Leptomeningeal disease in neurosurgical brain metastases patients: a systematic review and meta-analysis

Abstract Background Leptomeningeal disease (LMD) is a complication distinguished by progression of metastatic disease into the leptomeninges and subsequent spread via cerebrospinal fluid (CSF). Although treatments for LMD exist, it is considered fatal with a median survival of two to four months. A broader overview of the risk factors that increase the brain metastasis (BM) patient’s risk of LMD is needed. This meta-analysis aimed to systematically review and quantitatively assess risk factors for LMD after surgical resection for BM. Methods A systematic literature search was performed on 7 May 2021. Pooled effect sizes were calculated using a random-effects model for variables reported by three or more studies. Results Among 503 studies, thirteen studies met the inclusion criteria with a total surgical sample size of 2105 patients, of which 386 patients developed LMD. The median incidence of LMD across included studies was 16.1%. Eighteen unique risk factors were reported as significantly associated with LMD occurrence, including but not limited to: larger tumor size, infratentorial BM location, proximity of BM to cerebrospinal fluid spaces, ventricle violation during surgery, subtotal or piecemeal resection, and postoperative stereotactic radiosurgery. Pooled results demonstrated that breast cancer as the primary tumor location (HR = 2.73, 95% CI: 2.12 -3.52) and multiple BMs (HR = 1.37, 95% CI: 1.18-1.58) were significantly associated with a higher risk of LMD occurrence. Conclusion Breast cancer origin and multiple BMs increase the risk of LMD occurrence after neurosurgery. Several other risk factors which might play a role in LMD development were also identified.

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TP53 codon 72 polymorphisms and breast carcinoma susceptibility: A meta-analysis

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e22171 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e22171-e22171

Author(s):

B. Zhu ◽

W. Zhuo ◽

Z. Chen

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Breast Carcinoma ◽

Meta Analysis ◽

Inclusion Criteria ◽

Codon 72 ◽

Knowledge Infrastructure ◽

Increased Risk ◽

Meta Analyses ◽

Chinese National Knowledge Infrastructure

e22171 Background: Previously, TP53 codon 72 polymorphisms have been implicated as risk factors for various cancers. Several studies have conducted on the association of TP53 codon 72 polymorphisms with susceptibility to breast carcinoma and have yielded inconclusive results. The aim of the present study was to assess possible associations of breast cancer risk with TP53 codon 72 polymorphisms. Methods: We conducted a search in the Medline, EMBASE, OVID, Sciencedirect, and Chinese National Knowledge Infrastructure (CNKI) without a language limitation, covering all papers published up to Dec 2008. The associated literature was acquired through deliberate searching and selected based on the established inclusion criteria for publications. Results: Consequently, fifteen studies, including 3436 cases and 4394 controls, met the included criteria and thus were selected. Ultimately, the relevant data were extracted and further analyzed using systematic meta- analyses. The results showed that individuals carrying homozygote Arg/Arg genotype have a significant increased risk of breast cancer compared with those carrying Pro/Pro genotype (OR: 1.58, 95%CI:1.10–2.28). For Arg allele, no evidence indicated that individuals with Arg/Arg genotype have an increased risk of breast cancer compared with those with a combined Pro genotype (Arg/Pro+Pro/Pro) (OR: 1.68, 95%CI:1.24–2.29). For Pro allele, individuals with homozygote Pro/Pro genotype have a marked decreased susceptibility to breast cancer relative to those with a combined Arg genotype (Arg/Pro+Arg/Arg) (OR: 0.84, 95%CI:0.73–0.98). Conclusions: The results of the present study suggest that TP53 codon 72 polymorphisms might be a risk factor for breast cancer. Homozygote Arg allele genotype could significantly increase susceptibility to breast cancer, while Pro/Pro allele markedly decreases breast risk. No significant financial relationships to disclose.

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AB0558 RISK FACTORS FOR THE DEVELOPMENT OF BREAST CANCER IN SYSTEMIC SCLEROSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2016 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1575.1-1576

Author(s):

C. Carbonell ◽

A. J. Chamorro ◽

M. Marcos ◽

A. Guillén del Castillo ◽

D. Colunga Argüelles ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Systemic Sclerosis ◽

General Population ◽

Meta Analysis ◽

Tumor Location ◽

Population Based ◽

Prior Literature ◽

Independent Association ◽

Risk Of Cancer

Background:Prior literature shows a global increase of cancer risk among patients with systemic sclerosis (SSc). Although breast cancer (BC) is one of the most frequent malignancies in SSc patients, the characteristics of this neoplasm among SSc patients is not well established and it is uncertain whether SSc significantly increases the risk of this cancer.Objectives:Describe the characteristics and risk factors for BC among Spanish patients with SSc.Methods:Ambispective and multicenter study of patients with a diagnosis of SSc according to ACR/EULAR criteria and/or LeRoy classification included in the Spanish Scleroderma Registry (RESCLE) from 2006 to 2018. Characteristics of patients with BC were described and incidence was compared with that of the general population.Results:Among 1930 patients with SSc, 206 (10.7%) had cancer. BC was the most frequent tumor location (47 patients of 206 with cancer [22.8%]), followed by lung cancer (29, 14.1%). The risk of BC was increased in patients with SSc compared to the general population (standardized incidence ratio [SIR] 1.31; 95% CI 1.10-1.54;P= 0.003).The comparison of patients with BC and those without cancer showed that patients with BC had older age at diagnosis of SSc (50.9 vs 45.9 years, respectively;P=0.004), were more frequently diagnosed of interstitial lung disease (ILD) (30/47 [63.8%] vs 694/1714 [40.5];P= 0.002) and pulmonary hypertension (12/24 [50.0%] vs 262/917 [28.6%];P= 0.037), had higher frequency of puffy hands as the first manifestation of SSc (4/45 [8.9%] vs 38/1664 [2.3 %];P= 0.023) and had more frequently primary biliary colangitis (PBC) (7 /46 [15.2%] vs 72 /1708 [4.2%];P= 0.004). Regarding autoimmunity profile, patients with SSc and BC had a significantly higher presence of anti-Ro (11/44 [25.0%] vs 214/1528 [14.0%];P= 0.049) and anti-mitochondrial antibodies (7/28 [25.0%] vs 96/837 [11.5%];P= 0.039). Multivariable regression analysis showed an independent association between the puffy hands (OR = 6.40; 95% CI 1.73-23.60;P= 0.005), diagnosis of PBC (OR = 5.70; 95% CI 2.16-15.07;P= 0.001), presence of ILD (OR = 3.29, 95% CI 1.69-6.39;P<0.001) and the presence of the anti-Ro antibody (OR 2.14; 95% CI 1.01-4.56;P= 0.048) with the presence of BC.Conclusion:BC risk was increased in patients with SSc. The development of ILD, PBC, the presence of anti Ro and puffy hands as the first clinical manifestation of SSc were identified as independent factors associated with the development of BC in our cohort.References:Colaci M et al. Breast cancer in systemic sclerosis: results of a cross-linkage of an Italian Rheumatologic Center and a population-based Cancer Registry and review of the literaure. Autoimmun Rev. 2014;13(2):132-7.Zhang JQ et al. The risk of cancer development in systemic sclerosis: a meta-analysis. Cancer Epidemiol. 2013;37(5):523-7.Disclosure of Interests:Cristina Carbonell: None declared, Antonio-J Chamorro: None declared, Miguel Marcos: None declared, Alfredo Guillén del Castillo: None declared, Dolores Colunga Argüelles Consultant of: Actelion pharmaceuticals, GSK, MSD., Manuel Rubio-Rivas: None declared, Ana Argibay: None declared, Begoña Marí-Alfonso: None declared, Adela Marín Ballvé: None declared, Antoni Castro Consultant of: Actelion pharmaceuticals, GSK, MSD., Ana Belén Madroñero-Vuelta: None declared, Eduardo L. Callejas-Moraga: None declared, Vicent Fonollosa-Pla Consultant of: Actelion pharmaceuticals, GSK, MSD., Carmen Pilar Simeón-Aznar Consultant of: Actelion pharmaceuticals, GSK, MSD., on behalf of RESCLE Investigators, Autoimmune Diseases Study Group (GEAS): None declared

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Cerebrospinal fluid leakage after cranial surgery in the pediatric population—a systematic review and meta-analysis

Child s Nervous System ◽

10.1007/s00381-021-05036-8 ◽

2021 ◽

Author(s):

Emma M. H. Slot ◽

Kirsten M. van Baarsen ◽

Eelco W. Hoving ◽

Nicolaas P. A. Zuithoff ◽

Tristan P. C van Doormaal

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Cerebrospinal Fluid ◽

Pediatric Population ◽

Meta Analysis ◽

Leakage Rate ◽

Csf Leak ◽

Cerebrospinal Fluid Leakage ◽

Cranial Surgery ◽

Csf Leakage

Abstract Background Cerebrospinal fluid (CSF) leakage is a common complication after neurosurgical intervention. It is associated with substantial morbidity and increased healthcare costs. The current systematic review and meta-analysis aim to quantify the incidence of cerebrospinal fluid leakage in the pediatric population and identify its risk factors. Methods The authors followed the PRISMA guidelines. The Embase, PubMed, and Cochrane database were searched for studies reporting CSF leakage after intradural cranial surgery in patients up to 18 years old. Meta-analysis of incidences was performed using a generalized linear mixed model. Results Twenty-six articles were included in this systematic review. Data were retrieved of 2929 patients who underwent a total of 3034 intradural cranial surgeries. Surprisingly, only four of the included articles reported their definition of CSF leakage. The overall CSF leakage rate was 4.4% (95% CI 2.6 to 7.3%). The odds of CSF leakage were significantly greater for craniectomy as opposed to craniotomy (OR 4.7, 95% CI 1.7 to 13.4) and infratentorial as opposed to supratentorial surgery (OR 5.9, 95% CI 1.7 to 20.6). The odds of CSF leakage were significantly lower for duraplasty use versus no duraplasty (OR 0.41 95% CI 0.2 to 0.9). Conclusion The overall CSF leakage rate after intradural cranial surgery in the pediatric population is 4.4%. Risk factors are craniectomy and infratentorial surgery. Duraplasty use is negatively associated with CSF leak. We suggest defining a CSF leak as “leakage of CSF through the skin,” as an unambiguous definition is fundamental for future research.

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Conventional cardiac risk factors associated with trastuzumab-induced cardiotoxicity in breast cancer: Systematic review and meta-analysis

Current Problems in Cancer ◽

10.1016/j.currproblcancer.2021.100723 ◽

2021 ◽

pp. 100723

Author(s):

George Koulaouzidis ◽

Amanda E. Yung ◽

Diana E. Yung ◽

Karolina Skonieczna-Żydecka ◽

Wojciech Marlicz ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Systematic Review ◽

Meta Analysis ◽

Cardiac Risk ◽

Factors Associated ◽

Cardiac Risk Factors

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Abstract P311: Effect of Non-Invasive Imaging on Cardiovascular Risk Factors and Downstream Testing: A Meta-Analysis of Randomized Controlled Trials

Circulation ◽

10.1161/circ.125.suppl_10.ap311 ◽

2012 ◽

Vol 125 (suppl_10) ◽

Author(s):

Seamus P Whelton ◽

Khurram Nasir ◽

Michael J Blaha ◽

Daniel S Berman ◽

Roger S Blumenthal

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Statistical Power ◽

Controlled Trial ◽

Meta Analysis ◽

Cardiovascular Imaging ◽

Significant Trend ◽

Inclusion Criteria ◽

Non Invasive ◽

Randomized Controlled

Introduction: Non-invasive cardiovascular imaging has been proposed as a method to improve risk stratification and motivate improved patient and physician risk factor modification. Despite increasing use of these technologies there remains limited evidence documenting its effect on downstream testing and improvement in risk factor control. Hypothesis: Addition of the EISNER study to a prior meta-analysis will improve statistical power to demonstrate the downstream consequences of non-invasive cardiovascular imaging. Methods: A comprehensive literature search of the MEDLINE database (1966 through July 2011) was conducted. Major inclusion criteria required: 1) randomized controlled trial design, 2) participants with no known history of coronary heart disease or stroke, and 3) comparison of a group provided with results of a non-invasive imaging scan versus those without results. A total of eight trials with 4,084 participants met the inclusion criteria for this analysis. We analyzed the data using a random effects model to allow for heterogeneity. Results: Among imaging groups there was a significant increase in prescribing for statins (RR, 1.15; 95% CI, 1.01–1.32) and a non-significant trend for increased prescription of aspirin (RR, 1.15; 95% CI, 0.97–1.35), ACE/ARB (RR, 1.12; 95% CI, 0.96–1.31), and insulin (RR, 1.54; 95% CI, 0.75–3.18). There was a non-significant trend towards increased smoking cessation (RR, 1.35; 95% CI, 0.88–2.08). For downstream outcomes there was a non-significant increase in coronary angiography (RR, 1.20; 95% CI, 0.92–1.57), but not for revascularization (RR, 0.92; 95% CI, 0.55–1.53). There was no significant effect of imaging on the change in traditional risk factors. Limitations: There remains a limited number of trials in this important area. Therefore, trials included in this analysis use a variety of different imaging modalities and we were not able to pool the results based on appropriate clinical action (intensification at high risk and reduction at low risk). Conclusions: Non-invasive cardiovascular imaging leads to increased statin use, but associations with other downstream treatments and change in risk factors are not statistically significant. Our results highlight the limited amount of data for describing the downstream consequences after CAC testing.

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Breast Cancer Risk Factors in Iran: A Systematic Review and Meta-analysis

10.20944/preprints202004.0074.v1 ◽

2020 ◽

Author(s):

Amir Shamshirian ◽

Keyvan Heydari ◽

Zahra Shams ◽

Amir Reza Aref ◽

Danial Shamshirian ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Stress Condition ◽

Vegetable Consumption ◽

Meta Analysis ◽

Cancer Risk Factors ◽

Daily Exercise ◽

Breast Cancer Risk Factors

To systematically investigate the epidemiology of breast cancer risk factors in Iran, we performed a systematic search via PubMed, Scopus, Web of Science and Persian databases for identifying studies published on breast cancer risk factors up to March 2019. Meta-analyses were done for risk factors reported in more than one study. We calculated odds ratios (ORs) with corresponding 95% confidence intervals (CIs) using a fixed/random-effects models.Thirty-nine studies entered into the meta-analysis. Pooling of ORs showed a significant harmful effect for risk factors including family history (OR: 1.80, 95%CI 1.47-2.12), HRT (OR: 5.48, 95%CI 0.84-1.74), ER positive (OR: 1.87, 95%CI 1.41-2.33), PR positive (OR: 1.84, 95%CI 1.38-2.29), stress condition (OR: 2.67, 95%CI 1.84-3.50), passive smokers (OR: 1.68, 95%CI 1.34-2.03), full-term pregnancy at age 30 (OR: 3.41, 95%CI 1.19-5.63), abortion (OR: 1.84, 95%CI 1.35-2.33), sweets consumption (OR: 1.71, 95%CI 1.32-2.11) and genotype Arg/Arg (crude OR: 1.59, 95%CI 1.07-2.10), whereas a significant protective effect for late menarche (OR: 0.58, 95%CI 0.32-0.83), nulliparity (OR: 0.68, 95%CI 0.39-0.96), 13 to 24 months of breastfeeding (OR: 0.68, 95%CI 0.46-0.90), daily exercise (OR: 0.59, 95%CI 0.44-0.73) and vegetable consumption (crude OR: 0.28, 95%CI 0.10-0.46).This study suggest that factors such as family history, HRT, ER and PR positive status, stress condition, passive smokers, late full-term pregnancy, abortion, sweets consumption and genotype Arg/Arg might increase risk of breast cancer development, whereas late menarche, nulliparity, 13-24 months breastfeeding, daily exercise and vegetable consumption had an inverse association with breast cancer development.

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Minor Physical Anomalies in Bipolar Disorder—A Meta-Analysis

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.598734 ◽

2021 ◽

Vol 12 ◽

Author(s):

Eszter Varga ◽

András Hajnal ◽

Alexandra Soós ◽

Péter Hegyi ◽

Dóra Kovács ◽

...

Keyword(s):

Bipolar Disorder ◽

Meta Analysis ◽

Bipolar Disorders ◽

Effect Sizes ◽

Inclusion Criteria ◽

Weighted Mean ◽

Quality Of Evidence ◽

Minor Physical Anomalies ◽

The Brain

Introduction: Minor physical anomalies (MPAs) may reflect basic neurobiological features underlying bipolar disorders (BPD), as they are sensitive physical indicators of morphogenetic failure of the brain. Despite several researches about the presence of MPAs in BPD, the results are still controversial.Objectives: The aim of the present meta-analysis was to assess the standardized weighted mean effect sizes of MPAs in BPD and to examine if MPAs may be found predominantly in the head and/or facial regions in BPD patients compared to controls (HC).Methods: Four studies, involving 155 patients with BPD, and 187 HC, were involved in the analysis after searching the literature. For the investigation of MPAs in the peripheral (MPA-P) and in the head and facial regions (MPA-CF), two studies involving 121 BPD patients, and 133 HC passed the inclusion criteria.Results: The number of the MPAs in the BPD group was significantly higher compared to HC. Another important finding of the present study is that BPD patients' MPA-P scores do not significantly differ from those of the HC. In contrast, BPD patients' MPA-CF scores were found to be significantly higher compared to HC subjects. It is important to note that there was a low number of eligible publications included, which caused higher heterogeneity.Conclusions: Low quality of evidence suggests that MPAs are more common in patients with BPD than in HC and the higher rate of MPAs is found predominantly in the head and facial regions.

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A Meta-Analysis of Incidence and Risk Factors of Trastuzumab-Induced Cardiotoxicity in Breast Cancer

Journal of Patient-Centered Research and Reviews ◽

10.17294/2330-0698.1229 ◽

2015 ◽

Vol 2 (4) ◽

pp. 207-208

Author(s):

Zeeshan Ali Jawa ◽

Ruth M Perez ◽

Lydia Garlie ◽

Maharaj Singh ◽

Rubina Qamar ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Meta Analysis

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Factors Associated With C5 Palsy Following Cervical Spine Surgery: A Systematic Review

Global Spine Journal ◽

10.1177/2192568219874771 ◽

2019 ◽

Vol 9 (8) ◽

pp. 881-894 ◽

Cited By ~ 5

Author(s):

Andrew Jack ◽

Wyatt L. Ramey ◽

Joseph R. Dettori ◽

Zane A. Tymchak ◽

Rod J. Oskouian ◽

...

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Meta Analysis ◽

Foraminal Stenosis ◽

Pathophysiological Mechanism ◽

Inclusion Criteria ◽

Cervical Spine Surgery ◽

Factors Associated ◽

C5 Palsy ◽

Study Heterogeneity

Study Design: Systematic review. Objectives: C5 palsy (C5P) is a not uncommon and disabling postoperative complication with a reported incidence varying between 0% and 30%. Among others, one explanation for its occurrence includes foraminal nerve root tethering. Although different risk factors have been reported, controversy about its causation and prevention persists. Inconsistent study findings contribute to the persistent ambiguity leading to an assumption of a multifactorial nature of the underlying C5P pathophysiology. Here, we report the results of a systematic review on C5P with narrow inclusion criteria in the hope of elucidating risk factors for C5P due to a common pathophysiological mechanism. Methods: Electronic databases from inception to March 9, 2019 and references of articles were searched. Narrow inclusion criteria were applied to identify studies investigating demographic, clinical, surgical, and radiographic factors associated with postoperative C5P. Results: Sixteen studies were included after initial screening of 122 studies. Eighty-four risk factors were analyzed; 27 in ≥2 studies and 57 in single studies. The pooled prevalence of C5P was 6.0% (range: 4.2%-24.1%) with no consistent evidence that C5P was associated with demographic, clinical, or specific surgical factors. Of the radiographic factors assessed, specifically decreased foraminal diameter and preoperative cord rotation were identified as risk factors for C5P. Conclusion: Although risk factors for C5P have been reported, ambiguity remains due to potentially multifactorial pathophysiology and study heterogeneity. We found foraminal diameter and cord rotation to be associated with postoperative C5P occurrence in our meta-analysis. These findings support the notion that factors contributing to, and acting synergistically with foraminal stenosis increase the risk of postoperative C5P.

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56. TUMOR-HOMING STEM CELL THERAPY INHIBITS THE PROGRESSION OF BREAST CANCER LEPTOMENINGEAL CARCINOMATOSIS

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa073.044 ◽

2020 ◽

Vol 2 (Supplement_2) ◽

pp. ii11-ii12

Author(s):

Wulin Jiang ◽

Alain Valdivia ◽

Alison Mercer-Smith ◽

Carey Anders ◽

Shawn Hingtgen

Keyword(s):

Breast Cancer ◽

Spinal Cord ◽

Cancer Cells ◽

Limit Of Detection ◽

Human Fibroblasts ◽

Leptomeningeal Carcinomatosis ◽

Leptomeningeal Disease ◽

Breast Cancer Patients ◽

Tumor Homing ◽

The Brain

Abstract INTRODUCTION Leptomeningeal carcinomatosis remains one of the most lethal forms of central nervous system metastasis, with a median survival of only 4 months. Effective new therapies are urgently needed to treat this highly aggressive cancer. In this study, we used models of both prophylactic and established leptomeningeal disease to investigate the efficacy of engineered tumor-homing neural stem cells (NSCs) therapy for breast cancer leptomeningeal carcinomatosis. METHODS Personalized NSC carriers were created using Sox2 overexpression to transdifferentiate human fibroblasts into induced NSCs (iNSCs) that home to cancer cells and carry therapeutic agents to induce tumor kill. Leptomeningeal models were created by engineering MDA-MB231-Br human breast cancer cells with fluorescent and bioluminescent reporters, then using intracisternal injection to inoculate Nude mice with the tumor cells. iNSC therapy was evaluated by infusing iNSCs releasing the pro-apoptotic agent TRAIL into the lateral ventricle of mice either 1 week prior to or 3 days after tumor inoculation for prophylactic or established tumor treatment respectively. Tumor progression in the brain and spinal cord was monitored by serial bioluminescence imaging (BLI). RESULTS Serial BLI showed that intracerebroventricular (ICV) iNSC-TRAIL therapy reduced the volume of metastatic tumor burden 99.49% in the brain and 99.80% in the spine within 2 weeks post-infusion and extended survival from 24 to 42 days. Additionally, prophylactic iNSC-TRAIL therapy delivered ICV markedly delayed tumor development, with tumors in the brain remaining >1000-fold smaller than control through 1-month post-treatment, below the limit of detection in the spinal cord through 1 month, and eliminating mortality through 50 days post-therapy. CONCLUSION These data suggest that iNSC therapy could be a promising treatment option for breast cancer patients with leptomeningeal carcinomatosis.

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