New Advantage in Stereotactic Treatment of Lung and Pancreatic Cancer. Performance of Ultra-High Energy Electron (VHEE) Therapy Adjuvanted to the FLASH Effect: Clinical Implications and Treatment Plans Analysis

Abstract

Very High-Energy Electron (VHEE) beams delivered at ultra-high dose rates and hence profiting from the FLASH effect, may be a viable alternative to conventional treatment plans for the treatment of deep-seated tumors. Experimental data support the evidence of a considerable normal tissue sparing effect when treatments are delivered with dose rates much larger (100 times or more) compared to the conventional ones. Lung cancer and pancreatic cancer are considered the two biggest cancer killers. We urgently need more research in these areas, more awareness that support improvement in treatment strategies. To evaluate the potential of FLASH VHEE irradiation in these two clinical situations, we investigated the achievable sparing of healthy tissues and critical dose-limiting structures, with the goal of performing a higher dose prescription. The study on the potential of VHEE for the stereotactic treatment of pancreatic and lung lesions was carried out on two clinical cases treated with Volumetric Modulated Arc Therapy (VMAT) techniques at University Hospital Campus Bio-Medico of Rome. The Planning Target Volume (PTV) was identified and the constraints on the Organs at Risk (OAR) and details on the irradiation approach were defined. The VHEE plan was designed to optimize the dose delivery to best activate the modelled FLASH effect based on the current experimental knowledge. In particular the impact on a dose threshold to activate the effect was studied. The VHEE treatment plan was based on an accurate Monte Carlo simulation of the electrons interactions and the results achievable with different FLASH effect models were studied. The simulation allowed the estimation of dose maps, which were used as input to an optimization algorithm that modified the fluence of each beam to meet treatment prescriptions in terms of dose to PTV. At the end the VHEE DVH plans were compared to VMAT plans. The results demonstrated that FLASH therapy with VHEE beams of 70-130 MeV, could represent a promising alternative to standard radiotherapy allowing a comparable sparing of the healthy tissues. In the case of pancreatic cancer, the Dose Volume Histograms (DVH) showed how such a technique can be effective in sparing the duodenum. In case of lung cancers, the result showed how pulmonary tissue sparing can lead to a substantial reduction of pulmonary toxicity in comparison with the VMAT technique. In the case of pancreatic cancer and assuming a non-negligible contribution from the FLASH effect, the DVH showed how the duodenum healthy tissue sparing could allow a higher dose to be prescribed at the target while keeping the constraints respected, improving the therapeutic ratio. In the case of lung cancer, the advantages of the technique are additionally increased by the significant benefit that could be related to the treatment delivery time reduction (<1s) and to the corresponding advantage coming from a reduced organ movement that translates in a lower risk of lung toxicity.