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International Journal of Environmental... Nov 2022There is evidence for the positive effects of neurodynamic techniques in some peripheral entrapment neuropathies, but the rationale for these effects has not been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is evidence for the positive effects of neurodynamic techniques in some peripheral entrapment neuropathies, but the rationale for these effects has not been validated. We aimed to estimate the direct effect of neurodynamic techniques on the dispersion of artificially induced intraneural edema measured by dye spread in cadavers.
METHODS
We systematically searched the MEDLINE, WOS, Scopus, and the Cochrane databases from inception to February 2020 for experimental studies addressing the efficacy of neurodynamic techniques on the dispersion of artificially induced intraneural edema. The DerSimonian and Laird method was used to compute pooled estimates of the mean differences (MDs) and its respective 95% confidence intervals (CIs). Subgroup analyses were conducted according to the type of neurodynamic technique. In addition, a 95% prediction interval was calculated to reflect the variation in true treatment effects in different settings, including the effect to be expected in future patients.
RESULTS
Pooled results showed a significant increase in fluid dispersion (MD = 2.57 mm; 95%CI: 1.13 to 4.01). Subgroup analysis showed increased dye spread in the tensioning techniques group (MD = 2.22 mm; 95%CI: 0.86 to 3.57).
CONCLUSION
Neurodynamic techniques improved the intraneural edema dispersion and should be considered for the management of peripheral compression neuropathies. Furthermore, tensioning techniques appear to be effective in helping to disperse intraneural edema.
Topics: Humans; Edema; Treatment Outcome
PubMed: 36361353
DOI: 10.3390/ijerph192114472 -
AJNR. American Journal of Neuroradiology Sep 2018Accurate diagnosis of tumefactive demyelinating lesions is clinically important to avoid unnecessary invasive biopsy or inappropriate treatment. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Accurate diagnosis of tumefactive demyelinating lesions is clinically important to avoid unnecessary invasive biopsy or inappropriate treatment.
PURPOSE
We aimed to evaluate conventional and advanced MR imaging findings of tumefactive demyelinating lesions and determine the diagnostic performance of MR imaging for differentiating tumefactive demyelinating lesions from primary brain tumor.
DATA SOURCES
A systematic search of Ovid MEDLINE and EMBASE up to December 6, 2017, was conducted.
STUDY SELECTION
Original articles describing MR imaging findings in patients with tumefactive demyelinating lesions were selected.
DATA ANALYSIS
The pooled incidences of conventional MR imaging findings of tumefactive demyelinating lesions were obtained with the DerSimonian and Liard random-effects model. The pooled sensitivity and specificity of MR imaging for differentiating tumefactive demyelinating lesions from primary brain tumor were obtained using the bivariate random-effects model.
DATA SYNTHESIS
Nineteen eligible studies with 476 patients with tumefactive demyelinating lesions were included. The pooled incidence of open ring or incomplete rim enhancement was 35% (95% CI, 24%-47%), which was significantly higher than the incidence of closed ring or complete rim enhancement (18% [95% CI, 11%-29%]; = .0281). The pooled incidences of T2 hypointense rim, absent or mild mass effect, and absent or mild perilesional edema were 48%, 67%, and 57%, respectively. On advanced MR imaging, tumefactive demyelinating lesions showed a high apparent diffusion coefficient, peripheral restricted diffusion, and low cerebral blood volume. The pooled sensitivity and specificity of MR imaging for differentiating tumefactive demyelinating lesions from primary brain tumor were 89% (95% CI, 82%-93%) and 94% (95% CI, 89%-97%), respectively.
LIMITATIONS
Seventeen of 19 studies were retrospective studies.
CONCLUSIONS
Conventional MR imaging findings may help differentiate tumefactive demyelinating lesions from primary brain tumor, though further study is needed to determine the added value of advanced MR imaging.
Topics: Adult; Brain Neoplasms; Demyelinating Diseases; Diagnosis, Differential; Female; Humans; Magnetic Resonance Imaging; Male; Neuroimaging; Sensitivity and Specificity
PubMed: 30115676
DOI: 10.3174/ajnr.A5775 -
Wellcome Open Research 2023Currently, there are no specific medical treatments for intracerebral haemorrhage (ICH), but the inflammatory response may provide a potential route to treatment. Given...
BACKGROUND
Currently, there are no specific medical treatments for intracerebral haemorrhage (ICH), but the inflammatory response may provide a potential route to treatment. Given the known effects of acute brain injury on peripheral immunity, we hypothesised that inflammatory biomarkers in peripheral blood may be associated with clinical outcome following ICH, as well as perihaematomal oedema (PHO), which is an imaging marker of the neuroinflammatory response.
METHODS
We searched OVID Medline and EMBASE on 07 April 2021 for studies of humans with ICH measuring an inflammatory biomarker in peripheral blood and PHO or clinical outcome. Risk of bias was assessed both by using a scale comprising features of the Newcastle-Ottawa Assessment Scale, STROBE-ME and REMARK guidelines, and for studies included in meta-analysis, also by the QUIPS tool.We used random effects meta-analysis to pool standardised mean differences (SMD) if ≥1 study quantified the association between identical biomarkers and measures of PHO or functional outcome.
RESULTS
Of 8,615 publications, 16 examined associations between 21 inflammatory biomarkers and PHO (n=1,299 participants), and 93 studies examined associations between ≥1 biomarker and clinical outcome (n=17,702 participants). Overall, 20 studies of nine biomarkers (n=3,199) met criteria for meta-analysis of associations between inflammatory biomarkers and clinical outcome. Death or dependency (modified Rankin Scale (mRS) 3‒6) 90 days after ICH was associated with higher levels of fibrinogen (SMD 0.32; 95%CI [0.04, 0.61]; p=0.025), and high mobility group box protein 1 (HMGB1) (SMD 1.67; 95%CI [0.05, 3.30]; p=0.04). Higher WBC was associated with death or dependency at 90 days (pooled SMD 0.27; 95% CI [0.11, 0.44]; p=0.001; but the association was no longer significant when the analysis was restricted to studies with a low risk of bias (pooled SMD 0.22; 95% CI -0.04-0.48). Higher CRP seemed to be associated with death or dependency at 90 days (pooled SMD 0.80; 95% CI [0.44, 1.17]; p<0.0001) but this association was no longer significant when adjusted OR were pooled (OR 0.99 (95% CI 0.98-1.01)).
CONCLUSIONS
Higher circulating levels of, fibrinogen and HMGB1 are associated with poorer outcomes after ICH. This study highlights the clinical importance of the inflammatory response to ICH and identifies additional research needs in determining if these associations are mediated via PHO and are potential therapeutic targets.
REGISTRATION
PROSPERO ( CRD42019132628; 28/05/2019).
PubMed: 38037559
DOI: 10.12688/wellcomeopenres.19187.2 -
Chemotherapy 2022Crizotinib and alectinib are the 2 most commonly used anaplastic lymphoma kinase (ALK) inhibitors for ALK-positive non-small cell lung cancer (NSCLC). We compared their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Crizotinib and alectinib are the 2 most commonly used anaplastic lymphoma kinase (ALK) inhibitors for ALK-positive non-small cell lung cancer (NSCLC). We compared their antitumor efficacies and adverse effects based on a pooled analysis of the ALEX, ALESIA, and J-ALEX clinical trials.
METHODS
Seven databases were searched for eligible articles. The primary endpoints included overall survival (OS), progression-free survival (PFS), central nervous system (CNS)-PFS, drug responses, and adverse effects (AEs).
RESULTS
Seven articles on 3 randomized controlled clinical trials (ALEX, ALESIA, and J-ALEX) that included 697 patients were included. Compared with crizotinib, alectinib exhibited superior efficacy in PFS (HR [hazard ratio]: 0.35 [0.25-0.49], p < 0.00001), OS (HR: 0.66 [0.47-0.92], p = 0.02), CNS-PFS (HR: 0.17 [0.11-0.24], p < 0.00001), duration of response (HR: 0.31 [0.23-0.42], p < 0.00001), objective response rate (risk ratio [RR]: 0.87 [0.80-0.94], p = 0.0003), partial response (RR: 0.88 [0.81-0.96], p = 0.004), and grade 3-5 AEs (RR: 1.43 [1.09-1.87], p = 0.009). Additionally, compared with crizotinib, alectinib exhibited a survival advantage that increased with its prolongation of survival time. The disease control rate, complete response, and total AEs were comparable between the 2 groups. The crizotinib group reported higher rates of constipation, nausea, diarrhea, vomiting, peripheral edema, dysgeusia, visual impairment, and levels of alanine aminotransferase and aspartate aminotransferase as well as greater decreases in appetite and neutrophil count.
CONCLUSIONS
In both antitumor efficacy and safety, alectinib appears to be superior to crizotinib for the treatment of ALK-positive NSCLC.
Topics: Anaplastic Lymphoma Kinase; Carbazoles; Carcinoma, Non-Small-Cell Lung; Crizotinib; Humans; Lung Neoplasms; Piperidines; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic
PubMed: 34915469
DOI: 10.1159/000521452 -
Diagnostics (Basel, Switzerland) Aug 2023This study evaluates the role of high-intensity focused ultrasound (HIFU) ablative therapy in treating primary breast cancer. (Review)
Review
BACKGROUND
This study evaluates the role of high-intensity focused ultrasound (HIFU) ablative therapy in treating primary breast cancer.
METHODS
PubMed and Scopus databases were searched according to the PRISMA guidelines to identify studies from 2002 to November 2022. Eligible studies were selected based on criteria such as experimental study type, the use of HIFU therapy as a treatment for localised breast cancer with objective clinical evaluation, i.e., clinical, radiological, and pathological outcomes. Nine studies were included in this study.
RESULTS
Two randomised controlled trials and seven non-randomised clinical trials fulfilled the inclusion criteria. The percentage of patients who achieved complete (100%) coagulation necrosis varied from 17% to 100% across all studies. Eight of the nine studies followed the treat-and-resect protocol in which HIFU-ablated tumours were surgically resected for pathological evaluation. Most breast cancers were single, solitary, and palpable breast tumours. Haematoxylin and eosin stains used for histopathological evaluation showed evidence of coagulation necrosis. Radiological evaluation by MRI showed an absence of contrast enhancement in the HIFU-treated tumour and 1.5 to 2 cm of normal breast tissue, with a thin peripheral rim of enhancement indicative of coagulation necrosis. All studies did not report severe complications, i.e., haemorrhage and infection. Common complications related to HIFU ablation were local mammary oedema, pain, tenderness, and mild to moderate burns. Only one third-degree burn was reported. Generally, the cosmetic outcome was good. The five-year disease-free survival rate was 95%, as reported in two RCTs.
CONCLUSIONS
HIFU ablation can induce tumour coagulation necrosis in localised breast cancer, with a favourable safety profile and cosmetic outcome. However, there is variable evidence of complete coagulation necrosis in the HIFU-treated tumour. Histopathological evidence of coagulation necrosis has been inconsistent, and there is no reliable radiological modality to assess coagulation necrosis confidently. Further exploration is needed to establish the accurate ablation margin with a reliable radiological modality for treatment and follow-up. HIFU therapy is currently limited to single, palpable breast tumours. More extensive and randomised clinical trials are needed to evaluate HIFU therapy for breast cancer, especially where the tumour is left in situ.
PubMed: 37568958
DOI: 10.3390/diagnostics13152595 -
Archives of Cardiovascular Diseases 2020The risk of cardiovascular adverse events from rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK)... (Meta-Analysis)
Meta-Analysis
Cardiovascular safety of rapidly accelerated fibrosarcoma B-type and/or mitogen-activated extracellular signal-regulated kinase inhibitors: A mixed approach combining a meta-analysis and a pharmacovigilance disproportionality analysis.
BACKGROUND
The risk of cardiovascular adverse events from rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors is not fully characterized.
AIM
To evaluate the cardiovascular adverse events risks related to BRAF and/or MEK inhibitors in randomized placebo-controlled clinical trials and in the real-life setting.
METHODS
We used two approaches. First, we conducted a systematic review and meta-analysis of randomized placebo-controlled clinical trials reporting the incidence of cardiovascular adverse events for BRAF and/or MEK inhibitors in cancer patients. Second, we performed a disproportionality analysis, using age- and sex-adjusted reporting odds ratios (arORs) and their 95% confidence intervals (CIs) from the World Health Organization's pharmacovigilance database (VigiBase®) of anticancer drug-associated reports, to investigate real-life data.
RESULTS
MEK inhibitors increased the risk of ejection fraction decrease (odds ratio [OR] 3.35, 95% CI 1.58-7.07), peripheral oedema (OR 2.87 95% CI 1.93-4.27) and syncope (OR 6.71, 95% CI 3.00-14.99) compared with placebo in randomized placebo-controlled clinical trials. BRAF and MEK inhibitor combination therapy further increased the risk of ejection fraction decrease. In the disproportionality analysis, we found over-reporting of ejection fraction decrease (arOR 8.42, 95% CI 7.03-10.09), peripheral oedema (arOR 1.39, 95% CI 1.17-1.66), syncope (arOR 1.56, 95% CI 1.22-1.99), torsade de pointes/QT prolongation (arOR 6.13, 95% CI 5.04-7.47) and supraventricular arrhythmias (arOR 1.50, 95% CI 1.21-1.85) for BRAF and MEK inhibitors. BRAF and MEK inhibitors were not associated with hypertension in either approach.
CONCLUSIONS
In conclusion, MEK inhibitors increase the risk of ejection fraction decrease, peripheral oedema and syncope in randomized placebo-controlled clinical trials. Real-life data confirm these findings, and suggested additional risks of torsade de pointes/QT prolongation and supraventricular arrhythmias with BRAF/MEK inhibitors.
Topics: Adverse Drug Reaction Reporting Systems; Aged; Antineoplastic Agents; Cardiovascular Diseases; Databases, Factual; Female; Fibrosarcoma; Humans; Male; Middle Aged; Mitogen-Activated Protein Kinase Kinases; Patient Safety; Pharmacovigilance; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 32418884
DOI: 10.1016/j.acvd.2020.03.014 -
BMC Sports Science, Medicine &... 2018Swimming induced pulmonary oedema is an uncommon occurrence and usually presents during strenuous distance swimming in cold water. The prevalence is most likely...
BACKGROUND
Swimming induced pulmonary oedema is an uncommon occurrence and usually presents during strenuous distance swimming in cold water. The prevalence is most likely underreported and the underlying mechanisms are controversial. The purpose of this study was to summarize the evidence with regards to prevalence, pathophysiology and treatment of swimming induced pulmonary oedema in endurance athletes.
METHODS
Medline, Embase, Scopus and Google Scholar were searched and level I-IV from 1970 to 2017 were included. For clinical studies, only publications reporting on swimming-induced pulmonary oedema were considered. Risk of bias was assessed with the ROBINS-I tool, and the quality of evidence was assessed with the Cochrane GRADE system. For data synthesis and analysis, a best evidence synthesis was used.
RESULTS
A total of 29 studies were included (174 athletes). The most common symptom was cough, dyspnoea, froth and haemoptysis. The risk of bias for the clinical studies included 13 with moderate risk, 3 with serious, and 4 with critical. Four of the pathophysiology studies had a moderate risk, 3 a serious risk, and 1 a critical risk of bias. A best evidence analysis demonstrated a strong association between cold water immersion and in increases of CVP (central venous pressure), MPAP (mean pulmonary arterial pressure), PVR (peripheral vascular resistance) and PAWP (pulmonary arterial wedge pressure) resulting in interstitial asymptomatic oedema.
CONCLUSION
The results of this study suggest a moderate association between water temperature and the prevalence of SIPE. The presence of the clinical symptoms cough, dyspnoea, froth and haemoptysis are strongly suggestive of SIPE during or immediately following swimming. There is only limited evidence to suggest that there are pre-existing risk factors leading to SIPE with exposure to strenuous physical activity during swimming. There is strong evidence that sudden deaths of triathletes are often associated with cardiac abnormalities.
PubMed: 30410770
DOI: 10.1186/s13102-018-0107-3 -
The Cochrane Database of Systematic... Feb 2015Dehydration is an important cause of death in patients with Ebola virus disease (EVD). Parenteral fluids are often required in patients with fluid requirements in excess... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dehydration is an important cause of death in patients with Ebola virus disease (EVD). Parenteral fluids are often required in patients with fluid requirements in excess of their oral intake. The peripheral intravenous route is the most commonly used method of parenteral access, but inserting and maintaining an intravenous line can be challenging in the context of EVD. Therefore it is important to consider the advantages and disadvantages of different routes for achieving parenteral access (e.g. intravenous, intraosseous, subcutaneous and intraperitoneal).
OBJECTIVES
To compare the reliability, ease of use and speed of insertion of different parenteral access methods.
SEARCH METHODS
We ran the search on 17 November 2014. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, Ovid MEDLINE(R) and Ovid OLDMEDLINE(R), Embase Classic + Embase (OvidSP), CINAHL (EBSCOhost), clinicaltrials.gov and screened reference lists.
SELECTION CRITERIA
Randomised controlled trials comparing different parenteral routes for the infusion of fluids or medication.
DATA COLLECTION AND ANALYSIS
Two review authors examined the titles and abstracts of records obtained by searching the electronic databases to determine eligibility. Two review authors extracted data from the included trials and assessed the risk of bias. Outcome measures of interest were success of insertion; time required for insertion; number of insertion attempts; number of dislodgements; time period with functional access; local site reactions; clinicians' perception of ease of administration; needlestick injury to healthcare workers; patients' discomfort; and mortality. For trials involving the administration of fluids we also collected data on the volume of fluid infused, changes in serum electrolytes and markers of renal function. We rated the quality of the evidence as 'high', 'moderate', 'low' or 'very low' according to the GRADE approach for the following outcomes: success of insertion, time required for insertion, number of dislodgements, volume of fluid infused and needlestick injuries.
MAIN RESULTS
We included 17 trials involving 885 participants. Parenteral access was used to infuse fluids in 11 trials and medications in six trials. None of the trials involved patients with EVD. Intravenous and intraosseous access was compared in four trials; intravenous and subcutaneous access in 11; peripheral intravenous and intraperitoneal access in one; saphenous vein cutdown and intraosseous access in one; and intraperitoneal with subcutaneous access in one. All of the trials assessing the intravenous method involved peripheral intravenous access.We judged few trials to be at low risk of bias for any of the assessed domains.Compared to the intraosseous group, patients in the intravenous group were more likely to experience an insertion failure (risk ratio (RR) 3.89, 95% confidence interval (CI) 2.39 to 6.33; n = 242; GRADE rating: low). We did not pool data for time to insertion but estimates from the trials suggest that inserting intravenous access takes longer (GRADE rating: moderate). Clinicians judged the intravenous route to be easier to insert (RR 0.15, 95% CI 0.04 to 0.61; n = 182). A larger volume of fluids was infused via the intravenous route (GRADE rating: moderate). There was no evidence of a difference between the two routes for any other outcomes, including adverse events.Compared to the subcutaneous group, patients in the intravenous group were more likely to experience an insertion failure (RR 14.79, 95% CI 2.87 to 76.08; n = 238; GRADE rating: moderate) and dislodgement of the device (RR 3.78, 95% CI 1.16 to 12.34; n = 67; GRADE rating: low). Clinicians also judged the intravenous route as being more difficult to insert and patients were more likely to be agitated in the intravenous group. Patients in the intravenous group were more likely to develop a local infection and phlebitis, but were less likely to develop erythema, oedema or swelling than those in the subcutaneous group. A larger volume of fluids was infused into patients via the intravenous route. There was no evidence of a difference between the two routes for any other outcome.There were insufficient data to reliably determine if the risk of insertion failure differed between the saphenous vein cutdown (SVC) and intraosseous method (RR 4.00, 95% CI 0.51 to 31.13; GRADE rating: low). Insertion using SVC took longer than the intraosseous method (MD 219.60 seconds, 95% CI 135.44 to 303.76; GRADE rating: moderate). There were no data and therefore there was no evidence of a difference between the two routes for any other outcome.There were insufficient data to reliably determine the relative effects of intraperitoneal or central intravenous access relative to any other parenteral access method.
AUTHORS' CONCLUSIONS
There are several different ways of achieving parenteral access in patients who are unable meet their fluid requirements with oral intake alone. The quality of the evidence, as assessed using the GRADE criteria, is somewhat limited because of the lack of adequately powered trials at low risk of bias. However, we believe that there is sufficient evidence to draw the following conclusions: if peripheral intravenous access can be achieved easily, this allows infusion of larger volumes of fluid than other routes; but if this is not possible, the intraosseous and subcutaneous routes are viable alternatives. The subcutaneous route may be suitable for patients who are not severely dehydrated but in whom ongoing fluid losses cannot be met by oral intake.A film to accompany this review can be viewed here (http://youtu.be/ArVPzkf93ng).
Topics: Dehydration; Disease Management; Hemorrhagic Fever, Ebola; Humans; Hypodermoclysis; Infusions, Intraosseous; Infusions, Intravenous; Infusions, Parenteral; Saphenous Vein
PubMed: 25914907
DOI: 10.1002/14651858.CD011386.pub2 -
Frontiers in Pharmacology 2019Whereas the cardiovascular safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors has been well reported, there is limited data from controlled clinical trials...
Appraisal of Non-Cardiovascular Safety for Sodium-Glucose Co-Transporter 2 Inhibitors: A Systematic Review and Meta-Analysis of Placebo-Controlled Randomized Clinical Trials.
Whereas the cardiovascular safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors has been well reported, there is limited data from controlled clinical trials regarding the non-cardiovascular safety. This was the focus of our study. We systematically searched MEDLINE, EMBASE, and Cochrane Library (5 Sep 2018) for randomized controlled trials (RCTs) that reported safety data for SGLT2 inhibitors and placebo. Relative risks (RRs) and their 95% confidence intervals (CIs) were pooled using random-effects models. Seventy RCTs (83 studies enrolling 36,958 patients in 78 publications) were identified. SGLT2 inhibitors were associated with a lower risk of serious adverse events (RR 0.90, 95% CI 0.86 to 0.94, < 0.001), death (RR 0.78, 95% CI 0.64 to 0.94, < 0.05), gastroenteritis (RR 0.38, 95% CI 0.20 to 0.72, < 0.05), arthralgia (RR 0.72, 95% CI 0.54 to 0.96, < 0.05), hypertension (RR 0.61, 95% CI 0.50 to 0.75, < 0.001), and edema/peripheral edema (RR 0.49, 95% CI 0.33 to 0.72, < 0.001) compared to placebo. SGLT2 inhibitors were associated with higher risk of infections compared to placebo (RR 1.27, 95% CI 1.17 to 1.37, < 0.001), especially for genital mycotic infection (GMI) (RR 3.71, 95% CI 3.19 to 4.32, < 0.001). Other significant effects were observed for osmotic diuresis-related AEs (RR 2.73, 95% CI 2.20 to 3.40, < 0.001), volume-related AEs (RR 1.26, 95% CI 1.08 to 1.46, < 0.05), renal-related AEs (RR 1.36, 95% CI 1.02 to 1.80, < 0.05), hypoglycemia (RR 1.18, 95% CI 1.10 to 1.26, < 0.001), and increased blood ketone bodies (RR 2.00, 95% CI 1.01 to 3.97, < 0.05). Subgroup and sensitivity analyses strengthened the robustness of primary results. Results from RCTs confirmed lower risk of death, serious adverse events, hypertension, and edema associated with type 2 diabetes mellitus (T2DM) patients treated with SGLT2 inhibitors when compared with placebo. The use of SGLT2 inhibitors were associated with higher risk of infection, osmotic diuresis, volume depletion effects, renal related AEs, and higher blood ketone bodies when compared with placebo.
PubMed: 31616297
DOI: 10.3389/fphar.2019.01066 -
PloS One 2022Trastuzumab is a valuable therapy option for women with ERBB2(HER2)+ breast cancer tumours, often used in combination with chemotherapy and alongside other therapies. It... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Trastuzumab is a valuable therapy option for women with ERBB2(HER2)+ breast cancer tumours, often used in combination with chemotherapy and alongside other therapies. It is known to have adverse effects, but these have proved difficult to separate from the effects of other concurrent therapies patients are usually taking. This study aims to assess the adverse effects specifically attributable to trastuzumab, and whether they vary by patient subgroup or concurrent therapies.
METHODS
As registered on PROSPERO (CRD42019146541), we used previous systematic reviews as well as the clinicaltrials.gov registry to identify randomised controlled trials in breast cancer which compared treatment regimes with and without trastuzumab. Neoadjuvant, adjuvant and metastatic settings were examined. Data was extracted from those which had, as of July 2022, reported adverse events. Risk of bias was assessed using ROB2. Primary outcomes were adverse events of any type or severity (excluding death). A standard random-effects meta-analysis was performed for each outcome independently. In order to ascertain whether adverse effects differed by individual factors such as age or tumour characteristics, or by use of trastuzumab concurrently with hormone therapy, we examined individual-level patient data for one large trial, HERA.
RESULTS
79 relevant trials were found, of which 20 contained comparable arms of trastuzumab-containing therapy and corresponding matched therapy without trastuzumab. This allowed a comparison of 8669 patients receiving trastuzumab versus 9556 receiving no trastuzumab, which gave a list of 25 statistically and clinically significant adverse effects related to trastuzumab alone: unspecified pain, asthenia, nasopharyngitis, skin disorders (mainly rash), dyspepsia, paraesthesia, infections (often respiratory), increased lacrimation, diarrhoea, myalgia, oedema (limb/peripheral), fever, nose bleeds, cardiac events, insomnia, cough, back pain, dyspnoea, chills, dizziness or vertigo, hypertension, congestive heart failure, increased levels of aspartate aminotransferase, gastrointestinal issues and dehydration. Analysis of individual patient-level data from 5102 patients suggested that nausea is slightly more likely for women taking trastuzumab who are ER+ /also taking hormone therapy than for those who are ER-/not taking hormone therapy; no other potential treatment-subgroup interactions were detected. We found no evidence for significantly increased rates of neutropenia, anaemia or lymphopenia in patients on trastuzumab-containing regimes compared to those on comparable regimes without trastuzumab.
CONCLUSIONS
This meta-analysis should allow clinicians and patients to better identify and quantify the potential adverse effects of adding trastuzumab to their treatment regime for breast cancer, and hence inform their decision-making. However, limitations include serious risk of bias due to heterogeneity in reporting of the outcomes and the open-label nature of the trials.
Topics: Humans; Female; Trastuzumab; Breast Neoplasms; Drug-Related Side Effects and Adverse Reactions; Neutropenia; Hormones
PubMed: 36454979
DOI: 10.1371/journal.pone.0275321