Prognostic Impact and Utility of Immunoprofiling in the Selection of Patients with Colorectal Peritoneal Carcinomatosis for Cytoreductive Surgery (CRS) and Heated Intraperitoneal Chemotherapy (HIPEC).

Publication Title

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract

Authors

Mary Garland-Kledzik, John Wayne Cancer Institute, Providence St. John's Medical Center, 2200 Santa Monica Boulevard, Santa Monica, CA, USA.
Abhineet Uppal, John Wayne Cancer Institute at Providence Saint John's Hospital, Santa Monica, CAFollow
Yalda Naeini, Department of Pathology, Providence St. John's Medical Center, Santa Monica, CA, USAFollow
Stacey L Stern, John Wayne Cancer Institute at Providence Saint John's Hospital, Santa Monica, CAFollow
Richard Erali
Anthony J Scholer, Department of Surgical Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USAFollow
Adam Khader, Department of Surgical Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USAFollow
Juan A Santamaria-Barria, Department of Surgical Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USAFollow
Kathleen Cummins-Perry
Yi Zhou
Konstantinos I Votanopoulos
Perry Shen
Edward A Levine
Anton J Bilchik, John Wayne Cancer Institute at Providence St John's Health Center, 2200 Santa Monica Blvd, Santa Monica, CA, 90404, USAFollow

Document Type

Article

Publication Date

12-2-2020

Abstract

BACKGROUND: Recent studies have shown an association 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 selected patients who undergo cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). However, current patient selection for CRS/HIPEC is suboptimal. The purpose of this study is to evaluate immune profiles of patients with peritoneal carcinomatosis and their correlation with overall survival (OS).

METHODS: The study cohort included 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 was performed. IHC image density was calculated using ImageJ software, and an immunoscore was determined.

RESULTS: Eighty tumors were evaluated from 66 patients. These included 14 primary sites and 66 metastatic sites. R0/R1 resection was achieved in 44 (66.7%) patients. Known prognostic factors including resection status (HR 1.99, p = 0.004) and lymph node status (HR 3.49, p = 0.002) were associated with overall survival. On multivariate analysis, increased CD3/CD4 IM (HR 0.54, p = 0.03) ratio positively was associated with improved OS.

DISCUSSION: This is the first study to assess the utility of subtypes of T cells as prognostic markers in patients with colorectal peritoneal carcinomatosis, which may play a role in patients with low-volume disease. Further studies into immune mechanisms may improve patient selection for cytoreductive surgery and HIPEC as well as provide novel pathways for effective immunotherapy.

Clinical Institute

Cancer

Clinical Institute

Digestive Health

Specialty/Research Institute

Gastroenterology

Specialty/Research Institute

Surgery

Specialty/Research Institute

Oncology