The Role of Carbon Ion Therapy in the Changing Oncology Landscape-A Narrative Review of the Literature and the Decade of Carbon Ion Experience at the Italian National Center for Oncological Hadrontherapy.

Background: Currently, 13 Asian and European facilities deliver carbon ion radiotherapy (CIRT) for preclinical and clinical activity, and, to date, 55 clinical studies including CIRT for adult and paediatric solid neoplasms have been registered. The National Center for Oncological Hadrontherapy (CNAO) is the only Italian facility able to accelerate both protons and carbon ions for oncological treatment and research.

Methods: To summarise and critically evaluate state-of-the-art knowledge on the application of carbon ion radiotherapy in oncological settings, the authors conducted a literature search till December 2022 in the following electronic databases: PubMed, Web of Science, MEDLINE, Google Scholar, and Cochrane.

A new system for in-room image guidance in particle therapy at CNAO.

This paper describes the design, installation, and commissioning of an in-room imaging device developed at the Centro Nazionale di Adroterapia Oncologica (CNAO, Pavia, Italy). The system is an upgraded version of the one previously installed in 2014, and its design accounted for the experience gained in a decade of clinical practice of patient setup verification and correction through robotic-supported, off-isocenter in-room image guidance. The system's basic feature consists of image-based setup correction through 2D/3D and 3D/3D registration through a dedicated HW/SW platform.

Virtual 4DCT generated from 4DMRI in gated particle therapy: phantom validation and application to lung cancer patients.

. Respiration negatively affects the outcome of a radiation therapy treatment, with potentially severe effects especially in particle therapy (PT). If compensation strategies are not applied, accuracy cannot be achieved.

Synthetic CT in Carbon Ion Radiotherapy of the Abdominal Site.

The generation of synthetic CT for carbon ion radiotherapy (CIRT) applications is challenging, since high accuracy is required in treatment planning and delivery, especially in an anatomical site as complex as the abdomen. Thirty-nine abdominal MRI-CT volume pairs were collected and a three-channel cGAN (accounting for air, bones, soft tissues) was used to generate sCTs. The network was tested on five held-out MRI volumes for two scenarios: (i) a CT-based segmentation of the MRI channels, to assess the quality of sCTs and (ii) an MRI manual segmentation, to simulate an MRI-only treatment scenario.

Microstructural parameters from DW-MRI for tumour characterization and local recurrence prediction in particle therapy of skull-base chordoma.

Background: Quantitative imaging such as Diffusion-Weighted MRI (DW-MRI) can be exploited to non-invasively derive patient-specific tumor microstructure information for tumor characterization and local recurrence risk prediction in radiotherapy.

Purpose: To characterize tumor microstructure according to proliferative capacity and predict local recurrence through microstructural markers derived from pre-treatment conventional DW-MRI, in skull-base chordoma (SBC) patients treated with proton (PT) and carbon ion (CIRT) radiotherapy.

Methods: Forty-eight patients affected by SBC, who underwent conventional DW-MRI before treatment and were enrolled for CIRT (n = 25) or PT (n = 23), were retrospectively selected.

Dosimetric Impact of Inter-Fraction Anatomical Changes in Carbon Ion Boost Treatment for High-Risk Prostate Cancer (AIRC IG 14300).

Rectum and bladder volumes play an important role in the dose distribution reproducibility in prostate cancer adenocarcinoma (PCa) radiotherapy, especially for particle therapy, where density variation can strongly affect the dose distribution. We investigated the reliability and reproducibility of our image-guided radiotherapy (IGRT) and treatment planning protocol for carbon ion radiotherapy (CIRT) within the phase II mixed beam study (AIRC IG 14300) for the treatment of high-risk PCa. In order to calculate the daily dose distribution, a set of synthetic computed tomography (sCT) images was generated from the cone beam computed tomography (CBCT) images acquired in each treatment session.

Image-based shading correction for narrow-FOV truncated pelvic CBCT with deep convolutional neural networks and transfer learning.

Purpose: Cone beam computed tomography (CBCT) is a standard solution for in-room image guidance for radiation therapy. It is used to evaluate and compensate for anatomopathological changes between the dose delivery plan and the fraction delivery day. CBCT is a fast and versatile solution, but it suffers from drawbacks like low contrast and requires proper calibration to derive density values.

Dosimetric effect of variable rectum and sigmoid colon filling during carbon ion radiotherapy to sacral chordoma.

Purpose: Carbon ion radiotherapy (CIRT) is sensitive to anatomical density variations. We examined the dosimetric effect of variable intestinal filling condition during CIRT to ten sacral chordoma patients.

Methods: For each patient, eight virtual computed tomography scans (vCTs) were generated by varying the density distribution within the rectum and the sigmoid in the planning computed tomography (pCT) with a density override approach mimicking a heterogeneous combination of gas and feces.

Convolutional Neural Networks Cascade for Automatic Pupil and Iris Detection in Ocular Proton Therapy.

Eye tracking techniques based on deep learning are rapidly spreading in a wide variety of application fields. With this study, we want to exploit the potentiality of eye tracking techniques in ocular proton therapy (OPT) applications. We implemented a fully automatic approach based on two-stage convolutional neural networks (CNNs): the first stage roughly identifies the eye position and the second one performs a fine iris and pupil detection.

FRoG dose computation meets Monte Carlo accuracy for proton therapy dose calculation in lung.

Purpose: To benchmark and evaluate the clinical viability of novel analytical GPU-accelerated and CPU-based Monte Carlo (MC) dose-engines for spot-scanning intensity-modulated-proton-therapy (IMPT) towards the improvement of lung cancer treatment.

Methods: Nine patient cases were collected from the CNAO clinical experience and The Cancer Imaging Archive-4D-Lung-Database for in-silico study. All plans were optimized with 2 orthogonal beams in RayStation (RS) v.

An MRI framework for respiratory motion modelling validation.

Introduction: Respiratory motion models establish a correspondence between respiratory-correlated (RC) 4-dimensional (4D) imaging and respiratory surrogates, to estimate time-resolved (TR) 3D breathing motion. To evaluate the performance of motion models on real patient data, a validation framework based on magnetic resonance imaging (MRI) is proposed, entailing the use of RC 4DMRI to build the model, and on both (i) TR 2D cine-MRI and (ii) additional 4DMRI data for testing intra-/inter-fraction breathing motion variability.

Methods: Repeated MRI data were acquired in 7 patients with abdominal lesions.

Microbial Community Field Surveys Reveal Abundant Population in Sorghum Rhizosphere Composed of Many Closely Related Phylotypes.

While the root-associated microbiome is typically less diverse than the surrounding soil due to both plant selection and microbial competition for plant derived resources, it typically retains considerable complexity, harboring many hundreds of distinct bacterial species. Here, we report a time-dependent deviation from this trend in the rhizospheres of field grown sorghum. In this study, 16S rRNA amplicon sequencing was used to determine the impact of nitrogen fertilization on the development of the root-associated microbiomes of 10 sorghum genotypes grown in eastern Nebraska.

Development and validation of a new set-up simulator dedicated to ocular proton therapy at CNAO.

An Eye Tracking System (ETS) is used at CNAO for providing a stable and reproducible ocular proton therapy (OPT) set-up, featuring a fixation light (FL) and monitoring stereo-cameras embedded in a rigid case. The aim of this work is to propose an ETS set-up simulation algorithm, that automatically provides the FL positioning in space, according to patient-specific gaze direction and avoiding interferences with patient, beam and collimator. Two configurations are provided: one in the CT room for acquiring images required for treatment planning with the patient lying on a couch, and one related to the treatment room with the patient sitting in front of the beam.

Investigating the use of virtual 4DCT from 4DMRI in gated carbon ion radiation therapy of abdominal tumors.

Purpose: To generate virtual 4DCT from 4DMRI with field of view (FOV) extended to the entire involved patient anatomy, in order to evaluate its use in carbon ion radiation therapy (CIRT) of the abdominal site in a clinical scenario.

Materials And Methods: The virtual 4DCT was generated by deforming a reference CT in order to (1) match the anatomy depicted in the 4DMRI within its FOV, by calculating deformation fields with deformable image registration to describe inter-fractional and breathing motion, and (2) obtain physically plausible deformation outside of the 4DMRI FOV, by propagating and modulating the previously obtained deformation fields. The implemented method was validated on a digital anthropomorphic phantom, for which a ground truth (GT) 4DCT was available.

4D strategies for lung tumors treated with hypofractionated scanning proton beam therapy: Dosimetric impact and robustness to interplay effects.

Purpose: To investigate the impact of four-dimensional robust optimization (4DRO) on dose delivered to lung cancer patients in pencil beam scanning proton therapy.

Methods And Materials: 2 strategies were compared for 20 lung cancer patients, using a different number of breathing phases of the reconstructed 4D computed tomography (CT) included in the plan optimization problem. In the restricted approach combined with gating, only 3 phases close to reference end-exhale were considered instead of the whole breathing cycle.

Virtual 4DCT from 4DMRI for the management of respiratory motion in carbon ion therapy of abdominal tumors.

Purpose: To evaluate a method for generating virtual four-dimensional computed tomography (4DCT) from four-dimensional magnetic resonance imaging (4DMRI) data in carbon ion radiotherapy with pencil beam scanning for abdominal tumors.

Methods: Deformable image registration is used to: (a) register each respiratory phase of the 4DMRI to the end-exhale MRI; (b) register the reference end-exhale CT to the end-exhale MRI volume; (c) generate the virtual 4DCT by warping the registered CT according to the obtained deformation fields. A respiratory-gated carbon ion treatment plan is optimized on the planning 4DCT and the corresponding dose distribution is recalculated on the virtual 4DCT.

Long-time clinical experience in patient setup for several particle therapy clinical indications: management of patient positioning and evaluation of setup reproducibility and stability.

Objective: Accurate patient positioning is crucial in particle therapy due to the geometrical selectivity of particles. We report and discuss the National Center for Oncological Hadrontherapy (CNAO) experience in positioning accuracy and stability achieved with solid thermoplastic masks fixed on index base plates and assessed by daily orthogonal X-ray imaging.

Methods: Positioning data were retrospectively collected (between 2012 and 2018) and grouped according to the treated anatomical site.

Validation of a model for physical dose variations in irregularly moving targets treated with carbon ion beams.

Purpose: In particle therapy, conventional treatment planning systems rely on an imaging representation of the irradiated region to compute the dose. For irregular breathing, when an imaging dataset describing the actual motion is not available, a different approach for dose estimation is needed. To this aim, we validate a method for the estimation of physical dose variations in gated carbon ion treatments, providing also a demonstration of the feasibility of physical dose metrics to assess the method performance.

MRI-based tumour control probability in skull-base chordomas treated with carbon-ion therapy.

Purpose: To derive personalized tumour control probability (TCP) models, using diffusion-weighted (DW-) MRI for defining initial tumour cellular density in skull-base chordoma patients undergoing carbon-ion radiotherapy (CIRT).

Materials And Methods: 67 patients affected by skull-base chordoma were enrolled for a standardized CIRT treatment (70.4 Gy (RBE) prescription dose).

A platform for patient positioning and motion monitoring in ocular proton therapy with a non-dedicated beamline.

Purpose: At Centro Nazionale di Adroterapia Oncologica (CNAO, Pavia, Italy) ocular proton therapy (OPT) is delivered using a non-dedicated beamline. This paper describes the novel clinical workflow as well as technologies and methods adopted to achieve accurate target positioning and verification during ocular proton therapy at CNAO.

Method: The OPT clinical protocol at CNAO prescribes a treatment simulation and a delivery phase, performed in the CT and treatment rooms, respectively.

Evaluation of residual abdominal tumour motion in carbon ion gated treatments through respiratory motion modelling.

At the Italian National Centre for Oncologic Hadrontherapy (CNAO) patients with upper-abdominal tumours are being treated with carbon ion therapy, adopting the respiratory gating technique in combination with layered rescanning and abdominal compression to mitigate organ motion. Since online imaging of the irradiated volume is not feasible, this study proposes a modelling approach for the estimation of residual motion of the target within the gating window. The model extracts a priori respiratory motion information from the planning 4DCT using deformable image registration (DIR), then combines such information with the external surrogate signal recorded during dose delivery.

Commissioning of the 4-D treatment delivery system for organ motion management in synchrotron-based scanning ion beams.

Purpose: The aim of this work was the commissioning of delivery procedures for the treatment of moving targets in scanning pencil beam hadrontherapy.

Methods: EBT3 films fixed to the Anzai Respiratory Phantom were exposed to carbon ion scanned homogeneous fields (E=332MeV/u). To evaluate the interplay effect, field size and flatness for 3 different scenarios were compared to static condition: gated irradiation or repainting alone and combination of both.

MRI quantification of pancreas motion as a function of patient setup for particle therapy -a preliminary study.

Particle therapy (PT) has shown positive therapeutic results in local control of locally advanced pancreatic lesions. PT effectiveness is highly influenced by target localization accuracy both in space, since the pancreas is located in proximity to radiosensitive vital organs, and in time as it is subject to substantial breathing-related motion. The purpose of this preliminary study was to quantify pancreas range of motion under typical PT treatment conditions.