-
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 -
Life Sciences Sep 2021Pneumonitis and lung fibrosis, as the most common compliances of lung irradiation, can affect the quality of life. The use of radio-protective agents can ameliorate...
PURPOSE
Pneumonitis and lung fibrosis, as the most common compliances of lung irradiation, can affect the quality of life. The use of radio-protective agents can ameliorate these injuries. This study aimed to review the potential protective role of melatonin in the treatment of radiation-induced Pneumonitis and lung fibrosis.
METHODS
The current systematic study was conducted based on PRISMA guidelines to identify relevant literature on " the effect of melatonin on radiation-induced pneumonitis and lung fibrosis" in the electronic databases of Web of Science, Embase, PubMed, and Scopus up to January 2021. Eighty-one articles were screened in accordance with the inclusion and exclusion criteria of the study. Finally, eight articles were included in this systematic review.
RESULTS
The finding showed that the lung irradiation-induced pneumonitis and lung fibrosis. The co-treatment with melatonin could alleviate these compliances through its anti-oxidant and anti-inflammatory actions. Melatonin through upregulation of some enzymes such as catalase, superoxide dismutase, glutathione, NADPH oxidases 2 and 4, dual oxidases 1 and 2, and also downregulation of malondialdehyde reduced oxidative stress following lung radiation. Moreover, melatonin through its anti-inflammatory effects, can attenuate the increased levels of nuclear factor kappa B, tumor necrosis factor alpha, transforming growth factor beta 1, SMAD2, interleukin (IL)-4, IL-4 receptor-a1 (IL4ra1), and IL-1 beta following lung radiation. The histological damages induced by ionizing radiation were also alleviated by co-treatment with melatonin.
CONCLUSION
According to the obtained results, it was found that melatonin can have anti-pneumonitis and anti-fibrotic following lung irradiation.
Topics: Animals; Humans; Lung; Lung Neoplasms; Melatonin; Pneumonia; Pulmonary Fibrosis; Radiation Injuries; Radiation-Protective Agents
PubMed: 34146555
DOI: 10.1016/j.lfs.2021.119721 -
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 -
International Journal of Radiation... Oct 2021Neoadjuvant concurrent chemoradiation therapy (nCRT) plus surgery has been a standard treatment for locoregionally advanced esophageal cancer and carcinoma of the... (Comparative Study)
Comparative Study
Comparison of Clinical Efficacy of Neoadjuvant Chemoradiation Therapy Between Lower and Higher Radiation Doses for Carcinoma of the Esophagus and Gastroesophageal Junction: A Systematic Review.
PURPOSE
Neoadjuvant concurrent chemoradiation therapy (nCRT) plus surgery has been a standard treatment for locoregionally advanced esophageal cancer and carcinoma of the gastroesophageal junction (EC/GEJ), but the optimal preoperative radiation dose is still unclear. We performed this systematic review to explore the treatment efficacy and toxicity of different radiation dose levels and find an optimal dose-fractionation strategy in EC/GEJ patients receiving nCRT.
METHODS AND MATERIALS
Embase and Ovid Medline were searched for articles involving cases of operable squamous and adenocarcinoma of the esophagus and GEJ in which patients received nCRT up to a dose of 50.4 Gy in 28 fractions that were published until July 2019, when the search was performed. Physical dose distributions were converted to biologically equivalent doses (BEDs), which were described in units of gray (alpha/beta). Pooled rates of overall survival (OS), progression-free survival (PFS), failure patterns, and toxicities were compared between lower-dose radiation therapy (LDRT; BED ≤48.85 Gy) and higher-dose radiation therapy (HDRT; BED >48.85 Gy) for patients treated with nCRT.
RESULTS
A total of 110 studies with 7577 EC/GEJ patients receiving nCRT were included in this pooled analysis. Both the PFS and OS rates of patients receiving LDRT were significantly higher than those of patients receiving HDRT. Patients receiving LDRT had improved safety regarding treatment-related adverse events and lower distant failure rates than patients receiving HDRT. Utilization of modern radiation therapy (RT) techniques, including 3-dimensional conformal RT and intensity modulated RT, was associated with improved oncologic outcomes compared with 2-dimensional methods. Subgroup analysis showed that EC/GEJ patients receiving conventionally fractionated radiation to a dose of 40.0 to 41.4 Gy in 20-23 fractions showed improved OS compared with those receiving radiation above this dose.
CONCLUSIONS
Based on the limited data, nCRT using BED ≤48.85 Gy was suitable for locoregionally advanced, resectable EC/GEJ. A total dose of 40.0 to 41.4 Gy in 20 to 23 fractions using modern RT techniques might provide the optimal therapeutic ratio.
Topics: Chemoradiotherapy; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagogastric Junction; Humans; Neoadjuvant Therapy; Radiotherapy Dosage; Treatment Failure; Treatment Outcome
PubMed: 33964352
DOI: 10.1016/j.ijrobp.2021.04.031 -
Clinical Oral Investigations Apr 2021This integrative review aimed to report the toxic effect of submicron and nano-scale commercially pure titanium (cp Ti) debris on cells of peri-implant tissues. (Review)
Review
OBJECTIVE
This integrative review aimed to report the toxic effect of submicron and nano-scale commercially pure titanium (cp Ti) debris on cells of peri-implant tissues.
MATERIALS AND METHODS
A systematic search was carried out on the PubMed electronic platform using the following key terms: Ti "OR" titanium "AND" dental implants "AND" nanoparticles "OR" nano-scale debris "OR" nanometric debris "AND" osteoblasts "OR "cytotoxicity" OR "macrophage" OR "mutagenic" OR "peri-implantitis". The inclusion criteria involved articles published in the English language, until December 26, 2020, reporting the effect of nano-scale titanium particles as released from dental implants on the toxicity and damage of osteoblasts.
RESULTS
Of 258 articles identified, 14 articles were selected for this integrative review. Submicron and nano-scale cp Ti particles altered the behavior of cells in culture medium. An inflammatory response was triggered by macrophages, fibroblasts, osteoblasts, mesenchymal cells, and odontoblasts as indicated by the detection of several inflammatory mediators such as IL-6, IL-1β, TNF-α, and PGE2. The formation of a bioactive complex composed of calcium and phosphorus on titanium nanoparticles allowed their binding to proteins leading to the cell internalization phenomenon. The nanoparticles induced mutagenic and carcinogenic effects into the cells.
CONCLUSIONS
The cytotoxic effect of debris released from dental implants depends on the size, concentration, and chemical composition of the particles. A high concentration of particles on nanometric scale intensifies the inflammatory responses with mutagenic potential of the surrounding cells.
CLINICAL RELEVANCE
Titanium ions and debris have been detected in peri-implant tissues with different size, concentration, and forms. The presence of metallic debris at peri-implant tissues also stimulates the migration of immune cells and inflammatory reactions. Cp Ti and TiO micro- and nano-scale particles can reach the bloodstream, accumulating in lungs, liver, spleen, and bone marrow.
Topics: Dental Implants; Humans; Macrophages; Osteoblasts; Peri-Implantitis; Titanium
PubMed: 33616805
DOI: 10.1007/s00784-021-03785-z -
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 -
Journal of the American Academy of... Mar 2021
Meta-Analysis
Incidence of dermatologic adverse events in patients with cancer treated with concurrent immune checkpoint inhibitors and radiation therapy: A systematic review and meta-analysis.
Topics: Chemoradiotherapy; Clinical Trials as Topic; Drug Eruptions; Humans; Immune Checkpoint Inhibitors; Incidence; Neoplasms; Radiodermatitis
PubMed: 33137440
DOI: 10.1016/j.jaad.2020.10.071 -
Cytokine Jan 2021COVID-19, as a newly-emerged viral infection has now spread all over the world after originating in Wuhan, China. Pneumonia is the hallmark of the disease, with dyspnea...
BACKGROUND
COVID-19, as a newly-emerged viral infection has now spread all over the world after originating in Wuhan, China. Pneumonia is the hallmark of the disease, with dyspnea in half of the patients and acute respiratory distress syndrome (ARDS) in up to one -third of the cases. Pulmonary edema, neutrophilic infiltration, and inflammatory cytokine release are the pathologic signs of this disease. The anti-inflammatory effect of the photobiomodulation (PBM) has been confirmed in many previous studies. Therefore, this review study was conducted to evaluate the direct effect of PBM on the acute lung inflammation or ARDS and also accelerating the regeneration of the damaged tissues. The indirect effects of PBM on modulation of the immune system, increasing the blood flow and oxygenation in other tissues were also considered.
METHODOLOGY
The databases of PubMed, Cochrane library, and Google Scholar were searched to find the relevant studies. Keywords included the PBM and related terms, lung inflammation, and COVID-19 -related signs. Studies were categorized with respect to the target tissue, laser parameters, and their results.
RESULTS
Seventeen related papers were included in this review. All of them were in animal models. They showed that the PBM could significantly decrease the pulmonary edema, neutrophil influx, and generation of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), intracellular adhesion molecule (ICAM), reactive oxygen species (ROS), isoform of nitric oxide synthase (iNOS), and macrophage inflammatory protein 2 (MIP-2)).
CONCLUSION
Our findings revealed that the PBM could be helpful in reducing the lung inflammation and promoting the regeneration of the damaged tissue. PBM can increase the oxygenation indirectly in order to rehabilitate the affected organs. Thus, the infra-red lasers or light-emitting diodes (LEDs) are recommended in this regard.
Topics: COVID-19; Cytokines; Humans; Low-Level Light Therapy; Lung; Macrophages; Neutrophils; Pneumonia; PubMed; Pulmonary Edema; Reactive Oxygen Species; Respiratory Distress Syndrome
PubMed: 33128927
DOI: 10.1016/j.cyto.2020.155312 -
Advances in Radiation Oncology 2020Reirradiation (re-RT) using external beam radiation therapy (EBRT) is a novel salvage strategy for local failure in prostate cancer. We performed a systematic review...
PURPOSE
Reirradiation (re-RT) using external beam radiation therapy (EBRT) is a novel salvage strategy for local failure in prostate cancer. We performed a systematic review describing oncologic and toxicity outcomes for salvage EBRT/stereotactic radiation therapy (SBRT) re-RT.
METHODS AND MATERIALS
A International Prospective Register of Systematic Reviews registered (#141466) systematic review, meta-analysis, and meta-regression was conducted using preferred reporting items for systematic reviews and meta-analyses guidelines. PubMed and EMBASE were searched from inception through September 2019. Outcome measures included local control (LC), biochemical relapse free survival (BRFS), and ≥grade 3 genitourinary (GU)/gastrointestinal (GI) toxicity. EBRT and SBRT data were collected separately. Meta-regression explored disease and toxicity outcomes as a function of equivalent dose in 2 Gy fractions (EQD2), length of follow-up, and partial versus whole prostate reirradiation.
RESULTS
Nineteen studies representing 13 cohorts were included (428 patients). Weighted mean follow-up was 26.1 months. Median re-RT EQD2 was 77.1 Gy (α/β = 1.5), with 92% of patients receiving SBRT, 52.1% of patients receiving partial prostate re-RT, and 30.1% of patients receiving androgen deprivation therapy with re-RT. LC was 83.2% (95% confidence interval [CI], 75.5%-90.9%) and BRFS was 59.3% (47.9%-70.7%). Reported late toxicity ≥grade 3 was 3.4% (95% CI, 1.0%-5.8%) for GU and 2.0% (95% CI, 0.1%-4.0%) for GI. Meta-regression found higher LC, BRFS, and reported GU/GI toxicity with increasing EQD2, with partial prostate re-RT associated with less reported GU/GI toxicity and no detriment to LC and BRFS.
CONCLUSIONS
Salvage re-RT using EBRT, particularly with SBRT, is an emerging technique to treat isolated local failure of prostate cancer. With short-term follow-up, LC, BRFS, and reported toxicities appear reasonable, although further follow-up is required before definitive statements on late toxicities can be made. Our review is limited by incomplete reporting of androgen deprivation therapy use in the primary literature. Further prospective studies and longer follow-up are needed before considering re-RT as standard practice.
PubMed: 33083660
DOI: 10.1016/j.adro.2020.04.022 -
SAGE Open Medicine 2020In this study, we evaluated the use and the contribution of radiopharmaceuticals to the field of lung neoplasms imaging using positron emission tomography/computed... (Review)
Review
INTRODUCTION
In this study, we evaluated the use and the contribution of radiopharmaceuticals to the field of lung neoplasms imaging using positron emission tomography/computed tomography.
METHODS
We conducted review of the current literature at PubMed/MEDLINE until February 2020. The search language was English.
RESULTS
The most widely used radiopharmaceuticals are the following:Experimental/pre-clinical approaches: (18)F-Misonidazole (18F-MISO) under clinical development, D(18)F-Fluoro-Methyl-Tyrosine (18F-FMT), 18F-FAMT (L-[3-18F] (18)F-Fluorothymidine (18F-FLT)), (18)F-Fluoro-Azomycin-Arabinoside (18F-FAZA), (68)Ga-Neomannosylated-Human-Serum-Albumin (68Ga-MSA) (23), (68)Ga-Tetraazacyclododecane (68Ga-DOTA) (as theranostic agent), (11)C-Methionine (11C-MET), 18F-FPDOPA, αβ integrin, Ga-RGD, Cu-DOTA-RGD, F-Alfatide, Folate Radio tracers, and immuno-positron emission tomography radiopharmaceutical agents.Clinically approved procedures/radiopharmaceuticals agents: (18)F-Fluoro-Deoxy-Glucose (18F-FDG), (18)F-sodium fluoride (18F-NaF) (bone metastases), and (68)Ga-Tetraazacyclododecane (68Ga-DOTA). The quantitative determination and the change in radiopharmaceutical uptake parameters such as standard uptake value, metabolic tumor volume, total lesion glycolysis, FAZA tumor to muscle ratio, standard uptake value tumor to liver ratio, standard uptake value tumor to spleen ratio, standard uptake value maximum ratio, and the degree of hypoxia have prognostic and predictive (concerning the therapeutic outcome) value. They have been associated with the assessment of overall survival and disease free survival. With the positron emission tomography/computed tomography radiopharmaceuticals, the sensitivity and the specificity of the method have increased.
CONCLUSION
In terms of lung cancer, positron emission tomography/computed tomography may have clinical application and utility (a) in personalizing treatment, (b) as a biomarker for the estimation of overall survival, disease free survival, and (c) apply a cost-effective patient approach because it reveals focuses of the disease, which are not found with the other imaging methods.
PubMed: 33062275
DOI: 10.1177/2050312120961594