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Internal or common carotid artery encasement (CAE) is observed in almost 2-7% of head and neck cancers (HNC) and designates the tumor with the T4b category. This clinical scenario is associated with a dismal prognosis, owing to the risk for thrombosis and bleeding that usually characterizes such an advanced cancer. Standardized radiological criteria to infer invasion of the carotid artery are lacking. Complete surgical resection in the context of a multimodality treatment is supposed to offer the greatest chances of cure. Surgery can either be carotid-sparing or include carotidectomy. Data on probability of cerebrovascular and non-cerebrovascular complications, risk of carotid blowout, poor oncologic outcomes, and less-than-certain efficacy of diagnostic and interventional preventive procedures against cerebral infarction make it difficult to define surgery as the recommended option among other therapeutic strategies. Non-surgical therapies based on radiation therapy possibly combined with chemotherapy are more frequently employed in HNC with CAE. In this context, carotid blowout is the most feared complication, and its probability increases with tumor stage and cumulative radiation dose received by the vessel. The use of highly conformal radiotherapies such as intensity-modulated particle therapy might substantially improve the manageability of HNC with CAE by possibly reducing the risk of late sequalae. Despite evidence is frail, it appears logical that a case-by-case evaluation through multidisciplinary decision making between head and neck surgeons, radiation oncologists, medical oncologists, diagnostic and interventional radiologists, and vascular surgeons are of paramount value to offer the best therapeutic solution to patients affected by HNC with CAE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Orlandi, Ferrari, Lafe, Preda, Benazzo, Vischioni, Bonora, Rampinelli, Schreiber, Licitra and Nicolai.)

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Objective: The theoretical advantages of augmented reality (AR) with diffusion tensor imaging (DTI)-based high-definition fiber tractography (HDFT) and sodium fluorescein (F) in high-grade glioma (HGG) surgery have not been investigated in detail. In this study, the authors aimed to evaluate the safety and efficacy profiles of HDFT-F microscope-based AR cytoreductive surgery for newly diagnosed supratentorial HGGs., Methods: Data of patients with newly diagnosed supratentorial HGGs who underwent surgery using the AR HDFT-F technique were reviewed and compared with those of a cohort of patients who underwent conventional white-light surgery assisted by infrared neuronavigation. The safety and efficacy of the techniques were reported based on the postoperative Neurological Assessment in Neuro-Oncology (NANO) scores, extent of resection (EOR), and Kaplan-Meier curves, respectively. The chi-square test was conducted for categorical variables. A p value < 0.05 was considered statistically significant., Results: A total of 54 patients underwent surgery using the AR HDFT-F technique, and 63 underwent conventional white-light surgery assisted by infrared neuronavigation. The mean postoperative NANO scores were 3.8 ± 2 and 5.2 ± 4 in the AR HDFT-F group and control group, respectively (p < 0.05). The EOR was higher in the AR HDFT-F group (p < 0.05) than in the control group. With a mean follow-up of 12.2 months, the rate of progression-free survival (PFS) was longer in the study group (log-rank test, p = 0.006) than in the control group. Moreover, the complication rates were 9.2% and 9.5% in the study and control groups, respectively., Conclusions: Overall, AR HDFT-F-assisted surgery is safe and effective in maximizing the EOR and PFS rate for patients with newly diagnosed supratentorial HGGs, and in optimizing patient functional outcomes.

Objectives: The aim of this study was to describe the radiological features of chronic thromboembolic pulmonary disease (CTEPD), not yet systematically described in the literature. Furthermore, we compared vascular scores between CTEPD and chronic thromboembolic pulmonary hypertension (CTEPH) patients, trying to explain why pulmonary hypertension does not develop at rest in CTEPD patients., Methods: Eighty-five patients (40 CTEPD, 45 CTEPH) referred to our centre for pulmonary endarterectomy underwent dual-energy computed tomography pulmonary angiography (DE-CTPA) with iodine perfusion maps; other 6 CTEPD patients underwent single-source CTPA. CT scans were reviewed independently by an experienced cardiothoracic radiologist and a radiology resident to evaluate scores of vascular obstruction, hypoperfusion and mosaic attenuation, signs of pulmonary hypertension and other CT features typical of CTEPH., Results: Vascular obstruction burden was similar in the two groups (p = 0.073), but CTEPD patients have a smaller extension of perfusion defects in the iodine map (p = 0.009) and a smaller number of these patients had mosaic attenuation (p < 0.001) than CTEPH patients, suggesting the absence of microvascular disease. Furthermore, as expected, the two groups were significantly different considering the indirect signs of pulmonary hypertension (p < 0.001)., Conclusions: CTEPD and CTEPH patients have significantly different radiological characteristics, in terms of signs of pulmonary hypertension, mosaic attenuation and iodine map perfusion extension. Importantly, our results suggest that the absence of peripheral microvascular disease, even in presence of an important thrombotic burden, might be the reason for the absence of pulmonary hypertension in CTEPD., Key Points: • CTEPD and CTEPH patients have significantly different radiological characteristics. • The absence of peripheral microvascular disease might be the reason for the absence of pulmonary hypertension in CTEPD., (© 2021. The Author(s).)

Purpose: To assess early microstructural changes of meningiomas treated with proton therapy through quantitative analysis of intravoxel incoherent motion (IVIM) and diffusion-weighted imaging (DWI) parameters., Methods: Seventeen subjects with meningiomas that were eligible for proton therapy treatment were retrospectively enrolled. Each subject underwent a magnetic resonance imaging (MRI) including DWI sequences and IVIM assessments at baseline, immediately before the 1st (t0), 10th (t10), 20th (t20), and 30th (t30) treatment fraction and at follow-up. Manual tumor contours were drawn on T2-weighted images by two expert neuroradiologists and then rigidly registered to DWI images. Median values of the apparent diffusion coefficient (ADC), true diffusion (D), pseudo-diffusion (D*), and perfusion fraction (f) were extracted at all timepoints. Statistical analysis was performed using the pairwise Wilcoxon test., Results: Statistically significant differences from baseline to follow-up were found for ADC, D, and D* values, with a progressive increase in ADC and D in conjunction with a progressive decrease in D*. MRI during treatment showed statistically significant differences in D values between t0 and t20 (p = 0.03) and t0 and t30 (p = 0.02), and for ADC values between t0 and t20 (p = 0.04), t10 and t20 (p = 0.02), and t10 and t30 (p = 0.035). Subjects that showed a volume reduction greater than 15% of the baseline tumor size at follow-up showed early D changes, whereas ADC changes were not statistically significant., Conclusion: IVIM appears to be a useful tool for detecting early microstructural changes within meningiomas treated with proton therapy and may potentially be able to predict tumor response.

Objectives: The main aim was to assess the performance and cutoff value for the detection of liver steatosis (grade S > 0) with the Attenuation Imaging-Penetration (ATI-Pen) algorithm available on the Aplio i-series ultrasound systems (Canon Medical Systems, Otawara, Japan). The magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) was used as the reference standard. Secondary aims were to compare the results to those obtained with the previous ATI algorithm (Attenuation Imaging-General [ATI-Gen]) and with the controlled attenuation parameter (CAP) and to generate a regression equation between ATI-Pen and ATI-Gen values., Methods: Consecutive adult patients potentially at risk of liver steatosis were prospectively enrolled. Each patient underwent ultrasound quantification of liver steatosis with ATI-Pen and ATI-Gen and a CAP assessment with the FibroScan system (Echosens, Paris, France). The MRI-PDFF evaluation was performed within a week. The correlations between ATI-Pen, ATI-Gen, the CAP, and the MRI-PDFF were analyzed with the Pearson rank correlation coefficient. The diagnostic performance of ATI-Pen, ATI-Gen, and the CAP was assessed with receiver operating characteristic curves and an area under the receiver operating characteristic curve (AUROC) analysis., Results: Seventy-two individuals (31 male and 41 female) were enrolled. Correlation coefficients of ATI-Pen, ATI-Gen, and the CAP with the MRI-PDFF were 0.78, 0.83, and 0.58, respectively. The AUROCs of ATI-Pen, ATI-Gen, and the CAP for detecting steatosis (S > 0) were 0.90 (95% confidence interval, 0.81-0.96), 0.92 (0.82-0.98), and 0.85 (0.74-0.92), and the cutoffs were greater than 0.69 dB/cm/MHz, greater than 0.62 dB/cm/MHz, and greater than 273 dB/m. The regression equation between ATI-Pen and ATI-Gen was ATI-Pen = 0.88 ATI-Gen + 0.13., Conclusions: Attenuation Imaging is a reliable tool for detecting liver steatosis, showing an excellent correlation with the MRI-PDFF and high performance with AUROCs of 0.90 or higher., (© 2020 The Authors. Journal of Ultrasound in Medicine published by Wiley Periodicals LLC on behalf of American Institute of Ultrasound in Medicine.)

Background and objectives: In patients who receive antiplatelet therapy (APT), the bleeding risk profile after mild head trauma (MHT) still needs clarification. Some studies have demonstrated an association with bleeding risk, whereas others have not. We studied the population of our level II emergency department (ED) trauma center to determine the risk of bleeding in patients receiving APT and whether bleeding results not from antiplatelet agents but rather from age. We assessed the bleeding risk, the incidence of intracranial hemorrhage (ICH) that necessitated hospitalization for observation, the need for cranial neurosurgery, the severity of the patient's condition at discharge, and the frequency of ED revisits for head trauma in patients receiving APT. Materials and Methods: This retrospective single-center study included 483 patients receiving APT who were in the ED for MHT in 2019. The control group consisted of 1443 patients in the ED with MHT over the same period who were not receiving APT or anticoagulant therapy. Our ED diagnostic therapeutic protocol mandates both triage and the medical examination to identify patients with MHT who are taking any anticoagulant or APT. Results: APT was not significantly associated with bleeding risk ( p > 0.05); as a risk factor, age was significantly associated with the risk of bleeding, even after adjustment for therapy. Patients receiving APT had a greater need of surgery (1.2% vs. 0.4%; p < 0.0001) and a higher rate of hospitalization (52.9% vs. 37.4%; p < 0.0001), and their clinical condition was more severe (evaluated according to the exit code value on a one-dimensional quantitative five-point numerical scale) at the time of discharge ( p = 0.013). The frequency of ED revisits due to head trauma did not differ between the two groups. Conclusions: The risk of bleeding in patients receiving APT who had MHT was no higher than that in the control group. However, the clinical condition of patients receiving APT, including hospital admission for ICH monitoring and cranial neurosurgical interventions, was more severe.

Introduction : Radiomics extracts a large amount of quantitative information from medical images using specific data characterization algorithms. This information, called radiomic features, can be combined with clinical data to build prediction models for prognostic evaluation and treatment selection. Areas covered : We outlined a series of studies investigating the correlation between radiomics features and outcome (prognostic) as well as response to therapy (predictive) in non-small cell lung cancer (NSCLC). We performed our analysis both in the setting of early and advanced stage of disease, with a focus on the different therapies and imaging modalities adopted. Expert opinion : The prognostic and predictive potential of the radiomic approach, combined with clinical models, could help decision-making process and guide toward the creation of an optimal and 'tailored' therapeutic strategy for lung cancer patients. However, due to the low reproducibility of most of the conducted studies and the lack of validated results, such a desirable scenario has not yet been translated to routine clinical practice.

Purpose: We aimed to evaluate the feasibility, accuracy, and safety of Programmed Death-1/ Programmed Death-Ligand 1 (PD-1/ PD-L1) expression quantification in cytology cell-block samples obtained through transthoracic CT-guided fine-needle aspiration cytology (FNAC) from the interventional radiologist's perspective., Methods: We performed a consecutive unselected series of 361 CT-guided biopsies of pulmonary nodules and masses which came to our observation from June 2017 to October 2018. For each case, exhaustive clinical, morphologic, molecular and tomographic data were available. All the material obtained was fixed in formalin to obtain a cell-block for the pathologist, who performed immunohistochemical analysis to detect PD-L1 expression levels on each sample., Results: Of all the analyzed samples, 93.6% (338/361) were defined to be diagnostic, including neoplastic (72%, 260/361) and non-neoplastic lesions (21.6%, 78/361); only 6.4% (23/361) of them resulted in nondiagnostic specimens. Non-small cell lung cancer (NSCLC) accounted for 73.8% of neoplastic lesions (192/260): most of them were adenocarcinoma (83%, 160/192), followed by squamous carcinoma (14%, 27/192) and poorly differentiated carcinoma (3%, 5/192). In 96% of NSCLC (184/192), the diagnosis was reached either in the absence of complications or with early minor complications. PD-L1 expression was evaluated in all 192 NSCLC cytology specimens: 180 immunostainings were found to be adequate for PD-L1 testing. In 76% of cases, PD-L1 expression level was lower than 50%., Conclusion: The findings of our study indicate that PD-L1 quantification using a cell-block approach on CT-guided FNAC is a feasible and safe technique and should be taken into account alongside with core biopsy approach, especially in case of advanced disease and/or fragile and older patients.

Purpose: Proton therapy could benefit from noninvasively gaining tumor microstructure information, at both planning and monitoring stages. The anatomical location of brain tumors, such as meningiomas, often hinders the recovery of such information from histopathology, and conventional noninvasive imaging biomarkers, like the apparent diffusion coefficient (ADC) from diffusion-weighted MRI (DW-MRI), are nonspecific. The aim of this study was to retrieve discriminative microstructural markers from conventional ADC for meningiomas treated with proton therapy. These markers were employed for tumor grading and tumor response assessment., Methods: DW-MRIs from patients affected by meningioma and enrolled in proton therapy were collected before (n = 35) and 3 months after (n = 25) treatment. For the latter group, the risk of an adverse outcome was inferred by their clinical history. Using Monte Carlo methods, DW-MRI signals were simulated from packings of synthetic cells built with well-defined geometrical and diffusion properties. Patients' ADC was modeled as a weighted sum of selected simulated signals. The weights that best described a patient's ADC were determined through an optimization procedure and used to estimate a set of markers of tumor microstructure: diffusion coefficient (D), volume fraction (vf), and radius (R). Apparent cellularity (ρ app ) was estimated from vf and R for an easier clinical interpretability. Differences between meningothelial and atypical subtypes, and low- and high-grade meningiomas were assessed with nonparametric statistical tests, whereas sensitivity and specificity with ROC analyses. Similar analyses were performed for patients showing low or high risk of an adverse outcome to preliminary evaluate response to treatment., Results: Significant (P < 0.05) differences in median ADC, D, vf, R, and ρ app values were found when comparing meningiomas' subtypes and grades. ROC analyses showed that estimated microstructural parameters reached higher specificity than ADC for subtyping (0.93 for D and vf vs 0.80 for ADC) and grading (0.75 for R vs 0.67 for ADC). High- and low-risk patients showed significant differences in ADC and microstructural parameters. The skewness of ρ app was the parameter with highest AUC (0.90) and sensitivity (0.75)., Conclusions: Matching measured with simulated ADC yielded a set of potential imaging markers for meningiomas grading and response monitoring in proton therapy, showing higher specificity than conventional ADC. These markers can provide discriminative information about spatial patterns of tumor microstructure implying important advantages for patient-specific proton therapy workflows., (© 2020 American Association of Physicists in Medicine.)

Objectives: Changes in mechanical loading as well as pathology can modify the Achilles tendon mechanical properties and therefore detection of these changes is relevant for the diagnosis and management of Achilles tendinopathy. The aim of this study was to evaluate strain and shear wave sonoelastography for their ability to detect changes in the Achilles tendon mechanical properties during a series of isometric contractions., Methods: Longitudinal sonoelastography images of the Achilles tendon were acquired from 20 healthy participants using four different ultrasound devices; two implementing strain sonoelastography technology (SE1, SE2) and two, shear wave elastography technology (SWE1, SWE2)., Results: SE1 measured a decreasing strain ratio (tendon become harder) during the different contraction levels from 1.51 (0.92) to 0.33 (0.16) whereas SE2 mesaured a decreasing strain ratio from 1.08 (0.76) to 0.50 (0.32). SWE1 measured decreasing tendon stiffness during contractions of increasing intensity from 33.40 (19.61) to 16.19 (2.68) whereas SWE2 revealed increasing tendon stiffness between the first two contraction levels from 428.65 (131.5) kPa to 487.9 (121.5) kPa followed by decreasing stiffness for the higher contraction levels from 459.35 (113.48) kPa to 293.5 (91.18) kPa., Conclusions: Strain elastography used with a reference material was able to detect elasticity changes between the different contraction levels whereas shear wave elastography was less able to detect changes in Achilles tendon stiffness when under load. Inconsistent results between the two technologies should be further investigated.

Skull-base chordoma (SBC) can be treated with carbon ion radiotherapy (CIRT) to improve local control (LC). The study aimed to explore the role of multi-parametric radiomic, dosiomic and clinical features as prognostic factors for LC in SBC patients undergoing CIRT. Before CIRT, 57 patients underwent MR and CT imaging, from which tumour contours and dose maps were obtained. MRI and CT-based radiomic, and dosiomic features were selected and fed to two survival models, singularly or by combining them with clinical factors. Adverse LC was given by in-field recurrence or tumour progression. The dataset was split in development and test sets and the models' performance evaluated using the concordance index (C-index). Patients were then assigned a low- or high-risk score. Survival curves were estimated, and risk groups compared through log-rank tests (after Bonferroni correction α = 0.0083). The best performing models were built on features describing tumour shape and dosiomic heterogeneity (median/interquartile range validation C-index: 0.80/024 and 0.79/0.26), followed by combined (0.73/0.30 and 0.75/0.27) and CT-based models (0.77/0.24 and 0.64/0.28). Dosiomic and combined models could consistently stratify patients in two significantly different groups. Dosiomic and multi-parametric radiomic features showed to be promising prognostic factors for LC in SBC treated with CIRT.

Objective: The aim of the study was to retrospectively evaluate the prevalence of reported and unreported potentially important incidental findings (PIFs) in consecutive nonenhanced abdominal CTs performed specifically for renal colic in the urgent setting., Methods: One radiologist, blinded to the finalized report, retrospectively re-evaluated nonenhanced abdominal CTs performed from January to December 2017 on adult patients from the emergency department with the specific request of urgent evaluation for renal colic, searching for PIFs., Results: The CTs of 312 patients were included in the study. Thirty-eight findings were reported in 38 different CTs, whereas the re-evaluation added 47 unreported findings in 47 different CTs, adding to total of 85 findings (27%). The difference in the proportion of reported and unreported PIFs between the original report and re-evaluation was significant (p < 0.001). No significant difference was found between the age of patients with and without reported findings. The proportion of potentially important findings did not vary significantly among the 3 shifts in the original report and in re-evaluation. The most frequent findings, both reported and unreported, were pleural effusion, lymphadenopathies, and liver nodules., Conclusions: Potentially important additional findings are frequently present in urgent nonenhanced abdominal CTs performed for renal colic, and many are not described in the finalized reports. Radiologists should take care not to underreport PIFs even in the urgent setting because of the possible consequences on the patient's health and in order to avoid legal issues, while at the same time satisfying the need for timely and efficient reporting., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Objective: Postoperative radiotherapy (PORT) is indicated in almost two-thirds of patients treated with transoral robotic surgery (TORS) for head and neck tumors. The aim of this study was to quantify the toxicity profile of patients treated with PORT after TORS in oropharyngeal and supraglottic laryngeal cancer focusing on soft tissue necrosis (STN)., Methods: We retrospectively reviewed 28 patients. Acute and late toxicity were examined. Incidence and severity of STN were recorded., Results: No patient experienced acute grade 3 skin or mucosal toxicity; 1 patient had grade 3 dysphagia. At 12 months, no evaluated patient required enteral nutrition and 2 patients had tracheostomy. STN occurred in 4 (14%) patients: 3 out of 4 (75%) patients with STN had diabetes, whereas 6 out of 13 (25%) patients without STN had diabetes ( p = 0.05)., Conclusion: We found an acceptable toxicity profile of PORT performed after a TORS procedure. Diabetes mellitus might be a risk factor for STN.

Purpose: Meningiomas are mainly benign tumors, though a considerable proportion shows aggressive behaviors histologically consistent with atypia/anaplasia. Histopathological grading is usually assessed through invasive procedures, which is not always feasible due to the inaccessibility of the lesion or to treatment contraindications. Therefore, we propose a multi-parametric MRI assessment as a predictor of meningioma histopathological grading., Methods: Seventy-three patients with 74 histologically proven and previously treated meningiomas were retrospectively enrolled (42 WHO I, 24 WHO II, 8 WHO III) and studied with MRI including T2 TSE, FLAIR, Gradient Echo, DWI, and pre- and post-contrast T1 sequences. Lesion masks were segmented on post-contrast T1 sequences and rigidly registered to ADC maps to extract quantitative parameters from conventional DWI and intravoxel incoherent motion model assessing tumor perfusion. Two expert neuroradiologists assessed morphological features of meningiomas with semi-quantitative scores., Results: Univariate analysis showed different distributions (p < 0.05) of quantitative diffusion parameters (Wilcoxon rank-sum test) and morphological features (Pearson's chi-square; Fisher's exact test) among meningiomas grouped in low-grade (WHO I) and higher grade forms (WHO II/III); the only exception consisted of the tumor-brain interface. A multivariate logistic regression, combining all parameters showing statistical significance in the univariate analysis, allowed discrimination between the groups of meningiomas with high sensitivity (0.968) and specificity (0.925). Heterogeneous contrast enhancement and low ADC were the best independent predictors of atypia and anaplasia., Conclusion: Our multi-parametric MRI assessment showed high sensitivity and specificity in predicting histological grading of meningiomas. Such an assessment may be clinically useful in characterizing lesions without histological diagnosis. Key points • When surgery and biopsy are not feasible, parameters obtained from both conventional and diffusion-weighted MRI can predict atypia and anaplasia in meningiomas with high sensitivity and specificity. • Low ADC values and heterogeneous contrast enhancement are the best predictors of higher grade meningioma.

Radiomics focuses on extracting a large number of quantitative imaging features and testing both their correlation with clinical characteristics and their prognostic and predictive values. We propose a radiomic approach using magnetic resonance imaging (MRI) to decode the tumor phenotype and local recurrence in oropharyngeal squamous cell carcinoma (OPSCC). The contrast-enhanced T1-weighted sequences from baseline MRI examinations of OPSCC patients treated between 2008 and 2016 were retrospectively selected. Radiomic features were extracted using the IBEX software, and hiegrarchical clustering was applied to reduce features redundancy. The association of each radiomic feature with tumor grading and stage, HPV status, loco-regional recurrence within 2 years, considered as main endpoints, was assessed by univariate analysis and then corrected for multiple testing. Statistical analysis was performed with SAS/STAT® software. Thirty-two eligible cases were identified. For each patient, 1286 radiomic features were extracted, subsequently grouped into 16 clusters. Higher grading (G3 vs. G1/G2) was associated with lower values of GOH/65Percentile and GOH/85Percentile features (p=0.04 and 0.01, respectively). Positive HPV status was associated with higher values of GOH/10Percentile (p=0.03) and lower values of GOH/90Percentile (p=0.03). Loco-regional recurrence within 2 years was associated with higher values of GLCM3/4-7Correlation (p=0.04) and lower values of GLCM3/2-1InformationMeasureCorr1 (p=0.04). Results lost the statistical significance after correction for multiple testing. T stage was significantly correlated with 9 features, 4 of which (GLCM25/180-4InformationMeasureCorr2, Shape/MeanBreadth, GLCM25/90-1InverseDiffMomentNorm, and GLCM3/6-1InformationMeasureCorr1) retained statistical significance after False Discovery Rate correction. MRI-based radiomics is a feasible and promising approach for the prediction of tumor phenotype and local recurrence in OPSCC. Some radiomic features seem to be correlated with tumor characteristics and oncologic outcome however, larger collaborative studies are warranted in order to increase the statistical power and to obtain robust and validated results.

Aim: To provide a literature review on risk factors and strategies to prevent acute carotid blowout (CBO) syndrome in patients who underwent reirradiation (reRT) for recurrent head and neck (HN) malignancies., Patients and Methods: Inclusion criteria were: 1) CBO following reRT in the HN region, 2) description on patient-, tumor- or treatment-related risk factors, 3) clinical or radiological signs of threatened or impending CBO, and 4) CBO prevention strategies., Results: Thirty-five studies were selected for the analysis from five hundred seventy-seven records. Results provided indications on clinical, radiological and dosimetric parameters possibly associated with higher risk of CBO. Endovascular procedures (artery occlusion and stenting) to prevent acute massive hemorrhage in high risk patients were discussed., Conclusion: Literature data are still scarce with a low level of evidence. Nevertheless, the present work provides a comprehensive review useful for clinicians as a multidisciplinary pragmatic tool in their clinical practice., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To analyze the most frequent radiographic features of COVID-19 pneumonia and assess the effectiveness of chest X-ray (CXR) in detecting pulmonary alterations., Materials and Methods: CXR of 240 symptomatic patients (70% male, mean age 65 ± 16 years), with SARS-CoV-2 infection confirmed by RT-PCR, was retrospectively evaluated. Patients were clustered in four groups based on the number of days between symptom onset and CXR: group A (0-2 days), 49 patients; group B (3-5), 75 patients; group C (6-9), 85 patients; and group D (> 9), 31 patients. Alteration's type (reticular/ground-glass opacity (GGO)/consolidation) and distribution (bilateral/unilateral, upper/middle/lower fields, peripheral/central) were noted. Statistical significance was tested using chi-square test., Results: Among 240 patients who underwent CXR, 180 (75%) showed alterations (group A, 63.3%; group B, 72%; group C, 81.2%; group D, 83.9%). GGO was observed in 124/180 patients (68.8%), reticular alteration in 113/180 (62.7%), and consolidation in 71/180 (39.4%). Consolidation was significantly less frequent (p < 0.01). Distribution among groups was as follows: reticular alteration (group A, 70.9%; group B, 72.2%; group C, 57.9%; group D, 46.1%), GGO (group A, 67.7%; group B, 62.9%; group C, 71%; group D, 76.9%), and consolidation (group A, 35.5%; group B, 31.4%; group C, 47.8%; group D, 38.5%). Alterations were bilateral in 73.3%. Upper, middle, and lower fields were involved in 36.7%, 79.4%, and 87.8%, respectively. Lesions were peripheral in 49.4%, central in 11.1%, or both in 39.4%. Upper fields and central zones were significantly less involved (p < 0.01)., Conclusions: The most frequent lesions in COVID-19 patients were GGO (intermediate/late phase) and reticular alteration (early phase) while consolidation gradually increased over time. The most frequent distribution was bilateral, peripheral, and with middle/lower predominance. Overall rate of negative CXR was 25%, which progressively decreased over time., Key Points: • The predominant lung changes were GGO and reticular alteration, while consolidation was less frequent. • The typical distribution pattern was bilateral, peripheral, or both peripheral and central and involved predominantly the lower and middle fields. • Chest radiography showed lung abnormalities in 75% of patients with confirmed SARS-CoV-2 infection, range varied from 63.3 to 83.9%, respectively, at 0-2 days and > 9 days from the onset of symptoms.

Background: The aim of this study is to evaluate results in terms of local control (LC), overall survival (OS), and toxicity profile and to better identify factors influencing clinical outcome of skull base chordoma treated with proton therapy (PT) and carbon ion radiotherapy (CIRT)., Methods: We prospectively collected and analyzed data of 135 patients treated between November 2011 and December 2018. Total prescription dose in the PT group (70 patients) and CIRT group (65 patients) was 74 Gy relative biological effectiveness (RBE) delivered in 37 fractions and 70.4 Gy(RBE) delivered in 16 fractions, respectively (CIRT in unfavorable patients). LC and OS were evaluated using the Kaplan-Meier method. Univariate and multivariate analyses were performed, to identify prognostic factors on clinical outcomes., Results: After a median follow-up of 44 (range, 6-87) months, 14 (21%) and 8 (11%) local failures were observed in CIRT and PT group, respectively. Five-year LC rate was 71% in CIRT cohort and 84% in PT cohort. The estimated 5-year OS rate in the CIRT and PT group was 82% and 83%, respectively. On multivariate analysis, gross tumor volume (GTV), optic pathways, and/or brainstem compression and dose coverage are independent prognostic factors of local failure risk. High rate toxicity grade ≥3 was reported in 11% of patients., Conclusions: Particle radiotherapy is an effective treatment for skull base chordoma with acceptable late toxicity. GTV, optic pathways, and/or brainstem compression and target coverage were independent prognostic factors for LC., Key Points: • Proton and carbon ion therapy are effective and safe in skull base chordoma.• Prognostic factors are GTV, organs at risk compression, and dose coverage.• Dual particle therapy and customized strategy was adopted., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Carpal tunnel release for compression of the median nerve at the wrist is a common procedure, often resulting in good clinical outcomes. There are, however, many anatomical variations in and around the carpal tunnel and it is important to be aware of these during carpal tunnel release. After surgery, recurrent carpal tunnel syndrome is uncommon, but difficult to diagnose and treat. Ultrasonography is often necessary for the evaluation of the anatomical variations before carpal tunnel release and to evaluate the most common complications after carpal tunnel release.

Disorders affecting the ulnar nerve in the elbow are common in clinical practice. The diagnosis is based on clinical evaluation and electrodiagnostic tests, but imaging examinations are frequently necessary, particularly for the identification of the structures associated with nerve compression. The purpose of this video article is to review the anatomy, the pathology, scanning techniques, and sonographic appearance of the ulnar nerve in the elbow.

Lung ultrasound gained a leading position in the last year as an imaging technique for the assessment and management of patients with acute respiratory failure. In coronavirus disease 2019 (COVID-19), its role may be of further importance because it is performed bedside and may limit chest X-ray and the need for transport to radiology for computed tomography (CT) scan. Since February 21, we progressively turned into a coronavirus-dedicated intensive care unit and applied an ultrasound-based approach to avoid traditional imaging and limit contamination as much as possible. We performed a complete daily examination with lung ultrasound score computation and systematic search of complications (pneumothorax, ventilator-associated pneumonia); on-duty physicians were free to perform CT or chest X-ray when deemed indicated. We compared conventional imaging exams performed in the first 4 wk of the COVID-19 epidemic with those in the same time frame in 2019: there were 84 patients in 2020 and 112 in 2019; 64 and 22 (76.2% vs. 19.6%, p < 0.001) had acute respiratory failure, respectively, of which 55 (85.9%) were COVID-19 in 2020. When COVID-19 patients in 2020 were compared with acute respiratory failure patients in 2019, the median number of chest X-rays was 1.0 (1.0-2.0) versus 3.0 (1.0-4.0) (p = 0.0098); 2 patients 2 (3.6%) versus 7 patients (31.8%) had undergone at least one thoracic CT scan (p = 0.001). A self-imposed ultrasound-based approach reduces the number of chest X-rays and thoracic CT scans in COVID-19 patients compared with patients with standard acute respiratory failure, thus reducing the number of health care providers exposed to possible contamination and sparing personal protective equipment., Competing Interests: Conflict of interest disclosure S.M. received fees for lectures from GE Healthcare, outside the present work. A.O. received fees for manuscript preparation from Hamilton Medical, outside the present work. M.P. received fees for lectures from Hamilton Medical, outside the present work. L.C. received fees for lectures by GE Healthcare, outside the present work. G.T. received fees for lectures by GE Healthcare, outside the present work. G.A.I. received fees for lectures by Hamilton Medical, Eurosets, Getinge, Intersurgical SpA, and Burke & Burke, outside the present work. F.M. received fees for lectures from GE Healthcare, Hamilton Medical, and SEDA SpA, outside the present work. There is an active research agreement between University of Pavia and Hamilton Medical, outside the present work., (Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Purpose: In image-guided particle radiotherapy of abdominal lesions, respiratory motion hinders treatment accuracy. In this study, 2D cineMRI data were used to quantify the tumor (GTV) motion and to evaluate the clinical approach based on deriving an internal target volume (ITV) from a planning 4DCT for gating treatments., Methods: Seven patients with abdominal lesions were treated with carbon-ion therapy at the National Centre of Oncological Hadron-therapy (Italy). The MR scan was performed on the same day of the 4DCT acquisition. For four patients, an additional MR was acquired approximately after 1 week. The cineMRI combined with deformable image registration algorithm was used to quantify tumor motion. Afterwards, two ITVs were defined considering (1) all phases (ITV FB ) and (2) only phases within the gating window (ITV G ), and then compared with the clinical (4DCT-derived) ITVs (ITV CG and ITV CFB )., Results: Tumor residual motion estimated by cineMRI data in the two MRI sessions resulted not significantly different from 4DCT, although cineMRI accounted for cycle-to-cycle variations. The ITV normalized for the GTV median values were higher for ITV FB with respect to ITV G , ITV CFB and ITV CG . The Hausdorff distances with respect to the GTV were up to 10.55 mm, 3.13 mm, 5.56 mm and 2.51 mm, for ITV FB , ITV G , ITV CFB and ITV CG , respectively. According to both metrics, ITV CG and ITV G were not found significantly different., Conclusions: CineMRI acquisitions allowed to quantify organ motion without delivering additional dose to the patient and to verify treatment margins in gated carbon-ion therapy of abdominal lesions., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Background/aim: Re-irradiation of locally recurrent rectal cancer poses challenges due to the proximity of critical organs, such as the bowel. This study aimed at evaluating the safety and efficacy of re-irradiation with Carbon Ion Radiotherapy (CIRT) in rectal cancer patients with local recurrence., Patients and Methods: Between 2014 and 2018, 14 patients were treated at the National Center of Oncological Hadrontherapy (CNAO Foundation) with CIRT for locally recurrent rectal cancer., Results: All patients concluded the treatment. No G≥3 acute/late reaction nor pelvic infections were observed. The 1-year and 2-year local control rates were, 78% and 52%, respectively, and relapse occurred close to the bowel in 6 patients. The 1-year and 2-year overall survival rates were 100% and 76.2% each; while the 1-year and 2-year metastasis free survival rates were 64.3% and 43%., Conclusion: CIRT as re-irradiation for locally recurrent rectal cancer emerges as a safe and valid treatment with an acceptable rate of morbidity of surrounding healthy tissue., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To evaluate if baseline ADC from DWI sequences could predict response to treatment in patients with sacral chordoma not suitable for surgery treated with carbon ion radiotherapy (CIRT) alone compared with volume changes., Methods: Fifty-nine patients with sacral chordoma not suitable for surgery underwent one cycle of CIRT alone and a minimum of 12-months follow-up. All patients underwent MRI before treatment (baseline), every three months in the first two years after treatment, and every six months afterwards. For each MRI, lesion volume was obtained and median, kurtosis, and skewness ADC were analyzed within the whole lesion volume. Volume changes between baseline and the last available follow-up were used to divide patients with partial response, progression of disease and stable disease (PR, PD, and SD)., Results: Ten patients were excluded since DWI sequences from baseline MRI were not available. ADC maps obtained from baseline DWI examinations of 50 lesions in the remaining 49 patients were considered. Seven lesions were categorized as PD, 30 PR, and 13 SD. PD showed significantly higher median ADC values at baseline (p = 0.003) compared with both PR and SD (1665vs1253vs1263 *10 -6 mm²/s), and more negative skewness values (-0.26vs0.26vs0.08), although not significantly different (p = 0.16)., Conclusions: Preliminary results suggest that baseline ADC could predict response to treatment with CIRT, particularly to detect potential non-responder patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background/aim: Definitive radiotherapy for bone and soft tissues sarcomas benefits patients deemed unfit for surgery; poor outcomes have been reported with conventional photons, while interesting preliminary results have been described with particle in single-Institution experiences. The aim of the study was to retrospectively evaluate preliminary results of carbon ion radiotherapy (CIRT) in patients with axial bone and soft tissue sarcomas (BSTS) treated with curative intent at the National Center for Oncological Hadrontherapy (CNAO)., Patients and Methods: From January 2013 to September 2018, 54 patients with axial BSTS were treated with CIRT at CNAO. Their median age was 50 years (range=19-79 years), males/females=1.4:1. Tumor site was the pelvis in 50% of cases (n=27), thoracic region in 24% (n=13), cervical spine in 15% (n=8) and lumbar in 11% (n=6). A total of 76% (n=41) of patients had primary disease, while 24% (n=13) had recurrent disease. Before CIRT, surgery was performed in 47% of cases, including positive margins (R1) in 8 patients, and macroscopic residual disease (R2) in 17. Histological subtypes were mainly represented by chondrosarcomas in 39% (n=21) of patients and osteosarcomas in 24% (n=13). Pre-treatment chemotherapy was administered in 40% of cases (n=22); no patient received previous radiotherapy. All treatments were performed with active scanning CIRT for a median total dose of 73.6 Gy (range=70.4-76.8 Gy), in 16 fractions (4 fractions per week)., Results: Median follow-up was 24 months (range=4-61 months). Four patients were lost to follow-up. Acute toxicities were mild, no >G2 event was reported and no treatment interruption was required. For late toxicity, only G3 neuropathy was detected in 4% of cases (n=2). With a median time to local progression of 13 months (3-35), 15 local failures were observed, resulting in 2- and 3-year local control rates of 67.4% for both. Distant progression occurred in 12 patients, with 1-year progression-free survival (PFS) rate of 97.5%; 2- and 3-year rates were 92.2%. Fifteen patients died resulting in 1- 2- and 3-years overall survival (OS) rates of 87.1%, 75.4% and 64%, respectively. At log-rank test, gross total volume (GTV) >1,000 ml was found to be predictive of local failure (p=0.04), pre-treatment chemotherapy was found to be significantly related to PFS and OS (p=0.02 and p=0.016); also, recurrent disease and distant progression were significantly related to OS (p=0.019 and p=0.0013). Cox proportional-hazards model confirmed that GTV >1,000 ml was related to worse local control (p=0.0010)., Conclusion: CIRT for axial BSTS resulted in mild toxicity, showing promising results in terms of clinical outcomes. A longer follow-up is warranted., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Preoperative imaging impacts treatment planning and prognosis in laryngeal cancers. We investigated the accuracy of standard computed tomography (CT) in evaluating tumor invasions at critical glottic areas., Methods: CT scans of glottic cancers treated by partial or total laryngectomy between Jan 2015 and Aug 2019 were reviewed to assess levels of tumor invasion at critical glottic subsites. CT accuracy in the identification of tumor extensions was determined against the gold standard of histopathological analysis of surgical samples., Results: This study included 64 patients. In the anterior commissure, CT showed high rates of false positives at all levels (sensitivity 56.2-70%, specificity 87.8-92.3%); in the anterior vocal fold, it overestimated the deep invasion (19.5% specificity, 90.3% sensitivity), while it underestimated the extralaryngeal spread (63.6% sensitivity, 98.1% specificity). In the posterior paraglottic space (pPGS), false negative results were more frequent for superficial extensions (25% sensitivity, 95.8% specificity) and deep invasions (58.8% sensitivity, 82.3% specificity). Shorter disease-specific and disease-free survivals were associated with pStage IV ( p : 0.045 and 0.008) and with the pathological involvement of pPGS ( p : 0.045 and 0.015)., Conclusions: Negative prognostic correlation of pPGS involvement was confirmed on histopathological data. CT staging did not provide a satisfactory prognostic stratification and should be complemented with magnetic resonance imaging.

Multiparametric MRI is a remarkable imaging method for the assessment of patho-physiological processes. In particular, brain tumor characterization has taken advantage of the development of advanced techniques such as Diffusion- (DWI) and Perfusion- (PWI) Weighted Imaging, but a thorough analysis of meningiomas is still lacking despite the variety of computational methods proposed. We compute perfusion and diffusion parametric maps relying on a well-defined methodological workflow, investigating possible correlations between pure and diffusion-based perfusion parameters in a cohort of 26 patients before proton therapy. A preliminary investigation of meningioma staging biomarkers based on IntraVoxel Incoherent Motion and Dynamic Susceptibility Contrast is also reported. We observed significant differences between the gross target volume and the normal appearing white matter for every investigated parameter, confirming the higher vascularization of the neoplastic tissue. DWI and PWI parameters appeared to be weakly correlated and we found that diffusion parameters - the perfusion fraction in particular - could be promising biomarkers for tumor staging., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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. The method was validated on a digital anthropomorphic phantom and tested on eight patients (18 acquisitions). For the phantom, a ground truth dataset was available to assess the method performances from the geometrical and dosimetric standpoints. For the patients, the virtual 4DCT was compared with the planning 4DCT., Results: In the phantom, the method exhibits a geometrical accuracy within the voxel size and Dose Volume Histograms deviations up to 3.3% for target V 95% (mean dose difference ≤ 0.2% of the prescription dose, gamma pass rate > 98%). For patients, the virtual and the planning 4DCTs show good agreement at end-exhale (3% median D 95% difference), whereas other respiratory phases exhibit moderate motion variability with consequent dose discrepancies, confirming the need for motion mitigation strategies during treatment., Conclusions: The virtual 4DCT approach is feasible to evaluate treatment plan robustness against intra- and interfraction motion in carbon ion therapy delivered at the abdominal site., (© 2019 American Association of Physicists in Medicine.)

Purposes: To explore the feasibility of 3D printed salivary duct models for the sialendoscopic skills training., Methods: Healthy volunteers and patients affected by obstructive salivary gland disorders were submitted to 3 Tesla MR sialography. The MR data underwent an image segmentation process to produce the 3D printed salivary duct prototypes. Sialendoscopies were carried out by three groups of investigators with different levels of endoscopic experience. Realism, usefulness of the training process and potential advantages of the 3D printed models in the preoperative surgical planning were evaluated by means of a specific survey., Results: Four cases were included in our study: one healthy parotid, one submandibular gland, one case of lithiasis and one of stenosis involving the parotid gland. In all cases, the three groups of investigators successfully explored the salivary ducts up to the tertiary branches, detected the cause of obstruction and correctly treated it. Seven untoward events occurred during the operative sialendoscopies. Overall, the questionnaire score was about 79.3%, reflecting a positive impression regarding the models on behalf of all the investigators., Conclusions: 3D printed salivary duct models resulted feasible for the sialendoscopic skills training. The opportunity to reproduce the patient-specific anatomy may add further information useful in the preoperative decision making. These positive results should be verified by further researches and experiences.

In inoperable patients, the management of angiosarcoma of the scalp is challenging. Due to intrinsic, dosimetric and radiobiological properties, proton beam radiotherapy may be an effective and safe option to offer to these difficult-to-cure patients. Here, we report a case of angiosarcoma of the scalp treated successfully with proton beam radiotherapy. Angiosarcoma is a rare malignancy concerning around 2% of soft-tissue sarcomas and 5% of cutaneous soft-tissue sarcomas. Cutaneous angiosarcomas can occur in any part of the body, but the head and neck region is a common primary site and the scalp is a frequent site in elderly patients., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Mandibular fractures are among the most common maxillofacial fractures observed in emergency rooms and are mainly caused by road accidents. The clinical features of mandibular fractures include malocclusion and loss of mandibular function. Panoramic radiography is usually limited to isolated lesions, whereas computed tomography is the tool of choice for all other facial traumatic events. No reference standard classification system for the different types of mandibular fractures is defined. Therapeutic options include a conservative approach or surgical treatment based on the anatomic area and the severity of fracture. The main purpose of this pictorial review is to illustrate a practical description of the pathophysiology of mandibular fractures and describe both the imaging techniques to recognise them and the therapeutic indications.

Background: Few data are known regarding the molecular features and patterns of growth and presentation which characterize those lung neoplastic lesions presenting as non-solid nodules (NSN)., Methods: We retrospectively reviewed two different cohorts of NSNs detected by CT scan which, after transthoracic fine-needle aspiration (FNA) and core needle biopsy (CNB) received a final diagnosis of malignancy. All the enrolled patients were then addressed to surgical removal of lung cancer nodules or to exclusive radiotherapy. Exhaustive clinical and radiological features were available for each case., Results: In all 62 analysed cases the diagnosis of adenocarcinoma (ADC) was reached. In cytologic samples, EGFR activating mutations were identified in 2 of the 28 cases (7%); no case showed ALK/EML4 or ROS1 translocations. In the histologic samples EGFR activating mutation were found in 4 out of 25 cases (16%). PD-L1 immunostains could be evaluated in 30 cytologic samples, while the remaining 7 did not reach the cellularity threshold for evaluation. TPS was < 1% in 26 cases,  > 1% < 50% in 3, and > 50% in 1. All surgical samples showed TPS < 1%. Of the 17 cases that could be evaluated on both samples, 15 were concordantly TPS 0, and 2 showed TPS > 1% < 50 on the biopsy samples. TPS was < 1% in 14 cases, > 1%/< 5% in 4 cases, > 5%/< 50% in 2 cases, > 50% in 1 case., Conclusions: Overall PD-L1 immunostaining documented the predominance of low/negative TPS, with high concordance in FNA and corresponding surgical samples. It can be hypothesized that lung ADC with NSN pattern and predominant in situ (i.e. lepidic) components represent the first steps in tumor progression, which have not yet triggered immune response, and/or have not accumulated a significant rate of mutations and neoantigen production, or that they belong to the infiltrated-excluded category of tumors. The negative prediction of response to immunomodulating therapy underlines the importance of rapid surgical treatment of these lesions. Notably, cell block cytology seems to fail in detecting EGFR mutations, thus suggesting that this kind of sampling technique should be not adequate in case of DNA direct sequencing.

Background: When undergoing magnetic resonance (MR) exams, patients need to lie still in a noisy and enclosed environment for a long time. This condition, together with the anxiety burden related to the possible implications of the scan results, can entail a diagnostic outcome of poor quality., Objective: The aim of the study was to evaluate the personal perception and experience of adult patients undergoing unenhanced musculoskeletal MR., Methods: Consecutive outpatients undergoing unenhanced MR of spine, knee or shoulder were asked to respond to a 10-item questionnaire at the end of the exam., Results: 263 patients (54% males, mean age 50.6 ±15.8 years, range 18-83 years) completed the questionnaire. Patients declared that the most disturbing elements of the exam were forced immobility and noise (30% in both cases). Females perceived significantly higher degree of anxiety than males (56% vs. 21%, p<0.001). Exam duration was correctly perceived by 83% of the population. Patients' satisfaction was generally high (mean above 9 over 10)., Conclusion: Explanations and clarifications given before the exam were considered satisfactory by the patients. Despite some negative aspects such as noise, immobility and anxiety especially in females, patients' satisfaction with our service was high, as well as the willingness to return., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and summary: Among all vulvar cancers, primary adenoid cystic carcinoma (ACC) of Bartholin's gland is a very rare tumor characterized by a slow growth, a high local aggressiveness, and a remarkable recurrence rate. Due to its rarity, treatment remains a challenge for oncologists and gynecological surgeons. Key message: The present paper reports clinical, radiological, and histological features of ACC of Bartholin's gland and reviews the literature data on the treatment options with a particular focus on the potential role of particle radiation therapy., (© 2020 S. Karger AG, Basel.)

Purpose: To devise a novel Spatial Normalization framework for Voxel-based analysis (VBA) in brain radiotherapy. VBAs rely on accurate spatial normalization of different patients' planning CTs on a common coordinate system (CCS). The cerebral anatomy, well characterized by MRI, shows instead poor contrast in CT, resulting in potential inaccuracies in VBAs based on CT alone., Methods: We analyzed 50 meningioma patients treated with proton-therapy, undergoing planning CT and T1-weighted (T1w) MRI. The spatial normalization pipeline based on MR and CT images consisted in: intra-patient registration of CT to T1w, inter-patient registration of T1w to MNI space chosen as CCS, doses propagation to MNI. The registration quality was compared with that obtained by Statistical Parametric Mapping software (SPM), used as benchmark. To evaluate the accuracy of dose normalization, the dose organ overlap (DOO) score was computed on gray matter, white matter and cerebrospinal fluid before and after normalization. In addition, the trends in the DOOs distribution were investigated by means of cluster analysis., Results: The registration quality was higher for the proposed method compared to SPM (p < 0.001). The DOO scores showed a significant improvement after normalization (p < 0.001). The cluster analysis highlighted 2 clusters, with one of them including the majority of data and exhibiting acceptable DOOs., Conclusions: Our study presents a robust tool for spatial normalization, specifically tailored for brain dose VBAs. Furthermore, the cluster analysis provides a formal criterion for patient exclusion in case of non-acceptable normalization results. The implemented framework lays the groundwork for future reliable VBAs in brain irradiation studies., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Mammary analogue secretory carcinoma (MASC) is a recently described low-grade salivary gland malignancy with histologic, immunohistochemical and molecular similarities to secretory carcinoma of the breast, including a specific t(12;15)(p13;q25) resulting in an ETV6-NTRK3 gene fusion. Ultrasound and magnetic resonance imaging frequently document a macrocystic structure. The main differential diagnosis of secretory carcinoma is with low grade acinic cell carcinoma (AciCC). The two can be differentiated with immunohistochemical stains for S100, mammaglobin, carbonic anhydrase VI and DOG-1; the identification of the specific translocation can help to characterize non-typical cases. We report a unique case of synchronous MASC and AciCC presenting in a parotid gland and discuss the implications of the correct identification of the two tumors.

Purpose/objective: The purpose of this study is to assess the impact of the conversion scheme for relative biological effectiveness (RBE)-weighted dose (D RBE ), implemented at our center, on treatment outcomes of adenoid cystic carcinoma (ACC) patients., Material/methods: Treatment plans of 78 ACC patients, optimized with the Local Effect Model (LEM), were recalculated with the modified Microdosimetric Kinetic Model (mMKM). D RBE to 95%, 50% and 2% (D V% ) of the clinical target volume (CTV), were selected as relevant parameters to compare LEM and mMKM D RBE . The pattern of failure of ACC treatments was analyzed in relation to uncertainties involved in the D RBE translation methodology., Results: mMKM recalculations of LEM plans, optimized to a prescription dose of 68.8 Gy(RBE), showed a D 50% 8% higher, on average, than the expected value (60.8 Gy(RBE)), closer to the most frequently used mMKM prescription D RBE (64 Gy(RBE)). D 95% and D 2% deviations, with respect to the optimization goals in the two RBE systems, increased of 0.5% and 14.2%, respectively, due to the steeper mMKM RBE variation along the beam path. Local recurrences were mainly (63%) reported in areas where CTV coverage was not satisfactory in the original LEM plan and the mMKM analysis showed that OARs constraints were too conservative., Conclusion: No case of local recurrence could be explained by inadequate mMKM target coverage that was not already present in the LEM plan. New constraints have been defined for optic pathways and brainstem to improve target coverage with no expected increase in tissue complications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Magnetic resonance imaging (MRI) is a widely used diagnostic technique. Patients wearing orthodontic appliances are often requested to remove their appliances, even when the MRI exam involves anatomical areas far from mouth, in order to avoid heating of the metal and detachment of the appliance. The purpose of the present investigation was to measure and compare temperature changes and orthodontic appliances' adhesion to enamel after different MRIs. A total of 220 orthodontic brackets were bonded on bovine incisors and wires with different materials (stainless steel and nickel titanium). Moreover, various sizes (0.014″ and 0.019″ × 0.025″) were engaged. Appliances were submitted to MRI at two different powers (1.5 T and 3 T). The temperatures of brackets and wires were measured before and after MRI. Subsequently, the shear bond strength (SBS) and adhesive remnant index (ARI) scores were recorded. Statistical analysis was performed. After MRI, a significant increase in the temperature was found for both the brackets and wires in some groups, even if the mean temperature increase was clinically insignificant, as the temperature ranged between 0.05 °C and 2.4 °C for brackets and between 0.42 °C and 1.74 °C for wires. The MRI did not condition bracket adhesion in any group. No differences were reported when comparing the 1.5 T with 3 T groups. The ARI Scores were also significantly lower after MRI. The results of the present report show that, under MRI, orthodontic appliances present a low temperature rise and no debonding risk. Therefore, the removal of orthodontic appliance is not recommended routinely, but is suggested only in the case of a void risk or potential interference in image quality.

Nowadays, hadrontherapy is increasingly used for the treatment of various tumors, in particular of those resistant to conventional radiotherapy. Proton and carbon ions are characterized by physical and biological features that allow a high radiation dose to tumors, minimizing irradiation to adjacent normal tissues. For this reason, radioresistant tumors and tumors located near highly radiosensitive critical organs, such as skull base tumors, represent the best target for this kind of therapy. However, also hadrontherapy can be associated with radiation adverse effects, generally referred as acute, early-delayed and late-delayed. Among late-delayed effects, the most severe form of injury is radiation necrosis. There are various underlying mechanisms involved in the development of radiation necrosis, as well as different clinical presentations requiring specific treatments. In most cases, radiation necrosis presents as a single focal lesion, but it can be multifocal and involve a single or multiple lobes simulating brain metastasis, or it can also involve both cerebral hemispheres. In every case, radiation necrosis results always related to the extension of radiation delivery field. Multiple MRI techniques, including diffusion, perfusion imaging, and spectroscopy, are important tools for the radiologist to formulate the correct diagnosis. The aim of this paper is to illustrate the possible different radiologic patterns of radiation necrosis that can be observed in different MRI techniques in patients treated with hadrontherapy for tumors involving the skull base. The images of exemplary cases of radiation necrosis are also presented.

Background: Pancreatic adenocarcinoma is a high-mortality neoplasm with a documented 5-years-overall survival around 5%. In the last decades, a real breakthrough in the treatment of the disease has not been achieved. Here we propose a prospective, phase II, multicentre, single-arm study aiming to assess the efficacy and the feasibility of a therapeutic protocol combining chemotherapy, carbon ion therapy and surgery for resectable and borderline resectable pancreatic adenocarcinoma., Method: The purpose of this trial (PIOPPO Protocol) is to assess the efficacy and the feasibility of 3 cycles of FOLFIRINOX neoadjuvant chemotherapy followed by a short-course of carbon ion radiotherapy (CIRT) for resectable or borderline resectable pancreatic adenocarcinoma patients. Primary outcome of this study is the assessment of local progression free survival (L-PFS). The calculation of sample size is based on the analysis of the primary endpoint "progression free survival" according to Fleming's Procedure., Discussion: Very preliminary results provide initial evidence of the feasibility of the combined chemotherapy and CIRT in the neoadjuvant setting for resectable or borderline resectable pancreatic cancer. Completion of the accrual and long term results are awaited to see if this combination of treatment is advisable and will provide the expected benefits., Trial Registration: ClinicalTrials.gov Identifier: NCT03822936 registered on January 2019.

A selective electrochemical sensor based on poly(3,4-ethylenedioxythiophene) (PEDOT) - Prussian blue nanoparticles (PBNPs) for hydrogen peroxide (H 2 O 2 ) determination was prepared by innovative sinusoidal voltage (SV) method. The successful incorporation of citrate-stabilized PBNPs into PEDOT matrix was confirmed by energy dispersive X-ray analysis (EDX), Raman spectroscopy, UV-Vis spectroelectrochemistry and cyclic voltammetry measurements. The SV preparation method provides a PEDOT-PBNPs coating with rough surface morphology and good electrocatalytic activity toward H 2 O 2 reduction. The amperometric response of PEDOT-PBNPs-based sensor at -50 mV vs. Ag/AgCl is linear within the range of concentrations from 5 μM to 1 mM H 2 O 2 with a detection limit of 1.4 μM H 2 O 2 . The proposed Pt/PEDOT-PBNPs sensor displays good repeatability, reproducibility, operational stability as well as good selectivity toward H 2 O 2 determination in the presence of interfering species like dopamine (DA), uric acid (UA), KNO 2 glucose (Glu), KNO 3 and ascorbic acid (AA), and was successfully applied to H 2 O 2 determination in human blood samples without biofouling., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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). Local control information was clinically assessed. For 20 of them, apparent diffusion coefficient (ADC) maps were computed from DW-MRI and then converted into cellular density. Radiosensitivity parameters (α, β) were estimated from the available data through an optimization procedure, taking advantage of a relationship observed between local control and the dose received by at least the 98% of the gross tumour volume. These parameters were fed into two poissonian TCP models, based on the LQ model, being the first (TCP LIT ) computed from literature parameters and the second (TCP ADC ) enriched by a personalized initial cellular density derived from ADC maps., Results: The inclusion of the cellular density derived from ADC into TCP ADC yielded slightly higher dose values at which TCP = 0.5 (D 50  = 38.91 Gy (RBE)) with respect to TCP LIT (D 50 34.16 Gy (RBE)). This suggested a more conservative approach, even if the prognostic power of TCP ADC and TCP LIT , tested with respect to local control, was equivalent in terms of sensitivity (0.867) and specificity (0.600)., Conclusions: Both TCP ADC and TCP LIT exhibited good agreement with a clinically validated information of local control, the former providing more conservative predictions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Pulmonary nodules and masses are the typical presentations of lung cancer. However, a spectrum of focal opacities cannot be defined as either "pulmonary nodule" or "mass," despite representing cancer. We aimed to assess the morphology of screening-detected lung cancers at low-dose computed tomography LDTC and to evaluate inter-observer agreement in their classification., Methods: Four radiologists with different experiences in thoracic imaging retrospectively reviewed 273 screening-detected lung cancers. Readers were asked to assess if morphology at the time of diagnosis was consistent with the Fleischner Society definition of pulmonary "nodule" or "mass." Cancers not consistent were defined as "non-nodular/non-mass" (NN/NM) and sub-classified as follows: associated with cystic airspaces, stripe-like, scar-like, endobronchial, or not otherwise defined (NOD). Inter-observer agreement was evaluated using Cohen's K statistic among pairs of readers and modified Fleiss' kappa statistic for overall agreement., Results: Two hundred forty-one of the 273 (88%) lesions were defined as pulmonary nodule or mass by complete agreement, while 20/273 (7.3%) were defined as NN/NM. Six (2.2%) of 273 were sub-classified as lesions associated with cystic airspace, six (2.2%) as scar-like, five (1.8%) as endobronchial, and one (0.7%) as NOD by complete agreement. The concordance in defining morphology was excellent (261/273; 96%, 95%CI 92-98%; k 0.85, 95%CI 0.75-0.92) and also in the sub-classification (18/20; 90%, 95%CI 68-99%, k 0.93, 95%CI 0.86-1.00). There was incomplete agreement regarding lesion morphology in 4.4% (12/273) of cases., Conclusions: A non-negligible percentage of screening-detected lung cancers has a NN/NM appearance at LDCT. The concordance in defining lesion morphology was excellent. The awareness of various presentations can avoid missed or delayed diagnosis., Key Points: • A non-negligible percentage of screening-detected lung cancers have neither nodular nor mass appearance at low-dose CT. • The awareness of various LDCT presentations of lung cancer can avoid missed or delayed diagnosis. • Optimal protocol management in CT screening should take into consideration lung nodules as well as various other focal abnormalities.

Purpose: The evaluation of the surgical margin in breast conservative surgery is a matter of general interest as such treatments are subject to the critical issue of margin status as positive surgical margins can undermine the effectiveness of the procedure. The relatively unexplored ability of millimeter-wave (mm-wave) spectroscopy to provide insight into the dielectric properties of breast tissues was investigated as a precursor to their possible use in assessment of surgical margins., Methods: We assessed the ability of a mm-wave system with a roughly hemispherical sensitive volume of ∼3 mm radius to distinguish malignant breast lesions in prospectively and consecutively collected tumoral and non-tumoral ex-vivo breast tissue samples from 91 patients. We characterized the dielectric properties of 346 sites in these samples, encompassing malignant, fibrocystic disease and normal breast tissues. An expert pathologist subsequently evaluated all measurement sites., Results: At multivariate analysis, mm-wave dielectric properties were significantly correlated to histologic diagnosis and fat content. Further, using 5-fold cross-validation in a Bayesian logistic mixed model that considered the patient as a random effect, the mm-wave dielectric properties of neoplastic tissues were significantly different from normal breast tissues, but not from fibrocystic tissue., Conclusion: Reliable discrimination of malignant from normal, fat-rich breast tissue to a depth compatible with surgical margin assessment requirements was achieved with mm-wave spectroscopy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Malignant melanoma of the lower genital tract is a rare disease known to have a poor prognosis. Because of the high rate of distant metastasis and unsatisfactory survival benefit, a more conservative treatment approach, instead of extensive surgery, may be warranted. Gynecological melanoma is a radioresistant tumor, an ideal disease to test the biological efficacy of carbon ion radiotherapy (CIRT)., Aim: To report our preliminary experience with CIRT in the treatment of gynecological melanoma at the National Center of Oncological Hadrontherapy (CNAO)., Patients and Methods: Between January 2016 and February 2017, four patients were admitted for CIRT at CNAO. A case of cervical melanoma was treated with palliative aim because of large volume macroscopic disease, while three cases of vaginal melanoma were irradiated with a total dose of 68.8 Gy (relative biological effectiveness) in 16 fractions delivered over 4 weeks (4 days a week)., Results: The age of women ranged between 49 and 72 (median=60.5 years) years. Treatment was well tolerated in all patients and all women completed the scheduled treatment course. During CIRT, toxicity was mild. For patients with vaginal disease, local control was 10.23 and 12.6 months, while that for cervical malignant melanoma was 7.3 months. All patients experienced systemic progression, with median distant metastasis-free survival of 11.7 months. The median overall survival for the whole patient group was 11.41 months., Conclusion: In our first experiences, CIRT appears to be a safe non-invasive option for malignant melanoma of the lower genital tract, but more data and longer follow-up are necessary in order to evaluate the effectiveness and late effects., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Liposarcomas are the most common soft-tissue sarcomas in adulthood. Orbital and spermatic cord liposarcomas are uncommon and there is no consensus on their management. The treatment of choice is wide excision, which may be destructive and lead to unacceptable morbidity. When surgery is declined by patients and in recurrent disease, management can be challenging. We report two cases of liposarcoma treated with carbon ion radiotherapy at the National Center for Oncological Hadrontherapy (Fondazione CNAO) in Italy., Case Report: A woman with orbital liposarcoma and a man with spermatic cord liposarcoma were referred to our Center and accepted for carbon ion radiotherapy. The treatment was well tolerated and late toxicities were mild. Good local control was achieved in patients., Conclusion: In our experience, carbon ion radiotherapy is an effective and safe option, especially in cases of tumor at high risk for local relapse, in patients with multiple local recurrences, and in patients who refuse destructive surgery., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)