Neoadjuvant therapy in locally advanced colon cancer: a meta-analysis and systematic review.

BACKGROUND: The role of perioperative or neoadjuvant chemotherapy for locally advanced colon cancer is unclear. Emerging evidence such as the FOXTROT trial is challenging the conventional norm of upfront operation for these patients. However, these trials have yet to reach statistical significance. METHODS: MEDLINE, Embase, Cochrane Library, China Knowledge Resource Integrated Database (CNKI) and ClinicalTrials.gov were searched. Randomized controlled trials (RCTs) and observational studies of patients with locally advanced colon cancer were included. The intervention arm was neoadjuvant chemotherapies while the comparator arm was adjuvant chemotherapies. Studies which reported outcomes of interests included overall survival, disease-free survival, R0 resection rate, perioperative complications and adverse effects of chemotherapy were chosen. RESULTS: We identified five eligible randomized trials and two observational studies, including 29,504 patients. Neoadjuvant therapies exhibited statistically significant improvement in overall survival [hazard ratio (HR) =0.76, 95% confidence interval (CI): 0.65-0.89, P=0.0005], and disease-free survival (HR =0.74, 95% CI: 0.58-0.95, P=0.02). R0 resection rate fell slightly short of significance [odds ratio (OR) =1.86, 95% CI: 0.95-3.62, P=0.07]. Risk of peri-operative complications did not differ between groups when examining abdominal infection [risk ratio (RR) =1.14, 95% CI: 0.59-2.18, P=0.70] and anastomotic leakage (RR =0.83, 95% CI: 0.53-1.31, P=0.42). No statistical differences in complications from chemotherapy were reported. CONCLUSIONS: This meta-analysis highlights the potential survival benefit of neoadjuvant chemotherapy compared to adjuvant chemotherapy for locally advanced colon cancer, without an increase in surgical morbidity. Neoadjuvant or perioperative approaches may be considered an alternative to upfront surgery followed by chemotherapy for locally advanced colon cancer.

Modern-day palliative chemotherapy for metastatic colorectal cancer: does colonic resection affect survival?

BACKGROUND: Patients with metastatic colorectal cancer (mCRC) with surgically incurable metastases would be recommended for palliative chemotherapy (PC). The role of surgical intervention is debatable with no conclusive evidence for routine primary tumour resection (PTR) or stoma creation. We aimed to study if surgical intervention conferred a survival benefit in patients with mCRC who received upfront systemic therapy. METHODS: A retrospective review of a prospectively collected database in a single centre was performed. Patients diagnosed with mCRC from January 2004 to December 2014 were included. We excluded patients who had an upfront surgical intervention, had no treatment with systemic therapy or had attained curative resection. The decision for surgery was based on the outcome of a multidisciplinary tumour board. Demographic, clinicopathological, treatment and follow-up data were collected. Univariate and multivariate analyses were performed. RESULTS: Out of 408 patients with mCRC with incurable metastases, we analysed 124 patients who had upfront PC. Twenty-nine had PC + PTR (group A), 10 had PC + stoma (group B) and 85 had PC only (group C). Undergoing PTR led to significant improvement in overall survival (OS; 30.8 versus 13.4 versus 11.0 months, P < 0.001). With multivariate analysis, undergoing PTR and receiving biologics were independent good prognostic variables. Surgical resection was safe with minimal complications. CONCLUSIONS: PTR was found to increase OS while stoma creation had no impact on OS. The benefits and safety of undergoing PTR may be a result of selection bias. Further prospective studies are required to confirm the observations of this study.

Extent of field change in colorectal cancers with BRAF mutation.

INTRODUCTION: Sporadic colorectal cancers with BRAF mutations constitute two distinct subgroups of colorectal cancers. Recent studies have linked the presence of the BRAF mutation to a familial inheritance pattern. This was a proof-of-concept study that aimed to examine: (a) the extent of field change in sporadic colorectal cancers with BRAF mutation; and (b) the extent of resection margins required and the pattern of DNA mismatch repair protein loss in these tumours. METHODS: Eight microsatellite instability-high tumours with positive BRAF mutation from an existing histopathological database were selected for BRAF mutation and mismatch repair protein analysis. RESULTS: All the resection margins were negative for BRAF mutation. Three tumours had loss of MLH1 and PMS2 expressions, and five tumours had no protein loss. Six peritumoral tissues were negative and one was positive for BRAF mutation. CONCLUSION: The results suggest that any early field change effect is restricted to the immediate vicinity of the tumour and is not a pan-colonic phenomenon. Current guidelines on resection margins are adequate for BRAF mutation-positive colorectal cancers. Any suggestion of a hereditary link to these tumours is likely not related to germline BRAF gene mutations. The pattern of protein loss reinforces previous findings for the two subgroups of BRAF mutation-positive colorectal cancers.