External-beam Therapy Research Articles

Side effects and complications of high dose-rate brachytherapy: literature review and our own observations

Background. Among malignant tumors in men in Russia, prostate cancer is the most common comprising 17 %. Despite the high effectiveness of radiotherapy for prostate cancer in about 20 % of patients, radiation damage of the pelvic organs develops affecting bladder, rectum, and intrapelvic cellular tissue.Aim. To evaluate early and late complications of high dose-rate brachytherapy.Materials and methods. Literature review was performed, and our own results of treatment of 276 patients using high dose-rate brachytherapy as monotherapy with different fractionation regimens: 19 Gy per 1 fraction and 15 Gy per 2 fractions were analyzed.Results. High dose-rate brachytherapy as monotherapy is associated with low complication rate. There were no statistically significant differences between singleand two-fraction regimens. Evaluation of complication severity per the RTOG (Radiation Therapy Oncology Group) classification did not show complication severity above grade III. Early complications were diagnosed in 1.1 %, late in 3.3 % of cases. Between the treatment and comparison groups, no statistically significant differences in the frequency of urinary system organ symptoms per the IPSS (International Prostate Symptom Score) questionnaire were registered. Mean score per the IPSS prior to treatment was 4.0 (3.0–6.0) in the treatment group and 4.0 (3.0–8.5) in the comparison group. Mean follow-up duration in the treatment group was 65.0 (60.0–70.0) months, in the comparison group – 55.0 (49.5–65.0) months. After the treatment, mean IPSS score was 5.0 (4.0–5.0) in the treatment group and 5.0 (3.0–7.0) in the comparison group.Conclusion. High dose-rate brachytherapy as monotherapy and in combination with external beam therapy is a safe and effective treatment method in prostate cancer. Serious and late complications are rare, however toxic effects of severity grades I or II can develop. Careful patient selection for brachytherapy, therapy planning methods, as well as active management of early and late toxicity by a multidisciplinary team with knowledge and experience in treatment of side effects of radiotherapy can help optimize treatment with high dose-rate brachytherapy.

Theranostic Intratumoral Convection-Enhanced Delivery of 124I-Omburtamab in Patients with Diffuse Intrinsic Pontine Glioma: Pharmacokinetics and Lesion Dosimetry.

Diffuse intrinsic pontine glioma (DIPG) is a rare childhood malignancy with poor prognosis. There are no effective treatment options other than external beam therapy. We conducted a pilot, first-in-human study using 124I-omburtamab imaging and theranostics as a therapeutic approach using a localized convection-enhanced delivery (CED) technique for administering radiolabeled antibody. We report the detailed pharmacokinetics and dosimetry results of intratumoral delivery of 124I-omburtamab. Methods: Forty-five DIPG patients who received 9.0-370.7 MBq of 124I-omburtamab intratumorally via CED underwent serial brain and whole-body PET/CT imaging at 3-5 time points after injection within 4, 24-48, 72-96, 120-144, and 168-240 h from the end of infusion. Serial blood samples were obtained for kinetic analysis. Whole-body, blood, lesion, and normal-tissue activities were measured, kinetic parameters (uptake and clearance half-life times) estimated, and radiation-absorbed doses calculated using the OLINDA software program. Results: All patients showed prominent activity within the lesion that was retained over several days and was detectable up to the last time point of imaging, with a mean 124I residence time in the lesion of 24.9 h and dose equivalent of 353 ± 181 mSv/MBq. Whole-body doses were low, with a dose equivalent of 0.69 ± 0.28 mSv/MBq. Systemic distribution and activities in normal organs and blood were low. Radiation dose to blood was very low, with a mean value of 0.27 ± 0.21 mGy/MBq. Whole-body clearance was monoexponential with a mean biologic half-life of 62.7 h and an effective half-life of 37.9 h. Blood clearance was biexponential, with a mean biologic half-life of 22.2 h for the rapid α phase and 155 h for the slower β phase. Conclusion: Intratumoral CED of 124I-omburtamab is a novel theranostics approach in DIPG. It allows for delivery of high radiation doses to the DIPG lesions, with high lesion activities and low systemic activities and high tumor-to-normal-tissue ratios and achieving a wide safety margin. Imaging of the actual therapeutic administration of 124I-omburtamab allows for direct estimation of the therapeutic lesion and normal-tissue-absorbed doses.

Investigation of dosimetric characteristics of radiochromic film in response to alpha particles emitted from Americium-241.

In radiotherapy, it is essential to deliver prescribed doses to tumors while minimizing damage to surrounding healthy tissue. Accurate measurements of absorbed dose are required for this purpose. Gafchromic® external beam therapy (EBT) radiochromic films have been widely used in radiotherapy. While the dosimetric characteristics of the EBT3 model film have been extensively studied for photon and charged particle beams (protons, electrons, and carbon ions), little research has been done on -particle dosimetry. -emitting radionuclides have gained popularity in cancer treatment due to their high linear energy transfer, short range in tissue, and ability to spare surrounding organs at risk, thereby delivering a more localized dose distribution to the tumor. Therefore, a dose-calibration film protocol for -particles isrequired. This study aimed to develop a dose-calibration protocol for the -particle emitting radionuclide 241Am, using Monte Carlo (MC) simulations and measurements with unlaminated EBT3films. In this study, a MC-based user code was developed using the Geant4 simulation toolkit to model and simulate an 241Am source and an unlaminated EBT3 film. Two simulations were performed: one with voxelized geometries of the EBT3 active volume composition and the other using water. The dose rate was calculated within a region of interest in the voxelized geometries. Unlaminated EBT3 film pieces were irradiated with the 241Am source at various exposure times inside a black box. Film irradiations were compared to a 6-MV photon beam from a Varian TrueBeam machine. The simulated dose rate was used to convert the exposure times into absorbed doses to water, describing a radiochromic-film-based reference dosimetry protocol for -particles. The irradiated films were scanned and through an in-house Python script, the normalized pixel values from the green-color channel of scanned film images wereanalyzed. The 241Am energy spectra obtained from the simulations were in good agreement with IAEA and NIST databases, having differences 0.516% for the emitted -rays and produced characteristic x-rays and 0.006% for the -particles. Due to the short range of -particles, there was no energy deposition in the voxels outside the active 241Am source region projected onto the film surface. Thus, the total dose rate within the voxels covering the source was 0.847 0.003 Gy/min within the sensitive layer of the film (LiPCDA) and 0.847 0.004 Gy/min in water, indicating that the active volume can be considered water equivalent for the 241Am beam quality. A novel approach was employed in -film dosimetry using an exponential fit for the green channel, which showed promising results by reducing the uncertainty in dose estimation within 5%. Although the statistical analysis did not reveal significant differences between the 6-MV photon beam and the calibration curves, the dose-response curves exhibited the expected behavior. The developed MC user code simulated the experimental setup for -dosimetry using radiochromic film with acceptable uncertainty. Unlaminated EBT3 film is suitable for the dosimetry of -radiation at low doses and can be used in conjunction with other unlaminated GafChromic® films for quality assurance and researchpurposes.

TEAM participation in the irradiation of IROC phantoms for cooperative group clinical trials

The participation of radiation oncology team members in the irradiation of Imaging and Radiation Oncology Core (IROC) phantom for cooperative group clinical trials is essential to comply with the latest quality management philosophy. Medical dosimetrists are expected to develop treatment plans for the irradiation of IROC phantoms. For advanced treatment techniques, such as three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT), the irradiation of the IROC phantoms serves as quality audit. If successful, the irradiation processes demonstrate that the institution has the knowledge of the protocol, and has the appropriate equipment to comply with the protocol requirements. This article describes three IROC phantoms used for credentialing external beam photon beam therapy, delivered using conventional medical linear accelerators, to the medical dosimetry community. Guidance and strategies for the development of treatment plans are discussed. Our institutional irradiation of the three IROC phantoms, delivered using the Truebeam medical linear accelerator, resulted in consistent dose accuracy to within ±1%. The participation of the team members may reduce the overall published failing rate stated to be about one-third of all participating institutions.

Dosimetry of Neutron Flow and Gamma-Radiation for two Neutron Beam Shaping Assembly at the VITA Facility using a Scintillator Detector

The BNCT method is considered one of the promising methods of external beam therapy in the treatment of radioresistant tumors such as glioblastoma, melanoma and others, which selectively destroy cancer cells due to previous accumulations of boron-10 isotopes stable inside them, and subsequent irradiation with epithermal neutrons. As a result of neutron capture by boron, nuclear radiation interacts with the release of a large amount of energy (charged particles with a high linear energy transfer), which leads to the destruction of the cancer cell. This method is distinguished by a short number of treatment sessions compared to traditional radiation therapy (photons and electrons). In this study, the boron dose rate and the dose rate of gamma radiation in air and in a water phantom are measured using a small-sized neutron detector with a pair of cast polystyrene scintillators, one of which is enriched with boron, developed at BINP. Two neutron beam shaping assembly were used, one with a magnesium fluoride crystal moderator and the other with a Plexiglas moderator. The article will present the experimental results, discuss the features of the neutron beam shaping assembly and formulate recommendations for conducting clinical trials of the BNCT technique

A Novel Dual ATM/DNA-PK Inhibitor, XRD-0394, Potently Radiosensitizes and Potentiates PARP and Topoisomerase I Inhibitors.

A majority of patients with cancer receive radiotherapy as part of their treatment regimens whether using external beam therapy or locally-delivered radioisotopes. While often effective, some tumors are inadequately controlled with radiation and radiotherapy has significant short-term and long-term toxicities for cancer survivors. Insights into molecular mechanisms involved in cellular responses to DNA breaks introduced by radiation or other cancer therapies have been gained in recent years and approaches to manipulate these responses to enhance tumor cell killing or reduce normal tissue toxicity are of great interest. Here, we report the identification and initial characterization of XRD-0394, a potent and specific dual inhibitor of two DNA damage response kinases, ATM and DNA-PKcs. This orally bioavailable molecule demonstrates significantly enhanced tumor cell kill in the setting of therapeutic ionizing irradiation in vitro and in vivo. XRD-0394 also potentiates the effectiveness of topoisomerase I inhibitors in vitro. In addition, in cells lacking BRCA1/2 XRD-0394 shows single-agent activity and synergy in combination with PARP inhibitors. A phase Ia clinical trial (NCT05002140) with XRD-0394 in combination with radiotherapy has completed. These results provide a rationale for future clinical trials with XRD-0394 in combination with radiotherapy, PARP inhibitors, and targeted delivery of topoisomerase I inhibitors.

Abstract LB181: First disclosure of XRD-0394, a novel dual ATM/DNA-PK inhibitor, that potently radiosensitizes and potentiates PARP and topoisomerase inhibitors

Abstract A majority of cancer patients receive radiation therapy (RT) as part of their treatment regimens, whether using external beam therapy or locally-delivered radioisotopes. While often effective, RT may not be efficacious for some tumors while exerting significant short-term and long-term toxicities. Thus, enhancing therapeutic effectiveness of radiation therapy remains an important goal. ATM (ataxia-telangiectasia, mutated) and DNA-PKcs (deoxyribonucleic acid [DNA]-dependent protein kinase, catalytic subunit) are related protein kinases and both are critical regulators of cellular responses to ionizing radiation. We report here the identification and initial characterization of XRD-0394, a potent, specific dual inhibitor of both ATM and DNA-PKcs, whose chemical structure will be disclosed. A dual ATM/DNA-PK inhibitor has practical and theoretical advantages over compounds which inhibit just one of these kinases: 1) blunting both DNA damage response (DDR) pathways enhances radiation-induced tumor cell kill compared to single target inhibition; and 2) simultaneous inhibition of two DDR pathways should overcome intrinsic or acquired resistance of tumor cells to either target alone. Notably, transient inhibition of both kinases by XRD-0394 has little adverse effects on cells in the absence of irradiation. XRD-0394 is orally bioavailable, with excellent pharmacological profiles, demonstrating significant in vitro and in vivo sensitizing activity in combination with ionizing radiation and in combination with immunotherapy and radiation. In addition, a CRISPR screen identified alterations in the Fanconi A/BRCA pathway as an opportunity for synthetic lethality in tumor cells exposed to XRD-0394, an insight that was validated in multiple tumor cell types. In vitro studies demonstrated synergy of XRD-0394 in combination with PARP inhibitors, particularly in BRCA-mutant cells. XRD-0394 also potentiates the effectiveness of topoisomerase inhibitors in vitro. Single doses of XRD-0394 were well-tolerated in combination with palliative RT in subjects with advanced cancer in a Phase Ia clinical trial (NCT05002140). No DLTs were observed. At a dose of 160 mg, plasma concentrations were well above the preclinical target plasma level of 530 ng/mL (1 µM) for up to 15 h and inhibition of ATM kinase activity was demonstrated by inhibition of radiation-induced pKAP1 in tumor tissue. Importantly, this concentration of drug is sufficient to induce potent radiosensitization in numerous preclinical models. The median tmax (2.3 h) and mean terminal t½ (11.1 h) at the 160 mg dose in subjects support coadministration of XRD-0394 and RT within a clinically feasible time frame. These results provide a rationale for future clinical trials with XRD-0394 in combination with RT, RT and immunotherapy, PARP inhibitors and targeted delivery of topoisomerase inhibitors. Citation Format: Tona M. Gilmer, Chun-Hsiang Lai, Kexiao Guo, Katherine Deland, Kathleen A. Ashcraft, Amy E. Stewart, Yaode Wang, Jianmin Fu, Kris C. Wood, Deborah A. Smith, Jonathan T. Yang, Christopher T. Chen, Michael F. Gensheimer, Paul B. Romesser, Steven H. Lin, David G. Kirsch, Michael B. Kastan. First disclosure of XRD-0394, a novel dual ATM/DNA-PK inhibitor, that potently radiosensitizes and potentiates PARP and topoisomerase inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB181.

A Comprehensive Primer on Radiation Oncology for Non-Radiation Oncologists.

Background: Multidisciplinary management is crucial in cancer diagnosis and treatment. Multidisciplinary teams include specialists in surgery, medical therapies, and radiation therapy (RT), each playing unique roles in oncology care. One significant aspect is RT, guided by radiation oncologists (ROs). This paper serves as a detailed primer for non-oncologists, medical students, or non-clinical investigators, educating them on contemporary RT practices. Methods: This report follows the process of RT planning and execution. Starting from the decision-making in multidisciplinary teams to the completion of RT and subsequent patient follow-up, it aims to offer non-oncologists an understanding of the RO's work in a comprehensive manner. Results: The first step in RT is a planning session that includes obtaining a CT scan of the area to be treated, known as the CT simulation. The patients are imaged in the exact position in which they will receive treatment. The second step, which is the primary source of uncertainty, involves the delineation of treatment targets and organs at risk (OAR). The objective is to ensure precise irradiation of the target volume while sparing the OARs as much as possible. Various radiation modalities, such as external beam therapy with electrons, photons, or particles (including protons and carbon ions), as well as brachytherapy, are utilized. Within these modalities, several techniques, such as three-dimensional conformal RT, intensity-modulated RT, volumetric modulated arc therapy, scattering beam proton therapy, and intensity-modulated proton therapy, are employed to achieve optimal treatment outcomes. The RT plan development is an iterative process involving medical physicists, dosimetrists, and ROs. The complexity and time required vary, ranging from an hour to a week. Once approved, RT begins, with image-guided RT being standard practice for patient alignment. The RO manages acute toxicities during treatment and prepares a summary upon completion. There is a considerable variance in practices, with some ROs offering lifelong follow-up and managing potential late effects of treatment. Conclusions: Comprehension of RT clinical effects by non-oncologists providers significantly elevates long-term patient care quality. Hence, educating non-oncologists enhances care for RT patients, underlining this report's importance.

Experimental validation of multi-fraction online adaptations in magnetic resonance guided radiotherapy

Background and purposeRadiotherapy plan verification is generally performed on the reference plan based on the pre-treatment anatomy. However, the introduction of online adaptive treatments demands a new approach, as plans are created daily on different anatomies. The aim of this study was to experimentally validate the accuracy of total doses of multi-fraction plan adaptations in magnetic resonance imaging guided radiotherapy in a phantom study, isolated from the uncertainty of deformable image registration. Materials and methodsWe experimentally verified the total dose, measured on external beam therapy 3 (EBT3) film, using a treatment with five online adapted fractions. Three series of experiments were performed, each focusing on a category of inter-fractional variation; translations, rotations and body modifications. Variations were introduced during each fraction and adapted plans were generated and irradiated. Single fraction doses and total doses over five online adapted fractions were investigated. ResultsThe online adapted measurements and calculations showed a good agreement for single fractions and multi-fraction treatments for the dose profiles, gamma passing rates, dose deviations and distances to agreement. The gamma passing rate using a 2%/2 mm criterion ranged from 99.2% to 99.5% for a threshold dose of 10% of the maximum dose (Dmax) and from 96.2% to 100% for a threshold dose of 90% of Dmax, for the total translations, rotations and body modifications. ConclusionsThe total doses of multi-fraction treatments showed similar accuracies compared to single fraction treatments, indicating an accurate dosimetric outcome of a multi-fraction treatment in adaptive magnetic resonance imaging guided radiotherapy.

PSOR03 Presentation Time: 4:40 PM: A 3-D Printed Platform for Preclinical In Vitro Studies Incorporating Clinically Relevant HDR and External Beam Therapy Workflows

PSOR03 Presentation Time: 4:40 PM: A 3-D Printed Platform for Preclinical In Vitro Studies Incorporating Clinically Relevant HDR and External Beam Therapy Workflows

The Role of Salvage Resection After Definitive Radiation Therapy for Non-small Cell Lung Cancer

BackgroundThis study evaluated outcomes of patients who undergo extended delay to resection after definitive radiation therapy for non-small cell lung cancer (NSCLC). MethodsPerioperative outcomes and 5-year overall survival of patients with NSCLC who underwent definitive radiation therapy, followed by resection, from 2004 to 2020 in the National Cancer Database were evaluated. Patients who underwent resection >180 days after the initiation of radiation therapy (including any external beam therapy at a total dose of >60 Gy) were included in the analysis. Subgroup analyses were conducted by operation type and pathologic nodal status. ResultsFrom 2004 to 2020, 293 patients had an extended delay to resection after definitive radiation therapy. The clinical stage distribution was stage I to II in 53 patients (18.1%), stage IIIA in 111 (37.9%), stage IIIB in 106 (36.2%), stage IIIC in 13 (4.4%), and stage IV in 10 (3.4%). Median dose of radiation therapy received was 64.8 Gy (interquartile range, 60.0-66.6 Gy). Median days from radiation therapy to resection were 221.0 (interquartile range, 193.0-287.0) days. Lobectomy (64.5%) was the most common operation, followed by pneumonectomy (17.1%) and wedge resection (7.5%). For wedge resection, lobectomy, and pneumonectomy, the 30-day readmission rate was 4.8%, 4.8%, and 8.3%, the 30-day mortality rate was 0%, 3.4%, and 6.4%, and the 90-day mortality rate was 0%, 6.2%, and 12.8%, respectively. Overall survival at 5 years for patients with pN0, pN1, and pN2 disease was 38.6% (95% CI, 30.0-47.2), 43.3% (95% CI, 16.3-67.9), and 24.0% (95% CI, 9.8-41.7), respectively. ConclusionsIn this national analysis, extended delay to resection after definitive radiation therapy was associated with acceptable perioperative outcomes among a highly selected patient cohort.

Surgical Management of Meningiomas Involving the Torcula, Transverse Sinus, and Jugular Bulb: A Technical Note and Review of the Literature.

Meningiomas that invade the confluens sinuum are rare and require extensive preoperative planning. Here, we describe the surgical and radio-oncological management of an aggressive large occipital meningioma invading the superior sagittal sinus, torcula, right and left transverse sinus down to the level of the jugular bulb in a 21-year-old female patient. Details of the surgical approach are presented to highlight the planned staged resection of this tumor at the level of the torcula to initially debulk the lesion while preserving venous outflow through the patent's sinus. Once the tumor fully occluded the confluens, a second-stage en bloc resection ensued. Postsurgical adjuvant radiation therapy was delivered via fractionated external beam therapy which has provided local control of the tumor since. This case is being discussed in the context of the pertinent literature to demonstrate the highly complex interdisciplinary and staged management of partially intravascular meningiomas involving the major venous sinuses.

Application of Conditional Generative Adversarial Networks to Efficiently Generate Photon Phase Space in Medical Linear Accelerators of Different Primary Beam Parameters

Successful application of external photon beam therapy in oncology requires that the dose delivered by a medical linear accelerator and distributed within the patient’s body is accurately calculated. Monte Carlo simulation is currently the most accurate method for this purpose but is computationally too extensive for routine clinical application. A very elaborate and time-consuming part of such Monte Carlo simulation is generation of the full set (phase space) of ionizing radiation components (mainly photons) to be subsequently used in simulating dose delivery to the patient. We propose a method of generating phase spaces in medical linear accelerators through learning, by artificial intelligence models, the joint multidimensional probability density distribution of the photon properties (their location in space, energy, and momentum). The models are conditioned with respect to the parameters of the primary electron beam (unique to each medical accelerator), which, through Bremsstrahlung, generates the therapeutical beam of ionizing radiation. Two variants of conditional generative adversarial networks are chosen, trained, and compared. We also present the second-best type of deep learning architecture that we studied: a variational autoencoder. Differences between dose distributions obtained in a water phantom, in a test phantom, and in real patients using generative-adversarial-network-based and Monte-Carlo-based phase spaces are very close to each other, as indicated by the values of standard quality assurance tools of radiotherapy. Particle generation with generative adversarial networks is three orders of magnitude faster than with Monte Carlo. The proposed GAN model, together with our earlier machine-learning-based method of tuning the primary electron beam of an MC simulator, delivers a complete solution to the problem of tuning a Monte Carlo simulator against a physical medical accelerator.

Resource Allocations for Common Radiation Oncology Procedures

Radiation Oncology is a complex, resource-intensive discipline. The complexity of the radiation oncology treatment process has increased significantly in recent years with the introduction of more advanced imaging, planning, and treatment delivery technology and enhanced use of multidisciplinary care paths. We conducted a multi-institutional study to estimate the average time by functional unit for a wide range of modern radiation oncology treatment regimens. Structured process mapping was performed for 24 treatment categories, and average time estimates for 6 functional groups were obtained for each process step through consultation with the full clinical team at each institution. Six geographically dispersed institutions participated in the study. Significant effort was invested in aggregate data analysis and clarification of assumptions. The findings show significant variability in the resources expended for many treatment categories as well as the distribution of workload between functional units. Major factors in the variability include the rate of adoption of hypofractionation in external beam therapy, adoption of automation tools and standardization, and the transition to multimodality image-based planning in brachytherapy. The data obtained from this study may be useful in designing institution-specific staffing models appropriate to the scope of radiation therapy services provided at each institution.

Dosimetry Evaluation of Treatment Planning Systems in Patient-Specific 3D Printed Anthropomorphic Phantom for Breast Cancer after Mastectomy using a Single-Beam 3D-CRT Technique for Megavoltage Electron Radiation Therapy.

The patient-specific 3D printed anthropomorphic phantom is used for breast cancer after mastectomy developed by the laboratory of medical physics and biophysics, Department of Physics, Institut Teknologi Sepuluh Nopember, Indonesia. This phantom is applied to simulate and measure the radiation interactions occurring in the human body either using the treatment planning system (TPS) or direct measurement with external beam therapy (EBT) 3 film. This study aimed to provide dose measurements in the patient-specific 3D printed anthropomorphic phantom using a TPS and direct measurements using single-beam three-dimensional conformal radiation therapy (3DCRT) technique with electron energy of 6 MeV. In this experimental study, the patient-specific 3D printed anthropomorphic phantom was used for post-mastectomy radiation therapy. TPS on the phantom was conducted using a 3D-CRT technique with RayPlan 9A software. The single-beam radiation was delivered to the phantom with an angle perpendicular to the breast plane at 337.3° at 6 MeV with a total prescribed dose of 5000 cGy/25 fractions with 200 cGy per fraction. The doses at planning target volume (PTV) and right lung confirmed a non-significant difference both for TPS and direct measurement with P-values of 0.074 and 0.143, respectively. The dose at the spinal cord showed statistically significant differences with a P-value of 0.002. The result presented a similar skin dose value using either TPS or direct measurement. The patient-specific 3D printed anthropomorphic phantom for breast cancer after mastectomy on the right side has good potential as an alternative to the evaluation of dosimetry for radiation therapy.

Photoneutrons and Gamma Capture Dose Rates at the Maze Entrance of Varian TrueBeam and Elekta Versa HD Medical Linear Accelerators

Herein, we evaluated the neutron and gamma capture dose equivalent rates at the maze entrance of Varian TrueBeam and Elekta Versa HD™ medical linear accelerators (linacs) using experimental measurements as well as empirical calculations. Dose rates were measured using calibrated neutron and gamma area survey meters placed side-by-side at the measurement point of interest. Measurements were performed at a source-to-detector distance of 100 cm, with a 10 × 10 cm2 field size therapeutic X-ray beam, and a 30 × 30 × 15 cm3 solid water patient equivalent phantom, with a linac operating at 15, 10 MV, and 10 MV flattened filter-free (FFF). Dose rates were also measured at different points at the centerline along the maze towards the maze entrance. The measured dose equivalent rates at the maze entrance were comparable to those reported in the literature. The dose rates along the maze decreased exponentially towards the maze entrance and were significant for short maze lengths. The evaluated empirical methods for estimating neutron dose rates at the maze entrance of a linac proposed by Kersey, the modified Kersey method and Falcão method, agree by a factor of two from the experimental measurements. The results revealed vital radiation protection considerations owing to neutron contamination in external beam therapy.

Dosimetric Impact of Air Pockets in the Vaginal Cuff Brachytherapy Using Model-based Dose Calculation Algorithm.

Endometrial cancer is the most common disease of the female reproductive system. Vaginal cuff brachytherapy (VCB) has intrinsic advantages compared to external beam therapy when treated with radiation. A single-channel cylinder is a standard applicator in VCB. The present study aims to estimate a change in the dose to vaginal mucosa due to air pockets between the cylinder and vaginal mucosa by calculating with the Acuros BV algorithm and comparing it to the Task Group 43 (TG-43) algorithm. Patients who presented with air packets were included retrospectively. For each patient, three plans were created: the first plan used TG-43, the second plan used dose recalculation with Acuros BV, and the third plan was generated by re-optimization by Acuros BV. On the same axial computed tomography image, the point doses at the cylinder's surface and the displaced mucosa were recorded and the ratios were then estimated. The average volume of air pockets was 0.08 cc (range of 0.01-0.3 cc), and 84% of air pockets displaced the vaginal mucosa by ≥0.2 cm. The average ratios of dose were 0.77 ± 0.09 (1 standard deviation [SD]) and 0.78 ± 0.09 (1 SD) for TG-43 and Acuros BV algorithms, respectively. Due to the air pocket, mucosa received a reduced dose by an average of 22.72% and an average of 23.29% for TG-43 and Acuros BV, respectively. The maximum displacement of mucosa and the ratio of doses were negatively correlated for both. In the Optimized Acuros BV plan, total dwell time increased by 1.8% but no considerable change in the dose ratios. The calculated dose of mucous membrane forced out of the cylinder surface by air pockets by the Acuros BV algorithm was nonsignificantly different from TG-43. Therefore, even in the presence of air pockets, the TG-43 algorithm for calculating the VCB dose is appropriate.

Development and benchmarking of the first fast Monte Carlo engine for helium ion beam dose calculation: MonteRay.

Monte Carlo (MC) simulations are considered the gold-standard for accuracy in radiotherapy dose calculation; however, general purpose MC engines are computationally demanding and require long runtimes. For this reason, several groups have recently developed fast MC systems dedicated mainly to photon and proton external beam therapy, affording both speed and accuracy. To support research and clinical activities at the Heidelberg Ion-beam Therapy Center (HIT) with actively scanned helium ion beams, this work presents MonteRay, the first fast MC dose calculation engine for helium ion therapy. MonteRay is a CPU MC dose calculation engine written in C++, capable of simulating therapeutic proton and helium ion beams. In this work, development steps taken to include helium ion beams in MonteRay are presented. A detailed description of the newly implemented physics models for helium ions, for example, for multiple coulomb scattering and inelastic nuclear interactions, is provided. MonteRay dose computations of helium ion beams are evaluated using a comprehensive validation dataset, including measurements of spread-out Bragg peaks (SOBPs) with varying penetration depths/field sizes, measurements with an anthropomorphic phantom and FLUKA simulations of a patient plan. Improvement in computational speed is demonstrated in comparison against reference FLUKA simulations. Dosimetric comparisons between MonteRay and measurements demonstrated good agreement. Comparing SOBPs at 5, 12.5, and 20cm depth, mean absolute percent dose differences were 0.7%, 0.7%, and 1.4%, respectively. Comparison against measurements behind an anthropomorphic head phantom revealed mean absolute dose differences of about 1.2% (FLUKA: 1.5%) with per voxel errors ranging from -4.5% to 4.1% (FLUKA: -6% to 3%). Computed global 3%/3mm 3D-gamma passing rates of ∼99% were achieved, exceeding those previously reported for an analytical dose engine. Comparisons against FLUKA simulations for a patient plan revealed local 2%/2mm 3D-gamma passing rates of 98%. Compared to FLUKA in voxelized geometries, MonteRay saw run-time reductions ranging from 20× to 60×, depending on the beam's energy. MonteRay, the first fast MC engine dedicated to helium ion therapy, has been successfully developed with a focus on both speed and accuracy. Validations against dosimetric measurements in homogeneous and heterogeneous scenarios and FLUKA MC calculations have proven the validity of the physical models implemented. Timing comparisons have shown significant speedups between 20 and 60 when compared to FLUKA, making MonteRay viable for clinical routine. MonteRay will support research and clinical practice at HIT, for example, TPS development, validation and treatment design for upcoming clinical trials for raster-scanned helium ion therapy.

EVALUATION OF PATIENT-SPECIFIC IMRT QUALITY ASSURANCE AND POINT DOSE MEASUREMENT FOR COMPLEX HEAD AND NECK AND BRAIN CANCER USING GAFCHROMIC EBT3 FILM.

Patient-specific intensity-modulated radiation therapy (IMRT) quality assurance (QA) is essential for complex radiotherapy treatment as it involves complex intensity modulation and high-dose gradient regions. IMRT QA was performed by point dose verification and two-dimensional (2D) dose distribution measurement using gamma method. Calibrated External Beam Therapy 3 (EBT3) film was used for point dose and pre-treatment verification of 10 IMRT plans, five complex Head and Neck (HN) and five brain cases. The gamma passing rate (GPR) was evaluated for 3%/3mm gamma criteria and compared with 2D array. Isocentre dose was measured for all 10 IMRT plans on EBT3 film. Percentage deviation of point dose measurement from TPS calculated was found 0.4% for brain cases and 2.9% for HN cases. The GPR for 3%/3mm criteria was obtained higher than 95% for brain and HN cases. Results suggest that film dosimetry is also a reliable verification system for patient-specific IMRT QA as the 2D array.

Selection of the most sensitive configuration of strip array detectors for x-ray beam monitoring in radiotherapy of cancer utilizing singular value decomposition

We propose a concise mathematical framework in order to compare detector configurations efficiently for x-ray beam monitoring in radiotherapy of cancer. This framework consists of the singular value decomposition (SVD) of the system matrix and the definition of an effective information threshold based on the relative error inequality utilizing the condition number of a matrix. The goal of this paper is to present the mathematical argument as well as to demonstrate its use for modeling the best detector configuration for monitoring x-ray beams in external beam therapy. This analysis depends neither on specific measurements of a given set of x-ray beams, nor does it depend in specific reconstruction algorithms of the beam shape, and therefore represents a configuration meta-analysis. In the results section, we compare three possible detector designs, each leading to a highly underdetermined system, and are able to determine their effective information content relative to each other. Furthermore, by changing design parameters, such as the geometric detector configuration, number of detectors, detector pixel size, and the x-ray beam blur, deeper insight in this challenging inverse problem is achieved and the most sensitive monitoring scheme is determined.Graphical Illustration of the general approach for performing configuration meta–analysis.