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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.

Background Recently, a flexible DROP-IN gamma-probe was introduced for robot-assisted radioguided surgery, using traditional low-energy SPECT-isotopes. In parallel, a novel approach to achieve sensitive radioguidance using beta-emitting PET isotopes has been proposed. Integration of these two concepts would allow to exploit the use of PET tracers during robot-assisted tumor-receptor-targeted. In this study, we have engineered and validated the performance of a novel DROP-IN beta particle (DROP-INβ) detector. Methods Seven prostate cancer patients with PSMA-PET positive tumors received an additional intraoperative injection of ~ 70 MBq 68Ga-PSMA-11, followed by robot-assisted prostatectomy and extended pelvic lymph node dissection. The surgical specimens from these procedures were used to validate the performance of our DROP-INβ probe prototype, which merged a scintillating detector with a housing optimized for a 12-mm trocar and prograsp instruments. Results After optimization of the detector and probe housing via Monte Carlo simulations, the resulting DROP-INβ probe prototype was tested in a robotic setting. In the ex vivo setting, the probe—positioned by the robot—was able to identify 68Ga-PSMA-11 containing hot-spots in the surgical specimens: signal-to-background (S/B) was > 5 when pathology confirmed that the tumor was located 3). The rotational freedom of the DROP-IN design and the ability to manipulate the probe with the prograsp tool allowed the surgeon to perform autonomous beta-tracing. Conclusions This study demonstrates the feasibility of beta-radioguided surgery in a robotic context by means of a DROP-INβ detector. When translated to an in vivo setting in the future, this technique could provide a valuable tool in detecting tumor remnants on the prostate surface and in confirmation of PSMA-PET positive lymph nodes.

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.

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.

Particle therapy in which deep seated tumours are treated using 12C ions (Carbon Ions RadioTherapy or CIRT) exploits the high conformity in the dose release, the high relative biological effectiveness and low oxygen enhancement ratio of such projectiles. The advantages of CIRT are driving a rapid increase in the number of centres that are trying to implement such technique. To fully profit from the ballistic precision achievable in delivering the dose to the target volume an online range verification system would be needed, but currently missing. The 12C ions beams range could only be monitored by looking at the secondary radiation emitted by the primary beam interaction with the patient tissues and no technical solution capable of the needed precision has been adopted in the clinical centres yet. The detection of charged secondary fragments, mainly protons, emitted by the patient is a promising approach, and is currently being explored in clinical trials at CNAO. Charged particles are easy to detect and can be back-tracked to the emission point with high efficiency in an almost background-free environment. These fragments are the product of projectiles fragmentation, and are hence mainly produced along the beam path inside the patient. This experimental signature can be used to monitor the beam position in the plane orthogonal to its flight direction, providing an online feedback to the beam transverse position monitor chambers used in the clinical centres. This information could be used to cross-check, validate and calibrate, whenever needed, the information provided by the ion chambers already implemented in most clinical centres as beam control detectors. In this paper we study the feasibility of such strategy in the clinical routine, analysing the data collected during the clinical trial performed at the CNAO facility on patients treated using 12C ions and monitored using the Dose Profiler (DP) detector developed within the INSIDE project. On the basis of the data collected monitoring three patients, the technique potential and limitations will be discussed.

In particle therapy, the uncertainty of the delivered particle range during the patient irradiation limits the optimization of the treatment planning. Therefore, an in vivo treatment verification device is required, not only to improve the plan robustness, but also to detect significant interfractional morphological changes during the treatment itself. In this article, an effective and robust analysis to detect regions with a significant range discrepancy is proposed. This study relies on an in vivo treatment verification by means of in-beam Positron Emission Tomography (PET) and was carried out with the INSIDE system installed at the National Center of Oncological Hadrontherapy (CNAO) in Pavia, which is under clinical testing since July 2019. Patients affected by head-and-neck tumors treated with protons have been considered. First, in order to tune the analysis parameters, a Monte Carlo (MC) simulation was carried out to reproduce a patient who required a replanning because of significant morphological changes found during the treatment. Then, the developed approach was validated on the experimental measurements of three patients recruited for the INSIDE clinical trial (ClinicalTrials.gov ID: NCT03662373), showing the capability to estimate the treatment compliance with the prescription both when no morphological changes occurred and when a morphological change did occur, thus proving to be a promising tool for clinicians to detect variations in the patients treatments.

Secondary neutrons produced in particle therapy (PT) treatments are responsible for the delivery of a large fraction of the out-of-target dose as they feebly interact with the patient body. To properly account for their contribution to the total dose delivered to the patient, a high precision experimental characterisation of their production energy and angular distributions is eagerly needed. The experimental challenge posed by the detection and tracking of such neutrons will be addressed by the MONDO tracker: a compact scintillating fiber detector exploiting single and double elastic scattering interactions allowing for a complete neutron four-momentum reconstruction. To achieve a high detection efficiency while matching the fiber (squared, 250 μm side) high granularity, a single photon sensitive readout has been developed using the CMOS-based SPAD technology. The readout sensor, with pixels of 125×250 μm2 size, will be organised in tiles covering the full detector surface and will implement an autotrigger strategy to identify the events of interest. The expected detector performance in the context of neutron component characterisation in PT treatments delivered using carbon ions has been evaluated using a Monte Carlo simulation accounting for the detector response and the neutrons production spectra.