PURPOSE To ascertain if preoperative short-term radiotherapy followed by chemotherapy is not inferior to a standard schedule of long-term chemoradiotherapy in patients with locally advanced rectal cancer. MATERIALS AND METHODS Patients with distal or middle-third, clinical primary tumor stage 3-4 and/or regional lymph node–positive rectal cancer were randomly assigned (1:1) to short-term radiotherapy (25 Gy in five fractions over 1 week) followed by four cycles of chemotherapy (total neoadjuvant therapy [TNT]) or chemoradiotherapy (50 Gy in 25 fractions over 5 weeks, concurrently with capecitabine [chemoradiotherapy; CRT]). Total mesorectal excision was undertaken 6-8 weeks after preoperative treatment, with two additional cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) in the TNT group and six cycles of CAPOX in the CRT group. The primary end point was 3-year disease-free survival (DFS). RESULTS Between August 2015 and August 2018, a total of 599 patients were randomly assigned to receive TNT (n = 302) or CRT (n = 297). At a median follow-up of 35.0 months, 3-year DFS was 64.5% and 62.3% in TNT and CRT groups, respectively (hazard ratio, 0.883; one-sided 95% CI, not applicable to 1.11; P < .001 for noninferiority). There was no significant difference in metastasis-free survival or locoregional recurrence, but the TNT group had better 3-year overall survival than the CRT group (86.5% v 75.1%; P = .033). Treatment effects on DFS and overall survival were similar regardless of prognostic factors. The prevalence of acute grade III-V toxicities during preoperative treatment was 26.5% in the TNT group versus 12.6% in the CRT group ( P < .001). CONCLUSION Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to CRT for locally advanced rectal cancer.

1. The aim of the present study was to investigate the effect of hydrogen sulphide (H(2)S) on cobalt chloride (CoCl(2))-induced injury in H9c2 embryonic rat cardiac cells. 2. After 36 h incubation in the presence of 600 micromol/L CoCl(2), reduced cell viability of H9c2 cells was observed, as well as the induction of apoptosis. In addition, CoCl(2) (600 micromol/L) enhanced the production of reactive oxygen species (ROS) and the expression of cleaved caspase 3, induced a loss of mitochondrial membrane potential (MMP) and decreased reduced glutathione (GSH) production. These results suggest that CoCl(2) induces similar responses to hypoxia/ischaemia. 3. Pretreatment of cells with 400 micromol/L NaHS (a H(2)S donor) for 30 min prior to exposure to CoCl(2) (600 micromol/L) significantly protected H9c2 cells against CoCl(2)-induced injury. Specifically, increased cell viability and decreased apoptosis were observed. In addition, NaHS pretreatment blocked the CoCl(2)-induced increases in ROS production and cleaved caspase 3 expression, as well as the decreases in GSH production and loss of MMP. 4. Pretreatment of cells with 2000 micromol/L N-acetylcysteine (NAC), a ROS scavenger, for 1 h prior to CoCl(2) exposure significantly protected H9c2 cells against CoCl(2)-induced injury, specifically enhancing cell viability, decreasing ROS production and preventing loss of MMP. 5. The findings of the present study suggest that H(2)S protects H9c2 cells against CoCl(2)-induced injury by suppressing oxidative stress and caspase 3 activation.

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