Systematic Review and Meta-Analysis of the Association Between Transfusion Independence (TI) and Overall Survival (OS) in Patients (pts) with Myelodysplastic Syndromes (MDS)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1934-1934
Author(s):  
Sue Harnan ◽  
Shijie Ren ◽  
Tim Gomersall ◽  
Emma Everson-Hock ◽  
Anthea Sutton ◽  
...  
Keyword(s):  
Systematic Review ◽  
Random Effects ◽  
Lower Risk ◽  
Research Funding ◽  
Meta Analysis ◽  
Type A ◽  
Type B ◽  
Risk Of Death ◽  
Meta Regression ◽  
The Impact

Abstract Introduction: MDS are a diverse group of haematological disorders affecting bone marrow function and necessitating frequent blood transfusions. A number of studies, from retrospective cohort and registry analyses to randomized controlled trials (RCTs), have shown transfusion status to impact OS in MDS. While transfusion status is considered a prognostic indicator in MDS, no systematic review has been conducted to consolidate and analyze all available evidence to date. This systematic review and meta-analysis is the first to assess the association between TI and OS, and also considers patient risk and acquisition of TI post treatment. Methods: Comprehensive electronic searches were conducted in five key bibliographic databases. Relevant conference proceedings were searched electronically, experts were contacted, grey literature (national and international guidelines, unpublished and unindexed studies) was searched online, and the reference lists of relevant reviews and guidelines were checked. The protocol was published a priori on PROSPERO (ID CRD42014007264). Studies which recruited adults aged ≥ 18 years with confirmed MDS, and reported OS for TI versus transfusion-dependent (TD) pts were included. Any expression of OS and any definition of transfusion status (x transfusions per unit time) were acceptable. RCTs, cohort studies, consecutive case series ≥ 10 cases, before-after studies and case-control studies were eligible for inclusion. Where a hazard ratio (HR) was expressed for TD vs. TI, the ratio was converted by dividing 1 by the reported HR to obtain HR for TI vs. TD. A narrative synthesis and a random effects meta-analysis were conducted. The meta-analysis synthesised the multivariate HR for OS of TI compared with TD pts from non-overlapping cohorts. A random effects meta-regression assessed whether the effect of being TI on OS depends on the risk group (according to IPSS or WHO criteria) of the included pts. Results: Searches identified 1821 titles of which 89 were included, representing 60 separate analyses. Study quality (by the Quality in Prognosis Studies [QUIPS] criteria) was moderate overall, with some limitations in reporting of attrition, correction of confounders, and patient spectrum. Three types of studies were identified: a) recruited TD and TI pts and compared OS between groups (n = 45); b) recruited TD only, and compared those who became TI to those who remained TD after treatment (n = 8); c) recruited TD only, compared those with high transfusion burden to those with low (n = 7). Amongst type a studies (n = 45), TI was consistently associated with an OS benefit whether results were expressed as HRs or as other metrics such as mean survival. In a meta-analysis of all eligible type a studies (n = 11) a 57% decrease in the risk of death compared with TD pts (HR 0.43; 95% credible interval (CrI) 0.31 to 0.56) was estimated. When considering the impact of the risk category of pts through meta-regression (lower-risk and all-risk cohorts only; no higher-risk cohorts were eligible for inclusion), the coefficient of the interaction term was estimated to be HR 1.33 (95% CrI 0.6 to 2.98), which suggested that the magnitude of the benefit for pts being TI on OS was higher for all-risk groups. However, this effect was inconclusive. A meta-analysis of type b studies was not possible as study cohorts overlapped. The multivariate HR in the 3 type b studies which reported this ranged from 0.53 to 0.36, indicating a mortality reduction between 47% and 64% associated with acquisition of TI. Studies reporting other metrics also reported TI pts fared better. A meta-analysis of type c studies was neither planned nor conducted. All studies reported that pts with fewer transfusions per unit time demonstrated better OS than those with more, regardless of the high/low transfusion burden cut point used. Conclusion: A number of studies have previously suggested that MDS pts who are TI have better survival relative to those who are TD, but no meta-analysis has been conducted to date. Our findings revealed a consistent, substantial reduction in mortality among TI pts when compared with TD pts confirming the positive TI-OS association. A meta-regression analysis indicated that the impact of TI was higher in all-risk cohorts versus lower-risk cohorts, but this effect was not conclusive. A similar association was seen for those who acquired TI through treatment (Figure 1). Figure 1 Figure 1. Disclosures Harnan: Celgene Ltd: Research Funding. Ren:Celgene: Research Funding. Gomersall:Celgene Corporation: Research Funding. Everson-Hock:Celgene Ltd: Research Funding. Dhanasiri:Celgene Corp: Employment, Equity Ownership. Kulasekararaj:Celgene: Honoraria, Speakers Bureau; Alexion: Honoraria, Speakers Bureau.

scholarly journals High burden of acute kidney injury in COVID-19 pandemic: systematic review and meta-analysis

2020 ◽  
pp. jclinpath-2020-207023
Author(s):  
Camila Barbosa Oliveira ◽  
Camilla Albertina Dantas Lima ◽  
Gisele Vajgel ◽  
Antonio Victor Campos Coelho ◽  
Paula Sandrin-Garcia
Keyword(s):  
Systematic Review ◽  
Acute Kidney Injury ◽  
Critically Ill ◽  
Random Effects ◽  
Meta Analysis ◽  
Kidney Injury ◽  
Random Effects Model ◽  
Risk Of Death ◽  
Meta Analyses ◽  
The Impact

AimsHospitalised patients with COVID-19 have a variable incidence of acute kidney injury (AKI) according to studies from different nationalities. The present systematic review and meta-analysis describes the incidence of AKI, need for renal replacement therapy (RRT) and mortality among patients with COVID-19-associated AKI.MethodsWe systematically searched electronic database PubMed, SCOPUS and Web of Science to identify English articles published until 25 May 2020. In case of significant heterogeneity, the meta-analyses were conducted assuming a random-effects model.ResultsFrom 746 screened publications, we selected 21 observational studies with 15 536 patients with COVID-19 for random-effects model meta-analyses. The overall incidence of AKI was 12.3% (95% CI 7.3% to 20.0%) and 77% of patients with AKI were critically ill (95% CI 58.9% to 89.0%). The mortality among patients with AKI was 67% (95% CI 39.8% to 86.2%) and the risk of death was 13 times higher compared with patients without AKI (OR=13.3; 95% CI 6.1 to 29.2). Patients with COVID-19-associated AKI needed for RRT in 23.4% of cases (95% CI 12.6% to 39.4%) and those cases had high mortality (89%–100%).ConclusionThe present study evidenced an incidence of COVID-19-associated AKI higher than previous meta-analysis. The majority of patients affected by AKI were critically ill and mortality rate among AKI cases was high. Thus, it is extremely important for health systems to be aware about the impact of AKI on patients’ outcomes in order to establish proper screening, prevention of additional damage to the kidneys and adequate renal support when needed.

scholarly journals The Effect of Anakinra in Hospitalized Patients with COVID-19: An Updated Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (19) ◽  
pp. 4462
Author(s):  
Konstantinos G. Kyriakoulis ◽  
Anastasios Kollias ◽  
Garyphallia Poulakou ◽  
Ioannis G. Kyriakoulis ◽  
Ioannis P. Trontzas ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Interleukin 1 ◽  
Severe Pneumonia ◽  
Hospitalized Patients ◽  
Current Evidence ◽  
Adjusted Risk ◽  
Risk Of Death ◽  
The Impact

The role of immunomodulatory agents in the treatment of hospitalized patients with COVID-19 has been of increasing interest. Anakinra, an interleukin-1 inhibitor, has been shown to offer significant clinical benefits in patients with COVID-19 and hyperinflammation. An updated systematic review and meta-analysis regarding the impact of anakinra on the outcomes of hospitalized patients with COVID-19 was conducted. Studies, randomized or non-randomized with adjustment for confounders, reporting on the adjusted risk of death in patients treated with anakinra versus those not treated with anakinra were deemed eligible. A search was performed in PubMed/EMBASE databases, as well as in relevant websites, until 1 August 2021. The meta-analysis of six studies that fulfilled the inclusion criteria (n = 1553 patients with moderate to severe pneumonia, weighted age 64 years, men 66%, treated with anakinra 50%, intubated 3%) showed a pooled hazard ratio for death in patients treated with anakinra at 0.47 (95% confidence intervals 0.34, 0.65). A meta-regression analysis did not reveal any significant associations between the mean age, percentage of males, mean baseline C-reactive protein levels, mean time of administration since symptoms onset among the included studies and the hazard ratios for death. All studies were considered as low risk of bias. The current evidence, although derived mainly from observational studies, supports a beneficial role of anakinra in the treatment of selected patients with COVID-19.

Abstract WMP112: Cilostazol versus Aspirin for Secondary Stroke Prevention: Systematic Review and Meta-Analysis

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Michelle P Lin ◽  
Kevin M Barrett ◽  
James F Meschia ◽  
Benjamin H Eidelman ◽  
Josephine F Huang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Ischemic Stroke ◽  
Random Effects ◽  
Intracranial Hemorrhage ◽  
Stroke Prevention ◽  
Lower Risk ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Secondary Stroke Prevention

Introduction: Cilostazol has promise as an alternative to aspirin for secondary stroke prevention given its vasodilatory and anti-inflammatory properties in addition to platelet aggregation inhibition. We conducted a systematic review and meta-analysis to estimate the comparative effectiveness and safety of cilostazol compared to aspirin for stroke prevention in patients with previous stroke or TIA. Hypothesis: Cilostazol is more effective than aspirin in preventing recurrent ischemic stroke with lower risk of intracranial hemorrhage and bleeding. Methods: We searched PubMed and the Cochrane Central Register of Controlled Trials from inception to 2019. Randomized clinical trials that compared cilostazol vs aspirin and reported the endpoints of ischemic stroke, intracranial hemorrhage and bleeding were included. A random-effects estimate was computed based on Mantel-Haenszel methods. The pooled estimates with 95% confidence intervals were compared between cilostazol and aspirin and displayed as forest plots (Figure). Results: The search identified 5 randomized clinical trials comparing cilostazol vs aspirin for secondary stroke prevention that enrolled 7,240 patients from primarily Asian countries (3,615 received cilostazol and 3,625 received aspirin). The pooled results from the random-effects model showed that cilostazol was associated with significantly lower risk of recurrent ischemic stroke (Hazard ratio [HR] 0.70; 95%CI, 0.54-0.89), intracranial hemorrhage (HR 0.41; 95%CI, 0.25-0.65) and bleeding (HR 0.71; 95%CI, 0.55-0.91). See forest plots. Conclusion: This meta-analysis suggests cilostazol is more effective than aspirin in the prevention of recurrent ischemic stroke with lower risk of intracranial hemorrhage and bleeding. Confirmatory randomized trials of cilostazol for secondary stroke prevention to be performed in more generalizable populations are needed.

Carbapenem Resistance, Initial Antibiotic Therapy, and Mortality inKlebsiella pneumoniaeBacteremia: A Systematic Review and Meta-Analysis

2017 ◽  
Vol 38 (11) ◽  
pp. 1319-1328 ◽  
Author(s):  
Philipp P. Kohler ◽  
Cheryl Volling ◽  
Karen Green ◽  
Elizabeth M. Uleryk ◽  
Prakesh S. Shah ◽  
...  
Keyword(s):  
Systematic Review ◽  
Antibiotic Therapy ◽  
Meta Analysis ◽  
Carbapenem Resistance ◽  
Carbapenem Resistant ◽  
Initial Antibiotic Therapy ◽  
Meta Regression ◽  
The Difference ◽  
Meta Regression Analysis ◽  
The Impact

BACKGROUNDMortality associated with infections caused by carbapenem-resistantEnterobacteriaceae(CRE) is higher than mortality due to carbapenem-sensitive pathogens.OBJECTIVETo examine the association between mortality from bacteremia caused by carbapenem-resistant (CRKP) and carbapenem-sensitiveKlebsiella pneumoniae(CSKP) and to assess the impact of appropriate initial antibiotic therapy (IAT) on mortality.DESIGNSystematic review and meta-analysisMETHODSWe searched MEDLINE, EMBASE, CINAHL, and Wiley Cochrane databases through August 31, 2016, for observational studies reporting mortality among adult patients with CRKP and CSKP bacteremia. Search terms were related toKlebsiella, carbapenem-resistance, and infection. Studies including fewer than 10 patients per group were excluded. A random-effects model and meta-regression were used to assess the relationship between carbapenem-resistance, appropriateness of IAT, and mortality.RESULTSMortality was higher in patients who had CRKP bacteremia than in patients with CSKP bacteremia (15 studies; 1,019 CRKP and 1,148 CSKP patients; unadjusted odds ratio [OR], 2.2; 95% confidence interval [CI], 1.8–2.6; I2=0). Mortality was lower in patients with appropriate IAT than in those without appropriate IAT (7 studies; 658 patients; unadjusted OR, 0.5; 95% CI, 0.3–0.8; I2=36%). CRKP patients (11 studies; 1,326 patients; 8-year period) were consistently less likely to receive appropriate IAT (unadjusted OR, 0.5; 95% CI, 0.3–0.7; I2=43%). Our meta-regression analysis identified a significant association between the difference in appropriate IAT and mortality (OR per 10% difference in IAT, 1.3; 95% CI, 1.0–1.6).CONCLUSIONSAppropriateness of IAT is an important contributor to the observed difference in mortality between patients with CRKP bacteremia and patients with CSKP bacteremia.Infect Control Hosp Epidemiol2017;38:1319–1328

scholarly journals Tea Flavonoids and Risk of Cardiovascular and All-Cause Mortality: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Ding Ding Wang ◽  
Aedin Cassidy ◽  
Mario G. Ferruzzi ◽  
Paul Jacques ◽  
Elizabeth Johnson ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cohort Studies ◽  
Green Tea ◽  
Lower Risk ◽  
Meta Analysis ◽  
Black Tea ◽  
Tea Consumption ◽  
Prospective Cohort Studies ◽  
All Cause Mortality ◽  
Meta Regression

AbstractThere is increasing evidence that both black and green tea are beneficial for prevention of cardiovascular disease (CVD). We conducted a systematic review and meta-analysis evaluating the effects of tea flavonoids on cardiovascular (CVD) and all-cause mortality outcomes.Searches across five databases including PubMed and Embase were conducted through November 2018 to identify randomized controlled trials (RCTs) and prospective cohort studies reporting cardiovascular and all-cause mortality outcomes. Two investigators independently conducted abstract and full-text screenings, data extractions, and risk of bias (ROB) assessments using the Nutrition Evidence Library Bias Assessment Tool (NEL BAT). Mixed-effects dose-response meta-regression and standard random-effects meta-analyses for outcomes with ≥ 4 studies were performed. 0 RCTs and 38 prospective cohort studies were included in the systematic review. NEL BAT scores ranged from 0–15 (0 being the lowest risk). Our linear meta-regression model showed that each cup increase in daily tea consumption (about 280 mg and 338 mg of total flavonoids for black and green tea, respectively) was associated with 3–4% lower risk of CVD mortality (predicted adjusted RR = 0.96; CI 0.93–0.99 for green tea and RR = 0.97; CI 0.94–0.99 for black tea). Furthermore, eachcup increase in daily tea consumption was associated a 2% lower risk of all-cause mortality (predicted adjusted relative risk (RR) = 0.98; 95% CI 0.97–0.99 for black tea and RR = 0.98; CI 0.96–0.99 for green tea, respectively). Two studies reported multivariable Cox regression analysis results for the relationship between black tea intake and risks of all-cause mortality outcomes. The results from these two studies were combined with our linear meta-regression result in a random-effects model meta-analysis and showed that each cup increase in daily black tea consumption was associated with an average of 3% lower risk of all-cause mortality (pooled adjusted RR = 0.97; 95% CI 0.87- 1.00) with large heterogeneity (I2 = 81.4%; p = 0.005). Current evidence indicates that increased tea consumption may reduce cardiovascular and all-cause mortality in a dose-response manner. This systematic review was registered on PROSPERO.

scholarly journals Drug treatments for covid-19: living systematic review and network meta-analysis

BMJ ◽  
2020 ◽  
pp. m2980 ◽  
Author(s):  
Reed AC Siemieniuk ◽  
Jessica J Bartoszko ◽  
Long Ge ◽  
Dena Zeraatkar ◽  
Ariel Izcovich ◽  
...  
Keyword(s):  
Systematic Review ◽  
Mechanical Ventilation ◽  
Standard Care ◽  
Interferon Beta ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Drug Discontinuation ◽  
Duration Of Symptoms ◽  
Risk Of Death ◽  
The Impact

Abstract Objective To compare the effects of treatments for coronavirus disease 2019 (covid-19). Design Living systematic review and network meta-analysis. Data sources WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2020 and six additional Chinese databases up to 12 November 2020. Study selection Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. Methods After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. Results 85 trials enrolling 41 669 patients met inclusion criteria as of 21 October 2020; 50 (58.8%) trials and 25 081 (60.2%) patients are new from the previous iteration; 43 (50.6%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, corticosteroids probably reduce death (risk difference 17 fewer per 1000 patients, 95% credible interval 34 fewer to 1 more, moderate certainty), mechanical ventilation (29 fewer per 1000 patients, 54 fewer to 1 more, moderate certainty), and days free from mechanical ventilation (2.6 fewer, 0.2 fewer to 5.0 fewer, moderate certainty). The impact of remdesivir on mortality, mechanical ventilation, length of hospital stay, and duration of symptoms is uncertain, but it probably does not substantially increase adverse effects leading to drug discontinuation (0 more per 1000, 9 fewer to 40 more, moderate certainty). Azithromycin, hydroxychloroquine, lopinavir/ritonavir, interferon-beta, and tocilizumab may not reduce risk of death or have an effect on any other patient-important outcome. The certainty in effects for all other interventions was low or very low. Conclusion Corticosteroids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care, whereas azithromycin, hydroxychloroquine, interferon-beta, and tocilizumab may not reduce either. Whether or not remdesivir confers any patient-important benefit remains uncertain. Systematic review registration This review was not registered. The protocol is included as a supplement. Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is the second update of the original article published on 30 July 2020 ( BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.

Prognostic Impact of Transfusions Intensity on Survival and Development of Thrombocytopenia in Newly Diagnosed Lower-Risk MDS Patients Participating in the European Leukemianet EU-MDS Registry

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1677-1677
Author(s):  
Louise De Swart ◽  
Tom Johnston ◽  
Alexandra Smith ◽  
Pierre Fenaux ◽  
Argiris Symeonidis ◽  
...  
Keyword(s):  
Lower Risk ◽  
Research Funding ◽  
Control Group ◽  
Rapid Decline ◽  
Prognostic Impact ◽  
Platelet Counts ◽  
Risk Of Death ◽  
Increased Risk ◽  
The Impact

Abstract Background The outcome of lower-risk MDS patients with red blood cell transfusions (RBCT) dependency is inferior to that of RBCT independent patients, but whether the intensity of RBCT is important for prognosis is unknown. The EUMDS Registry is a non-interventional, observational longitudinal study enrolling patients with lower-risk MDS from 142 sites in 17 countries as described elsewhere (1). The EUMDS registry has accrued 1,902 patients as of July 21, 2015. We hypothesized that RBCT intensity is an independent prognostic factor for survival. Methods We first assessed the impact of RBCT intensity in the first year post-diagnosis (1yrPD) on progression-free survival among the 1034 patients who survived at least 1yrPD and had potential for a further year of follow-up. Secondly, we developed a longitudinal model of platelet counts throughout follow-up for 1660 patients in the registry with potential for at least one year follow-up. Results Among the 1034 patients, 323 patients had died: 67 after progression to higher-risk MDS/AML and 256 without progression. A further 41 surviving patients had progressed to AML. The overall 5-year survival was 52%. In a proportional hazards regression model (Table), the risk of death or progression increased in a non-linear fashion with age at diagnosis (p<0.001). The risk of death was increased in the intermediate IPSS-R risk group compared to low risk. Patients with RARS and 5q- syndrome had a better outcome compared to RCMD. Increased RBCT intensity in 1yrPD (Table, Figure) was strongly associated with an increased risk of death (p<0.001). In the 1660 patients no significant decline in platelet counts was observed (0.16x109 platelets/l average monthly decline, p=0.16) among patients who were not RBC transfused at any time during follow-up. However platelet counts of patients receiving RBCT declined more quickly (p<0.0001) at an average rate of 1.14x109 platelets/l/month. Among the 920 RBCT dependent patients, lower platelet counts were associated with receiving more RBCT units in the preceding six months. 185 Patients had at least 2 observations both before and after becoming RBCT dependent, defined as 1st RBCT. 50% of these patients had a decreasing trend of platelets prior to their 1st RBCT and 67% had a decreasing slope of platelets after their 1st RBCT. In the control group of RBC untransfused patients, decreasing slopes of platelets occurred in around 50% of the patients throughout the whole observation period of 4 visits. Logistic regression of the risk of having a post-1st RBCT decreasing trend in platelets showed that transfused patients were at a greater risk (OR=1.7, 95% CI: 1.1-2.7) of having a post-1st RBCT decreasing trend in platelets than untransfused patients. Conclusion These multivariate regression models including age, sex, country, IPSS and WHO classification showed that more intensive RBCT treatment is associated with poor prognosis and a more rapid decline of platelets. This indicates that the intensity of RBCT should be incorporated in the regular prognostic scoring systems and the choice of therapeutic interventions. (1): De Swart L et al. Br J Haematol 2015; 170: 372-83. Disclosures Fenaux: NOVARTIS: Honoraria, Research Funding; CELGENE: Honoraria, Research Funding; JANSSEN: Honoraria, Research Funding; AMGEN: Honoraria, Research Funding. Hellström-Lindberg:Celgene Corporation: Research Funding. Sanz:JANSSEN CILAG: Honoraria, Research Funding, Speakers Bureau. Mittelman:Roche: Research Funding; Novartis Pharmaceuticals Corporation: Research Funding; GlaxoSmithKline: Research Funding; Johnson & Johnson: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Amgen: Research Funding. Almeida:Bristol Meyer Squibb: Speakers Bureau; Shire: Speakers Bureau; Celgene: Consultancy; Novartis: Consultancy. Park:Hospira: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Itzykson:Oncoethix: Research Funding. de Witte:Novartis: Research Funding.

The impact of time to adjuvant chemotherapy (AC) on survival in colorectal cancer (CRC): A systematic review and meta-analysis.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 364-364 ◽  
Author(s):  
J. J. Biagi ◽  
M. Raphael ◽  
W. D. King ◽  
W. Kong ◽  
W. J. Mackillop ◽  
...  
Keyword(s):  
Systematic Review ◽  
Prognostic Factors ◽  
Adjuvant Chemotherapy ◽  
Publication Bias ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Significant Heterogeneity ◽  
Risk Of Death ◽  
The Impact ◽  
The Relationship

364 Background: The optimal timing from CRC surgery to initiation of AC is unknown. We report a systematic review and meta-analysis to determine the relationship between time to adjuvant chemotherapy (TTAC) and survival. Methods: A systematic review of literature was done to identify studies that described the relationship between TTAC and survival. Studies were only included if the distribution of relevant prognostic factors was adequately described, and either comparative groups were balanced or results adjusted for the prognostic factors. Hazard ratio (HR) and TTAC for overall survival (OS) and disease free survival (DFS) from each study were converted to a regression coefficient (β) and standard error (SE) corresponding to a continuous representation per 4 weeks of TTAC. The adjusted β from individual studies were combined using a fixed-effect model. Inverse-variance (1/SE2) was used to weight individual studies. The possible effect of publication bias was investigated using the trim and fill approach. Results: We identified 9 eligible studies involving 14,357 patients (4 published articles, 5 abstracts). Two studies were randomized trials and 7 were cohort studies. Six studies reported TTAC as a binary variable and 3 reported TTAC as ≥3 categories. An estimate of HR for OS was derived from all 9 studies and estimate for DFS was derived from 5 studies. Meta-analysis demonstrated that a 4-week increase in TTAC was associated with a significant decrease in both OS (HR = 1.12, 95% CI 1.09-1.15), and DFS (HR = 1.15, 95% CI 1.11-1.20). The analysis showed no significant heterogeneity among studies. These TTAC associations remained significant after analysis for potential publication bias, and when the analysis was repeated excluding the two studies of largest weight. Conclusions: This study demonstrates a 12% increase in the risk of death for each 4 week of delay in the start of AC for CRC. These findings indicate the need for clinicians and health systems managers to take the steps necessary to keep TTAC as short as reasonably achievable. In addition, our results suggest there may be some benefit to AC after a 3-month TTAC delay. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document