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597 Background: We reported in a retrospective study that the presence of micrometastasis in lymph nodes (LNs), when assessed by CEA-specific RT-PCR, is a significant prognostic factor in stage II colorectal cancer (CRC). The aim of this study was to clarify the clinical value of micrometastasis in a prospective multicenter trial. Methods: From November 2001 to December 2005, a total of 419 CRC cases were preoperatively registered at a central data center. Of them, 315 node-negative stage II CRC were enrolled. After RNA quality check, 304 CRC cases were analyzed for CEA mRNA in LNs by both conventional RT-PCR (a band method) and quantitative RT-PCR. Long-term prognosis of the patients was determined by each method. Results: A positive band for CEA mRNA was detected in 73 (24.0%) of 304 patients. Post-operative adjuvant chemotherapy was applied in 31 CEA band-positive cases with an oral 5-FU derivative HCFU (1-hexylcarbamoyl-5-fluorouracil) for one year, while chemotherapy was not administered to CEA band-negative group. Multivariate Cox regression analyses revealed that a high micrometastasis volume (High-MMV, n = 95) was an independent poor prognostic factor for 5-year DFS ( P= 0.001) and 5-year OS ( P= 0.016). Conclusions: This prospective clinical trial demonstrates that micrometastasis volume is a useful marker in identifying patients who are at high or low risk for recurrence of stage II CRC.

566 Background: Chemoradiotherapy (CRT) followed by surgery is a standard treatment for locally advanced rectal cancer. Although preoperative CRT decreases local recurrence (LR), pelvic radiation is associated with long-term morbidity. We conducted this study to evaluate the feasibility of neoadjuvant XELOX with bevacizumab (Bmab) in patients (pts) with locally advanced rectal cancer. Methods: Pts with T4 or lymph node (LN) positive rectal cancer were treated with 3 cycles of XELOX with Bmab and one additional cycle of XELOX. Total mesorectal excision was performed 3-8 weeks after the last chemotherapy. The primary endpoint was to assess feasibility and secondary endpoints were R0 resection rate, down staging rate, pathological complete response (pCR) rate and pathological effect over grade 2 (tumor cell death in more than two-thirds of the entire lesion). Results: Twenty five pts were recruited between December 2009 and November 2011. Characteristics of pts were as the following: male/female, 18/7; median age, 63 years (range, 37-75); median diameter of tumor, 52.8mm (range, 38.3-110); T2-T3/T4a/T4b, 7/8/10 and N0/N1/N2, 3/14/8. In 4% of the pts (7 pts), following grade 3-4 adverse events occurred; neutropenia, hypertension, bleeding, rectal obstruction, pelvic infection, anorexia and nausea. The down staging rate of T2-T3/T4a/T4b and N1/N2 were 29/63/50 % and 86/63 %, respectively. Seven pts (28%) discontinued the treatment after 2-3 cycles of XELOX with Bmab (13% in T2-T4a, 50% in T4b). The rate of conducting surgery was 92% and all of them had R0 resections. Postoperative complications were found in 9 pts (39%). The pCR rate was 4%, and the rate of pathological effect over grade 2 was 61%. Two LR (LN positive) and two distant recurrences (1 lung, 1 liver) were reported. Conclusions: XELOX with Bmab followed by surgery was safely performed for locally advanced rectal cancer. The down staging rate was 50% even in T4b pts although half of T4b pts discontinued the study treatment. Based on these preliminary results, we are planning a phase II trial of perioperative XELOX and surgery in locally advanced rectal cancer. Clinical trial information: 000003219.

e14078 Background: In recurrent or metastatic colorectal cancer, a combination of leucovorin and fluorouracil with oxaliplatin (FOLFOX) is a standard first-line regimen. Although a variety of FOLFO...

e15122 Objective: The aim of this study was to evaluate the efficacy and tolerability of treatment with mFOLFOX6 followed by surgical tumor removal in patients (pts) with initially unresectable liver metastases and/or extrahepatic disease from colorectal cancer (CRC). Methods: This study was a multicenter, open-label clinical trial. Eligibility criteria defined pts with advanced and metastatic CRC deemed not optimally resectable. mFOLFOX6 (oxaliplatin 85 mg/m2, l-leucovorin 200 mg/m2, and fluorouracil [400 mg/m2 bolus followed by 2,400mg /m2 as a continuous 46-hour infusion]) was administered every 2 weeks for a maximum of 10 cycles. Resectability was the primary end point. Results: 26 pts (15M/11F; PS 0/1 19/7; median age: 60 years, rage 37–73) received 181cycles (median 7, range, 3–10) of mFOLFOX6. Main unresectable lesions were liver metastases in 10 pts and extrahepatic disease in 16 pts. Eleven pts (42%) had at least one grade 3 or greater adverse events. Sixteen pts (61%) achieved an objective response to mFOLFOX6 and 8 pts (31%) had a best overall response of stable disease. In 16 of these 24 pts who achieved the disease control, surgical tumor removal was performed (resectability 61%). The main reasons for initial unresectability in these 16 pts were the presence of liver metastases (6 pts), para-aortic lymph-node metastases (4 pts), carcinomatous peritonitis (4 pts), direct invasion to neighboring organ (2 pts). Four complications (25%) which were anastomotic leak, wound infection, chylous ascites, and cholangitis, were observed. At a median follow-up of 13 months (range 5 -21), 5 pts had relapsed after surgical tumor removal. The median time to progression (TTP) of the pts who underwent operation is not reached to date and those who did not undergo surgical removal is 8.6 months (log-rank p No significant financial relationships to disclose.

4059 Background: We previously reported that mitochondrial transcription factor A (mtTFA; also designated Tfam) preferentially recognizes cisplatin-damaged DNA via physical interaction with p53 and is upregulated by the treatment with cisplatin and 5-FU (Yoshida et al, Cancer Res. 2003). The aim of this study was to evaluate whether expression of mtTFA predicts clinical outcome in patients with metastatic colorectal cancer treated with modified FOLFOX6 (mFOLFOX6). Methods: From January 2006 to April 2008, 59 patients who had metastatic lesions from colorectal cancer treated with mFOLFOX6 at the Osaka Rosai Hospital were included in this study. They consisted of 25 women (42.4%) and 34 men (57.6%), with a median age of 62 years (29–84). Patients were treated with oxaliplatin 85mg/m2 plus leucovorin 200mg/m2 as a 2-h infusion at day 1, followed by 5-FU bolus 400mg/m2 and 46-h continuous infusion of 2400 mg/m2. Treatment was repeated in 2-week intervals for at least 4 cycles. The expressions of mtTFA and p53 of resected primary tumors were examined by immunohistochemistry. Results: Among 59 patients, one complete response and 32 partial responses were observed (response rate, 55.9%) . The positive rates was 44.1% (26/59; CR 1, PR 7, SD/PD 18) for mtTFA and 59.3% (35/59; CR 1, PR 19, SD/PD 15) for p53, respectively. Strong expression of mtTFA was detected in 8 of 33 CR/PR (24.2%) and in 18 of 26 SD/PD (69.2%), indicating that the expression of mtTFA correlated significantly with response to chemotherapy (P No significant financial relationships to disclose.

15079 Background: We previously reported that mitochondrial transcription factor A (mtTFA) preferentially recognizes cisplatin- damaged DNA via physical interaction with p53 and is upregulated by t...