1056PD - Prognostic impact of immune response in resectable colorectal liver metastases treated with and without perioperative FOLFOX chemotherapy

Date 28 September 2014
Event ESMO 2014
Session Immunotherapy of cancer
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Cancer Immunology and Immunotherapy
Rectal Cancer
Presenter Erik Tanis
Citation Annals of Oncology (2014) 25 (suppl_4): iv361-iv372. 10.1093/annonc/mdu342
Authors E. Tanis1, C. Julie2, J. Emile2, B. Nordlinger3, M. Mauer4, D. Aust5, A.D. Roth6, M.P. Lutz7, T. Ruers8
  • 1Fellowship, EORTC, 1200 - Brussels/BE
  • 2Pathology, CHU Ambroise Pare, Paris/FR
  • 3Surgery, CHU Ambroise Pare, Paris/FR
  • 4Department Of Statistics, EORTC, Brussels/BE
  • 5Pathology, Universitatsklinikum Dresden, Dresden/DE
  • 6Oncosurgery, Hôpitaux Universitaires de Genève - HUG, 1211 - Geneva/CH
  • 7Medizinische Klinik, Caritasklinik St. Theresia, 66113 - Saarbrücken/DE
  • 8Surgical Oncology, Netherlands Cancer Institute, 1066CX - Amsterdam/NL

 

Abstract

Aim

Chemotherapy can have a stimulating effect on local immune response and is associated with improved prognosis in primary colorectal cancer. It is unclear how the immune response in colorectal liver metastases is related to PFS and whether this may be influenced by systemic therapy.

Methods

A retrospective central collection of tumour tissue from patients included in the EORTC study 40983 was organised to assess the local immune response in relation to progression free survival (PFS) and FOLFOX chemotherapy. Patients with colorectal liver metastases were treated by either resection or resection with perioperative FOLFOX. Immunostaining on whole slides was performed to recognize T-lymphocytes (CD3+, CD4+, CD8+), B-lymphocytes (CD20+), macrophages (CD68+) and mastocytes (CD117+). Immunological response was quantified by image analysis on virtual slides at the tumour border (TNI), inside the tumour and in normal liver tissue surrounding the tumour (<2mm from the TNI). An immunoscore (0-4 pts) consisting of CD3+ and CD8+ lymphocytes at the TNI and inside the tumour was calculated. Immunological response was compared between arms and correlated to PFS. No type I error adjustment was made for multiple testing.

Results

Tumour tissue and immune response profiles were available for 82 resected patients, 38 in the perioperative chemotherapy arm and 44 in the surgery alone arm. Median follow-up was 8.8 years. Patient demographics and baseline disease characteristics were similar between the treatment arms. After chemotherapy, we have observed higher CD3+ lymphocyte and mastocyte counts inside the tumour (p < 0.01), lower CD4+ lymphocytes (p = 0.02) and macrophage count in the normal liver tissue (p < 0.01) and also lower macrophage count at the TNI (p = 0.02). PFS was improved for higher mastocyte count in the tumour (HR 0.54 [95% CI 0.32-0.93], p = 0.03), higher CD3+ lymphocyte count at the TNI (HR 0.57 [95% CI 0.34-0.95], p = 0.03) and an immunoscore >2 (HR 0.51 [95% CI 0.27-0.96], p = 0.04).

Conclusions

Our analyses conducted for the first time in a randomised study suggest that chemotherapy independently influences immune cell profiles, and the immunoscore and intratumoral mastocytes appear to be of prognostic in a metastatic setting.

Disclosure

All authors have declared no conflicts of interest.