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International Journal of Radiation... Jun 2024The Pediatric Normal Tissue Effects in the Clinic (PENTEC) hearing loss (HL) task force reviewed investigations on cochlear radiation dose-response relationships and...
PURPOSE
The Pediatric Normal Tissue Effects in the Clinic (PENTEC) hearing loss (HL) task force reviewed investigations on cochlear radiation dose-response relationships and risk factors for developing HL. Evidence-based dose-response data are quantified to guide treatment planning.
METHODS AND MATERIALS
A systematic review of the literature was performed to correlate HL with cochlear dosimetry. HL was considered present if a threshold exceeded 20 dB at any frequency. Radiation dose, ototoxic chemotherapy exposure, hearing profile including frequency spectra, interval to HL, and age at radiation therapy (RT) were analyzed.
RESULTS
Literature was systematically reviewed from 1970 to 2021. This resulted in 739 abstracts; 19 met inclusion for meta-analysis, and 4 included data amenable to statistical modeling. These 4 studies included 457 cochleas at risk in patients treated with RT without chemotherapy, and 398 cochlea treated with chemotherapy. The incidence and severity of cochlear HL from RT exposure alone is related to dose and age. Risk of HL was <5% in cochlea receiving a mean dose ≤35 Gy but increased to 30% at 50 Gy. HL risk ranged from 25% to 40% in children under the age of 5 years at diagnosis, declining to 10% in older children for any radiation dose. Probability of similar severe HL occurred at doses 18.3 Gy higher for children <3 versus >3 years of age. High-frequency HL was most common, with average onset occurring 3.6 years (range, 0.4-13.2 years) after RT. Exposure to platinum-based chemotherapies added to the rates of HL at a given cochlear dose level, with 300 mg/m shifting the dose response by 7 Gy.
CONCLUSIONS
In children treated with RT alone, risk of HL was low for cochlear dose <35 Gy and rose when dose exceeded 35 Gy without clear RT dose dependence. High-frequency HL was most prevalent, but all frequencies were affected. Children younger than 5 years were at highest risk of developing HL, although independent effects of dose and age were not fully elucidated. Future reports with more granular data are needed to better delineate time to onset of HL and the effects of chemoradiotherapy.
Topics: Humans; Hearing Loss; Child; Cochlea; Cancer Survivors; Child, Preschool; Dose-Response Relationship, Radiation; Adolescent; Age Factors; Risk Factors; Infant; Radiotherapy; Radiotherapy Dosage; Organs at Risk
PubMed: 37855793
DOI: 10.1016/j.ijrobp.2023.08.016 -
EClinicalMedicine Oct 2023Pneumonitis is a common complication for patients with locally advanced non-small cell lung cancer undergoing definitive chemoradiotherapy (CRT). It remains unclear...
Comparison of post-chemoradiotherapy pneumonitis between Asian and non-Asian patients with locally advanced non-small cell lung cancer: a systematic review and meta-analysis.
BACKGROUND
Pneumonitis is a common complication for patients with locally advanced non-small cell lung cancer undergoing definitive chemoradiotherapy (CRT). It remains unclear whether there is ethnic difference in the incidence of post-CRT pneumonitis.
METHODS
PubMed, Embase, Cochrane Library, and Web of Science were searched for eligible studies from January 1, 2000 to April 30, 2023. The outcomes of interest were incidence rates of pneumonitis. The random-effect model was used for statistical analysis. This meta-analysis was registered with PROSPERO (CRD42023416490).
FINDINGS
A total of 248 studies involving 28,267 patients were included. Among studies of CRT without immunotherapy, the pooled rates of pneumonitis for Asian patients were significantly higher than that for non-Asian patients (all grade: 66.8%, 95% CI: 59.2%-73.9% vs. 28.1%, 95% CI: 20.4%-36.4%; P < 0.0001; grade ≥2: 25.1%, 95% CI: 22.9%-27.3% vs. 14.9%, 95% CI: 12.0%-18.0%; P < 0.0001; grade ≥3: 6.5%, 95% CI: 5.6%-7.3% vs. 4.6%, 95% CI: 3.4%-5.9%; P = 0.015; grade 5: 0.6%, 95% CI: 0.3%-0.9% vs. 0.1%, 95% CI: 0.0%-0.2%; P < 0.0001). Regarding studies of CRT plus immunotherapy, Asian patients had higher rates of all-grade (74.8%, 95% CI: 63.7%-84.5% vs. 34.3%, 95% CI: 28.7%-40.2%; P < 0.0001) and grade ≥2 (34.0%, 95% CI: 30.7%-37.3% vs. 24.6%, 95% CI: 19.9%-29.3%; P = 0.001) pneumonitis than non-Asian patients, but with no significant differences in the rates of grade ≥3 and grade 5 pneumonitis. Results from subgroup analyses were generally similar to that from the all studies. In addition, the pooled median/mean of lung volume receiving ≥20 Gy and mean lung dose were relatively low in Asian studies compared to that in non-Asian studies.
INTERPRETATION
Asian patients are likely to have a higher incidence of pneumonitis than non-Asian patients, which appears to be due to the poor tolerance of lung to radiation. Nevertheless, these findings are based on observational studies and with significant heterogeneity, and need to be validated in future large prospective studies focusing on the subject.
FUNDING
None.
PubMed: 37781162
DOI: 10.1016/j.eclinm.2023.102246 -
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 -
International Journal of Radiation... Jun 2024Radiation therapy (RT) is an essential component in the treatment of many pediatric malignancies. Thoracic RT may expose the heart to radiation dose and thereby increase... (Review)
Review
PURPOSE
Radiation therapy (RT) is an essential component in the treatment of many pediatric malignancies. Thoracic RT may expose the heart to radiation dose and thereby increase the risk of late cardiac disease. This comprehensive review from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative focused on late cardiac disease in survivors of childhood cancer treated with RT.
METHODS AND MATERIALS
This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. We identified 1496 articles; 4 were included for dose-response modeling between mean cardiac radiation dose and risk of late coronary artery disease, heart failure (HF), valvular disease, and any cardiac disease.
RESULTS
For each 10-Gy increase in corrected mean cardiac radiation dose in 1.8- to 2.0-Gy fractions, we estimated a hazard ratio of 2.01 (95% confidence interval [CI], 1.79-2.25) for coronary artery disease, of 1.87 (95% CI, 1.70-2.06) for HF, of 1.87 (95% CI, 1.78-1.96) for valvular disease, and of 1.88 (95% CI, 1.75-2.03) for any cardiac disease. From the same model, for each 100-mg/m increase in cumulative anthracycline dose, the hazard ratio for the development of HF was 1.93 (95% CI, 1.58-2.36), equivalent to an increase in mean heart dose of approximately 10.5 Gy. Other nontreatment factors were inconsistently reported in the analyzed articles.
CONCLUSIONS
Radiation dose to the heart increases the risk of late cardiac disease, but survivors of childhood cancer who receive a mean dose <10 Gy at standard fractionation are at low absolute risk (<∼2% approximately 30 years after exposure) of late cardiac disease in the absence of anthracycline exposure. Minimizing cardiac radiation dose is especially relevant in children receiving anthracyclines. When cardiac sparing is not possible, we recommend prioritizing target coverage. It is likely that individual cardiac substructure doses will be a better predictor of specific cardiac diseases than mean dose, and we urge the pediatric oncology community to further study these relationships.
Topics: Humans; Cancer Survivors; Child; Heart Diseases; Coronary Artery Disease; Heart Valve Diseases; Heart; Heart Failure; Neoplasms; Dose-Response Relationship, Radiation; Radiotherapy Dosage
PubMed: 37061912
DOI: 10.1016/j.ijrobp.2023.03.045 -
Supportive Care in Cancer : Official... Mar 2023To evaluate the effectiveness and safety of oral supplementation as a radioprotective intervention in the management of radiation dermatitis (RD). (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the effectiveness and safety of oral supplementation as a radioprotective intervention in the management of radiation dermatitis (RD).
METHODS
Systematic review and meta-analysis. Six databases and the gray literature were searched for randomized controlled clinical trials (RCTs). Meta-analysis was performed only with studies that evaluated the same intervention. Methodology of included studies was evaluated by the Cochrane risk-of-bias tool for randomized trials (RoB 2.0), and the certainty of evidence was assessed by the GRADE instrument.
RESULTS
Seventeen RCTs were included in this review. These evaluated different types of oral supplementations. Findings from three meta-analyses demonstrated no significant benefits to the more severe grades of RD, as oral curcuminoids (RR, 0.59; 95% CI, 0.27 to 1.29; P = 0.19; I = 88%), glutamine (RR, 0.40; 95% CI, 0.15 to 1.03; P = 0.06; I = 78%) or Wobe-Mugos (RR, 0.57; 95% CI, 0.29 to 1.14; P = 0.11; I = 72%). Also, the certainty of the evidence of outcomes evaluated was moderate or low. Except for a few gastrointestinal adverse events, oral supplementation was well tolerated.
CONCLUSION
Most oral supplements cannot yet be recommended to manage RD due to insufficient or conflicting evidence. However, despite no significant results, glutamine was shown to be a promising substance in terms of the potential radioprotective effect and may be well tolerated. These results suggest that more RCTs with larger samples are needed to evaluate the efficacy, safety, and tolerance of glutamine in the management of RD.
Topics: Humans; Glutamine; Neoplasms; Radiodermatitis; Dietary Supplements
PubMed: 36976404
DOI: 10.1007/s00520-023-07685-8 -
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 -
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 -
European Journal of Medical Research Dec 2022Charged particle beams from protons to carbon ions provide many significant physical benefits in radiation therapy. However, preclinical studies of charged particle... (Review)
Review
BACKGROUND
Charged particle beams from protons to carbon ions provide many significant physical benefits in radiation therapy. However, preclinical studies of charged particle therapy for prostate cancer are extremely limited. The aim of this study was to comprehensively investigate the biological effects of charged particles on prostate cancer from the perspective of in vitro studies.
METHODS
We conducted a systematic review by searching EMBASE (OVID), Medline (OVID), and Web of Science databases to identify the publications assessing the radiobiological effects of charged particle irradiation on prostate cancer cells. The data of relative biological effectiveness (RBE), surviving fraction (SF), standard enhancement ratio (SER) and oxygen enhancement ratio (OER) were extracted.
RESULTS
We found 12 studies met the eligible criteria. The relative biological effectiveness values of proton and carbon ion irradiation ranged from 0.94 to 1.52, and 1.67 to 3.7, respectively. Surviving fraction of 2 Gy were 0.17 ± 0.12, 0.55 ± 0.20 and 0.53 ± 0.16 in carbon ion, proton, and photon irradiation, respectively. PNKP inhibitor and gold nanoparticles were favorable sensitizing agents, while it was presented poorer performance in GANT61. The oxygen enhancement ratio values of photon and carbon ion irradiation were 2.32 ± 0.04, and 1.77 ± 0.13, respectively. Charged particle irradiation induced more G0-/G1- or G2-/M-phase arrest, more expression of γ-H2AX, more apoptosis, and lower motility and/or migration ability than photon irradiation.
CONCLUSIONS
Both carbon ion and proton irradiation have advantages over photon irradiation in radiobiological effects on prostate cancer cell lines. Carbon ion irradiation seems to have further advantages over proton irradiation.
Topics: Male; Humans; Protons; Gold; Dose-Response Relationship, Radiation; Metal Nanoparticles; Prostatic Neoplasms; Carbon; Oxygen; Phosphotransferases (Alcohol Group Acceptor); DNA Repair Enzymes
PubMed: 36572945
DOI: 10.1186/s40001-022-00942-2 -
Journal of Geriatric Oncology Apr 2023There is an increasing incidence of cancer in older people, but limited data on radiotherapy uptake, and in particular, radiotherapy utilisation (RTU) rates. The RTU... (Review)
Review
INTRODUCTION
There is an increasing incidence of cancer in older people, but limited data on radiotherapy uptake, and in particular, radiotherapy utilisation (RTU) rates. The RTU rate for older adults with cancer may be lower than recommended due to lower tolerance for radiotherapy as well as additional comorbidities, reduced life expectancy and travel for treatment. Radiotherapy use must be aligned with best available, age-specific evidence to ensure older adults with cancer receive optimal benefit without harms.
MATERIALS AND METHODS
A systematic review was conducted to synthesise the published data on the actual RTU rate for patients with cancer as a function of age. MEDLINE and EMBASE were systematically searched to identify relevant population-based and hospital-based cohort studies on radiotherapy utilisation for all age groups, published in English, from 1 January 1990 to 1 July 2020. We focused on the following common cancers in older adults for which radiotherapy is recommended: breast, prostate, lung, rectal cancer, glioblastoma multiforme (GBM), and cervical cancer. Age-specific radiotherapy utilisation data were extracted and analysed as a narrative synthesis.
RESULTS
From 2606 studies screened, 75 cohort and population-based studies were identified with age-specific radiotherapy utilisation data. The total number of patients in the 75 studies was 4,792,138. The RTU rate decreased with increasing age for all tumour sites analysed, except for patients receiving curative radiotherapy as definitive treatment for prostate or cervical cancer. This reduction with increasing age was demonstrated in both palliative and curative settings.
DISCUSSION
There is a global reduction in radiotherapy utilisation with increasing age for most tumour sites. The reduction in delivery of radiotherapy warrants further examination and evidence-based guidelines specific to this population.
Topics: Male; Female; Humans; Aged; Uterine Cervical Neoplasms; Radiation Oncology; Rectal Neoplasms; Life Expectancy
PubMed: 36272958
DOI: 10.1016/j.jgo.2022.10.002 -
Frontiers in Pharmacology 2022The purpose of this study is to evaluate the efficacy and safety of anlotinib in patients with advanced non-small cell lung cancer (NSCLC) who had previously received...
The purpose of this study is to evaluate the efficacy and safety of anlotinib in patients with advanced non-small cell lung cancer (NSCLC) who had previously received bevacizumab. The participants were histopathologically or cytologically diagnosed advanced NSCLC patients whose disease progressed after at least one type of systemic therapy and who had previously received bevacizumab treatment. The patients were on 3-week administration cycles, including 2 weeks on-treatment (12 mg anlotinib oral route, once a day) and 1 week off-treatment. The primary end point of the trial was overall survival (OS). The secondary end points were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and safety. As of the data collection deadline (31 March 2021), 30 patients were enrolled in the study and received anlotinib treatment. All patients were included in the data set except one, who withdrew their consent after the start of treatment. The median follow-up period was 12.1 months (range, 3.6-25.0 months), and 29 patients were included in the evaluation of the treatment. Of the 29 patients, no CR cases occurred. In total, three patients (10.2%) showed a PR, 21 (72.4%) had SD, and five patients (17.2%) had PD. The objective response rate (ORR) was 10.2% (3 of 29 patients), and the disease control rate (DCR) was 82.7% (24 of 29 patients). The median progression-free survival (PFS) was 5.6 months (95% CI, 5.0-6.1 months; Figure 2). The median overall survival (OS) was 10.6 months (95% CI, 9.4-11.8 months; Figure 3). The overall tolerance of the anlotinib treatment was high among the enrolled patients. No treatment-related grade four or five toxicities were observed. Of the 29 patients, one patient's anlotinib administration was reduced to 8 mg/day due to hypertension and headache. Most adverse events (AEs) were grade one or two; the most common AEs were fatigue (51.7%), hypertension (41.3%), hand-foot syndrome (41.4%), anorexia (34.5%) and hypertriglyceridemia (34.5%). Anlotinib demonstrated favourable activity and manageable toxicity in NSCLC patients who were treated with bevacizumab previously.
PubMed: 36238567
DOI: 10.3389/fphar.2022.973448