The impact of red blood cell transfusion on mortality and treatment efficacy in patients treated with radiation: A systematic review
Clinical and translational radiation oncology. 2022;33:23-29
INTRODUCTION Packed red blood cell (RBC) transfusion is frequently used in patients undergoing radiotherapy (RT) because retrospective data suggest that anemic patients may respond sub-optimally to RT. No high-quality evidence currently exists to guide transfusion practices and establish hemoglobin (Hb) transfusion thresholds for this patient population, and practice varies significantly across centers. This systematic review investigated whether maintaining higher Hb via transfusion in radiation oncology patients leads to improved outcomes. METHODS We performed a literature search of studies comparing RBC transfusion thresholds in radiation oncology patients. Included studies assessed patients receiving RT for malignancy of any diagnosis or stage. Excluded studies did not evaluate Hb or transfusion as an intervention or outcome. The primary outcome was overall survival. Secondary outcomes included locoregional control, number of transfusions and adverse events. RESULTS One study met inclusion criteria. The study pooled results from two randomized controlled trials that stratified anemic patients with head and neck squamous cell carcinoma to RBC transfusion versus no transfusion. The study found no significant differences in overall survival or locoregional control after five years, despite increased Hb levels in the transfused group. We conducted a narrative review by extracting data from 10 non-comparative studies involving transfusion in patients receiving RT. Results demonstrated no consistent conclusions regarding whether transfusions improve or worsen outcomes. CONCLUSIONS There is a lack of data on the effects of RBC transfusion on outcomes in patients undergoing RT. Well-designed prospective studies are needed in this area.
Patients undergoing radiotherapy (11 studies).
Red blood cell transfusion.
Only one study met the inclusion criteria which pooled results from two randomized controlled trials (DAHANCA 5 and 7). The study found no significant differences in overall survival or locoregional control after five years, despite increased haemoglobin levels in the transfused group (n= 235) vs. no transfused group (n= 230). A narrative review was conducted by extracting data from 10 other non-comparative studies involving transfusion in patients receiving radiotherapy. There were no consistent conclusions from these 10 studies on whether transfusions improve or worsen outcomes.
Efficacy of Different Interventions to Reduce Pre- or Perioperative Blood Transfusion Rate in Patients with Colorectal Cancer: A Network Meta-Analysis of Randomized Controlled Trials
Current oncology (Toronto, Ont.). 2021;28(4):3214-3226
BACKGROUND The high proportion of blood transfusions before and during surgery carries unnecessary risk and results in poor prognosis in colorectal cancer patients. Different pharmacological interventions (i.e., iron supplement or recombinant erythropoietin) to reduce blood transfusion rates have shown inconclusive results. METHODS This network meta-analysis (NMA) consisted of randomized controlled trials (RCTs) comparing the efficacy of different pharmacologic interventions (i.e., iron supplementation or recombinant erythropoietin) to reduce the blood transfusion rate. NMA statistics were conducted using the frequentist model. Results: Seven RCTs (688 participants) were included in this study. The NMA demonstrated that the combination of high-dose recombinant human erythropoietin and oral iron supplements was associated with the least probability of receiving a blood transfusion [odds ratio = 0.24, 95% confidence intervals (95% CIs): 0.08 to 0.73] and best reduced the amount of blood transfused if blood transfusion was necessary (mean difference = -2.62 U, 95% CI: -3.55 to -1.70 U) when compared to the placebo/control group. None of the investigated interventions were associated with any significantly different dropout rate compared to the placebo/control group. CONCLUSIONS The combination of high-dose recombinant human erythropoietin and oral iron supplements might be considered as a choice for reducing the rate of blood transfusion in patients with colorectal cancer. However, future large-scale RCT with long-term follow-up should be warranted to approve the long-term safety.
Risk of thrombocytopenia with Platelet-derived Growth Factor Receptor Kinase Inhibitors (PDGFR-TKIs) in cancer patients: A systematic review and meta-analysis of phase II/III randomized controlled trials
Journal of clinical pharmacology. 2021
We performed a systematic review and meta-analysis to fully investigate the thrombocytopenia of Platelet-derived Growth Factor Receptor Kinase Inhibitors (PDGFR-TKIs) in cancer patients. Databases were searched for randomized controlled trials (RCTs) treated with PDGFR-TKIs till January 2021. The relevant RCTs in cancer patients treated with PDGFR-TKIs were retrieved and the systematic evaluation was conducted. Nineteen RCTs and 3962 patients were included. Our study suggests that PDGFR-TKIs significantly increased the risks of all-grade (RR, 5.72; 95%CI, 4.32-7.59;p<0.00001; I(2) = 32%) and high-grade (RR, 5.65; 95%CI, 3.28- 9.75; p<0.00001; I(2) = 0%) thrombocytopenia in cancer patients. Sunitinib tend to be associated with the highest risk of thrombocytopenia among the included PDGFR-TKIs. The RR of high-grade thrombocytopenia varies significantly according to treatment line and median age. The available data suggested that the use of PDGFR-TKIs were associated with a significantly increased risk of thrombocytopenia. This article is protected by copyright. All rights reserved.
Restrictive versus liberal transfusion strategies in patients with malignant neoplasm -a meta-analysis of randomized controlled trials
Transfus Apher Sci. 2020;:102825
BACKGROUND Transfusion strategies are involving the survival and prognosis of patients with malignant neoplasm and the rational utilization of medical resources, but there are still controversy between different transfusion strategies. The aim of this article is to compare the benefit and harm of restrictive and liberal red blood cell (RBC) transfusion strategies in patients with malignant tumors. METHODS We searched articles in the databases of PubMed, Cochrane Library, Web of Science, Embase and major conference proceedings, identified all randomized controlled trials (RCTs) and compared restrictive transfusion strategies with those that are liberal until MARCH 18, 2019. We used risk ratio (RR) and and 95 % confidence interval (95 %CI) to calculate the results of dichotomous variables, and the study heterogeneity was assessed by using the I(2) statistics. Also, we did sensitivity analysis and quality assessment. RESULTS Restrictive transfusion policies appear to have no effect on all-cause mortality (RR 1.33; 95 % CI 0.74-2.38; P = 0.34), compared with liberal policies. 2 trials including 498 patients were included of renal replacement therapy (RR 1.38; 95 % CI, 0.73-2.59; P = 0.32; I(2) = 0%). Myocardial infarction (RR 1.17; 95 % CI, 0.33-4.1; P = 0.81; I(2) = 0%) and ICU readmission were also mentioned in these articles (RR 1.19; 95 % CI, 0.7-2.04; P = 0.52; I(2) = 0%). However, the RR of hospital length can't be evaluated. CONCLUSION Restrictive transfusion strategies were not associated with all-cause mortality and other clinical outcomes in malignant tumors, and may be more suitable for patients' quality of life and medical economy than liberal.
Patients with malignant tumours (3 randomised controlled trials (RCTs) n= 587).
Restrictive red blood cell transfusion strategy (n= 311).
Liberal red blood cell transfusion strategy (n= 276).
Restrictive transfusion strategies were not associated with all-cause mortality and other clinical outcomes in malignant tumours. Secondary outcomes reported included incidence of renal replacement therapy (2 RCTs, n=498; RR 1.38), myocardial infarction (RR 1.17) and intensive care unit readmission (RR 1.19).
Perioperative transfusion and the prognosis of colorectal cancer surgery: a systematic review and meta-analysis
World journal of surgical oncology. 2019;17(1):7
BACKGROUND Perioperative transfusion can reduce the survival rate in colorectal cancer patients. The effects of transfusion on the short- and long-term prognoses are becoming intriguing. OBJECTIVE This systematic review and meta-analysis aimed to define the effects of perioperative transfusion on the short- and long-term prognoses of colorectal cancer surgery. RESULTS Thirty-six clinical observational studies, with a total of 174,036 patients, were included. Perioperative transfusion decreased overall survival (OS) (hazard ratio (HR), 0.33; 95% confidence interval (CI), 0.24 to 0.41; P < 0.0001) and cancer-specific survival (CSS) (HR, 0.34; 95% CI, 0.21 to 0.47; P < 0.0001), but had no effect on disease-free survival (DFS) (HR, 0.17; 95% CI, - 0.12 to 0.47; P = 0.248). Transfusion could increase postoperative infectious complications (RR, 1.89, 95% CI, 1.56 to 2.28; P < 0.0001), pulmonary complications (RR, 2.01; 95% CI, 1.54 to 2.63; P < 0.0001), cardiac complications (RR, 2.20; 95% CI, 1.75 to 2.76; P < 0.0001), anastomotic complications (RR, 1.51; 95% CI, 1.29 to 1.79; P < 0.0001), reoperation(RR, 2.88; 95% CI, 2.05 to 4.05; P < 0.0001), and general complications (RR, 1.86; 95% CI, 1.66 to 2.07; P < 0.0001). CONCLUSION Perioperative transfusion causes a dramatically negative effect on long-term prognosis and increases short-term complications after colorectal cancer surgery.
Survival analysis of intraoperative blood salvage for patients with malignancy disease: A PRISMA-compliant systematic review and meta-analysis
BACKGROUND Intraoperative blood salvage as a blood-saving strategy has been widely used in surgery. Considering its theoretic risk of malignant tumor cells being reinfused and the corresponding blood metastases, the safety of intraoperative blood salvage in cancer surgery remains controversial. METHODS Following the Preferred Reporting Items for Systemic Review and Meta-Analysis (PRISMA), we searched the Cochrane Library, MEDLINE and EMBASE to November 2017. We included only studies comparing intraoperative blood salvage with allogeneic blood transfusion. RESULTS This meta-analysis included 9 studies with 4354 patients with 1346 patients in the intraoperative blood salvage group and 3008 patients in the allogeneic blood transfusion group. There were no significant differences in the 5-year overall survival outcome (odds ratio [OR] 1.12; 95% confidence interval [CI], 0.80-1.58), 5-year disease-free survival outcome (OR 1.08; 95% CI 0.86-1.35), or 5-year recurrence rate (OR 0.86; 95% CI 0.71-1.05) between the 2 study groups. Subgroup analysis also showed no significant differences in the 5-year overall survival outcome (OR 0.97; 95% CI 0.57-1.67) of hepatocellular carcinoma patients in liver transplantation. CONCLUSIONS For patients with malignant disease, intraoperative blood salvage did not increase the tumor recurrence rate and had comparable survival outcomes with allogeneic blood transfusion.
The prognostic role of perioperative allogeneic blood transfusions in gastric cancer patients undergoing curative resection: A systematic review and meta-analysis of non-randomized, adjusted studies
European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2018;44((4):):404-419
The impact of allogeneic perioperative blood transfusions (APTs) on the prognosis of gastric cancer patients undergoing curative-intent gastrectomy is still a highly debated topic. Two meta-analyses were published in 2015, and new studies report conflicting results. A literature review was conducted using PubMed, Scopus, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews, updated to March 1, 2016. Thirty-eight non-randomized studies reporting data on overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS) and postoperative complications (PCs) were included. An inverse variance random-effects meta-analysis was conducted. APTs showed an association with worse OS, DFS, DSS and an increased number of PCs. The hazard ratio (HR) for OS was 1.49, with a 95% confidence interval (95% CI) of 1.32-1.69 (p < .00001; Q-test p = .001, I-squared = 56%). After outlier exclusion, the HR for OS was 1.34 (95% CI = 1.23-1.45, p < .00001; Q-test p = .64, I-squared = 0%). The HR for DFS was 1.48 (95% CI = 1.18-1.86, p = .0007; Q-test p = .31, I-squared = 16%), and the HR for DSS was 1.66 (95% CI = 1.5-2.19, p = .0004; Q-test p = .96, I-squared = 0%). The odds ratio for PCs was 3.33 (95% CI = 2.10-5.29, p < .00001; Q-test p = .14, I-squared = 42%). This meta-analysis showed a significant association between transfusions and OS, DFS, DSS and PCs. The quality of the evidence was low. Aggregation, selection and selective reporting bias were detected. The biases shifted the results towards significance. Further studies using accurate adjustment methods are needed. Until such additional studies are performed, caution in administering transfusions and optimization of cancer patient blood management are warranted.
How low should we go: a systematic review and meta-analysis of the impact of restrictive red blood cell transfusion strategies in oncology
Cancer Treatment Reviews. 2016;46:1-8.
BACKGROUND Most non-oncologic clinical practice guidelines recommend restrictive allogeneic blood transfusion practices; however, there is a lack of consensus regarding the best transfusion practice in oncology. We conducted a systematic review of the literature to compare the efficacy and safety of restrictive versus liberal transfusion strategies in patients with cancer. METHODS A literature search using MEDLINE, PUBMED and EMBASE identified all controlled studies comparing the use of restrictive with liberal transfusion in adult oncology participants up to August 10, 2015. Two review authors independently assessed studies for inclusion, extracted data and appraised the quality of the included studies. The primary outcomes of interest were blood utilization and all-cause mortality. RESULTS Out of 4241 citations, six studies (3 randomized and 3 non-randomized) involving a total of 983 patients were included in the final review. The clinical context of the studies varied with 3 chemotherapy and 3 surgical studies. The overall risk of bias in all studies was moderate to high. Restrictive transfusion strategies were associated with a 36% reduced risk of receiving a perioperative transfusion (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.49-0.83). There was no difference in mortality between the strategies (RR 1.00, 95% CI 0.32-3.18). There were no differences in adverse events reported between the restrictive and liberal transfusion strategies. CONCLUSION Restrictive strategy appears to decrease blood utilization without increasing morbidity or mortality in oncology. This review is limited by a paucity of high quality studies on this topic. Better designed studies are warranted.
Perioperative blood transfusion and the prognosis of pancreatic cancer surgery: systematic review and meta-analysis
Annals of Surgical Oncology. 2015;22((13)):4382-91.
BACKGROUND Perioperative blood transfusion (PBT) is common in pancreatic surgery. Recent studies have suggested that PBT may be associated with worse long-term outcomes. METHODS A systematic review and meta-analysis of studies comparing long-term clinical outcomes of cancer patients undergoing curative-intent pancreatic surgery with regard to occurrence of PBT was performed. RESULTS A total of 23 studies (4339 patients) were included in the systematic review, and 19 studies (3646 patients) were included in the meta-analysis. Nearly half (45.8 %) of all patients were female (range 25-60 %), and median age ranged from 59 to 72 years. About half (46.5 %, range 19-72 %) of the patients were transfused. Most had pancreatic ductal adenocarcinoma (69.5 %), while others had ampullary carcinoma (15.0 %), cholangiocarcinoma (7.4 %), or exocrine tumors of pancreas (8.1 %). Most (91.1 %) underwent pancreaticoduodenectomy, while the remaining patients underwent a total or distal pancreatectomy. The 5-year overall survival for all patients ranged from 0 to 65 %. Thirteen and nine of 19 studies reported a detrimental effect of PBT on survival on univariable and multivariable analysis, respectively. Overall, PBT was associated with shorter overall survival (pooled odds ratio 2.43, 95 % confidence interval 1.90-3.10); this finding was reproduced in sensitivity analysis. CONCLUSIONS Patients receiving PBT had significantly lower 5-year survival after curative-intent pancreatic surgery. Further research should focus on implementing guidelines for and discerning factors associated with the poor outcomes after PBT.
Allogeneic blood transfusion and the prognosis of gastric cancer patients: Systematic review and meta-analysis
International Journal Of Surgery. 2015;13:102-10.
BACKGROUND Perioperative allogeneic blood transfusion (ABT) may be a deleterious predictor on the prognosis of gastric cancer (GC) for subjects who had undergone curative surgeries. In this article we proposed to figure out the effect of ABT with a systematic review and meta-analysis. METHODS Relevant articles were identified by searching Pubmed and Embase to March 2014. A random-effects model or fixed-effects model was used to calculate pooled odds ratios (ORs). Sensitivity analysis, meta-regression, stratified analysis, dose-response meta-analysis were conducted, and publication bias tested. RESULTS Eighteen studies (9120 GC patients) were included, of which 36.3% received transfusions. ABT was associated with increased all-cause mortality (OR, 2.17; 95% confidence interval [CI], 1.72-2.74; p < 0.001; I(2) = 75%). Sensitivity analysis showed significant changes in ORs while meta-regression had little influence on ORs. Galbraith plot revealed the OR reduced to 2.10 (95% CI, 1.86-2.37; p < 0.001) with tau(2) reduced to 0.00 and I(2) reduced to 0%. RESULTS of stratified analysis were robust and consistent. Dose-response meta-analysis revealed that all-cause mortality was significantly lower in patients transfused with <800 mL of blood than those transfused with >800 mL (OR, 0.58; 95% CI, 0.37-0.92; p = 0.02; I(2) = 54%). ABT was also associated with increased cancer-related mortality (OR, 2.57, p = 0.011) and recurrence (OR, 1.52, p = 0.017). CONCLUSIONS In GC patients undergoing curative surgeries, ABTs are associated with a worse prognosis, including all-cause mortality, cancer-related mortality and recurrence. Patient blood management should be investigated further to minimize use of ABT.Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.