Recurrences of ventricular tachycardia after stereotactic arrhythmia radioablation arise outside the treated volume: analysis of the Swiss cohort.

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.

Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species.

Here, we highlight the potential translational benefits of delivering FLASH radiotherapy using ultra-high dose rates (>100 Gy⋅s-1). Compared with conventional dose-rate (CONV; 0.07-0.1 Gy⋅s-1) modalities, we showed that FLASH did not cause radiation-induced deficits in learning and memory in mice. Moreover, 6 months after exposure, CONV caused permanent alterations in neurocognitive end points, whereas FLASH did not induce behaviors characteristic of anxiety and depression and did not impair extinction memory. Mechanistic investigations showed that increasing the oxygen tension in the brain through carbogen breathing reversed the neuroprotective effects of FLASH, while radiochemical studies confirmed that FLASH produced lower levels of the toxic reactive oxygen species hydrogen peroxide. In addition, FLASH did not induce neuroinflammation, a process described as oxidative stress-dependent, and was also associated with a marked preservation of neuronal morphology and dendritic spine density. The remarkable normal tissue sparing afforded by FLASH may someday provide heretofore unrealized opportunities for dose escalation to the tumor bed, capabilities that promise to hasten the translation of this groundbreaking irradiation modality into clinical practice.

Commissioning and validation of RayStation treatment planning system for CyberKnife M6.

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.

Validation of Monte Carlo dose calculation algorithm for CyberKnife multileaf collimator.

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.

Implementation and validation of a beam-current transformer on a medical pulsed electron beam LINAC for FLASH-RT beam monitoring.

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.

Retrospective analysis of the impact of respiratory motion in treatment margins for frameless lung SBRT based on respiratory-correlated CBCT data-sets.

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.

Lausanne checklist for safe stereotactic radiosurgery.

INTRODUCTION: Stereotactic radiosurgery (SRS) is increasingly used as a minimally invasive alternative in many neurosurgical conditions, including benign and malignant tumors, vascular malformations, and functional procedures. As for any surgical procedure, strict safety guidelines and checklists are necessary to avoid errors and the inherent unnecessary complications. With regard to the former, other groups have already reported human and/or technical errors. We describe our safety checklist for Gamma Knife radiosurgical procedures. METHODS: We describe our checklist protocol after an experience gained over 1500 radiosurgical procedures, using Gamma Knife radiosurgery, performed over a period of 8 years, while employing the same list of items. Minor implementation has been performed over time to address some safety issues that could be improved. RESULTS: Two types of checklist are displayed. One is related to the indications when a specific tissue volume is irradiated, including tumors or vascular disorders. The second corresponds to functional disorders, such as when the dose is prescribed to one specific point. Using these checklists, no human error had been reported during the past 8 years of practice in our institution. CONCLUSION: The use of a safety checklist for SRS procedures promotes a zero-tolerance attitude for errors. This can lower the complications and is of major help in promoting multidisciplinary cooperation. We highly recommend the use of such tool, especially in the context of the increased use of SRS in the neurosurgical field.

[Management of refractory ventricular tachycardia using stereotactic body radiotherapy]. / Prise en charge des tachycardies ventriculaires réfractaires par radiothérapie stéréotaxique.

Stereotactic body radiotherapy (SBRT) is routinely used in oncology to treat non-invasively solid tumors with high precision and efficacy. Recently, this technology has been evaluated in the treatment of ventricular tachycardia (VT). This article presents the basic underlying principles, proofs of concept and main results of clinical studies that used SBRT for the treatment of VT.

La radiothérapie stéréotaxique (SBRT) est une technologie couramment utilisée en oncologie pour traiter de façon non invasive les tumeurs solides avec précision et efficacité. Récemment, cette technologie a été évaluée dans le traitement des tachycardies ventriculaires (TV). Cet article présente les principes de base sous-jacents, le concept ainsi que les résultats des premières études cliniques ayant traité avec succès des patients souffrant de TV avec la SBRT.

Implementation of TomoEDGE in the independent dose calculator CheckTomo.

PURPOSE: CheckTomo is an independent dose calculation software for tomotherapy. Recently, Accuray (Accuray Inc., Sunnyvale, CA, USA) released an upgrade of its tomotherapy treatment device, called TomoEDGE Dynamic Jaws, which improves the quality of treatment plans by enhancing the dose delivery with the help of jaws motion. This study describes the upgrade of CheckTomo to that new feature. METHODS: To account for the varying width and off-axis shift of dynamic jaws fields, the calculation engine of CheckTomo multiplies the treatment field profile by a penumbral filter and shifts the dose calculation grid. Penumbral filters were obtained by dividing the edge field profiles by that of the corresponding nominal field. They were sampled at widths 1.0, 1.8, and 2.5 cm at isocenter in the edges of the 2.5 and 5 cm treatment field. RESULTS: The upgrade of CheckTomo was tested on 30 patient treatments planned with dynamic jaws. The gamma pass rate averaged over 10 abdomen plans was 95.9%, with tolerances of 3 mm/3%. For 10 head and neck plans, the mean pass rate was 95.9% for tolerances of 4 mm/4%. Finally, misplacement and overdosage errors were simulated. In each tested cases, the 2 mm/3% gamma pass rate fell below 95% when a 4 mm shift or 3% dose difference was applied. CONCLUSIONS: These results are equivalent to what CheckTomo achieves in static jaws cases. So, in terms of dose calculation accuracy and errors detection, the upgraded version of CheckTomo is as reliable for dynamic jaws plans as the former release was for static cases.

Difference in performance between 3D and 4D CBCT for lung imaging: a dose and image quality analysis.

The study was to describe and to compare the performance of 3D and 4D CBCT imaging modalities by measuring and analyzing the delivered dose and the image quality. The 3D (Chest) and 4D (Symmetry) CBCT Elekta XVI lung IGRT protocols were analyzed. Dose profiles were measured with TLDs inside a dedicated phantom. The dosimetric indicator cone-beam dose index (CBDI) was evaluated. The image quality analysis was performed by assessing the contrast transfer function (CTF), the noise power spectrum (NPS) and the noise-equivalent quanta (NEQ). Artifacts were also evaluated by simulating irregular breathing variations. The two imaging modalities showed different dose distributions within the phantom. At the center, the 3D CBCT delivered twice the dose of the 4D CBCT. The CTF was strongly reduced by motion compared to static conditions, resulting in a CTF reduction of 85% for the 3D CBCT and 65% for the 4D CBCT. The amplitude of the NPS was two times higher for the 4D CBCT than for the 3D CBCT. In the presence of motion, the NEQ of the 4D CBCT was 50% higher than the 3D CBCT. In the presence of breathing irregularities, the 4D CBCT protocol was mainly affected by view-aliasing artifacts, which were typically cone-beam artifacts, while the 3D CBCT protocol was mainly affected by duplication artifacts. The results showed that the 4D CBCT ensures a reasonable dose and better image quality when mov-ing targets are involved compared to 3D CBCT. Therefore, 4D CBCT is a reliable imaging modality for lung free-breathing radiation therapy.

Stability of the Helical TomoTherapy Hi·Art II detector for treatment beam irradiations.

The Hi·Art II Helical TomoTherapy (HT) unit is equipped with a built-in onboard MVCT detector used for patient imaging and beam monitoring. Our aim was to study the detector stability for treatment beam measurements. We studied the MVCT detector response with the 6 MV photon beam over time, throughout short-term (during an irradiation) and long-term (two times 50 days) periods. Our results show a coefficient of variation ≤ 1% for detector chambers inside the beam (excluding beam gradients) for short- and long-term response of the MVCT detector. Larger variations were observed in beam gradients and an influence of the X-ray target where degradation was found. The results assume that an 'air scan' procedure is performed daily to recalibrate the detector with the imaging beam. On short term, the detector response stability is comparable to other devices. Long-term measure- ments during two 50-day periods show a good reproducibility. 

Comparison of volumetric modulated arc therapy and helical tomotherapy for prostate cancer using Pareto fronts.

BACKGROUND: Studies comparing different radiotherapy treatment techniques-such as volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT)-typically compare one treatment plan per technique. Often, some dose metrics favor one plan and others favor the other, so the final plan decision involves subjective preferences. Pareto front comparisons provide a more objective framework for comparing different treatment techniques. A Pareto front is the set of all treatment plans where improvement in one criterion is possible only by worsening another criterion. However, different Pareto fronts can be obtained depending on the chosen machine settings. PURPOSE: To compare VMAT and HT using Pareto fronts and blind expert evaluation, to explain the observed differences, and to illustrate limitations of using Pareto fronts. METHODS: We generated Pareto fronts for twenty-four prostate cancer patients treated at our clinic for VMAT and HT techniques using an in-house script that controlled a commercial treatment planning system. We varied the PTV under-coverage (100% - V95%) and the rectum mean dose, and fixed the mean doses to the bladder and femoral heads. In order to ensure a fair comparison, those fixed mean doses were the same for the two treatment techniques and the sets of objective functions were chosen so that the conformity indexes of the two treatment techniques were also the same. We used the same machine settings as are used in our clinic. Then, we compared the VMAT and HT Pareto fronts using a specific metric (clinical distance measure) and validated the comparison using a blinded expert evaluation of treatment plans on these fronts for all patients in the cohort. Furthermore, we investigated the observed differences between VMAT and HT and pointed out limitations of using Pareto fronts. RESULTS: Both clinical distance and blind treatment plan comparison showed that VMAT Pareto fronts were better than HT fronts. VMAT fronts for 10 and 6 MV beam energy were almost identical. HT fronts improved with different machine settings, but were still inferior to VMAT fronts. CONCLUSIONS: That VMAT Pareto fronts are better than HT fronts may be explained by the fact that the linear accelerator can rapidly vary the dose rate. This is an advantage in simple geometries that might vanish in more complex geometries. Furthermore, one should be cautious when speaking about Pareto optimal plans as the best possible plans, as their calculation depends on many parameters.

Sensitivity of automated and manual treatment planning approaches to contouring variation in early-breast cancer treatment.

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 (ΔDrcM,ΔDrcA) and reoptimized dose (ΔDroM,ΔDroA) 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 (ΔDrcM=-0.4 Gy, ΔDrcA=-0.3 Gy) and right breast (ΔDrcM=-1.2 Gy, ΔDrcA=-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 (ΔDroM=-0.2 Gy, ΔDroA=-0.2 Gy) and right breast (ΔDroM =-0.3 Gy, ΔDroA=-0.9 Gy) maximum dose. Twenty-one correlations were found for ΔDrcM,A (M=8,A=13) that reduced to four for ΔDroM,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.

Randomized phase II selection trial of FLASH and conventional radiotherapy for patients with localized cutaneous squamous cell carcinoma or basal cell carcinoma: A study protocol.

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.

Very high-energy electron therapy as light-particle alternative to transmission proton FLASH therapy - An evaluation of dosimetric performances.

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.

On the acceptance, commissioning, and quality assurance of electron FLASH units.

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.

Influence of optimisation parameters on directly deliverable Pareto fronts explored for prostate cancer.

PURPOSE: In inverse radiotherapy treatment planning, the Pareto front is the set of optimal solutions to the multi-criteria problem of adequately irradiating the planning target volume (PTV) while reducing dose to organs at risk (OAR). The Pareto front depends on the chosen optimisation parameters whose influence (clinically relevant versus not clinically relevant) is investigated in this paper. METHODS: Thirty-one prostate cancer patients treated at our clinic were randomly selected. We developed an in-house Python script that controlled the commercial treatment planning system RayStation to calculate directly deliverable Pareto fronts. We calculated reference Pareto fronts for a given set of objective functions, varying the PTV coverage and the mean dose of the primary OAR (rectum) and fixing the mean doses of the secondary OARs (bladder and femoral heads). We calculated the fronts for different sets of objective functions and different mean doses to secondary OARs. We compared all fronts using a specific metric (clinical distance measure). RESULTS: The in-house script was validated for directly deliverable Pareto front calculations in two and three dimensions. The Pareto fronts depended on the choice of objective functions and fixed mean doses to secondary OARs, whereas the parameters most influencing the front and leading to clinically relevant differences were the dose gradient around the PTV, the weight of the PTV objective function, and the bladder mean dose. CONCLUSIONS: Our study suggests that for multi-criteria optimisation of prostate treatments using external therapy, dose gradient around the PTV and bladder mean dose are the most influencial parameters.

Comprehensive evaluation and new recommendations in the use of Gafchromic EBT3 film.

BACKGROUND: Gafchromic film's unique properties of tissue-equivalence, dose-rate independence, and high spatial resolution make it an attractive choice for many dosimetric applications. However, complicated calibration processes and film handling limits its routine use. PURPOSE: We evaluated the performance of Gafchromic EBT3 film after irradiation under a variety of measurement conditions to identify aspects of film handling and analysis for simplified but robust film dosimetry. METHODS: The short- (from 5 min to 100 h) and long-term (months) film response was evaluated for clinically relevant doses of up to 50 Gy for accuracy in dose determination and relative dose distributions. The dependence of film response on film-read delay, film batch, scanner type, and beam energy was determined. RESULTS: Scanning the film within a 4-h window and using a standard 24-h calibration curve introduced a maximum error of 2% over a dose range of 1-40 Gy, with lower doses showing higher uncertainty in dose determination. Relative dose measurements demonstrated <1 mm difference in electron beam parameters such as depth of 50% of the maximum dose value (R50 ), independent of when the film was scanned after irradiation or the type of calibration curve used (batch-specific or time-specific calibration curve) if the same default scanner was used. Analysis of films exposed over a 5-year period showed that using the red channel led to the lowest variation in the measured net optical density values for different film batches, with doses >10 Gy having the lowest coefficient of variation (<1.7%). Using scanners of similar design produced netOD values within 3% after exposure to doses of 1-40 Gy. CONCLUSIONS: This is the first comprehensive evaluation of the temporal and batch dependence of Gafchromic EBT3 film evaluated on consolidated data over 8 years. The relative dosimetric measurements were insensitive to the type of calibration applied (batch- or time-specific) and in-depth time-dependent dosimetric signal behaviors can be established for film scanned outside of the recommended 16-24 h post-irradiation window. We generated guidelines based on our findings to simplify film handling and analysis and provide tabulated dose- and time-dependent correction factors to achieve this without reducing the accuracy of dose determination.

3D-conformal very-high energy electron therapy as candidate modality for FLASH-RT: A treatment planning study for glioblastoma and lung cancer.

BACKGROUND: Pre-clinical ultra-high dose rate (UHDR) electron irradiations on time scales of 100 ms have demonstrated a remarkable sparing of brain and lung tissues while retaining tumor efficacy when compared to conventional dose rate irradiations. While clinically-used gantries and intensity modulation techniques are too slow to match such time scales, novel very-high energy electron (VHEE, 50-250 MeV) radiotherapy (RT) devices using 3D-conformed broad VHEE beams are designed to deliver UHDR treatments that fulfill these timing requirements. PURPOSE: To assess the dosimetric plan quality obtained using VHEE-based 3D-conformal RT (3D-CRT) for treatments of glioblastoma and lung cancer patients and compare the resulting treatment plans to those delivered by standard-of-care intensity modulated photon RT (IMRT) techniques. METHODS: Seven glioblastoma patients and seven lung cancer patients were planned with VHEE-based 3D-CRT using 3 to 16 coplanar beams with equidistant angular spacing and energies of 100 and 200 MeV using a forward planning approach. Dose distributions, dose-volume histograms, coverage (V95% ) and homogeneity (HI98% ) for the planning target volume (PTV), as well as near-maximum doses (D2% ) and mean doses (Dmean ) for organs-at-risk (OAR) were evaluated and compared to clinical IMRT plans. RESULTS: Mean differences of V95% and HI98% of all VHEE plans were within 2% or better of the IMRT reference plans. Glioblastoma plan dose metrics obtained with VHEE configurations of 200 MeV and 3-16 beams were either not significantly different or were significantly improved compared to the clinical IMRT reference plans. All OAR plan dose metrics evaluated for VHEE plans created using 5 beams of 100 MeV were either not significantly different or within 3% on average, except for Dmean for the body, Dmean for the brain, D2% for the brain stem, and D2% for the chiasm, which were significantly increased by 1, 2, 6, and 8 Gy, respectively (however below clinical constraints). Similarly, the dose metrics for lung cancer patients were also either not significantly different or were significantly improved compared to the reference plans for VHEE configurations with 200 MeV and 5 to 16 beams with the exception of D2% and Dmean to the spinal canal (however below clinical constraints). For the lung cancer cases, the VHEE configurations using 100 MeV or only 3 beams resulted in significantly worse dose metrics for some OAR. Differences in dose metrics were, however, strongly patient-specific and similar for some patient cases. CONCLUSIONS: VHEE-based 3D-CRT may deliver conformal treatments to simple, mostly convex target shapes in the brain and the thorax with a limited number of critical adjacent OAR using a limited number of beams (as low as 3 to 7). Using such treatment techniques, a dosimetric plan quality comparable to that of standard-of-care IMRT can be achieved. Hence, from a treatment planning perspective, 3D-conformal UHDR VHEE treatments delivered on time scales of 100 ms represent a promising candidate technique for the clinical transfer of the FLASH effect.

Effect of Conventional and Ultrahigh Dose Rate FLASH Irradiations on Preclinical Tumor Models: A Systematic Analysis.

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 (TCD50) 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 TCD50 experiments, are needed to confirm the assumption of isoeffectiveness in curative settings.