Neoadjuvant chemoradiation did not increase survival, local control or late toxicity compared with short-course radiotherapy alone.

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Background: This trial evaluated whether preoperative short-course radiotherapy and consolidation chemotherapy (CCT) were superior to chemoradiation in rectal cancers with clinical (c)T4 or fixed cT3. Previously, we reported early results showing no differences in the radical surgery rate (primary end point). In the short-course/CCT group, we observed lower acute toxicity of preoperative treatment and better overall survival (OS). We updated results to determine whether the benefit in OS was sustained and to evaluate late complications.Patients and methods: Patients with cT4 or fixed cT3 rectal cancer were randomized either to preoperative 5 Â 5 Gy and three cycles of FOLFOX4 or to chemoradiation (50.4 Gy with bolus 5-Fu, leucovorin and oxaliplatin).Results: Patients (N ¼ 515) were eligible for analysis, 261 in the short-course/CCT group and 254 in the chemoradiation group. The median follow-up was 7.0 years. The difference in OS was insignificant [hazard ratio (HR) 0.90; 95% confidence interval (CI) 0.70-1.15; P ¼ 0.38). However, the difference in early OS favouring short-course/CCT previously reported was observed again, being 9% at 3 years (95% CI 0.5% to 17%). This difference disappeared later; at 8 years OS was 49% in both groups. There was no difference in disease-free survival (HR 0.95; 95% CI 0.75-1.19; P ¼ 0.65) at 8 years 43% versus 41% in the short-course/CCT group versus the chemoradiation group, respectively. The corresponding values for cumulative incidences of local failure and distant metastases did not differ and were HR ¼ 1.08, 95% CI 0.70-1.23, P ¼ 0.60, 35% versus 32% and HR ¼ 1.10, 95% CI 0.68-1.23, P ¼ 0.54, 36% versus 34%, respectively. The rate of late complications was similar (P ¼ 0.66), grade 3þ being 11% versus 9% in the short-course/CCT group versus the chemoradiation group, respectively. Conclusion:The superiority of preoperative short-course/CCT over chemoradiation was not demonstrated.

The aim of this study was to exploit the potential clinical use of circulating cytokine measurements in colorectal cancer (CRC) patients. The levels of cytokines and cytokine receptors were assessed by ELISA in the sera of 50 healthy volunteers and 157 patients with previously untreated CRC and then related to clinicopathological features and prognosis. All tumors were verified histologically as colorectal adenocarcinomas and staged according to TNM classification. The levels of circulating interleukin (IL)-6, IL-8, macrophage colony-stimulating factor (M-CSF) and interleukin 1 receptor antagonist (IL-1ra) significantly increased with the clinical stage of CRC, and the levels of IL-6, soluble tumor necrosis factor (sTNF) receptor type I (RI), soluble interleukin 2 receptor α and TNFα with tumor grade, while IL-6, IL-8, M-CSF, IL-1ra and sTNF RI levels significantly rose with bowel wall invasion. None of the cytokine or soluble cytokine receptor levels were influenced by age, gender and colon versus rectum localization. sTNF RI, IL-8, IL-6 and vascular endothelial growth factor measurements demonstrated the highest diagnostic sensitivity. sTNF RI was found elevated in the greatest percentage of all CRC patients, in the greatest proportion of stage I patients and presented the best diagnostic sensitivity. In addition, the sTNF RI level strongly correlated with tumor grade and invasion and proved to be an independent prognostic factor.

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BackgroundDistal intramural spread is present within 1 cm from visible tumor in a substantial proportion of patients. Therefore, ≥1 cm of distal bowel clearance is recommended as minimally acceptable. However, clinical results are contradictory in answering the question of whether this rule is valid. The aim of this review was to evaluate whether in patients undergoing anterior resection, a distal bowel gross margin of <1 cm jeopardizes oncologic safety.MethodsA systematic review of the literature identified 17 studies showing results in relation to margins of approximately <1 cm (948 patients) versus >1 cm (4626 patients); five studies in relation to a margin of ≤5 mm (173 patients) versus >5 mm (1277 patients), and five studies showing results in a margin of ≤2 mm (73 patients). In most studies, pre- or postoperative radiation was provided.ResultsA multifactorial process was identified resulting in selection of favorable tumors for anterior resection with the short bowel margin and unfavorable tumors for abdominoperineal resection or for anterior resection with the long margin. In total, the local recurrence rate was 1.0% higher in the <1-cm margin group compared to the >1-cm margin group (95% confidence interval [CI] −0.6 to 2.7; P = 0.175). The corresponding figures for ≤5 mm cutoff point were 1.7% (95% CI −1.9 to 5.3; P = 0.375). The pooled local recurrence rate in patients having ≤2 mm margin was 2.7% (95% CI 0 to 6.4).ConclusionsIn the selected group of patients, <1 cm margin did not jeopardize oncologic safety.