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Journal of Applied Clinical Medical... Jun 2024Noncoplanar arc optimization has been shown to reduce OAR doses in SRS/SRT and has the potential to reduce doses to OARs in SBRT. Extracranial targets have additional...
Noncoplanar arc optimization has been shown to reduce OAR doses in SRS/SRT and has the potential to reduce doses to OARs in SBRT. Extracranial targets have additional considerations, including large OARs and, in the case of the liver, volume constraints on the healthy liver. Considering pathlengths through OARs that encompass target volumes may lead to specific dose reductions as in the encompassing healthy liver tissue. These optimizations must also leverage delivery efficiency and trajectory sampling to ensure ease of clinical translation. The purpose of this research is to generate optimized static-couch arcs that separately consider serial and parallel OARs and arc delivery efficiency, with a trajectory sampling metric, towards the aim of reducing dose to OARs and the surrounding healthy liver tissue. Separate BEV cost maps were created for parallel, and serial OARs by means of a fast ray-triangle intersection algorithm. An additional BEV cost map was created for the liver which, by definition, encompasses the liver tumors. The individual costs of these maps were summed and combined with the sampling metric for 100 000 random combinations of arc trajectories. A search algorithm was applied to find an arc trajectory solution that satisfied BEV cost and sampling optimization, while also ensuring an efficient delivery was possible with a low number of arcs. This method of arc selection was evaluated for 16 liver SBRT patients characterized by small and large target volumes. Comparisons were made with a clinical arc template of coplanar arcs. Dosimetric plan quality was evaluated using published guidelines and metrics from RTOG1112. Four of five plan quality metrics for the liver were significantly reduced when planned with optimized noncoplanar arcs. Median (range) reductions of the volumes receiving 10, 18, and 21 Gy were found of 140.4 (295.8) cc (p = 0.001), 28.2 (230.6) cc (p = 0.002) and 18.5 (155.5) cc (p = 0.04). A significant increase in median (range) dose to the right kidney of 0.2 ± 0.9 Gy (p = 0.03) was also found using optimized noncoplanar arcs, which was below the tolerance of 10 Gy for all cases. The average number of arcs chosen was 4 ± 1. Optimizing serial and parallel OARs separately during static couch noncoplanar arc selection significantly reduced the dose to the liver during SBRT using a moderate number of arcs.
PubMed: 38894588
DOI: 10.1002/acm2.14396 -
Journal of Clinical Medicine May 2024State-of-the-art therapy improves the five-year survival rate of patients under the age of 20 with cranial and craniospinal tumors by up to 74%. The urgency of dealing...
State-of-the-art therapy improves the five-year survival rate of patients under the age of 20 with cranial and craniospinal tumors by up to 74%. The urgency of dealing effectively with late treatment-associated cardiovascular complications is rising. : We aimed to assess echocardiographic parameters and exercise performance in subjects with a history of complex treatment for cranial and craniospinal tumors in childhood. : the study of 48 subjects who underwent cranial and craniospinal irradiation for CNS tumors in childhood and 20 healthy age- and sex-matched volunteers was conducted. The examination included hormone studies, cardiopulmonary exercise testing, and, in the main group, echocardiography (ECHO). In five (10.4%) patients, ECHO changes were detected after complex anti-cancer treatment: thickening and calcification of the aortic valve leaflets (2%), and reduction in the systolic LV and RV function (8% and 6%, respectively). Irradiation of various areas was a significant predictor for reduced exercise tolerance, hyperventilation at rest and upon exertion, and an increased ventilatory equivalent for carbon dioxide. Low exercise tolerance was associated with a younger age at the time of treatment initiation. Significant differences were noted between the control group and the childhood cancer survivors with endocrine disorders. The obtained data confirm the importance of regular cardiovascular and endocrine monitoring of this group of cancer survivors.
PubMed: 38892756
DOI: 10.3390/jcm13113045 -
Journal of Clinical Medicine May 2024The treatment of head and neck cancers (HNCs) encompasses a complex paradigm involving a combination of surgery, radiotherapy, and systemic treatment. Locoregional... (Review)
Review
The treatment of head and neck cancers (HNCs) encompasses a complex paradigm involving a combination of surgery, radiotherapy, and systemic treatment. Locoregional recurrence is a common cause of treatment failure, and few patients are suitable for salvage surgery. Reirradiation with conventional radiation techniques is challenging due to normal tissue tolerance limits and the risk of significant toxicities. Stereotactic body radiotherapy (SBRT) has emerged as a highly conformal modality that offers the potential for cure while limiting the dose to surrounding tissue. There is also growing research that shows that those with oligometastatic disease can benefit from curative intent local ablative therapies such as SBRT. This review will look at published evidence regarding the use of SBRT in locoregional recurrent and oligometastatic HNCs.
PubMed: 38892731
DOI: 10.3390/jcm13113020 -
International Journal of Molecular... Jun 2024In order to overcome the resistance to radiotherapy in human chondrosarcoma cells, the prevention from efficient DNA repair with a combined treatment with the...
In order to overcome the resistance to radiotherapy in human chondrosarcoma cells, the prevention from efficient DNA repair with a combined treatment with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) inhibitor AZD7648 was explored for carbon ion (C-ion) as well as reference photon (X-ray) irradiation (IR) using gene expression analysis, flow cytometry, protein phosphorylation, and telomere length shortening. Proliferation markers and cell cycle distribution changed significantly after combined treatment, revealing a prominent G/M arrest. The expression of the G/M checkpoint genes cyclin B, CDK1, and WEE1 was significantly reduced by IR alone and the combined treatment. While IR alone showed no effects, additional AZD7648 treatment resulted in a dose-dependent reduction in AKT phosphorylation and an increase in Chk2 phosphorylation. Twenty-four hours after IR, the key genes of DNA repair mechanisms were reduced by the combined treatment, which led to impaired DNA repair and increased radiosensitivity. A time-dependent shortening of telomere length was observed in both cell lines after combined treatment with AZD7648 and 8 Gy X-ray/C-ion IR. Our data suggest that the inhibition of DNA-PKcs may increase sensitivity to X-rays and C-ion IR by impairing its functional role in DNA repair mechanisms and telomere end protection.
Topics: Humans; DNA-Activated Protein Kinase; Cell Line, Tumor; Chondrosarcoma; Heavy Ion Radiotherapy; Telomere; Cell Cycle Checkpoints; DNA Repair; Radiation Tolerance; Pyrazoles; Cell Proliferation; Bone Neoplasms; G2 Phase Cell Cycle Checkpoints
PubMed: 38892366
DOI: 10.3390/ijms25116179 -
International Journal of Molecular... May 2024We aimed to determine whether monitoring tumor-derived exosomal microRNAs (miRNAs) could be used to assess radiotherapeutic sensitivity in patients with locally advanced...
We aimed to determine whether monitoring tumor-derived exosomal microRNAs (miRNAs) could be used to assess radiotherapeutic sensitivity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). RNA sequencing was employed to conduct a comparative analysis of miRNA expression levels during radiotherapy, focusing on identifying miRNAs associated with progression. Electron microscopy confirmed the existence of exosomes, and co-cultivation assays and immunofluorescence validated their capacity to infiltrate macrophages. To determine the mechanism by which exosomal miR-143-3p regulates the interplay between ESCC cells and M2 macrophages, ESCC cell-derived exosomes were co-cultured with macrophages. Serum miR-143-3p and miR-223-3p were elevated during radiotherapy, suggesting resistance to radiation and an unfavorable prognosis for ESCC. Increased levels of both miRNAs independently predicted shorter progression-free survival ( = 0.015). We developed a diagnostic model for ESCC using serum microRNAs, resulting in an area under the curve of 0.751. Radiotherapy enhanced the release of miR-143-3p from ESCC cell-derived exosomes. Immune cell infiltration analysis at the Cancer Genome Atlas (TCGA) database revealed that ESCC cell-derived miR-143-3p triggered M2 macrophage polarization. Mechanistically, miR-143-3p upregulation affected chemokine activity and cytokine signaling pathways. Furthermore, ESCC cell exosomal miR-143-3p could be transferred to macrophages, thereby promoting their polarization. Serum miR-143-3p and miR-223-3p could represent diagnostic and prognostic markers for patients with ESCC undergoing radiotherapy. Unfavorable prognosis could be linked to the increased levels of ESCC cell-derived exosomal miR-143-3p, which might promote tumor progression by interacting with macrophages.
Topics: MicroRNAs; Humans; Exosomes; Esophageal Squamous Cell Carcinoma; Macrophages; Radiation Tolerance; Esophageal Neoplasms; Cell Line, Tumor; Male; Female; Gene Expression Regulation, Neoplastic; Middle Aged; Prognosis; Aged; Macrophage Activation
PubMed: 38892269
DOI: 10.3390/ijms25116082 -
International Journal of Molecular... May 2024The primary emphasis of photoimmunology is the impact of nonionizing radiation on the immune system. With the development of terahertz (THz) and sub-terahertz (sub-THz)...
The primary emphasis of photoimmunology is the impact of nonionizing radiation on the immune system. With the development of terahertz (THz) and sub-terahertz (sub-THz) technology, the biological effects of this emerging nonionizing radiation, particularly its influence on immune function, remain insufficiently explored but are progressively attracting attention. Here, we demonstrated that 0.1 sub-THz radiation can modulate the immune system and alleviate symptoms of arthritis in collagen-induced arthritis (CIA) mice through a nonthermal manner. The application of 0.1 sub-THz irradiation led to a decrease in proinflammatory factors within the joints and serum, reducing the levels of blood immune cells and the quantity of splenic CD4 T cells. Notably, 0.1 sub-THz irradiation restored depleted Treg cells in CIA mice and re-established the Th17/Treg equilibrium. These findings suggested that sub-THz irradiation plays a crucial role in systemic immunoregulation. Further exploration of its immune modulation mechanisms revealed the anti-inflammatory properties of 0.1 sub-THz on LPS-stimulated skin keratinocytes. Through the reduction in NF-κB signaling and NLRP3 inflammasome activation, 0.1 sub-THz irradiation effectively decreased the production of inflammatory factors and immune-active substances, including IL-1β and PGE, in HaCaT cells. Consequently, 0.1 sub-THz irradiation mitigated the inflammatory response and contributed to the maintenance of immune tolerance in CIA mice. This research provided significant new evidence supporting the systemic impacts of 0.1 sub-THz radiation, particularly on the immune system. It also enhanced the field of photoimmunology and offered valuable insights into the potential biomedical applications of 0.1 sub-THz radiation for treating autoimmune diseases.
Topics: Animals; Arthritis, Experimental; Mice; Terahertz Radiation; Anti-Inflammatory Agents; Male; NLR Family, Pyrin Domain-Containing 3 Protein; Inflammasomes; NF-kappa B; Mice, Inbred DBA; T-Lymphocytes, Regulatory; Humans; Signal Transduction; Keratinocytes
PubMed: 38892148
DOI: 10.3390/ijms25115963 -
Plants (Basel, Switzerland) May 2024The Valdivian region has a temperate rainy climate with differences in rainfall throughout the year. This heterogeneity results in periods of summer drought that expose...
The Valdivian region has a temperate rainy climate with differences in rainfall throughout the year. This heterogeneity results in periods of summer drought that expose the poikilohydric epiphytes to desiccation. With this research, we aim to answer different research questions related to phorophyte preference, response to desiccation, and response to radiation. How does the diversity of macrolichens vary at a local and microclimate scale in three tree species within an evergreen forest? What is the tolerance limit of macrolichens against prolonged desiccation, according to evaluation of the maximum efficiency of PSII (Fv/Fm) and pigment concentration? What is the tolerance limit against a potential increase in radiation? We found that macrolichen communities are determined by tree species, which regulate the suitability of the substrate by modifying the temperature and humidity conditions. In addition, our results show a rapid photosynthetic alteration in temporal exposure to desiccation, measured through Fv/Fm and pigment concentration. Our results showed that the most sensitive lichens to radiation and desiccation are not coincident. We confirm the low tolerance of macrolichen species to high radiation, reflected in the saturation profile obtained for the set studied. The lichen community in the evergreen forest showed high complexity and vulnerability, pointing to the importance of more research.
PubMed: 38891327
DOI: 10.3390/plants13111519 -
Plant Biology (Stuttgart, Germany) Jun 2024In Mediterranean regions, severe summers are becoming more common, leading to restrictions to vine productivity and yield quality, requiring sustainable practices to...
In Mediterranean regions, severe summers are becoming more common, leading to restrictions to vine productivity and yield quality, requiring sustainable practices to support this sector. We assessed the behaviour of three red grapevine varieties from the Douro Region to examine their tolerance to summer climate stress from the perspective that the less common varieties may have potential for increased use in a climate change scenario. Leaf and fruit biochemical profile, antioxidant activity and fruit colorimetric parameters were assessed at different phenological stages in Aragonez (AR), Tinto Cão (TC) and Touriga Nacional (TN) grape varieties. All three varieties exhibit significant variability in phenological timing, influenced by genetic and environmental factors. Photosynthetic pigment strategies differed among varieties. Chlorophyll content in AR was high to cope with high radiation, while TN displaying a balanced approach, and TC had lower pigment levels, with higher levels of phenolics, antioxidants, and soluble sugars, particularly during stress. The variations in berry biochemical profile highlight the distinct characteristics of the varieties. TC and TN show potential for coping with climate change, having elevated total acidity, while AR has larger and heavier berries with distinct coloration. These findings reinforce the need to study the behaviour of different varieties in each Terroir, to understand their diverse strategies to deal with summer climate stress. This will help in selecting the most suitable variety for these conditions under vineyard management in the Douro Region.
PubMed: 38886872
DOI: 10.1111/plb.13671 -
Radiation Oncology (London, England) Jun 2024Rare but severe toxicities of the optic apparatus have been observed after treatment of intracranial tumours with proton therapy. Some adverse events have occurred at...
BACKGROUND AND PURPOSE
Rare but severe toxicities of the optic apparatus have been observed after treatment of intracranial tumours with proton therapy. Some adverse events have occurred at unusually low dose levels and are thus difficult to understand considering dose metrics only. When transitioning from double scattering to pencil beam scanning, little consideration was given to increased dose rates observed with the latter delivery paradigm. We explored if dose rate related metrics could provide additional predicting factors for the development of late visual toxicities.
MATERIALS AND METHODS
Radiation-induced intracranial visual pathway lesions were delineated on MRI for all index cases. Voxel-wise maximum dose rate (MDR) was calculated for 2 patients with observed optic nerve toxicities (CTCAE grade 3 and 4), and 6 similar control cases. Additionally, linear energy transfer (LET) related dose enhancing metrics were investigated.
RESULTS
For the index cases, which developed toxicities at low dose levels (mean, 50 Gy), some dose was delivered at higher instantaneous dose rates. While optic structures of non-toxicity cases were exposed to dose rates of up to 1 to 3.2 Gy/s, the pre-chiasmatic optic nerves of the 2 toxicity cases were exposed to dose rates above 3.7 Gy/s. LET-related metrics were not substantially different between the index and non-toxicity cases.
CONCLUSIONS
Our observations reveal large variations in instantaneous dose rates experienced by different volumes within our patient cohort, even when considering the same indications and beam arrangement. High dose rate regions are spatially overlapping with the radiation induced toxicity areas in the follow up images. At this point, it is not feasible to establish causality between exposure to high dose rates and the development of late optic apparatus toxicities due to the low incidence of injury.
Topics: Humans; Proton Therapy; Brain Neoplasms; Radiotherapy Dosage; Female; Male; Middle Aged; Adult; Radiation Injuries; Aged; Optic Nerve; Organs at Risk; Radiotherapy Planning, Computer-Assisted; Dose-Response Relationship, Radiation
PubMed: 38886727
DOI: 10.1186/s13014-024-02464-z -
Molecular Pharmaceutics Jul 2024Squamous cell carcinoma (SCC) is a common nonmelanoma skin cancer. Radiotherapy plays an integral role in treating SCC due to its characteristics, such as diminished...
Squamous cell carcinoma (SCC) is a common nonmelanoma skin cancer. Radiotherapy plays an integral role in treating SCC due to its characteristics, such as diminished intercellular adhesion, heightened cell migration and invasion capabilities, and immune evasion. These problems lead to inaccurate tumor boundary positioning and radiotherapy tolerance in SCC treatment. Thus, accurate localization and enhanced radiotherapy sensitivity are imperative for effective SCC treatment. To address the existing limitations in SCC therapy, we developed monoglyceride solid lipid nanoparticles (MG SLNs) and enveloped them with the A431 cell membrane (A431 CM) to create A431@MG. The characterization results showed that A431@MG was spherical. Furthermore, A431@MG had specific targeting for A431 cells. In A431 tumor-bearing mice, A431@MG demonstrated prolonged accumulation within tumors, ensuring precise boundary localization of SCC. We further advanced the approach by preparing MG SLNs encapsulating 5-aminolevulinic acid methyl ester (MLA) and desferrioxamine (DFO) with an A431 CM coating to yield A431@MG-MLA/DFO. Several studies have revealed that DFO effectively reduced iron content, impeding protoporphyrin IX (PpIX) biotransformation and promoting PpIX accumulation. Simultaneously, MLA was metabolized into PpIX upon cellular entry. During radiotherapy, the heightened PpIX levels enhanced reactive oxygen species (ROS) generation, inducing DNA and mitochondrial damage and leading to cell apoptosis. In A431 tumor-bearing mice, the A431@MG-MLA/DFO group exhibited notable radiotherapy sensitization, displaying superior tumor growth inhibition. Combining A431@MG-MLA/DFO with radiotherapy significantly improved anticancer efficacy, highlighting its potential to serve as an integrated diagnostic and therapeutic strategy for SCC.
Topics: Animals; Mice; Nanoparticles; Humans; Cell Line, Tumor; Skin Neoplasms; Carcinoma, Squamous Cell; Radiation-Sensitizing Agents; Cell Membrane; Aminolevulinic Acid; Lipids; Xenograft Model Antitumor Assays; Deferoxamine; Mice, Nude; Female; Mice, Inbred BALB C; Reactive Oxygen Species; Apoptosis; Liposomes
PubMed: 38885477
DOI: 10.1021/acs.molpharmaceut.3c01247