Bengt Glimelius

BACKGROUND: Short-term preoperative radiotherapy and total mesorectal excision have each been shown to improve local control of disease in patients with resectable rectal cancer. We conducted a multicenter, randomized trial to determine whether the addition of preoperative radiotherapy increases the benefit of total mesorectal excision. METHODS: We randomly assigned 1861 patients with resectable rectal cancer either to preoperative radiotherapy (5 Gy on each of five days) followed by total mesorectal excision (924 patients) or to total mesorectal excision alone (937 patients). The trial was conducted with the use of standardization and quality-control measures to ensure the consistency of the radiotherapy, surgery, and pathological techniques. RESULTS: Of the 1861 patients randomly assigned to one of the two treatment groups, 1805 were eligible to participate. The overall rate of survival at two years among the eligible patients was 82.0 percent in the group assigned to both radiotherapy and surgery and 81.8 percent in the group assigned to surgery alone (P=0.84). Among the 1748 patients who underwent a macroscopically complete local resection, the rate of local recurrence at two years was 5.3 percent. The rate of local recurrence at two years was 2.4 percent in the radiotherapy-plus-surgery group and 8.2 percent in the surgery-only group (P<0.001). CONCLUSIONS: Short-term preoperative radiotherapy reduces the risk of local recurrence in patients with rectal cancer who undergo a standardized total mesorectal excision.

Cancer is one of the leading causes of death, and there is great interest in understanding the underlying molecular mechanisms involved in the pathogenesis and progression of individual tumors. We used systems-level approaches to analyze the genome-wide transcriptome of the protein-coding genes of 17 major cancer types with respect to clinical outcome. A general pattern emerged: Shorter patient survival was associated with up-regulation of genes involved in cell growth and with down-regulation of genes involved in cellular differentiation. Using genome-scale metabolic models, we show that cancer patients have widespread metabolic heterogeneity, highlighting the need for precise and personalized medicine for cancer treatment. All data are presented in an interactive open-access database (www.proteinatlas.org/pathology) to allow genome-wide exploration of the impact of individual proteins on clinical outcomes.