Applications of Monte Carlo methods to special radiotherapeutic techniques

Monte Carlo (MC) methods are considered one of the most powerful and precise approaches to study and solve medical physics issues. They, indeed, can be applied in all the situations where to use deterministic algorithms is infeasible or impossible. Surprising improvements in computer technology have promoted a wide diffusion of this technique, giving rise to the born of several Monte Carlo codes, such as the GEANT4 toolkit. In this paper we show some of the applications we developed using GEANT4. In particular, the simulation of two different radiotherapy techniques, such as proton/ion therapy and stereotactic radiosurgery will be discussed. In the first case we show the main features of our last public version of the GEANT4 Hadrontherapy program, also discussing the issues related to the nuclear fragmentation. In the second case, we show the procedures followed for the simulation of a Gamma Knife device, in order to validate the Treatment Planning System (TPS) used for the dose computation

Robustness of pet radiomics features: Impact of co-registration with mri

Radiomics holds great promise in the field of cancer management. However, the clinical application of radiomics has been hampered by uncertainty about the robustness of the features extracted from the images. Previous studies have reported that radiomics features are sensitive to changes in voxel size resampling and interpolation, image perturbation, or slice thickness. This study aims to observe the variability of positron emission tomography (PET) radiomics features under the impact of co-registration with magnetic resonance imaging (MRI) using the difference percentage coefficient, and the Spearman’s correlation coefficient for three groups of images: (i) original PET, (ii) PET after co-registration with T1-weighted MRI and (iii) PET after co-registration with FLAIR MRI. Specifically, seventeen patients with brain cancers undergoing [11C]-Methionine PET were considered. Successively, PET images were co-registered with MRI sequences and 107 features were extracted for each mentioned group of images. The variability analysis revealed that shape features, first-order features and two subgroups of higher-order features possessed a good robustness, unlike the remaining groups of features, which showed large differences in the difference percentage coeffi-cient. Furthermore, using the Spearman’s correlation coefficient, approximately 40% of the selected features differed from the three mentioned groups of images. This is an important consideration for users conducting radiomics studies with image co-registration constraints to avoid errors in cancer diagnosis, prognosis, and clinical outcome prediction

CATANA protontherapy facility: The state of art of clinical and dosimetric experience

After nine years of activity, about 220 patients have been treated at the CATANA Eye Protontherapy facility. A 62MeV proton beam produced by a Superconducting Cyclotron is dedicated to radiotherapy of eye lesions, as uveal melanomas. Research and development work has been done to test different dosimetry devices to be used for reference and relative dosimetry, in order to achieve dose delivering accuracy. The follow-up results demonstrated the efficacy of proton beams and encouraged us in our activity in the fight against cancer

Online measurement of fluence and position for protontherapy beams

Tumour therapy with proton beams has been used for several decades in many centres with very good results in terms of local control and overall survival. Typical pathologies treated with this technique are located in head and neck, eye, prostate and in general at big depths or close to critical organs. The Experimental Physics Department of the University of Turin and the local Section of INFN, in collaboration with INFN Laboratori Nazionali del Sud Catania and Centre de Protontherapie de Orsay Paris, have developed detector systems that allow the measurement of beam position and fluence, obtained in real time during beam delivery. The centre in Catania (CATANA: Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) has been treating patients with eye pathologies since spring 2002 using a superconducting cyclotron accelerating protons up to 62 MeV. This kind of treatments need high-resolution monitor systems and for this reason we have developed a 256-strip segmented ionisation chamber, each strip being 400 μm wide, with a total sensitive area 13 × 13 cm2. The Centre de Protontherapie de Orsay (CPO) has been operational since 1991 and features a synchrocyclotron used for eye and head and neck tumours with proton beams up to 200 MeV. The monitor system has to work on a large surface and for this purpose we have designed a pixel-segmented ionisation chamber, each pixel being 5×5 mm2, for a total active area of 16 × 16 cm2. The results obtained with two prototypes of the pixel and strip chambers demonstrate that the detectors allow the measurement of fluence and centre of gravity as requested by clinical specifications

Clinical and Research Activities at the CATANA Facility of INFN-LNS: From the Conventional Hadrontherapy to the Laser-Driven Approach

The CATANA proton therapy center was the first Italian clinical facility making use of energetic (62 MeV) proton beams for the radioactive treatment of solid tumors. Since the date of the first patient treatment in 2002, 294 patients have been successful treated whose majority was affected by choroidal and iris melanomas. In this paper, we report on the current clinical and physical status of the CATANA facility describing the last dosimetric studies and reporting on the last patient follow-up results. The last part of the paper is dedicated to the description of the INFN-LNS ongoing activities on the realization of a beamline for the transport of laser-accelerated ion beams for future applications. The ELIMED (ELI-Beamlines MEDical and multidisciplinary applications) project is introduced and the main scientific aspects will be described

'The nourishing soil of the soul': The role of horticultural therapy in promoting well-being in community-dwelling people with dementia.

Two-thirds of people with dementia reside in their own homes; however, support for community-dwelling people with dementia to continue to participate in everyday activities is often lacking, resulting in feelings of depression and isolation among people living with the condition. Engagement in outdoor activities such as gardening can potentially counteract these negative experiences by enabling people with dementia to interact with nature, helping to improve their physical and psychological well-being. Additionally, the collaborative nature of community gardening may encourage the development of a sense of community, thereby enhancing social integration. Despite increasing evidence supporting its therapeutic value for people with dementia in residential care, the benefits of horticultural therapy have yet to be transposed into a community setting. This paper will examine the theoretical support for the application of horticultural therapy in dementia care, before exploring the potential of horticultural therapy as a means of facilitating improved physical and psychological well-being and social integration for people living with dementia within the community

A 62 MeV proton beam for the treatment of ocular melanoma at Laboratori Nazionali del Sud-INFN (CATANIA)

At the Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali del Sud (INFN-LNS) in Catania, Italy, the first Italian protontherapy facility, named Centro di AdroTerapia e Applicazioni Nucleari Avanzate (CATANA) has been built in collaboration with the University of Catania. It is based on the use of the 62-MeV proton beam delivered by the K=800 Superconducting Cyclotron installed and working at INFN-LNS since 1995. The facility is mainly devoted to the treatment of ocular diseases like uveal melanoma. A beam treatment line in air has been assembled together with a dedicated positioning patient system. The facility has been in operation since the beginning of 2002 and 66 patients have been successfully treated up to now. The main features of CATANA together with the clinical and dosimetric features will be extensively described; particularly, the proton beam line, that has been entirely built at LNS, with all its elements, the experimental transversal and depth dose distributions of the 62-MeV proton beam obtained for a final collimator of 25-mm diameter and the experimental depth dose distributions of a modulated proton beam obtained for the same final collimator. Finally, the clinical results over 1 yr of treatments, describing the features of the treated diseases will be reported

Cellular and molecular effects of protons: apoptosis induction and potential implications for cancer therapy.

Due to their ballistic precision, apoptosis induction by protons could be a strategy to specifically eliminate neoplastic cells. To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D, MCF7) to increasing doses of protons and examining them with FACS, RT-PCR, and electron spin resonance (ESR). Irradiation with a dose of 10 Gy of a 26,7 Mev proton beam altered cell structures such as membranes, caused DNA double strand breaks, and significantly increased intracellular levels of hydroxyl ions, are active oxygen species (ROS). This modified the transcriptome of irradiated cells, activated the mitochondrial (intrinsic) pathway of apoptosis, and resulted in cycle arrest at the G2/M boundary. The number of necrotic cells within the irradiated cell population did not significantly increase with respect to the controls. The effects of irradiation with 20 Gy were qualitatively as well as quantitatively similar, but exposure to 40 Gy caused massive necrosis. Similar experiments with photons demonstrated that they induce apoptosis in a significantly lower number of cells and in a temporally delayed manner. These data advance our knowledge on the cellular and molecular effects of proton irradiation and could be useful for improving current hadrontherapy protocols

Expression of Trichoderma reesei β-Mannanase in Tobacco Chloroplasts and Its Utilization in Lignocellulosic Woody Biomass Hydrolysis

Lignocellulosic ethanol offers a promising alternative to conventional fossil fuels. One among the major limitations in the lignocellulosic biomass hydrolysis is unavailability of efficient and environmentally biomass degrading technologies. Plant-based production of these enzymes on large scale offers a cost-effective solution. Cellulases, hemicellulases including mannanases and other accessory enzymes are required for conversion of lignocellulosic biomass into fermentable sugars. β-mannanase catalyzes endo-hydrolysis of the mannan backbone, a major constituent of woody biomass. In this study, the man1 gene encoding β-mannanase was isolated from Trichoderma reesei and expressed via the chloroplast genome. PCR and Southern hybridization analysis confirmed site-specific transgene integration into the tobacco chloroplast genomes and homoplasmy. Transplastomic plants were fertile and set viable seeds. Germination of seeds in the selection medium showed inheritance of transgenes into the progeny without any Mendelian segregation. Expression of endo-β-mannanase for the first time in plants facilitated its characterization for use in enhanced lignocellulosic biomass hydrolysis. Gel diffusion assay for endo-β-mannanase showed the zone of clearance confirming functionality of chloroplast-derived mannanase. Endo-β-mannanase expression levels reached up to 25 units per gram of leaf (fresh weight). Chloroplast-derived mannanase had higher temperature stability (40°C to 70°C) and wider pH optima (pH 3.0 to 7.0) than E.coli enzyme extracts. Plant crude extracts showed 6–7 fold higher enzyme activity than E.coli extracts due to the formation of disulfide bonds in chloroplasts, thereby facilitating their direct utilization in enzyme cocktails without any purification. Chloroplast-derived mannanase when added to the enzyme cocktail containing a combination of different plant-derived enzymes yielded 20% more glucose equivalents from pinewood than the cocktail without mannanase. Our results demonstrate that chloroplast-derived mannanase is an important component of enzymatic cocktail for woody biomass hydrolysis and should provide a cost-effective solution for its diverse applications in the biofuel, paper, oil, pharmaceutical, coffee and detergent industries