In-vivo range verification analysis with in-beam PET data for patients treated with proton therapy at CNAO.

Morphological changes that may arise through a treatment course are probably one of the most significant sources of range uncertainty in proton therapy. Non-invasive in-vivo treatment monitoring is useful to increase treatment quality. The INSIDE in-beam Positron Emission Tomography (PET) scanner performs in-vivo range monitoring in proton and carbon therapy treatments at the National Center of Oncological Hadrontherapy (CNAO). It is currently in a clinical trial (ID: NCT03662373) and has acquired in-beam PET data during the treatment of various patients. In this work we analyze the in-beam PET (IB-PET) data of eight patients treated with proton therapy at CNAO. The goal of the analysis is twofold. First, we assess the level of experimental fluctuations in inter-fractional range differences (sensitivity) of the INSIDE PET system by studying patients without morphological changes. Second, we use the obtained results to see whether we can observe anomalously large range variations in patients where morphological changes have occurred. The sensitivity of the INSIDE IB-PET scanner was quantified as the standard deviation of the range difference distributions observed for six patients that did not show morphological changes. Inter-fractional range variations with respect to a reference distribution were estimated using the Most-Likely-Shift (MLS) method. To establish the efficacy of this method, we made a comparison with the Beam's Eye View (BEV) method. For patients showing no morphological changes in the control CT the average range variation standard deviation was found to be 2.5 mm with the MLS method and 2.3 mm with the BEV method. On the other hand, for patients where some small anatomical changes occurred, we found larger standard deviation values. In these patients we evaluated where anomalous range differences were found and compared them with the CT. We found that the identified regions were mostly in agreement with the morphological changes seen in the CT scan.

FLASH radiotherapy treatment planning and models for electron beams.

The FLASH effect designates normal tissue sparing at ultra-high dose rate (UHDR, >40 Gy/s) compared to conventional dose rate (∼0.1 Gy/s) irradiation while maintaining tumour control and has the potential to improve the therapeutic ratio of radiotherapy (RT). UHDR high-energy electron (HEE, 4-20 MeV) beams are currently a mainstay for investigating the clinical potential of FLASH RT for superficial tumours. In the future very-high energy electron (VHEE, 50-250 MeV) UHDR beams may be used to treat deep-seated tumours. UHDR HEE treatment planning focused at its initial stage on accurate dosimetric modelling of converted and dedicated UHDR electron RT devices for the clinical transfer of FLASH RT. VHEE treatment planning demonstrated promising dosimetric performance compared to clinical photon RT techniques in silico and was used to evaluate and optimise the design of novel VHEE RT devices. Multiple metrics and models have been proposed for a quantitative description of the FLASH effect in treatment planning, but an improved experimental characterization and understanding of the FLASH effect is needed to allow for an accurate and validated modelling of the effect in treatment planning. The importance of treatment planning for electron FLASH RT will augment as the field moves forward to treat more complex clinical indications and target sites. In this review, TPS developments in HEE and VHEE are presented considering beam models, characteristics, and future FLASH applications.

A Data-Driven Fragmentation Model for Carbon Therapy GPU-Accelerated Monte-Carlo Dose Recalculation.

The advent of Graphics Processing Units (GPU) has prompted the development of Monte Carlo (MC) algorithms that can significantly reduce the simulation time with respect to standard MC algorithms based on Central Processing Unit (CPU) hardware. The possibility to evaluate a complete treatment plan within minutes, instead of hours, paves the way for many clinical applications where the time-factor is important. FRED (Fast paRticle thErapy Dose evaluator) is a software that exploits the GPU power to recalculate and optimise ion beam treatment plans. The main goal when developing the FRED physics model was to balance accuracy, calculation time and GPU execution guidelines. Nowadays, FRED is already used as a quality assurance tool in Maastricht and Krakow proton clinical centers and as a research tool in several clinical and research centers across Europe. Lately the core software has been updated including a model of carbon ions interactions with matter. The implementation is phenomenological and based on carbon fragmentation data currently available. The model has been tested against the MC FLUKA software, commonly used in particle therapy, and a good agreement was found. In this paper, the new FRED data-driven model for carbon ion fragmentation will be presented together with the validation tests against the FLUKA MC software. The results will be discussed in the context of FRED clinical applications to 12C ions treatment planning.

Deep Seated Tumour Treatments With Electrons of High Energy Delivered at FLASH Rates: The Example of Prostate Cancer.

Different therapies are adopted for the treatment of deep seated tumours in combination or as an alternative to surgical removal or chemotherapy: radiotherapy with photons (RT), particle therapy (PT) with protons or even heavier ions like 12C, are now available in clinical centres. In addition to these irradiation modalities, the use of Very High Energy Electron (VHEE) beams (100-200 MeV) has been suggested in the past, but the diffusion of that technique was delayed due to the needed space and budget, with respect to standard photon devices. These disadvantages were not paired by an increased therapeutic efficacy, at least when comparing to proton or carbon ion beams. In this contribution we investigate how recent developments in electron beam therapy could reshape the treatments of deep seated tumours. In this respect we carefully explored the application of VHEE beams to the prostate cancer, a well-known and studied example of deep seated tumour currently treated with high efficacy both using RT and PT. The VHEE Treatment Planning System was obtained by means of an accurate Monte Carlo (MC) simulation of the electrons interactions with the patient body. A simple model of the FLASH effect (healthy tissues sparing at ultra-high dose rates), has been introduced and the results have been compared with conventional RT. The study demonstrates that VHEE beams, even in absence of a significant FLASH effect and with a reduced energy range (70-130 MeV) with respect to implementations already explored in literature, could be a good alternative to standard RT, even in the framework of technological developments that are nowadays affordable.