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Objectives Treatment options for malignant pleural mesothelioma (MPM) are limited but some studies on immune checkpoint inhibitors (ICIs) in MPM have reported antitumor activity. Very little is known about immune-related predictive factors. Materials and methods Here we report the case of a 45-year-old woman presenting with dyspnea and evidence of pleural effusion. She was diagnosed with malignant epithelioid pleural mesothelioma with brain metastasis and peritoneal carcinosis, refractory to initial standard chemotherapy treatment. Because of high PDL1 expression (100 %), she was treated with the anti-PD1 agent, pembrolizumab. Results Chemotherapy with cisplatin and pemetrexed was started, imaging studies showing stable disease after 3 treatment cycles. The patient underwent pleural decortication but rapidly progressed and thus started chemotherapy with carboplatin and gemcitabine. After 2 cycles she experienced seizures caused by a brain metastasis. This secondary lesion was surgically removed and confirmed as a metastasis from mesothelioma. Samples from both the primary tumor and the metastasis were molecularly characterized, the pleural sample proving ALK-positive and the brain sample, ALK-negative. PD-L1 was positive in 10 % of tumor cells in the pleural biopsy and 100 % in the brain lesion. Next generation sequencing analysis was negative for both samples. It was decided to start alectinib. Disease progression (peritoneal carcinosis and liver metastases) was documented after one month followed by complete bowel obstruction and recurrence in the site of the brain surgery. Alectinib was stopped and supportive care begun with parenteral nutrition via nasogastric tube. Pembrolizumab was started and after 15 days the patient’s condition had significantly improved, enabling recanalization and restoration of enteral nutrition. Imaging displayed complete response of the brain metastasis, peritoneal carcinosis, bone lesions and mediastinal nodal metastases. A partial response was documented in the pleural and pulmonary nodules, with stable liver metastases. The patient is still undergoing immunotherapy and has no cancer-related symptoms. Conclusions Our findings indicate that the use of immunotherapy in MPM warrants further investigation. Furthermore, the impressive clinical response obtained by our patient suggests that immune checkpoint inhibitors could help in the management of the disease after the failure of other treatments.

Bone metastases (BM) are still the main cause of morbidity and mortality in cancer patients, not only because of their complications, defined as skeletal-related events (SREs), but also because of the negative impact bone pain has on quality of life (QoL) and survival, especially when opioid analgesics and locoregional treatments fail.A single-center prospective study was carried out on 12 patients with symptomatic BM treated with MRI-guided focused ultrasound (MR-HIFU). The primary endpoint was the effectiveness of MR-HIFU in reducing current and breakthrough cancer pain (BTCP) scores. The main secondary aims were the evaluation of circulating markers at different time-points and their relation to pain and procedure efficacy. Other secondary objectives included temporal evolution of pain response, evaluation of QoL, and side effects of the treatment. Descriptive statistics were used to evaluate primary and secondary endpoints. Questionnaires on pain and QoL completed at baseline and at 30 days were compared using appropriate statistical tests with exploratory intent.MR-HIFU was successfully completed in all 12 patients enrolled between September 2015 and December 2018. On day 30, 6 (50.0%) patients showed a complete response of current pain and 6 a partial response, while 5 (41.7%) obtained a complete BTCP response. A partial response of BM evaluated by MD Anderson criteria was obtained in 9 (81.8%) patients. Only one patient progressed in the target lesion after MR-HIFU. No treatment-related adverse events were recorded. Bone turnover markers CTX/RANK-L (P) do not demonstrate any significant change with the pain or BM response.In our patients, targeted therapy of painful BM with MRI-guided focused ultrasound ablation was safe and showed encouraging early-onset and functional results.

Rationale: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor that is prevalent among children and adolescents. Surgery is the most important therapeutic approach for IMT and complete resection is recommended. Although 50% of IMTs show anaplastic lymphoma kinase (ALK) rearrangements, crizotinib has proven an effective therapeutic approach. However, the genetic landscape of this tumor is still not fully understood and treatment options are limited, especially in the majority of ALK-negative tumors. Patient concerns: We describe the clinical case of a healthy 18-year-old female in whom a pulmonary nodule was incidentally detected Diagnoses: Following a small increase in the size of the nodule, the patient underwent both 18FDG-PET/CT and 68Ga-PET/CT, resulting in a suspicion of bronchial hamartoma. Interventions: The patient underwent surgery and a salivary gland-like lung tumor was diagnosed. Outcomes: After surgery, the patient was referred to our cancer center, where a review of the histology slides gave a final diagnosis of ALK-negative lung IMT. Given the histology, it was decided not to administer adjuvant therapy and the patient was placed in a 3-monthly follow-up program. The patient is still disease-free 2 years post-surgery. Lessons: Although there is no standard of care for the treatment of IMT, identifying genomic alterations could help to redefine the management of patients with negative-ALK disease. Our review of the literature on IMT and other kinase fusions revealed, in addition to ALK rearrangements, the potential association of ROS1, NTRK, RET, or PDGFR beta alterations with the tumor.

PURPOSE: FDG-positive neuroendocrine tumors (NETs) have a poorer prognosis and exhibit shorter response duration to peptide receptor radionuclide therapy (PRRT). The aim of this prospective phase II study was to evaluate the efficacy and toxicity of PRRT with (177)Lu-DOTATATE associated with metronomic capecitabine as a radiosensitizer agent in patients with advanced progressive FDG-positive gastro-entero-pancreatic (GEP) NETs. PATIENTS AND METHODS: Patients with advanced somatostatin receptor- and FDG-positive G1-G3 GEP-NETs (Ki6720%) NETs. Grade 3 (G3) or 4 (G4) hematological toxicity occurred in 16.2% of patients. Other G3-G4 adverse events were diarrhea in 5.4% of cases and asthenia in 5.4%. No renal toxicity was observed for the duration of follow-up. Thirty-three of 37 patients were evaluable for response. Objective responses included partial response (PR) in 10 patients (30%), stable disease (SD) in 18 patients (55%), with a DCR of 85%. Median follow up was 38 months (range 4.6–51.1 months). Median PFS was 31.4 months (17.6–45.4) and mOS was not reached. CONCLUSIONS: This study demonstrated that the combination of PRRT with (177)Lu-DOTATATE and metronomic capecitabine is active and well tolerated in patients with aggressive FDG-positive G1-G3 GEP-NETs. These data constitute the basis for a randomized study of PPRT alone vs. PRRT plus metronomic capecitabine.

OBJECTIVE: The aim of this study was to test the relationship between anthropometry, ultrasonography, and dual-energy x-ray absorptiometry (DXA) for the assessment of body composition in clinical practice. METHODS: The study was carried out in Italian blood donor volunteers belonging to five different age groups (18-70 y old; 25 men and 25 women per group; N = 250 participants; n = 125 men, n = 125 women). A complete history was collected and routine blood analyses were performed to confirm healthy status. All participants were submitted to whole-body DXA (tricompartmental analysis, regional, and total body), ultrasonography (abdominal adiposity evaluation), and anthropometric measurements. DXA was used as gold standard and its biomarkers were taken as reference for fat-lean mass balance, central-peripheral fat distribution, central or visceral fat, and subcutaneous fat. RESULTS: Anthropometric and ultrasound parameters were closely associated with most of DXA parameters. Composite markers representative of central and abdominal visceral fat compartments were significantly correlated with waist circumference, waist-to-hip ratio, and intra-abdominal fat thickness by ultrasound, in both men and women (P < 0.025). As expected, subcutaneous depots were significantly correlated with maximum subcutaneous fat thickness measured by ultrasonography (P < 0.025). CONCLUSIONS: Both anthropometry and ultrasonography provide a reliable estimate of visceral adipose tissue in a non-obese population compared with DXA, whereas anthropometry prediction of subcutaneous adiposity is weak. Physicians should be aware of the limits of these techniques for the assessment of body composition.

The aim of this study was to investigate the diagnostic performance of new dual-energy X-ray absorptiometry (DXA) technologies in the detection of vertebral fractures (VFs). Sixty-eight patients were submitted to DXA and conventional radiography (XR) on the same day. Lateral images of the spine were independently evaluated by three radiologists with different experience in skeletal imaging, in two sessions with 7 days between evaluations of the same anonymous images. The most expert physician repeated the analysis in a subsequent reading session after further 7 days. Results from expert XR evaluation were considered as gold standard. A semiquantitative approach was used to interpret images and morphometric analysis was performed when a VF was suspected. Seventy vertebrae (70/884, 7.9%) were excluded from the lesion-based analysis, as not evaluable: 11/70 (15.7%) missed by XR only, 56/70 (80.0%) missed by DXA only, 3/70 (4.3%) missed by both techniques (upper thoracic spine). Forty “true” fractures were detected (4.9% out of 814 vertebrae) in 26 patients (38.2% of the 68 studied patients). Twenty-five (62.5%) were mild fractures. DXA sensitivity and specificity were 70.0% and 98.3% on a lesion-based analysis, 73.1% and 90.5% on a patient-based analysis. Intra-observer agreement was excellent with no significant difference between the two techniques. Inter-observer agreement among the 3 observers was higher for XR (k = 0.824 versus 0.720 in the detection of VFs, p = 0.011). DXA accuracy was not influenced by radiologist experience; T4-L4 assessability as well as reproducibility and repeatability of the two techniques and accuracy of DXA were independent from sex, age, body mass index, grade of arthrosis. However DXA sensitivity was affected by mild VFs. Vertebral level did not affect the diagnostic performance with exception of vertebral body assessability. Latest improvements make VFs assessment by DXA competitive with traditional radiographic gold standard, providing consistent advantages and attractions. Few limitations still affect DXA performance and need to be overcome.

Summary: The detection of changes in lean mass (LM) distribution can help to prevent disability. This study assessed the degree of association between anthropometric measurements and dual-energy X-ray absorptiometry (DXA) body composition (BC) parameters of the upper and lower limbs in a healthy general population and collected DXA age- and sex-specific values of BC that can be useful to build a reference standard. Purpose: The primary aim of this study was to investigate the reliability of some widely available anthropometric measurements in the assessment of body composition (BC) at the limbs, especially in terms of muscle mass, in a large sample of healthy subjects of different age bands and sex, using fat mass (FM) and lean mass (LM) parameters derived by dual-energy X-ray absorptiometry (DXA) as the gold standard. The secondary aim was to collect DXA age- and sex-specific values of BC of left and right limbs (upper and lower) in a healthy Italian population to be used as reference standards. Methods: Two hundred fifty healthy volunteers were enrolled. Arm circumference (AC) and thigh circumference (ThC) were measured, and total and regional BC parameters were obtained by a whole-body DXA scan (Lunar iDXA, Madison, WI, USA; enCORE™ 2011 software version 13.6). Results: FM/LM showed only fair correlation with AC and ThC in females (r = 0.649 and 0.532, respectively); in males and in the total population, the correlation was low (r = 0.360 or lower, and p non-statistically significant). AC and ThC were not well representative of arms LM in both genders (females r = 0.452, males r = 0.530) independently of age. In general, men of all age groups showed higher values of LM and lean mass index (LMI) in both total and segmental upper and lower limbs. In males, the maximum LM and LMI were achieved in the fifth decade in both upper and lower limbs and then started to decrease with aging. In females, no significant modification with aging was identified in LM and LMI. Conclusion: According to our results, anthropometry is not well representative of LM of arms in both genders, independently of age; therefore, a densitometric examination should be considered for a correct assessment of BC at limbs.

Aims To provide a reference standard database of ultrasonographic parameters of abdominal adiposity in healthy people. Methods Italian non-obese volunteers among blood donors were enrolled in 5 age bands (from 18 to 70 year-old) to reach the threshold of 25 males and 25 females per single band (total: 250). All subjects were measured for weight, height and waist circumference and underwent ultrasonography (US) by an expert radiologist for the assessment of several abdominal fat thicknesses ( minimum and maximum subcutaneous fat thickness , maximum preperitoneal fat thickness , intrabdominal fat thickness , aorto-mesenteric thickness , and mesenteric fat thickness ). In addition, US data were normalized per waist circumference. Results From 30s to 50s no statistically significant differences were achieved between males and females for the adiposity markers of visceral fat, while a relevant divergence was proved from 60s to 70s. During ageing a marked increase of the visceral fat compartment was observed in males, while only the preperitoneal circumference was significantly modified in females. Conclusions This paper reports on US parameters of abdominal adiposity of healthy Italian adults, to be used as a reference for daily clinical practice. Data could be also considered as control group for future investigations on physiology, pathological conditions, and differences between countries.

The aim of the present study was to evaluate the performance of sagittal MR localizer (MR-loc), in terms of diagnostic accuracy and intra- and inter-observer agreement in the detection of vertebral fractures (VFs). Three-hundred MR examinations of the thoracic and/or lumbar spine were randomly collected. A semi-quantitative approach was used and morphometric analysis was performed when a VF was suspected. MR-loc images were evaluated blindly by three radiologists in two different sessions. A full diagnostic sagittal T1-weighted fast spin echo MR sequence was used as standard of reference (RS). Degenerative arthritis was also scored on RS. Only vertebral bodies which were assessable by both MR-loc and RS were considered for the analysis. Area under the receiver operating characteristic curve (AUROC), Cohen kappa statistic, and linear-by-linear association were used for statistical analysis. Kappa values were compared by means of the z distribution. A total of 2186 vertebrae were analysed in 300 MRI exams (147 males, 153 females, 59.4±16.4y.o.). Sixty-seven out of 2136 (3.1%) VFs were identified in 23/300 (7.7%) patients submitted to MRI. In the detection of VFs, sensitivity and specificity of MR-loc were both 100% (accuracy AUROC=1.000). Inter-observer agreement was excellent (k=0.938±0.013), while intra-observer agreement was perfect (k=1.000). The diagnostic performance was independent from degenerative arthritis, vertebral level, type and grade of VFs. MR-loc is a simple but accurate tool in the detection of VFs. It should be introduced for systematic evaluation in the detection of VFs in MR examinations performed in daily clinical practice.

Dual energy X-ray absorptiometry (DXA) is a well-established method for the diagnosis of osteoporosis and monitoring of treatment. Recent advances in DXA technologies have improved accuracy and precision. Nevertheless, errors in bone mineral density measurement and interpretation could occur and negatively affect the diagnosis and management of patients. These errors can result from improper equipment installation and maintenance, inadequate education and training in bone densitometry, and insufficient knowledge of current clinical guidelines. This review describes the current procedures of quality assurance in bone densitometry and emphasizes strict adherence of technicians and clinicians to manufacturers’ recommendations and current clinical guidelines.

Summary What is already known about this subject Obesity is an increasingly prevalent metabolic disorder and it is associated with a large number of comorbidities, including cardiovascular diseases. Adipose tissue is an active endocrine organ and its ectopic depots and distribution have different metabolic meanings on risks for health; as a matter of fact, epicardial fat seems to play a specific role in cardiovascular diseases. The use of dual-energy X-ray absorptiometry (DXA) to evaluate and follow-up patients affected by obesity is becoming a very important point in the management of the disease. What this study adds An investigation of the association between epicardial fat and regional adiposity by DXA in female obese patients. The total amount of central (trunk) fat mass is more strongly correlated than android visceral fat mass to epicardial thickness in obese women. In the interpretation of whole-body DXA data, physician should consider trunk fat mass for good and independent predictivity on epicardial fat depots. Our aim was to analyse in a population of obese women the relationship between the amount of epicardial fat as measured by transthoracic echocardiography (US) and the parameters of regional adiposity by dual-energy X-ray absorptiometry (DXA), with particular reference to a new software for visceral fat assessment and to a new ‘heart-suited’ regions of interests (ROIs). Sixty patients who satisfied technical inclusion criteria underwent whole-body DXA scan and US on the same day. Total and android fat mass (FM) and FM percentage (FM%) were considered as well as visceral fat (VAT) subcompartment in the android region; moreover, six new ROIs were designed on whole-body DXA images for the investigation of adiposity parameters at heart level. US provided epicardial fat thickness (EPI-thickness) and area (EPI-area), as measured following previously validated methods. Body mass index (BMI), gynoid and lower limbs (FM and FM%) were found not statistically correlated with EPI-thickness. The highest correlation was achieved by trunk FM (and FM%, with r = 0.544 and 0.480 respectively, P

The objective of this study was to evaluate the diagnostic performance of the new dual-energy X-ray absorptiometry equipment vs digital radiography (DR) in the detection and scoring of abdominal aortic calcifications (AACs). Seventy-five patients with indication for morphometric evaluation of the spine underwent vertebral fracture assessment (VFA) and spinal DR (gold standard). The radiographic and VFA images were analyzed to detect AAC using a previously validated 24-point scale (AAC-24) and a simplified 8-point scale (AAC-8). The evaluation was conducted by 2 expert radiologists and repeated by the more experienced of the 2 after 7d to verify the results. Patients with a score of 5 or more in AAC-24 and 3 or more in AAC-8 were considered at risk for cardiovascular diseases (CVDs). The aorta was not completely visible in 11 VFA and 1 DR images. DR detected AAC in 42 of the 63 patients (66.7%), whereas 15 patients (23.8%) were considered at risk for CVD. The VFA showed sensitivity, specificity, and accuracy in the detection of AAC with values of 78.6%, 85.7%, and 81.0%, respectively, with both AAC-24 and AAC-8; in the identification of patients at risk for CVD, VFA demonstrated sensitivity, specificity, and accuracy, respectively, with values of 86.7%, 100%, and 96.8% using AAC-24 and 86.7%, 93.8%, and 92.1% using AAC-8. In the detection of AAC, intraobserver agreement was superimposable using both the techniques (κ=1.00), whereas in the identification of patients at risk for CVD, kappa values were 0.96 and 0.95 using AAC-24 and 1.00 and 0.96 using AAC-8 for DR and VFA, respectively. Interobserver agreement in the evaluation of the presence/absence of AAC showed a kappa value of 0.76 for DR and 0.71 for VFA, whereas kappa values of 0.91 and 0.87 for DR and 0.85 and 0.83 for VFA were achieved for CVD risk using AAC-24 and AAC-8, respectively. AAC can be easily and accurately diagnosed by VFA with satisfactory accuracy, reproducibility, and repeatability. VFA may be used in the assessment and monitoring of AAC.

To investigate the predictive value for hepatic steatosis of a new software for the quantification of visceral fat by dual-energy X-ray absorptiometry (DXA) and to design new regions of interest (ROIs).Adult volunteers were prospectively screened for hepatic steatosis by ultrasonography to obtain a well-balanced population according to the presence/absence of the disease. 90 adult patients without steatosis and 90 with steatosis (mild, 53.3%; moderate, 37.7%; and severe, 10.0%) were recruited. On the same day, all subjects were submitted to blood testing and to anthropometric and whole-body DXA for body composition evaluation. A new software for android visceral fat assessment was employed, and six new "liver-suited" ROIs as well as two modified android ROIs were designed. Their association with steatosis grade was tested by correlation analysis.Fat mass (FM) of the new ROIs showed the highest correlation coefficients with steatosis grade (ρ = 0.610-0.619; p0.001), which was also confirmed by multivariate analysis. On the whole population, the new ROIs maintained the highest predictive role for liver steatosis, with areas under the receiver operating characteristic curve up to 0.820 ± 0.032. Inter- and intra-operator agreement for the new ROIs was excellent (k = 0.915-1.000 and k = 0.927-1.000).New ROIs could be designed, standardized and implemented in DXA whole-body scan to provide more specific and predictive values of hepatic lipid content.This is the first study to investigate the predictive value for hepatic steatosis of visceral and regional FM assessed on the hepatic site by DXA in comparison with ultrasonography, anthropometry and surrogate markers derived by previously validated algorithms (fatty liver index).

A man and a woman in their early 50s underwent CT for diff erent clinical indications, unrelated to endocrino logical or metabolic interests. The patients had almost identical sagittal abdominal diameters (supine abdominal height), and similar waist circumferences. Body-mass index (BMI) of the man was 29 kg/m2 and for the woman 32 kg/m2. The distribution of abdominal fat, however, was completely diff erent between the two individuals (fi gure). The man showed a predominance of visceral fat, whereas the woman’s large abdominal girth was mainly a result of

Purpose: Our aim was to investigate the link between adiposity fat indexes obtained using ultrasound (US) examination, total and android fat amount by dual-energy x-ray absorptiometry (DXA), and body weight (BW) in normal-weight, over-weight and obese subjects. Material & Methods: We retrospectively analyzed body composition (BC) parameters of 138 normal-weight (62M, 76F, age 41.2613.6year-old, BMI 22.361.5Kg/m2), 92 over-weight (60M, 32F, age 48.2613.3year-old, BMI 27.061.4Kg/m2) and 42 obese (4M, 38F, age 49.9612.8year-old, BMI 37.066.0Kg/m2) subjects. Data were collected from different studies in our Hospital where US and DXA evaluations were simultaneously performed for BC assessment. The carotid intimal-medial-thickness (CIMT), the ratio between minimum subcutaneous fat-thickness and maximum pre-peritoneal fat-thickness (wall-fat-index – WFI), and that one between maximum subcutaneous fat-thickness and intra-abdominal fat-thickness (MAR) were considered for US evaluations. Simple regression and ANOVA were used for the analysis (only p,0.05 were considered). Results: In all groups, WFI had significant correlations with total fat mass (FM) and FM percentage, while MAR got a relation with only BW; moreover, CIMT was related to android and whole-body FM. FM percentage in android region was linked to MAR and WFI only in normal-weight and over-weight subjects. Android FM was correlated with MAR only in normal-weight subjects. Conclusion: DXA, US and BW look at the human body from different points of view. An integration of these three techniques should be considered when the assessment of BC is needed.

Professor Romeo Canini’s name did not appear in the list of authors of the following abstract that was presented at the Special Scientific session of the ISS held in Athens in September 2010 and published in Skeletal Radiology (2010,10,1051). The title and complete list of authors is as follows; New dual-energy x-ray absorptiometry equipments in the assessment of vertebral fractures: technical limits and software accuracy. Alberto Bazzocchi, Danila Diano, Claudia Sassi, Giuseppe Battista, Giuseppe Guglielmi, Romeo Canini.