-
European Journal of Nuclear Medicine... Dec 2021Fibroblast activation protein-α (FAPα) is overexpressed on cancer-associated fibroblasts in approximately 90% of epithelial neoplasms, representing an appealing target... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Fibroblast activation protein-α (FAPα) is overexpressed on cancer-associated fibroblasts in approximately 90% of epithelial neoplasms, representing an appealing target for therapeutic and molecular imaging applications. [ Ga]Ga-labelled radiopharmaceuticals-FAP-inhibitors (FAPI)-have been developed for PET. We systematically reviewed and meta-analysed published literature to provide an overview of its clinical role.
MATERIALS AND METHODS
The search, limited to January 1st, 2018-March 31st, 2021, was performed on MedLine and Embase databases using all the possible combinations of terms "FAP", "FAPI", "PET/CT", "positron emission tomography", "fibroblast", "cancer-associated fibroblasts", "CAF", "molecular imaging", and "fibroblast imaging". Study quality was assessed using the QUADAS-2 criteria. Patient-based and lesion-based pooled sensitivities/specificities of FAPI PET were computed using a random-effects model directly from the STATA "metaprop" command. Between-study statistical heterogeneity was tested (I-statistics).
RESULTS
Twenty-three studies were selected for systematic review. Investigations on staging or restaging head and neck cancer (n = 2, 29 patients), abdominal malignancies (n = 6, 171 patients), various cancers (n = 2, 143 patients), and radiation treatment planning (n = 4, 56 patients) were included in the meta-analysis. On patient-based analysis, pooled sensitivity was 0.99 (95% CI 0.97-1.00) with negligible heterogeneity; pooled specificity was 0.87 (95% CI 0.62-1.00), with negligible heterogeneity. On lesion-based analysis, sensitivity and specificity had high heterogeneity (I = 88.56% and I = 97.20%, respectively). Pooled sensitivity for the primary tumour was 1.00 (95% CI 0.98-1.00) with negligible heterogeneity. Pooled sensitivity/specificity of nodal metastases had high heterogeneity (I = 89.18% and I = 95.74%, respectively). Pooled sensitivity in distant metastases was good (0.93 with 95% CI 0.88-0.97) with negligible heterogeneity.
CONCLUSIONS
FAPI-PET appears promising, especially in imaging cancers unsuitable for [F]FDG imaging, particularly primary lesions and distant metastases. However, high-level evidence is needed to define its role, specifically to identify cancer types, non-oncological diseases, and clinical settings for its applications.
Topics: Endopeptidases; Fluorodeoxyglucose F18; Gelatinases; Head and Neck Neoplasms; Humans; Membrane Proteins; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Serine Endopeptidases
PubMed: 34173007
DOI: 10.1007/s00259-021-05475-0 -
Nutrition, Metabolism, and... Feb 2024The aim of this study was to systematically review and analyze differences in the levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis... (Meta-Analysis)
Meta-Analysis
AIMS
The aim of this study was to systematically review and analyze differences in the levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) comparing metabolically healthy but obese (MHO) with metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO) subjects.
DATA SYNTHESIS
We searched PubMed, Embase, Web of Science, and Scopus for studies that matched the relevant search terms. Differences in inflammatory marker levels between MHO and the other three phenotypes were pooled as standardized mean differences (SMD) or differences of medians (DM) using a random-effects model. We included 91 studies reporting data on 435,007 individuals. The CRP levels were higher in MHO than in MHNO subjects (SMD = 0.63, 95% CI: 0.49, 0.76; DM = 0.83 mg/L, 95% CI: 0.56, 1.11). The CRP levels were higher in MHO than in MUNO subjects (SMD = 0.16, 95% CI: 0.05, 0.28; DM = 0.39 mg/L, 95% CI: 0.09, 0.69). The CRP levels were lower in MHO than in MUO individuals (SMD = -0.43, 95% CI: -0.54, -0.31; DM = -0.82 mg/L, 95% CI: -1.16, -0.48). The IL-6 levels in MHO were higher than in MHNO while lower than in MUO subjects. The TNF-α levels in MHO were higher than in MHNO individuals.
CONCLUSIONS
This review provides evidence that CRP levels in MHO are higher than in MHNO and MUNO subjects but lower than in MUO individuals. Additionally, IL-6 levels in MHO are higher than in MHNO but lower than in MUO subjects, and TNF-α levels in MHO are higher than in MHNO individuals.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO number: CRD42021234948.
Topics: Adult; Humans; Interleukin-6; Tumor Necrosis Factor-alpha; Obesity; Obesity, Morbid; Phenotype; Obesity, Metabolically Benign; Risk Factors; Body Mass Index; Metabolic Syndrome
PubMed: 37968171
DOI: 10.1016/j.numecd.2023.09.002 -
Frontiers in Pediatrics 2020Given the relatively low rate and limited publicly available data regarding children with SARS-CoV-2 infection, this knowledge gap should be addressed with urgency. This...
Given the relatively low rate and limited publicly available data regarding children with SARS-CoV-2 infection, this knowledge gap should be addressed with urgency. This systematic review with meta-analysis aimed to evaluate the epidemiological spectrum and clinical characteristics of children infected with SARS-CoV-2. Relevant international and Chinese public databases were systematically searched to identify all case studies from January 1, 2020 to May 7, 2020. This study consisted of 96 studies involving 7004 cases. The mean age of pediatric cases was 6.48 years (95% CI 52.0-77.5), 90% had household contact, and 66% presented with mild to moderate clinical syndromes. The main symptoms were fever (47%, 95% CI 41-53%) and cough (42%, 95% CI 36-48%). About 23% of children were asymptomatic, 27% had comorbidity, and 29% had a co-infection. The pooled mean incubation period was 9.57 days (95% CI 7.70-11.44). The shedding of SARS-CoV-2 in the upper respiratory tract lasted 11.43 days, and 75% of patients had virus particles in their stool. A total of 34% of the children had neutropenia and 26% had lymphocytosis. Interferon-alpha (81%) was the most commonly used antiviral drug in the children. The discharge and death rates were 79 and 1%. In conclusion, the transmissibility of pediatric COVID-19 should be not ignored because of the relatively long incubation period, shedding duration, and mild clinical syndromes.
PubMed: 33224909
DOI: 10.3389/fped.2020.591132 -
Environmental Research May 2022Air pollution is one of the most serious environmental problems that afflict our planet and one of the greatest risk factors for human health. In particular, PM is able...
Air pollution is one of the most serious environmental problems that afflict our planet and one of the greatest risk factors for human health. In particular, PM is able to cross the blood-alveolar and blood-brain barriers, thus increasing the onset of respiratory, cardiovascular and neurodegenerative diseases. Neurodegenerative disease is a progressive neuronal dysfunction that leads to neuronal lesions in both structure and function, and includes several diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), vascular dementia (VaD), multiple sclerosis (MS), and others. We carried out a systematic review using PRISMA approach to investigate on the possible association between exposure to PM and neurodegenerative diseases. The international databases (PubMed, Science Direct, Web of Sciences) were used to find published studies on the topic. The search period was between January 2011 and June 2021. About 2000 full research articles were selected, and finally, we included 20 full-research articles. Selected studies have highlighted how PM exposure can be associated with the onset of neurodegenerative diseases (AD, PD, MS, VaD). This association depends not only on age, PM levels and exposure time, but also on exposure to other air pollutants, proximity to areas with high vehicular traffic, and the presence of comorbidities. Exposure to PM promotes neuroinflammation processes, because through breathing the particles can reach the nasal epithelial mucosa and transferred to the brain through the olfactory bulb. Furthermore, exposure to PM has been associated with an increased expression of markers of neurodegenerative diseases (e.g. alpha-synuclein or beta-amyloid), which can contribute to the etiopathogenesis of neurodegenerative diseases. Although many studies have revealed the pathological relationship between PM exposure and cognitive impairment, the potential cellular and molecular mechanisms of PM leading to neurodegenerative disease remain not entirely clear, and then, further studies need to be carried out on the topic.
Topics: Air Pollutants; Air Pollution; Alzheimer Disease; Environmental Exposure; Humans; Neurodegenerative Diseases; Particulate Matter
PubMed: 34979121
DOI: 10.1016/j.envres.2021.112581 -
International Immunopharmacology Jul 2021Radiation therapy is one of the main cancer treatment modalities applied in 50-70% of cancer patients. Despite the many advantages of this treatment, such as...
PURPOSE
Radiation therapy is one of the main cancer treatment modalities applied in 50-70% of cancer patients. Despite the many advantages of this treatment, such as non-invasiveness, organ-preservation, and spatiotemporal flexibility in tumor targeting, it can lead to complications in irradiated healthy cells/tissues. In this regard, the use of radio-protective agents can alleviate radiation-induced complications. This study aimed to review the potential role of alpha-lipoic acid in the prevention/reduction of radiation-induced toxicities on healthy cells/tissues.
METHODS
A systematic search was performed following PRISMA guidelines to identify relevant literature on the "role of alpha-lipoic acid in the treatment of radiotherapy-induced toxicity" in the electronic databases of Web of Science, Embase, PubMed, and Scopus up to January 2021. Based on the inclusion and exclusion criteria of the present study, 278 articles were screened. Finally, 29 articles were included in this systematic review.
RESULTS
The obtained results showed that in experimental in vivo models, the radiation-treated groups had decreased survival rate and body weight compared to the control groups. It was also found that radiation can induce mild to severe toxicities on gastrointestinal, circulatory, reproductive, central nervous, respiratory, endocrine, exocrine systems, etc. However, the use of alpha-lipoic acid could alleviate the radiation-induced toxicities in most cases. This radio-protective agent exerts its effects through mechanisms of anti-oxidant, anti-apoptosis, anti-inflammatory, and so on.
CONCLUSION
According to the obtained results, it can be mentioned that co-treatment of alpha-lipoic acid with radiotherapy ameliorates the radiation-induced toxicities in healthy cells/tissues.
Topics: Animals; Antioxidants; Humans; Neoplasms; Radiation Injuries; Radiation-Protective Agents; Radiotherapy; Thioctic Acid
PubMed: 33989970
DOI: 10.1016/j.intimp.2021.107741 -
Radiotherapy and Oncology : Journal of... May 2020To perform a systematic review/meta-analysis of outcomes for patients with spinal metastases treated with stereotactic radiosurgery (SRS) (either single-fraction... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
To perform a systematic review/meta-analysis of outcomes for patients with spinal metastases treated with stereotactic radiosurgery (SRS) (either single-fraction (SF-SRS) or multiple-fraction (MF-SRS)) or conventional radiotherapy (RT).
MATERIALS AND METHODS
Thirty-seven studies were identified. Primary outcomes were 1-year local control (LC) and acute/late grade 3-5 toxicities (including vertebral compression fractures (VCF)). Weighted random effects meta-analyses using the DerSimonian and Laird methods and meta-regressions were conducted to characterize and compare effect sizes. Mixed effects regression models were used in dose analyses.
RESULTS
A total of 3237 patients with 4911 lesions were included; 43.8%, 19.7%, and 36.5% of lesions received SF-SRS, MF-SRS, or RT, respectively. SF-SRS resulted in improved 1-year LC (92.9% (95% CI: 86.4-97.4%); p = 0.007) compared to RT (81.0% (95% CI: 69.2-90.5%)) with no difference between MF-SRS (82.1%; p = 0.86) and RT. On subgroup analysis of de novo metastases, superior 1-year LC following SF-SRS (95.5% (95% CI: 87.4-99.6%)) was maintained compared to RT (83.6% (95% CI: 70.4-93.5%); p = 0.007). A 4.7% increase in LC was noted for each 10 Gy increase in biologically effective dose (BED, assuming an alpha/beta = 10) with SRS (p < 0.001). No difference in toxicities were found between SF-SRS (0.4%), MF-SRS (0.2%), or RT (0%). Higher VCF rates were noted following SF-SRS (19.5%) vs. MF-SRS (9.6%; p = 0.039)) with no correlation between dose and VCF rates.
CONCLUSION
SF-SRS resulted in superior LC with a roughly 5% LC benefit for every 10 Gy increase in BED with higher VCF rates compared to MF-SRS. If LC is the goal of treatment, then SRS may be a preferred treatment modality. However, these results are hypothesis-generating, and prospective randomized clinical trials are indicated to definitively address the question of whether SRS results in improved LC compared to RT.
Topics: Brain Neoplasms; Crocus; Fractures, Compression; Humans; Prospective Studies; Radiosurgery; Retrospective Studies; Spinal Fractures; Spinal Neoplasms; Treatment Outcome
PubMed: 32114269
DOI: 10.1016/j.radonc.2020.01.030 -
International Journal of Radiation... May 2020To perform a systematic review and pooled meta-analysis of adrenal metastasis stereotactic body radiation therapy (SBRT) outcomes, treatment characteristics, and... (Meta-Analysis)
Meta-Analysis
PURPOSE
To perform a systematic review and pooled meta-analysis of adrenal metastasis stereotactic body radiation therapy (SBRT) outcomes, treatment characteristics, and toxicity to define the efficacy and propose guidelines for intervention.
METHODS AND MATERIALS
We performed a comprehensive literature search of the Embase and PubMed databases of studies reporting outcome or toxicity data for photon-based SBRT of adrenal metastases in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We then conducted a meta-analysis to estimate pooled overall response, local control (LC), and overall survival and analyzed these outcomes in the context of dosimetric parameters and toxicity using metaregression.
RESULTS
Thirty-nine studies published between 2009 and 2019 reporting outcomes on 1006 patients were included. The median follow-up was 12 months, and the median biological equivalent dose (BED10, alpha/beta = 10) was 67 Gy. The pooled overall response was 54.6% (95% confidence interval [CI], 46.5%-62.5%). The pooled 1- and 2-year rates of LC were 82% (95% CI, 74%-88%) and 63% (95% CI, 50%-74%), respectively, and the pooled 1- and 2-year overall survival rates were 66% (95% CI, 57%-74%) and 42% (95% CI, 31%-53%), respectively. There was a strong positive association between SBRT dose and 1- and 2-year LC (P < .0001, P = .0002) and an association with 2-year OS (P = .03). Based on a metaregression of dose and LC, BED10 of 60 Gy, 80 Gy, and 100 Gy predicted 1-year LC of 70.5%, 84.8%, and 92.9% and 2-year LC of 47.8%, 70.1%, and 85.6%, respectively. The overall rate of grade 3 or higher toxicity was 1.8%.
CONCLUSIONS
SBRT of adrenal metastases provides good 1-year LC with an excellent safety profile, and dose escalation may be associated with improved LC. Prospective studies are needed to validate these findings and determine whether there are subsets of patients for whom adrenal metastasis-directed SBRT may confer a survival advantage.
Topics: Adrenal Gland Neoplasms; Humans; Patient Reported Outcome Measures; Radiosurgery; Safety
PubMed: 32001383
DOI: 10.1016/j.ijrobp.2020.01.017 -
Clinical Neurology and Neurosurgery Mar 2018Cushing once described craniopharyngiomas as the most forbidding tumor; and, despite surgical advances decades later, craniopharyngioma resection is still extremely...
Cushing once described craniopharyngiomas as the most forbidding tumor; and, despite surgical advances decades later, craniopharyngioma resection is still extremely complex due to its location and infiltration into local structures, making gross total resection challenging. Adjuvant treatments include radiation and chemotherapy, but intratumoral therapy may emerge as an adjuvant treatment for craniopharyngiomas. Here, we present a review of the literature on this treatment modality; and, summarize the available reported cases to underline usefulness and effectiveness of this treatment method. Our review of the literature included all articles from MEDLINE/PubMed and Ovid from 1974 to 2017. All articles were assessed for relevancy before inclusion into this review. Although the role for intratumoral therapy is unclear, multiple studies have reported efficacy in the treatment of craniopharyngiomas, and current results are promising. Out of the intratumoral agents utilized, intratumoral alpha interferon seems to provide the best response and least side effects for the treatment of craniopharyngiomas. The use of intratumoral therapy has led to delay in treatment with definitive surgery or radiation, both of which are associated with significant morbidities, detrimental in developmental years of childhood. Out of the intratumoral agents utilized, intratumoral alpha interferon seems to provide the best response and least side effects for the treatment of craniopharyngiomas. These findings need to be explored further with randomized controlled trials, outlining a standard dosing regimen. Furthermore, trials in craniopharyngioma patients with these combination therapies must be performed to determine the optimal therapeutic regimen for the successful treatment of these patients.
Topics: Antineoplastic Agents; Craniopharyngioma; Humans; Immunologic Factors; Injections, Intralesional; Interferon-alpha; Pituitary Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 29408768
DOI: 10.1016/j.clineuro.2018.01.039 -
International Journal of Radiation... Jun 2024Reirradiation is increasingly used in children and adolescents/young adults (AYA) with recurrent primary central nervous system tumors. The Pediatric Normal Tissue... (Review)
Review
PURPOSE
Reirradiation is increasingly used in children and adolescents/young adults (AYA) with recurrent primary central nervous system tumors. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) reirradiation task force aimed to quantify risks of brain and brain stem necrosis after reirradiation.
METHODS AND MATERIALS
A systematic literature search using the PubMed and Cochrane databases for peer-reviewed articles from 1975 to 2021 identified 92 studies on reirradiation for recurrent tumors in children/AYA. Seventeen studies representing 449 patients who reported brain and brain stem necrosis after reirradiation contained sufficient data for analysis. While all 17 studies described techniques and doses used for reirradiation, they lacked essential details on clinically significant dose-volume metrics necessary for dose-response modeling on late effects. We, therefore, estimated incidences of necrosis with an exact 95% CI and qualitatively described data. Results from multiple studies were pooled by taking the weighted average of the reported crude rates from individual studies.
RESULTS
Treated cancers included ependymoma (n = 279 patients; 7 studies), medulloblastoma (n = 98 patients; 6 studies), any CNS tumors (n = 62 patients; 3 studies), and supratentorial high-grade gliomas (n = 10 patients; 1 study). The median interval between initial and reirradiation was 2.3 years (range, 1.2-4.75 years). The median cumulative prescription dose in equivalent dose in 2-Gy fractions (EQD2; assuming α/β value = 2 Gy) was 103.8 Gy (range, 55.8-141.3 Gy). Among 449 reirradiated children/AYA, 22 (4.9%; 95% CI, 3.1%-7.3%) developed brain necrosis and 14 (3.1%; 95% CI, 1.7%-5.2%) developed brain stem necrosis with a weighted median follow-up of 1.6 years (range, 0.5-7.4 years). The median cumulative prescription EQD2 was 111.4 Gy (range, 55.8-141.3 Gy) for development of any necrosis, 107.7 Gy (range, 55.8-141.3 Gy) for brain necrosis, and 112.1 Gy (range, 100.2-117 Gy) for brain stem necrosis. The median latent period between reirradiation and the development of necrosis was 5.7 months (range, 4.3-24 months). Though there were more events among children/AYA undergoing hypofractionated versus conventionally fractionated reirradiation, the differences were not statistically significant (P = .46).
CONCLUSIONS
Existing reports suggest that in children/AYA with recurrent brain tumors, reirradiation with a total EQD2 of about 112 Gy is associated with an approximate 5% to 7% incidence of brain/brain stem necrosis after a median follow-up of 1.6 years (with the initial course of radiation therapy being given with conventional prescription doses of ≤2 Gy per fraction and the second course with variable fractionations). We recommend a uniform approach for reporting dosimetric endpoints to derive robust predictive models of late toxicities following reirradiation.
Topics: Humans; Re-Irradiation; Necrosis; Child; Neoplasm Recurrence, Local; Central Nervous System Neoplasms; Adolescent; Brain; Brain Stem; Ependymoma; Young Adult; Child, Preschool; Medulloblastoma; Radiation Injuries
PubMed: 38300187
DOI: 10.1016/j.ijrobp.2023.12.043 -
Frontiers in Oncology 2021We report the first case of hepatoid adenocarcinoma of the lung (HAL) with PIK3CA mutation. In addition, we analyzed data from HAL cases over the past 40 years to study...
OBJECTIVES
We report the first case of hepatoid adenocarcinoma of the lung (HAL) with PIK3CA mutation. In addition, we analyzed data from HAL cases over the past 40 years to study its main treatment methods, prognosis, and the relationship between prognosis and the serum alpha-fetoprotein (AFP) level before treatment.
METHODS
We report a 66-year-old male case who was diagnosed with locally advanced HAL with PIK3CA mutation and carried out a systematic literature search for HAL cases documented between 1981 and 2020. General patient information including case characteristics was extracted and summarized. The median OS (mOS) of HAL patients was determined using the KM survival curve. The Cox proportional hazards regression model was used to evaluate the effect of tumor size, location, and serum AFP value before treatment and radical surgery (RS) on the prognosis of patients.
RESULTS
A total of 46 studies including 51 HAL patients was included in our review. Our study revealed that 52.9% of tumors were located in the upper lobe of the right lung. The proportion of serum AFP-positive patients before treatment, early-stage patients (TNM stage I and II), and patients who had received surgery were 69.2%, 34.1%, and 40%, respectively. The mOS of HAL patients was 16.0 months. The 2-year and 5-year survival rates of the patients were 35.3% and 8.0%, respectively. In the subgroup analysis, the 2-year survival rate for patients who received RS was 62.5%, while for patients who were unable to undergo RS, it was only 12.5% ( = 0.009). The Cox proportional hazards regression model indicated that RS can significantly improve the prognosis of HAL patients ( = 0.011), although the location and size of tumor as well as the serum AFP value before treatment had no significant effect on their prognosis ( = 0.82, = 0.96, = 0.25).
CONCLUSIONS
HAL patients have a poor prognosis, and the survival benefits for patients receiving chemoradiotherapy or chemotherapy alone appear to be limited. We demonstrate statistically for the first time that pretreatment serum AFP values are not related to the prognosis of HAL patients and RS can significantly improve patient prognosis.
PubMed: 34422656
DOI: 10.3389/fonc.2021.702216