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

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.

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Abbreviations

AJCC:

American Joint Committee on Cancer

BMI:

body mass index

CRC:

colorectal cancer

CRS:

cytoreductive surgery

DFS:

disease-free survival

FFPE:

formalin-fixed paraffin-embedded

HIPEC:

heated intraperitoneal chemotherapy

IM:

invasive margin

IRB:

institutional review board

mFOLFOX:

modified folinic acid, fluorouracil, and oxaliplatin treatment

MSI:

microsatellite instability

MSS:

microsatellite stability

OS:

overall survival

PCI:

Peritoneal Cancer Index

R:

residual tumor status

R0:

cure/complete remission

R1:

microscopic residual tumor

R2:

macroscopic residual tumor

TC:

tumor center

TILs:

tumor-infiltrating lymphocytes

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Funding

This study was supported, in part, by the Smith Family Fund and the Comprehensive Cancer Center of Wake Forest University, and the tumor tissue pathology shared resource supported by NCI CCSG P30CA012197.

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Authors

Contributions

Garland-Kledzik: project development, data analysis, data collection, manuscript writing/editing; Uppal: project development, manuscript writing/editing; Naeini: data analysis; Stern: data analysis; Erali: project development; Yi: data collection; Cummins-Perry: data collection; Scholer: data analysis; Khader: data analysis; Santamaria-Barria: data analysis; Votanopoulos: data collection; Shen: data collection; Levine: project design, data collection; Bilchik: project development, manuscript writing/editing.

Corresponding author

Correspondence to Anton J. Bilchik MD.

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The authors declare that they have no conflict of interest.

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Garland-Kledzik, M., Uppal, A., Naeini, Y.B. et al. Prognostic Impact and Utility of Immunoprofiling in the Selection of Patients with Colorectal Peritoneal Carcinomatosis for Cytoreductive Surgery (CRS) and Heated Intraperitoneal Chemotherapy (HIPEC). J Gastrointest Surg (2020). https://doi.org/10.1007/s11605-020-04886-y

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Keywords

  • Peritoneal carcinomatosis
  • Immune profiling
  • HIPEC