The 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.
Central 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.
The 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.
Pre-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.
Clinical trial identification
Legal entity responsible for the study
University of Birmingham.
All authors have declared no conflicts of interest.