Search

Brainstem metastases are challenging to manage owing to the critical neurological structures involved. Although stereotactic radiotherapy (SRT) offers targeted high doses while minimizing damage to adjacent normal tissues, the optimal dose fractionation remains undefined. This study evaluated the efficacy and safety of multifraction SRT with an inhomogeneous dose distribution. This retrospective study included 31 patients who underwent 33 treatments for 35 brainstem lesions using linear accelerator-based multifraction SRT (30 Gy in five fractions, 35 Gy in five fractions or 42 Gy in 10 fractions) with an inhomogeneous dose distribution (median isodose, 51.9%). The outcomes of interest were local failure, toxicity and symptomatic failure. The median follow-up time after brainstem SRT for a lesion was 18.6 months (interquartile range, 10.0–24.3 months; range, 1.8–39.0 months). Grade 2 toxicities were observed in two lesions, and local failure occurred in three lesions. No grade 3 or higher toxicities were observed. The 1-year local and symptomatic failure rates were 8.8 and 16.7%, respectively. Toxicity was observed in two of seven treatments with a gross tumor volume (GTV) greater than 1 cc, whereas no toxicity was observed in treatments with a GTV less than 1 cc. No clear association was observed between the biologically effective dose of the maximum brainstem dose and the occurrence of toxicity. Our findings indicate that multifraction SRT with an inhomogeneous dose distribution offers a favorable balance between local control and toxicity in brainstem metastases. Larger multicenter studies are needed to validate these results and determine the optimal dose fractionation. [ABSTRACT FROM AUTHOR]

Background/aim: Intensity-modulated radiation therapy can deliver a highly conformal dose to a target while minimizing the dose to the organs at risk (OARs). Delineating the contours of OARs is time-consuming, and various automatic contouring software programs have been employed to reduce the delineation time. However, some software operations are manual, and further reduction in time is possible. This study aimed to automate running atlas-based auto-segmentation (ABAS) and software operations using a scripting function, thereby reducing work time., Materials and Methods: Dice coefficient and Hausdorff distance were used to determine geometric accuracy. The manual delineation, automatic delineation, and modification times were measured. While modifying the contours, the degree of subjective correction was rated on a four-point scale., Results: The model exhibited generally good geometric accuracy. However, some OARs, such as the chiasm, optic nerve, retina, lens, and brain require improvement. The average contour delineation time was reduced from 57 to 29 min (p<0.05). The subjective revision degree results indicated that all OARs required minor modifications; only the submandibular gland, thyroid, and esophagus were rated as modified from scratch., Conclusion: The ABAS model and scripted automation in head and neck cancer reduced the work time and software operations. The time can be further reduced by improving contour accuracy., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Endoplasmic reticulum-mitochondrial contact sites (ERMCS) play an important role in mitochondrial dynamics, calcium signaling, and autophagy. Disruption of the ERMCS has been linked to several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). However, the etiological role of ERMCS in these diseases remains unclear. We previously established tyrosine hydroxylase reporter ( TH- GFP) iPSC lines from a PD patient with a PRKN mutation to perform correlative light-electron microscopy (CLEM) analysis and live cell imaging in GFP-expressing dopaminergic neurons. Here, we analyzed ERMCS in GFP-expressing PRKN- mutant dopaminergic neurons from patients using CLEM and a proximity ligation assay (PLA). The PLA showed that the ERMCS were significantly reduced in PRKN- mutant patient dopaminergic neurons compared to the control under normal conditions. The reduction of the ERMCS in PRKN -mutant patient dopaminergic neurons was further enhanced by treatment with a mitochondrial uncoupler. In addition, mitochondrial calcium imaging showed that mitochondrial Ca 2+ flux was significantly reduced in PRKN -mutant patient dopaminergic neurons compared to the control. These results suggest a defect in calcium flux from ER to mitochondria is due to the decreased ERMCS in PRKN -mutant patient dopaminergic neurons. Our study of ERMCS using TH- GFP iPSC lines would contribute to further understanding of the mechanisms of dopaminergic neuron degeneration in patients with PRKN mutations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yokota, Yoshino, Hosoi, Hashimoto, Kakuta, Shiga, Ishikawa, Okano, Hattori, Akamatsu and Koike.)