In the postoperative arm, MLN8237 price patients began CMT within 4 weeks after surgery, with the same concurrent chemotherapy and radiation therapy schedule as the neoadjuvant CMT arm. After the completion of the initial

50.4 Gy, a 5.4 Gy boost in 3 fractions was delivered to the tumor bed, followed by 4 cycles of bolus 5-FU as in the preoperative CMT arm. Five-year LR was significantly lower in the preoperative arm (6% vs. 13%, p=0.006), while there was no significant difference in DFS and OS. Eight percent of patients had a pathological CR, and there was a greater percentage of sphincter-preserving operations performed (39% vs. 19%, p=0.004) in the preoperative group. Acute Inhibitors,research,lifescience,medical grade 3 or 4 toxicity was significantly less in the neoadjuvant group (27% vs. 40%, p=0.001), as was the rate of late grade 3 or 4 toxicity

(14% vs. 24%, p=0.01). It should be noted that 18% Inhibitors,research,lifescience,medical of patients in the immediate surgery arm were found to have stage I disease upon pathologic assessment of the surgical specimen. Since all patients were staged before treatment and were felt to have stage II/III disease, the authors concluded that this number (18%) represents the approximate number of patients Inhibitors,research,lifescience,medical at risk of overtreatment with neoadjuvant CMT, again stressing the importance of accurate pre-treatment staging (43). The results of the Medical Research Council (MRC) CR07 study were recently published, evaluating the Inhibitors,research,lifescience,medical merits of short-course preoperative radiation (44). In this randomized study, patients were treated with 25 Gy in 5 fractions followed by surgery or were treated with immediate resection with selective postoperative CMT (45 Gy in 25 fractions with concurrent 5-FU) in patients with positive circumferential surgical margin. It should also be noted that all patients found to have stage III disease were to receive postoperative 5-FU. In patients receiving preoperative radiation, there was a 61% reduction

in the relative risk of LR (hazard ratio [HR]: 0.39, 95% confidence interval [CI] 0.27-0.58, p<0.0001), with 3-year LR of 4.4% in the preoperative radiation therapy arm vs. 10.6% in the selective postoperative CMT Inhibitors,research,lifescience,medical arm (95% CI 5.3-7.1). In addition, there was a statistically significant improvement in DFS in the preoperative radiation therapy arm (HR 0.76, 95% CI 0.62-0.94, p=0.013), however OS did not differ significantly between the two groups. This study further confirmed the value of preoperative radiation therapy. Preferred techniques/regimens In the United States, it is recommended DNA ligase that patients staged with resectable stage II or III rectal cancer should be treated initially with preoperative CMT unless there are medical contraindications (4). Radiation therapy should employ multiple treatment portals and the treatment volume should include the tumor with margin, along with the internal iliac and presacral lymph nodes (as well as the external iliac lymph nodes with T4 disease) (Figures 1 and ​and2).2).