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Bioengineered Jun 2022Triple-negative breast cancer (TNBC) is the most aggressive breast cancer. Neoadjuvant chemotherapy was widely accepted for treating TNBC. This systematic review and... (Meta-Analysis)
Meta-Analysis
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer. Neoadjuvant chemotherapy was widely accepted for treating TNBC. This systematic review and meta-analysis aimed to evaluate the efficacy, safety, and survival benefit of platinum-based adjuvant therapy (PBAT) in treating TNBC. The keywords were searched in Medline, Embase, Pubmed, and Cochrane Library database up to July 24, 2022. All the randomized control trials (RCTs) comparing PBAT and non-PBAT in treating TNBC were included in our study. The pathological complete remission (pCR) and complications were compared by odds ratio (OR) and 95% confidence intervals (CIs). The overall survival (OS) and relapse-free survival (RFS) were compared by hazard ratio (HR) and 95% CIs. A total of 19 RCTs were included in our meta-analysis, among which 2,501 patients were treated with PBAT and 2,290 with non-PBAT. The patients treated with PBAT combined a significantly higher pCR rate compared to those patients treated with non-PBAT (49.8% versus 36.4%, OR = 1.27, 95%CI = 1.14-1.43, P < 0.001). Besides, patients treated with PBAT had a significantly better RFS (HR = 0.78, 95%CI = 0.63-0.95, P = 0.016), but not in OS (HR = 0.84, P = 0.304). Although the occurrence of neutropenia and nausea were slightly different between the PBAT group (51.5% and 24.4%) and the non-PBAT group (47.0% and 29.4%), the complications were acceptable in the two treatments groups. Our results demonstrated that TNBC patients treated with PBAT could achieve a higher pCR rate and better RFS benefit without a higher complication rate. Platinum-based adjuvant therapy provided a higher pCR rate for TNBC.Platinum-based adjuvant therapy prolonged the RFS but without prolongingthe OS.Neutropenia and nausea rate was different between group PBAT and non-PBAT.
Topics: Humans; Triple Negative Breast Neoplasms; Platinum; Antineoplastic Combined Chemotherapy Protocols; Randomized Controlled Trials as Topic; Nausea; Neutropenia
PubMed: 36278891
DOI: 10.1080/21655979.2022.2115616 -
Annals of Palliative Medicine Jul 2022Long-term benefit of nanoparticle-albumin-bound paclitaxel (Nab-P) over conventional taxanes in breast cancer patients is still controversial. We conducted a systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Long-term benefit of nanoparticle-albumin-bound paclitaxel (Nab-P) over conventional taxanes in breast cancer patients is still controversial. We conducted a systematic review of studies to identify the optimal taxanes for selection in clinical practice.
METHODS
We enrolled studies if they enrolled adults (age ≥18) with breast cancer, compared Nab-P (at any dose) to conventional paclitaxel or docetaxel, provided information on survival data, the response rate, or adverse events, were randomized controlled trials, case-control studies, or cohort studies, and were published in English (including those published online, ahead of the print publication). Cochrane Collaboration tool and Newcastle-Ottawa scale were used for bias-risk assessment. Grading of recommendations assessment, development, and evaluation approach were adopted for the quality of evidence evaluation. The outcomes included the overall response rate, pathological complete response rate, progression-free survival, overall survival, allergic reaction, leukopenia, neutropenia, and sensory neuropathy.
RESULTS
A total of 20 eligible clinical studies comprising 11,046 patients were included in the analysis. No significant publication bias was observed based on a visual inspection of the funnel plots for progressionfree survival (PFS), and overall survival (OS). Compared to the conventional taxanes group (n=2,743), the Nab-P group (n=1,680) had a significantly higher ORR (RR =1.21, 95% CI: 1.07-1.37; P=0.003) and pCR (RR =1.33, 95% CI: 1.17-1.51; P<0.001). The Nab-P group also had a lower risk of disease progression and death than the conventional taxanes group (HR =0.89, P=0.269). Additionally, the Nab-P group had fewer treatment-related allergic reactions (RR =0.74, 95% CI: 0.59-0.93; P=0.009) and less grade ≥4 neutropenia (RR =0.39, 95% CI: 0.20-0.77; P=0.007) than the conventional taxanes group. The incidence of any-grade of neutropenia and sensory neuropathy were significantly higher in the Nab-P group than the conventional taxanes group (P=0.009 and P<0.001, respectively).
DISCUSSION
The Nab-P in all stages of breast cancer patients had significantly better efficacy and tolerance than the conventional taxanes. Moreover, preventive strategies for reducing the incidence of Nab-P induced sensory neuropathy should be explored in future studies.
Topics: Adult; Albumin-Bound Paclitaxel; Breast Neoplasms; Female; Humans; Nanoparticles; Neutropenia; Paclitaxel; Randomized Controlled Trials as Topic; Taxoids
PubMed: 35927773
DOI: 10.21037/apm-22-690 -
Scientific Reports Jan 2016Currently, amrubicin is permitted for relapsed small-cell lung carcinoma (SCLC) only in Japan. The efficacy and adverse effects of amrubicin as reported by previous... (Meta-Analysis)
Meta-Analysis Review
Currently, amrubicin is permitted for relapsed small-cell lung carcinoma (SCLC) only in Japan. The efficacy and adverse effects of amrubicin as reported by previous studies varied greatly. The inclusion criterion was a prospective study that was able to provide data for efficacy and safety by the AMR single agent regimen as second-line chemotherapy for a patient with SCLC. Binary data were meta-analyzed with the random-model generic inverse variance method. We included nine articles consisted of 803 patients. The pooled three-, six-, and nine-month progression-free survival were 63% (95% CI 57-69%, I(2) = 53%), 28% (95% CI 21-35%, I(2) = 71%), and 10% (95% CI 6-14%, I(2) = 41%), respectively. The pooled six-, 12-, and 18-month overall survival were 69% (95% CI 61-78%, I(2) = 83%), 36% (95% CI 28-44%, I(2) = 80%), and 15% (95% CI 8-21%, I(2) = 81%), respectively. Amrubicin seemed much more beneficial for Japanese patients. However, compared to the efficacy of topotecan presented in a previous meta-analysis, amrubicin may be a better treatment option than topotecan for both Japanese and Euro-American. Adverse effects by amrubicin were almost exclusively observed to be hematological. Notably, grade III/IV neutropenia incidence was 70% and febrile neutropenia incidence was 12%.
Topics: Anthracyclines; Antineoplastic Agents; Asian People; Humans; Japan; Lung Neoplasms; Neutropenia; Recurrence; Small Cell Lung Carcinoma; Survival Analysis; Topotecan; Treatment Outcome; White People
PubMed: 26750506
DOI: 10.1038/srep18999 -
Journal of Diabetes and Its... Jan 2017Conduct a systematic review with meta-analysis to determine the association between incident chemotherapy-induced neutropenia (CIN) and either diabetes mellitus (DM) or... (Meta-Analysis)
Meta-Analysis Review
AIM
Conduct a systematic review with meta-analysis to determine the association between incident chemotherapy-induced neutropenia (CIN) and either diabetes mellitus (DM) or hyperglycemia in patients with cancer.
METHODS
Observational studies in cancer patients of any age receiving chemotherapy and having diabetes or hyperglycemia either during or before chemotherapy induction were included. Studies were retrieved by searching four databases (PubMed, EBSCO, ProQuest, and Cochrane) and cross-referencing. The metric for combining studies was the odds ratio (OR). Results were pooled using a random-effects model, while heterogeneity and inconsistency were assessed using the Q and I statistic, respectively. Potential small-study effects were assessed using the funnel plot.
RESULTS
Ten studies met the criteria for inclusion. Overall, the odds of having CIN were 32% higher among cancer patients with either DM or hyperglycemia compared with those without DM or hyperglycemia (OR=1.32, 95% CI, 1.06-1.64). Statistically significant heterogeneity and inconsistency were found (Q=33.15, p<0.05, I=72.9%). Funnel plot asymmetry reflecting potential small-study effects was observed.
CONCLUSIONS
Diabetes mellitus and hyperglycemia may be associated with an increased risk for CIN among cancer patients. However, additional well-designed studies are needed before any final and definitive recommendations can be made.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Diabetes Complications; Humans; Hyperglycemia; Neoplasms; Neutropenia; Reproducibility of Results; Risk
PubMed: 27751709
DOI: 10.1016/j.jdiacomp.2016.09.006 -
British Journal of Clinical Pharmacology Sep 2019Antithyroid drug (ATD)-induced agranulocytosis is a life-threatening adverse drug reaction. Previous studies suggested that HLA genotypes may play an important role in... (Meta-Analysis)
Meta-Analysis
AIMS
Antithyroid drug (ATD)-induced agranulocytosis is a life-threatening adverse drug reaction. Previous studies suggested that HLA genotypes may play an important role in ATD-induced agranulocytosis. To examine the associations between HLA genotypes and ATD-induced agranulocytosis, we conducted a systematic review and meta-analysis of pharmacogenomics studies.
METHODS
We searched the MEDLINE, Embase and CENTRAL databases on 16 June 2018 for case-control studies on the associations between HLA genotypes with ATD-induced agranulocytosis. The Newcastle-Ottawa scale was used to evaluate the risk of bias of included studies. We conducted random-effects model meta-analysis to obtain pooled odds ratios (ORs) with 95% confidence intervals (CIs) to determine the associations between HLA genotypes and ATD-induced agranulocytosis.
RESULTS
We included 5 studies with 142 ATD-induced agranulocytosis cases, 1529 matched ATD-tolerant controls and 5945 healthy controls. The risk of bias of included studies was generally low. ATD-induced agranulocytosis was associated with HLA-B*27:05 (OR 10.97; 95% CI 0.75-159.99), HLA-B*38:02 (OR 19.85; 95% CI 7.94-49.57) and HLA-DRB1*08:03 (OR 5.29; 95% CI 3.44-8.14). After excluding propylthiouracil, the associations of ATD-induced agranulocytosis with HLA-B*27:05 and HLA-B*38:02 were strengthened (OR being 20.61 (95% CI 5.21-81.58) and 40.59 (95% CI 13.24-124.47), respectively). The associations of ATD-induced agranulocytosis with HLA-B*27:05, HLA-B*38:02 and HLA-DRB1*08:03 remained significant when compared to population controls (OR being 7.37 (95% CI 3.86-14.07), 36.43 (95% CI 12.80-103.70) and 5.42 (95% CI 2.36-12.47), respectively). HLA-B*27:05, HLA-B*38:02, and HLA-DRB1*08:03 alleles were associated with ATD-induced agranulocytosis, especially in carbimazole/methimazole-induced agranulocytosis.
CONCLUSIONS
HLA-B*27:05, HLA-B*38:02 and HLA-DRB1*08:03 alleles were associated with ATD-induced agranulocytosis, especially in carbimazole/methimazole-induced agranulocytosis.
Topics: Agranulocytosis; Alleles; Antithyroid Agents; Graves Disease; HLA Antigens; Humans
PubMed: 31108563
DOI: 10.1111/bcp.13989 -
The Cochrane Database of Systematic... Jun 2017The pattern of infections among neutropenic patients with cancer has shifted in the last decades to a predominance of gram-positive infections. Some of these... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The pattern of infections among neutropenic patients with cancer has shifted in the last decades to a predominance of gram-positive infections. Some of these gram-positive bacteria are increasingly resistant to beta-lactams and necessitate specific antibiotic treatment.
OBJECTIVES
To assess the effectiveness of empirical anti-gram-positive (antiGP) antibiotic treatment for febrile neutropenic patients with cancer in terms of mortality and treatment failure. To assess the rate of resistance development, further infections and adverse events associated with additional antiGP treatment.
SEARCH METHODS
For the review update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 2), MEDLINE (May 2012 to 2017), Embase (May 2012 to 2017), LILACS (2012 to 2017), conference proceedings, ClinicalTrials.gov trial registry, and the references of the included studies. We contacted the first authors of all included and potentially relevant trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing one antibiotic regimen versus the same regimen with the addition of an antiGP antibiotic for the treatment of febrile neutropenic patients with cancer.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial eligibility and risk of bias, and extracted all data. Risk ratios (RR) with 95% confidence intervals (CIs) were calculated. A random-effects model was used for all comparisons showing substantial heterogeneity (I > 50%). Outcomes were extracted by intention-to-treat and the analysis was patient-based whenever possible.
MAIN RESULTS
Fourteen trials and 2782 patients or episodes were included. Empirical antiGP antibiotics were tested at the onset of treatment in 12 studies, and for persistent fever in two studies. The antiGP treatment was a glycopeptide in nine trials. Eight studies were assessed in the overall mortality comparison and no significant difference was seen between the comparator arms, RR of 0.90 (95% CI 0.64 to 1.25; 8 studies, 1242 patients; moderate-quality data). Eleven trials assessed failure, including modifications as failures, while seven assessed overall failure disregarding treatment modifications. Failure with modifications was reduced, RR of 0.72 (95% CI 0.65 to 0.79; 11 studies, 2169 patients; very low-quality data), while overall failure was the same, RR of 1.00 (95% CI 0.79 to 1.27; 7 studies, 943 patients; low-quality data). Sensitivity analysis for allocation concealment and incomplete outcome data did not change the results. Failure among patients with gram-positive infections was reduced with antiGP treatment, RR of 0.56 (95% CI 0.38 to 0.84, 5 studies, 175 patients), although, mortality among these patients was not changed.Data regarding other patient subgroups likely to benefit from antiGP treatment were not available. Glycopeptides did not increase fungal superinfection rates and were associated with a reduction in documented gram-positive superinfections. Resistant colonisation was not documented in the studies.
AUTHORS' CONCLUSIONS
Based on very low- or low-quality evidence using the GRADE approach and overall low risk of bias, the current evidence shows that the empirical routine addition of antiGP treatment, namely glycopeptides, does not improve the outcomes of febrile neutropenic patients with cancer.
Topics: Anti-Bacterial Agents; Febrile Neutropenia; Glycopeptides; Gram-Positive Bacterial Infections; Humans; Neoplasms; Randomized Controlled Trials as Topic; Treatment Failure
PubMed: 28577308
DOI: 10.1002/14651858.CD003914.pub4 -
PloS One 2022We systematically assessed benefits and harms of tocilizumab (TCZ), which is an antibody blocking IL-6 receptors, in hospitalized COVID-19 patients. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
We systematically assessed benefits and harms of tocilizumab (TCZ), which is an antibody blocking IL-6 receptors, in hospitalized COVID-19 patients.
METHODS
Five electronic databases and two preprint webpages were searched until March 4, 2021. Randomized controlled trials (RCTs) and inverse probability treatment weighting (IPTW) cohorts assessing TCZ effects in hospitalized, COVID-19 adult patients were included. Primary outcomes were all-cause mortality, clinical worsening, clinical improvement, need for mechanical ventilation, and adverse events (AE). Inverse variance random-effects meta-analyses were performed with quality of evidence (QoE) evaluated using GRADE methodology.
RESULTS
Nine RCTs (n = 7,021) and nine IPTW cohorts (n = 7,796) were included. TCZ significantly reduced all-cause mortality in RCTs (RR 0.89, 95%CI 0.81-0.98, p = 0.03; moderate QoE) and non-significantly in cohorts (RR 0.67, 95%CI 0.44-1.02, p = 0.08; very low QoE) vs. control (standard of care [SOC] or placebo). TCZ significantly reduced the need for mechanical ventilation (RR 0.80, 95%CI 0.71-0.90, p = 0.001; moderate QoE) and length of stay (MD -1.92 days, 95%CI -3.46 to -0.38, p = 0.01; low QoE) vs. control in RCTs. There was no significant difference in clinical improvement or worsening between treatments. AEs, severe AEs, bleeding and thrombotic events were similar between arms in RCTs, but there was higher neutropenia risk with TCZ (very low QoE). Subgroup analyses by disease severity or risk of bias (RoB) were consistent with main analyses. Quality of evidence was moderate to very low in both RCTs and cohorts.
CONCLUSIONS
In comparison to SOC or placebo, TCZ reduced all-cause mortality in all studies and reduced mechanical ventilation and length of stay in RCTs in hospitalized COVID-19 patients. Other clinical outcomes were not significantly impacted. TCZ did not have effect on AEs, except a significant increased neutropenia risk in RCTs. TCZ has a potential role in the treatment of hospitalized COVID-19 patients.
Topics: Adult; Antibodies, Monoclonal, Humanized; Humans; Neutropenia; Randomized Controlled Trials as Topic; COVID-19 Drug Treatment
PubMed: 35657993
DOI: 10.1371/journal.pone.0269368 -
Oncotarget Jan 2017Whether neutropenia has an impact on the mortality of critically ill cancer patients remains controversial, yet it is widely used as an admission criterion and... (Meta-Analysis)
Meta-Analysis Review
Outcomes in adult critically ill cancer patients with and without neutropenia: a systematic review and meta-analysis of the Groupe de Recherche en Réanimation Respiratoire du patient d'Onco-Hématologie (GRRR-OH).
PURPOSE
Whether neutropenia has an impact on the mortality of critically ill cancer patients remains controversial, yet it is widely used as an admission criterion and prognostic factor.
METHODS
Systematic review and meta-analysis. Studies on adult cancer patients and intensive care units were searched on PubMed and Cochrane databases (2005-2015). Summary estimates of mortality risk differences were calculated using the random-effects model.
RESULTS
Among the 1,528 citations identified, 38 studies reporting on 6,054 patients (2,097 neutropenic patients) were included. Median mortality across the studies was 54% [45-64], with unadjusted mortality in neutropenic and non-neutropenic critically ill patients of 60% [53-74] and 47% [41-68], respectively. Overall, neutropenia was associated with a 10% increased mortality risk (6%-14%; I² = 50%). The admission period was not associated with how neutropenia affected mortality. Mortality significantly dropped throughout the study decade [-11% (-13.5 to -8.4)]. This mortality drop was observed in non-neutropenic patients [-12.1% (-15.2 to -9.0)] but not in neutropenic patients [-3.8% (-8.1 to +5.6)].Sensitivity analyses disclosed no differences in underlying malignancy, mechanical ventilation use, or Granulocyte-colony stimulating factor use. Seven studies allowed the adjustment of severity results (1,350 patients). Although pooled risk difference estimates were similar to non-adjusted results, there was no significant impact of neutropenia on mortality (risk difference of mortality, 9%; 95% CI, -15 to +33).
CONCLUSION
Although the unadjusted mortality of neutropenic patients was 11% higher, this effect disappeared when adjusted for severity. Therefore, when cancer patients become critically ill, neutropenia cannot be considered as a decision-making criterion.
Topics: Adult; Critical Illness; Granulocyte Colony-Stimulating Factor; Humans; Intensive Care Units; Neoplasms; Neutropenia; Respiration, Artificial; Treatment Outcome
PubMed: 27661125
DOI: 10.18632/oncotarget.12165 -
Pediatrics Jan 2022Immune system dysfunction is poorly represented in pediatric organ dysfunction definitions.
CONTEXT
Immune system dysfunction is poorly represented in pediatric organ dysfunction definitions.
OBJECTIVE
To evaluate evidence for criteria that define immune system dysfunction in critically ill children and associations with adverse outcomes and develop consensus criteria for the diagnosis of immune system dysfunction in critically ill children.
DATA SOURCES
We conducted electronic searches of PubMed and Embase from January 1992 to January 2020, using medical subject heading terms and text words to define immune system dysfunction and outcomes of interest.
STUDY SELECTION
Studies of critically ill children with an abnormality in leukocyte numbers or function that is currently measurable in the clinical laboratory in which researchers assessed patient-centered outcomes were included. Studies of adults or premature infants, animal studies, reviews and commentaries, case series (≤10 subjects), and studies not published in English with inability to determine eligibility criteria were excluded.
DATA EXTRACTION
Data were abstracted from eligible studies into a standard data extraction form along with risk of bias assessment by a task force member.
RESULTS
We identified the following criteria for immune system dysfunction: (1) peripheral absolute neutrophil count <500 cells/μL, (2) peripheral absolute lymphocyte count <1000 cells/μL, (3) reduction in CD4+ lymphocyte count or percentage of total lymphocytes below age-specific thresholds, (4) monocyte HLA-DR expression <30%, or (5) reduction in ex vivo whole blood lipopolysaccharide-induced TNFα production capacity below manufacturer-provided thresholds.
LIMITATIONS
Many measures of immune system function are currently limited to the research environment.
CONCLUSIONS
We present consensus criteria for the diagnosis of immune system dysfunction in critically ill children.
Topics: Child; Critical Illness; HLA-DR Antigens; Humans; Immune System; Immune System Diseases; Leukocyte Count; Lymphocyte Count; Lymphopenia; Multiple Organ Failure; Neutropenia; Neutrophils; Severity of Illness Index; Tumor Necrosis Factor-alpha
PubMed: 34970674
DOI: 10.1542/peds.2021-052888N -
Clinical Microbiology and Infection :... Oct 2017To compare the effectiveness and safety of antipseudomonal β-lactam empiric monotherapy for febrile neutropenia by network meta-analysis. (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVES
To compare the effectiveness and safety of antipseudomonal β-lactam empiric monotherapy for febrile neutropenia by network meta-analysis.
METHODS
Searches using Pubmed, Cochrane CENTRAL, EMBASE and Web of Science Core Collection were carried out in June 2016. English articles, non-English articles, full-length articles, short articles and conference abstracts were allowed. Eligible trial design was a parallel-group individual randomization. We included febrile neutropenia adult and paediatric patients undergoing chemotherapy for either solid tumours or haematological malignancies and treated with intravenous antipseudomonal β-lactams for initial empiric therapy. Protocol was registered with PROSPERO ID 42016043377.
RESULTS
Of 1275 articles detected by the search, 50 studies with 10 872 patients were finally included. Among the guideline-recommended cefepime, meropenem, imipenem/cilastatin, piperacillin/tazobactam and ceftazidime; imipenem/cilastatin showed the highest odds of treatment success without modification, which was the primary endpoint, based on the random-effect model network analysis. Ceftazidime was related to lower treatment success rate without modification compared with imipenem/cilastatin with OR of 0.71 (95% CI 0.57-0.89, p 0.006). Imipenem/cilastatin showed the lowest odds of all-cause death. Patients treated with cefepime had higher risk for all-cause death compared with those treated with imipenem/cilastatin (OR 2.05, 95% CI 1.11-3.78, p 0.029). Any adverse event was significantly more prevalent in the imipenem/cilastatin arm; however, there was no difference concerning adverse events leading to discontinuation.
CONCLUSIONS
Imipenem/cilastatin, piperacillin/tazobactam and meropenem may be reasonable first-choice medications for empiric therapy of febrile neutropenia.
Topics: Anti-Bacterial Agents; Drug-Related Side Effects and Adverse Reactions; Febrile Neutropenia; Humans; Neoplasms; Survival Analysis; Treatment Outcome; beta-Lactams
PubMed: 28377312
DOI: 10.1016/j.cmi.2017.03.024