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

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. 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. 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. 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.

Böhlen TT ，Germond JF ，Desorgher L ，Veres I ，Bratel A ，Landström E ，Engwall E ，Herrera FG ，Ozsahin EM ，Bourhis J ，Bochud F ，Moeckli R ... -  《-》

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

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. 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. 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. 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. 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.

Böhlen TT ，Germond JF ，Traneus E ，Vallet V ，Desorgher L ，Ozsahin EM ，Bochud F ，Bourhis J ，Moeckli R ... -  《-》

Treatment planning for radiotherapy with very high-energy electron beams and comparison of VHEE and VMAT plans.

Bazalova-Carter M ，Qu B ，Palma B ，Hårdemark B ，Hynning E ，Jensen C ，Maxim PG ，Loo BW Jr ... -  《-》

Characteristics of very high-energy electron beams for the irradiation of deep-seated targets.

Driven by advances in accelerator technology and the potential of exploiting the FLASH effect for the treatment of deep-seated targets (>5 cm), there is an active interest in the construction of devices to deliver very high-energy electron (VHEE) beams for radiation therapy. The application of novel VHEE devices, however, requires an assessment of the tradeoffs between the different beam parameter choices including beam energies, beam divergences, and maximal field sizes. This study systematically examines the dosimetric beam properties of VHEE beams, determining their clinical usefulness while marking their limits of applications for different beam configurations. We performed Monte Carlo simulations of the dose distributions of electron beams for different energies (25-250 MeV), source-to-surface distances (SSD) (50 cm, 100 cm, parallel), and field sizes (2 cm2  × 2 cm2 to 15 cm2  × 15 cm2 ) in water using a research version of the RayStation treatment planning system (RaySearch Labs 9A IONPG). The beam was simulated using a monoenergetic point source and perfect collimation. Central axis percentage depth dose (PDD) and transverse dose profiles at multiple depths were evaluated and compared to those of MV photon beams. Profile characteristics including therapeutic range (TR) at 90%, proximal fall-off (PFO) at 90%, lateral penumbra (LP) at 90%-10%, and field width (FW) at 90% were obtained. Very high-energy electrons beams with SSD 100 cm and parallel beams (infinite SSD) exhibit a linear to near-linear increase of TR as a function of energy in the simulated energy range and reach values well beyond the typical depths of lesions encountered in clinics (<20 cm). Their TR show a marked field size dependence only for field sizes <10 cm2  × 10 cm2 . For VHEE beams with SSD 50 cm, TR are largely reduced (4-8 cm). For beam energies >150 MeV with large SSD (>100 cm), for many configurations, there is no substantial difference in PDD when adding an opposed beam. This may potentially reduce the number of VHEE beams needed for treatment by a factor of two compared to a treatment using lower energies and lower SSD. In order to cover deep-seated targets homogeneously, VHEE devices with a parallel beam must provide a maximum field size up to several centimeters larger than the tumor size. For the investigated diverging beams, there is not such a significant field width reduction with depth for larger fields as it is compensated by divergence. Penumbrae of VHEE beams are smaller than those of clinical MV photon beams for lower depths (<5 cm) but increase quickly for larger depths. There is only a relatively small dependence of penumbra on the SSD of the beam. The findings presented in this study assess the performance of VHEE beams and offer a first estimate of treatment indications and tradeoffs for a given design of a VHEE device. SSD >100 cm results in clinically more favorable PDD. Beam energies of 100 MeV and above are needed to cover common tumors (5-15 cm in-depth) conformally. Higher energies provide an additional benefit specifically for small and deep-seated lesions due to their reduced lateral penumbrae.

Böhlen TT ，Germond JF ，Traneus E ，Bourhis J ，Vozenin MC ，Bailat C ，Bochud F ，Moeckli R ... -  《-》

Very high-energy electron (VHEE) beams in radiation therapy; Treatment plan comparison between VHEE, VMAT, and PPBS.

The aim of this study was to evaluate the performance of very high-energy electron beams (VHEE) in comparison to clinically derived treatment plans generated with volumetric modulated arc therapy (VMAT) and proton pencil beam scanning (PPBS) technology. We developed a custom optimization script that could be applied automatically across modalities to eliminate operator bias during IMRT optimization. Four clinical cases were selected (prostate cancer, lung cancer, pediatric brain tumor, and head and neck cancer (HNC)). The VHEE beams were calculated in the EGSnrc/DOSXYZnrc Monte Carlo code for 100 and 200 MeV beams. Treatment plans with VHEE, VMAT, and PPBS were optimized in a research version of RayStation using an in-house developed script to minimize operator bias between the different techniques. The in-house developed script generated similar or superior plans to the clinically used plans. In the comparisons between the modalities, the integral dose was lowest for the PPBS-generated plans in all cases. For the prostate case, the 200 MeV VHEE plan showed reduced integral dose and reduced organ at risk (OAR) dose compared to the VMAT plan. For all other cases, both the 100 and the 200 MeV VHEE plans were superior to the VMAT plans, and the VHEE plans showed better conformity and lower spinal cord dose in the pediatric brain case and lower brain stem dose in the HNC case when compared to the PPBS plan. The automated optimization developed in this study generated similar or superior plans as compared to the clinically used plan and represents an unbiased approach to compare treatment plans generated for different modalities. In the present study, we also show that VHEE plans are similar or superior to VMAT plans with reduced mean OAR dose and increased target conformity for a variety of clinical cases, and VHEE plans can even achieve reductions in OAR doses compared to PPBS plans for shallow targets. With increased VHEE energy, better conformity and even higher reductions in mean OAR doses are achieved. On the whole, VHEE was intermediate between photon VMAT and PPBS for OAR sparing.

Schüler E ，Eriksson K ，Hynning E ，Hancock SL ，Hiniker SM ，Bazalova-Carter M ，Wong T ，Le QT ，Loo BW Jr ，Maxim PG ... -  《-》