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The Cochrane Database of Systematic... Feb 2024Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive or relapsing weakness and numbness of the limbs, which lasts for at least two months.... (Review)
Review
BACKGROUND
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive or relapsing weakness and numbness of the limbs, which lasts for at least two months. Uncontrolled studies have suggested that intravenous immunoglobulin (IVIg) could help to reduce symptoms. This is an update of a review first published in 2002 and last updated in 2013.
OBJECTIVES
To assess the efficacy and safety of intravenous immunoglobulin in people with chronic inflammatory demyelinating polyradiculoneuropathy.
SEARCH METHODS
We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and two trials registers on 8 March 2023.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) and quasi-RCTs that tested any dose of IVIg versus placebo, plasma exchange, or corticosteroids in people with definite or probable CIDP.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcome was significant improvement in disability within six weeks after the start of treatment, as determined and defined by the study authors. Our secondary outcomes were change in mean disability score within six weeks, change in muscle strength (Medical Research Council (MRC) sum score) within six weeks, change in mean disability score at 24 weeks or later, frequency of serious adverse events, and frequency of any adverse events. We used GRADE to assess the certainty of evidence for our main outcomes.
MAIN RESULTS
We included nine RCTs with 372 participants (235 male) from Europe, North America, South America, and Israel. There was low statistical heterogeneity between the trial results, and the overall risk of bias was low for all trials that contributed data to the analysis. Five trials (235 participants) compared IVIg with placebo, one trial (20 participants) compared IVIg with plasma exchange, two trials (72 participants) compared IVIg with prednisolone, and one trial (45 participants) compared IVIg with intravenous methylprednisolone (IVMP). We included one new trial in this update, though it contributed no data to any meta-analyses. IVIg compared with placebo increases the probability of significant improvement in disability within six weeks of the start of treatment (risk ratio (RR) 2.40, 95% confidence interval (CI) 1.72 to 3.36; number needed to treat for an additional beneficial outcome (NNTB) 4, 95% CI 3 to 5; 5 trials, 269 participants; high-certainty evidence). Since each trial used a different disability scale and definition of significant improvement, we were unable to evaluate the clinical relevance of the pooled effect. IVIg compared with placebo improves disability measured on the Rankin scale (0 to 6, lower is better) two to six weeks after the start of treatment (mean difference (MD) -0.26 points, 95% CI -0.48 to -0.05; 3 trials, 90 participants; high-certainty evidence). IVIg compared with placebo probably improves disability measured on the Inflammatory Neuropathy Cause and Treatment (INCAT) scale (1 to 10, lower is better) after 24 weeks (MD 0.80 points, 95% CI 0.23 to 1.37; 1 trial, 117 participants; moderate-certainty evidence). There is probably little or no difference between IVIg and placebo in the frequency of serious adverse events (RR 0.82, 95% CI 0.36 to 1.87; 3 trials, 315 participants; moderate-certainty evidence). The trial comparing IVIg with plasma exchange reported none of our main outcomes. IVIg compared with prednisolone probably has little or no effect on the probability of significant improvement in disability four weeks after the start of treatment (RR 0.91, 95% CI 0.50 to 1.68; 1 trial, 29 participants; moderate-certainty evidence), and little or no effect on change in mean disability measured on the Rankin scale (MD 0.21 points, 95% CI -0.19 to 0.61; 1 trial, 24 participants; moderate-certainty evidence). There is probably little or no difference between IVIg and prednisolone in the frequency of serious adverse events (RR 0.45, 95% CI 0.04 to 4.69; 1 cross-over trial, 32 participants; moderate-certainty evidence). IVIg compared with IVMP probably increases the likelihood of significant improvement in disability two weeks after starting treatment (RR 1.46, 95% CI 0.40 to 5.38; 1 trial, 45 participants; moderate-certainty evidence). IVIg compared with IVMP probably has little or no effect on change in disability measured on the Rankin scale two weeks after the start of treatment (MD 0.24 points, 95% CI -0.15 to 0.63; 1 trial, 45 participants; moderate-certainty evidence) or on change in mean disability measured with the Overall Neuropathy Limitation Scale (ONLS, 1 to 12, lower is better) 24 weeks after the start of treatment (MD 0.03 points, 95% CI -0.91 to 0.97; 1 trial, 45 participants; moderate-certainty evidence). The frequency of serious adverse events may be higher with IVIg compared with IVMP (RR 4.40, 95% CI 0.22 to 86.78; 1 trial, 45 participants, moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Evidence from RCTs shows that IVIg improves disability for at least two to six weeks compared with placebo, with an NNTB of 4. During this period, IVIg probably has similar efficacy to oral prednisolone and IVMP. Further placebo-controlled trials are unlikely to change these conclusions. In one large trial, the benefit of IVIg compared with placebo in terms of improved disability score persisted for 24 weeks. Further research is needed to assess the long-term benefits and harms of IVIg relative to other treatments.
Topics: Male; Humans; Immunoglobulins, Intravenous; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Neoplasm Recurrence, Local; Adrenal Cortex Hormones; Methylprednisolone
PubMed: 38353301
DOI: 10.1002/14651858.CD001797.pub4 -
Journal of Bodywork and Movement... Jul 2024To investigate the effects of combined exercise on fatigue, anxiety, depression, quality of life and physical functioning in gastroinstestinal neoplasm in people under... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To investigate the effects of combined exercise on fatigue, anxiety, depression, quality of life and physical functioning in gastroinstestinal neoplasm in people under chemotherapy with oxaliplatin treatment.
METHODS
We searched pubmed/MEDLINE, Cochrane Central Register of Controlled Trials, PEDro data base, and SciELO (until Nov 2023) for randomized controlled trials that investigated the effects of combined exercise in gastroinstestinal neoplasm people under chemotherapy with oxaliplatin treatment. Two comparisons were made: combined exercise versus usual care, combined aerobic and versus usual care (follow up). The main outcomes were muscle strength, aerobic capacity, fatigue, anxiety, depression and quality of life. Mean differences (MD) with 95% confidence interval (CI) were calculated.
RESULTS
Seven randomized controlled trials met the eligibility criteria, which included 464 people. Compared to usual care, combined aerobic and resistance resulted in decrease of general fatigue (-2.82; IC: 4.92 to -0.69, N = 48), physical fatigue (-5.08; IC: 8.41 to -1.74, N = 48) and improvement of domain physical functioning of quality of life (9.40; IC: 2.74 to 16.06, N = 48). Compared to usual care, combined aerobic and resistance - Follow up resulted in decrease of general fatigue (-2.32; IC: 4.41 to - 0.28, N = 48), physical fatigue (-0.92; IC: 3.31 to -1.47, N = 48) and improvement ofdomain physical functioning of (9.83; IC: 0.66 to 19.01, N = 48).
CONCLUSIONS
Our results demonstrate that combined exercises improves fatigue (general; physical), domain physical functioning of quality of life in gastrointestinal neoplasm people under chemotherapy treatment when compared to usual care.
Topics: Humans; Quality of Life; Fatigue; Oxaliplatin; Antineoplastic Agents; Exercise Therapy; Muscle Strength; Depression; Randomized Controlled Trials as Topic; Anxiety; Gastrointestinal Neoplasms
PubMed: 38876699
DOI: 10.1016/j.jbmt.2024.02.004 -
Journal of Cachexia, Sarcopenia and... Apr 2024There is no consensus on the optimal endpoint(s) in cancer cachexia trials. Endpoint variation is an obstacle when comparing interventions and their clinical value. The... (Review)
Review
There is no consensus on the optimal endpoint(s) in cancer cachexia trials. Endpoint variation is an obstacle when comparing interventions and their clinical value. The aim of this systematic review was to summarize and evaluate endpoints used to assess appetite and dietary intake in cancer cachexia clinical trials. A search for studies published from 1 January 1990 until 2 June 2021 was conducted using MEDLINE, Embase and Cochrane Central Register of Controlled Trials. Eligible studies examined cancer cachexia treatment versus a comparator in adults with assessments of appetite and/or dietary intake as study endpoints, a sample size ≥40 and an intervention lasting ≥14 days. Reporting was in line with PRISMA guidance, and a protocol was published in PROSPERO (2022 CRD42022276710). This review is part of a series of systematic reviews examining cachexia endpoints. Of the 5975 articles identified, 116 were eligible for the wider review series and 80 specifically examined endpoints of appetite (65 studies) and/or dietary intake (21 studies). Six trials assessed both appetite and dietary intake. Appetite was the primary outcome in 15 trials and dietary intake in 7 trials. Median sample size was 101 patients (range 40-628). Forty-nine studies included multiple primary tumour sites, while 31 studies involved single primary tumour sites (15 gastrointestinal, 7 lung, 7 head and neck and 2 female reproductive organs). The most frequently reported appetite endpoints were visual analogue scale (VAS) and numerical rating scale (NRS) (40%). The appetite item from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30/C15 PAL (38%) and the appetite question from North Central Cancer Treatment Group anorexia questionnaire (17%) were also frequently applied. Of the studies that assessed dietary intake, 13 (62%) used food records (prospective registrations) and 10 (48%) used retrospective methods (24-h recall or dietary history). For VAS/NRS, a mean change of 1.3 corresponded to Hedge's g of 0.5 and can be considered a moderate change. For food records, a mean change of 231 kcal/day or 11 g of protein/day corresponded to a moderate change. Choice of endpoint in cachexia trials will depend on factors pertinent to the trial to be conducted. Nevertheless, from trials assessed and available literature, NRS or EORTC QLQ C30/C15 PAL seems suitable for appetite assessments. Appetite and dietary intake endpoints are rarely used as primary outcomes in cancer cachexia. Dietary intake assessments were used mainly to monitor compliance and are not validated in cachexia populations. Given the importance to cachexia studies, dietary intake endpoints must be validated before they are used as endpoints in clinical trials.
Topics: Humans; Appetite; Cachexia; Eating; Neoplasms; Prospective Studies; Quality of Life; Retrospective Studies; Clinical Trials as Topic
PubMed: 38343065
DOI: 10.1002/jcsm.13434 -
Journal of Cachexia, Sarcopenia and... Jun 2024Regulatory agencies require evidence that endpoints correlate with clinical benefit before they can be used to approve drugs. Biomarkers are often considered surrogate... (Review)
Review
Regulatory agencies require evidence that endpoints correlate with clinical benefit before they can be used to approve drugs. Biomarkers are often considered surrogate endpoints. In cancer cachexia trials, the measurement of biomarkers features frequently. The aim of this systematic review was to assess the frequency and diversity of biomarker endpoints in cancer cachexia trials. A comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990-2023) was completed. Eligible trials met the following criteria: adults (≥18 years), prospective design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a biomarker(s) as an endpoint. Biomarkers were defined as any objective measure that was assayed from a body fluid, including scoring systems based on these assays. Routine haematology and biochemistry to monitor intervention toxicity were not considered. Data extraction was performed using Covidence, and reporting followed PRISMA guidance (PROSPERO: CRD42022276710). A total of 5975 studies were assessed, of which 52 trials (total participants = 6522) included biomarkers as endpoints. Most studies (n = 29, 55.7%) included a variety of cancer types. Pharmacological interventions (n = 27, 51.9%) were most evaluated, followed by nutritional interventions (n = 20, 38.4%). Ninety-nine different biomarkers were used across the trials, and of these, 96 were assayed from blood. Albumin (n = 29, 55.8%) was assessed most often, followed by C-reactive protein (n = 22, 42.3%), interleukin-6 (n = 16, 30.8%) and tumour necrosis factor-α (n = 14, 26.9%), the latter being the only biomarker that was used to guide sample size calculations. Biomarkers were explicitly listed as a primary outcome in six trials. In total, 12 biomarkers (12.1% of 99) were used in six trials or more. Insulin-like growth factor binding protein 3 (IGFBP-3) and insulin-like growth factor 1 (IGF-1) levels both increased significantly in all three trials in which they were both used. This corresponded with a primary outcome, lean body mass, and was related to the pharmacological mechanism. Biomarkers were predominately used as exploratory rather than primary endpoints. The most commonly used biomarker, albumin, was limited by its lack of responsiveness to nutritional intervention. For a biomarker to be responsive to change, it must be related to the mechanism of action of the intervention and/or the underlying cachexia process that is modified by the intervention, as seen with IGFBP-3, IGF-1 and anamorelin. To reach regulatory approval as an endpoint, the relationship between the biomarker and clinical benefit must be clarified.
Topics: Cachexia; Humans; Neoplasms; Biomarkers; Clinical Trials as Topic
PubMed: 38783477
DOI: 10.1002/jcsm.13491 -
Urology Jun 2024To determine whether neoadjuvant gemcitabine and cisplatin (GC) vs dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) before radical cystectomy... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine whether neoadjuvant gemcitabine and cisplatin (GC) vs dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) before radical cystectomy improves overall survival (OS), progression-free survival (PFS), and pathologic complete response (pCR) for patients with muscle-invasive bladder cancer with secondary analyses of pathological downstaging and toxicity.
MATERIALS AND METHODS
This systematic review and meta-analysis identified studies of patients with muscle-invasive bladder cancer treated with neoadjuvant GC compared to ddMVAC from PubMed, Web of Science, and EMBASE. Random-effect models for pooled log-transformed hazard ratios (HR) for OS and PFS and pooled odds ratios for pCR and downstaging were developed using the generic inverse variance method and Mantel-Haenszel method, respectively.
RESULTS
Ten studies were identified (4 OS, 2 PFS, and 6 pCR clinical endpoints). Neoadjuvant ddMVAC improved OS (HR 0.71 [95% confidence intervals 0.56; 0.90]), PFS (HR 0.76 [95% confidence intervals 0.60; 0.97]), and pathological downstaging (odds ratio 1.34 [95% confidence interval 1.01; 1.78]) as compared to GC. There was no significant difference between regimens for pCR rates (odds ratio 1.38 [95% confidence interval 0.90; 2.12]). Treatment toxicity was greater with ddMVAC. Limitations result from differences in number of ddMVAC cycles and patient selection between studies.
CONCLUSION
Neoadjuvant ddMVAC is associated with improved OS and PFS vs gemcitabine/cisplatin for patients with muscle-invasive bladder cancer before radical cystectomy. Although rates of pathological complete response were not significantly different, pathological downstaging correlated with OS. ddMVAC should be preferred over gemcitabine/cisplatin for patients with muscle-invasive bladder cancer who can tolerate its greater toxicity.
Topics: Urinary Bladder Neoplasms; Humans; Cisplatin; Neoadjuvant Therapy; Neoplasm Invasiveness; Antineoplastic Combined Chemotherapy Protocols; Gemcitabine; Deoxycytidine; Cystectomy; Doxorubicin; Vinblastine; Methotrexate; Chemotherapy, Adjuvant
PubMed: 38685388
DOI: 10.1016/j.urology.2024.04.034 -
Journal of Cachexia, Sarcopenia and... Jun 2024Low skeletal muscle mass (LSMM) and/or, function associated with an increased risk of treatment-related toxicities and inferior overall survival (OS) among adults with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Low skeletal muscle mass (LSMM) and/or, function associated with an increased risk of treatment-related toxicities and inferior overall survival (OS) among adults with solid malignancies. However, the association between LSMM and treatment-related toxicities among adults with haematologic malignancies remains unclear.
METHODS
Using a pre-published protocol (CRD42020197814), we searched seven bibliographic databases from inception to 08/2021 for studies reporting the impact of LSMM among adults ≥18 years with a known haematologic malignancy. The primary outcome of interest was OS, and secondary outcomes included progression free survival (PFS) and non-relapse mortality (NRM). These effect sizes were quantified in terms of hazards ratio (HR) along with 95% confidence interval (CI) and pooled across studies using a DerSimonian-Laird random-effects model. Heterogeneity was assessed using the Cochran's Q and the I statistic. All hypothesis testing was two-sided with an alpha of 0.05.
RESULTS
Of 3791 studies screened, we identified 20 studies involving 3468 patients with a mean age of 60 years; 44% were female and the most common malignancy was diffuse large B-cell lymphoma (42%). Most studies measured muscle mass using single slice computed tomography imaging at the L3 level. The presence of LSMM was associated with worse OS (pooled HR = 1.81, 95% CI = 1.48-2.22, P < 0.001) with moderate heterogeneity (Cochran's Q, I = 60.4%), PFS (pooled HR = 1.61, 95% CI = 1.28-2.02, P < 0.001) with moderate heterogeneity (Cochran's Q, I = 66.0%). Similarly, LSMM was associated with worse NRM (HR = 1.72, 95% CI = 1.34-2.22, P < 0.001) with little evidence of heterogeneity (Cochran's Q, I = 0.0%).
CONCLUSIONS
LSMM is associated with worse survival outcomes among adults with haematologic malignancies. Further research into understanding the underlying mechanism of this association and mitigating the negative effects of LSMM among adults with haematologic malignancies is needed.
Topics: Humans; Hematologic Neoplasms; Muscle, Skeletal; Treatment Outcome; Adult; Middle Aged; Female; Male
PubMed: 38558541
DOI: 10.1002/jcsm.13446 -
Cardio-oncology (London, England) Jun 2024The effects of exercise in patients with breast cancer (BC), has shown some profit, but consistency and magnitude of benefit remains unclear. We aimed to conduct a... (Review)
Review
BACKGROUND
The effects of exercise in patients with breast cancer (BC), has shown some profit, but consistency and magnitude of benefit remains unclear. We aimed to conduct a meta-analysis to assess the benefits of varying types of exercises in patients with BC.
METHODS
Literature search was conducted across five electronic databases (MEDLINE, Web of Science, Scopus, Google Scholar and Cochrane) from 1st January 2000 through 19th January 2024. Randomized controlled trials (RCTs) assessing the impact of different types of exercise on outcomes related to fitness and quality of life (QOL) in patients with BC were considered for inclusion. Outcomes of interest included cardiorespiratory fitness (CRF), health-related quality of life (HRQOL), muscle strength, fatigue and physical function. Evaluations were reported as mean differences (MDs) with 95% confidence intervals (CIs) and pooled using random effects model. A p value < 0.05 was considered significant.
RESULTS
Thirty-one relevant articles were included in the final analysis. Exercise intervention did not significantly improved the CRF in patients with BC when compared with control according to treadmill ergometer scale (MD: 4.96; 95%Cl [-2.79, 12.70]; P = 0.21), however exercise significantly improved CRF according to cycle ergometer scales (MD 2.07; 95% Cl [1.03, 3.11]; P = 0.0001). Physical function was significantly improved as well in exercise group reported by 6-MWT scale (MD 80.72; 95% Cl [55.67, 105.77]; P < 0.00001). However, exercise did not significantly improve muscle strength assessed using the hand grip dynamometer (MD 0.55; 95% CI [-1.61, 2.71]; P = 0.62), and fatigue assessed using the MFI-20 (MD -0.09; 95% CI [-5.92, 5.74]; P = 0.98) and Revised Piper scales (MD -0.26; 95% CI [-1.06, 0.55] P = 0.53). Interestingly, exercise was found to improve HRQOL when assessed using the FACT-B scale (MD 8.57; 95% CI [4.53, 12.61]; P < 0.0001) but no significant improvements were noted with the EORTIC QLQ-C30 scale (MD 1.98; 95% CI [-1.43, 5.40]; P = 0.25).
CONCLUSION
Overall exercise significantly improves the HRQOL, CRF and physical function in patients with BC. HRQOL was improved with all exercise types but the effects on CRF vary with cycle versus treadmill ergometer. Exercise failed to improve fatigue-related symptoms and muscle strength. Large RCTs are required to evaluate the effects of exercise in patients with BC in more detail.
PubMed: 38890692
DOI: 10.1186/s40959-024-00235-z -
PloS One 2023One of the most complex surgeries including radical cystectomy (RC) has a high rate of morbidity. The standard approach for the muscle-invasive bladder is conventional... (Meta-Analysis)
Meta-Analysis
BACKGROUND
One of the most complex surgeries including radical cystectomy (RC) has a high rate of morbidity. The standard approach for the muscle-invasive bladder is conventional transperitoneal radical cystectomy. However, the procedure is associated with significant morbidities like ileus, urinary leak, bleeding, and infection. The aim of this study is to compare the transperitoneal RC approach with the extraperitoneal RC approach in the treatment of bladder cancer patients. The outcomes of this study are Operative time, Estimated Blood Loss, Hospital Stay, Post-Operative Ileus, Infection, and Major Complication (Clavien-Dindo Grade 3-5).
METHODS
PubMed, Cochrane Library, and Science Direct were systematically searched for different publications related to the meta-analysis. Keywords used for searching were Radical Cystectomy AND Extraperitoneal AND Transperitoneal up until 31st August 2022. The studies were screened for our eligibility criteria. Demographic parameters, perioperative variables, and postoperative complications were recorded and analyzed. The Newcastle-Ottawa Scale was used to evaluate the risk of bias in each study. The Review Manager (RevMan) software version 5.4.1 was used for statistical analysis.
RESULTS
Eight studies (3 laparoscopic and 5 open methods) involving 1207 subjects (588 patients using the extraperitoneal approach and 619 using the transperitoneal approach) were included. The incidence of postoperative ileus is significantly lower after the extraperitoneal approach compared to the transperitoneal approach (p < 0.00001). The two techniques did not differ in operative time, estimated blood loss, duration of hospital stay, total infection, and major complication events.
CONCLUSION
This meta-analysis shows that extraperitoneal radical cystectomy benefits in terms of reduced postoperative ileus.
Topics: Humans; Cystectomy; Urinary Bladder; Treatment Outcome; Urinary Bladder Neoplasms; Postoperative Complications; Ileus
PubMed: 38032964
DOI: 10.1371/journal.pone.0294809 -
Facial Plastic Surgery & Aesthetic... 2024To systematically analyze the outcomes of reanimation techniques that have been described for patients undergoing non-fascicle sparing resection of intratemporal facial... (Review)
Review
To systematically analyze the outcomes of reanimation techniques that have been described for patients undergoing non-fascicle sparing resection of intratemporal facial schwannomas. A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines of the PubMed, MEDLINE, and Cochrane Central Register of Controlled Trials databases. Eight hundred forty studies were screened with 22 meeting inclusion criteria comprising 266 patients. Most facial nerve reanimations (81.2%) were performed using an interposition nerve graft. The remaining patients underwent hypoglossal-facial nerve transposition (13.9%), primary anastomosis (3.4%), and free muscle transfer (0.1%). Of the reported interposition grafts, the two most utilized were the great auricular (113/199) and sural (86/199) nerves. Interposition nerve grafts resulted in significantly better outcomes in facial nerve function postoperatively than hypoglossal-facial transposition (3.48 vs. 3.92; < 0.01). There was no difference between interposition grafts. This study systematically reports that interposition nerve grafts, after resection of intratemporal facial schwannoma, result in superior outcomes than hypoglossal-facial nerve transposition in these patients.
Topics: Humans; Neurilemmoma; Facial Nerve; Facial Paralysis; Nerve Transfer; Cranial Nerve Neoplasms; Hypoglossal Nerve
PubMed: 38150513
DOI: 10.1089/fpsam.2023.0229 -
PeerJ 2024To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting treatment.
METHODOLOGY
PubMed, Web of Science, Cochrane, and Embase databases were searched for CAFs-related studies of breast cancer patients from their inception to September, 2023. Meta-analysis was performed using R 4.2.2 software. Sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger's test were used to assess the publication bias.
RESULTS
Twenty-seven studies including 6,830 patients were selected. Univariate analysis showed that high expression of platelet-derived growth factor receptor- (PDGFR-) ( = 0.0055), tissue inhibitor of metalloproteinase-2 (TIMP-2) ( < 0.0001), matrix metalloproteinase (MMP) 9 ( < 0.0001), MMP 11 ( < 0.0001) and MMP 13 ( = 0.0009) in CAFs were correlated with reduced recurrence-free survival (RFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/event-free survival (EFS) respectively. Multivariate analysis showed that high expression of -smooth muscle actin (-SMA) ( = 0.0002), podoplanin (PDPN) ( = 0.0008), and PDGFR- ( = 0.0470) in CAFs was associated with reduced RFS/DFS/MFS/EFS respectively. Furthermore, PDPN and PDGFR- expression in CAFs of poorly differentiated breast cancer patients were higher than that of patients with relatively better differentiated breast cancer. In addition, there is a positive correlation between the expression of PDPN and human epidermal growth factor receptor-2 (HER-2).
CONCLUSIONS
The high expression of -SMA, PDPN, PDGFR- in CAFs leads to worse clinical outcomes in breast cancer, indicating their roles as prognostic biomarkers and potential therapeutic targets.
Topics: Humans; Female; Breast Neoplasms; Cancer-Associated Fibroblasts; Tissue Inhibitor of Metalloproteinase-2; Biomarkers, Tumor; Breast; Receptor, Platelet-Derived Growth Factor beta
PubMed: 38410801
DOI: 10.7717/peerj.16958