RFA was used as an adjunct to resection in patients with greater disease burden. Despite this, RFA was not significantly associated with a higher risk of local failure and was not associated with worse survival, when compared with liver resection alone.

ConclusionsCompared with patients who did not receive chemotherapy, those who received chemotherapy, regardless of timing, experienced improved overall survival and disease-free survival. Use of rfa where required as an adjunct to hepatic resection appears to be effective and is not associated with worse overall survival. KEY WORDSColorectal cancer, hepatic resection, timing of chemotherapy, radiofrequency ablation INTRODUCTIONOf the estimated 23,800 Canadians diagnosed with colorectal cancer (crc) annually, approximately 9200 (40%) will die from their disease, most with distant metastatic spread 1 . When feasible, hepatic resection offers the greatest probability of cure for patients with isolated liver metastases 2 . However, even for those with disease that is largely liver-limited, there are barriers to curative resection such as the extent and distribution of lesions within the liver, extrahepatic disease, comorbidities, and age 3 .The maldistribution of lesions within the liver, making complete excision of all disease impossible without the risk of subsequent liver insufficiency, is one barrier that has received considerable attention. Strategies include serial resection, portal vein embolization, and the adjuvant use of radiofrequency ablation (rfa). The rfa procedure uses heat derived from radiofrequency waves at the end of a probe inserted into a metastasis to induce tumour necrosis. The use of rfa as an adjunct to hepatic resection is gaining acceptance. However, its efficacy in comparison with resection is controversial because of high rates of recurrence at the ablation site in some studies 4 .Despite the increasing opportunity for potentially curative hepatic resection, recurrence in resected patients is the most frequent outcome. Chemotherapy, ABSTRACT BackgroundAlmost 40% of people diagnosed with colorectal cancer will die from their disease, most with metastatic spread. When feasible, hepatic resection offers the greatest probability of cure for isolated liver metastases, but there are barriers to curative resection. Those barriers include the extent and distribution of lesions within the liver, extrahepatic disease, comorbidities, and age. Chemotherapy is often administered before or after resection with the intention of improving disease-free and overall survival. The timing of chemotherapy (adjuvant vs. neoadjuvant vs. perioperative) for patients undergoing potentially curative hepatic resection of metastasis of colorectal cancer origin is controversial. MethodsColorectal cancer patients with liver metastases resected at The Ottawa Hospital between January 1, 2003, and December 31, 2009, were identified, and their clinical records were retrospectively reviewed. Patients receiving intraoperative radiofrequency ablation (rfa) as part of their management were included. Factors associated with overall and diseasefree survival were evaluated. ResultsThe 168 identified patients (57% men, 43% women) had a median age of 63 years (range: 31-84 years). After hepatectomy, 10% had positive resection margi...

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436 Background: Mutations affecting the KRAS gene are established predictive markers of outcome with anti–epithelial growth factor receptor antibodies in metastatic colorectal cancer (mCRC). The relevance of these markers for chemotherapy has not been established. This analysis was performed to assess the predictive impact of KRAS mutation status in patients receiving chemotherapy. Methods: KRAS mutational status was available for 223 patients treated for mCRC. Predictive analysis of mutational status by type of fluoropyrmidine the 1st-line regimen contained (either capecitabine [C] based chemotherapy or infusional 5Fluorouracil [I-5Fu]) for clinical outcomes: progression-free survival (PFS), time to chemotherapy resistance (TTCR) and overall survival (OS). Results: KRAS mutations were observed in 43.5% of the patients. 165 patients received I-5Fu, 44 patients received C. KRAS mutation status (wild type [WT] v mutated [MT]) had no prognostic impact for OS (hazard ratio [HR], 0.81; CI, 0.69 to 1.1 p=0.17) for PFS (hazard ratio [HR], 0.87; CI, 0.66 to 1.14 p=0.3) and TTCR (hazard ratio [HR], 0.85; CI, 0.65to 1.12 p=0.26). C based 1st-line chemotherapy vs. I- 5FU based was predictive of PFS (hazard ratio [HR], 0.52; CI, 0.37 to 0.74 p=0.0003) and TTCR (hazard ratio [HR], 0.54; CI, 0.38 to 0.75p=0.0005) and not of OS (hazard ratio [HR], 0.74; CI, 0.52 to 1.1 p=0.1). KRAS mutational status had predictive impact in patients receiving C based 1st-line chemotherapy on OS (hazard ratio [HR], 0.47; CI, 0.23 to 0.948 p<0.0001) TTCR (hazard ratio [HR], 0.49; CI, 0.25 to 0.97 p=0.0398) and was not predictive of PFS (hazard ratio [HR], 0.78; CI, 0.4 to 1.53 p=0.47) Conclusions: KRAS gene mutation status was predicitve for OS and for TTCR in patients who received C based 1st-line chemotherapy.

e14154 Background: The timing of chemotherapy (adjuvant vs neoadjuvant) for patients undergoing potentially curative hepatic resection of metastasis from colorectal cancer origin is controversial. Methods: We performed a retrospective review of all patients at TOHCC who underwent successful surgical resection of hepatic metastasis from CRC between 2002-2009. Patients receiving intra-operative radiofrequency ablation (RFA) as part of their management were included. Factors associated with overall survival were evaluated. Results: 168 patients had median age 62 years (31-84), 57/43% male/female. Median pre-op CEA was 5.5 ng/ml (0.3 - 529.2). Primary tumor location included 40% left, 35% rectum, 20% right, 5% transverse. 61.5% patients were node positive. Following hepatectomy 10.2% had positive resection margins. Intra-operative RFA was used in 26 (15.4%) patients. Chemotherapy was administered in a neo-adjuvant (47.6%), adjuvant (58.4%) or “perioperative” (both neoadjuvant and adjuvant; 36.1% ) setting. Use of intraoperative RFA vs. no RFA was not associated with overall survival (HR: 0.94 [95%CI: 0.49-1.80],p=0.85). In both univariate and multivariate analysis, the only adverse factor found associated with survival was R1 status (HR 2.38 [95% CI 1.49-5.0], p=0.0198). Other baseline variables (age, gender, node status, histologic grade, primary tumour site, timing of metastatic diagnosis [metachronous vs. synchronous]) did not reach statistical significance. Conclusions: While statistical significance was not achieved, ability to demonstrate benefit of chemotherapy may have been limited by sample size. Hazard ratios suggest trend to greatest benefit with use of post-operative adjuvant chemotherapy. 3y and 5y survival data is encouraging. Use of RFA where required as an adjunct to hepatic resection appeared as effective as resection of all disease in this series. Recurrence and morbidity data will be presented. [Table: see text]

504 Background: KRAS mutations (MUT), present in ~40% of CRC, predict benefit from EGFR MAb treatment. The effect of mutation status on benefit from chemotherapy alone is less clear. Methods: Following ethics approval, 223 CRC patients with known KRAS status treated at a single institution were retrospectively analyzed for response to chemotherapy prior to initiation of EGFR MAb therapy. Tumour response rate and progression-free survival (PFS) were determined retrospectively. Given chemotherapy sequencing variability, a measure of the time to chemotherapy-refractory state (TTCR) was defined as time from start of first line therapy to progression on all drugs; ie fluoropyrimidines (F), irinotecan (I), and oxaliplatin (O), +/- bevacizumab (B). Results: Patients were median age 60 years (25-86), 58/42% male/female, 38% rectal or rectosigmoid, 18% liver-only metastases, 45.6% stage I-III and 54.4% stage IV at initial diagnosis, 43% prior adjuvant chemotherapy, 43/57% KRAS MUT/wild-type(WT) status. With a median follow-up of 27 months, 64 (29%) are alive. TTCR did not vary by KRAS status, with median 16.7 vs 14.8 months in WT vs MUT status patients, respectively, HR 0.85 [0.65-1.12], p=0.26. Overall survival (which now includes influence of any subsequent EGFR MAb therapy, received by 76/126 (60%) of KRAS WT status patients) did not differ significantly by KRAS status, with median survival 34.3 vs 29.2 months for WT vs MUT status, respectively, 0.79 [0.58-1.08], p=0.14. Conclusions: For most treatment strategies KRAS status did not affect 1st line PFS or time to chemotherapy-refractory state. However, for patients who received triple combination therapy, MUT status was associated with early progression. Small sample size, chance or some yet-to-be-elucidated molecular interaction may account for this finding. [Table: see text]

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