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Scientific Reports Sep 2022Many studies on ionizing radiation (IR) exposure during childhood have shown deleterious effects on the central nervous system (CNS), however results regarding adult... (Meta-Analysis)
Meta-Analysis
Many studies on ionizing radiation (IR) exposure during childhood have shown deleterious effects on the central nervous system (CNS), however results regarding adult exposure are inconsistent, and no systematic reviews have been performed. The objectives are to synthesize the findings and draw evidence-based conclusions from epidemiological studies on the risk of benign and malignant brain and CNS tumors in humans exposed to low-to-moderate doses (< 0.5 Gy) of IR during adulthood/young adulthood. A systematic literature search of four electronic databases, supplemented by a hand search, was performed to retrieve relevant epidemiological studies published from 2000 to 2022. Pooled excess relative risk (ERR) was estimated using a random effect model. Eighteen publications were included in the systematic review and twelve out of them were included in a meta-analysis. The following IR sources were considered: atomic bombs, occupational, and environmental exposures. No significant dose-risk association was found for brain/CNS tumors (ERR at 100 mGy = - 0.01; 95% CI: - 0.05, 0.04). Our systematic review and meta-analysis did not show any association between exposure to low-to-moderate doses of IR and risk of CNS tumors. Further studies with histological information and precise dose assessment are needed.
Topics: Adult; Central Nervous System Neoplasms; Environmental Exposure; Humans; Nuclear Weapons; Occupational Exposure; Radiation Exposure; Radiation, Ionizing; Young Adult
PubMed: 36171442
DOI: 10.1038/s41598-022-20462-7 -
Cancer Treatment Reviews Mar 2017It is assumed that DNA methylation plays a key role in both tumour development and therapy resistance. Demethylating agents have been shown to be effective in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It is assumed that DNA methylation plays a key role in both tumour development and therapy resistance. Demethylating agents have been shown to be effective in the treatment of haematological malignancies. Based on encouraging preclinical results, demethylating agents may also be effective in solid tumours. This systematic review summarizes the evidence of the effect of demethylating agents on clinical response, methylation and the immune system in solid tumours.
METHODS
We conducted a systematic literature search from 1949 to December 2016, according to the PRISMA guidelines. Studies which evaluated treatment with azacitidine, decitabine, guadecitabine, hydralazine, procaine, MG98 and/or zebularine in patients with solid tumours were included. Data on clinical response, effects on methylation and immune response were extracted.
RESULTS
Fifty-eight studies were included: in 13 studies complete responses (CR) were observed, 35 studies showed partial responses (PR), 47 studies stable disease (SD) and all studies except two showed progressive disease (PD). Effects on global methylation were observed in 11/15 studies and demethylation/re-expression of tumour specific genes was seen in 15/17 studies. No clear correlation between (de)methylation and clinical response was observed. In 14 studies immune-related responses were reported, such as re-expression of cancer-testis antigens and upregulation of interferon genes.
CONCLUSION
Demethylating agents are able to improve clinical outcome and alter methylation status in patients with solid tumours. Although beneficial effect has been shown in individual patients, overall response is limited. Further research on biomarker predicting therapy efficacy is indicated, particularly in earlier stage and highly methylated tumours.
Topics: Antimetabolites, Antineoplastic; Azacitidine; Cytidine; DNA Methylation; Decitabine; Humans; Hydralazine; Immune System; Methylation; Neoplasms; Procaine; Treatment Outcome
PubMed: 28189913
DOI: 10.1016/j.ctrv.2017.01.004 -
Radiotherapy and Oncology : Journal of... Jan 2020Pseudoprogression (PsP) following radiation therapy (RT) for low grade glioma (LGG, WHO grade I and II), including both photon-based intensity-modulated RT (IMRT) and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pseudoprogression (PsP) following radiation therapy (RT) for low grade glioma (LGG, WHO grade I and II), including both photon-based intensity-modulated RT (IMRT) and proton beam therapy (PBT), has been described. However, its incidence has yet to be consolidated. The aim of this systematic review and meta-analysis was to pool the current literature and establish the incidence of PsP in these groups to better inform surveillance protocols in the future.
METHODS
Searches of 4 electronic databases from inception to April 2019 were conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. The incidence of outcomes was then extracted and pooled by random-effects meta-analysis of proportions.
RESULTS
A total of 5 pediatric and 4 adult cohort studies describing 517 and 424 LGG subjects respectively satisfied all selection criteria. The estimated incidences of PsP in pediatric subjects following IMRT and PBT were 33% (95% CI, 20-47%) and 34% (95% CI, 23-45%) respectively, with no difference between modalities. The estimated incidences of PsP in adult subjects following IMRT and PBT were 18% (95% CI, 12-25%) and 30% (95% CI, 21-39%) respectively, with PsP significantly less common following IMRT than PBT (P-heterogeneity = 0.04). Median time from radiation initiation to first detection of PsP ranged from 6 to 12 months across all modalities and age groups.
CONCLUSIONS
The incidence of PsP following both IMRT and PBT in the management of pediatric and adult LGG is not negligible, and should therefore be recognized as a pertinent sequala within the first year at least following treatment. However, a lack of accountability in the current literature for the differences in PsP interpretation, radiation modality, radiobiology and molecular biology of LGGs precludes any firm surveillance recommendations at this time.
Topics: Adult; Brain Neoplasms; Child; Disease Progression; Glioma; Humans; Proton Therapy; Radiotherapy, Intensity-Modulated
PubMed: 31431375
DOI: 10.1016/j.radonc.2019.07.013 -
Scientific Reports Sep 2018Targeted therapy is lagging behind in esophageal adenocarcinoma (EAC). To guide the development of new treatment strategies, we provide an overview of the prognostic... (Meta-Analysis)
Meta-Analysis
Targeted therapy is lagging behind in esophageal adenocarcinoma (EAC). To guide the development of new treatment strategies, we provide an overview of the prognostic biomarkers in resectable EAC treated with curative intent. The Medline, Cochrane and EMBASE databases were systematically searched, focusing on overall survival (OS). The quality of the studies was assessed using a scoring system ranging from 0-7 points based on modified REMARK criteria. To evaluate all identified prognostic biomarkers, the hallmarks of cancer were adapted to fit all biomarkers based on their biological function in EAC, resulting in the features angiogenesis, cell adhesion and extra-cellular matrix remodeling, cell cycle, immune, invasion and metastasis, proliferation, and self-renewal. Pooled hazard ratios (HR) and 95% confidence intervals (CI) were derived by random effects meta-analyses performed on each hallmarks of cancer feature. Of the 3298 unique articles identified, 84 were included, with a mean quality of 5.9 points (range 3.5-7). The hallmarks of cancer feature 'immune' was most significantly associated with worse OS (HR 1.88, (95%CI 1.20-2.93)). Of the 82 unique prognostic biomarkers identified, meta-analyses showed prominent biomarkers, including COX-2, PAK-1, p14ARF, PD-L1, MET, LC3B, IGFBP7 and LGR5, associated to each hallmark of cancer.
Topics: Adenocarcinoma; Biomarkers, Tumor; Esophageal Neoplasms; Humans; Prognosis; Proportional Hazards Models; Survival Analysis
PubMed: 30185893
DOI: 10.1038/s41598-018-31548-6 -
Cancers Apr 2019The tumor microenvironment plays an important role in the initiation and progression of pancreatic adenocarcinoma (PDAC). In this systematic review, we provide an... (Review)
Review
The tumor microenvironment plays an important role in the initiation and progression of pancreatic adenocarcinoma (PDAC). In this systematic review, we provide an overview of clinical trials with stroma-targeting agents. We systematically searched MEDLINE/PubMed and the EMBASE database, using the PRISMA guidelines, for eligible clinical trials. In total, 2330 records were screened, from which we have included 106 articles. A meta-analysis could be performed on 51 articles which describe the targeting of the vascular endothelial growth factor (VEGF) pathway, and three articles which describe the targeting of hyaluronic acid. Anti-VEGF therapies did not show an increase in median overall survival (OS) with combined hazard ratios (HRs) of 1.01 (95% confidence interval (CI) 0.90-1.13). Treatment with hyaluronidase PEGPH20 showed promising results, but, thus far, only in combination with gemcitabine and nab-paclitaxel in selected patients with hyaluronic acid (HA) tumors: An increase in median progression free survival (PFS) of 2.9 months, as well as a HR of 0.51 (95% CI 0.26-1.00). In conclusion, we found that anti-angiogenic therapies did not show an increased benefit in median OS or PFS in contrast to promising results with anti-hyaluronic acid treatment in combination with gemcitabine and nab-paclitaxel. The PEGPH20 clinical trials used patient selection to determine eligibility based on tumor biology, which underlines the importance to personalize treatment for pancreatic cancer patients.
PubMed: 31035512
DOI: 10.3390/cancers11050588 -
International Journal of Health Policy... 2023Circular economy (CE) has raised great interest as a concept and as a development model worldwide. This concept aims to provide a substitute for the linear economic... (Review)
Review
BACKGROUND
Circular economy (CE) has raised great interest as a concept and as a development model worldwide. This concept aims to provide a substitute for the linear economic model, which was based on production and consumption, continuous growth, and resources depletion. CE allows a greener economy with sustainable development and promotes more balanced societies. The healthcare sector is a major contributor to the climate crisis, with a carbon footprint representing 4.4% of global net emissions. It is thus essential to rethink the applicability of CE in healthcare.
METHODS
We conducted a scoping review guided by the Arksey and O'Malley methodological framework and utilised PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) checklist. A systematic search from MEDLINE complete, SCOPUS, and Web of Science databases published between 1992 and 2022.
RESULTS
Through database searching a total of 1018 records were identified and 475 duplicates were removed. From the total search, 543 articles were screened by title/abstract according to the inclusion and exclusion criteria. After screening, 38 full-text articles were selected and assessed for eligibility. Forty-seven additional records were also identified through other sources and screened for eligibility. Other sources included: 12 articles from snowballing of previous papers; 9 articles following peer-reviewers suggestions; 19 reports from relevant organisations in CE and healthcare; two webpage, and one book.
CONCLUSION
Specific areas were identified where hospitals could reduce their greenhouse gas (GHG) emissions and consequently their negative environmental impact, namely through waste management, energy, water, transportation/travel, hospital design, food optimisation, green procurement, and behaviour. Also, lack of staff awareness and knowledge of the environmental impact of healthcare, and hospitals sustainability were identified as major contributors.
Topics: Humans; Conservation of Natural Resources; Hospitals; Delivery of Health Care
PubMed: 37579377
DOI: 10.34172/ijhpm.2023.6947 -
Cancer Metastasis Reviews Mar 2015A nearly universal feature of pancreatic ductal adenocarcinoma (PDAC) is an extensive presence of activated stroma. This stroma is thought to aid in various... (Review)
Review
A nearly universal feature of pancreatic ductal adenocarcinoma (PDAC) is an extensive presence of activated stroma. This stroma is thought to aid in various tumor-promoting processes and hampers response to therapy. Here, we aim to evaluate the evidence that supports this role of the stroma in PDAC with functional experiments in relevant models, discuss the clinical trials that have aimed to target the stroma in this disease, and examine recent work that explains why these clinical trials based on stroma-targeting strategies have thus far not achieved the expected success. We systematically searched PubMed through August 2014 with no restrictions to identify published peer-reviewed research articles assessing the effect of targeting the stroma on tumor growth or metastases in preclinical animal models. Five hundred and thirty articles were extracted of which 31 were included in the analysis. Unfortunately, due to the large variety in models and outcome measures, we could not perform a meta-analysis of our data. We find that despite an abundance of positive outcomes reported in previous studies on stroma targeting, a strong discrepancy exists with the outcomes of clinical trials and the more recent preclinical work that is in line with these trials. We explain the incongruities by the duration of stroma targeting and propose that chronic stroma targeting treatment is possibly detrimental in the treatment of this disease.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Humans; Pancreas; Pancreatic Neoplasms; Stromal Cells; Treatment Outcome; Tumor Microenvironment
PubMed: 25566685
DOI: 10.1007/s10555-014-9541-1 -
The Cochrane Database of Systematic... Mar 2017This is an update of the review published in Issue 4, 2003. Bone metastasis cause severe pain as well as pathological fractures, hypercalcaemia and spinal cord... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of the review published in Issue 4, 2003. Bone metastasis cause severe pain as well as pathological fractures, hypercalcaemia and spinal cord compression. Treatment strategies currently available to relieve pain from bone metastases include analgesia, radiotherapy, surgery, chemotherapy, hormone therapy, radioisotopes and bisphosphonates.
OBJECTIVES
To determine efficacy and safety of radioisotopes in patients with bone metastases to improve metastatic pain, decrease number of complications due to bone metastases and improve patient survival.
SEARCH METHODS
We sought randomised controlled trials (RCTs) in MEDLINE, EMBASE, CENTRAL, and the PaPaS Trials Register up to October 2010.
SELECTION CRITERIA
Studies selected had metastatic bone pain as a major outcome after treatment with a radioisotope, compared with placebo or another radioisotope.
DATA COLLECTION AND ANALYSIS
We assessed the risk of bias of included studies by their sequence generation, allocation concealment, blinding of study participants, researchers and outcome assessors, and incomplete outcome data. Two review authors extracted data. We performed statistical analysis as an "available case" analysis, and calculated global estimates of effect using a random-effects model. We also performed an intention-to-treat (ITT) sensitivity analysis.
MAIN RESULTS
This update includes 15 studies (1146 analyzed participants): four (325 participants) already included and 11 new (821 participants). Only three studies had a low risk of bias. We observed a small benefit of radioisotopes for complete relief (risk ratio (RR) 2.10, 95% CI 1.32 to 3.35; Number needed to treat to benefit (NNT) = 5) and complete/partial relief (RR 1.72, 95% CI 1.13 to 2.63; NNT = 4) in the short and medium term (eight studies, 499 participants). There is no conclusive evidence to demonstrate that radioisotopes modify the use of analgesia with respect to placebo. Leucocytopenia and thrombocytopenia are secondary effects significantly associated with the administration of radioisotopes (RR 5.03; 95% CI 1.35 to 18.70; Number needed to treat to harm (NNH) = 13). Pain flares were not higher in the radioisotopes group (RR 0.74; 95% CI 0.27 to 2.06). There are scarce data of moderate quality when comparing Strontium-89 (Sr) with Samarium-153 (Sm), Rhenium-186 (Re) and Phosphorus-32 (P). We observed no significant differences between treatments. Similarly, we observed no differences when we compared different doses of Sm (0.5 versus 1.0 mCi).
AUTHORS' CONCLUSIONS
This update adds new evidence on efficacy of radioisotopes versus placebo, Sr compared with other radioisotopes, and dose-comparisons of Sm and Re. There is some evidence indicating that radioisotopes may provide complete reduction in pain over one to six months with no increase in analgesic use, but severe adverse effects (leucocytopenia and thrombocytopenia) are frequent.
Topics: Bone Neoplasms; Fractures, Bone; Humans; Hypercalcemia; Pain; Pain Measurement; Phosphorus Radioisotopes; Radioisotopes; Randomized Controlled Trials as Topic; Ruthenium Radioisotopes; Samarium; Spinal Cord Compression; Strontium Radioisotopes
PubMed: 28334435
DOI: 10.1002/14651858.CD003347.pub3 -
Brachytherapy 2014To review and analyze the published data on high-dose-rate brachytherapy as monotherapy in the treatment of prostate cancer. (Review)
Review
PURPOSE
To review and analyze the published data on high-dose-rate brachytherapy as monotherapy in the treatment of prostate cancer.
METHODS
A literature search and a systematic review of the high-dose-rate (HDR) brachytherapy (monotherapy) prostate literature were performed on PubMed using "high-dose-rate, brachytherapy, prostate, monotherapy" as search terms. More than 80 articles and abstracts published between 1990 and 2013 were identified. Data tables were generated and summary descriptions created. Commentary and opinion was formulated through discussion and consensus based on the critical review of the literature and the author's combined personal experience and knowledge.
RESULTS
Thirteen articles reported clinical outcome and toxicity with followup ranging from 1.5 to 8.0 years. Results were available for all risk groups. A variety of dose and fractionation schedules were described. Prostate-specific antigen progression-free survival ranged from 79% to 100% and local control from 97% to 100%. The toxicity rates were low. Genitourinary toxicity, mainly frequency/urgency, was 0-16% (Grade 3). Gastrointestinal toxicity was 0-2% (Grade 3). Erectile function preservation was 67-89%. The radiobiological, clinical, and technical features of HDR brachytherapy were reviewed and discussed.
CONCLUSIONS
Consistently high local tumor control and low complications rates are reported with HDR monotherapy. It provides reproducible high-quality dosimetry, it has an advantage from a radiobiology perspective, and it has a good radiation safety profile. HDR brachytherapy is a safe and effective local treatment modality for prostate cancer.
Topics: Brachytherapy; Disease-Free Survival; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy Dosage; Tomography, X-Ray Computed
PubMed: 25085454
DOI: 10.1016/j.brachy.2014.03.002 -
Strahlentherapie Und Onkologie : Organ... Dec 2023Tumor-associated macrophages (TAMs) are the most represented cells of the immune system in the tumor microenvironment (TME). Besides its effects on cancer cells,... (Review)
Review
OBJECTIVE
Tumor-associated macrophages (TAMs) are the most represented cells of the immune system in the tumor microenvironment (TME). Besides its effects on cancer cells, radiation therapy (RT) can alter TME composition. With this systematic review, we provide a better understanding on how RT can regulate macrophage characterization, namely the M1 antitumor and the M2 protumor polarization, with the aim of describing new effective RT models and exploration of the possibility of integrating radiation with other available therapies.
METHODS
A systematic search in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was carried out in PubMed, Google Scholar, and Scopus. Articles from January 2000 to April 2020 which focus on the role of M1 and M2 macrophages in the response to RT were identified.
RESULTS
Of the 304 selected articles, 29 qualitative summary papers were included in our analysis (16 focusing on administration of RT and concomitant systemic molecules, and 13 reporting on RT alone). Based on dose intensity, irradiation was classified into low (low-dose irradiation, LDI; corresponding to less than 1 Gy), moderate (moderate-dose irradiation, MDI; between 1 and 10 Gy), and high (high-dose irradiation, HDI; greater than 10 Gy). While HDI seems to be responsible for induced angiogenesis and accelerated tumor growth through early M2-polarized TAM infiltration, MDI stimulates phagocytosis and local LDI may represent a valid treatment option for possible combination with cancer immunotherapeutic agents.
CONCLUSION
TAMs seem to have an ambivalent role on the efficacy of cancer treatment. Radiation therapy, which exerts its main antitumor activity via cell killing, can in turn interfere with TAM characterization through different modalities. The plasticity of TAMs makes them an attractive target for anticancer therapies and more research should be conducted to explore this potential therapeutic strategy.
Topics: Humans; Tumor-Associated Macrophages; Neoplasms; Macrophages; Tumor Microenvironment
PubMed: 37347290
DOI: 10.1007/s00066-023-02097-3