Background And Purpose: Anatomical changes during the stereotactic body radiation therapy (SBRT) of early stage non-small cell lung cancer (NSCLC) may cause the delivered dose to deviate from the planned dose. We investigate if normal tissue complication probability (NTCP) models based on the delivered dose predict radiation-induced rib fractures better than models based on the planned dose.
Material And Methods: 437 NSCLC patients treated to a median dose of 3x18 Gy were included. Delivered dose was estimated by accumulating EQD2-corrected fraction doses after being deformed with daily CBCT-to-planning CT deformable image registration. Dosimetric parameters D (dose to a relative volume x) were extracted for each rib included in the CBCTs field-of-view. An NTCP model was constructed for both planned and delivered dose, optimizing the parameters TD (dose with 50% toxicity risk), m (steepness of the curve) and x, using maximum likelihood estimation. Best NTCP model was determined using Akaike weights (Aw). Differences between the models were tested for significance using the Vuong's test.
Results: Median time to fracture of 110 fractured ribs was 22.5 months. The maximum rib dose, D, best predicted fractures for both planned and delivered dose. The average delivered D was significantly lower than planned (p < 0.001). NTCP model based on the delivered D was the best, with Aw = 0.95. The models were not significantly different.
Conclusion: Delivered maximum dose to the ribs was significantly lower than planned. The NTCP model based on delivered dose improved predictions of radiation-induced rib fractures but did not reach statistical significance.
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http://dx.doi.org/10.1016/j.radonc.2021.06.028 | DOI Listing |
Lancet Microbe
January 2025
Jenner Institute, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
Background: R21 is a novel malaria vaccine, composed of a fusion protein of the malaria circumsporozoite protein and hepatitis B surface antigen. Following favourable safety and immunogenicity in a phase 1 study, we aimed to assess the efficacy of R21 administered with Matrix-M (R21/MM) against clinical malaria in adults from the UK who were malaria naive in a controlled human malaria infection study.
Methods: In this open-label, partially blinded, phase 1-2A controlled human malaria infection study undertaken in Oxford, Southampton, and London, UK, we tested five novel vaccination regimens of R21/MM.
Appl Radiat Isot
January 2025
Particle Radiation Oncology Research Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University, 2-Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan.
Recent decades have seen the development of accelerator neutron sources suitable for installation in a hospital setting. Numerous challenges have been faced and solved to deliver technology which continues to transform the field of BNCT. This paper begins by briefly reviewing the technologies which are currently, or soon will be, in clinical use.
View Article and Find Full Text PDFBiomed Phys Eng Express
January 2025
Department of Medical Physics, Osaka Heavy Ion Therapy Center, Otemae, Chuo-ku, Osaka, Osaka, 5400008, JAPAN.
Objective Applying carbon ion beams, which have high linear energy transfer and low scatter within the human body, to Spatially Fractionated Radiation Therapy (SFRT) could benefit the treatment of deep-seated or radioresistant tumors. This study aims to simulate the dose distributions of spatially fractionated beams (SFB) to accurately determine the delivered dose and model the cell survival rate following SFB irradiation. Approach Dose distributions of carbon ion beams are calculated using the Triple Gaussian Model.
View Article and Find Full Text PDFAm J Respir Cell Mol Biol
January 2025
Ottawa Hospital Research Institute & CHEO Research Institute, Pediatrics, Ottawa, Ontario, Canada.
Surfactant protein-B (SP-B) deficiency is a lethal neonatal respiratory disease with few therapeutic options. Gene therapy using adeno-associated viruses (AAV) to deliver human cDNA (AAV-hSPB) can improve survival in a mouse model of SP-B deficiency. However, the effect of this gene therapy wanes.
View Article and Find Full Text PDFGenetic medicines, including CRISPR/Cas technologies, extend tremendous promise for addressing unmet medical need in inherited retinal disorders and other indications; however, there remain challenges for the development of therapeutics. Herein, we evaluate genome editing by engineered Cas9 ribonucleoproteins (eRNP) in vivo via subretinal administration using mouse and pig animal models. Subretinal administration of adenine base editor and double strand break-inducing Cas9 nuclease eRNPs mediate genome editing in both species.
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