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 ... -  《-》

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 ... -  《-》

Potential for reduced toxicity and dose escalation in the treatment of inoperable non-small-cell lung cancer: a comparison of intensity-modulated radiation therapy (IMRT), 3D conformal radiation, and elective nodal irradiation.

Grills IS ，Yan D ，Martinez AA ，Vicini FA ，Wong JW ，Kestin LL ... -  《INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS》

Treatment planning consideration for very high-energy electron FLASH radiotherapy.

Very high-energy electron (VHEE) can make up the insufficient treatment depth of the low-energy electron while offering an intermediate dosimetric advantage between photon and proton. Combining FLASH with VHEE, a quantitative comparison between different energies was made, with regard to plan quality, dose rate distribution (both in PTV and OAR), and total duration of treatment (beam-on time). In two patient cases (head and lung), we created the treatment plans utilizing the scanning pencil beam via the Monte Carlo simulation and a PTV-based optimization algorithm. Geant4 was used to simulate VHEE pencil beams and sizes of 0.3-5 mm defined by the full width at half maximum (FWHM). Monoenergetic beams with Gaussian distribution in x and y directions (ISOURC = 19) were used as the source of electrons. A large-scale non-linear solver (IPOPT) was used to calculate the optimal spot weights. After optimization, a quantitative comparison between different energies was made regarding treatment plan quality, dose rate distribution (both in PTV and OAR), and total beam duration. For head (80 MeV, 100 MeV, and 120 MeV) and lung cases (100 MeV, 120 MeV, and 140 MeV), the minimum beam intensity needs to be ∼2.5 × 1011 electrons/s and ∼9.375 × 1011 electrons/s to allow > 90 % volume of PTV reaching the average dose rate (DADR) higher than 40 Gy/s. At this beam intensity (fraction dose: 10 Gy), the overall irradiation time for the head case is 5258.75 ms (80 MeV), 5149.75 ms (100 MeV), and 4976.75 ms (120 MeV), including scanning time 872.75 ms. For lung cases, this number is 1034.25 ms (100 MeV), 981.55 ms (120 MeV), and 928.15 ms (140 MeV), including scanning time 298.75 ms. The plan of higher energy always performs with a higher dose rate (both in PTV and OAR) and thereby costs less delivery time (beam-on time). The study systematically investigated the currently known FLASH parameters for VHEE radiotherapy and successfully established a benchmark reference for its FLASH dose rate performance.

Zhang G ，Zhang Z ，Gao W ，Quan H ... -  《-》