology. There was no significant association between radiologic response and any baseline or tumor characteristics. (Table 2) After a median follow-up of 15 months, neither the median PFS nor OS was reached.

Conclusion/Discussion: In this study, we found a high rate of discordance between pathologic and imaging response in dMMR CRC patients undergoing surgery after ICI therapy, consistent with published studies. This remains a significant issue, as the primary indication for surgery was residual disease, there is a high complication rate in this patient group, and a substantial rate of pathologic complete response suggests these patients could potentially avoid surgery. We found no significant association, possibly due to the small sample size. As ICI therapy becomes more widely applied, further research is needed to improve the prediction of which patients will benefit from surgery.