Steep Dose Gradients Research Articles

Synthesis and structural characterization of AI2O3 nanoparticles: Towards 3D optically stimulated luminescence dosimetry

Advanced radiotherapy techniques, which plan and deliver a treatment in complicated 3D geometries with steep dose gradients, push 3D dosimetry with correspondingly high spatial resolution to the top of scientific and clinical agendas. This paper presents the first steps taken towards an inexpensive and reusable material for 3D dosimetry based on optically stimulated luminescence (OSL). Carbon-doped alumina (Al2O3:C) nanoparticles were synthesized using supercritical flow synthesis, in which product properties can be finely controlled. The particles were characterized using electron microscopy and powder x-ray diffraction. C-doping did not alter the crystallographic structure appreciably, and a high elemental signal from C could be measured. Nanoparticles of amorphous γ-Al2O3:C were achieved, however calcining these to produce the OSL-relevant α-phase yielded microparticles. Future work will aim at producing phase-pure α-Al2O3:C nanoparticles with a narrow size distribution below 10 nm, and controllable C-concentration and O-deficiency.

Feasibility Study of Stereotactic Radiosurgery Treatment of Glomus Jugulare Tumors via HyperArc VMAT.

This study aims to report on the clinical validation and feasibility of utilizing a novel fully automated treatment planning and delivery system, HyperArc VMAT stereotactic radiosurgery (SRS) for glomus jugulare tumors (GJT). Independent dose verification of the HyperArc module via the MD Anderson's SRS head phantom irradiation and credentialing results showed compliance with the SRS treatment requirements per IROC MD Anderson's standard. Following the Alliance clinical trial, AAPM, RTOG protocols, and QUANTEC requirements, utilizing selected three-partial arc geometry of HyperArc module on TrueBeam Linac with 6MV-FFF beam, GJT SRS plans were generated for nine previously treated Gamma Knife (GK) radiosurgery patients using advanced Acuros-based algorithm to account for tissue inhomogeneity corrections and frameless immobilization with Q-fix mask and Encompass device insert. HyperArc VMAT produced highly conformal SRS dose distributions to GJT, a steep dose gradient around the GJT, and spared adjacent critical organs including the spinal cord (< 3.0 Gy). Due to faster patient setup and less MLC modulation through the target (average beam-on time, 6.2 minutes), the HyperArc VMAT plan can deliver a single high-dose of 18 Gy to the GJT in less than 15 minutes overall treatment time, significantly improving patient comfort and clinic workflow. Pretreatment portal dosimetry quality assurance results and independent dose verification via Monte Carlo-based physics second check met our clinical SRS protocol's requirements for treatment. Due to the highly conformal dose distribution, rapid dose fall-off, excellent sparing of adjacent critical organs, and highly precise and accurate treatment, clinical implementation of frameless HyperArc VMAT for GJT patients who may not have access to nor tolerate frame-based GK SRS treatment are underway.

Dynamic 18F-FET PET/CT to differentiate recurrent primary brain tumor and brain metastases from radiation necrosis after single-session robotic radiosurgery

ObjectiveCyberknife robotic radiosurgery (RRS) provides single-session high-dose radiotherapy of brain tumors with a steep dose gradient and precise real-time image-guided motion correction. Although RRS appears to cause more radiation necrosis (RN), the radiometabolic changes after RRS have not been fully clarified. 18F-FET-PET/CT is used to differentiate recurrent tumor (RT) from RN after radiosurgery when MRI findings are indecisive. We explored the usefulness of dynamic parameters derived from 18F-FET PET in differentiating RT from RN after Cyberknife treatment in a single-center study population. MethodsWe retrospectively identified brain tumor patients with static and dynamic 18F-FET-PET/CT for suspected RN after Cyberknife. Static (tumor-to-background ratio) and dynamic PET parameters (time-activity curve, time-to-peak) were quantified. Analyses were performed for all lesions taken together (TOTAL) and for brain metastases only (METS). Diagnostic accuracy of PET parameters (using mean tumor-to-background ratio >1.95 and time-to-peak of 20 min for RT as cut-offs) and their respective improvement of diagnostic probability were analyzed. ResultsFourteen patients with 28 brain tumors were included in quantitative analysis. Time-activity curves alone provided the highest sensitivities (TOTAL: 95%, METS: 100%) at the cost of specificity (TOTAL: 50%, METS: 57%). Combined mean tumor-to-background ratio and time-activity curve had the highest specificities (TOTAL: 63%, METS: 71%) and led to the highest increase in diagnosis probability of up to 16% p. – versus 5% p. when only static parameters were used. ConclusionsThis preliminary study shows that combined dynamic and static 18F-FET PET/CT parameters can be used in differentiating RT from RN after RRS.

Validation of spine SBRT using a 3D printed Anthropomorphic phantom

A segment of a spine was 3D-printed based on real patient anatomy, using metal-doped high density plastic to radiographically mimic bone. This spine was submerged in a water tank to create an anthropomorphic phantom. The spine print incorporated a slot for Gafchromic EBT3 film dosimeters and fiducials for alignment of measured and calculated dose distributions. Spine SBRT treatment plans were generated for both 6 MV and 10FFF energies based on oncologist-drawn contours transferred from real anatomy. Plans were delivered under image guidance using our clinical procedures, to evaluate the dosimetric accuracy of our planning system in high density inhomogeneities and the geometric accuracy of delivery. Results show that the Acuros XB algorithm (dose-to-water) agrees well with film measurements throughout the measured region, including within the bone substitute material. Alignment of the steep dose gradients in planned and measured doses was within 0.5 mm in the ANT-POST direction and within 0.9 mm in the SUP-INF direction, both within machine tolerances. Our results give us confidence in our ability to plan and accurately deliver spinal SBRT treatments.

Evaluation of setup errors of immobilization device for radiation therapy in companion animals.

Intensity-modulated radiotherapy (IMRT), which allows generating steep dose gradients, is a beneficial treatment for companion animals with adjacent target and risk organs. IMRT is essential for high setup accuracy for avoiding overdose to risk organs, and optimal radiotherapy is important for evaluating the setup accuracy of companion animals. To use an immobilization device to evaluate setup errors in radiotherapy for companion animals. We calculated setup errors in radiotherapy for 386 animals (dogs and cats; 3,261 registration images) that underwent radiotherapy between 2016 and 2022. The companion animals were immobilized with a customized bite block and vacuum lock device. A quantile-quantile plot with 95% confidence interval (CI) was used to evaluate the histogram of the setup errors, and the systematic and random setup errors were calculated for each region (brain, head and neck, chest and abdomen, pelvis, and spine). The setup error in each direction presented an extremely narrow-interval histogram, with the following lower and upper 95% CIs: cranial-caudal (-0.08, -0.06 cm); left-right (-0.04, -0.02 cm); and dorsal-ventral (-0.13, -0.11 cm). The mean systematic setup error was 0.16 cm (range: 0.12-0.36 cm), and the random error was 0.15 cm (range: 0.08-0.34 cm). The pelvis showed the highest systematic and random setup errors (mean: 0.36 and 0.23 cm, respectively). The use of an immobilization device enables highly accurate radiotherapy for companion animals (95% CI < 0.15 cm).

Treatment Planning and Dose Verification for Combined Internal and External Radiotherapy (CIERT)

The combined internal and external radiotherapy (CIERT) take advantage of the benefits from radionuclide therapy and external beam irradiation. These include steep dose gradients and a low toxicity to normal tissue due to the use of unsealed radioisotopes as well as homogeneous dose distribution within the tumor due to external beam irradiation. For a combined irradiation planning, an infrastructure has to be developed that takes into account the dose contributions from both modalities. A physical verification of the absorbed dose distribution should follow by measurements using OSL detectors. Internal irradiation was performed using Re-188 in a cylindrical phantom with three inserts. SPECT images were acquired to calculate the internal dose using the software STRATOS. The dose distribution was exported as DICOM-RT data and imported in the software Pinnacle. Based on the internal dose distribution the external irradiation using 6 MV photons was planned. The dose contributions of both modalities separately as well as for combined irradiation was measured using OSL detectors made out of Beryllium oxide. The planed doses of combined irradiation (1 Gy, 2 Gy, 4 Gy) could be verified within the uncertainty of the detectors. The mean energy response to Re-188 was (88.6 ± 2.4) % with respect to the calibration with 200 kV X-ray irradiation. The energy response to 6 MV photons was (146.0 ± 4.9) %. A workflow for the treatment planning of combined internal and external radiotherapy has been developed and tested. Measurements verified the calculated doses. Therefore, the physical and technical basis for the dosimetry of combined irradiation were worked out.

Optimization of treatment isocenter location in single-isocenter LINAC-based stereotactic radiosurgery for management of multiple brain metastases.

Single-isocenter linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) has become a promising treatment technique for the management of multiple brain metastases. Because of the high prescription dose and steep dose gradient, SRS plans are sensitive to geometric errors, resulting in loss of target coverage and suboptimal local tumor control. Current planning techniques rely on adding a uniform and isotropic setup margin to all gross tumor volumes (GTVs) to account for rotational uncertainties. However, this setup margin may be insufficient, since the magnitude of rotational uncertainties varies and is dependent upon the distance between a GTV and the isocenter. In this study, we designed a framework to determine the optimal isocenter of a single-isocenter SRS plan for multiple brain metastases using stochastic optimization to mitigate potential errors resulting from rotational uncertainties. Planning target volumes (PTVs), defined as GTVs plus a 1-mm margin following common SRS planning convention, were assumed to be originally treated with a prescription dose and therefore covered by the prescription isodose cloud. The dose distribution, including the prescription isodose, was considered invariant assuming small rotations throughout the study. A stochastic optimization scheme was developed to determine the location of the optimal isocenter, so that the prescription dose coverage of rotated GTVs, equivalent to the intersecting volumes between the rotated GTVs and original PTVs, was maximized for any random small rotations about the isocenter. To evaluate the coverage of GTVs, the expected undergoing random rotations was approximated as the sample average undergoing a predetermined number of rotations. The expected of each individual GTV and total GTVs was then compared between the plans using the optimal isocenter and the center-of-mass (CoM), respectively. Twenty-two patients previously treated for multiple brain metastases in a single institute were included in this retrospective study. Each patient was initially treated for more than three brain metastases (mean: 7.6; range: 3-15) with the average GTV volume of 0.89 cc (range: 0.03-11.78 cc). The optimal isocenter found for each patient was significantly different from the CoM, with the average Euclidean distance between the optimal isocenter and the CoM being 4.36±2.59cm. The dose coverage to GTVs was also significantly improved (paired t-test; p<0.001) when the optimal isocenter was used, with the average of total GTVs increasing from 87.1% (standard deviation as std: 11.7%; range: 39.9-98.2%) to 94.2% (std: 5.4%; range: 77.7-99.4%). The volume of a GTV was positively correlated with the expected regardless of the isocenter used (Spearman coefficient: ; p<0.001). The distance between a GTV and the isocenter was negatively correlated with the expected when the CoM was used ( ; p=0.004), however no significant correlation was found when the optimal isocenter was used ( ; p=0.137). The proposed framework provides an effective approach to determine the optimal isocenter of single-isocenter LINAC-based SRS plans for multiple brain metastases. The implementation of the optimal isocenter results in SRS plans with consistently higher target coverage despite potential rotational uncertainties, and therefore significantly improves SRS plan robustness against random rotational uncertainties.

Dosimetric Impact of Deformable Image Registration-Based Target Volume Propagation in Stereotactic Body Radiotherapy of Ultracentral Lung Tumors

In stereotactic body radiotherapy (SBRT) of non-small cell lung cancer (NSCLC), the use of steep dose gradients and reduced margins has improved local control while limiting toxicity. Clinical benefit of these techniques is dependent on accurate target definition. NSCLC patients are vulnerable to errors in target definition because lung tumors deform with respiratory motion. For ultracentral lung tumors, phantom studies suggest that auto-propagation of internal gross tumor volumes (IGTVs) can be inaccurate. In SBRT of ultracentral tumors, deformable image registration (DIR) is widely used for target volume propagation. We hypothesized that errors in DIR-based IGTV propagation could jeopardize SBRT target coverage for ultracentral tumors despite use of population-based safety margins.Nine patients with ultracentral NSCLC tumors appropriate for SBRT were studied. For each patient, (1) 4D CT was acquired into 10 discrete phase-based bins; (2) the GTV was manually segmented on all phases; and (3) DIR-based IGTV propagation was carried out for each manual GTV on every phase, resulting in 10 propagated IGTVs (P-IGTVs) per patient and 90 for the entire cohort. Ground truth IGTV (GT-IGTV) was defined as the union of all manual GTVs from all 10 phases. Dice coefficient was used to measure the similarity of P-IGTV relative to GT-IGTV. For each patient, SBRT plans were generated for P-IGTVs with greatest (Plan A) and least (Plan B) Dice coefficients using a PTV margin of 5 mm. Prescriptions were 60 Gy in 8 fractions with V60 Gy > 95% PTV. Dose constraints for organs-at-risk (OARs) were defined according to published prospective trials. For each patient, dosimetric differences between Plans A and B for the ground truth PTV (GT-IGTV + 5 mm margin) and OARs were examined.All tumors (6 in the right lung, 3 in the left) were within 2 cm of the proximal bronchial tree and at hilar level. Table 1 compares IGTVs and target coverage with median and range values. Plans A and B differed significantly in ground truth PTV (GT-PTV) coverage at both 99% and 95% of Rx dose (Kruskal-Wallis tests; P = 0.003). There were no significant differences between plans for dose to OARs. For Plan A, 7 out 9 plans were generated from GTVs at near-end of inhalation (respiratory phases 8 or 9); for Plan B, 7/9 plans were generated from GTVs at end of inhalation through mid-exhalation (phases 0 through 3).In SBRT of ultracentral tumors, patterns of error exist in DIR-based IGTV propagation that can compromise target coverage despite the use of population-based safety margins. These findings are important to enhance efforts for more robust and accurate targeting in lung SBRT.

Ion chamber and film-based quality assurance of mixed electron-photon radiation therapy.

In previous work, we demonstrated that mixed electron-photon radiation therapy (MBRT) produces treatment plans with improved normal tissue sparing and similar target coverage, when compared to photon-only plans. The purpose of this work was to validate the MBRT delivery process on a Varian TrueBeam accelerator and laying the groundwork for a patient-specific quality assurance (QA) protocol based on ion chamber point measurements and 2D film measurements. MC beam models used to calculate the MBRT dose distributions of each modality (photons/electrons) were validated with a single-angle beam MBRT treatment plan delivered on a slab of Solid Water phantom with a film positioned at a depth of 2cm. The measured film absorbed dose was compared to the calculated dose. To validate clinical deliveries, a polymethyl methacrylate (PMMA) cylinder was machined and holes were made to fit an ionization chamber. A complex MBRT plan involving a photon arc and three electron delivery angles was created with the aim of reproducing a clinically realistic dose distribution in typical soft tissue sarcoma tumours of the extremities. The treatment plan was delivered on the PMMA cylinder. Point measurements were taken with an Exradin A1SL chamber at two nominal depths: 1.4cm and 2.1cm. The plan was also delivered on a second identical phantom with an insert at 2cm depth, where a film was placed. An existing EGSnrc user-code, SPRRZnrc, was modified to calculate the stopping power ratios between any materials in the same voxelized geometry used for dose calculation purposes. This modified code, called SPRXYZnrc, was used to calculate a correction factor, , accounting for the differences in electron fluence spectrum at the measurement point compared to that at reference conditions. The uncertainty associated with neglecting potential ionization chamber fluence perturbation correction factors using this approach was estimated. The film measurement from the Solid Water phantom treatment plan was in good agreement with the simulated dose distribution, with a gamma pass rate of 96.1% for a 3%/2mm criteria. For the PMMA phantom delivery, for the same gamma criteria, the pass rate was 97.3%. The ion chamber measurements of the total delivered dose agreed with the MC-simulated dose within 2.1%. The beam quality correction factors amounted to, at most, a 4% correction on the ion chamber measurement. However, individual contribution of low electron energies proved difficult to precisely measure due to their steep dose gradients, with disagreements of up to 28%±15% at 2.1cm depth (6MeV). Ion chamber measurement procedure of electron beams was achieved in less than 5min, and the entire validation process including phantom setup was performed in less than 30min. The agreement between measured and simulated MBRT doses indicates that the dose distributions obtained from the MBRT treatment planning algorithm are realistically achievable. The SPRXYZnrc MC code allowed for convenient calculations of simultaneously with the dose distributions, laying the groundwork for patient-specific QA protocol practical for clinical use. Further investigation is needed to establish the accuracy of our ionization chamber correction factors calculations at low electron energies.

Interfractional target changes in brain metastases during 13-fraction stereotactic radiotherapy

BackgroundThe risk for radiation necrosis is lower in fractionated stereotactic radiotherapy (SRT) than in conventional radiotherapy, and 13-fraction SRT is our method of choice for the treatment of brain metastases ≥ around 2 cm or patients who are expected to have a good prognosis. As 13-fraction SRT lasts for at least 17 days, adaptive radiotherapy based on contrast-enhanced mid-treatment magnetic resonance imaging (MRI) is often necessary for patients undergoing 13-fraction SRT. In this study, we retrospectively analyzed interfractional target changes in patients with brain metastases treated with 13-fraction SRT.MethodsOur analyses included data from 23 patients and 27 metastatic brain lesions treated with 13-fraction SRT with dynamic conformal arc therapy. The peripheral dose prescribed to the planning target volume (PTV) was 39–44.2 Gy in 13-fractions. The gross tumor volume (GTV) of the initial SRT plan (initial GTV), initial PTV, and modified GTV based on the mid-treatment MRI scan (mid-treatment GTV) were assessed.ResultsThe median initial GTV was 3.8 cm3 and the median time from SRT initiation to the mid-treatment MRI scan was 6 days. Compared to the initial GTV, the mid-treatment GTV increased by more than 20% in five lesions and decreased by more than 20% in five lesions. Interfractional GTV volume changes of more than 20% were not significantly associated with primary disease or the presence of cystic components/necrosis. The mid-treatment GTV did not overlap perfectly with the initial PTV in more than half of the lesions.ConclusionsCompared to the initial GTV, the mid-treatment GTV changed by more than 20% in almost one-third of lesions treated with 13-fraction SRT. As SRT usually generates a steep dose gradient as well as increasing the maximum dose of PTV compared to conventional radiotherapy, assessment of the volume and locational target changes and adaptive radiotherapy should be considered as the number of fractions increases.

Hydrogels for Three-Dimensional Ionizing-Radiation Dosimetry.

Radiation-sensitive gels are among the most recent and promising developments for radiation therapy (RT) dosimetry. RT dosimetry has the twofold goal of ensuring the quality of the treatment and the radiation protection of the patient. Benchmark dosimetry for acceptance testing and commissioning of RT systems is still based on ionization chambers. However, even the smallest chambers cannot resolve the steep dose gradients of up to 30–50% per mm generated with the most advanced techniques. While a multitude of systems based, e.g., on luminescence, silicon diodes and radiochromic materials have been developed, they do not allow the truly continuous 3D dose measurements offered by radiation-sensitive gels. The gels are tissue equivalent, so they also serve as phantoms, and their response is largely independent of radiation quality and dose rate. Some of them are infused with ferrous sulfate and rely on the radiation-induced oxidation of ferrous ions to ferric ions (Fricke-gels). Other formulations consist of monomers dispersed in a gelatinous medium (Polyacrylamide gels) and rely on radiation-induced polymerization, which creates a stable polymer structure. In both gel types, irradiation causes changes in proton relaxation rates that are proportional to locally absorbed dose and can be imaged using magnetic resonance imaging (MRI). Changes in color and/or opacification of the gels also occur upon irradiation, allowing the use of optical tomography techniques. In this work, we review both Fricke and polyacrylamide gels with emphasis on their chemical and physical properties and on their applications for radiation dosimetry.

8+ Year Performance of the Gamma Knife Perfexion/Icon Patient Positioning System and Possibilities for Preemptive Fault Detection Using Statistical Process Control.

The large fractional doses, steep dose gradients, and small targets found in intracranial radiosurgery require extremely low beam delivery uncertainty. In the case of Gamma Knife radiosurgery (GKRS), this includes minimizing patient positioning system (PPS) positioning uncertainty. Existing QA techniques are recipe based, and feature point in time pass/fail tolerances. However, modern treatment machines, including the Gamma Knife Perfexion/Icon systems, record extensive internal data in treatment logs. These data can be analyzed through statistical process control (SPC) methods which are designed to detect changes in process behavior. The purpose of this study was to characterize the long-term (8+ year) performance of a Perfexion/Icon unit and use SPC methods to determine if performance changes could be detected at levels lower than existing QA and internal manufacturer performance tolerances. In-house software was developed to parse Perfexion/Icon log-files and store relevant information on shot delivery in a relational database. A last-in, first-out (LIFO) queuing algorithm was created to heuristically match messages associated with a given delivered shot. Filtering criteria were developed to filter QA and uncompleted shots. The resulting matched shots were extracted. Achieved versus planned PPS position was determined for each PPS motor as well as for the vector magnitude difference in PPS position. Exponentially weighted moving average (EWMA) control charts were plotted to determine when process behavior changed over time. 53833 shots were delivered over an 8+ year span in the study. The mean vector magnitude PPS difference was 32.7µm, with 97.5% of all shots within 70.1µm. Several changes in PPS positioning behavior were observed over time, corresponding with control system faults on several occasions requiring PPS recalibration. EWMA control charts clearly demonstrate that these faults could be identified and possibly predicted as many as 3years before there were faults beyond control system tolerance. The PPS of Gamma Knife Perfexion/Icon systems has extremely low positioning uncertainties. EWMA control chart method can be utilized to track PPS performance over time and can potentially detect changes in performance that may indicate a component requiring maintenance. This would allow planned service visits to mitigate problems and prevent unplanned downtime.

Impact of Multileaf Collimator Width on Dose Distribution in HyperArc Fractionated Stereotactic Irradiation for Multiple (-) Brain Metastases.

To assess the impact of the width of multileaf collimator (MLC) on dose distributions on HyperArc fractionated stereotactic irradiation for multiple (5-10) brain metastases. Twenty-one HyperArc (HA) plans were generated using the high definition (HD) MLC (2.5 mm) to deliver 30-35 Gy in 3-5 fractions (HA-HD). The HyperArc plans using Millennium (ML) MLC (5 mm) were retrospectively generated (HA-ML) using the same planning parameters with HA-HD. Dosimetric parameters between the planning target volume (PTV) and organs at risk (OARs) were compared. The conformity index was significantly higher (p<0.0001) in the HA-HD plans (0.95±0.04) than that in the HA-ML plans (0.92±0.06). The HA-HD provided significantly lower (p<0.0001) gradient index (5.6±2.5) than HA-ML (6.2±3.5). For the brainstem and retina (right), a statistically significant difference (p<0.05) was observed between the HA-HD (12.8±10.9 and 2.8±1.7 Gy, for brainstem and retina, respectively) and HA-ML (13.6±11.1 and 3.0±1.8 Gy) plans. For the brain tissue, the HA-HD plans statistically significantly reduced dosimetric parameters (p<0.0001) in all evaluated dose range (V6Gy-V28Gy). The narrower MLC provided significantly higher conformity, steeper dose gradient, and better normal tissue sparing.

Clinical Implementation of Proton Therapy Using Pencil-Beam Scanning Delivery Combined With Static Apertures.

Proton therapy makes use of the favorable depth-dose distribution with its characteristic Bragg peak to spare normal tissue distal of the target volume. A steep dose gradient would be desired in lateral dimensions, too. The widespread spot scanning delivery technique is based, however, on pencil-beams with in-air spot full-widths-at-half-maximum of typically 1 cm or more. This hampers the sparing of organs-at-risk if small-scale structures adjacent to the target volume are concerned. The trimming of spot scanning fields with collimating apertures constitutes a simple measure to increase the transversal dose gradient. The current study describes the clinical implementation of brass apertures in conjunction with the pencil-beam scanning delivery mode at a horizontal, clinical treatment head based on commercial hardware and software components. Furthermore, clinical cases, which comprised craniopharyngiomas, re-irradiations and ocular tumors, were evaluated. The dosimetric benefits of 31 treatment plans using apertures were compared to the corresponding plans without aperture. Furthermore, an overview of the radiation protection aspects is given. Regarding the results, robust optimization considering range and setup uncertainties was combined with apertures. The treatment plan optimizations followed a single-field uniform dose or a restricted multi-field optimization approach. Robustness evaluation was expanded to account for possible deviations of the center of the pencil-beam delivery and the mechanical center of the aperture holder. Supplementary apertures improved the conformity index on average by 15.3%. The volume of the dose gradient surrounding the PTV (evaluated between 80 and 20% dose levels) was decreased on average by 17.6%. The mean dose of the hippocampi could be reduced on average by 2.9 GyRBE. In particular cases the apertures facilitated a sparing of an organ-at-risk, e.g. the eye lens or the brainstem. For six craniopharyngioma cases the inclusion of apertures led to a reduction of the mean dose of 1.5 GyRBE (13%) for the brain and 3.1 GyRBE (16%) for the hippocampi.

PO07: Calibration Protocol for a Planar 32P Beta Emitting Brachytherapy Source: A Multi-Institutional Validation

Purpose: This is a multi-institutional report on inter-observer and inter-instrument variation in the calibration of a planar 32P beta emitting brachytherapy source. Calibration accuracy is essential since the dose profile is steep and the source is used for the treatment of tumors that are located in close proximity to healthy nervous system structures. Due to its steep dose gradient, the calibration of the 32P source is non-trivial and particularly sensitive to the detector's effective point of measurement and/or variations in measurement material densities.

Calibration of the EBT3 Gafchromic Film Using HNN Deep Learning.

To achieve a dose distribution conformal to the target volume while sparing normal tissues, intensity modulation with steep dose gradient is used for treatment planning. To successfully deliver such treatment, high spatial and dosimetric accuracy are crucial and need to be verified. With high 2D dosimetry resolution and a self-development property, the Ashland Inc. product EBT3 Gafchromic film is a widely used quality assurance tool designed especially for this. However, the film should be recalibrated each quarter due to the “aging effect,” and calibration uncertainties always exist between individual films even in the same lot. Recently, artificial neural networks (ANN) are applied to many fields. If a physicist can collect the calibration data, it could be accumulated to be a substantial ANN data input used for film calibration. We therefore use the Keras functional Application Program Interface to build a hierarchical neural network (HNN), with the inputs of net optical densities, pixel values, and inverse transmittances to reveal the delivered dose and train the neural network with deep learning. For comparison, the film dose calculated using red-channel net optical density with power function fitting was performed and taken as a conventional method. The results show that the percentage error of the film dose using the HNN method is less than 4% for the aging effect verification test and less than 4.5% for the intralot variation test; in contrast, the conventional method could yield errors higher than 10% and 7%, respectively. This HNN method to calibrate the EBT film could be further improved by adding training data or adjusting the HNN structure. The model could help physicists spend less calibration time and reduce film usage.

A Probability-Based Investigation on the Setup Robustness of Pencil-beam Proton Radiation Therapy for Skull-Base Meningioma.

IntroductionThe intracranial skull-base meningioma is in proximity to multiple critical organs and heterogeneous tissues. Steep dose gradients often result from avoiding critical organs in proton treatment plans. Dose uncertainties arising from setup errors under image-guided radiation therapy are worthy of evaluation.Patients and MethodsFourteen patients with skull-base meningioma were retrospectively identified and planned with proton pencil beam scanning (PBS) single-field uniform dose (SFUD) and multifield optimization (MFO) techniques. The setup uncertainties were assigned a probability model on the basis of prior published data. The impact on the dose distribution from nominal 1-mm and large, less probable setup errors, as well as the cumulative effect, was analyzed. The robustness of SFUD and MFO planning techniques in these scenarios was discussed.ResultsThe target coverage was reduced and the plan dose hot spot increased by all setup uncertainty scenarios regardless of the planning techniques. For 1 mm nominal shifts, the deviations in clinical target volume (CTV) coverage D99% was −11 ± 52 cGy and −45 ± 147 cGy for SFUD and MFO plans. The setup uncertainties affected the organ at risk (OAR) dose both positively and negatively. The statistical average of the setup uncertainties had <100 cGy impact on the plan qualities for all patients. The cumulative deviations in CTV D95% were 1 ± 34 cGy and −7 ± 18 cGy for SFUD and MFO plans.ConclusionIt is important to understand the impact of setup uncertainties on skull-base meningioma, as the tumor target has complex shape and is in proximity to multiple critical organs. Our work evaluated the setup uncertainty based on its probability distribution and evaluated the dosimetric consequences. In general, the SFUD plans demonstrated more robustness than the MFO plans in target coverages and brainstem dose. The probability-weighted overall effect on the dose distribution is small compared to the dosimetric shift during single fraction.

Monte Carlo calculation of the relative TG-43 dosimetry parameters for the INTRABEAM electronic brachytherapy source

The INTRABEAM system (Carl Zeiss Meditec AG, Jena, Germany) is an electronic brachytherapy (eBT) device designed for intraoperative radiotherapy applications. To date, the INTRABEAM x-ray source has not been characterized according to the AAPM TG-43 specifications for brachytherapy sources. This restricts its modelling in commercial treatment planning systems (TPSs), with the consequence that the doses to organs at risk are unknown. The aim of this work is to characterize the INTRABEAM source according to the TG-43 brachytherapy dosimetry protocol. The dose distribution in water around the source was determined with Monte Carlo (MC) calculations. For the validation of the MC model, depth dose calculations along the source longitudinal axis were compared with measurements using a soft x-ray ionization chamber (PTW 34013) and two synthetic diamond detectors (microDiamond PTW TN60019). In our results, the measurements in water agreed with the MC model calculations within uncertainties. The use of the microDiamond detector yielded better agreement with MC calculations, within estimated uncertainties, compared to the ionization chamber at points of steeper dose gradients. The radial dose function showed a steep fall-off close to the INTRABEAM source (10 mm) with a gradient higher than that of commonly used brachytherapy radionuclides (192Ir, 125I and 103Pd), with values of 2.510, 1.645 and 1.232 at 4, 6 and 8 mm, respectively. The radial dose function partially flattens at larger distances with a fall-off comparable to that of the Xoft Axxent® (iCAD, Inc., Nashua, NH) eBT system. The simulated 2D polar anisotropy close to the bare probe walls showed deviations from unity of up to 55% at 10 mm and 155°. This work presents the MC calculated TG-43 parameters for the INTRABEAM, which constitute the necessary data for the characterization of the source as required by a TPS used in clinical dose calculations.

Simultaneous Integrated Boost Intensity-Modulated Radiotherapy for Locally Advanced Drug-Resistant Gastrointestinal Stromal Tumors: A Feasibility Study.

BackgroundAs an emerging clinical problem, locally advanced drug-resistant gastrointestinal stromal tumors (LADRGISTs) has relatively few therapeutic schemes. Although radiotherapy is not often considered for GISTs, it could be a valuable contributing modality. The aim of our study is to explore a safe and effective radiation regimen for LADR-GISTs.MethodsThree patients with LADR-GISTs were treated with simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) plans. In the SIB-IMRT plans, gross target volume (GTV) was divided into GTV-outer, GTV-mid, and GTV-center. And the prescribed dose of planning gross target volume (PGTV) and GTV-outer were both set to 50.4 Gy in 28 fractions. GTV-mid and GTV-center were simultaneously boosted to 60–62 Gy and 62–64 Gy respectively. For comparison purposes, conventional IMRT (Con-IMRT) plans with uniform dose distribution were generated for same optimization objectives without a dose boost to GTV-mid and GTV-center. All plans were optimized to make sure that deliver at least 95% of the prescription dose was delivered to PGTV. Isodose distribution, dose profiles, conformity indexes (CIs), monitor units (MUs), and dose volume histogram (DVH) was evaluated for each individual patient. After the three patients were treated with SIB-IMRT plans, the relative changes in the tumor size and CT values by CT scanning were also tracked.ResultsCompared with Con-IMRT plans, SIB-IMRT plans saw a significant increase from D95 to D2 of the GTV. With steeper dose gradients in the dose profiles, SIB-IMRT plans had GTV-mid and GTV-center accumulated with higher dose mainly by delivering extra 93 MUs in average. However, there was no significant difference in CIs and organs at risks (OARs) DVH. The relative changes in tumor size and CT values of the three patients in follow up were up to the Choi criteria and the three patients were all assessed as partial response.ConclusionsThe proposed SIB-IMRT may be a potential technique for achieving objective response and prolonging survival of selected GISTs patients.

Abstract PO-61: Rethinking radiation therapy in the modern era of advanced systemic treatments of malignant lymphoma

Abstract Radiation therapy (RT) is the single most effective treatment modality for achieving local control in most types of lymphomas. RT causes DNA damage, which can be modulated very accurately in space and time. Modern advanced imaging (PET, MRI, image fusion) and treatment techniques (3-dimensional conformal RT, intensity modulated therapy [IMRT], volumetric arc therapy [VMAT], proton therapy, breathing adaptation, MR-accelerators) have changed lymphoma RT dramatically. The prescribed radiation dose is now delivered very precisely to the macroscopic lymphoma volume, and no more than that (1). This makes RT eminently suited for combination with systemic treatments, either as consolidation using spatial cooperation with cytotoxic systemic treatments, or as immune stimulators in combination with immunomodulatory treatments, the so-called abscopal effect. RT in the curative setting has always been given in many small fractions to protect the critical normal tissues from serious long-term effects. However, with modern conformal RT and very steep dose gradients around targets, the surrounding normal tissues get a much lower dose than before. Hence, even if large fractions to the tumor tissue are employed (so-called hypofractionation) the fraction size for the normal tissues will be in the desired low-dose range. During the recent COVID-19 pandemic RT resources became scarce, and the International Lymphoma Radiation Oncology Group (ILROG) published emergency guidelines for hypofractionation for lymphomas in order to reduce the pressure on RT departments (2). Preliminary experience has been encouraging. Delivering RT to lymphomas in a few large fractions may make it even more convenient for combination with systemic treatments. We and others have shown that the lymphocyte count decreases during a course of RT, most pronounced when many fractions are given, and that it does not reach its former level even a year after treatment (3). A low lymphocyte count increases the risk of infections and may also lead to an increased risk of long-term side effects. Hypofractionation may therefore prove not more but less toxic, challenging the radiobiologic paradigm that has hitherto formed the basis of RT in the curative setting. In conclusion, technological progress and innovative implementation of RT open new possibilities for combinations with systemic treatments to benefit patients with malignant lymphoma.