Prognostic Impact and Utility of Immunoprofiling in the Selection of Patients with Colorectal Peritoneal Carcinomatosis
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SSAT PLENARY PRESENTATION
Prognostic Impact and Utility of Immunoprofiling in the Selection of Patients with Colorectal Peritoneal Carcinomatosis for Cytoreductive Surgery (CRS) and Heated Intraperitoneal Chemotherapy (HIPEC) Mary Garland-Kledzik, MD 1 & Abhineet Uppal, MD 1 & Yalda B. Naeini, MD 2 & Stacey Stern, MS 1 & Richard Erali, MD 3 & Anthony J. Scholer, MD 1 & Adam M. Khader, MD 1 & Juan A. Santamaria-Barria, MD 1 & Kathleen Cummins-Perry, MSc 3 & Yi Zhou, MD 3 & Konstantinos I. Votanopoulos, MD 3 & Perry Shen, MD 3 & Edward A. Levine, MD 3 & Anton J. Bilchik, MD 1 Received: 27 July 2020 / Accepted: 12 November 2020 # 2020 The Society for Surgery of the Alimentary Tract
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. Keywords Peritoneal carcinomatosis . Immune profiling . HIPEC
Background * Anton J. Bilchik, MD [email protected] 1
John Wayne Cancer Institute, Providence St. John’s Medical Center, 2200 Santa Monica Boulevard, Santa Monica, CA, USA
2
St. John’s Providence Health System, Santa Monica, CA, USA
3
Wake Forest University, Winston-Salem, NC, USA
Immune profiling has recently been shown to be an important prognostic factor in colorectal cancer (CRC). 1–5 The presence of tumor-infiltrating
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