Publications by authors named "Alessandro Vai"

: Primary gynecological melanomas are rare malignancies with lower survival rates compared to cutaneous melanomas. Both preclinical and clinical data support the evidence that mucosal melanomas are photon-radioresistant but responsive to carbon ion radiotherapy (CIRT). The aim of this study is to assess, in a real-world cohort, the effectiveness and tolerability of radical CIRT in patients with inoperable gynecological mucosal melanoma.

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Purpose: There is debate about the optimal management of borderline resectable (bRe) and resectable (Re) pancreatic ductal adenocarcinoma (PDAC). Both preclinical and clinical evidence showed that carbon ion radiotherapy (CIRT) produces superior control on radioresistant histologies compared to conventional photon beam radiotherapy (RT). However, so far there is a lack of data concerning the integration of CIRT in a multimodal approach with chemotherapy and surgery for bRe/Re.

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Purpose: Modern photon radiotherapy effectively spares cardiac structures more than previous volumetric approaches. Still, it is related to non-negligible cardiac toxicity due to the low-dose bath of surrounding normal tissues. However, the dosimetric advantages of particle radiotherapy make it a promising treatment for para- and intra-cardiac tumours.

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The growing interest in proton therapy (PT) in recent decades is justified by the evidence that protons dose distribution allows maximal dose release at the tumor depth followed by sharp distal dose fall-off. But, in the holistic management of head and neck cancer (HNC), limiting the potential of PT to a mere dosimetric advantage appears reductive. Indeed, the precise targeting of PT may help evaluate the effectiveness of de-escalation strategies, especially for patients with human papillomavirus associated-oropharyngeal cancer (OPC) and nasopharyngeal cancer (NPC).

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Histone posttranslational modifications (PTMs) have crucial roles in a multitude of cellular processes, and their aberrant levels have been linked with numerous diseases, including cancer. Although histone PTM investigations have focused so far on methylations and acetylations, alternative long-chain acylations emerged as new dimension, as they are linked to cellular metabolic states and affect gene expression through mechanisms distinct from those regulated by acetylation. Mass spectrometry is the most powerful, comprehensive, and unbiased method to study histone PTMs.

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Article Synopsis
  • * A study involving 26 patients assessed the effectiveness of CIRT, finding a high overall response rate (97%) and robust local control rates (92% at 1 year and 83% at 2 years) without severe toxicity recorded.
  • * Results indicated that higher doses and more effective fractionation correlated with improved outcomes, suggesting that CIRT can be a safe option for patients, even those undergoing re-irradiation.
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Purpose: As carbon ion radiotherapy increases in use, there are limited phantom materials for heterogeneous or anthropomorphic phantom measurements. This work characterized the radiological clinical equivalence of several phantom materials in a therapeutic carbon ion beam.

Methods: Eight materials were tested for radiological material-equivalence in a carbon ion beam.

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  • Preserving hormone and reproductive functions in young female cancer patients undergoing pelvic radiation is crucial, yet the effects of carbon ion radiotherapy on fertility are not well understood.
  • This study highlights a successful pregnancy resulting from a case involving carbon ion radiotherapy for sacral chondrosarcoma.
  • A coordinated medical approach was used to position the ovaries and uterus away from radiation, allowing for both effective cancer treatment and the preservation of reproductive abilities, culminating in the birth of a healthy infant.
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In eukaryotes, the combination of different histone post-translational modifications (PTMs) - the histone code - impacts the chromatin organization as compact and transcriptionally silent heterochromatin or accessible and transcriptionally active euchromatin. Although specific histone PTMs have been studied in fungi, an overview of histone PTMs and their relative abundance is still lacking. Here, we used mass spectrometry to detect and quantify histone PTMs in three fungal species belonging to three distinct taxonomic sections of the genus Aspergillus (Aspergillus niger, Aspergillus nidulans (two strains), and Aspergillus fumigatus).

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Background And Purpose: Studies have shown large variations in stopping-power ratio (SPR) prediction from computed tomography (CT) across European proton centres. To standardise this process, a step-by-step guide on specifying a Hounsfield look-up table (HLUT) is presented here.

Materials And Methods: The HLUT specification process is divided into six steps: Phantom setup, CT acquisition, CT number extraction, SPR determination, HLUT specification, and HLUT validation.

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Purpose: To fully characterize the flat panel detector of the new Sphinx Compact device with scanned proton and carbon ion beams.

Materials And Methods: The Sphinx Compact is designed for daily QA in particle therapy. We tested its repeatability and dose rate dependence as well as its proportionality with an increasing number of particles and potential quenching effect.

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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.

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Epigenetics includes a complex set of processes that alter gene activity without modifying the DNA sequence, which ultimately determines how the genetic information common to all the cells of an organism is used to generate different cell types. Dysregulation in the deposition and maintenance of epigenetic features, which include histone posttranslational modifications (PTMs) and histone variants, can result in the inappropriate expression or silencing of genes, often leading to diseased states, including cancer. The investigation of histone PTMs and variants in the context of clinical samples has highlighted their importance as biomarkers for patient stratification and as key players in aberrant epigenetic mechanisms potentially targetable for therapy.

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Background: With rapid evolutions of fast and sophisticated calculation techniques and delivery technologies, clinics are almost facing a daily patient-specific (PS) plan adaptation, which would make a conventional experimental quality assurance (QA) workflow unlikely to be routinely feasible. Therefore, in silico approaches are foreseen by means of second-check independent dose calculation systems possibly handling machine log-files.

Purpose: To validate the in-house developed GPU-dose engine, FRoG, for light ion beam therapy (protons and carbon ions) as a second-check independent calculation system and to integrate machine log-file analysis into the patient-specific quality assurance (PSQA) program.

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Purpose /objective: To quantify benefits of robust optimization on multiple 4DCT acquisitions combined with off-line treatment adaptation for neoadjuvant carbon ion therapy (CIRT) of pancreatic cancer.

Material/methods: For 10 previously treated patients, 4DCTs were acquired around -15 (CT), -5 (RE), -1 (RE) and +6 (RE) days from RT start. Treatment plans were newly optimized to a dose prescription of 38.

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Undifferentiated carcinoma of the nasopharynx (NPC) is a rare disease, which usually occurs in the Asian population. Due to its anatomic location, it is characterised by rich lymph node drainage and has a high incidence of cervical node metastasis. However, cervical nodal metastasis commonly involves retropharyngeal nodes and level II nodes, followed by level III nodes.

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To evaluate the association between pretreatment diffusion-weighted MRI (DW-MRI) and 12-month radiological response in locally recurrent rectal cancer treated with carbon ion radiotherapy. Histogram analysis was performed on pretreatment DW-MRI for patients re-irradiated with carbon ion radiotherapy for local recurrence of rectal cancer. A total of 17 patients were enrolled in the study.

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Article Synopsis
  • The study focuses on identifying criteria for selecting sinonasal cancer patients with orbital invasion who may benefit from proton therapy, using NTCP models and dose-volume histogram parameters.
  • Twenty-two patients were evaluated with two radiation techniques—IMPT and VMAT—focusing on toxicity risk at different dose levels and analyzing various toxic endpoints.
  • Results indicated that a significant percentage (77.3%) of patients could benefit from IMPT over VMAT, particularly in terms of reducing damage to critical organs like the eyes and brain.
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(1) Background: we proposed an integrated strategy to support clinical allocation of nasopharyngeal patients between proton and photon radiotherapy. (2) Methods: intensity-modulated proton therapy (IMPT) plans were optimized for 50 consecutive nasopharyngeal carcinoma (NPC) patients treated with volumetric modulated arc therapy (VMAT), and differences in dose and normal tissue complication probability (ΔNTCPx-p) for 16 models were calculated. Patient eligibility for IMPT was assessed using a model-based selection (MBS) strategy following the results for 7/16 models describing the most clinically relevant endpoints, applying a model-specific ΔNTCPx-p threshold (15% to 5% depending on the severity of the complication) and a composite threshold (35%).

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Article Synopsis
  • - This study explores the effectiveness of using MRI to improve treatment accuracy in carbon-ion radiotherapy for pancreatic cancer, specifically focusing on respiratory motion variability that standard 4DCT might miss.
  • - Researchers developed a method to create virtual CT images from MRI data, allowing them to assess tumor movement and dose delivery more accurately across different treatment sessions and breathing cycles.
  • - Findings indicate that MRI can enhance treatment planning by effectively monitoring tumor displacement and dose variations, showing potential benefits in clinical settings for targeting pancreatic cancers with reduced risks to surrounding organs.
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Purpose: The robustness against setup and motion uncertainties of gated four-dimensional restricted robust optimization (4DRRO) was investigated for hypofractionated carbon ion radiotherapy (CIRT) of lung tumors.

Methods: CIRT plans of 9 patients were optimized using 4DRRO strategy with 3 mm setup errors, 3% density errors and 3 breathing phases related to the gate window. The prescription was 60 Gy(RBE) in 4 fractions.

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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.

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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.

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