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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 -
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 -
The Journal of Surgical Research Jun 2024Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissue types as a solution for devastating injuries. Despite the highly encouraging... (Review)
Review
INTRODUCTION
Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissue types as a solution for devastating injuries. Despite the highly encouraging functional outcomes of VCA, the consequences of long-term immunosuppression remain the main obstacle in its application. In this review, we provide researchers and surgeons with a summary of the latest advances in the field of cell-based therapies for VCA tolerance.
METHODS
Four electronic databases were searched: PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature , and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis as the basis of our organization.
RESULTS
Hematopoietic stem cells prolonged VCA survival. A combination of immature dendritic cells and tacrolimus was superior to tacrolimus alone. T cell Ig domain and mucin domain modified mature dendritic cells increased VCA tolerance. Bone marrow-derived mesenchymal stem cells prolonged survival of VCAs. A combination of adipose-derived mesenchymal stem cells, cytotoxic T-lymphocyte antigen 4 immunoglobulin, and antilymphocyte serum significantly improved VCA tolerance. Ex-vivo allotransplant perfusion with recipient's bone marrow-derived mesenchymal stem cells increased VCA survival. Recipient's adipose-derived mesenchymal stem cells and systemic immunosuppression prolonged VCA survival more than any of those agents alone. Additionally, a combination of peripheral blood mononuclear cells shortly incubated in mitomycin and cyclosporine significantly improved VCA survival. Finally, a combination of donor recipient chimeric cells, anti-αβ-T cell receptor (TCR), and cyclosporine significantly prolonged VCA tolerance.
CONCLUSIONS
Evidence from animal studies shows that cell-based therapies can prolong survival of VCAs. However, there remain many obstacles for these therapies, and they require rigorous clinical research given the rarity of the subjects and the complexity of the therapies. The major limitations of cell-based therapies include the need for conditioning with immunosuppressive drugs and radiation, causing significant toxicity. Safety concerns also persist as most research is on animal models. While completely replacing traditional immunosuppression with cell-based methods is unlikely soon, these therapies could reduce the need for high doses of immunosuppressants and improve VCA tolerance.
PubMed: 38851085
DOI: 10.1016/j.jss.2024.04.079 -
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 -
International Journal of Radiation... Jun 2024From the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative, a systematic review and meta-analysis of publications reporting on radiation dose-volume... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
From the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative, a systematic review and meta-analysis of publications reporting on radiation dose-volume effects for risk of primary hypothyroidism after radiation therapy for pediatric malignancies was performed.
METHODS AND MATERIALS
All studies included childhood cancer survivors, diagnosed at age <21 years, whose radiation therapy fields exposed the thyroid gland and who were followed for primary hypothyroidism. Children who received pituitary-hypothalamic or total-body irradiation were excluded. PubMed and the Cochrane Library were searched for studies published from 1970 to 2017. Data on age at treatment, patient sex, radiation dose to neck or thyroid gland, specific endpoints for hypothyroidism that were used in the studies, and reported risks of hypothyroidism were collected. Radiation dose-volume effects were modeled using logistic dose response. Relative excess risk of hypothyroidism as a function of age at treatment and sex was assessed by meta-analysis of reported relative risks (RR) and odds ratios.
RESULTS
Fifteen publications (of 1709 identified) were included for systematic review. Eight studies reported data amenable for dose-response analysis. At mean thyroid doses of 10, 20, and 30 Gy, predicted rates of uncompensated (clinical) hypothyroidism were 4%, 7%, and 13%, respectively. Predicted rates of compensated (subclinical) hypothyroidism were 12%, 25%, and 44% after thyroid doses of 10, 20, and 30 Gy, respectively. Female sex (RR = 1.7, P < .0001) and age >15 years at radiation therapy (RR = 1.3, P = .005) were associated with higher risks of hypothyroidism. After a mean thyroid dose of 20 Gy, predicted risks of hypothyroidism were 13% for males <14 years of age, increasing to 29% for females >15 years of age.
CONCLUSION
A radiation dose response for risk of hypothyroidism is evident; a threshold radiation dose associated with no risk is not observed. Thyroid dose exposure should be minimized when feasible. Data on hypothyroidism after radiation therapy should be better reported to facilitate pooled analyses.
Topics: Humans; Hypothyroidism; Cancer Survivors; Child; Adolescent; Thyroid Gland; Male; Female; Child, Preschool; Dose-Response Relationship, Radiation; Neoplasms; Young Adult; Age Factors; Radiation Injuries; Radiotherapy Dosage; Sex Factors; Organs at Risk; Infant
PubMed: 33810948
DOI: 10.1016/j.ijrobp.2021.02.001 -
Head & Neck Jun 2024Sarcopenia is an increasingly recognized biomarker associated with poorer outcomes. The objective of this study was to ascertain the effect of sarcopenia on treatment... (Meta-Analysis)
Meta-Analysis Review
Sarcopenia is an increasingly recognized biomarker associated with poorer outcomes. The objective of this study was to ascertain the effect of sarcopenia on treatment tolerance and short-term toxicity in head and neck cancer (HNC). A systematic review was performed using multiple databases. An inverse-variation, random-effects model was used to perform the meta-analysis to evaluate the effect of sarcopenia on severe treatment toxicity and poor treatment tolerance. Sixteen observational studies, including 3187 patients with HNC, were analyzed. The combined odds ratio (OR) for severe treatment toxicity and tolerance was 2.22 (95%CI 1.50-3.29) and 1.40 (95%CI 0.84-2.32), respectively. The effect of sarcopenia on short-term severe treatment toxicity was similar with upfront surgery (OR 2.03, 95%CI 1.22-3.37) and definitive radiotherapy (OR 2.24, 95%CI 1.18-4.27) Patients with sarcopenia are more than twice as likely to suffer a short-term treatment-related toxicity when undergoing curative-intent HNC treatment.
Topics: Sarcopenia; Humans; Head and Neck Neoplasms; Male; Female
PubMed: 38353170
DOI: 10.1002/hed.27688 -
International Journal of Radiation... Jun 2024Radiation myelitis (RM) is a rare complication of radiation therapy (RT). The Pediatric Normal Tissue Effects in the Clinic spinal cord task force aimed to identify RT... (Review)
Review
PURPOSE
Radiation myelitis (RM) is a rare complication of radiation therapy (RT). The Pediatric Normal Tissue Effects in the Clinic spinal cord task force aimed to identify RT dose effects and assess risk factors for RM in children. Through systematic review, we analyzed RT dose, fraction size, latency between completion of RT and toxicity, chemotherapy use, age when irradiated, and sex.
METHODS AND MATERIALS
We conducted literature searches of peer-reviewed manuscripts published from 1964 to June 2017 evaluating RM among children. Normality of variables was assessed with Kolmogorov-Smirnov or Shapiro-Wilk tests. Spearman's rank correlation coefficients were used to test correlations between RT dose/fraction size and latency between RT and development of toxicity.
RESULTS
Of 1329 identified and screened reports, 144 reports were fully reviewed and determined to have adequate data for analysis; 16 of these reports had a total of 33 cases of RM with a median age of 13 years (range, 0.2-18) at the time of RT. The most common primary tumor histologies were rhabdomyosarcoma (n = 9), medulloblastoma (n = 5), and Hodgkin lymphoma (n = 2); the most common chemotherapy agents given were vincristine (n = 15), intrathecal methotrexate (n = 12), and intrathecal cytarabine (n = 10). The median RT dose and fraction size were 40 Gy (range, 24-57.4 Gy) and 1.8 Gy (range, 1.3-2.6 Gy), respectively. RT dose resulting in RM in patients who also received chemotherapy was lower than in those not receiving chemotherapy (mean 39.6 vs 49.7 Gy; P = .04). There was no association of age with RT dose. The median latency period was 7 months (range, 1-29). Higher RT dose was correlated with longer latency periods (P = .03) to RM whereas sex, age, fraction size, and chemotherapy use were not. Two of 17 patients with adequate follow-up recovered from RM; unfortunately, it was fatal in 6 of 15 evaluable patients. Complication probability modeling was not possible because of the rarity of events.
CONCLUSIONS
This report demonstrates a relatively short latency from RT (with or without chemotherapy) to RM and a wide range of doses (including fraction sizes) associated with RM. No apparent association with age at the time of RT could be discerned. Chemotherapy appears to reduce spinal cord tolerance. Recovery from RM is rare, and it is often fatal.
Topics: Humans; Child; Adolescent; Child, Preschool; Male; Infant; Radiation Injuries; Female; Neoplasms; Radiotherapy Dosage; Myelitis; Medulloblastoma; Risk Factors; Rhabdomyosarcoma; Hodgkin Disease; Age Factors; Spinal Cord Diseases
PubMed: 38323945
DOI: 10.1016/j.ijrobp.2023.12.020 -
NPJ Microgravity Apr 2024A systematic review of literature was conducted to evaluate the effectiveness of passive countermeasures in ameliorating the cardiopulmonary and musculoskeletal effects... (Review)
Review
A systematic review of literature was conducted to evaluate the effectiveness of passive countermeasures in ameliorating the cardiopulmonary and musculoskeletal effects of gravitational unloading on humans during spaceflight. This systematic review is the third of a series being conducted by the European Space Agency to evaluate the effectiveness of countermeasures to physiologic deconditioning during spaceflight. With future long-duration space missions on the horizon, it is critical to understand the effectiveness of existing countermeasures to promote astronaut health and improve the probability of future mission success. An updated search for studies examining passive countermeasures was conducted in 2021 to supplement results from a broader search conducted in 2017 for all countermeasures. Ground-based analogue and spaceflight studies were included in the search. A total of 647 articles were screened following removal of duplicates, of which 16 were included in this review. Data extraction and analysis, quality assessment of studies, and transferability of reviewed studies to actual spaceflight based on their bed-rest protocol were conducted using dedicated tools created by the Aerospace Medicine Systematic Review Group. Of the 180 examined outcomes across the reviewed studies, only 20 were shown to have a significant positive effect in favour of the intervention group. Lower body negative pressure was seen to significantly maintain orthostatic tolerance (OT) closer to baseline as comparted to control groups. It also was seen to have mixed efficacy with regards to maintaining resting heart rate close to pre-bed rest values. Whole body vibration significantly maintained many balance-related outcome measures close to pre-bed rest values as compared to control. Skin surface cooling and centrifugation both showed efficacy in maintaining OT. Centrifugation also was seen to have mixed efficacy with regards to maintaining VO2max close to pre-bed rest values. Overall, standalone passive countermeasures showed no significant effect in maintaining 159 unique outcome measures close to their pre-bed rest values as compared to control groups. Risk of bias was rated high or unclear in all studies due to poorly detailed methodologies, poor control of confounding variables, and other sources of bias (i.e. inequitable recruitment of participants leading to a higher male:female ratios). The bed-rest transferability (BR) score varied from 2-7, with a median score of 5. Generally, most studies had good BR transferability but underreported on factors such as control of sunlight or radiation exposure, diet, level of exercise and sleep-cycles. We conclude that: (1) Lack of standardisation of outcome measurement and methodologies has led to large heterogeneity amongst studies; (2) Scarcity of literature and high risk of bias amongst existing studies limits the statistical power of results; and (3) Passive countermeasures have little or no efficacy as standalone measures against cardiopulmonary and musculoskeletal deconditioning induced by spaceflight related to physiologic deterioration due to gravity un-loading.
PubMed: 38664498
DOI: 10.1038/s41526-024-00389-1 -
Cureus May 2024Graves' disease (GD) is an autoimmune condition of the thyroid. The hyperthyroidism manifested by patients affected by this disease is caused by the production of... (Review)
Review
Graves' disease (GD) is an autoimmune condition of the thyroid. The hyperthyroidism manifested by patients affected by this disease is caused by the production of autoantibodies against the thyroid-stimulating hormone (TSH, or thyrotropin) receptor (TSHR), which mimic the effects of the hormone on thyroid cells, thereby stimulating autonomic production of thyroxine and triiodothyronine. Deciding on a therapeutic approach to this condition presents intricate dilemmas for both clinicians and patients. Each of the three available treatment modalities is grounded in evidence-based medicine, affirming its efficacy. This systematic review and meta-analysis aimed to assess the effect of carbimazole (CBM), radioactive iodine (RAI), and surgery in treating GD and provide evidence-based recommendations for healthcare providers regarding the optimal management of the condition based on a comprehensive analysis of effectiveness, safety, patient satisfaction, and recovery outcomes. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We used the PubMed and Google Scholar databases to conduct a thorough web search for articles published between January 2019 and September 2023. The meta-analysis was carried out using Resource Manager (Revman) 5.4.1. The study found that propylthiouracil (PTU) or methimazole/carbimazole (MMI/CBM) treatment increases the risk of hyperlipidemia in patients with hyperthyroidism. Once in a euthyroid state, glucose tolerance increases; for children with GD, a computer model for customized dosing has been created. To sum up, CBM, surgery, and RAI are all useful treatment options for GD. Using steroids in conjunction with radiation therapy may help prevent Graves' ophthalmopathy (GO).
PubMed: 38910658
DOI: 10.7759/cureus.60829 -
The Science of the Total Environment Jan 2024Reef-building corals create one of the most biodiverse and economically important ecosystems on the planet. Unfortunately, global coral reef ecosystems experience... (Review)
Review
Reef-building corals create one of the most biodiverse and economically important ecosystems on the planet. Unfortunately, global coral reef ecosystems experience threats from numerous natural stressors, which are amplified by human activities. One such threat is ultraviolet radiation (UVR) from the sun; a genotoxic stressor that is a double-edged sword for corals as they rely on sunlight for energy. More intense UVR has been shown to have greater direct impacts on animal physiology, and these may be exacerbated by co-occurring stressors. The aim of this systematic literature review was to examine if the same applies to corals; that is, if the co-exposure of a constant stressor (UVR) with other stressors has a greater impact on coral physiology than if these stressors occurred separately. We reviewed the biochemical and cellular processes impacted by UVR and the defenses corals have against UVR. The main stressors investigated with UVR were temperature, nitrate, nutrient, oil, water motion, and photosynthetically active radiation (PAR). UVR generally worsened the physiological impacts of other stressors (e.g., by decreasing zooxanthellae and chlorophyll densities). There were species-specific differences in their tolerance to UVR (differences in zooxanthellae populations, sunscreen production and depth) and environmental stress (e.g., resilience to some oils), and that ambient levels of UVR were often beneficial (i.e., nullifying impacts of nitrates). We highlight areas of future investigation including examining and assessing other interacting stressors and their impacts (e.g., ocean acidification, ocean deoxygenation, toxins and pollutants), investigating impacts of multiple stressors with UVR on the coral microbiome, and elucidating the effects of multi-stressors with UVR across early-life history stages (especially larvae). UVR is a pervasive stressor to corals and can interact with other environmental conditions to compromise the resilience of corals. This environmental driver needs to be more comprehensively examined alongside climate change stressors (e.g., temperature increases, ocean acidification and hypoxia) to better understand future climate scenarios on reefs.
Topics: Animals; Humans; Anthozoa; Ecosystem; Ultraviolet Rays; Hydrogen-Ion Concentration; Seawater; Coral Reefs
PubMed: 37890630
DOI: 10.1016/j.scitotenv.2023.168066