Purpose/objective(s): Radionecrosis (RN) has previously been correlated with radiosurgery (RS) dose, lesion volume, and the volume of the brain receiving specific doses, i.e. V10-14Gy. A knowledge-based individualized estimation of the optimum RS dose has been derived based on lesional volume and brain toxicity parameters.
Methods And Materials: A prediction model for brain toxicity parameters and estimation of the optimum RS dose was derived using 30 historical linac-based dynamic conformal arc RS plans for single brain metastases (BM) (0.2-20.3cc) with risk-adapted dose prescription ranging from 15 to 24Gy. Derivation of the model followed a three-step process: (1) Derivation of formulas for the prediction of brain toxicity parameters V10-18Gy; (2) Establishing the relationship of the coefficients used for the prediction of V12Gy with prescription dose; (3) Derivation of the optimum prescription dose for a given maximum V12Gy as a function of a given lesion volume. Model validation was performed on 65 new patients with 138 lesions (44 with multiple BM) treated with non-coplanar volumetric modulated stereotactic arc treatment (VMAT).
Results: A linear dependence with the PTV size was found for all investigated brain toxicity parameters (V10-18Gy). Individualized RS prescription doses can be calculated for any given PTV size based on a linear relationship between V12Gy and PTV size, according to the formula PD=[V12Gy+0.96+(1.44×PTV)]/[0.12+(0.12×PTV)]. A very good correlation (R(2)=0.991) was found between the predicted V12Gy and the resulting V12Gy in 65 new patients with 138 lesions treated with non-coplanar VMAT technique in our clinic.
Conclusions: A simple formula is proposed for estimation of the optimal individual RS dose for any given lesion volume for patients with (multiple) BM. This formula is based on calculation of the brain toxicity parameter, V12Gy, for the normal brain minus PTV.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.radonc.2016.05.001 | DOI Listing |
Curr Environ Health Rep
January 2025
AJ Drexel Autism Institute, Drexel University, Philadelphia, USA, PA.
Purpose Of Review: Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals with many modern applications, leading to widespread contamination and universal human exposure. PFAS exposure during early life is of particular concern, given susceptibility of the developing fetal and infant brain to toxic exposures. This review aims to synthesize current evidence, discuss methodological challenges, and highlight research gaps to guide future studies on the impact of PFAS on neurodevelopment.
View Article and Find Full Text PDFBasic Clin Pharmacol Toxicol
March 2025
Department of Biology, Faculty of Science, Hacettepe University, Ankara, Turkey.
The pineal gland secretes melatonin, which regulates various physiological processes; damage to this gland disrupts these functions. This study aimed to investigate the effect of nonylphenol on the pineal gland and the pituitary-adrenal axis, which is associated with this system. The study was initiated using Wistar albino male rats on their postnatal 21st day, a critical developmental stage for endocrine regulation.
View Article and Find Full Text PDFMol Neurodegener
January 2025
Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.
Gastrointestinal (GI) involvement in Lewy body diseases (LBDs) has been observed since the initial descriptions of patients by James Parkinson. Recent experimental and human observational studies raise the possibility that pathogenic alpha-synuclein (⍺-syn) might develop in the GI tract and subsequently spread to susceptible brain regions. The cellular and mechanistic origins of ⍺-syn propagation in disease are under intense investigation.
View Article and Find Full Text PDFFluids Barriers CNS
January 2025
Laboratory for Therapeutic and Diagnostic Antibodies, KU Leuven - University of Leuven, O&N II Herestraat 49 box 820, 3000, Leuven, Belgium.
Background: Therapeutic antibodies for the treatment of neurological disease show great potential, but their applications are rather limited due to limited brain exposure. The most well-studied approach to enhance brain influx of protein therapeutics, is receptor-mediated transcytosis (RMT) by targeting nutrient receptors to shuttle protein therapeutics over the blood-brain barrier (BBB) along with their endogenous cargos. While higher brain exposure is achieved with RMT, the timeframe is short due to rather fast brain clearance.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Pharmaceutical Chemistry Research Laboratory I, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, India. Electronic address:
The multi-target directed ligands (MTDLs) strategy has been evolved as the propitious approach for the development of therapeutics for Alzheimer's disease (AD). In an earlier report, we described the novel series of chalcone derivatives bearing N-aryl piperazine scaffold as MTDLs for the treatment of AD. Herein, we report the lead optimization of the series culminating in potent, multi-targeting compounds (32-57), evaluated through in-vitro and in-vivo biological studies.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!