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Purpose: Radiosurgery (RS) is gaining increasing acceptance in the upfront management of brain metastases (BM). We present our single institution experience focusing on criteria that led to the selection of RS treatment with Gamma Knife (GK) in lieu of Linac. Methods: Leksell Gamma Knife Perfexion (Elekta, Sweden) was installed in our center in July 2010. Currently, the Swiss Federal Health Care supports the costs of RS for BM with Linac but not with GK. Therefore, we always consider first the possibility to use Linac for this indication, and only select patients for GK in specific situations. All cases of BM treated with GK were retrospectively reviewed for criteria yielding to GK indication, clinical information, and treatment data. Further work in progress includes a posteriori dosimetry comparison with our Linac planning system (Brainscan V.5.3, Brainlab, Germany). Results: From July 2010 to July 2012, 31 patients had RS for BM with GK (11 single BM, and 20 multiple BM). During the same period, 35 had Linac-based RS (24 single BM, and 11 multiple BM). In single BM, the reason for choosing GK was the anatomical location close to, or in highly functional areas, especially since most of these tumors were intended to be treated with high-dose RS (24 Gy at margin) because of their histology (3 melanomas, 1 renal cell). In multiple BM, the reason for choosing GK in relation with the anatomical location of the lesions was either technical (limitations of Linac movements, especially in lower posterior fossa locations) or close distance of multiple lesions to functional areas (typically, multiple posterior fossa BM close to the brainstem), precluding optimal dosimetry with Linac. Again, this was made more critical for multiple BM needing high dose RS (6 melanoma, 2 hypernephroma). There were statistically significant differences (t-student test, p < 0.01) between GK and Linac patients, for the mean number of lesions/ patient (2.7 compared to 1.3) and for the mean dose prescription at the specific mean isodose prescription (21.5 Gy at the 52% compared to 19.6 Gy at the 81%). Conclusion: Radiosurgery for BM may represent some technical challenge in relation with the anatomical location and multiplicity of the lesions. These considerations may be accentuated for so-called radioresistant BM, when higher dose RS in needed. In our experience, Leksell Gamma Knife Perfexion proves to be useful in addressing these challenges for the treatment of BM. Disclosure: No significant relationships. [ABSTRACT FROM AUTHOR]

Background/objectives: Stereotactic body radiation therapy (SBRT) has demonstrated high local control rates for inoperable early-stage lung cancers. However, 5-15% of patients experience local relapse within the irradiated volume after treatment, with limited curative salvage options. The aim of this review is to clarify the modalities and outcomes after a second course of SBRT in patients with local relapse after a previous lung SBRT., Methods: An exhaustive literature review was conducted to identify, analyse and summarise the results of 21 main studies., Results: Local repeat lung SBRT after a first course of SBRT showed a favourable local control at 1 and 2 years, ranging from 70 to 90% and 45 to 80%, respectively. Good overall survival rates were also observed at 1 and 2 years reaching up to 95% and 85%, respectively. Toxicity was rare but could be severe, with cases of Grade 4 and 5 toxicities (≈5%). An important dose relationship was observed between re-irradiation dose levels and local control, highlighting the importance of precise dosing. The cumulative doses impacting organs at risk were similarly associated with increased radiation-induced toxicity. Central lung lesions presented a higher risk for severe side effects compared to peripheral ones., Conclusions: In conclusion, repeat lung SBRT after a first course of SBRT represents a feasible treatment option in cases of local recurrence. In order to limit severe toxicity, patients must be carefully selected, and particular attention should be given to cumulative doses to organs at risk, as well as tumour location. Thus, further investigations are still needed to refine the optimal parameters for SBRT lung re-irradiation.

Purpose: Treatment planning for CyberKnife (CK) (Accuray, USA) can be performed with Precision (Accuray, USA) or RayStation (RS) (RaySearch Laboratories, Sweden) treatment planning systems (TPS). RaySearch recently released a new version of the CK module in RS 12A. The objective of the study was to compare plan quality between RS 12A and Precision., Methods: Fifty nine plans were optimized with both TPS and compared; 39 were for brain metastases and 20 were for vertebral metastases. To avoid bias in plan comparison, Precision plans were recomputed in RS with the dose algorithm and beam model of RS, and then compared to RS plans. The comparison was divided into 3 parts in order to reflect the potential of RS and the differences with Precision, in terms of technical aspects of delivery efficiency and dose distribution. We compared the dose to the target and to the organs at risk (OAR), the conformity index (CI), the gradient, as well as the number of monitor units (MU), and the number of beams and nodes. Finally, a global plan quality index (PQI) was calculated., Results: RS plans showed an equivalent target coverage for brain metastases but worse for vertebrae. OAR sparing was improved in RS but with a lower CI compared to Precision. Using an appropriate planning methodology in RS, plans with comparable quality to Precision could be obtained, but at the cost of a longer optimization time. The PQI obtained with RS was better than Precision, except for some brain cases., Conclusion: RS is an adequate alternative for CK planning as it is possible to obtain plan quality comparable to Precision. However, the optimization time is longer compared to Precision and more attention must be paid to the choice of the initial conditions in terms of the number of beams and nodes., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

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.)

Background & Purpose: FLASH or ultra-high dose rate (UHDR) radiation therapy (RT) has gained attention in recent years for its ability to spare normal tissues relative to conventional dose rate (CDR) RT in various preclinical trials. However, clinical implementation of this promising treatment option has been limited because of the lack of availability of accelerators capable of delivering UHDR RT. Commercial options are finally reaching the market that produce electron beams with average dose rates of up to 1000 Gy/s. We established a framework for the acceptance, commissioning, and periodic quality assurance (QA) of electron FLASH units and present an example of commissioning., Methods: A protocol for acceptance, commissioning, and QA of UHDR linear accelerators was established by combining and adapting standards and professional recommendations for standard linear accelerators based on the experience with UHDR at four clinical centers that use different UHDR devices. Non-standard dosimetric beam parameters considered included pulse width, pulse repetition frequency, dose per pulse, and instantaneous dose rate, together with recommendations on how to acquire these measurements., Results: The 6- and 9-MeV beams of an UHDR electron device were commissioned by using this developed protocol. Measurements were acquired with a combination of ion chambers, beam current transformers (BCTs), and dose-rate-independent passive dosimeters. The unit was calibrated according to the concept of redundant dosimetry using a reference setup., Conclusions: This study provides detailed recommendations for the acceptance testing, commissioning, and routine QA of low-energy electron UHDR linear accelerators. The proposed framework is not limited to any specific unit, making it applicable to all existing eFLASH units in the market. Through practical insights and theoretical discourse, this document establishes a benchmark for the commissioning of UHDR devices for clinical use.

Background: Cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most prevalent skin cancers in western countries. Surgery is the standard of care for these cancers and conventional external radiotherapy (CONV-RT) with conventional dose rate (0.03-0.06 Gy/sec) represents a good alternative when the patients or tumors are not amenable to surgery but routinely generates skin side effects. Low energy electron FLASH radiotherapy (FLASH-RT) is a new form of radiotherapy exploiting the biological advantage of the FLASH effect, which consists in delivering radiation dose in milliseconds instead of minutes in CONV-RT. In pre-clinical studies, when compared to CONV-RT, FLASH-RT induced a robust, reproducible and remarkable sparing of the normal healthy tissues, while the efficacy on tumors was preserved. In this context, we aim to prospectively evaluate FLASH-RT versus CONV-RT with regards to toxicity and oncological outcome in localized cutaneous BCC and SCC., Methods: This is a randomized selection, non-comparative, phase II study of curative FLASH-RT versus CONV-RT in patients with T1-T2 N0 M0 cutaneous BCC and SCC. Patients will be randomly allocated to low energy electron FLASH-RT (dose rate: 220-270 Gy/s) or to CONV-RT arm. Small lesions (T1) will receive a single dose of 22 Gy and large lesions (T2) will receive 30 Gy in 5 fractions of 6 Gy over two weeks.The primary endpoint evaluates safety at 6 weeks after RT through grade ≥ 3 toxicity and efficacy through local control rate at 12 months. Approximately 60 patients in total will be randomized, considering on average 1-2 lesions and a maximum of 3 lesions per patients corresponding to the total of 96 lesions required. FLASH-RT will be performed using the Mobetron® (IntraOp, USA) with high dose rate functionality.LANCE (NCT05724875) is the first randomized trial evaluating FLASH-RT and CONV-RT in a curative setting., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JB reports advisory role for Roche, BMS, MSD, Astra-Zeneca, Debiopharm, Nanobiotix, Merck and Mevion, Grant research with IntraOp, PMB and Theryq. RM receives a research grant from Accuray. All other authors have nothing to declare., (© 2024 The Author(s).)

Aims: Stereotactic arrhythmia radioablation (STAR) has been recently introduced for the management of therapy-refractory ventricular tachycardia (VT). VT recurrences have been reported after STAR but the mechanisms remain largely unknown. We analysed recurrences in our patients after STAR., Methods and Results: From 09.2017 to 01.2020, 20 patients (68 ± 8 y, LVEF 37 ± 15%) suffering from refractory VT were enrolled, 16/20 with a history of at least one electrical storm. Before STAR, an invasive electroanatomical mapping (Carto3) of the VT substrate was performed. A mean dose of 23 ± 2 Gy was delivered to the planning target volume (PTV). The median ablation volume was 26 mL (range 14-115) and involved the interventricular septum in 75% of patients. During the first 6 months after STAR, VT burden decreased by 92% (median value, from 108 to 10 VT/semester). After a median follow-up of 25 months, 12/20 (60%) developed a recurrence and underwent a redo ablation. VT recurrence was located in the proximity of the treated substrate in nine cases, remote from the PTV in three cases and involved a larger substrate over ≥3 LV segments in two cases. No recurrences occurred inside the PTV. Voltage measurements showed a significant decrease in both bipolar and unipolar signal amplitude after STAR., Conclusion: STAR is a new tool available for the treatment of VT, allowing for a significant reduction of VT burden. VT recurrences are common during follow-up, but no recurrences were observed inside the PTV. Local efficacy was supported by a significant decrease in both bipolar and unipolar signal amplitude., Competing Interests: Conflict of interest: CHS received educational grants through her institution from Biosense Webster, Microport and Abbott; and speaker fees from Daiichi Sankyo. TR has received research grants from the Swiss National Science Foundation, the Swiss Heart Foundation and the sitem insel support fund, all for work outside the submitted study. Dr. Reichlin has received research support for investigator initiated projects from Biosense Webster, Biotronik, Boston Scientific and Medtronic, all for work outside the submitted study. He has received speaker/consulting honoraria or travel support from Abbott/SJM, Bayer, Biosense Webster, Biotronik, Boston Scientific, Daiichi Sankyo, Farapulse, Medtronic and Pfizer-BMS, all for work outside the submitted study. He has received support for his institution’s fellowship programme from Abbott/SJM, Biosense Webster, Biotronik, Boston Scientific and Medtronic for work outside the submitted study. BK received educational support from Medtronic, Abbott and Biotronik. AMS received educational grants through his institution from Abbott, Bayer Healthcare, Biosense Webster, Biotronik, Boston Scientific, BMS/Pfizer, and Medtronic; and speaker/advisory board/consulting fees from Abbott, Bayer Healthcare, Daiichi Sankyo, Medtronic, Novartis and Pfizer. EP received Educational Grants through his institution from Medtronic, and research grants from the Swiss National Science Foundation and from the European Community (H2020). All remaining authors have declared no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Purpose: Automation in radiotherapy treatment planning aims to improve both the quality and the efficiency of the process. The aim of this study was to report on a clinical implementation of a Deep Learning (DL) auto-planning model for left-sided breast cancer., Materials and Methods: The DL model was developed for left-sided breast simultaneous integrated boost treatments under deep-inspiration breath-hold. Eighty manual dose distributions were revised and used for training. Ten patients were used for model validation. The model was then used to design 17 clinical auto-plans. Manual and auto-plans were scored on a list of clinical goals for both targets and organs-at-risk (OARs). For validation, predicted and mimicked dose (PD and MD, respectively) percent error (PE) was calculated with respect to manual dose. Clinical and validation cohorts were compared in terms of MD only., Results: Median values of both PD and MD validation plans fulfilled the evaluation criteria. PE was < 1% for targets for both PD and MD. PD was well aligned to manual dose while MD left lung mean dose was significantly less (median:5.1 Gy vs 6.1 Gy). The left-anterior-descending artery maximum dose was found out of requirements (median values:+5.9 Gy and + 2.9 Gy, for PD and MD respectively) in three validation cases, while it was reduced for clinical cases (median:-1.9 Gy). No other clinically significant differences were observed between clinical and validation cohorts., Conclusion: Small OAR differences observed during the model validation were not found clinically relevant. The clinical implementation outcomes confirmed the robustness of the model., Competing Interests: 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., (© 2023 The Author(s).)

FLASH radiation therapy (RT) is a promising new paradigm in radiation oncology. However, a major question that remains is the robustness and reproducibility of the FLASH effect when different irradiators are used on animals or patients with different genetic backgrounds, diets, and microbiomes, all of which can influence the effects of radiation on normal tissues. To address questions of rigor and reproducibility across different centers, we analyzed independent data sets from The University of Texas MD Anderson Cancer Center and from Lausanne University (CHUV). Both centers investigated acute effects after total abdominal irradiation to C57BL/6 animals delivered by the FLASH Mobetron system. The two centers used similar beam parameters but otherwise conducted the studies independently. The FLASH-enabled animal survival and intestinal crypt regeneration after irradiation were comparable between the two centers. These findings, together with previously published data using a converted linear accelerator, show that a robust and reproducible FLASH effect can be induced as long as the same set of irradiation parameters are used.

A 40-year-old patient with cT4cN1M0 squamous cell lung cancer of the upper right lobe received preoperative induction chemotherapy. Systemic induction treatment failed to reverse tumour growth with the addition of conventional radiotherapy (RT). A salvage lattice RT boost of 12 Gy was administered immediately to increase the dose to the tumour. Conventional RT was resumed at the planned dose of 60 Gy. The tumour shrank rapidly, and the patient was surged. The postoperative pathology remained ypT0ypN0 status., Competing Interests: 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., (© 2022 The Authors.)

Background: Surgery and radiotherapy are well-established standards of care for unilateral stage 0 and I early-stage glottic cancer (ESGC). Based on comparative studies and meta-analyses, functional and oncological outcomes after both treatment modalities are similar. Historically, radiotherapy (RT) has been performed by irradiation of the whole larynx. However, only the involved vocal cord is being treated with recently introduced hypofractionated concepts that result in 8 to 10-fold smaller target volumes. Retrospective data argues for an improvement in voice quality with non-inferior local control. Based on these findings, single vocal cord irradiation (SVCI) has been implemented as a routine approach in some institutions for ESGC in recent years. However, prospective data directly comparing SVCI with surgery is lacking. The aim of VoiceS is to fill this gap., Methods: In this prospective randomized multi-center open-label phase III study with a superiority design, 34 patients with histopathologically confirmed, untreated, unilateral stage 0-I ESGC (unilateral cTis or cT1a) will be randomized to SVCI or transoral CO 2 -laser microsurgical cordectomy (TLM). Average difference in voice quality, measured by using the voice handicap index (VHI) will be modeled over four time points (6, 12, 18, and 24 months). Primary endpoint of this study will be the patient-reported subjective voice quality between 6 to 24 months after randomization. Secondary endpoints will include perceptual impression of the voice via roughness - breathiness - hoarseness (RBH) assessment at the above-mentioned time points. Additionally, quantitative characteristics of voice, loco-regional tumor control at 2 and 5 years, and treatment toxicity at 2 and 5 years based on CTCAE v.5.0 will be reported., Discussion: To our knowledge, VoiceS is the first randomized phase III trial comparing SVCI with TLM. Results of this study may lead to improved decision-making in the treatment of ESGC., Trial Registration: ClinicalTrials.gov NCT04057209. Registered on 15 August 2019. Cantonal Ethics Committee KEK-BE 2019-01506., (© 2022. The Author(s).)

Purpose: The FLASH effect is characterized by normal tissue sparing without compromising tumor control. Although demonstrated in various preclinical models, safe translation of FLASH-radiotherapy stands to benefit from larger vertebrate animal models. Based on prior results, we designed a randomized phase III trial to investigate the FLASH effect in cat patients with spontaneous tumors. In parallel, the sparing capacity of FLASH-radiotherapy was studied on mini pigs by using large field irradiation., Experimental Design: Cats with T1-T2, N0 carcinomas of the nasal planum were randomly assigned to two arms of electron irradiation: arm 1 was the standard of care (SoC) and used 10 × 4.8 Gy (90% isodose); arm 2 used 1 × 30 Gy (90% isodose) FLASH. Mini pigs were irradiated using applicators of increasing size and a single surface dose of 31 Gy FLASH., Results: In cats, acute side effects were mild and similar in both arms. The trial was prematurely interrupted due to maxillary bone necrosis, which occurred 9 to 15 months after radiotherapy in 3 of 7 cats treated with FLASH-radiotherapy (43%), as compared with 0 of 9 cats treated with SoC. All cats were tumor-free at 1 year in both arms, with one cat progressing later in each arm. In pigs, no acute toxicity was recorded, but severe late skin necrosis occurred in a volume-dependent manner (7-9 months), which later resolved., Conclusions: The reported outcomes point to the caveats of translating single-high-dose FLASH-radiotherapy and emphasizes the need for caution and further investigations. See related commentary by Maity and Koumenis, p. 3636., (©2022 The Authors; Published by the American Association for Cancer Research.)

Background: RaySearch (AB, Stockholm) has released a module for CyberKnife (CK) planning within its RayStation (RS) treatment planning system (TPS)., Purpose: To create and validate beam models of fixed, Iris, and multileaf collimators (MLC) of the CK M6 for Monte Carlo (MC) and collapsed cone (CC) algorithms in the RS TPS., Methods: Measurements needed for the creation of the beam models were performed in a water tank with a stereotactic PTW 60018 diode. Both CC and MC models were optimized in RS by minimizing the differences between the measured and computed profiles and percentage depth doses. The models were then validated by comparing dose from the plans created in RS with both single and multiple beams in different phantom conditions with the corresponding measured dose. Irregular field shapes and off-axis beams were also tested for the MLC. Validation measurements were performed using an A1SL ionization chamber, EBT3 Gafchromic films, and a PTW 1000 SRS detector. Finally, patient-specific QAs with gamma criteria of 3%/1 mm were performed for each model., Results: The models were created in a straightforward manner with efficient tools available in RS. The differences between computed and measured doses were within ±1% for most of the configurations tested and reached a maximum of 3.2% for measurements at a depth of 19.5-cm. With respect to all collimators and algorithms, the maximum averaged dose difference was 0.8% when considering absolute dose measurements on the central axis. The patient-specific QAs led to a mean result of 98% of points fulfilling gamma criteria., Conclusions: We created both CC and MC models for fixed, Iris, and MLC collimators in RS. The dose differences for all collimators and algorithms were within ±1%, except for depths larger than 9 cm. This allowed us to validate both models for clinical use., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Purpose: To commission and evaluate the Monte Carlo (MC) dose calculation algorithm for the CyberKnife equipped with a multileaf collimator (MLC)., Methods: We created a MC model for the MLC using an integrated module of the CyberKnife treatment planning software (TPS). Two parameters could be optimized: the maximum energy and the source full width at half-maximum (FWHM). The optimization was performed by minimizing the differences between the measured and the MC calculated tissue phantom ratios and profiles. MLC plans were calculated in the TPS with the MC algorithm and irradiated on different phantoms. The dose was measured using an A1SL ionization chamber and EBT3 Gafchromic films, and then compared to the TPS dose to obtain dose differences (ΔD). Finally, patient-specific quality assurances (QA) were performed with global gamma index criteria of 3%/1 mm., Results: The maximum energy and source FWHM showing the best agreement with measurements were 6.4 MeV and 1.8 mm. The output factors calculated with these parameters gave an agreement within ±1% with measurements. The ΔD showed that MC model systematically underestimated the dose with an average of -1.5% over all configurations tested. For depths deeper than 12 cm, the ΔD increased, up to -3.0% (maximum at 15.5 cm depth)., Conclusions: The MC model for MLC of CyberKnife is clinically acceptable but underestimates the delivered dose by an average of -1.5%. Therefore, we recommend using the MC algorithm with the MLC only in heterogeneous regions and for shallow-seated tumors., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Purpose: To implement and validate a beam current transformer as a passive monitoring device on a pulsed electron beam medical linear accelerator (LINAC) for ultra-high dose rate (UHDR) irradiations in the operational range of at least 3 Gy to improve dosimetric procedures currently in use for FLASH radiotherapy (FLASH-RT) studies., Methods: Two beam current transformers (BCTs) were placed at the exit of a medical LINAC capable of UHDR irradiations. The BCTs were validated as monitoring devices by verifying beam parameters consistency between nominal values and measured values, determining the relationship between the charge measured and the absorbed dose, and checking the short- and long-term stability of the charge-absorbed dose ratio., Results: The beam parameters measured by the BCTs coincide with the nominal values. The charge-dose relationship was found to be linear and independent of pulse width and frequency. Short- and long-term stabilities were measured to be within acceptable limits., Conclusions: The BCTs were implemented and validated on a pulsed electron beam medical LINAC, thus improving current dosimetric procedures and allowing for a more complete analysis of beam characteristics. BCTs were shown to be a valid method for beam monitoring for UHDR (and therefore FLASH) experiments., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

This article describes a ureter-sparing procedure used to treat lymph node metastases with SBRT. We delivered 35 Gy in 5 fractions of 7 Gy to patients with lesions located less than 7 mm from the ureters using a urography CT scan for planification. Two dosimetry plans were created, one using a CT scan urography-based contour and the other using the native phase. PTV coverage were not statistically different but this technique was able to significantly reduce median delivered Dmax to the ureters. These preliminary results demonstrate the feasibility of locating the ureters in a planning CT scan to protect them., Competing Interests: 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., (© 2021 The Authors.)

Purpose: Recent data have shown that single-fraction irradiation delivered to the whole brain in less than tenths of a second using FLASH radiotherapy (FLASH-RT), does not elicit neurocognitive deficits in mice. This observation has important clinical implications for the management of invasive and treatment-resistant brain tumors that involves relatively large irradiation volumes with high cytotoxic doses., Experimental Design: Therefore, we aimed at simultaneously investigating the antitumor efficacy and neuroprotective benefits of FLASH-RT 1-month after exposure, using a well-characterized murine orthotopic glioblastoma model. As fractionated regimens of radiotherapy are the standard of care for glioblastoma treatment, we incorporated dose fractionation to simultaneously validate the neuroprotective effects and optimized tumor treatments with FLASH-RT., Results: The capability of FLASH-RT to minimize the induction of radiation-induced brain toxicities has been attributed to the reduction of reactive oxygen species, casting some concern that this might translate to a possible loss of antitumor efficacy. Our study shows that FLASH and CONV-RT are isoefficient in delaying glioblastoma growth for all tested regimens. Furthermore, only FLASH-RT was found to significantly spare radiation-induced cognitive deficits in learning and memory in tumor-bearing animals after the delivery of large neurotoxic single dose or hypofractionated regimens., Conclusions: The present results show that FLASH-RT delivered with hypofractionated regimens is able to spare the normal brain from radiation-induced toxicities without compromising tumor cure. This exciting capability provides an initial framework for future clinical applications of FLASH-RT. See related commentary by Huang and Mendonca, p. 662 ., (©2020 American Association for Cancer Research.)

Purpose: To investigate the impact of respiratory motion in the treatment margins for lung SBRT frameless treatments and to validate our treatment margins using 4D CBCT data analysis., Methods: Two hundred and twenty nine fractions with early stage NSCLC were retrospectively analyzed. All patients were treated in frameless and free breathing conditions. The treatment margins were calculated according to van Herk equation in Mid-Ventilation. For each fraction, three 4D CBCT scans, pre- and postcorrection, and posttreatment, were acquired to assess target baseline shift, target localization accuracy and intra-fraction motion errors. A bootstrap analysis was performed to assess the minimum number of patients required to define treatment margins., Results: The retrospectively calculated target-baseline shift, target localization accuracy and intra-fraction motion errors agreed with the literature. The best tailored margins to our cohort of patients were retrospectively computed and resulted in agreement with already published data. The bootstrap analysis showed that fifteen patients were enough to assess treatment margins., Conclusions: The treatment margins applied to our patient's cohort resulted in good agreement with the retrospectively calculated margins based on 4D CBCT data. Moreover, the bootstrap analysis revealed to be a promising method to verify the reliability of the applied treatment margins for safe lung SBRT delivery., (© 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)