Introduction: The nature of the of Colorectal Liver Metastases (CRCLM) display mainly three distinct histologic growths patterns that impact on disease progression and patient outcome after surgical resection. However limited studies indicate that immune cell infiltration is dictated by the CRCLM growth pattern. Methods: 22 CRCLM specimens were assessed by histological evaluation, and Multiplex Immunohistochemistry (OPALTM) was used to examine density and distribution of T lymphocytes (CD3+), cytotoxic T cells (CD3+CD8+), resident memory T cells (CD3+CD8+CD103+)(TRM). Cell phenotyping algorithm was performed using inForm® software v3.5. The tissue segmentation algorithm determined the adjacent liver parenchyma (LP), invasive tumor margin (IM) and tumor core (TC) regions. Results: Histological evaluation of the 22 CRCLM specimens defined 7 desmoplastic, 8 replacement and 7 pushing growth patterns. The evaluation of the entire cohort of CRCLM showed that the spatial distribution total T lymphocytes as well as cytotoxic and TRM were found in significantly higher levels at the IM when compared with LP or TC. There was no significant difference between the IM and TC in the T lymphocytes cell count displayed by replacement pattern, whereas the desmoplastic and pushing pattern showed higher accumulation in the IM compared to the TC. The highest cell count of cytotoxic T cells occurred in the IM for all three growth patterns but only significantly different from the TC in the desmoplastic and pushing pattern. Conclusion: This study unveiled the spatial variation of immune profiles according to histologic growth patterns of CRCLM using a powerful systematic imaging approach.
1358 Learning Objectives Prognostic value of metabolic and pathological response in patients with colorectal liver metastases treated with preoperative chemotherapy. Background: The response of colorectal cancer liver metastases (CRCLM) to preoperative chemotherapy is a major determinant of patient outcome. Methods: 37 patients with 18F-FDG PET pre- and post-preoperative chemotherapy for CRCLM between 2004-2011 were included. Metabolic response was determined as change in SUVmax. Resected specimens were scored according to tumor regression grading (TRG), with significant (TRG 1 or 2) or insignificant pathological response (TRG 3-5). Prognostic indicators of RECIST response & clinicopathological scores were assessed. Correlation to recurrence-free (RFS) and overall survival (OS) was assessed using Kaplan-Meier survival and multivariate analysis. Results: Complete and partial metabolic response was observed in 24% and 50%, whilst stable and progressive metabolic disease was seen in 13%. Patients with metabolically responsive tumors had OS of 86% at 3 years vs. 38% with metabolically progressive tumors (p=0.003). Significant tumor regression was noted in 19% while insignificant tumor regression noted in 81% of patients. Patients with significant tumor regression had an OS of 100% at 3 years vs 72% in those with insignificant tumor regression (p=0.066). RECIST criteria did not predict outcome. On multivariate analysis, only metabolic response and the Fong prognostic score predicted OS while only metabolic response was predictive of RFS. Conclusion: Preoperative metabolic and pathological response both predict prognosis. Metabolic response strongly correlated to OS and RFS while major pathological response was highly specific (100%) for OS, but not RFS. Assessing tumor response to preoperative chemotherapy indicates systemic control of metastatic colorectal cancer and prognosis post-liver metastectomy.