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Journal of the National Cancer Institute Apr 2022The consensus molecular subtypes (CMSs) of colorectal cancer (CRC) capture tumor heterogeneity at the gene-expression level. Currently, a restricted number of molecular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The consensus molecular subtypes (CMSs) of colorectal cancer (CRC) capture tumor heterogeneity at the gene-expression level. Currently, a restricted number of molecular features are used to guide treatment for CRC. We summarize the evidence on the clinical value of the CMSs.
METHODS
We systematically identified studies in Medline and Embase that evaluated the prognostic and predictive value of CMSs in CRC patients. A random-effect meta-analysis was performed on prognostic data. Predictive data were summarized.
RESULTS
In local disease, CMS4 tumors were associated with worse overall survival (OS) compared with CMS1 (hazard ratio [HR] = 3.28, 95% confidence interval = 1.27 to 8.47) and CMS2 cancers (HR = 2.60, 95% confidence interval = 1.93 to 3.50). In metastatic disease, CMS1 consistently had worse survival than CMS2-4 (OS HR range = 0.33-0.55; progression-free survival HR range = 0.53-0.89). Adjuvant chemotherapy in stage II and III CRC was most beneficial for OS in CMS2 and CMS3 (HR range = 0.16-0.45) and not effective in CMS4 tumors. In metastatic CMS4 cancers, an irinotecan-based regimen improved outcome compared with oxaliplatin (HR range = 0.31-0.72). The addition of bevacizumab seemed beneficial in CMS1, and anti-epidermal growth factor receptor therapy improved outcome for KRAS wild-type CMS2 patients.
CONCLUSIONS
The CMS classification holds clear potential for clinical use in predicting both prognosis and response to systemic therapy, which seems to be independent of the classifier used. Prospective studies are warranted to support implementation of the CMS taxonomy in clinical practice.
Topics: Bevacizumab; Biomarkers, Tumor; Colorectal Neoplasms; Gene Expression Profiling; Humans; Oxaliplatin; Prognosis
PubMed: 34077519
DOI: 10.1093/jnci/djab106 -
Cancers May 2024Modern advanced radiotherapy techniques have improved the precision and accuracy of radiotherapy delivery, with resulting plans being highly personalised based on... (Review)
Review
Modern advanced radiotherapy techniques have improved the precision and accuracy of radiotherapy delivery, with resulting plans being highly personalised based on individual anatomy. Adaptation for individual tumour biology remains elusive. There is an unmet need for biomarkers of intrinsic radiosensitivity that can predict tumour response to radiation to facilitate individualised decision-making, dosing and treatment planning. Over the last few decades, the use of high throughput molecular biology technologies has led to an explosion of newly discovered cancer biomarkers. Gene expression signatures are now used routinely in clinic to aid decision-making regarding adjuvant systemic therapy. They have great potential as radiotherapy biomarkers. A previous systematic review published in 2015 reported only five studies of signatures evaluated for their ability to predict radiotherapy benefits in clinical cohorts. This updated systematic review encompasses the expanded number of studies reported in the last decade. An additional 27 studies were identified. In total, 22 distinct signatures were recognised (5 pre-2015, 17 post-2015). Seventeen signatures were 'radiosensitivity' signatures and five were breast cancer prognostic signatures aiming to identify patients at an increased risk of local recurrence and therefore were more likely to benefit from adjuvant radiation. Most signatures (15/22) had not progressed beyond the discovery phase of development, with no suitable validated clinical-grade assay for application. Very few signatures (4/17 'radiosensitivity' signatures) had undergone any laboratory-based biological validation of their ability to predict tumour radiosensitivity. No signatures have been assessed prospectively in a phase III biomarker-led trial to date and none are recommended for routine use in clinical guidelines. A phase III prospective evaluation is ongoing for two breast cancer prognostic signatures. The most promising radiosensitivity signature remains the radiosensitivity index (RSI), which is used to calculate a genomic adjusted radiation dose (GARD). There is an ongoing phase II prospective biomarker-led study of RSI/GARD in triple negative breast cancer. The results of these trials are eagerly anticipated over the coming years. Future work in this area should focus on (1) robust biological validation; (2) building biobanks alongside large radiotherapy randomised controlled trials with dose variance (to demonstrate an interaction between radiosensitivity signature and dose); (3) a validation of clinical-grade cost-effective assays that are deliverable within current healthcare infrastructure; and (4) an integration with biomarkers of other determinants of radiation response.
PubMed: 38792019
DOI: 10.3390/cancers16101942 -
Transfusion Medicine (Oxford, England) Apr 2023Hepatitis C virus (HCV) can be transmitted by blood transfusion. The aim of this meta-analysis is to estimate the anti-HCV reactive rate and to define the demographic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepatitis C virus (HCV) can be transmitted by blood transfusion. The aim of this meta-analysis is to estimate the anti-HCV reactive rate and to define the demographic characteristics of blood donors who have potential threats to blood safety in mainland China for nearly 30 years, in order to provide a safe reference for blood transfusion and corresponding guidance for policymakers to increase blood safety.
MATERIALS AND METHODS
Literature reporting the anti-HCV screening reactive rate in Chinese blood donors was identified by systematic searching of four electronic databases from 1991 to 2017. The Preferred Reporting of Items for Systematic Reviews and Meta-Analyses guidelines were strictly followed, and data manipulation and statistical analysis were performed by Stata 15.0.
RESULTS
Our results showed that the post-donation anti-HCV reactive rate was 0.53% (95% confidence interval [CI], 0.51%-0.55%) with a significant variation from 1.58% (95% CI, 1.13%-2.03%) before 1998 to 0.51% (95% CI, 0.48%-0.53%) after 1998 when the Blood Donation Law was implemented in China. In addition, anti-HCV screening reactive rate for family or replacement donors was significantly higher than that in individual voluntary blood donors.
CONCLUSION
Our results indicated that blood centres in China should convert more eligible first-time donors into repeat donors and turn the 'real family or replacement donors' into individual voluntary blood donors to reduce the risk of transfusion-transmitted HCV. In the meantime, large surveys should be carried out among volunteer donors from high-risk populations.
Topics: Humans; Hepacivirus; Blood Donors; Hepatitis C; Risk Factors; China; Antibodies
PubMed: 36349871
DOI: 10.1111/tme.12935 -
International Journal of Molecular... Jul 2021Medical staff represent the largest group of workers occupationally exposed to ionizing radiation (IR). Chronic exposure to low-dose IR may result in DNA damage and... (Meta-Analysis)
Meta-Analysis
Medical staff represent the largest group of workers occupationally exposed to ionizing radiation (IR). Chronic exposure to low-dose IR may result in DNA damage and genotoxicity associated with increased risk of cancer. This review aims to identify the genotoxicity biomarkers that are the most elevated in IR-exposed vs. unexposed health workers. A systematic review of the literature was performed to retrieve relevant studies with various biomarkers of genotoxicity. Subsequent meta-analyses produced a pooled effect size for several endpoints. The search procedure yielded 65 studies. Chromosome aberrations (CA) and micronuclei (MN) frequencies were significantly different between IR-exposed and unexposed workers (θ = 3.19, 95% CI 1.46-4.93; and θ = 1.41, 95% CI 0.97-1.86, for total aberrant cells and MN frequencies, respectively), which was not the case for ring chromosomes and nucleoplasmic bridges. Although less frequently used, stable translocations, sister chromatid exchanges (SCE) and comet assay endpoints were also statistically different between IR-exposed and unexposed workers. This review confirms the relevance of CA and MN as genotoxicity biomarkers that are consistently elevated in IR-exposed vs. unexposed workers. Other endpoints are strong candidates but require further studies to validate their usefulness. The integration of the identified biomarkers in future prospective epidemiological studies is encouraged.
Topics: Biomarkers; Chromosome Aberrations; DNA Damage; Dose-Response Relationship, Radiation; Health Personnel; Humans; Occupational Exposure; Radiation, Ionizing
PubMed: 34299125
DOI: 10.3390/ijms22147504 -
Radiography (London, England : 1995) Jan 2024
Re Anudjo et al. 'Considerations for environmental sustainability in clinical radiology and radiotherapy practice: A systematic literature review and recommendations for a greener practice'.
PubMed: 38035430
DOI: 10.1016/j.radi.2023.11.003 -
Molecular Diagnosis & Therapy Jul 2024HtrA1, HtrA2, HtrA3 and HtrA4 appear to be involved in the development of pathologies such as cancer. This systematic review reports the results of a literature search...
PURPOSE
HtrA1, HtrA2, HtrA3 and HtrA4 appear to be involved in the development of pathologies such as cancer. This systematic review reports the results of a literature search performed to compare the expression of HtrA family genes and proteins in cancer versus non-cancer tissues and cell lines, assess relationships between HtrA expression and cancer clinical features in cancer, and analyse the molecular mechanism, by which HtrA family affects cancer.
METHODS
The literature search was conducted according to the PRISMA statement among four databases (PubMed, Web of Science, Embase and Scopus).
RESULTS
A total of 38 articles met the inclusion criteria and involved the expression of HtrA family members and concerned the effect of HtrA expression on cancer and metastasis development or on the factor that influences it. Additionally, 31 reports were retrieved manually. Most articles highlighted that HtrA1 and HtrA3 exhibited tumour suppressor activity, while HtrA2 was associated with tumour growth and metastasis. There were too few studies to clearly define the role of the HtrA4 protease in tumours.
CONCLUSION
Although the expression of serine proteases of the HtrA family was dependent on tumour type, stage and the presence of metastases, most articles indicated that HtrA1 and HtrA3 expression in tumours was downregulated compared with healthy tissue or cell lines. The expression of HtrA2 was completely study dependent. The limited number of studies on HtrA4 expression made it impossible to draw conclusions about differences in expression between healthy and tumour tissue. The conclusions drawn from the study suggest that HtrA1 and HtrA3 act as tumour suppressors.
Topics: Humans; Neoplasms; High-Temperature Requirement A Serine Peptidase 1; Serine Endopeptidases; High-Temperature Requirement A Serine Peptidase 2; Gene Expression Regulation, Neoplastic; Mitochondrial Proteins
PubMed: 38717523
DOI: 10.1007/s40291-024-00712-2 -
Journal of Photochemistry and... Aug 2021Cutaneous leishmaniasis (CL) is a neglected disease that represents a serious global public health concern. We performed a systematic review with meta-analysis targeting... (Meta-Analysis)
Meta-Analysis
Cutaneous leishmaniasis (CL) is a neglected disease that represents a serious global public health concern. We performed a systematic review with meta-analysis targeting the use of light-based therapies on CL in preclinical studies since they are essential to identify the benefits, challenges, and limitations of proposing new technologies to fight CL. We searched Pubmed and Web of Science to include original preclinical researches in English that used light-based technologies to fight CL. Inclusion criteria encompassed any animal model for CL induction, an untreated infected group as the comparator, reliable and consistent methodology to develop and treat CL, focus on an antimicrobial therapeutic approach, and data for lesion size and/or parasite load in the infection site. We identified eight eligible articles, and all of them used photodynamic therapy (PDT). For the meta-analysis, three studies were included regarding the parasite load in the infection site and four comprised the lesion size. No overall statistically significant differences were observed between untreated control and PDT groups for parasite load. Differently, PDT significantly reduced the lesion size regardless of the protocol used to treat CL (in mm, SMD: -1.90; 95% CI: -3.74 to -0.07, p = 0.04). This finding is particularly encouraging since CL promotes disfiguring lesions that profoundly affect the quality of life of patients. We conclude that PDT is a new promising technology able to be topically used against CL if applied in more than one session, making it a promising ally for the management of CL.
Topics: Animals; Databases, Factual; Disease Models, Animal; Leishmaniasis, Cutaneous; Light; Parasite Load; Photochemotherapy; Photosensitizing Agents
PubMed: 34090038
DOI: 10.1016/j.jphotobiol.2021.112236 -
Critical Reviews in Oncology/hematology May 2020Brain metastasis (BM) is a complex process that implies immune cells and microglia. Stereotactic radiation therapy (SRT) and immunotherapy (IT) are established to...
INTRODUCTION
Brain metastasis (BM) is a complex process that implies immune cells and microglia. Stereotactic radiation therapy (SRT) and immunotherapy (IT) are established to increase the immune response; but their association has never been prospectively studied.
MATERIALS AND METHODS
Two reviewers performed a systematic review in original papers published up to September 2019. We analysed OS, local (mLRF) and regional (mBRF) median disease-free survival in patients with BMs after SRT with and without IT.
RESULTS
Upon 14 studies, eleven concerned melanoma, three concerned lung cancers. SRT-IT showed better OS, mLRF and mBRF than SRT. mBRF was better if SRT was performed with short delay from IT. No higher rates of radionecrosis and haemorrhage were found among groups.
CONCLUSION
This review suggests SRT combined to IT in melanoma is safe and could provide better BRF, suggesting a lymphocytic immune reaction in brain. No improvement trend was found in lung cancer BM.
Topics: Brain Neoplasms; Cranial Irradiation; Humans; Immunotherapy; Lung Neoplasms; Melanoma; Neoplasm Metastasis; Radiosurgery; Retrospective Studies
PubMed: 32199131
DOI: 10.1016/j.critrevonc.2020.102923 -
Cancer Treatment Reviews Nov 2021Esophageal and gastric malignancies are associated with poor prognosis, in part due to development of recurrences or metastases after curative treatment. The...
Esophageal and gastric malignancies are associated with poor prognosis, in part due to development of recurrences or metastases after curative treatment. The transforming growth factor β (TGF-β) pathway might play a role in the development of treatment resistance. In this systematic review, we provide an overview of preclinical studies investigating the role of TGF-β in esophageal and gastric malignancies. We systematically searched MEDLINE/PubMed and EMBASE for eligible preclinical studies describing the effect of TGF-β or TGF-β inhibition on hallmarks of cancer, such as proliferation, migration, invasion, angiogenesis and immune evasion. In total, 2107 records were screened and 45 articles were included, using mouse models and 45 different cell lines. TGF-β failed to induce apoptosis in twelve of sixteen tested cell lines. TGF-β could either decrease (five cell lines) or increase proliferation (seven cell lines) in gastric cancer cells, but had no effect in esophageal cancer cells. In all esophageal and all but two gastric cancer cell lines, TGF-β increased migratory, adhesive and invasive capacities. In vivo studies showed increased metastasis in response to TGF-β treatment. Additionally, TGF-β was shown to induce vascular endothelial growth factor production and differentiation of cancer-associated fibroblasts and regulatory T-cells. In conclusion, we found that TGF-β enhances hallmarks of cancer in most gastric and esophageal cancer cell lines, but not in all. Therefore, targeting the TGF-β pathway could be an attractive strategy in patients with gastric or esophageal cancer, but additional clinical trials are needed to define patient groups who would benefit most.
Topics: Animals; Esophageal Neoplasms; Humans; Mice; Stomach Neoplasms; Transforming Growth Factor beta
PubMed: 34536730
DOI: 10.1016/j.ctrv.2021.102285 -
Critical Reviews in Oncology/hematology Oct 2020Surgery and chemoradiotherapy can potentially cure esophageal and gastric cancer patients, although they may impact health-related quality of life (HRQoL). We aim to... (Meta-Analysis)
Meta-Analysis
Surgery and chemoradiotherapy can potentially cure esophageal and gastric cancer patients, although they may impact health-related quality of life (HRQoL). We aim to systemically review and meta-analyze literature to determine the effect of curative treatments on HRQoL in esophageal and gastric cancer.- A systematic search was performed identifying studies assessing HRQoL. Meta-analyses were performed on baseline and subsequent time-points.- From the 6067 articles retrieved, 49 studies were included (61 % low quality). Meta-analyses showed short-term HRQoL differences between esophageal cancer patients receiving definitive chemoradiotherapy (dCRT), neoadjuvant chemo(radio)therapy (nC(R)T), or surgery alone (p < 0.001), with better HRQoL with nC(R)T and surgery compared to dCRT. Over the course of 12 months, no HRQoL difference was identified between treatments in esophageal cancer (p = 0.633). Esophagectomy, but not gastrectomy, resulted in a clinically relevant decline in HRQoL. No long-term HRQoL differences were identified between curative treatments in esophageal and gastric cancer. More high-quality HRQoL studies are warranted.
Topics: Chemoradiotherapy; Esophageal Neoplasms; Esophagectomy; Humans; Quality of Life; Stomach Neoplasms
PubMed: 32818901
DOI: 10.1016/j.critrevonc.2020.103069