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Clinical and Translational Radiation... Sep 2019We performed a systematic review and meta-analysis of studies reporting the incidence of radiation induced brachial plexopathy (RIBP) and the associated radiotherapy...
PURPOSE
We performed a systematic review and meta-analysis of studies reporting the incidence of radiation induced brachial plexopathy (RIBP) and the associated radiotherapy doses to this structure.
METHODS
Databases were queried without language restriction for cohort studies reporting RIBP incidence and associated brachial plexus dose maximum dose (bpDmax). Studies specifying RIBP relative risk (RR) effect size were selected for meta-analysis. RRs for RIBP from each study were converted to a regression coefficient (β) and standard error corresponding to a continuous representation of bpDmax. The adjusted β from individual studies were combined using a random effects model and weighted by inverse variance (1/SE). The trim and fill approach was used to assess publication bias.
RESULTS
We identified 25 studies that included 37 unique patient cohorts eligible for analysis. Seventeen cohorts experienced an RIBP incidence ≤5%, of which 6 cohorts exceeded conventional plexus constraints of 60 Gy for bpDmax. Five of the 6 cohorts were simulated with 3D-CT techniques. Meta-analysis of eligible studies demonstrated a significant increase in RIBP risk for each Gy increase in bpDmax (RR, 1.11; 95% CI 1.07-1.15). Results remained significant after adjustment for publication bias and when sensitivity analysis was performed.
CONCLUSIONS
Our results suggest that current brachial plexus constraints of 60-66 Gy are safe. Meta-analysis provides a log-linear model to quantify the association of brachial plexus dose and RIBP risk, and thus inform the therapeutic ratio for dose escalation. Further prospective studies reporting dosimetric data can better refine this model and inform brachial plexus constraint guidelines.
PubMed: 31309161
DOI: 10.1016/j.ctro.2019.06.006 -
Cancer Radiotherapie : Journal de La... Apr 2023Hadrontherapy is a form of radiation therapy (RT) that relies on heavy particles, such as proton, heavy ions, or neutrons, to enhance anti-tumoral efficacy based on... (Review)
Review
Hadrontherapy is a form of radiation therapy (RT) that relies on heavy particles, such as proton, heavy ions, or neutrons, to enhance anti-tumoral efficacy based on their specific dosimetric and radio-biological properties. Neutrons are characterized by specific radiobiological properties that might deserve greater consideration, including the high linear energy transfer and the low oxygen enhancement ratio. Neutron brachytherapy, relying on interstitial or intracavitary neutron sources, has been developed since the 1950s using Californium-252 (252Cf) as a mixed emitter of fission fast neutrons and γ-photos. However, the place of NBT in the era of modern radiation therapy is yet to be precisely defined. In this systematic review, we aim to provide an up-to-date analysis of current experience and clinical evidence of NBT in the XXI century, by answering the following clinical questions: How is NBT currently delivered? What are the current efficacy data and tolerance profiles of NBT?
Topics: Humans; Brachytherapy; Neutrons; Neoplasms; Radiometry; Radiotherapy Dosage
PubMed: 36759242
DOI: 10.1016/j.canrad.2022.08.010 -
International Journal of Radiation... Feb 2020MicroRNAs (miRNAs) were hypothesized to be robust and easily measured biomarkers of radiation exposure, which has led to multiple studies in various clinical and... (Meta-Analysis)
Meta-Analysis
PURPOSE
MicroRNAs (miRNAs) were hypothesized to be robust and easily measured biomarkers of radiation exposure, which has led to multiple studies in various clinical and experimental scenarios. We sought to identify evolutionary conserved, radiation-induced circulating miRNAs through a multispecies, integrative systematic review and meta-analysis of miRNAs in radiation.
METHODS AND MATERIALS
The systematic review was registered in the PROSPERO database (ID: 81701). We downloaded a list of studies with the query: (circulating OR plasma OR serum) AND (miRNA or microRNA) AND (radiat* OR radiotherapy OR irradiati*) from MEDLINE (103 studies), EMBASE (364 studies), and Cochrane Database of Systematic Reviews (0 studies). After deleting 116 duplicates, the remaining 351 abstracts were reviewed. Inclusion criteria were experimental study; human, mice, rat or nonhuman primate study; and serum or plasma miRNA expression measured before and after radiation exposure.
RESULTS
The screening procedure yielded 62 research studies. After verification, 30 articles contained data on miRNA expression change after irradiation. Thus, we obtained a database of 131 miRNAs from 96 pairwise post-/preirradiation comparisons reporting 2508 fold changes (FCs) of circulating miRNAs. The meta-analysis showed 28 miRNAs with significant radiation-induced change of their expression in the serum. In metaregression analysis, 7 miRNAs-miR-150 (FC = 0.40; 95% confidence interval [CI], 0.35-0.45), miR-29a (FC = 0.87; 95% CI, 0.79-0.96), miR-29b (FC = 0.85; 95% CI, 0.76-0.96), miR-30c (FC = 1.19; 95% CI, 1.09-1.30), miR-200b (FC = 1.34; 95% CI, 1.21-1.48), miR-320a (FC = 1.13; 95% CI, 1.05-1.23), and miR-30a (FC = 1.18; 95% CI, 1.07-1.30)-significantly correlated with either total or fraction dose of radiation. Additionally, miR-150, miR-320a, miR-200b, and miR-30c correlated significantly with time elapsed since irradiation.
CONCLUSIONS
Circulating miRNAs reflect the impact of ionizing radiation irrespective of the studied species, often in a dose-dependent manner. This makes circulating miRNAs promising biomarkers of radiation exposure.
Topics: Animals; Biomarkers; Circulating MicroRNA; Databases, Factual; Dose-Response Relationship, Radiation; Female; Humans; Male; Mice; Primates; Radiation Exposure; Rats; Regression Analysis
PubMed: 31655196
DOI: 10.1016/j.ijrobp.2019.10.028 -
Breast Cancer Research and Treatment Jun 2022Radiation therapy (RT) for triple-negative breast cancer (TNBC) treatment is currently delivered in the adjuvant setting and is under investigation as a booster of... (Review)
Review
PURPOSE
Radiation therapy (RT) for triple-negative breast cancer (TNBC) treatment is currently delivered in the adjuvant setting and is under investigation as a booster of neoadjuvant treatments. However, TNBC radioresistance remains an obstacle, so new biomarkers are needed to select patients for any integration of RT in the TNBC therapy sequence. MicroRNAs (miRs) are important regulators of gene expression, involved in cancer response to ionizing radiation (IR) and assessable by tumor tissue or liquid biopsy. This systematic review aimed to evaluate the relationships between miRs and response to radiation in TNBC, as well as their potential predictive and prognostic values.
METHODS
A thorough review of studies related to miRs and RT in TNBC was performed on PubMed, EMBASE, and Web of Science. We searched for original English articles that involved dysregulation of miRs in response to IR on TNBC-related preclinical and clinical studies. After a rigorous selection, 44 studies were chosen for further analysis.
RESULTS
Thirty-five miRs were identified to be TNBC related, out of which 21 were downregulated, 13 upregulated, and 2 had a double-side expression in this cancer. Expression modulation of many of these miRs is radiosensitizing, among which miR-7, -27a, -34a, -122, and let-7 are most studied, still only in experimental models. The miRs reported as most influencing/reflecting TNBC response to IR are miR-7, -27a, -155, -205, -211, and -221, whereas miR-21, -33a, -139-5p, and -210 are associated with TNBC patient outcome after RT.
CONCLUSION
miRs are emerging biomarkers and radiosensitizers in TNBC, worth further investigation. Dynamic assessment of circulating miRs could improve monitoring and TNBC RT efficacy, which are of particular interest in the neoadjuvant and the high-risk patients' settings.
Topics: Biomarkers; Biomarkers, Tumor; Circulating MicroRNA; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Radiation Tolerance; Triple Negative Breast Neoplasms
PubMed: 35397079
DOI: 10.1007/s10549-022-06533-3 -
Head & Neck Dec 2023This systematic review study aims to provide comprehensive data on different radiobiological models, parameters, and endpoints used for calculating the normal tissue... (Review)
Review
This systematic review study aims to provide comprehensive data on different radiobiological models, parameters, and endpoints used for calculating the normal tissue complication probability (NTCP) based on clinical data from head and neck cancer patients treated with conformal radiotherapy. A systematic literature search was carried out according to the PRISMA guideline for the identification of relevant publications in six electronic databases of Embase, PubMed, Scopus, and Google Scholar to July 2022 using specific keywords in the paper's title and abstract. The initial search resulted in 1368 articles for all organs for the review article about the NTCP parameters. One hundred and seventy-eight articles were accepted for all organs with complete parameters for the mentioned models and finally, 20 head and neck cancer articles were accepted for review. Analysis of the studies shows that the Lyman-Kutcher-Burman (LKB) model properly links the NTCP curve parameters to the postradiotherapy endpoints. In the LKB model for esophagus, the minimum, and maximum corresponding parameters were reported as TD = 2.61 Gy with grade ≥3 radiation-induced esophagitis endpoints as the minimum TD and TD = 68 Gy as the maximum ones. n = 0.06, n = 1.04, m = 0.1, and m = 0.65, respectively. Unfortunately, there was not a wide range of published articles on other organs at risk like ear or cauda equina except Burman et al. (Fitting of normal tissue tolerance data to an analytic function. Int J Radiat Oncol Biol Phys Ther. 1991;21:123-135). Findings suggest that the validation of different radiobiological models and their corresponding parameters need to be investigated in vivo and in vitro for developing a more accurate NTCP model to be used for radiotherapy treatment planning optimization.
Topics: Humans; Radiotherapy, Conformal; Probability; Head and Neck Neoplasms; Radiotherapy Planning, Computer-Assisted; Radiobiology; Radiotherapy Dosage
PubMed: 37767820
DOI: 10.1002/hed.27469 -
The Medical Journal of Malaysia Jan 2022Treatment of head and neck cancer patients amidst the COVID-19 pandemic is challenging, whereas prolonged treatment initiation in head and neck squamous cell carcinoma...
INTRODUCTION
Treatment of head and neck cancer patients amidst the COVID-19 pandemic is challenging, whereas prolonged treatment initiation in head and neck squamous cell carcinoma may increase mortality and likelihood of recurrence. Special attention is needed to ensure safe and appropriate care of these patients. This article aims to review and discuss existing research on treatment prioritization and risk stratification of head and neck cancer patients during the pandemic.
MATERIALS AND METHODS
The authors conducted literature search in three databases (PubMed, Cochrane, and Clinical Key) on July 15th, 2020. The keywords were ("Head and Neck Mucosal Malignancy" OR "Head and Neck Cancer") AND ("Management" OR "Head and Neck Surgery") AND ("COVID-19" OR "Pandemic"). The inclusion criteria were cancer in adult patients, published from 2020 in English, and with available access to full text. The exclusion criteria were comments, letters, and case reports. The articles were critically appraised using the Centre of Evidence-based Medicine (CEBM), University of Oxford and Duke University. The literature search strategy is illustrated using Preferred Reporting Items for Systematic review and meta-analysis (PRISMA) flow diagram.
RESULTS
A total of 150 articles were identified; 21 articles were gathered from Clinical Key, 33 from Cochrane, and 96 from Pubmed. After screening abstracts and reviewing the full text, the authors determined five articles met the inclusion criteria. There are several key points of head and neck cancer management in the COVID-19 pandemic. Head and neck cancer management is considered a high-risk procedure; the clinician should use proper personal protective equipment. Before operative treatment, all patients should undergo a PCR test 14 days before surgery. In diagnosing head and neck cancer, laryngoscopy should be considered carefully; and cytology should be preferred instead. Medically Necessary, Time-sensitive (MeNTS) score is recommended for risk stratification and surgery prioritization; it has three domains: procedure, disease, and patient. However, it is not specified to head and neck cancer; therefore, it should be combined with other references. Stanford University Head and Neck Surgery Division Department of Otolaryngology made surgery prioritization into three groups, urgent (should be operated immediately), can be postponed for 30 days, and can be postponed for 30- 90 days. Some urgent cases and should be operated on immediately include cancers involving the airways, decreased renal function, and metastases. For chemoradiation decision to delay or continue should refer to the goal of treatment, current oncologic status, and tolerance to radiation. In terms of patient's follow up, telephone consultation should be maximized.
CONCLUSION
MeNTS scoring combined with Guideline from Department of Otolaryngology at Stanford University prioritizing criteria can be helpful in decision making of stratifying Risk and prioritizing surgery in head and neck cancer management.
Topics: COVID-19; Head and Neck Neoplasms; Humans; Pandemics; Referral and Consultation; Risk Assessment; SARS-CoV-2; Telephone
PubMed: 35086995
DOI: No ID Found -
The Science of the Total Environment Jun 2022The biphasic hormetic response to stress, defined by low-dose stimulation and high-dose inhibition is frequently observed in insects. Various molecular and biochemical...
The biphasic hormetic response to stress, defined by low-dose stimulation and high-dose inhibition is frequently observed in insects. Various molecular and biochemical responses associated with hormesis in insects have been reported in many studies, but no synthesis of all these findings has been undertaken. We conducted a systematic literature review, analyzing papers demonstrating phenotypic stimulatory effect(s) following exposure to stress where molecular or biochemical response(s) were also examined. Responses observed included stimulation of reproduction, survival and longevity, growth and development, and tolerance to temperature, chemical, or starvation and desiccation, in response to stressors including pesticides, oxidative stress, temperature, crowding and starvation, and radiation. Phenotypic stimulation ranged from <25% increased above controls to >100%. Reproductive stimulation was frequently <25% increased above controls, while stimulated temperature tolerance was frequently >100% increased. Molecular and biochemical responses had obvious direct connections to phenotypic responses in many cases, although not in all instances. Increased expression of heat shock proteins occurred in association with stimulated temperature tolerance, and increased expression of detoxification genes with stimulated pesticide or chemical tolerance, but also stimulated reproduction. Changes in the expression or activity of antioxidants were frequently associated with stimulation of longevity and reproduction. Stress induced changes in vitellogenin and juvenile hormone and genes in the IIS/TOR signalling pathway - which are directly responsible for regulating growth, development, and reproduction - were also reported. Our analysis showed that coordination of expression of genes or proteins associated with protection from oxidative stress and DNA and protein damage is important in the hormetic responses of insects.
Topics: Animals; Antioxidants; Hormesis; Insecta; Oxidative Stress; Reproduction
PubMed: 35218848
DOI: 10.1016/j.scitotenv.2022.154085 -
Plants (Basel, Switzerland) Jan 2023Agricultural crops are exposed to various abiotic stresses, such as salinity, water deficits, temperature extremes, floods, radiation, and metal toxicity. To overcome... (Review)
Review
Agricultural crops are exposed to various abiotic stresses, such as salinity, water deficits, temperature extremes, floods, radiation, and metal toxicity. To overcome these challenges, breeding programs seek to improve methods and techniques. Gene editing by Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR/Cas-is a versatile tool for editing in all layers of the central dogma with focus on the development of cultivars of plants resistant or tolerant to multiple biotic or abiotic stresses. This systematic review (SR) brings new contributions to the study of the use of CRISPR/Cas in gene editing for tolerance to abiotic stress in plants. Articles deposited in different electronic databases, using a search and predefined inclusion and exclusion criteria, were evaluated. This SR demonstrates that the CRISPR/Cas system has been applied to several plant species to promote tolerance to the main abiotic stresses. Among the most studied crops are rice and , an important staple food for the population, and a model plant in genetics/biotechnology, respectively, and more recently tomato, whose number of studies has increased since 2021. Most studies were conducted in Asia, specifically in China. The Cas9 enzyme is used in most articles, and only Cas12a is used as an additional gene editing tool in plants. Ribonucleoproteins (RNPs) have emerged as a DNA-free strategy for genome editing without exogenous DNA. This SR also identifies several genes edited by CRISPR/Cas, and it also shows that plant responses to stress factors are mediated by many complex-signaling pathways. In addition, the quality of the articles included in this SR was validated by a risk of bias analysis. The information gathered in this SR helps to understand the current state of CRISPR/Cas in the editing of genes and noncoding sequences, which plays a key role in the regulation of various biological processes and the tolerance to multiple abiotic stresses, with potential for use in plant genetic improvement programs.
PubMed: 36679018
DOI: 10.3390/plants12020305 -
International Journal of Radiation... May 2021Ultrahypofractionationed radiation therapy for prostate cancer is increasingly studied and adopted. The American Association of Physicists in Medicine Working Group on...
PURPOSE
Ultrahypofractionationed radiation therapy for prostate cancer is increasingly studied and adopted. The American Association of Physicists in Medicine Working Group on Biological Effects of Hypofractionated Radiotherapy therefore aimed to review studies examining toxicity and quality of life after stereotactic body radiation therapy (SBRT) for prostate cancer and model its effect.
METHODS AND MATERIALS
We performed a systematic PubMed search of prostate SBRT studies published between 2001 and 2018. Those that analyzed factors associated with late urinary, bowel, or sexual toxicity and/or quality of life were included and reviewed. Normal tissue complication probability modelling was performed on studies that contained detailed dose/volume and outcome data.
RESULTS
We found 13 studies that examined urinary effects, 6 that examined bowel effects, and 4 that examined sexual effects. Most studies included patients with low-intermediate risk prostate cancer treated to 35-40 Gy. Most patients were treated with 5 fractions, with several centers using 4 fractions. Endpoints were heterogeneous and included both physician-scored toxicity and patient-reported quality of life. Most toxicities were mild-moderate (eg, grade 1-2) with a very low overall incidence of severe toxicity (eg, grade 3 or higher, usually <3%). Side effects were associated with both dosimetric and non-dosimetric factors.
CONCLUSIONS
Prostate SBRT appears to be overall well tolerated, with determinants of toxicity that include dosimetric factors and patient factors. Suggested dose constraints include bladder V(Rx Dose)Gy <5-10 cc, urethra Dmax <38-42 Gy, and rectum Dmax <35-38 Gy, though current data do not offer firm guidance on tolerance doses. Several areas for future research are suggested.
Topics: Humans; Male; Models, Biological; Models, Theoretical; Organs at Risk; Patient Reported Outcome Measures; Penis; Prostatic Neoplasms; Quality of Life; Radiation Dose Hypofractionation; Radiosurgery; Rectum; Urethra; Urinary Bladder
PubMed: 33358229
DOI: 10.1016/j.ijrobp.2020.09.054 -
International Journal of Radiation... May 2021Dose escalation improves localized prostate cancer disease control, and moderately hypofractionated external beam radiation is noninferior to conventional fractionation....
PURPOSE
Dose escalation improves localized prostate cancer disease control, and moderately hypofractionated external beam radiation is noninferior to conventional fractionation. The evolving treatment approach of ultrahypofractionation with stereotactic body radiation therapy (SBRT) allows possible further biological dose escalation (biologically equivalent dose [BED]) and shortened treatment time.
METHODS AND MATERIALS
The American Association of Physicists in Medicine Working Group on Biological Effects of Hypofractionated Radiation Therapy/SBRT included a subgroup to study the prostate tumor control probability (TCP) with SBRT. We performed a systematic review of the available literature and created a dose-response TCP model for the endpoint of freedom from biochemical relapse. Results were stratified by prostate cancer risk group.
RESULTS
Twenty-five published cohorts were identified for inclusion, with a total of 4821 patients (2235 with low-risk, 1894 with intermediate-risk, and 446 with high-risk disease, when reported) treated with a variety of dose/fractionation schemes, permitting dose-response modeling. Five studies had a median follow-up of more than 5 years. Dosing regimens ranged from 32 to 50 Gy in 4 to 5 fractions, with total BED (α/β = 1.5 Gy) between 183.1 and 383.3 Gy. At 5 years, we found that in patients with low-intermediate risk disease, an equivalent doses of 2 Gy per fraction (EQD2) of 71 Gy (31.7 Gy in 5 fractions) achieved a TCP of 90% and an EQD2 of 90 Gy (36.1 Gy in 5 fractions) achieved a TCP of 95%. In patients with high-risk disease, an EQD2 of 97 Gy (37.6 Gy in 5 fractions) can achieve a TCP of 90% and an EQD2 of 102 Gy (38.7 Gy in 5 fractions) can achieve a TCP of 95%.
CONCLUSIONS
We found significant variation in the published literature on target delineation, margins used, dose/fractionation, and treatment schedule. Despite this variation, TCP was excellent. Most prescription doses range from 35 to 40 Gy, delivered in 4 to 5 fractions. The literature did not provide detailed dose-volume data, and our dosimetric analysis was constrained to prescription doses. There are many areas in need of continued research as SBRT continues to evolve as a treatment modality for prostate cancer, including the durability of local control with longer follow-up across risk groups, the efficacy and safety of SBRT as a boost to intensity modulated radiation therapy (IMRT), and the impact of incorporating novel imaging techniques into treatment planning.
Topics: Dose-Response Relationship, Radiation; Humans; Linear Models; Male; Models, Biological; Models, Theoretical; Probability; Prostatic Neoplasms; Radiation Dose Hypofractionation; Radiosurgery; Relative Biological Effectiveness; Risk; Time Factors; Treatment Outcome; Urethra
PubMed: 32900561
DOI: 10.1016/j.ijrobp.2020.08.014