scholarly journals Investigating dose homogeneity in radiotherapy of oral cancers in the presence of a dental implant system: an in vitro phantom study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Goli Khaleghi ◽  
Hoda Mahdavi ◽  
Rabi Mahdavi ◽  
Benyamin Khajetash ◽  
Alireza Nikoofar ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Dental Implant ◽  
Dose Distribution ◽  
Dose Calculation ◽  
Tumor Control ◽  
High Dose ◽  
Dose Calculations ◽  
Dose Homogeneity ◽  
Implant System

Abstract Background Materials with high atomic numbers are part of the composition of dental implant systems. In radiotherapy of oral cavity cancers, an implant can cause dose perturbations that affect target definition, dose calculation, and dose distribution. In consequence, this may result in poor tumor control and higher complications. In this study, we evaluated dose homogeneity when a dental implant replaced a normal tooth. We also aimed to evaluate the concordance of dose calculations with dose measurements. Materials and methods In this study, 2 sets of planning CT scans of a phantom with a normal tooth and the same phantom with the tooth replaced by a Z1 TBR dental implant system were used. The implant system was composed of a porcelain-fused-to-metal crown and titanium with a zirconium collar. Three radiotherapy plans were designed when the density of the implant material was corrected to match their elements, or when all were set to the density of water, or when using the default density conversion. Gafchromic EBT-3 films at the level of isocenter and crowns were used for measurements. Results At the level of crowns, upstream and downstream dose calculations were reduced when metal kernels were applied (M-plan). Moreover, relatively measured dose distribution patterns were most similar to M-plan. At this level, relative to the non-implanted phantom, mean doses values were higher with the implant (215.93 vs. 192.25), also, new high-dose areas appeared around a low-dose streak forward to the implant (119% vs. 95%). Conclusions Implants can cause a high dose to the oral cavity in radiotherapy because of extra scattered radiation. Knowledge of the implant dimensions and defining their material enhances the accuracy of calculations.

scholarly journals Development of Dosimetric Verification System for Patient-Specific Quality Assurance of High-Dose-Rate Brachytherapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Sang-Won Kang ◽  
Jin-Beom Chung ◽  
Kyeong-Hyeon Kim ◽  
Chang Heon Choi ◽  
Seonghee Kang ◽  
...  
Keyword(s):  
Dose Distribution ◽  
Dose Range ◽  
Radial Distance ◽  
Dose Calculation ◽  
High Dose Rate ◽  
Patient Specific ◽  
High Dose ◽  
Passing Rates ◽  
Dwell Position ◽  
Dosimetric Verification

Purpose: The aim of this study was to develop a dosimetric verification system (DVS) using a solid phantom for patient-specific quality assurance (QA) of high-dose-rate brachytherapy (HDR-BT).Methods: The proposed DVS consists of three parts: dose measurement, dose calculation, and analysis. All the dose measurements were performed using EBT3 film and a solid phantom. The solid phantom made of acrylonitrile butadiene styrene (ABS, density = 1.04 g/cm3) was used to measure the dose distribution. To improve the accuracy of dose calculation by using the solid phantom, a conversion factor [CF(r)] according to the radial distance between the water and the solid phantom material was determined by Monte Carlo simulations. In addition, an independent dose calculation program (IDCP) was developed by applying the obtained CF(r). To validate the DVS, dosimetric verification was performed using gamma analysis with 3% dose difference and 3 mm distance-to-agreement criterion for three simulated cases: single dwell position, elliptical dose distribution, and concave elliptical dose distribution. In addition, the possibility of applying the DVS in the high-dose range (up to 15 Gy) was evaluated.Results: The CF(r) between the ABS and water phantom was 0.88 at 0.5 cm. The factor gradually increased with increasing radial distance and converged to 1.08 at 6.0 cm. The point doses 1 cm below the source were 400 cGy in the treatment planning system (TPS), 373.73 cGy in IDCP, and 370.48 cGy in film measurement. The gamma passing rates of dose distributions obtained from TPS and IDCP compared with the dose distribution measured by the film for the simulated cases were 99.41 and 100% for the single dwell position, 96.80 and 100% for the elliptical dose distribution, 88.91 and 99.70% for the concave elliptical dose distribution, respectively. For the high-dose range, the gamma passing rates in the dose distributions between the DVS and measurements were above 98% and higher than those between TPS and measurements.Conclusion: The proposed DVS is applicable for dosimetric verification of HDR-BT, as confirmed through simulated cases for various doses.

scholarly journals Cancer Cells Can Exhibit a Sparing FLASH Effect at Low Doses Under Normoxic In Vitro-Conditions

2021 ◽  
Vol 11 ◽  
Author(s):  
Gabriel Adrian ◽  
Elise Konradsson ◽  
Sarah Beyer ◽  
Anders Wittrup ◽  
Karl T. Butterworth ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Lung Fibroblasts ◽  
Normal Lung ◽  
Tumor Control ◽  
High Dose ◽  
Low Doses ◽  
Early Passage

BackgroundIrradiation with ultra-high dose rate (FLASH) has been shown to spare normal tissue without hampering tumor control in several in vivo studies. Few cell lines have been investigated in vitro, and previous results are inconsistent. Assuming that oxygen depletion accounts for the FLASH sparing effect, no sparing should appear for cells irradiated with low doses in normoxia.MethodsSeven cancer cell lines (MDA-MB-231, MCF7, WiDr, LU-HNSCC4, HeLa [early passage and subclone]) and normal lung fibroblasts (MRC-5) were irradiated with doses ranging from 0 to 12 Gy using FLASH (≥800 Gy/s) or conventional dose rates (CONV, 14 Gy/min), with a 10 MeV electron beam from a clinical linear accelerator. Surviving fraction (SF) was determined with clonogenic assays. Three cell lines were further studied for radiation-induced DNA-damage foci using a 53BP1-marker and for cell cycle synchronization after irradiation.ResultsA tendency of increased survival following FLASH compared with CONV was suggested for all cell lines, with significant differences for 4/7 cell lines. The magnitude of the FLASH-sparing expressed as a dose-modifying factor at SF=0.1 was around 1.1 for 6/7 cell lines and around 1.3 for the HeLasubclone. Similar cell cycle distributions and 53BP1-foci numbers were found comparing FLASH to CONV.ConclusionWe have found a FLASH effect appearing at low doses under normoxic conditions for several cell lines in vitro. The magnitude of the FLASH effect differed between the cell lines, suggesting inherited biological susceptibilities for FLASH irradiation.

scholarly journals FLASH Radiotherapy: Current Knowledge and Future Insights Using Proton-Beam Therapy

2020 ◽  
Vol 21 (18) ◽  
pp. 6492 ◽  
Author(s):  
Jonathan R. Hughes ◽  
Jason L. Parsons
Keyword(s):  
Dose Rate ◽  
Proton Beam ◽  
Current Knowledge ◽  
Proton Beam Therapy ◽  
High Dose Rate ◽  
Tumor Control ◽  
High Dose ◽  
The Future

FLASH radiotherapy is the delivery of ultra-high dose rate radiation several orders of magnitude higher than what is currently used in conventional clinical radiotherapy, and has the potential to revolutionize the future of cancer treatment. FLASH radiotherapy induces a phenomenon known as the FLASH effect, whereby the ultra-high dose rate radiation reduces the normal tissue toxicities commonly associated with conventional radiotherapy, while still maintaining local tumor control. The underlying mechanism(s) responsible for the FLASH effect are yet to be fully elucidated, but a prominent role for oxygen tension and reactive oxygen species production is the most current valid hypothesis. The FLASH effect has been confirmed in many studies in recent years, both in vitro and in vivo, with even the first patient with T-cell cutaneous lymphoma being treated using FLASH radiotherapy. However, most of the studies into FLASH radiotherapy have used electron beams that have low tissue penetration, which presents a limitation for translation into clinical practice. A promising alternate FLASH delivery method is via proton beam therapy, as the dose can be deposited deeper within the tissue. However, studies into FLASH protons are currently sparse. This review will summarize FLASH radiotherapy research conducted to date and the current theories explaining the FLASH effect, with an emphasis on the future potential for FLASH proton beam therapy.

A brachytherapia szerepe az ajak-szájüregi daganatok kuratív ellátásában

2021 ◽  
Vol 162 (37) ◽  
pp. 1471-1479
Author(s):  
Örs Ferenczi ◽  
Tibor Major ◽  
Zoltán Takácsi-Nagy
Keyword(s):  
Oral Cavity ◽  
Dose Rate ◽  
Low Dose ◽  
High Dose Rate ◽  
Therapeutic Modality ◽  
Tumor Control ◽  
External Irradiation ◽  
High Dose ◽  
Low Dose Rate ◽  
Pulse Dose

Összefoglaló. A szájüregi daganatok kuratív kezelésében az elsődlegesen választandó műtét mellett a sugárterápiának is jelentős szerepe van. A lokális tumormentesség biztosításához azonban dóziseszkaláció szükséges. Ennek külső besugárzással való megvalósítása a környező normálszövetek fölösleges dózisterhelésével és az ebből következő mellékhatások előfordulásának emelkedésével jár. A brachytherapia (BT) – amelynek során radioaktív sugárforrást/sugárforrásokat juttatunk a tumorba vagy annak közelébe – lehetővé teszi a helyileg magasabb dózis leadását a környező ép szövetek kímélésével. A BT a korai, T1–2N0 stádiumú szájüregi tumoroknál – kedvező prognosztikai faktorok mellett – akár kizárólagosan vagy mint posztoperatíve egyedül alkalmazott terápiás modalitás jön szóba. Kedvezőtlenebb prognózis esetén vagy előrehaladottabb stádiumban (T3–4 vagy N+) a műtétet és/vagy a percutan irradiációt kiegészítő eljárásként alkalmazható kedvező sugárfizikai tulajdonságai miatt. A kis dózisteljesítményű (low-dose-rate, LDR) BT-t már évtizedek óta alkalmazzák a terápiában, de ezt kezdi kiszorítani a nagy dózisteljesítményű (high-dose-rate, HDR), illetve a pulzáló dózisteljesítményű (pulse-dose-rate, PDR) BT. A jelen áttekintő tanulmány célja irodalmi adatok alapján a BT szerepének és indikációjának ismertetése a szájüregi daganatok kuratív kezelésében, alrégiókra lebontva. Orv Hetil. 2021; 162(37): 1471–1479. Summary. Radiation therapy plays a significant role in the curative treatment of oral cavity tumors, in addition to the primary choice of surgery. However, dose escalation is required to ensure local tumor control. Its implementation with external irradiation is accompanied by an unnecessary dose exposure to the surrounding normal tissues and an increase in the incidence of consequent side effects. Brachytherapy (BT), in which a radiation source/sources is/are placed inside or close to the tumor, allows a higher dose to be delivered locally, sparing the surrounding intact tissues. In addition to favorable prognostic factors in early T1–2N0 stage oral cavity tumors, BT is considered either exclusively or as a sole postoperative therapeutic modality. At less favorable prognosis or at a more advanced stage (T3–4 or N+), BT can be used as a complementary procedure after surgery and/or percutaneous irradiation based on its favorable radio-physical properties. Low-dose-rate (LDR) BT has been used in the therapy for decades, but recently it has been replaced by high-dose-rate (HDR) and pulse-dose-rate (PDR) BT. The purpose of this review is to describe the role and indications of BT in the treatment of oral cavity tumors categorized into subregions, based on the literature data. Orv Hetil. 2021; 162(37): 1471–1479.

Significance of Platelet β-Adrenoceptors for Platelet Responses In Vivo and In Vitro

1992 ◽  
Vol 68 (06) ◽  
pp. 687-693 ◽  
Author(s):  
P T Larsson ◽  
N H Wallén ◽  
A Martinsson ◽  
N Egberg ◽  
P Hjemdahl
Keyword(s):  
Ex Vivo ◽  
High Dose ◽  
Platelet Aggregability ◽  
Adrenoceptor Agonist ◽  
Dose Infusion ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen

SummaryThe significance of platelet β-adrenoceptors for platelet responses to adrenergic stimuli in vivo and in vitro was studied in healthy volunteers. Low dose infusion of the β-adrenoceptor agonist isoprenaline decreased platelet aggregability in vivo as measured by ex vivo filtragometry. Infusion of adrenaline, a mixed α- and β-adrenoceptor agonist, increased platelet aggregability in vivo markedly, as measured by ex vivo filtragometry and plasma β-thromboglobulin levels. Adrenaline levels were 3–4 nM in venous plasma during infusion. Both adrenaline and high dose isoprenaline elevated plasma von Willebrand factor antigen levels β-Blockade by propranolol did not alter our measures of platelet aggregability at rest or during adrenaline infusions, but inhibited adrenaline-induced increases in vWf:ag. In a model using filtragometry to assess platelet aggregability in whole blood in vitro, propranolol enhanced the proaggregatory actions of 5 nM, but not of 10 nM adrenaline. The present data suggest that β-adrenoceptor stimulation can inhibit platelet function in vivo but that effects of adrenaline at high physiological concentrations are dominated by an α-adrenoceptor mediated proaggregatory action.

Quality-by-Design Enabled Chitosan Nanoparticles for Antitubercular Therapy: Formulation, Statistical Optimization, and In vitro Characterization

2020 ◽  
Vol 15 ◽  
Author(s):  
Manasi M. Chogale ◽  
Sujay S. Gaikwad ◽  
Savita P. Kulkarni ◽  
Vandana B. Patravale
Keyword(s):  
Side Effects ◽  
Treatment Regimen ◽  
Research Work ◽  
Chitosan Nanoparticles ◽  
In Vitro Release ◽  
Antitubercular Therapy ◽  
Prolonged Treatment ◽  
High Dose ◽  
Average Size

Background: Tuberculosis (TB) continues to be among the leading causes for high mortality among developing countries. Though a seemingly effective treatment regimen against TB is in place, there has been no significant improvement in the therapeutic rates. This is primarily owing to the high drug doses, their associated sideeffects, and prolonged treatment regimen. Discontinuation of therapy due to the severe side effects of the drugs results in the progression of the infection to the more severe drug-resistant TB. Objectives: Reformulation of the current existing anti TB drugs into more efficient dosage forms could be an ideal way out. Nanoformulations have been known to mitigate the side effects of toxic, high-dose drugs. Hence, the current research work involves the formulation of Isoniazid (INH; a first-line anti TB molecule) loaded chitosan nanoparticles for pulmonary administration. Methods: INH loaded chitosan nanoparticles were prepared by ionic gelation method using an anionic crosslinker. Drugexcipient compatibility was evaluated using DSC and FT-IR. The formulation was optimized on the principles of Qualityby-Design using a full factorial design. Results: The obtained nanoparticles were spherical in shape having an average size of 620±10.97 nm and zeta potential +16.87±0.79 mV. Solid state characterization revealed partial encapsulation and amorphization of INH into the nanoparticulate system. In vitro release study confirmed an extended release of INH from the system. In vitro cell line based safety and efficacy studies revealed satisfactory results. Conclusion: The developed nanosystem is thus an efficient approach for antitubercular therapy.

Methylprednisolone on circulating eicosanoids and vasomotor tone after endotoxin

1986 ◽  
Vol 61 (1) ◽  
pp. 185-191 ◽  
Author(s):  
C. A. Hales ◽  
R. D. Brandstetter ◽  
C. F. Neely ◽  
M. B. Peterson ◽  
D. Kong ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Resistance ◽  
Systemic Blood Pressure ◽  
Physiological Effect ◽  
High Dose ◽  
Systemic Blood ◽  
Eicosanoid Production ◽  
Circulating Levels

Acute pulmonary and systemic vasomotor changes induced by endotoxin in dogs have been related, at least in part, to the production of eicosanoids such as the vasoconstrictor thromboxane and the vasodilator prostacyclin. Steroids in high doses, in vitro, inhibit activation of phospholipase A2 and prevent fatty acid release from cell membranes to enter the arachidonic acid cascade. We, therefore, administered methylprednisolone (40 mg/kg) to dogs to see if eicosanoid production and the ensuing vasomotor changes could be prevented after administration of 150 micrograms/kg of endotoxin. The stable metabolites of thromboxane B2 (TxB2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) were measured by radioimmunoassay. Methylprednisolone by itself did not alter circulating eicosanoids but when given 2.5 h before endotoxin not only failed to inhibit endotoxin-induced eicosanoid production but actually resulted in higher circulating levels of 6-keto-PGF1 alpha (P less than 0.05) compared with animals receiving endotoxin alone. Indomethacin prevented the steroid-enhanced concentrations of 6-keto-PGF1 alpha after endotoxin and prevented the greater fall (P less than 0.05) in systemic blood pressure and systemic vascular resistance with steroid plus endotoxin than occurred with endotoxin alone. Administration of methylprednisolone immediately before endotoxin resulted in enhanced levels (P less than 0.05) of both TxB2 and 6-keto-PGF1 alpha but with a fall in systemic blood pressure and vascular resistance similar to the animals pretreated by 2.5 h. In contrast to the early steroid group in which all of the hypotensive effect was due to eicosanoids, in the latter group steroids had an additional nonspecific effect. Thus, in vivo, high-dose steroids did not prevent endotoxin-induced increases in eicosanoids but actually increased circulating levels of TxB2 and 6-keto-PGF1 alpha with a physiological effect favoring vasodilation.

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