Lung UltrasouNd Guided surfactant therapy in preterm infants: an international multicenter randomized control trial (LUNG study).

BACKGROUND: The management of respiratory distress syndrome (RDS) in premature newborns is based on different types of non-invasive respiratory support and on surfactant replacement therapy (SRT) to avoid mechanical ventilation as it may eventually result in lung damage. European guidelines currently recommend SRT only when the fraction of inspired oxygen (FiO2) exceeds 0.30. The literature describes that early SRT decreases the risk of bronchopulmonary dysplasia (BPD) and mortality. Lung ultrasound score (LUS) in preterm infants affected by RDS has proven to be able to predict the need for SRT and different single-center studies have shown that LUS may increase the proportion of infants that received early SRT. Therefore, the aim of this study is to determine if the use of LUS as a decision tool for SRT in preterm infants affected by RDS allows for the reduction of the incidence of BPD or death in the study group. METHODS/DESIGN: In this study, 668 spontaneously-breathing preterm infants, born at 25+0 to 29+6 weeks' gestation, in nasal continuous positive airway pressure (nCPAP) will be randomized to receive SRT only when the FiO2 cut-off exceeds 0.3 (control group) or if the LUS score is higher than 8 or the FiO2 requirements exceed 0.3 (study group) (334 infants per arm). The primary outcome will be the difference in proportion of infants with BPD or death in the study group managed compared to the control group. DISCUSSION: Based on previous published studies, it seems that LUS may decrease the time to administer surfactant therapy. It is known that early surfactant administration decreases BPD and mortality. Therefore, there is rationale for hypothesizing a reduction in BPD or death in the group of patients in which the decision to administer exogenous surfactant is based on lung ultrasound scores. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05198375 . Registered on 20 January 2022.

Association between Contrast-Enhanced Computed Tomography Radiomic Features, Genomic Alterations and Prognosis in Advanced Lung Adenocarcinoma Patients.

Non-invasive methods to assess mutational status, as well as novel prognostic biomarkers, are warranted to foster therapy personalization of patients with advanced non-small cell lung cancer (NSCLC). This study investigated the association of contrast-enhanced Computed Tomography (CT) radiomic features of lung adenocarcinoma lesions, alone or integrated with clinical parameters, with tumor mutational status (EGFR, KRAS, ALK alterations) and Overall Survival (OS). In total, 261 retrospective and 48 prospective patients were enrolled. A Radiomic Score (RS) was created with LASSO-Logistic regression models to predict mutational status. Radiomic, clinical and clinical-radiomic models were trained on retrospective data and tested (Area Under the Curve, AUC) on prospective data. OS prediction models were trained and tested on retrospective data with internal cross-validation (C-index). RS significantly predicted each alteration at training (radiomic and clinical-radiomic AUC 0.95-0.98); validation performance was good for EGFR (AUC 0.86), moderate for KRAS and ALK (AUC 0.61-0.65). RS was also associated with OS at univariate and multivariable analysis, in the latter with stage and type of treatment. The validation C-index was 0.63, 0.79, and 0.80 for clinical, radiomic, and clinical-radiomic models. The study supports the potential role of CT radiomics for non-invasive identification of gene alterations and prognosis prediction in patients with advanced lung adenocarcinoma, to be confirmed with independent studies.

Application of nnU-Net for Automatic Segmentation of Lung Lesions on CT Images and Its Implication for Radiomic Models.

Radiomics investigates the predictive role of quantitative parameters calculated from radiological images. In oncology, tumour segmentation constitutes a crucial step of the radiomic workflow. Manual segmentation is time-consuming and prone to inter-observer variability. In this study, a state-of-the-art deep-learning network for automatic segmentation (nnU-Net) was applied to computed tomography images of lung tumour patients, and its impact on the performance of survival radiomic models was assessed. In total, 899 patients were included, from two proprietary and one public datasets. Different network architectures (2D, 3D) were trained and tested on different combinations of the datasets. Automatic segmentations were compared to reference manual segmentations performed by physicians using the DICE similarity coefficient. Subsequently, the accuracy of radiomic models for survival classification based on either manual or automatic segmentations were compared, considering both hand-crafted and deep-learning features. The best agreement between automatic and manual contours (DICE = 0.78 ± 0.12) was achieved averaging 2D and 3D predictions and applying customised post-processing. The accuracy of the survival classifier (ranging between 0.65 and 0.78) was not statistically different when using manual versus automatic contours, both with hand-crafted and deep features. These results support the promising role nnU-Net can play in automatic segmentation, accelerating the radiomic workflow without impairing the models' accuracy. Further investigations on different clinical endpoints and populations are encouraged to confirm and generalise these findings.

Pre-operative evaluation of epithelial ovarian cancer patients: Role of whole body diffusion weighted imaging MR and CT scans in the selection of patients suitable for primary debulking surgery. A single-centre study.

PURPOSE: to evaluate the accuracy of Whole Body MRI including Diffusion-Weighted Imaging sequences (WB DWI MR) in the assessment of sites of disease in epithelial ovarian cancer (EOC), in comparison to CT; to evaluate whether a clinical-radiological score may predict suboptimal cytoreductive surgery. METHODS: patients with suspected EOC who underwent pre-operative WB DWI MR were included; CT scans were recorded. Data recorded included: age, staging, dates of examinations and surgery; tumour markers; sites of disease at imaging scans and at surgery. For calculation of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of WB DWI MR and CT, surgical evaluation represented the gold standard. The accuracy of WB DWI MR and CT was compared. The association between clinical and radiological criteria with sub-optimal cytoreduction was tested to identify a final model to predict sub-optimal cytoreduction. RESULTS: 92 patients were included; 77/92 (83.7 %) were optimally cytoreduced. Sixty-six CT and 92 MR examinations were evaluated. WB DWI MR showed overall higher accuracy than CT in assessing all sites, but it performed significantly better than CT specifically for involvement of mesentery, lumbo-aortic lymph nodes, pelvis, large bowel, sigmoid-rectum. The predicting score for suboptimal cytoreduction included: mesenteric carcinomatosis; mesenteric retraction; large bowel carcinomatosis. CONCLUSIONS: In pre-operative evaluation of EOC patients, WB DW MRI is accurate for assessment of multiple sites and it is significantly more accurate than CT for specific unresectable sites. In our series, significant sites of disease for suboptimal cytoreduction were mesenteric carcinomatosis, mesenteric retraction and large bowel carcinomatosis.

Do DWI and quantitative DCE perfusion MR have a prognostic value in high-grade serous ovarian cancer?

PURPOSE: To evaluate whether perfusion and diffusion parameters from staging MR in ovarian cancer (OC) patients may predict the presence of residual tumor at surgery and the progression-free survival (PFS) in 12 months. MATERIALS AND METHODS: Patients who are from a single institution, candidate for OC to cytoreductive surgery and undergoing MR for staging purposes were included in this study. Inclusion criteria were: preoperative MR including diffusion-weighted imaging (DWI) and perfusion dynamic contrast-enhanced (DCE) sequence; cytoreductive surgery performed within a month from MR; and minimum follow-up of 12 months. Patients' characteristics including the presence of residual tumor at surgery (R0 or R1) and relapse within 12 months from surgery were recorded. DWI parameters included apparent diffusion coefficient (ADC) of the largest ovarian mass (O-ADC) and normalized ovarian ADC as a ratio between ovarian ADC and muscle ADC (M-ADC). DCE quantitative parameters included were descriptors of tumor vascular properties such as forward and backward transfer constants, plasma volume and volume of extracellular space. Statistical analysis was performed, and p values < 0.05 were considered significant. RESULTS: Forty-nine patients were included. M-ADC showed a slightly significant association with the presence of residual tumor at surgery. None of the other functional parameters showed either difference between R0 and R1 patients or association with PFS in the first 12 months. CONCLUSIONS: This preliminary study demonstrated a slightly significant association between normalized ovarian ADC and the presence of residual tumor at surgery. The other perfusion and diffusion parameters were not significant for the endpoints of this study.

Genomics of non-small cell lung cancer (NSCLC): Association between CT-based imaging features and EGFR and K-RAS mutations in 122 patients-An external validation.

OBJECTIVE: To validate previously identified associations between radiological features and clinical features with Epidermal Growth Factor Receptor (EGFR)/ Kirsten RAt Sarcoma (KRAS) alterations in an independent group of patients with Non-Small Cell Lung Cancer (NSCLC). MATERIAL AND METHODS: A total of 122 patients with NSCLC tested for EGFR/KRAS alterations were included. Clinical and radiological features were recorded. Univariate analysis were performed to look at the associations of the studied features with EGFR/KRAS alterations. Previously calculated composite model parameters for each gene alteration prediction were applied to this validation cohort. ROC (Receiver Operating Characteristic) curves were drawn using the previously validated composite models, and also for each significant individual characteristic of the previous training cohort model. The Area Under the ROC Curve (AUC) with 95% Confidence Intervals (CI) was calculated and compared between the full models. RESULTS: At univariate analysis, EGFR+ confirmed an association with an internal air bronchogram, pleural retraction, emphysema and lack of smoking; KRAS+ with round shape, emphysema and smoking. The AUC (95%CI) in the new cohort was confirmed to be high for EGFR+ prediction, with a value of: 0.82 (0.69-0.95) vs. 0.82 in the previous cohort, whereas it was smaller for KRAS+ prediction, with a value of 0.60 (0.48-0.72) vs. 0.67 in the previous cohort. Looking at single features in the new cohort, we found that the AUC for the models including only smoking was similar to that of the full model (including radiological and clinical features) for both gene alterations. CONCLUSIONS: Although this study validated the significant association of clinical and radiological features with EGFR/KRAS alterations, models based on these composite features are not superior to smoking history alone to predict the mutations.

A cancer-mimicking diagnosis of peritoneal carcinosis: report of a case of abdominal non-tuberculous mycobacterial infection.

Abdominal non-tuberculous mycobacterial infection is a rare condition in healthy patients. When it occurs, it leads to the appearance of typical findings of peritoneal involvement, such as thickening of the peritoneal leaflets and the omentum, ascites and enlargement of lymph nodes and of mesenteric nodules. These findings may be misdiagnosed as tumour peritoneal implants. In case of spontaneous regression of the peritoneal involvement and ascites, as well as in the absence of malignancy, the suspicion of infectious disease, including abdominal nontuberculous mycobacterial infection, should be considered.

Unindicated multiphase CT scans in non-traumatic abdominal emergencies for women of reproductive age: a significant source of unnecessary exposure.

PURPOSE: To determine the frequency of unindicated CT phases and the resultant excess of absorbed radiation doses to the uterus and ovaries in women of reproductive age who have undergone CT for non-traumatic abdomino-pelvic emergencies. MATERIALS AND METHODS: We reviewed all abdomino-pelvic CT examinations in women of reproductive age (40 years or less), between 1 June 2012 and 31 January 2015. We evaluated the appropriateness of each CT phase on the basis of clinical indications, according to ACR appropriateness criteria and evidence-based data from the literature. The doses to uterus and ovaries for each phase were calculated with the CTEXPO software, taking into consideration the size-specific dose estimate (SSDE) after measuring the size of every single patient. RESULTS: The final cohort was composed of 76 female patients with an average age of 30 (from 19 to 40 years). In total, 197 CT phases were performed with an average of 2.6 phases per patient. Out of these, 93 (47%) were unindicated with an average of 1.2 inappropriate phases per patient. Unindicated scans were most frequent for appendicitis and unlocalized abdominal pain. The excesses of mean radiation doses to the uterus and ovaries due to unindicated phases were, respectively, of 38 and 33 mSv per patient. CONCLUSION: In our experience, unindicated additional CT phases were numerous with a significant excess radiation dose without an associated clinical benefit. This excess of radiation could have been avoided by widespread adoption of the ACR appropriateness criteria and evidence-based data from the literature.

Evaluation of inter-observer variability according to RECIST 1.1 and its influence on response classification in CT measurement of liver metastases.

OBJECTIVE: The aim of this study is the evaluation of inter-observer variability in the measurement of liver metastases according to RECIST and its influence on response classification. PATIENTS AND METHODS: A total of 100 radiologists measured liver target lesions, on pre- and post-chemotherapy CT scans of three patients. Each observer filled out a questionnaire about his personal and work features. The evaluations of a well experienced radiologist, considered as "the gold standard", were compared to those taken by the observers. The percentage of the observers in agreement with the reviewer, in terms of the response category and in terms of inter-observer variability, was calculated for each patient. RESULTS: The percentage of the inter-observer agreement was elevated. Most of the observers in agreement with the reviewer were senior radiologists, while those who disagreed were junior radiologist, but this result did not reach a statistical significance. More than 30% of observers disagreed with the reviewer at least in one of the three cases. CONCLUSIONS: RECIST measurements are reproducible on a large and heterogeneous population of radiologists. Age and expertise of the radiologist remain the most critical factors: this suggests a revision by well-experienced radiologists in clinical trials.

Signal intensity change on unenhanced T1-weighted images in dentate nucleus and globus pallidus after multiple administrations of gadoxetate disodium: an intraindividual comparative study.

PURPOSE: To investigate whether there is an increased signal intensity (SI) of dentate nucleus (DN) and globus pallidus (GP) on unenhanced T1-weighted magnetic resonance imaging (MRI), in patients who had undergone multiple administrations of gadoxetate disodium. MATERIALS AND METHODS: We retrospectevely included stage III melanoma patients, who had been previously enrolled in a trial of adjuvant therapy and who had undergone whole-body contrast-enhanced MRIs with gadoxetate disodium every three months for their follow-up. The SI ratios of DN-to-pons and GP-to-thalamus on unenhanced T1-weighted images were calculated. The difference in SI ratios between the first and the last MRI examinations was assessed and a linear mixed model was performed to detect how SI ratios varied with the number of administrations. RESULTS: Eighteen patients were included in our study. The number of gadoxetate disodium administrations ranged from 2 to 18. Paired t-test did not show any significant difference in DN-to-pons (p=0.21) and GP-to-thalamus (p=0.09) SI ratios by the end of the study. DN-to-pons SI ratio and GP-to-thalamus SI ratio did not significantly increase with increasing the number of administrations (p=0.14 and p=0.06, respectively). CONCLUSION: Multiple administrations of gadoxetate disodium are not associated with increased SI in DN and GP in the brain. KEY POINTS: • Gadolinium may deposit in the human brain after multiple GBCA administrations. • Gadolinium deposition is associated with increased T1W signal intensity • Increase in signal intensity is most apparent within the DN and GP • Multiple administrations of gadoxetate disodium do not increase T1W signal.