Assessment of bias in scoring of AI-based radiotherapy segmentation and planning studies using modified TRIPOD and PROBAST guidelines as an example.

BACKGROUND AND PURPOSE: Studies investigating the application of Artificial Intelligence (AI) in the field of radiotherapy exhibit substantial variations in terms of quality. The goal of this study was to assess the amount of transparency and bias in scoring articles with a specific focus on AI based segmentation and treatment planning, using modified PROBAST and TRIPOD checklists, in order to provide recommendations for future guideline developers and reviewers. MATERIALS AND METHODS: The TRIPOD and PROBAST checklist items were discussed and modified using a Delphi process. After consensus was reached, 2 groups of 3 co-authors scored 2 articles to evaluate usability and further optimize the adapted checklists. Finally, 10 articles were scored by all co-authors. Fleiss' kappa was calculated to assess the reliability of agreement between observers. RESULTS: Three of the 37 TRIPOD items and 5 of the 32 PROBAST items were deemed irrelevant. General terminology in the items (e.g., multivariable prediction model, predictors) was modified to align with AI-specific terms. After the first scoring round, further improvements of the items were formulated, e.g., by preventing the use of sub-questions or subjective words and adding clarifications on how to score an item. Using the final consensus list to score the 10 articles, only 2 out of the 61 items resulted in a statistically significant kappa of 0.4 or more demonstrating substantial agreement. For 41 items no statistically significant kappa was obtained indicating that the level of agreement among multiple observers is due to chance alone. CONCLUSION: Our study showed low reliability scores with the adapted TRIPOD and PROBAST checklists. Although such checklists have shown great value during development and reporting, this raises concerns about the applicability of such checklists to objectively score scientific articles for AI applications. When developing or revising guidelines, it is essential to consider their applicability to score articles without introducing bias.

Quality management in radiotherapy treatment delivery.

Radiation Oncology continues to rely on accurate delivery of radiation, in particular where patients can benefit from more modulated and hypofractioned treatments that can deliver higher dose to the target while optimising dose to normal structures. These deliveries are more complex, and the treatment units are more computerised, leading to a re-evaluation of quality assurance (QA) to test a larger range of options with more stringent criteria without becoming too time and resource consuming. This review explores how modern approaches of risk management and automation can be used to develop and maintain an effective and efficient QA programme. It considers various tools to control and guide radiation delivery including image guidance and motion management. Links with typical maintenance and repair activities are discussed, as well as patient-specific quality control activities. It is demonstrated that a quality management programme applied to treatment delivery can have an impact on individual patients but also on the quality of treatment techniques and future planning. Developing and customising a QA programme for treatment delivery is an important part of radiotherapy. Using modern multidisciplinary approaches can make this also a useful tool for department management.

Analysis of the Dose Drop at the Edge of the Target Area in Heavy Ion Radiotherapy.

BACKGROUND: The dose distribution of heavy ions at the edge of the target region will have a steep decay during radiotherapy, which can better protect the surrounding organs at risk. OBJECTIVE: To analyze the dose decay gradient at the back edge of the target region during heavy ion radiotherapy. METHODS: Treatment planning system (TPS) was employed to analyze the dose decay at the edge of the beam under different incident modes and multiple dose segmentation conditions during fixed beam irradiation. The dose decay data of each plan was collected based on the position where the rear edge of the beam began to fall rapidly. Uniform scanning mode was selected in heavy ion TPS. Dose decay curves under different beam setup modes were drawn and compared. RESULTS: The dose decay data analysis showed that in the case of single beam irradiation, the posterior edge of the beam was 5 mm away, and the posterior dose could drop to about 20%. While irradiation in opposite direction, the posterior edge of the beam was 5 mm away, and the dose could drop to about 50%. In orthogonal irradiation of two beams, the posterior edge of the beam could drop to about 30-38% in a distance of 5 mm. Through the data analysis in the TPS, the sharpness of the dose at the back edge of the heavy ion beam is better than that at the lateral edge, but the generated X-ray contamination cannot be ignored. CONCLUSIONS: The effect of uneven CT value on the dose decay of heavy ion beam should also be considered in clinical treatment.

Influence of Modulation Factor on Treatment Plan Quality and Irradiation Time in Hippocampus-Sparing Whole-Brain Radiotherapy Using Tomotherapy.

Objectives: Hippocampus-sparing whole-brain radiotherapy (HS-WBRT) using tomotherapy is known to provide a better dose distribution than volumetric-modulated arc therapy but requires an extended irradiation time. The present study aimed to investigate whether irradiation time can be shortened by reducing the modulation factor (MF) without losing the target dose distribution. Methods: Using six tilted computed tomography images in the head area, the planning target volume (PTV) and hippocampal doses, and the irradiation time was investigated with a jaw width of 1 cm, a pitch of 0.200, and the MF changed from 3.0 to 2.6, 2.2, 1.8, and 1.4. Results: No significant changes in the PTV or hippocampus were found with MF in the range from 3.0 to 1.8, but marked deterioration was found with that of 1.4. The irradiation time showed a linear relationship with the MF within the range from 3.0 to 1.8, with 1334, 1158, 986, and 817 s at modulation factors of 3.0, 2.6, 2.2, and 1.8, respectively. However, when the MF was 1.4, the irradiation time was 808 s. Conclusions: When HS-WBRT is performed with a tilted body position and a jaw width of 1 cm, with a MF of 1.8, a favorable balance between dose parameters and irradiation time is achieved, whereas with a MF of 1.4, the quality of the radiotherapy plan deteriorates, and the irradiation time is approximately the same as that with a MF of 1.8.

Personalising treatment plan quality review with knowledge-based planning in the TROG 15.03 trial for stereotactic ablative body radiotherapy in primary kidney cancer.

INTRODUCTION: Quality assurance (QA) of treatment plans in clinical trials improves protocol compliance and patient outcomes. Retrospective use of knowledge-based-planning (KBP) in clinical trials has demonstrated improved treatment plan quality and consistency. We report the results of prospective use of KBP for real-time QA of treatment plan quality in the TROG 15.03 FASTRACK II trial, which evaluates efficacy of stereotactic ablative body radiotherapy (SABR) for kidney cancer. METHODS: A KBP model was generated based on single institution data. For each patient in the KBP phase (open to the last 31 patients in the trial), the treating centre submitted treatment plans 7 days prior to treatment. A treatment plan was created by using the KBP model, which was compared with the submitted plan for each organ-at-risk (OAR) dose constraint. A report comparing each plan for each OAR constraint was provided to the submitting centre within 24 h of receiving the plan. The centre could then modify the plan based on the KBP report, or continue with the existing plan. RESULTS: Real-time feedback using KBP was provided in 24/31 cases. Consistent plan quality was in general achieved between KBP and the submitted plan. KBP review resulted in replan and improvement of OAR dosimetry in two patients. All centres indicated that the feedback was a useful QA check of their treatment plan. CONCLUSION: KBP for real-time treatment plan review was feasible for 24/31 cases, and demonstrated ability to improve treatment plan quality in two cases. Challenges include integration of KBP feedback into clinical timelines, interpretation of KBP results with respect to clinical trade-offs, and determination of appropriate plan quality improvement criteria.

FIELDRT: an open-source platform for the assessment of target volume delineation in radiation therapy.

OBJECTIVES: Target volume delineation (TVD) has been identified as a weakness in the accuracy of radiotherapy, both within and outside of clinical trials due to the intra/interobserver variations affecting the TVD quality. Sources of variations such as poor compliance or protocol violation may have adverse effect on treatment outcomes. In this paper, we present and describe the FIELDRT software developed for the ARENA project to improve the quality of TVD through qualitative and quantitative feedbacks and individual and personalized summary of trainee"s performance. METHODS: For each site-specific clinical case included in the FIELDRT software, reference volumes, minimum and maximum "acceptable" volumes and organ at risk were derived by outlines of consultants and senior trainees. The software components currently developed include: (a) user-friendly importing interface (b) analysis toolbox to compute quantitative and qualitative (c) visualiser and (d) structured report generator for personalised feedback. The FIELDRT software was validated by comparing the performance of 63 trainees and by measuring performance over time. In addition, a trainee evaluation day was held in 2019 to collect feedback on FIELDRT. RESULTS: Results show the trainees' improvement when reoutlining a case after reviewing the feedback generated from the FIELDRT software. Comments and feedback received after evaluation day were positive and confirmed that FIELDRT can be a useful application for training purposes. CONCLUSION: We presented a new open-source software to support education in TVD and ongoing continuous professional development for clinical oncology trainees and consultants. ARENA in combination with FIELDRT implements site-specific modules with reference target and organs at risk volumes and automatically evaluates individual performance using several quantitative and qualitative feedbacks. Pilot results suggests this software could be used as an education tool to reduce variation in TVD so to guarantee high quality in radiotherapy. ADVANCES IN KNOWLEDGE: FIELDRT is a new easy and free to use software aiming at supporting education in TVD and ongoing continuous professional development. The software provides quantitative/qualitative feedback and an exportable report with an individual and personalised summary of trainee's performance.

Adaptive planning based on single beam optimization in passive scattering carbon ion radiotherapy for patients with pancreatic cancer.

BACKGROUND: Daily anatomical deviations may distort the dose distribution in carbon ion radiotherapy (CIRT), which may cause treatment failure. Therefore, this study aimed to perform re-planning to maintain the dose coverage in patients with pancreatic cancer with passive scattering CIRT. METHODS: Eight patients with pancreatic cancer and 95 daily computed tomography (CT) sets were examined. Two types of adaptive plans based on new range compensators (RCs) (AP-1) and initial RCs (AP-2) were generated. In AP-2, each beam was optimized by manually adjusting the range shifter thickness and spread-out Bragg peak size to make dose reduction by < 3% of the original plan. Doses of the original plan with bone matching (BM) and tumor matching (TM) were examined for comparison. We calculated the accumulated dose using the contour and intensity-based deformable image registration algorithm. The dosimetric differences in respect to the original plan were compared between methods. RESULTS: Using TM and BM, mean ± standard deviations of daily CTV V95 (%) difference from the original plan was - 5.1 ± 6.2 and - 8.8 ± 8.8, respectively, but 1.2 ± 3.4 in AP-1 and - 0.5 ± 2.1 in AP-2 (P < 0.001). AP-1 and AP-2 enabled to maintain a satisfactory accumulated dose in all patients. The dose difference was 1.2 ± 2.8, - 2,1 ± 1.7, - 7.1 ± 5.2, and - 16.5 ± 15.0 for AP-1, AP-2, TM, and BM, respectively. However, AP-2 caused a dose increase in the duodenum, especially in the left-right beam. CONCLUSIONS: The possible dose deterioration should be considered when performing the BM, even TM. Re-planning based on single beam optimization in passive scattering CIRT seems an effective and safe method of ensuring the treatment robustness in pancreatic cancer. Further study is necessary to spare healthy tissues, especially the duodenum.

Interobserver variability in target volume delineation in definitive radiotherapy for thoracic esophageal cancer: a multi-center study from China.

PURPOSE: To investigate the interobserver variability (IOV) in target volume delineation of definitive radiotherapy for thoracic esophageal cancer (TEC) among cancer centers in China, and ultimately improve contouring consistency as much as possible to lay the foundation for multi-center prospective studies. METHODS: Sixteen cancer centers throughout China participated in this study. In Phase 1, three suitable cases with upper, middle, and lower TEC were chosen, and participants were asked to contour a group of gross tumor volume (GTV-T), nodal gross tumor volume (GTV-N) and clinical target volume (CTV) for each case based on their routine experience. In Phase 2, the same clinicians were instructed to follow a contouring protocol to re-contour another group of target volume. The variation of the target volume was analyzed and quantified using dice similarity coefficient (DSC). RESULTS: Sixteen clinicians provided routine volumes, whereas ten provided both routine and protocol volumes for each case. The IOV of routine GTV-N was the most striking in all cases, with the smallest DSC of 0.37 (95% CI 0.32-0.42), followed by CTV, whereas GTV-T showed high consistency. After following the protocol, the smallest DSC of GTV-N was improved to 0.64 (95% CI 0.45-0.83, P = 0.005) but the DSC of GTV-T and CTV remained constant in most cases. CONCLUSION: Variability in target volume delineation was observed, but it could be significantly reduced and controlled using mandatory interventions.

Radiotherapy plan evaluation indices: A dosimetrical suitability check.

PURPOSE: To classify the available plan evaluation indices and compare the dosimetric suitability of these indices. MATERIALS AND METHODS: Available published plan evaluation indices were categorized. Conformity index (CI) into two groups, one group contains those CI formulas which do not consider critical structure and other group contains those CI formulas which consider planning target volume (PTV) coverage, normal tissue and critical structure sparing simultaneously. Various homogeneity index (HI) formulas extracted from literature. Structure data sets of 25 patients were taken under consideration comprising of various sites. For each patient, two plans were created using Volumetric Arc Therapy technique. First type of plan (Plan-A) were generated considering all tissue objectives for targets and Organ at Risks (OARs) whereas second type of plan (Plan-B) were generated considering only targets tissue objectives and excluding OARs tissue objectives during plan optimization and dose calculation. Planning evaluation parameters were compared between Plan-A and Plan-B. RESULTS: CI calculated by various formulas in two different scenarios presented <2% variation. Any commonly used CI formula failed to differentiate the two different planning situations. On comparison between HI of two different scenario, it is observed that there are four formulas of HI which showed negligible variation but two formulae: S-index and HI (D) showed marginal variation. It is also observed that when OARs are removed from optimization dose homogeneity improved which is specifically pointed by sigma index formula. CONCLUSION: CI, which has assimilated the presence of OAR in their formulation, shows more reliability in plan evaluation. Sigma index was found to be more efficient formula while evaluating homogeneity of a treatment plan.

Quality assurance in radiation oncology.

The Children's Oncology Group (COG) has a strong quality assurance (QA) program managed by the Imaging and Radiation Oncology Core (IROC). This program consists of credentialing centers and providing real-time management of each case for protocol compliant target definition and radiation delivery. In the International Society of Pediatric Oncology (SIOP), the lack of an available, reliable online data platform has been a challenge and the European Society for Paediatric Oncology (SIOPE) quality and excellence in radiotherapy and imaging for children and adolescents with cancer across Europe in clinical trials (QUARTET) program currently provides QA review for prospective clinical trials. The COG and SIOP are fully committed to a QA program that ensures uniform execution of protocol treatments and provides validity of the clinical data used for analysis.

Hypofractionated Radiotherapy With Simultaneous-integrated Boost After Breast-conserving Surgery Compared to Standard Boost-applications Using Helical Tomotherapy With TomoEdge.

BACKGROUND/AIM: This comparative plan study examines a range of boost-radiation methods in adjuvant radiotherapy of breast cancer using helical intensity-modulated radiotherapy with TomoEdge-technique. Impact of hypofractionated radiation with simultaneous-integrated boost (SIB) and influence of differing assumed α/ß-values were examined. PATIENTS AND METHODS: For 10 patients with left-sided breast cancer each four helical IMRT-plans with TomoEdge-technique were created: hypofractionated+SIB (H-SIB) (42.4/54.4 Gy, 16 fractions), normofractionated+SIB (N-SIB) (50.4/64.4 Gy, 28 fractions), hypofractionated+sequential-boost (H-SB) (42.4 Gy/16 fractions+16 Gy/8 fractions), normofractionated+ sequential-boost (N-SB) (50.4 Gy/28 fractions+16 Gy/8 fractions). Equivalent doses (EQD2) to organs-at-risk (OAR) and irradiated mammary-gland were analysed for different assumed α/ß-values. RESULTS: The mean EQD2 to OAR was significantly lower using hypofractionated radiation-techniques. H-SIB and H-SB were not significantly different. H-SIB and N-SIB conformed significantly better to the breast planning-target volume (PTV) and boost-volume (BV) than H-SB and N-SB. Regarding BV, mean EQD2 was significantly higher for all α/ß-values investigated when using H-SIB and N-SIB. Regarding PTV, there were no clinically relevant differences. CONCLUSION: Relating to dosimetry, H-SIB is effective compared to standard-boost-techniques.

Optimal stereotactic body radiotherapy dosage for hepatocellular carcinoma: a multicenter study.

BACKGROUND: The optimal dose and fractionation scheme of stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) remains unclear due to different tolerated liver volumes and degrees of cirrhosis. In this study, we aimed to verify the dose-survival relationship to optimize dose selection for treatment of HCC. METHODS: This multicenter retrospective study included 602 patients with HCC, treated with SBRT between January 2011 and March 2017. The SBRT dosage was classified into high dose, moderate dose, and low dose levels: SaRT (BED10 ≥ 100 Gy), SbRT (EQD2 > 74 Gy to BED10 < 100 Gy), and ScRT (EQD2 < 74 Gy). Overall survival (OS), progression-free survival (PFS), local control (LC), and intrahepatic control (IC) were evaluated in univariable and multivariable analyses. RESULTS: The median tumor size was 5.6 cm (interquartile range [IQR] 1.1-21.0 cm). The median follow-up time was 50.0 months (IQR 6-100 months). High radiotherapy dose correlated with better outcomes. After classifying into the SaRT, SbRT, and ScRT groups, three notably different curves were obtained for long-term post-SBRT survival and intrahepatic control. On multivariate analysis, higher radiation dose was associated with improved OS, PFS, and intrahepatic control. CONCLUSIONS: If tolerated by normal tissue, we recommend SaRT (BED10 ≥ 100 Gy) as a first-line ablative dose or SbRT (EQD2 ≥ 74 Gy) as a second-line radical dose. Otherwise, ScRT (EQD2 < 74 Gy) is recommended as palliative irradiation.

MRI only in a patient with prostate cancer with bilateral metal hip prostheses: case study.

OBJECTIVE: To outline a practical method of performing prostate cancer radiotherapy in patients with bilateral metal hip prostheses with the standard resources available in a modern general hospital. The proposed workflow is based exclusively on magnetic resonance imaging (MRI) to avoid computed tomography (CT) artifacts. CASE DESCRIPTION: This study concerns a 73-year-old man with bilateral hip prostheses with an elevated risk prostate cancer. Magnetic resonance images with assigned electron densities were used for planning purposes, generating a synthetic CT (sCT). Imaging acquisition was performed with an optimized Dixon sequence on a 1.5T MRI scanner. The images were contoured by autosegmentation software, based on an MRI database of 20 patients. The sCT was generated assigning averaged electron densities to each contour. Two volumetric modulated arc therapy plans, a complete arc and a partial one, where the beam entrances through the prostheses were avoided for about 50° on both sides, were compared. The feasibility of matching daily cone beam CT (CBCT) with MRI reference images was also tested by visual evaluations of different radiation oncologists. CONCLUSIONS: The use of magnetic resonance images improved accuracy in targets and organs at risk (OARs) contouring. The complete arc plan was chosen because of 10% lower mean and maximum doses to prostheses with the same planning target volume coverage and OAR sparing. The image quality of the match between performed CBCTs and MRI was considered acceptable. The proposed method seems promising to improve radiotherapy treatments for this complex category of patients.

Long-Term Outcomes and Sequelae Analysis of Intracranial Germinoma: Need to Reduce the Extended-Field Radiotherapy Volume and Dose to Minimize Late Sequelae.

PURPOSE: We aimed to refine the radiotherapy (RT) volume and dose for intracranial germinoma considering recurrences and long-term toxicities. MATERIALS AND METHODS: Total 189 patients with intracranial germinoma were treated with RT alone (n=50) and RT with upfront chemotherapy (CRT) (n=139). All cases were confirmed histologically. RT fields comprised the extended-field and involved-field only for primary site. The extended-field, including craniospinal, whole brain (WB), and whole ventricle (WV) for cranial field, is followed by involved-field boost. The median follow-up duration was 115 months. RESULTS: The relapses developed in 13 patients (6.9%). For the extended-field, cranial RT dose down to 18 Gy exhibited no cranial recurrence in 34 patients. In CRT, 74 patients (56.5%) showed complete response to chemotherapy and no involved-field recurrence with low-dose RT of 30 Gy. WV RT with chemotherapy for the basal ganglia or thalamus germinoma showed no recurrence. Secondary malignancy developed in 10 patients (5.3%) with a latency of 20 years (range, 4 to 26 years) and caused mortalities in six. WB or craniospinal field rather than WV or involved-field significantly increased the rate of hormone deficiencies, and secondary malignancy. RT dose for extended-field correlated significantly with the rate of hormone deficiencies, secondary malignancy, and neurocognitive dysfunction. CONCLUSION: De-intensifying extended-field rather than involved-field or total scheme of RT will be critical to decrease the late toxicities. Upfront chemotherapy could be beneficial for the patients with complete response to minimize the RT dose down to 30 Gy. Prospective trials focused on de-intensification of the extended-field RT are warranted.

Probabilistic definition of the clinical target volume-implications for tumor control probability modeling and optimization.

Evidence has been presented that moving beyond the binary definition of clinical target volume (CTV) towards a probabilistic CTV can result in better treatment plans. The probabilistic CTV takes the likelihood of disease spread outside of the gross tumor into account. An open question is: how to optimize tumor control probability (TCP) based on the probabilistic CTV. We derive expressions for TCP under the assumptions of voxel independence and dependence. For the dependent case, we make the assumption that tumors grow outward from the gross tumor volume. We maximize the (non-convex) TCP under convex dose constraints for all models. For small numbers of voxels, and when a dose-influence matrix is not used, we use exhaustive search or Lagrange multiplier theory to compute optimal dose distributions. For larger cases we present (1) a multi-start strategy using linear programming with a random cost vector to provide random feasible starting solutions, followed by a local search, and (2) a heuristic strategy that greedily selects which subvolumes to dose, and then for each subvolume assignment runs a convex approximation of the optimization problem. The optimal dose distributions are in general different for the independent and dependent models even though the probabilities of each voxel being tumorous are set to the same in both cases. We observe phase transitions, where a subvolume is either dosed to a high level, or it gets 'sacrificed' by not dosing it at all. The greedy strategy often yields solutions indistinguishable from the multi-start solutions, but for the 2D case involving organs-at-risk and the dependent TCP model, discrepancies of around 5% (absolute) for TCP are observed. For realistic geometries, although correlated voxels is a more reasonable assumption, the correlation function is in general unknown. We demonstrate a tractable heuristic that works very well for the independent models and reasonably well for the dependent models. All data are provided.

TriB-RT: Simultaneous optimization of photon, electron and proton beams.

PURPOSE: To develop a novel treatment planning process (TPP) with simultaneous optimization of modulated photon, electron and proton beams for improved treatment plan quality in radiotherapy. METHODS: A framework for fluence map optimization of Monte Carlo (MC) calculated beamlet dose distributions is developed to generate treatment plans consisting of photon, electron and spot scanning proton fields. Initially, in-house intensity modulated proton therapy (IMPT) plans are compared to proton plans created by a commercial treatment planning system (TPS). A triple beam radiotherapy (TriB-RT) plan is generated for an exemplary academic case and the dose contributions of the three particle types are investigated. To investigate the dosimetric potential, a TriB-RT plan is compared to an in-house IMPT plan for two clinically motivated cases. Benefits of TriB-RT for a fixed proton beam line with a single proton field are investigated. RESULTS: In-house optimized IMPT are of at least equal or better quality than TPS-generated proton plans, and MC-based optimization shows dosimetric advantages for inhomogeneous situations. Concerning TriB-RT, for the academic case, the resulting plan shows substantial contribution of all particle types. For the clinically motivated case, improved sparing of organs at risk close to the target volume is achieved compared to IMPT (e.g. myelon and brainstem [Formula: see text] -37%) at cost of an increased low dose bath (healthy tissue V 10% +22%). In the scenario of a fixed proton beam line, TriB-RT plans are able to compensate the loss in degrees of freedom to substantially improve plan quality compared to a single field proton plan. CONCLUSION: A novel TPP which simultaneously optimizes photon, electron and proton beams was successfully developed. TriB-RT shows the potential for improved treatment plan quality and is especially promising for cost-effective single-room proton solutions with a fixed beamline in combination with a conventional linac delivering photon and electron fields.

ROAD: ROtational direct Aperture optimization with a Decoupled ring-collimator for FLASH radiotherapy.

Ultra-high dose rate in radiotherapy (FLASH) has been shown to increase the therapeutic index with markedly reduced normal tissue toxicity and the same or better tumor cell killing. The challenge to achieve FLASH using x-rays, besides developing a high output linac, is to intensity-modulate the high-dose-rate x-rays so that the biological gain is not offset by the lack of physical dose conformity. In this study, we develop the ROtational direct Aperture optimization with a Decoupled ring-collimator (ROAD) to achieve simultaneous ultrafast delivery and complex dose modulation. The ROAD design includes a fast-rotating slip-ring linac and a decoupled collimator-ring with 75 pre-shaped multi-leaf-collimator (MLC) modules. The ring-source rotates at 1 rotation per second (rps) clockwise while the ring-collimator is either static or rotating at 1 rps counterclockwise, achieving 75 (ROAD-75) or 150 (ROAD-150) equal-angular beams for one full arc. The Direct Aperture Optimization (DAO) for ROAD was formulated to include a least-square dose fidelity, an anisotropic total variation term, and a single segment term. The FLASH dose (FD) and FLASH biological equivalent dose (FBED) were computed voxelwise, with the latter using a spatiotemporal model accounting for radiolytic oxygen depletion. ROAD was compared with clinical volumetric modulated arc therapy (VMAT) on a brain, a lung, a prostate, and a head and neck cancer patient. The mean dose rate of ROAD-75 and ROAD-150 are 76.2 Gy s-1 and 112 Gy s-1 respectively to deliver 25 Gy single-fraction dose in 1 s. With improved PTV homogeneity, ROAD-150 reduced (max, mean) OAR physical dose by (4.8 Gy, 6.3 Gy). The average R50 and integral dose of (VMAT, ROAD-75, ROAD-150) are (4.8, 3.2, 3.2) and (89, 57, 56) Gy×Liter, respectively. The FD and FBED showed model dependent FLASH effects. The novel ROAD design achieves ultrafast dose delivery and improves physical dosimetry compared with clinical VMAT, providing a potentially viable engineering solution for x-ray FLASH radiotherapy.

Robust radiation therapy optimization using simulated treatment courses for handling deformable organ motion.

We describe a radiation therapy treatment plan optimization method that explicitly considers the effects of interfraction organ motion through optimization on the clinical target volume (CTV), and investigate how it compares to conventional planning using a planning target volume (PTV). The method uses simulated treatment courses generated using patient images created by a deformable registration algorithm to replicate the effects of interfraction organ motion, and performs robust optimization aiming to achieve CTV coverage under all simulated treatment courses. The method was applied to photon-mediated treatments of three prostate cases and compared to conventional, PTV-based planning with margins selected to achieve similar CTV coverage as the robustly optimized plans. Clinical goals for the CTV and healthy tissue were used in comparison between the two types of plans. Out of the two clinical goals for overdosage of the CTV, the three robustly optimized plans violated respectively 2, 2, and 0 goals in the mean over the scenarios, whereas none of the PTV plans violated these goals. Of the ten clinical goals for rectum, bladder, anal canal, and bulbus, the robustly optimized plans violated respectively 0, 1, and 1 goals in the mean, whereas the PTV plans violated 5, 7, and 4 goals. Compared to PTV-based planning, the inclusion of treatment course scenarios in the optimization has the potential to reduce the dose to healthy tissues while retaining a high probability of target coverage. This may reduce the need for adaptive replanning.

Efficacy and toxicity of FLASH radiotherapy: A systematic review.

In recent times, research on the use of ultrahigh-dose rates delivered in super-fast times in cancer treatment has been garnering interest. This has brought about the term "FLASH" radiotherapy (RT). Thus, in the present study, we systematically review these recent studies on FLASH RT with regard to its efficacy and safety. The reporting of this systematic review was done in line with the statement of Preferred Reporting Items for Systematic reviews and Meta-Analyses. Electronic search of the databases such as PubMed, Scopus, and Embase was conducted to retrieve relevant studies investigating the FLASH effect. From an initial search of 216 potential articles, 16 articles (in vivo, in vitro , and clinical studies) were finally included in this systematic review. Results showed that FLASH RT dose rates had protective effects on normal tissues in addition to antitumor effect. Although still in its early research stages, FLASH RT has the potential to rival present RT regimens in terms of safety and antitumor effect. However, further studies are needed to address the aspects such as optimal dose rate, effect on deep tumors, tumor recurrence, longer follow-up time, and mechanism of action.