Modulation of the wnt/β-catenin signal pathway in vitro by apoE COG1410 in IEC-18 after 5-FU injury

Abstract

dose modifications/delays. 93.5% received capecitabine concomitantly with radiother-apy (3.9% with 5-FU, and 2.6% had radiotherapy alone). 76.3% of 76 eligible patients had adjuvant chemotherapy (capecitabine and oxaliplatin in 65.5% of cases, and cape-citabine monotherapy in 27.6%). Median follow up was 4.4 years from diagnosis. Radiological indices of response (size/fibrosis) were observed in 70 of 74 evaluable cases, with 2 showing progression and 2 appearing stable. For patients eventually proceeding to surgery, pre-treatment (radiological) and post-treatment (surgical) staging was as follows (with post-treatment in parentheses): 29.9% (7.8%) were T4, 61.0% (53.2%) were T3, and 9.1% (18.2%) were T2. There were 11 local pathological complete responses (all in M0 patients; 18.0% of this group) and 74% were downstaged by neo-adjuvant treatment (T or N status). 84.4% had radiologically-involved nodes at base-line, and 37.7% at surgery. 10.4% were Mx and 10.4% had potentially operable M1 disease at baseline. 5 year overall survival (OS) for all patients who started treatment was 96.4%/44.4%/ 54.7% for the M0/Mx/M1 groups, respectively, and 98.0%/50.0%/54.7% for those patients who proceeded to surgery. For M0 patients who proceeded to surgery, the 5 year OS was 100% for radiologically node-negative patients (number at risk (NAR) at 5 years¼6) and 97.5% for node-positive patients (NAR at 5 years¼22). For patients that were M0 at the time of surgery (n ¼ 60), the 5 year recurrence-free survival was 82.1%. For patients who recurred post surgery (n ¼ 9), 5 proceeded to potentially curative metastasectomies and remain disease-free. Conclusion: These data provide further evidence for the safety, tolerability and long-term efficacy of neoadjuvant chemotherapy with capecitabine and oxaliplatin in this high-risk group of patients, compare favourably with trial data, and support its routine use in a real-world setting. rectal cancer: A Emanuele 4 , fico (IRCCS), proven to increase and surgery is still weeks or longer ogical complete to identify correl-radiotherapy) and rectal cancer (stage with 45-50 Gy con-surgery (total n radiotherapy and based on time to 58 pts). Statistical nonparametric esti-was observed in 22.7% (n ¼ 25/110 pts). pCR in group A was 19.2% (n ¼ 10/52 pts) and 25.8% (15/58) in group B with statistically significant difference (p < 0.001). Good responders (Dworak TRG4 þ 3) in group A were 39.6% vs 45.7% in group B. Bad responders (Dworak TRG2 þ 1þ0) in group A were 60.4% vs 54.3% in group B. At this time disease free survival rates in overall population was 90.3%, 85.2% respectively at 3 and 5 years and overall survival was 77.6%, 72.9% at 3 and 5 years. There was no statistically significant difference in DFS between group A vs group B (4 yrs DFS rate: 73.2% vs 72.2%, p ¼ 0.920). Conclusion: This study suggests delaying surgery beyond 13th week after the start of CRT seemed to result in the highest chance of a pCR and probably in downstaging, in accord to recent published data. The delayed surgery would seem to select a greater number of good responders. Obviously prospective randomized studies of appropriate statistical power comparing various time intervals are needed to examine the optimal timing for surgery and to plan the better management of these setting of patients. P À 364 Modulation of the wnt/b-catenin signal pathway in vitro by apoE COG1410 in IEC-18 after 5-FU injury