Dose Homogeneity Research Articles

Exploring beamline momentum acceptance for tracking respiratory variability in lung cancer proton therapy: a simulation study

Objective. Investigating the aspects of proton beam delivery to track organ motion with pencil beam scanning therapy. Considering current systems as a reference, specify requirements for next-generation units aiming at real-time image-guided treatments. Approach. Proton treatments for six non-small cell lung cancer (NSCLC) patients were simulated using repeated 4DCTs to model respiratory motion variability. Energy corrections required for this treatment site were evaluated for different approaches to tumour tracking, focusing on the potential for energy adjustment within beamline momentum acceptance (dp/p). A respiration-synchronised tracking, taking into account realistic machine delivery limits, was compared to ideal tracking scenarios, in which unconstrained energy corrections are possible. Rescanning and the use of multiple fields to mitigate residual interplay effects and dose degradation have also been investigated. Main results. Energy correction requirements increased with motion amplitudes, for all patients and tracking scenarios. Higher dose degradation was found for larger motion amplitudes, rescanning has beneficial effects and helped to improve dosimetry metrics for the investigated limited dp/p of 1.2% (realistic) and 2.4%. The median differences between ideal and respiratory-synchronised tracking show minimal discrepancies, 1% and 5% respectively for dose coverage (CTV V95) and homogeneity (D5-D95). Multiple-field planning improves D5-D95 up to 50% in the most extreme cases while it does not show a significant effect on V95. Significance. This work shows the potential of implementing tumour tracking in current proton therapy units and outlines design requirements for future developments. Energy regulation within momentum acceptance was investigated to tracking tumour motion with respiratory-synchronisation, achieving results in line with the performance of ideal tracking scenarios. ±5% Δp/p would allow to compensate for all range offsets in our NSCLC patient cohort, including breathing variability. However, the realistic momentum of 1.2% dp/p representative of existing medical units limitations, has been shown to preserve plan quality.

Development and Quality Assurance of Multileaf Collimator (MLC) Auto-Feathering Junctions for Multi-Isocenter Supine Volumetric Modulated Arc Therapy (VMAT) Craniospinal Axis Irradiation on Halcyon.

Currently, there is alack of methods and tools that efficiently evaluate the auto-feathering junctions created by multileaf collimator (MLCs) for supine volumetric modulated arc therapy (VMAT) craniospinalirradiation (CSI) plans. We have investigated the feasibility of stitching together multi-isocenter fluence maps to then analyze the feathered junctions for patient-specific quality assurance (QA). Furthermore, we investigated the capability of Halcyon for the treatment of CSI patients.Three patients, who previously underwent VMAT CSI treatment on TrueBeam (6-MV flattening filter-free (FFF)) for 36 Gy in 20 fractionswerereplanned for Halcyon. A multi-isocenter approach with only translational superior-inferior shifts was used for both platforms. Each isocenter consists of two full arcs with anterior avoidance sectors, ±5° collimator rotations between arcs, and 5-8 cm of overlapping MLC auto-feathering junctions. All plans were QA'd via electronicportalimaging device (EPID) portal dosimetry and analyzed with a gamma criteria of 3%/3 mm. A variety of plan quality metrics were analyzed to evaluate dose distributions to the target, doses to organs at risk (OARs), and integral dose to the patient. A MATLAB script was developed to stitch the calculated and measured fluence maps in order to perform patient-specific QA for the composite fluence.The Halcyon plans provided highly conformal and homogenous dose distributions to the entire CSI target, superior to the clinical TrueBeam plans, while sparing critical organs with significantly lower values of V10Gy and V18Gy by up to 2% and 2.5%, respectively.Qualitative depictions of vertical dose profiles from the stitched DICOM of the entire CSI target for both planned and delivered fluence maps demonstrated equivalency, with slightly lower average pass rates with Halcyon (97%) compared to TrueBeam(99.9%). This approach to stitch multiple measured versus calculated EPID fluence maps has shown to be a feasible and accurate method and will be helpful for comprehensive VMAT CSI QA on both platforms. Further implementation of this script will be used in examining dosimetric impacts of daily patient positioning errors at MLC auto-feathering junctions.

Hypoxia dose painting in SBRT – the virtual clinical trial approach

Background Treating hypoxic tumours remains a challenge in radiotherapy as hypoxia leads to enhanced tumour aggressiveness and resistance to radiation. As escalating the doses is rarely feasible within the healthy tissue constraints, dose-painting strategies have been explored. Consensus about the best of care for hypoxic tumours has however not been reached because, among other reasons, the limits of current functional in-vivo imaging systems in resolving the details and dynamics of oxygen transport in tissue. Computational modelling of the tumour microenvironment enables the design and conduction of virtual clinical trials by providing relationships between biological features and treatment outcomes. This study presents a framework for assessing the therapeutic influence of the individual characteristics of the vasculature and the resulting oxygenation of hypoxic tumours in a virtual clinical trial on dose painting in stereotactic body radiotherapy (SBRT) circumventing the limitations of the imaging systems. Material and methods The homogeneous doses required to overcome hypoxia in simulated SBRT treatments of 1, 3 or 5 fractions were calculated for tumours with heterogeneous oxygenation derived from virtual vascular networks. The tumour control probability (TCP) was calculated for different scenarios for oxygenation dynamics resulting on cellular reoxygenation. Results A three-fractions SBRT treatment delivering 41.9 Gy (SD 2.8) and 26.5 Gy (SD 0.1) achieved only 21% (SD 12) and 48% (SD 17) control in the hypoxic and normoxic subvolumes, respectively whereas fast reoxygenation improved the control by 30% to 50%. TCP values for the individual tumours with similar characteristics, however, might differ substantially, highlighting the crucial role of the magnitude and time evolution of hypoxia at the microscale. Conclusion The results show that local microvascular heterogeneities may affect the predicted outcome in the hypoxic core despite escalated doses, emphasizing the role of theoretical modelling in understanding of and accounting for the dominant factors of the tumour microenvironment.

Evaluation of intensity-modulated electron FLASH radiotherapy in a clinical setting using veterinary cases.

The increased normal tissue tolerance for FLASH radiotherapy (FLASH-RT), as compared to conventional radiotherapy, was first observed in ultra-high dose rate electron beams. Initial clinical trials in companion animals have revealed a high risk of developing osteoradionecrosis following high-dose single-fraction electron FLASH-RT, which may be related to inhomogeneities in the dose distribution. In the current study, we aim to evaluate the possibilities of intensity-modulated electron FLASH-RT in a clinical setting to ensure a homogeneous dose distribution in future veterinary and human clinical trials. Our beam model in the treatment planning system electronRT (.decimal, LLC, Sanford, FL, USA) was based on a 10-MeV electron beam from a clinical linear accelerator used to treat veterinary patients with FLASH-RT in a clinical setting. In electronRT, the beam can be intensity-modulated using tungsten island blocks in the electron block cutout, and range-modulated using a customized bolus with variable thickness. Modulations were first validated in a heterogeneous phantom by comparing measured and calculated dose distributions. To evaluate the impact of intensity modulation in superficial single-fraction FLASH-RT, a treatment planning study was conducted, including eight canine cancer patient cases with simulated tumors in the head-and-neck region. For each case, treatment plans with and without intensity modulation were created for a uniform bolus and a range-modulating bolus. Treatment plans were evaluated using a target dose homogeneity index (HI), a conformity index (CI), the near-maximum dose outside the target ( ), and the near-minimum dose to the target ( ). By adding intensity modulation to plans with a uniform bolus, the HI could be improved (p=0.017). The combination of a range-modulating bolus and intensity modulation provided a further significant improvement of the HI as compared to using intensity modulation in combination with a uniform bolus (p=0.036). The range-modulating bolus also improved the CI compared to using a uniform bolus, both with an open beam (p=0.046) and with intensity modulation (p=0.018), as well as increased the (p=0.036 with open beam and p=0.05 with intensity modulation) and reduced the median (not significant). By using intensity-modulated electron FLASH-RT in combination with range-modulating bolus, the target dose homogeneity and conformity in canine patients with simulated tumors in complex areas in the head-and-neck region could be improved. By utilizing this technique, we hope to decrease the dose outside the target volume and avoid hot spots in future clinical electron FLASH-RT studies, thereby reducing the risk of radiation-induced toxicity.

Dosimetry for radiobiological in vivo experiments at laser plasma-based proton accelerators

Objective. Laser plasma-based accelerators (LPAs) of protons can contribute to research of ultra-high dose rate radiobiology as they provide pulse dose rates unprecedented at medical proton sources. Yet, LPAs pose challenges regarding precise and accurate dosimetry due to the high pulse dose rates, but also due to the sources’ lower spectral stability and pulsed operation mode. For in vivo models, further challenges arise from the necessary small field dosimetry for volumetric dose distributions. For these novel source parameters and intended applications, a dosimetric standard needs to be established. Approach. In this work, we present a dosimetry and beam monitoring framework for in vivo irradiations of small target volumes with LPA protons, solving aforementioned challenges. The volumetric dose distribution in a sample (mean dose value and lateral/depth dose inhomogeneity) is provided by combining two independent dose measurements using radiochromic films (dose rate-independent) and ionization chambers (dose rate-dependent), respectively. The unique feature of the dosimetric setup is beam monitoring with a transmission time-of-flight spectrometer to quantify spectral fluctuations of the irradiating proton pulses. The resulting changes in the depth dose profile during irradiation of an in vivo sample are hence accessible and enable pulse-resolved depth dose correction for each dose measurement. Main results. A first successful small animal pilot study using an LPA proton source serves as a testcase for the presented dosimetry approach and proves its performance in a realistic setting. Significance. With several facilities worldwide either setting up or already using LPA infrastructure for radiobiological studies with protons, the importance of LPA-adapted dosimetric frameworks as presented in this work is clearly underlined.

Dosimetric evaluation of a spinal cord dose-limiting 3D-CRT technique for radiotherapy of spinal metastases.

To evaluate the possible advantages of a simple spinal cord (SC) dose-limiting three-dimensional conformal radiotherapy (3D-CRT) technique in comparison to conventional two-dimensional (2D) techniques and other 3D-CRT techniques for spinal bone irradiation. For 41 spinal target volumes, seven different techniques were evaluated, using a standard schedule of 30Gy in 10 fractions. The SC dose-limiting 3D-CRT technique 1F2S-18MV using a single posterior field (F) supplemented by two anterior segment fields (S) and 18-MV photon beams was compared to two conventional 2D techniques (a single posterior field, PA, and two opposed anterior-posterior fields, APPA), three other 3D-CRT techniques (a single posterior field supplemented by four segment fields, 1F4S; two wedged fields, WD, and the SC dose-limiting variant using 6 MV, 1F2S-6MV) along with the original clinically applied plans. 1F2S-18MV demonstrated notably better results for all target volume parameters compared to the conventional 2D techniques (p<0.001). Limitation of the SC dose was significantly superior with 1F2S-18MV in comparison to PA and APPA (SC Dmean: 28.9±0.4 vs. 30.1±0.6Gy and 30.1±0.4Gy; SC Dmax: 30.9±0.7 vs. 32.5±1.0Gy and 31.8±0.7Gy; SC D1cm3 : 30.1±0.6 vs. 31.7±0.9Gy and 31.1±0.6Gy; p<0.001). Likewise, lower mean SC doses with 1F2S-18MV were observed in comparison to the more treatment time-consuming 3D-CRT techniques (1F4S, WD) and the original plans without relevant compromises on the dose homogeneity in the target volume and the dose exposure to the other OARs. In treatment planning of spinal metastases, simple variants of 3D-CRT-techniques like 1F2S-18MV can offer a significant dose limitation to the SC while providing a sufficient dose coverage of the target volume. Especially in patients with favorable life expectancy and potential need for re-irradiation, such SC dose-limiting 3D-CRT techniques may be a reasonable approach.

Quantitative beta autoradiography of a heterogeneous granulite sample and implications for luminescence dating

Beta dose rate heterogeneity is a known source of scatter in OSL measurement and equivalent dose distributions. Without proper methods to describe and account for it, it can contribute significantly to the uncertainties in OSL ages. For this reason, investigating the beta dose rate (β Dr) distribution is necessary to improve the dating of heterogeneous samples. Here we present a method for quantitative and high sensitivity autoradiographic imaging of beta dose rates. It is demonstrated using highly heterogeneous granulite rock samples. The accuracy and sensitivity of this method is improved using pulsed laser stimulation, and by underground exposure of samples in an ultra-low background environment. Results are calibrated using gamma (γ)irradiation and Monte Carlo simulation and have been validated using homogeneous dose rate standards. Combining analysis of autoradiography results and SEM backscattered images of the same samples allows determination of the dose rate distributions in the different mineral phases. A significant difference between the dose rate of K-feldspar grains obtained from the imaging and the dose rates calculated using methods commonly used in OSL dating is noted because of the clustering of grains in the sample. This represents a risk of bias in age determination in coarse grained rock samples which can be analysed using dose rate imaging methods. The beta Dr spatial distributions result in a significant dose scattering received by single grains, even compared to the total dose rate. The effect of such beta dose rate distributions on OSL dating of coarse-grained crystalline materials is discussed.

Implementation and evaluation of the AAPM TG 111 for radiation dosimetry in a state-of-the-art C-arm cone beam CT system

The aim of this study was to assess the dosimetric characteristics of a state-of-the-art C-arm cone beam computed tomography (CBCT) system using the methodology proposed by the American Association of Physicists in Medicine (AAPM) Task Group (TG) 111. The dose measurement methodology described in AAPM TG 111 for wide cone beam acquisitions without table translation was employed to estimate equilibrium beam length () and equilibrium dose () in various interventional task-specific protocols with different tube arc projection geometries. Dose profiles were derived from point dose measurements in the centre and peripheral locations of the ICRU/AAPM and standard polymethyl methacrylate (PMMA) body phantom. Dose measurements were performed in phantom and free-in-air using a solid-state point detector. Monte Carlo (MC) based simulation dosimetry was performed to quantify the inhomogeneous dose patterns imparted in the phantoms. Estimated and on the ICRU/AAPM phantom was up to 49.4 cm and 6.17 mGy/100 mAs, respectively. Corresponding values determined on the PMMA phantom were 139 cm and 8.8 mGy/100 mAs, respectively. Free-in-air dose measurement ranged from 1.43 mGy/100 mAs to 5.93 mGy/100 mAs. Per cent difference in and between MC simulation and solid-state point detector measurement methods in the ICRU/AAPM phantom were within 16% and 18%, respectively. Manufacturers can use the presented methodology to characterize the dosimetric properties of C-arm CBCT systems. Clinical medical physicists may follow this methodology to verify corresponding data provided by the manufacturer and check for C-arm CBCT system performance dosimetric consistency.

Analytical HDR prostate brachytherapy planning with automatic catheter and isotope selection.

High dose rate (HDR) brachytherapy is commonly used to treat prostate cancer. Existing HDR planning systems solve the dwell time problem for predetermined catheters and a single energy source. Additional degrees of freedom can be obtained by relaxing the catheters' pre-designation and introducing more source types, and may have a dosimetric benefit, particularly in improving conformality to spare the urethra. This study presents a novel analytical approach to solving the corresponding HDR planning problem. The catheter and dual-energy source selection problem was formulated as a constrained optimization problem with a non-convex group sparsity regularization. The optimization problem was solved using the fast-iterative shrinkage-thresholding algorithm (FISTA). Two isotopes were considered. The dose rates for the HDR 4140 Ytterbium (Yb-169) source and the Elekta Iridium (Ir-192) HDR Flexisource were modeled according to the TG-43U1 formalism and benchmarked accordingly. Twenty-two retrospective HDR prostate brachytherapy patients treated with Ir-192 were considered. An Ir-192 only (IRO), Yb-169 only (YBO), and dual-source (DS) plan with optimized catheter location was created for each patient with N catheters, where N is the number of catheters used in the clinically delivered plans. The DS plans jointly optimized Yb-169 and Ir-192 dwell times. All plans and the clinical plans were normalized to deliver a 15Gy prescription (Rx) dose to 95% of the clinical treatment volume (CTV) and evaluated for the CTV D90%, V150%, and V200%, urethra D0.1cc and D1cc, bladder V75%, and rectum V75%. Dose-volume histograms (DVHs) were generated for each structure. The DS plans ubiquitously selected Ir-192 as the only treatment source. IRO outperformed YBO in organ at risk (OARs) OAR sparing, reducing the urethra D0.1cc and D1cc by 0.98% ( ) and 1.09% ( ) of the Rx dose, respectively, and reducing the bladder and rectum V75% by 0.09 ( ) and 0.13 cubic centimeters (cc) ( ), respectively. The YBO plans delivered a more homogenous dose to the CTV, with a smaller V150% and V200% by 3.20 ( ) and 1.91 cc ( ), respectively, and a lower CTV D90% by 0.49% ( ) of the prescription dose. The IRO plans reduce the urethral D1cc by 2.82% ( ) of the Rx dose compared to the clinical plans, at the cost of increased bladder and rectal V75% by 0.57 ( ) and 0.21 cc ( ), respectively, and increased CTV V150% by a mean of 1.46 cc ( ) and CTV D90% by an average of 1.40% of the Rx dose ( ). While these differences are statistically significant, the clinical differences between the plans are minimal. The proposed analytical HDR planning algorithm integrates catheter and isotope selection with dwell time optimization for varying clinical goals, including urethra sparing. The planning method can guide HDR implants and identify promising isotopes for specific HDR clinical goals, such as target conformality or OAR sparing.

Inhomogeneously distributed ferroptosis with a high peak-to-valley ratio may improve the antitumor immune response.

Combined radiotherapy (RT) and mild hyperthermia have been used clinically for decades to increase local control. Both modalities tend to achieve a homogeneous dose distribution within treatment targets to induce immunogenic cell death. However, marked, and long-lasting abscopal effects have not usually been observed. We proposed a hypothesis to emphasize the importance of the peak-to-valley ratio of the dose distribution inside the tumor to induce immunogenic ferrroptosis in peak area while avoid nonimmunogenic ferroptosis in valley area. Although inhomogeneous distributed energy absorption has been noted in many anticancer medical fields, the idea of sedulously created dose inhomogeneity related to antitumor immunity has not been discussed. To scale up the peak-to-valley ratio, we proposed possible implications by the combination of nanoparticles (NP) with conventional RT or hyperthermia, or the use of a high modulation depth of extremely low frequency hyperthermia or high resolution spatially fractionated radiotherapy (SFRT) to enhance the antitumor immune reactions.

Comparison of helical and TomoDirect techniques with simultaneous integrated boost in early breast cancer patients.

The aim of the study was to perform dosimetric comparisons of helical (H) and TomoDirect (TD) plans for whole-breast irradiation (WBI) with simultaneous integrated boost (SIB) in early-stage breast cancer patients undergoing breast conserving surgery. Fifty patients, 25 with left-side and 25 with right-side tumors, were determined for a treatment planning system for a total dose of 50.4Gy in 1.8Gy per fraction to WBI, with a SIB of 2.3Gy per fraction delivered to the tumor bed. The planning target volume (PTV) doses and the conformity (CI) and homogeneity indices (HI) for PTVbreast and PTVboost, as well as organ-at-risk (OAR) doses and treatment times, were compared between the H and TD plans. All plans met the PTV coverage criteria for the H plan, except for mean V107 of PTVbreast for TD plan. The H plan yielded better homogeneity and conformity of dose distribution compared to the TD plan. The ipsilateral mean lung doses were not significantly different between the two plans. The TD plans is advantageous for mean doses to the heart, contralateral breast and lung, spinal cord, and esophagus than the H plans. In both the H and TD plans, the right-sided breast patients had lower heart dose parameters than the left-sided breast patients. The TD plan is superior to the H plan in sparing the contralateral breast and lung by decreasing low-dose volumes. While the OAR dose advantages of TD are appealing, shorter treatment times or improved dose homogeneity and conformity for target volume may be advantageous for H plan.

A Review on Mouth Dissolving Tablet

Nowadays, dysphagia is an issue with traditional dosage forms like tablets and capsules, which leads to a high prevalence of non-compliance and renders therapy ineffective. Mouth dissolving tablets, which have good hardness, dose homogeneity, and ease of administration and serve as the preferred option of dosage form for paediatrics, geriatrics, and travelling patients, have been designed to eliminate the issues associated with conventional dosage forms. In order to have enough hardness, integrity, and speed up disintegration without water, the MDTs were invented. rapid dissolution Without the use of water, tablets easily dissolve or disintegrate in saliva. Some tablets are truly fast-dissolving tablets because they are made to dissolve in saliva amazingly quickly—within a few seconds. Others have additives that speed up the process of Tablet disintegration in the oral cavity is more properly referred to as fast-disintegrating tablets because it can take them up to a minute to do so. This tablet shape was created to make it possible to administer an oral solid dose form without drinking any liquids. These tablets easily dissolve or break down in the saliva, usually in under 60 seconds.

Optimized Conformal Total Body Irradiation with VMAT Using a Linear-Accelerator-Based Radiosurgery Treatment System in Comparison to the Golden Standard Helical TomoTherapy.

Modern irradiation techniques for optimized conformal TBI can be realized by Helical Tomotherapy (HT) or Volumetric Modulated Arc Therapy (VMAT), depending on the availability of suitable specialized equipment. In this dosimetric planning study, we compared both modalities and addressed the question of whether VMAT with small field sizes is also suitable as a backup in case of HT equipment malfunctions. For this purpose, we retrospectively used planning computed tomography (CT) data from 10 patients treated with HT with a total dose of 8 Gy (n = 5) or 12 Gy (n = 5) for treatment planning for VMAT with a small field size (36 × 22 cm). The target volume coverage, dose homogeneity at target volume, and dose reduction in organs at risk (OAR) (lungs, kidneys, lenses) were analyzed and compared. One patient was irradiated with both modalities due to a device failure of the HT equipment during the study, which facilitated a comparison in a real clinical setting. The findings indicate that in addition to a higher mean dose to the lenses in the 12 Gy group for VMAT and a better dose homogeneity in the target volume for HT, comparably good and adequate target dose coverage and dose reduction in the other OAR could be achieved for both modalities, with significantly longer treatment times for VMAT. In conclusion, after appropriate optimization of the treatment times, VMAT using linear accelerator radiosurgery technology can be used both as a backup in addition to HT and in clinical routines to perform optimized conformal TBI.

Dosimetric analysis of beam arrangement for intensity-modulated radiation therapy in the postoperative irradiation of thymoma

This study aimed to investigate the dosimetric effect of various beam arrangements (BAs), for intensity-modulated radiotherapy (IMRT) in female thymoma patients. Six-field IMRT plans with three different BAs, named IMRTCA, IMRTCS, and IMRTNC were created for each patient. The couch angles of all fields were selected at 0°, which made the fields coplanar in the axial plane in IMRTCA plans. The couch angles of all fields were selected to be 90°, which makes the fields coplanar in the sagittal plane in IMRTCS plans. The couch angles of the four fields and two fields were selected as 90° and 0°, respectively in IMRTNC plans. Plans were compared in terms of dose homogeneity, conformity, and OAR doses. IMRTCS plans created with coplanar beams in the sagittal plane could offer significant advantages in terms of breast and lung sparing. IMRTCS may be useful for young female thymoma patients to reduce the risk of developing a second cancer in the breast. In addition, it should be considered that IMRTCS contributes approximately 1 Gy to the mean heart dose.

A portable primary-standard level graphite calorimeter for absolute dosimetry in clinical pencil beam scanning proton beams

Objective. To report the use of a portable primary standard level graphite calorimeter for direct dose determination in clinical pencil beam scanning proton beams, which forms part of the recommendations of the proposed Institute of Physics and Engineering in Medicine (IPEM) Code of Practice (CoP) for proton therapy dosimetry. Approach. The primary standard proton calorimeter (PSPC) was developed at the National Physical Laboratory (NPL) and measurements were performed at four clinical proton therapy facilities that use pencil beam scanning for beam delivery. Correction factors for the presence of impurities and vacuum gaps were calculated and applied, as well as dose conversion factors to obtain dose to water. Measurements were performed in the middle of 10 × 10 × 10 cm3 homogeneous dose volumes, centred at 10.0, 15.0 and 25.0 g·cm−2 depth in water. The absorbed dose to water determined with the calorimeter was compared to the dose obtained using PTW Roos-type ionisation chambers calibrated in terms of absorbed dose to water in 60Co applying the recommendations in the IAEA TRS-398 CoP. Main results. The relative dose difference between the two protocols varied between 0.4% and 2.1% depending on the facility. The reported overall uncertainty in the determination of absorbed dose to water using the calorimeter is 0.9% (k = 1), which corresponds to a significant reduction of uncertainty in comparison with the TRS-398 CoP (currently with an uncertainty equal or larger than 2.0% (k = 1) for proton beams). Significance. The establishment of a purpose-built primary standard and associated CoP will considerably reduce the uncertainty of the absorbed dose to water determination and ensure improved accuracy and consistency in the dose delivered to patients treated with proton therapy and bring proton reference dosimetry uncertainty in line with megavoltage photon radiotherapy.

Radio-immune response modelling for spatially fractionated radiotherapy.

Radiation-induced cell death is a complex process influenced by physical, chemical and biological phenomena. Although consensus on the nature and the mechanism of the bystander effect were not yet made, the immune process presumably plays an important role in many aspects of the radiotherapy including the bystander effect. A mathematical model of immune response during and after radiation therapy is presented. Immune response of host body and immune suppression of tumor cells are modelled with four compartments in this study; viable tumor cells, T cell lymphocytes, immune triggering cells, and doomed cells.&#xD;The growth of tumor was analyzed in two distinctive modes of tumor status (immune limited and immune escape) and its bifurcation condition. Tumors in the immune limited mode can grow only up to a finite size, named as terminal tumor volume analytically calculated from the model. The dynamics of the tumor growth in the immune escape mode is much more complex than the tumors in the immune limited mode especially when the status of tumor is close to the bifurcation condition. Radiation can kill tumor cells not only by radiation damage but also by boosting immune reaction. The model demonstrated that the highly heterogeneous dose distribution in spatially fractionated radiotherapy (SFRT) can make a drastic difference in tumor cell killing compared to the homogeneous dose distribution. SFRT can not only enhance but also moderate the cell killing depending on the immune response triggered by many factors such as dose prescription parameters, tumor volume at the time of treatment and tumor characteristics. The model was applied to the lifted data of 67NR tumors on mice and a sarcoma patient treated multiple times over 1200 days for the treatment of tumor recurrence as a demonstration.&#xD.

3D-conformal very-high energy electron therapy as candidate modality for FLASH-RT: A treatment planning study for glioblastoma and lung cancer.

Pre-clinical ultra-high dose rate (UHDR) electron irradiations on time scales of 100ms have demonstrated a remarkable sparing of brain and lung tissues while retaining tumor efficacy when compared to conventional dose rate irradiations. While clinically-used gantries and intensity modulation techniques are too slow to match such time scales, novel very-high energy electron (VHEE, 50-250MeV) radiotherapy (RT) devices using 3D-conformed broad VHEE beams are designed to deliver UHDR treatments that fulfill these timing requirements. To assess the dosimetric plan quality obtained using VHEE-based 3D-conformal RT (3D-CRT) for treatments of glioblastoma and lung cancer patients and compare the resulting treatment plans to those delivered by standard-of-care intensity modulated photon RT (IMRT) techniques. Seven glioblastoma patients and seven lung cancer patients were planned with VHEE-based 3D-CRT using 3 to 16 coplanar beams with equidistant angular spacing and energies of 100 and 200MeV using a forward planning approach. Dose distributions, dose-volume histograms, coverage (V95% ) and homogeneity (HI98% ) for the planning target volume (PTV), as well as near-maximum doses (D2% ) and mean doses (Dmean ) for organs-at-risk (OAR) were evaluated and compared to clinical IMRT plans. Mean differences of V95% and HI98% of all VHEE plans were within 2% or better of the IMRT reference plans. Glioblastoma plan dose metrics obtained with VHEE configurations of 200MeV and 3-16 beams were either not significantly different or were significantly improved compared to the clinical IMRT reference plans. All OAR plan dose metrics evaluated for VHEE plans created using 5 beams of 100MeV were either not significantly different or within 3% on average, except for Dmean for the body, Dmean for the brain, D2% for the brain stem, and D2% for the chiasm, which were significantly increased by 1, 2, 6, and 8Gy, respectively (however below clinical constraints). Similarly, the dose metrics for lung cancer patients were also either not significantly different or were significantly improved compared to the reference plans for VHEE configurations with 200MeV and 5 to 16 beams with the exception of D2% and Dmean to the spinal canal (however below clinical constraints). For the lung cancer cases, the VHEE configurations using 100MeV or only 3 beams resulted in significantly worse dose metrics for some OAR. Differences in dose metrics were, however, strongly patient-specific and similar for some patient cases. VHEE-based 3D-CRT may deliver conformal treatments to simple, mostly convex target shapes in the brain and the thorax with a limited number of critical adjacent OAR using a limited number of beams (as low as 3 to 7). Using such treatment techniques, a dosimetric plan quality comparable to that of standard-of-care IMRT can be achieved. Hence, from a treatment planning perspective, 3D-conformal UHDR VHEE treatments delivered on time scales of 100ms represent a promising candidate technique for the clinical transfer of the FLASH effect.

Patient Dose Analysis Using GafchromicTM EBT3 Film: A Retrospective Study with a Four Dual-Field Technique in Total Skin Electron Therapy.

The Six dual-field is the most commonly used treatment technique in total skin electron therapy (TSET). Because of the prolonged treatment period, the patient may experience discomfort, and routine radiotherapy treatments may be affected. This reflects the idea of using a modified technique in TSET. The study aims to report our experience with the four dual-field technique and review the in-vivo dosimetry using gafchromic film. The in-vivo dosimetry reports using gafchromic EBT-3 films of 12 patients who received TSET with the four dual-field techniques in our hospital were analysed in this study. The dosimetric parameter including percentage depth dose, dose homogeneity, flatness and symmetry were analysed in this study. For all the patients, the mean dose to the skin was close to the prescription dose, and it was within 10% (99.3%-103%) of the prescription dose. The standard deviation was observed between 5.8 and 12.4 cGy. According to international standards, all of the measured dosimetric parameters were within the acceptable limit and thereby validating our technique. The in-vivo dosimetry study using radiochromic film in TSET is relatively uncommon. So, based on our results, gafchromic films are a viable choice. The objective of our four dual-field techniques is to reduce the overall treatment time on the machine, whereas our study shows a time reduction when compared to regular techniques, which aids in the smooth operation of daily routines. The preliminary results of this novel modified technique in TSET demonstrated favourable effectiveness with minimal skin toxicity. This four dual-field technique is simple and easy to implement. Comparatively, this study shows the dose homogeneity of ±10% and better dose in the underdose areas proving the reliability and homogeneity of four-dual field technique.

Comparison of h-BN material with metal implants in radiotherapy applications: Characterization and dose distribution measurements in LINAC

Patients with metal implants having high atomic numbers (Zeff) can be encountered in radiotherapy applications. These heterogeneous structures cause dose perturbations at the bone-tissue interface. These perturbations are undesired due to the lack of accurate dose calculation and contouring process through a higher image quality. In this study, the effect of 6–18 MV photon irradiation on hexagonal boron nitride (h-BN) in comparison with titanium and stainless-steel implants was proposed as an implant material due to its biocompatibility and low Zeff. First, h-BN material was characterized and its mass attenuation coefficient was determined. Then, the percent depth doses (PDD) were obtained for the implant materials. Next, the dose distributions were evaluated with both TPS using CT images and TLDs. A dose perturbation was not observed at the interface for h-BN material different from the metal implants as seen from the PDD distributions. The change in PDD varied between 1 and 3% for h-BN with respect to RW3 slab phantom, which was 4–7 times lower than that of metal implants, depending on the material thickness. No metal artifact was seen at h-BN implants compared to metal implants. Homogenous dose distribution was also seen from the isodose lines on the CT images, while dose perturbations were more pronounced in metal implants. In addition, a more severe dose reduction at the metal implant/bone tissue interface was observed at 6 MV photon beam energy compared to 18 MV. In contrast, no dose change was observed for the h-BN material at each photon beam energy. Hence, an accurate dose calculation can be done for h-BN as a result of these advantages. The results showed that, due to its biocompatible property, h-BN material can be evaluated as an implant material in radiotherapy applications if its mechanical properties were further improved.

Influence of physical and radiobiological models on evaluation of radiotherapy treatment fractionation schedules for GBM brain tumours

This study aims to evaluate the radiotherapy planning performance considering the clinical results of glioblastoma multiforme (GBM)-treated patients from both physical and radiobiological perspectives. Radiotherapy plans are done for 20 patients with GBM tumors who have received radical VMAT treatment on Eclipse-13.5. Dosimetric and radiobiological evaluation metrics are estimated to compare the two plans in terms of TCP, NTCP, and P+ in the context of the evaluated physical metrics. Both conventional and hypofractionation give better dose homogeneity and conformity to the tumour. In addition, hypofractionation schedule coverage targets cells with radiation doses higher than conventional schemes. However, both schedules are at acceptable and safe levels. Statistically, the calculated metrics showed good significance between conventional and hypofractionated radiotherapy schedules. The results have led to the safe use of hypofractionated radiotherapy that can be extended for different tumours, which helps in breaking down the waiting list of patients in many hospitals, especially in cases of pandemics such as COVID-19.