PROGNOSTIC IMPACT AND UTILITY OF IMMUNOPROFILING IN THE SELECTION OF PATIENTS WITH COLORECTAL PERITONEAL CARCINOMATOSIS FOR CYTOREDUCTIVE SURGERY AND HEATED INTRAPERITONEAL CHEMOTHERAPY
Mary Garland-Kledzik*1, Abhineet Uppal2, Yalda Naeini3, Stacey L. Stern1, Richard A. Erali4, Anthony Scholer1, Adam Khader1, Juan A. Santamaria-Barria1, Kathleen C. Perry4, Yi Zhou4, Konstantinos I. Votanopoulos4, Perry Shen4, Edward Levine4, Anton J. Bilchik1
1General Surgery, John Wayne Cancer Institute, Santa Monica, CA; 2University of California-Irvine, Irvine, CA; 3Providence St. Johns, Santa Monica, CA; 4Wake Forest University School of Medicin, Winston Salem, NC
Background: Recent studies have shown a correlation in non-metastatic colorectal cancer between patient survival and immunoprofiling (expression of CD3, CD4, CD8, CD45 and FOXP3 T cells at the invasive margin (IM) and the tumor center (TC)) regardless of stage. Patients with peritoneal carcinomatosis have a dismal prognosis, but survival can be significantly improved in select patients who undergo cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC). However, there are limited accurate methods to improve the selection of patients for CRS. The purpose of this study is to evaluate immune profiles of patients with peritoneal carcinomatosis and their correlation with overall survival (OS).
Methods: Our study cohort identified patients from a prospectively maintained database of adults with colorectal peritoneal carcinomatosis who underwent CRS/HIPEC. Immunohistochemistry (IHC) using antibodies to CD3, CD4, CD8, CD45RO, and FOXP3 T cells were performed. An immunoscore was calculated using image J software. Multivariable Cox proportional-hazards models were used to evaluate the relationship between marker expression and OS.
Results: Of the fifty-five patients analyzed, complete cytoreduction (CC 0) was achieved in thirty-three (60.0%). Known prognostic factors including resection status (HR 2.52, p=0.01), grade (HR 2.51, p=0.03), and lymph node status (HR 4.00, p=0.04) were associated with improved survival. On multivariate analysis increased CD4/CD8 TC (HR 0.23, p<0.001) and CD3/CD4 IM (HR 0.38, p=0.03) ratios positively predicted improved OS.
Discussion: This is the first study to demonstrate improved survival with higher expression of subtypes of T cells at both the IM and TC in patients with colorectal peritoneal carcinomatosis. Further study into immune mechanisms may improve patient selection for cytoreductive surgery and HIPEC as well as provide novel pathways for effective immunotherapy.
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