-
1.
Estimating Bleeding Risk in Patients with Cancer-Associated Thrombosis: Evaluation of Existing Risk Scores and Development of a New Risk Score
de Winter MA, Dorresteijn JAN, Ageno W, Ay C, Beyer-Westendorf J, Coppens M, Klok FA, Moustafa F, Riva N, Ruiz Artacho PC, et al
Thrombosis and haemostasis. 2021
Abstract
BACKGROUND Bleeding risk is highly relevant for treatment decisions in cancer-associated thrombosis (CAT). Several risk scores exist, but have never been validated in patients with CAT and are not recommended for practice. OBJECTIVES To compare methods of estimating clinically relevant (major and clinically relevant nonmajor) bleeding risk in patients with CAT: (1) existing risk scores for bleeding in venous thromboembolism, (2) pragmatic classification based on cancer type, and (3) new prediction model. METHODS In a posthoc analysis of the Hokusai VTE Cancer study, a randomized trial comparing edoxaban with dalteparin for treatment of CAT, seven bleeding risk scores were externally validated (ACCP-VTE, HAS-BLED, Hokusai, Kuijer, Martinez, RIETE, and VTE-BLEED). The predictive performance of these scores was compared with a pragmatic classification based on cancer type (gastrointestinal; genitourinary; other) and a newly derived competing risk-adjusted prediction model based on clinical predictors for clinically relevant bleeding within 6 months after CAT diagnosis with nonbleeding-related mortality as the competing event ("CAT-BLEED"). RESULTS Data of 1,046 patients (149 events) were analyzed. Predictive performance of existing risk scores was poor to moderate (C-statistics: 0.50-0.57; poor calibration). Internal validation of the pragmatic classification and "CAT-BLEED" showed moderate performance (respective C-statistics: 0.61; 95% confidence interval [CI]: 0.56-0.66, and 0.63; 95% CI 0.58-0.68; good calibration). CONCLUSION Existing risk scores for bleeding perform poorly after CAT. Pragmatic classification based on cancer type provides marginally better estimates of clinically relevant bleeding risk. Further improvement may be achieved with "CAT-BLEED," but this requires external validation in practice-based settings and with other DOACs and its clinical usefulness is yet to be demonstrated.
-
2.
Red blood cell transfusions and the survival in patients with cancer undergoing curative surgery: a systematic review and meta-analysis
Petrelli F, Ghidini M, Ghidini A, Sgroi G, Vavassori I, Petrò D, Cabiddu M, Aiolfi A, Bonitta G, Zaniboni A, et al
Surgery today. 2021
-
-
-
Full text
-
Editor's Choice
Abstract
Allogenic red blood cell transfusions exert a potential detrimental effect on the survival when delivered to cancer patients undergoing surgery with curative intent. We performed a systematic review and meta-analysis to assess the association between perioperative allogenic red blood cell transfusions and risk of death as well as relapse after surgery for localized solid tumors. PubMed, the Cochrane Library, and EMBASE were searched from inception to March 2019 for studies reporting the outcome of patients receiving transfusions during radical surgery for non-metastatic cancer. Risk of death and relapse were pooled to provide an adjusted hazard ratio with a 95% confidence interval [hazard ratio (HR) (95% confidence interval {CI})]. Mortality and relapse associated with perioperative transfusion due to cancer surgery were evaluated among participants (n = 123 studies). Overall, RBC transfusions were associated with an increased risk of death [HR = 1.50 (95% CI 1.42-1.57), p < 0.01] and relapse [HR = 1.36 (95% CI 1.26-1.46), p < 0.01]. The survival was reduced even in cancer at early stages [HR = 1.45 (1.36-1.55), p < 0.01]. In cancer patients undergoing surgery, red blood cell transfusions reduced the survival and increased the risk of relapse. Transfusions based on patients' blood management policy should be performed by applying a more restrictive policy, and the planned preoperative administration of iron, if necessary, should be pursued.
PICO Summary
Population
Cancer patients requiring intra- or perioperative blood transfusion for curative surgery (123 studies, n= 184,190).
Intervention
Systematic review and meta-analysis to assess the association between perioperative allogenic red blood cell transfusions and risk of death as well as relapse after surgery.
Comparison
Outcome
Overall, red blood cell transfusions were associated with an increased risk of death [HR = 1.50 ] and relapse [HR = 1.36]. The survival was reduced even in cancer at early stages [HR = 1.45].
-
3.
Efficacy of UVC-treated, pathogen-reduced platelets versus untreated platelets: a randomized controlled non-inferiority trial
Brixner V, Bug G, Pohler P, Krämer D, Metzner B, Voß A, Casper J, Ritter U, Klein S, Alakel N, et al
Haematologica. 2021
Abstract
Pathogen reduction (PR) technologies for blood components have been established to reduce the residual risk of known and emerging infectious agents. THERAFLEX UVPlatelets, a novel UVC light-based PR technology for platelet concentrates, works without photoactive substances. This randomized, controlled, double-blind, multicenter, noninferiority trial was designed to compare the efficacy and safety of UVC-treated platelets to that of untreated platelets in thrombocytopenic patients with hematologic-oncologic diseases. Primary objective was to determine non-inferiority of UVC-treated platelets, assessed by the 1-hour corrected count increment (CCI) in up to eight per-protocol platelet transfusion episodes. Analysis of the 171 eligible patients showed that the defined non-inferiority margin of 30% of UVC-treated platelets was narrowly missed as the mean differences in 1-hour CCI between standard platelets versus UVC-treated platelets for intention-to-treat and perprotocol analyses were 18.2% (95% confidence interval [CI]: 6.4%; 30.1) and 18.7% (95% CI: 6.3%; 31.1%), respectively. In comparison to the control, the UVC group had a 19.2% lower mean 24-hour CCI and was treated with an about 25% higher number of platelet units, but the average number of days to next platelet transfusion did not differ significantly between both treatment groups. The frequency of low-grade adverse events was slightly higher in the UVC group and the frequencies of refractoriness to platelet transfusion, platelet alloimmunization, severe bleeding events, and red blood cell transfusions were comparable between groups. Our study suggests that transfusion of pathogen-reduced platelets produced with the UVC technology is safe but non-inferiority was not demonstrated. (The German Clinical Trials Register number: DRKS00011156).
-
4.
Prognostic Value of Bleeding in Gastrointestinal Stromal Tumors: A Meta-Analysis
Fan X, Han H, Sun Z, Zhang L, Chen G, Mzee SAS, Yang H, Chen J
Technology in cancer research & treatment. 2021;20:15330338211034259
Abstract
BACKGROUND Gastrointestinal bleeding is the most common clinical manifestation of gastrointestinal stromal tumor. It is of great significance to the prognosis of patients. But the results are controversial. The purpose of this study was to evaluate the relationship between gastrointestinal bleeding and clinical prognosis in patients with GIST. METHODS A systematic literature search was performed in Pumbed, Cochrane Library, EMBASE, ClinicalTrials.gov, CNKI, VIP and wanfang databases with the pattern of unlimited languages. 12 studies with 2781 individuals were included in the final analysis. The overall survival (OS), recurrence-free survival/disease-free survival (RFS/DFS) and related factors affecting bleeding in patients with gastrointestinal stromal tumor (GIST) were extracted. Hazard ratio (HR) and 95% confidence interval (CI) were used for in the meta-analysis. RESULTS A total of 12 articles were included in the study, including 2781 patients with GIST, including 845 patients with gastrointestinal bleeding. The OS of GIST patients with gastrointestinal bleeding was significantly worse (HR = 2.54, 95% CI = 1.13-5.73, P = 0.025). But there was no significant difference in RFS between gastrointestinal bleeding patients and non-bleeding patients (HR = 1.35, 95% CI = 0.70-2.61, P = 0.371). Further analysis of the related factors of GI bleeding in GIST patients was observed, besides the aging factor (HR = 1.02, 95% CI = 0.69-1.50, P = 0.929), Small intestinal stromal tumor (HR = 0.56, 95% CI = 0.41-0.76, P < 0.001), tumor diameter ≥ 5 cm (HR = 2.09, 95% CI = 1.20-3.63, P = 0.009), Mitotic index ≥ 5/50 HPF (HR = 1.66, 95% CI = 1.11-2.49, P = 0.014) and tumor rupture (HR = 2.04, 95% CI = 1.0-3.82, P = 0.026) all increased the risk of GI bleeding in patients with GIST. CONCLUSIONS The OS of GIST patients with GI bleeding was worse than non-GI bleeding, but had no significant effect on RFS. Nevertheless the aging factor, the location of GIST in the small intestine, tumor diameter ≥ 5 cm, Mitotic index ≥ 5/50 HPF and tumor rupture all increased the risk of GI bleeding in patients with GIST.
-
5.
Blood transfusions may adversely affect survival outcomes of patients with lung cancer: a systematic review and meta-analysis
Cho S, Park J, Lee M, Lee D, Choi H, Gim G, Kim L, Kang CY, Oh Y, Viveiros P, et al
Translational lung cancer research. 2021;10(4):1700-1710
Abstract
BACKGROUND Despite common use in clinical practice, the impact of blood transfusions on prognosis among patients with lung cancer remains unclear. The purpose of the current study is to perform an updated systematic review and meta-analysis to evaluate the influence of blood transfusions on survival outcomes of lung cancer patients. METHODS We searched PubMed, Embase, Cochrane Library, and Ovid MEDLINE for publications illustrating the association between blood transfusions and prognosis among people with lung cancer from inception to November 2019. Overall survival (OS) and disease-free survival (DFS) were the outcomes of interest. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were computed using the random-effects model. Study heterogeneity was evaluated with the I(2) test. Publication bias was explored via funnel plot and trim-and-fill analyses. RESULTS We included 23 cohort studies with 12,175 patients (3,027 cases and 9,148 controls) for meta-analysis. Among these records, 22 studies investigated the effect of perioperative transfusions, while one examined that of transfusions during chemotherapy. Two studies suggested the possible dose-dependent effect in accordance with the number of transfused units. In pooled analyses, blood transfusions deleteriously influenced both OS (HR=1.35, 95% CI: 1.14-1.61, P<0.001, I(2)=0%) and DFS (HR=1.46, 95% CI: 1.15-1.86, P=0.001, I(2)=0%) of people with lung cancer. No evidence of significant publication bias was detected in funnel plot and trim-and-fill analyses (OS: HR=1.26, 95% CI: 1.07-1.49, P=0.006; DFS: HR=1.35, 95% CI: 1.08-1.69, P=0.008). CONCLUSIONS Blood transfusions were associated with decreased survival of patients with lung cancer.
-
6.
Postoperative bleeding in essential thrombocytosis patients with colorectal cancer: Case report and literature review
Varela C, Nassr M, Razak A, Yang SY, Kim NK
International journal of surgery case reports. 2021;86:106374
Abstract
INTRODUCTION AND IMPORTANCE Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by increased platelet count and a high risk of bleeding or thrombotic events due to platelet dysfunction. Patients with ET are treated according to their risk of complications with cytoreductive or anti-aggregant treatment. Neither guidelines for oncologic patients nor perioperative management of patients with ET have been determined. CASE PRESENTATION A 41-year-old female patient with ET who had alternating constipation and diarrhea was referred after a screening colonoscopy diagnosing a locally advanced rectosigmoid junction colon adenocarcinoma with liver metastases. Systemic preoperative chemotherapy was indicated. The patient underwent laparoscopic low anterior resection plus volume-preserving right lobectomy of the liver. Postoperative bleeding of the internal iliac artery (IIA) associated with hematoma at the lower pelvic cavity was diagnosed and treated by interventional radiology; the patient was discharged without other complications 16 days after surgery. CLINICAL DISCUSSION ET has been related to the development of hematologic complications or second non-hematologic malignancies. A systematic review was conducted to seek guidance for the management of such patients in the perioperative period. Special perioperative care must be taken, and complications management should avoid further hemorrhages or cloth formation. CONCLUSION Under oncologic and hematological guidance, minimally invasive surgery and non-invasive management of complications are advised in the lack of published perioperative management guidelines of ET patients with colorectal cancer.
-
7.
Intravenous iron is non-inferior to oral iron regarding cell growth and iron metabolism in colorectal cancer associated with iron-deficiency anaemia
Al-Hassi HO, Ng O, Evstatiev R, Mangalika M, Worton N, Jambrich M, Khare V, Phipps O, Keeler B, Gasche C, et al
Scientific reports. 2021;11(1):13699
Abstract
Oral iron promotes intestinal tumourigenesis in animal models. In humans, expression of iron transport proteins are altered in colorectal cancer. This study examined whether the route of iron therapy alters iron transport and tumour growth. Colorectal adenocarcinoma patients with pre-operative iron deficiency anaemia received oral ferrous sulphate (n = 15), or intravenous ferric carboxymaltose (n = 15). Paired (normal and tumour tissues) samples were compared for expression of iron loading, iron transporters, proliferation, apoptosis and Wnt signalling using immunohistochemistry and RT-PCR. Iron loading was increased in tumour and distributed to the stroma in intravenous treatment and to the epithelium in oral treatment. Protein and mRNA expression of proliferation and iron transporters were increased in tumours compared to normal tissues but there were no significant differences between the treatment groups. However, intravenous iron treatment reduced ferritin mRNA levels in tumours and replenished body iron stores. Iron distribution to non-epithelial cells in intravenous iron suggests that iron is less bioavailable to tumour cells. Therefore, intravenous iron may be a better option in the treatment of colorectal cancer patients with iron deficiency anaemia due to its efficiency in replenishing iron levels while its effect on proliferation and iron metabolism is similar to that of oral iron treatment.
-
8.
Efficacy and Safety of Ferric Carboxymaltose Infusion in Reducing Anemia in Patients Receiving Chemotherapy for Nonmyeloid Malignancies: a Randomized, Placebo-Controlled Study (IRON CLAD)
Makharadze T, Boccia R, Krupa A, Blackman N, Henry DH, Gilreath JA
American journal of hematology. 2021
Abstract
PURPOSE Erythropoiesis-stimulating agents (ESA) are effective for chemotherapy-induced anemia (CIA) but associated with serious adverse events. Safer alternatives would be beneficial in this population. The efficacy and safety of ferric carboxymaltose (FCM) as monotherapy for CIA was evaluated. METHODS This Phase 3, 18-week, double-blind, placebo-controlled study randomized adults with ≥4 weeks of chemotherapy remaining for treatment of nonmyeloid malignancies with CIA to FCM (two 15 mg/kg infusions 7 days apart; maximum dose, 750 mg single/1500 mg total) or placebo. The primary efficacy endpoint was percentage of patients with decreases in hemoglobin (Hb) ≥0.5 g/dL from weeks 3 to 18; the key secondary efficacy endpoint was change in Hb from baseline to week 18. Inclusion criteria included: (Hb) 8-11 g/dL, ferritin 100-800 ng/mL, and transferrin saturation (TSAT) ≤35%. RESULTS In 244 patients (n=122, both groups), the percent who maintained Hb within 0.5 g/dL of baseline from weeks 3 to 18 was significantly higher with FCM versus placebo (50.8% vs 35.3%; P=0.01). Mean change in Hb from baseline to week 18 was similar between FCM and placebo (1.04 vs 0.87 g/dL) but significantly greater with FCM with baseline Hb ≤9.9 g/dL (1.08 vs 0.42 g/dL; P=0.01). The percent with ≥1 g/dL increase from baseline was significantly higher with FCM versus placebo (71% vs 54%; P=0.01), occurring in a median 43 versus 85 days (P=0.001). Common adverse events in the FCM arm included neutropenia (17%), hypophosphatemia (16%), and fatigue (15%). CONCLUSION FCM monotherapy effectively maintained Hb and was well tolerated in CIA. This article is protected by copyright. All rights reserved.
-
9.
Treatment of Fanconi Anemia-Associated Head and Neck Cancer: Opportunities to Improve Outcomes
Lee RH, Kang H, Yom SS, Smogorzewska A, Johnson DE, Grandis JR
Clinical cancer research : an official journal of the American Association for Cancer Research. 2021
Abstract
Fanconi anemia, the most frequent genetic cause of bone marrow failure, is characterized by an extreme predilection towards multiple malignancies, including a greater than 500-fold incidence of head and neck squamous cell carcinoma (HNSCC) relative to the general population. Fanconi anemia-associated HNSCC and esophageal SCC (FA-HNSCC) often present at advanced stages with poor survival. Surgical resection remains the primary treatment for FA-HNSCC, and there is often great reluctance to administer systemic agents and/or radiation therapy (RT) to these patients given their susceptibility to DNA damage. The paucity of FA-HNSCC case reports limits evidence-based management, and such cases have not been analyzed collectively in detail. We present a systematic review of FA-HNSCC treatments reported from 1966 to 2020, defining a cohort of 119 FA-HNSCC patients including 16 esophageal SCCs (131 total primary tumors), who were treated with surgery, RT, systemic therapy (including cytotoxic agents, EGFR inhibitors, or immune checkpoint inhibitors), or a combination of modalities. We summarize the clinical responses and regimen-associated toxicities by treatment modality. The collective evidence suggests that when possible, surgical resection with curative intent should remain the primary treatment modality for FA-HNSCC. Radiation can be administered with acceptable toxicity in the majority of cases, including patients who have undergone stem cell transplantation (SCT). While there is little justification for cytotoxic chemotherapy, EGFR inhibitors and tyrosine kinase inhibitors (TKIs) may be both safe and effective. Immunotherapy may also be considered. Most oncologists have little personal experience with FA-HNSCC. This review is intended as a comprehensive resource for clinicians.
-
10.
Perioperative blood transfusion and ovarian cancer survival rates: A meta-analysis based on univariate, multivariate and propensity score matched data
Pergialiotis V, Thomakos N, Frountzas M, Haidopoulos D, Loutradis D, Rodolakis A
Eur J Obstet Gynecol Reprod Biol. 2020;252:137-143
Abstract
The negative impact of perioperative blood transfusion on survival outcomes has been reported in several cancer types. The purpose of the present study is to summarize existing evidence in ovarian cancer patients. We searched the Medline, Scopus, http://clinicaltrials.gov/ EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases for observational and randomized trials that assessed the impact of perioperative blood transfusion on the disease-free survival (DFS) and overall survival (OS) of ovarian cancer patients that undergone debulking surgery were selected for inclusion. The methodological quality of the included studies was assessed by using the Newcastle-Ottawa Scale. Statistical meta-analysis was performed with the RevMan 5.3 software using the Der-Simonian Laird random effects model. Seven studies were identified which included 2341 ovarian cancer patients. Meta-analyses that were based on univariate and multivariate reporting revealed that perioperative blood transfusion had a significant negative impact on the patient`s OS rates (OR 1.78, 95 %CI 1.16, 2.74 and OR 1.31, 95 %CI 1.00, 1.71 respectively). Disease free survival rates were also influenced according to the results of the univariate analysis (OR 1.58, 95 %CI 1.14, 2.19), however, the effect was not significant in the multivariate analysis. The analysis that was based on propensity score matched populations did not reveal differences among transfused and non-transfused. Concluding, the findings of our meta-analysis suggest that transfusion of blood products during the perioperative period is not an independent factor that may affect survival outcomes of ovarian cancer patients. Nevertheless, it should be noted that patients that receive transfusion have several potential confounders that may affect their survival outcomes.
