Efficacy and safety of extended duration to perioperative thromboprophylaxis with low molecular weight heparin on disease-free survival after surgical resection of colorectal cancer (PERIOP-01): multicentre, open label, randomised controlled trial

Abstract

Objective To determine the efficacy and safety of extended duration perioperative thromboprophylaxis by low molecular weight heparin when assessing disease-free survival in patients undergoing resection for colorectal cancer. Design Multicentre, open label, randomised controlled trial. Settings 12 hospitals in Quebec and Ontario, Canada, between 25 October 2011 and 31 December 2020. Participants 614 adults (age ≥18 years) were eligible with pathologically confirmed invasive adenocarcinoma of the colon or rectum, no evidence of metastatic disease, a haemoglobin concentration of ≥8 g/dL, and were scheduled to undergo surgical resection. Interventions Random assignment to extended duration thromboprophylaxis using daily subcutaneous tinzaparin at 4500 IU, beginning at decision to operate and continuing for 56 days postoperatively, compared with in-patient postoperative thromboprophylaxis only. Main outcome measures Primary outcome was disease-free survival at three years, defined as survival without locoregional recurrence, distant metastases, second primary (same cancer), second primary (other cancer), or death. Secondary outcomes included venous thromboembolism, postoperative major bleeding complications, and five year overall survival. Analyses were done in the intention-to-treat population. Results The trial stopped recruitment prematurely after the interim analysis for futility. The primary outcome occurred in 235 (77%) of 307 patients in the extended duration group and in 243 (79%) of 307 patients in the in-hospital thromboprophylaxis group (hazard ratio 1.1, 95% confidence interval 0.90 to 1.33; P=0.4). Postoperative venous thromboembolism occurred in five patients (2%) in the extended duration group and in four patients (1%) in the in-hospital thromboprophylaxis group (P=0.8). Major surgery related bleeding in the first postoperative week was reported in one person (<1%) in the extended duration and in six people (2%) in the in-hospital thromboprophylaxis group (P=0.1). No difference was noted for overall survival at five years in 272 (89%) patients in the extended duration group and 280 (91%) patients in the in-hospital thromboprophylaxis group (hazard ratio 1.12; 95% confidence interval 0.72 to 1.76; P=0.1). Conclusions Extended duration to perioperative anticoagulation with tinzaparin did not improve disease-free survival or overall survival in patients with colorectal cancer undergoing surgical resection compared with in-patient postoperative thromboprophylaxis alone. The incidences of venous thromboembolism and postoperative major bleeding were low and similar between groups. Trial registration ClinicalTrials.gov NCT01455831 .

Association between different types of preoperative anemia and tumor characteristics, systemic inflammation, and survival in colorectal cancer

“…Similarly, this study also found that different types of anemia were closely related to tumor location, tumor size, and TNM stage, consistent with Giudice & Selleri ’s ( 2022 ) study. Auer et al (2018) also found that compared with the distal colon and rectum, the hemoglobin of patients with proximal colon tumors was significantly lower. Disturbance of colonic microbiota can lead to the occurrence and development of colorectal cancer and interfere with the absorption of nutrients ( Gomes et al, 2022 ).…”

Prognostic value of anticoagulants in resectable gastric cancer

“…In our study we did not investigate the survival difference between prolonged perioperative anticoagulation and postoperative anticoagulation alone. One study reported that prolonged perioperative anticoagulation did not improve DFS or OS in patients with colorectal cancer undergoing surgical resection compared with in-hospital postoperative thromboprophylaxis [34]. The optimal timing of anticoagulation therapy in patients with GC needs to be further explored.…”

Anticoagulation for the Prevention of Arterial Thrombosis in Ambulatory Cancer Patients

“… 54 , 55 , 56 This finding from our meta-analysis is further supported by a recently published randomized controlled trial enrolling 614 adults with colorectal cancer comparing extended (8 weeks) to inpatient-only tinzaparin administration after surgical resection, which was halted for futility with no difference in 3-year disease-free survival or 5-year overall survival. 57 …”