532PD - Pre-operative FOLFOX chemotherapy in advanced colon cancer: Pathology analysis of the FOxTROT trial

Abstract

BackgroundThe phase III international FOxTROT trial assessed the effectiveness of pre-operative chemotherapy in locally advanced colon cancer. Patients were randomised across 85 centres to pre- and post-operative FOLFOX-based chemotherapy (pre-op) or to post-operative FOLFOX chemotherapy alone (post-op) in a 2:1 ratio. MethodsCentral pathological review was performed on scanned H&E stained slides in 904 out of 1,052 cases (86%) to include reassessment of the core pathology endpoints and an additional assessment of novel prognostic and immunological markers according to trial arm. ResultsThe pre-op group showed a lower pT stage (pT0-pT2 rate 18% vs 8%, p<0.0001), lower pN stage (pN0 rate 64% vs. 52%, p=0.0002), smaller tumour diameter (40mm vs. 51mm, p<0.0001), and greater R0 rate (99% vs. 96%, p=0.02). The pre-op group showed a lower rate of apical node metastases (3% vs. 8%, p=0.002), extracapsular spread (8% vs. 19%, p<0.0001), intramural venous invasion (20% vs. 33%, p<0.0001), extramural venous invasion (35% vs. 44%, p=0.004) and lymphatic invasion (46% vs. 55%, p=0.002). The percentage of the patients with high-grade tumour budding was lower in pre-op group (5% vs. 14%, p<0.0001). Significantly greater numbers of stromal tumour infiltrating lymphocytes (TILs) (14% vs. 9%, p<0.0001) and eosinophils (6% vs. 3%, p<0.0001) were observed in the pre-op group, however, intratumoural TILs were equivalent (5% vs. 5%, p=0.63). Significantly lower numbers of neutrophils (5% vs. 10%, p<0.0001) and reduced abscess formation (11% vs. 21%, p<0.0001) was seen in the pre-op group. The average area of all uninvolved lymph nodes was smaller in the preoperative group as was the average tumour area in metastatic nodes. ConclusionsPre-op chemotherapy in locally advanced colon cancer is associated with a significant reduction in many high-risk pathological features and potential mechanisms of metastatic spread. There is also a clear effect on tumour immunology. The association with 2 year DFS is currently being performed and will be presented at the meeting. Legal entity responsible for the studyUniversity of Birmingham. FundingAmgen. DisclosureAll authors have declared no conflicts of interest.