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Purpose: This study explores the dosimetric feasibility and plan quality of hybrid ultra-high dose rate (UHDR) electron and conventional dose rate (CDR) photon (HUC) radiotherapy for treating deep-seated tumours with FLASH-RT., Methods: HUC treatment planning was conducted optimizing a broad UHDR electron beam (between 20-250 MeV) combined with a CDR VMAT for a glioblastoma, a pancreatic cancer, and a prostate cancer case. HUC plans were based on clinical prescription and fractionation schemes and compared against clinically delivered plans. Considering a HUC boost treatment for the glioblastoma consisting of a 15-Gy-single-fraction UHDR electron boost supplemented with VMAT, two scenarios for FLASH sparing were assessed using FLASH-modifying-factor-weighted doses., Results: For all three patient cases, HUC treatment plans demonstrated comparable dosimetric quality to clinical plans, with similar PTV coverage (V 95% within 0.5 %), homogeneity, and critical OAR-sparing. At the same time, HUC plans delivered a substantial portion of the dose to the PTV (D median of 50-69 %) and surrounding tissues at UHDR. For the HUC boost treatment of the glioblastoma, the first FLASH sparing scenario showed a moderate FLASH sparing magnitude (10 % for D 2%,PTV ) for the 15-Gy UHDR electron boost, while the second scenario indicated a more substantial sparing of brain tissues inside and outside the PTV (32 % for D 2%,PTV , 31 % for D 2%,Brain )., Conclusions: From a planning perspective, HUC treatments represent a feasible approach for delivering dosimetrically conformal UHDR treatments, potentially mitigating technical challenges associated with delivering conformal FLASH-RT for deep-seated tumours. While further research is needed to optimize HUC fractionation and delivery schemes for specific patient cohorts, HUC treatments offer a promising avenue for the clinical transfer of FLASH-RT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Treatments at ultra-high dose rate (UHDR) have the potential to improve the therapeutic index of radiation therapy (RT) by sparing normal tissues compared to conventional dose rate irradiations. Insufficient and inconsistent reporting in physics and dosimetry of preclinical and translational studies may have contributed to a reproducibility crisis of radiobiological data in the field. Consequently, the development of a common terminology, as well as common recording, reporting, dosimetry, and metrology standards is required. In the context of UHDR irradiations, the temporal dose delivery parameters are of importance, and under-reporting of these parameters is also a concern.This work proposes a standardization of terminology, recording, and reporting to enhance comparability of both preclinical and clinical UHDR studies and and to allow retrospective analyses to aid the understanding of the conditions which give rise to the FLASH effect., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Till Tobias Böhlen employed by Lausanne University Hospital has a research collaboration with IntraOp, TheryQ (PMB-Alcen) and RaySearch. Serena Psoroulas received funding from Varian, a Siemens Healthineers Company. Jack D Aylward no conflict of interest. Sam Beddar no conflict of interest. Alexandros Douralis no conflict of interest. Grégory Delpon no conflict of interest. Cristina Garibaldi no conflict of interest. Alessia Gasparini has a researh collaboration with Sordina IORT Technologies. Emil Schüler no conflict of interest. Frank Stephan no conflict of interest. Raphaël Moeckli employed by Lausanne University Hospital that has research collaboration agreements on FLASH-RT with IntraOp, TheryQ (PMB-Alcen) and RaySearch. Anna Subiel no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Treatment delivery safety and accuracy are essential to control the disease and protect healthy tissues in radiation therapy. For usual treatment, a phantom-based patient specific quality assurance (PSQA) is performed to verify the delivery prior to the treatment. The emergence of adaptive radiation therapy (ART) adds new complexities to PSQA. In fact, organ at risks and target volume re-contouring as well as plan re-optimization and treatment delivery are performed with the patient immobilized on the treatment couch, making phantom-based pretreatment PSQA impractical. In this case, phantomless PSQA tools based on multileaf collimator (MLC) leaf open times (LOTs) verifications provide alternative approaches for the Radixact® treatment units. However, their validity is compromised by the lack of independent and reliable methods for calculating the LOT performed by the MLC during deliveries., Purpose: To provide independent and reliable methods of LOT calculation for the Radixact® treatment units., Methods: Two methods for calculating the LOTs performed by the MLC during deliveries have been implemented. The first method uses the signal recorded by the build-in detector and the second method uses the signal recorded by optical sensors mounted on the MLC. To calibrate the methods to the ground truth, in-phantom ionization chamber LOT measurements have been conducted on a Radixact® treatment unit. The methods were validated by comparing LOT calculations with in-phantom ionization chamber LOT measurements performed on two Radixact® treatment units., Results: The study shows a good agreement between the two LOT calculation methods and the in-phantom ionization chamber measurements. There are no notable differences between the two methods and the same results were observed on the different treatment units., Conclusions: The two implemented methods have the potential to be part of a PSQA solution for ART in tomotherapy., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics is published by Wiley Periodicals, Inc. on behalf of The American Association of Physicists in Medicine.)

Purpose: One of the advantages of integrating automated processes in treatment planning is the reduction of manual planning variability. This study aims to assess whether a deep-learning-based auto-planning solution can also reduce the contouring variation-related impact on the planned dose for early-breast cancer treatment., Methods: Auto- and manual plans were optimized for 20 patients using both auto- and manual OARs, including both lungs, right breast, heart, and left-anterior-descending (LAD) artery. Differences in terms of recalculated dose (ΔD rc M ,ΔD rc A ) and reoptimized dose (ΔD ro M ,ΔD ro A ) for manual (M) and auto (A)-plans, were evaluated on manual structures. The correlation between several geometric similarities and dose differences was also explored (Spearman's test)., Results: Auto-contours were found slightly smaller in size than manual contours for right breast and heart and more than twice larger for LAD. Recalculated dose differences were found negligible for both planning approaches except for heart (ΔD rc M =-0.4 Gy, ΔD rc A =-0.3 Gy) and right breast (ΔD rc M =-1.2 Gy, ΔD rc A =-1.3 Gy) maximum dose. Re-optimized dose differences were considered equivalent to recalculated ones for both lungs and LAD, while they were significantly smaller for heart (ΔD ro M =-0.2 Gy, ΔD ro A =-0.2 Gy) and right breast (ΔD ro M  =-0.3 Gy, ΔD ro A =-0.9 Gy) maximum dose. Twenty-one correlations were found for ΔD rc M,A (M=8,A=13) that reduced to four for ΔD ro M,A (M=3,A=1)., Conclusions: The sensitivity of auto-planning to contouring variation was found not relevant when compared to manual planning, regardless of the method used to calculate the dose differences. Nonetheless, the method employed to define the dose differences strongly affected the correlation analysis resulting highly reduced when dose was reoptimized, regardless of the planning approach., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Purpose: Clinical translation of FLASH-radiotherapy (RT) to deep-seated tumours is still a technological challenge. One proposed solution consists of using ultra-high dose rate transmission proton (TP) beams of about 200-250 MeV to irradiate the tumour with the flat entrance of the proton depth-dose profile. This work evaluates the dosimetric performance of very high-energy electron (VHEE)-based RT (50-250 MeV) as a potential alternative to TP-based RT for the clinical transfer of the FLASH effect., Methods: Basic physics characteristics of VHEE and TP beams were compared utilizing Monte Carlo simulations in water. A VHEE-enabled research treatment planning system was used to evaluate the plan quality achievable with VHEE beams of different energies, compared to 250 MeV TP beams for a glioblastoma, an oesophagus, and a prostate cancer case., Results: Like TP, VHEE above 100 MeV can treat targets with roughly flat (within ± 20 %) depth-dose distributions. The achievable dosimetric target conformity and adjacent organs-at-risk (OAR) sparing is consequently driven for both modalities by their lateral beam penumbrae. Electron beams of 400[500] MeV match the penumbra of 200[250] MeV TP beams and penumbra is increased for lower electron energies. For the investigated patient cases, VHEE plans with energies of 150 MeV and above achieved a dosimetric plan quality comparable to that of 250 MeV TP plans. For the glioblastoma and the oesophagus case, although having a decreased conformity, even 100 MeV VHEE plans provided a similar target coverage and OAR sparing compared to TP., Conclusions: VHEE-based FLASH-RT using sufficiently high beam energies may provide a lighter-particle alternative to TP-based FLASH-RT with comparable dosimetric plan quality., Competing Interests: Declaration of competing interest Andreas Bratel, Eric Landström and Erik Engwall are employees of RaySearch Laboratories AB. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Compared with conventional dose rate irradiation (CONV), ultrahigh dose rate irradiation (UHDR) has shown superior normal tissue sparing. However, a clinically relevant widening of the therapeutic window by UHDR, termed "FLASH effect," also depends on the tumor toxicity obtained by UHDR. Based on a combined analysis of published literature, the current study examined the hypothesis of tumor isoefficacy for UHDR versus CONV and aimed to identify potential knowledge gaps to inspire future in vivo studies., Methods and Materials: A systematic literature search identified publications assessing in vivo tumor responses comparing UHDR and CONV. Qualitative and quantitative analyses were performed, including combined analyses of tumor growth and survival data., Results: We identified 66 data sets from 15 publications that compared UHDR and CONV for tumor efficacy. The median number of animals per group was 9 (range 3-15) and the median follow-up period was 30.5 days (range 11-230) after the first irradiation. Tumor growth assays were the predominant model used. Combined statistical analyses of tumor growth and survival data are consistent with UHDR isoefficacy compared with CONV. Only 1 study determined tumor-controlling dose (TCD 50 ) and reported statistically nonsignificant differences., Conclusions: The combined quantitative analyses of tumor responses support the assumption of UHDR isoefficacy compared with CONV. However, the comparisons are primarily based on heterogeneous tumor growth assays with limited numbers of animals and short follow-up, and most studies do not assess long-term tumor control probability. Therefore, the assays may be insensitive in resolving smaller response differences, such as responses of radioresistant tumor subclones. Hence, tumor cure experiments, including additional TCD 50 experiments, are needed to confirm the assumption of isoeffectiveness in curative settings., (Copyright © 2023 Elsevier Inc. All rights reserved.)

FLASH radiation therapy (FLASH-RT) reference dosimetry to obtain traceability, repeatability and stability of irradiations cannot be performed with conventional dosimetric methods, such as monitor chambers or ionization chambers. Until now, only passive dosimeters have provided the necessary dosimetric data. Alanine dosimetry is accurate; however, to be used for FLASH-RT in biological experiments and for clinical transfer to humans, the reading time needs to be reduced, while preserving a maximum deviation to the reference of ±2%. Optimization of alanine dosimetry was based on the acquisition of electron paramagnetic resonance (EPR) spectra with a Bruker spectrometer. Reading parameters such as the conversion time, the number of scans, the time constant, the microwave power and the modulation amplitude of the magnetic field were optimized as a trade-off between the signal-to-noise ratio (SNR) and the reading time of one measurement using the reference 10.1 Gy alanine pellet. After optimizing the parameters, we compared the doses measured with alanine pellets up to 100 Gy with the reference doses, and then determined the number of measurements necessary to get a difference lower than ±2%. A low-dose alanine pellet of 4.9 Gy was also measured to evaluate the quality of the optimization for doses lower than 10 Gy. The optimization of the Bruker default parameters made it possible to reduce the reading time for one measurement from 5.6 to 2.6 min. That reduction was not at the cost of the SNR because it was kept comparable to the default parameters. Three measurements were enough to obtain a maximum dose deviation to the reference of 1.8% for the range of 10-100 Gy. The total reading time for the three measurements was 7.8 min (3 × 2.6 min). For lower doses such as 4.9 Gy, three measurements led to a deviation greater than 5%. By increasing the number of measurements to five, the average difference to the reference dose was reduced to less than 5% with a total reading time increased to 13.0 min. For doses between 10 Gy and 100 Gy, the optimized acquisition parameters made it possible to keep the average differences between the reference and the measured doses below ±2%, for a reading time of 7.8 min. This enabled an accurate and fast dose determination for biological preparations as part of FLASH-beam irradiations., (©2020 by Radiation Research Society. All rights of reproduction in any form reserved.)

Purpose: Image guided radiotherapy (IGRT) improves patient positioning for treatment delivery at the cost of an additional dose. This work aimed to calculate the effective dose (as an indicator of dose) for head & neck (H&N) and breast IGRT treatments by implementing dose calculation models to determine the dose distributions., Methods: The kV dose-models were created for the IGRT systems of Elekta Synergy (XVI) and Varian Clinac (OBI) linear accelerators within Philips Pinnacle TPS. Profiles and depth dose curves were measured in water. The models were validated in a CIRS thorax phantom. The IGRT dose distributions for five H&N and five breast patients were calculated. The effective dose was determined from the dose distributions following ICRP 103 recommendations. Moreover, time-saving approximations were studied in order to propose an alternative way of segmenting the tissues for a clinical implementation of the method., Results and Conclusion: The effective dose specifically associated with IGRT varied from 1 to 10mSv depending on the protocol. The kV dose-model allowed us to calculate the dose distributions from IGRT for different configurations and patients, and to determine effective dose for IGRT protocols. The clinical implementation of the method was found to reduce time and to introduce a small enough increase of uncertainty in the results to be clinically usable., (Copyright © 2018. Published by Elsevier GmbH.)

Purpose: A helical tomotherapy accelerator presents a dosimetric challenge because, to this day, there is no internationally accepted protocol for the determination of the absolute dose. Because of this reality, we investigated the different alternatives for characterizing and measuring the absolute dose of such an accelerator. We tested several dosimetric techniques with various metrological traceabilities as well as using a number of phantoms in static and helical modes., Methods: Firstly, the relationship between the reading of ionization chambers and the absorbed dose is dependent on the beam quality value of the photon beam. For high energy photons, the beam quality is specified by the tissue phantom ratio (TPR20,10) and it is therefore necessary to know the TPR20,10 to calculate the dose delivered by a given accelerator. This parameter is obtained through the ratio of the absorbed dose at 20 and 10 cm depths in water and was measured in the particular conditions of the tomotherapy accelerator. Afterward, measurements were performed using the ionization chamber (model A1SL) delivered as a reference instrument by the vendor. This chamber is traceable in absorbed dose to water in a Co-60 beam to a water calorimeter of the American metrology institute (NIST). Similarly, in Switzerland, each radiotherapy department is directly traceable to the Swiss metrology institute (METAS) in absorbed dose to water based on a water calorimeter. For our research, this traceability was obtained by using an ionization chamber traceable to METAS (model NE 2611A), which is the secondary standard of our institute. Furthermore, in order to have another fully independent measurement method, we determined the dose using alanine dosimeters provided by and traceable to the British metrology institute (NPL); they are calibrated in absorbed dose to water using a graphite calorimeter. And finally, we wanted to take into account the type of chamber routinely used in clinical practice and therefore measured the dose using a Farmer-type instrument (model NE 2571) as well., Results: We found the tomotherapy TPR20,10 value to be around 0.629, which is close to a 4 MV conventional linear accelerator value. During static irradiation, the secondary standard and the alanine dosimeters were compatible within 0.5%. The A1SL relative deviation to the secondary standard was 1.2% and the NE2571 relative deviation to the secondary standard was -1.7%. The measurement in dynamic helical mode found the different dosimeters compatible within 1.4% and the alanine dosimeters and the secondary standard were even found under 0.2%., Conclusions: We found that the different methods are all within uncertainties as well as globally coherent, and the specific limitations of the various dosimeters are discussed in order to help the medical physicist design an independent reference system. We demonstrated that, taking into account the particular reference conditions, one can use an ionization chamber calibrated for conventional linear accelerators to assert the absolute dose delivered by a tomotherapy accelerator.