Successful treatment with selpercatinib after pralsetinib-related pneumonitis and intracranial failure in a patient with RET-rearranged nonsmall cell lung cancer.

Pralsetinib and selpercatinib are two highly potent and selective rearranged during transfection (RET) inhibitors that substantially improved the clinical outcome of patients with RET-rearranged non-small cell lung cancer. Treatment with one RET inhibitor after failure of the other is generally not recommended because of cross-resistance mechanisms. We report the case of a patient affected by metastatic RET-rearranged non-small cell lung cancer who experienced long-lasting disease control with pralsetinib. After 13 months from treatment start, the patient developed recurrent drug-related pneumonitis, requiring temporary interruptions and dose reductions and eventually failing to control the disease. Selpercatinib was then started as an off-label treatment, allowing both clinical and radiological intracranial disease control. Selpercatinib was well-tolerated at full dosage, and no pulmonary event occurred. In our case report, after pralsetinib dose reduction due to pulmonary toxicity, the therapeutic switch to selpercatinib allowed the patient to receive a full-dose treatment, eventually restoring disease control. Our case report and a few literature data suggest that switching from pralsetinib to selpercatinib may represent a therapeutic opportunity, especially for patients with brain metastases.

Study rationale and design of the PEOPLHE trial.

PURPOSE: Lung cancer screening (LCS) by low-dose computed tomography (LDCT) demonstrated a 20-40% reduction in lung cancer mortality. National stakeholders and international scientific societies are increasingly endorsing LCS programs, but translating their benefits into practice is rather challenging. The "Model for Optimized Implementation of Early Lung Cancer Detection: Prospective Evaluation Of Preventive Lung HEalth" (PEOPLHE) is an Italian multicentric LCS program aiming at testing LCS feasibility and implementation within the national healthcare system. PEOPLHE is intended to assess (i) strategies to optimize LCS workflow, (ii) radiological quality assurance, and (iii) the need for dedicated resources, including smoking cessation facilities. METHODS: PEOPLHE aims to recruit 1.500 high-risk individuals across three tertiary general hospitals in three different Italian regions that provide comprehensive services to large populations to explore geographic, demographic, and socioeconomic diversities. Screening by LDCT will target current or former (quitting < 10 years) smokers (> 15 cigarettes/day for > 25 years, or > 10 cigarettes/day for > 30 years) aged 50-75 years. Lung nodules will be volumetric measured and classified by a modified PEOPLHE Lung-RADS 1.1 system. Current smokers will be offered smoking cessation support. CONCLUSION: The PEOPLHE program will provide information on strategies for screening enrollment and smoking cessation interventions; administrative, organizational, and radiological needs for performing a state-of-the-art LCS; collateral and incidental findings (both pulmonary and extrapulmonary), contributing to the LCS implementation within national healthcare systems.

Percutaneous injection of sclerosant agents as an effective treatment for cystic malformations of the head and neck.

PURPOSE: To evaluate the clinical and aesthetic outcome of percutaneous injection of sclerosant agents to treat head and neck cystic malformations (HNCM) and to assess their recurrence rate based on histology and site. METHODS: Fifty-four subjects (mean age 46 years) with HNCM treated by percutaneous injection of sclerosant agents between January and December 2017 were included. Imaging and clinical data before and after the procedure were collected. Quality of Life Index, Pain Visual Analogue Scale, and Aesthetic Scale scores were measured to assess clinical and aesthetic outcomes. A size reduction of ≥ 70% assessed through the visual scale was considered significant. RESULTS: Of the 54 HNCM, there were 26 (48%) lymphatic malformations (LM), 13 (24%) salivary epithelial duct cysts of the parotid gland, 12 (22%) salivary mucoceles, and 3 (5%) branchial cysts. A significant size reduction and a satisfactory clinical-aesthetic outcome were observed in all types of LM. The number of reinterventions was significantly associated with the number of lesions (p < 0.001). The lowest number of interventions was observed in macrocystic lymphatic malformations (average of 1.2 interventions). All salivary epithelial duct cysts showed a significant reduction in size, a satisfactory clinical-aesthetic outcome, and an average of 1.16 interventions per patient. Mucoceles had a worse response, with only 3/14 patients showing a satisfactory and long-lasting clinical outcome (average of 1.16 interventions). Treatment of branchial cysts showed the worst outcome with a limited clinical response (3/3). CONCLUSION: Percutaneous injection of sclerosant agents may be considered as a first-line treatment for LM and salivary epithelial duct cysts.

Quantitative CT at Follow-Up of COVID-19 Pneumonia: Relationship with Pulmonary Function Tests.

BACKGROUND: The role of quantitative chest computed tomography (CT) is controversial in the follow-up of patients with COVID-19 pneumonia. The aim of this study was to test during the follow-up of COVID-19 pneumonia the association between pulmonary function tests (PFTs) and quantitative parameters extrapolated from follow-up (FU) CT scans performed at least 6 months after COVID-19 onset. METHODS: The study included patients older than 18 years old, admitted to the emergency department of our institution between 29 February 2020 and 31 December 2020, with a diagnosis of COVID-19 pneumonia, who underwent chest CT at admission and FU CT at least 6 months later; PFTs were performed within 6 months of FU CT. At FU CT, quantitative parameters of well-aerated lung and pneumonia extent were identified both visually and by software using CT density thresholds. The association between PFTs and quantitative parameters was tested by the calculation of the Spearman's coefficient of rank correlation (rho). RESULTS: The study included 40 patients (38% females; median age 63 years old, IQR, 56-71 years old). A significant correlation was identified between low attenuation areas% (%LAAs) <950 Hounsfield units (HU) and both forced expiratory volume in 1s/forced vital capacity (FEV1/FVC) ratio (rho -0.410, 95% CIs -0.639--0.112, p = 0.008) and %DLCO (rho -0.426, 95% CIs -0.678--0.084, p = 0.017). The remaining quantitative parameters failed to demonstrate a significant association with PFTs (p > 0.05). CONCLUSIONS: At follow-up, CT scans performed at least 6 months after COVID-19 pneumonia onset showed %LAAs that were inversely associated with %DLCO and could be considered a marker of irreversible lung damage.

Beyond Visual Interpretation: Quantitative Analysis and Artificial Intelligence in Interstitial Lung Disease Diagnosis "Expanding Horizons in Radiology".

Diffuse lung disorders (DLDs) and interstitial lung diseases (ILDs) are pathological conditions affecting the lung parenchyma and interstitial network. There are approximately 200 different entities within this category. Radiologists play an increasingly important role in diagnosing and monitoring ILDs, as they can provide non-invasive, rapid, and repeatable assessments using high-resolution computed tomography (HRCT). HRCT offers a detailed view of the lung parenchyma, resembling a low-magnification anatomical preparation from a histological perspective. The intrinsic contrast provided by air in HRCT enables the identification of even the subtlest morphological changes in the lung tissue. By interpreting the findings observed on HRCT, radiologists can make a differential diagnosis and provide a pattern diagnosis in collaboration with the clinical and functional data. The use of quantitative software and artificial intelligence (AI) further enhances the analysis of ILDs, providing an objective and comprehensive evaluation. The integration of "meta-data" such as demographics, laboratory, genomic, metabolomic, and proteomic data through AI could lead to a more comprehensive clinical and instrumental profiling beyond the human eye's capabilities.

Structural changes in lung morphology detected by MRI after modulating therapy with elexacaftor/tezacaftor/ivacaftor in adolescent and adult patients with cystic fibrosis.

INTRODUCTION: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves CFTR function in cystic fibrosis (CF) patients homozygous or heterozygous for F508del mutation. The aim of the study was to evaluate the response to ELX/TEZ/IVA treatment both clinically and morphologically in terms of bronchiectasis, bronchial wall thickening, mucus plugging, abscess and consolidations. METHODS: We retrospectively collected data from CF patients followed at Parma CF Centre (Italy) treated by ELX/TEZ/IVA between March and November 2021. Post-treatment changes in respiratory function, quality of life, sweat chloride concentration, body mass index, pulmonary exacerbations and lung structure by chest magnetic resonance imaging (MRI) were assessed. T2-and T1-weighted sequences were acquired with a 20 min-long scanning protocol on a 1.5T MRI scanner (Philips Ingenia) without administration of intravenous contrast media. RESULTS: 19 patients (32.5 ± 10.2 years) were included in the study. After 6 months of treatment with ELX/TEZ/IVA, MRI showed significant improvements in the morphological score (p < 0.001), with a reduction in bronchial wall thickening (p < 0.001) and mucus plugging (p 0.01). Respiratory function showed significant improvement in predicted FEV1% (58.5 ± 17.5 vs 71.4 ± 20.1, p < 0.001), FVC% (79.0 ± 11.1 vs 88.3 ± 14.4, p < 0.001), FEV1/FVC (0.61 ± 0.16 vs 0.67 ± 0.15, <0.001) and LCI2.5% (17.8 ± 4.3 vs 15.8 ± 4.1 p < 0.005). Significant improvement was found in body mass index (20.6 ± 2.7 vs 21.9 ± 2.4, p < 0.001), pulmonary exacerbations (2.3 ± 1.3 vs 1.4 ± 1.3 p 0.018) and sweat chloride concentration (96.5 ± 36.6 vs 41.1 ± 16.9, p < 0.001). CONCLUSIONS: Our study confirms the efficacy of ELX/TEZ/IVA in CF patients not only from a clinical point of view but also in terms of morphological changes of the lungs.

Fully automated calcium scoring predicts all-cause mortality at 12 years in the MILD lung cancer screening trial.

Coronary artery calcium (CAC) is a known risk factor for cardiovascular (CV) events and mortality but is not yet routinely evaluated in low-dose computed tomography (LDCT)-based lung cancer screening (LCS). The present analysis explored the capacity of a fully automated CAC scoring to predict 12-year mortality in the Multicentric Italian Lung Detection (MILD) LCS trial. The study included 2239 volunteers of the MILD trial who underwent a baseline LDCT from September 2005 to January 2011, with a median follow-up of 190 months. The CAC score was measured by a commercially available fully automated artificial intelligence (AI) software and stratified into five strata: 0, 1-10, 11-100, 101-400, and > 400. Twelve-year all-cause mortality was 8.5% (191/2239) overall, 3.2% with CAC = 0, 4.9% with CAC = 1-10, 8.0% with CAC = 11-100, 11.5% with CAC = 101-400, and 17% with CAC > 400. In Cox proportional hazards regression analysis, CAC > 400 was associated with a higher 12-year all-cause mortality both in a univariate model (hazard ratio, HR, 5.75 [95% confidence interval, CI, 2.08-15.92] compared to CAC = 0) and after adjustment for baseline confounders (HR, 3.80 [95%CI, 1.35-10.74] compared to CAC = 0). All-cause mortality significantly increased with increasing CAC (7% in CAC ≤ 400 vs. 17% in CAC > 400, Log-Rank p-value <0.001). Non-cancer at 12 years mortality was 3% (67/2239) overall, 0.8% with CAC = 0, 1.0% with CAC = 1-10, 2.9% with CAC = 11-100, 3.6% with CAC = 101-400, and 8.2% with CAC > 400 (Grey's test p < 0.001). In Fine and Gray's competing risk model, CAC > 400 predicted 12-year non-cancer mortality in a univariate model (sub-distribution hazard ratio, SHR, 10.62 [95% confidence interval, CI, 1.43-78.98] compared to CAC = 0), but the association was no longer significant after adjustment for baseline confounders. In conclusion, fully automated CAC scoring was effective in predicting all-cause mortality at 12 years in a LCS setting.

Relationship Between the Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) and Lung Adenocarcinoma Patterns: New Possible Insights.

INTRODUCTION: This study aimed to evaluate a potential relationship between the diffusing capacity of the lung for carbon monoxide (DLCO) and the aggressiveness of lung adenocarcinoma (ADC). METHODS: Patients who underwent radical surgery for lung ADC between 2001 and 2018 were retrospectively reviewed. DLCO values were dichotomized into DLCOlow (<80% of predicted) and DLCOnormal (≥80%). Relationships between DLCO and ADC histopathological features, clinical features, as well as with overall survival (OS), were evaluated. RESULTS: Four-hundred and sixty patients were enrolled, of which 193 (42%) were included in the DLCOlow group. DLCOlow was associated with smoking status, low FEV1, micropapillary and solid ADC, tumour grade 3, high tumour lymphoid infiltrate and presence of tumour desmoplasia. In addition, DLCO values were higher in low-grade ADC and progressively decreased in intermediate and high-grade ADC (p=0.024). After adjusting for clinical variables, at multivariable logistic regression analysis, DLCOlow still showed a significant correlation with high lymphoid infiltrate (p=0.017), presence of desmoplasia (p=0.065), tumour grade 3 (p=0.062), micropapillary and solid ADC subtypes (p=0.008). To exclude the association between non-smokers and well-differentiated ADC, the relationship between DLCO and histopathological ADC patterns was confirmed in the subset of 377 former and current smokers (p=0.021). At univariate analysis, gender, DLCO, FEV1, ADC histotype, tumour grade, stage, pleural invasion, tumour necrosis, tumour desmoplasia, lymphatic and blood invasion were significantly related with OS. At multivariate analysis, only gender (p<0.001), tumour stage (p<0.001) and DLCO (p=0.050) were significantly related with the OS. CONCLUSIONS: We found a relationship between DLCO and ADC patterns as well as with tumour grade, tumour lymphoid infiltrate and desmoplasia, suggesting that lung damage may be associated with tumour aggressiveness.

Ultra-low dose computed tomography protocols using spectral shaping for lung cancer screening: Comparison with low-dose for volumetric LungRADS classification.

PURPOSE: To compare Low-Dose Computed Tomography (LDCT) with four different Ultra-Low-Dose Computed Tomography (ULDCT) protocols for PN classification according to the Lung Reporting and Data System (LungRADS). METHODS: Three hundred sixty-one participants of an ongoing lung cancer screening (LCS) underwent single-breath-hold double chest Computed Tomography (CT), including LDCT (120kVp, 25mAs; CTDIvol 1,62 mGy) and one ULDCT among: fully automated exposure control ("ULDCT1"); fixed tube-voltage and current according to patient size ("ULDCT2"); hybrid approach with fixed tube-voltage ("ULDCT3") and tube current automated exposure control ("ULDCT4"). Two radiologists (R1, R2) assessed LungRADS 2022 categories on LDCT, and then after 2 weeks on ULDCT using two different kernels (R1: Qr49ADMIRE 4; R2: Br49ADMIRE 3). Intra-subject agreement for LungRADS categories between LDCT and ULDCT was measured by the k-Cohen Index with Fleiss-Cohen weights. RESULTS: LDCT-dominant PNs were detected in ULDCT in 87 % of cases on Qr49ADMIRE 4 and 88 % on Br49ADMIRE 3. The intra-subject agreement was: κULDCT1 = 0.89 [95 %CI 0.82-0.96]; κULDCT2 = 0.90 [0.81-0.98]; κULDCT3 = 0.91 [0.84-0.99]; κULDCT4 = 0.88 [0.78-0.97] on Qr49ADMIRE 4, and κULDCT1 = 0.88 [0.80-0.95]; κULDCT2 = 0.91 [0.86-0.96]; κULDCT3 = 0.87 [0.78-0.95]; and κULDCT4 = 0.88 [0.82-0.94] on Br49ADMIRE 3. LDCT classified as LungRADS 4B were correctly identified as LungRADS 4B at ULDCT3, with the lowest radiation exposure among the tested protocols (median effective doses were 0.31, 0.36, 0.27 and 0.37 mSv for ULDCT1, ULDCT2, ULDCT3, and ULDCT4, respectively). CONCLUSIONS: ULDCT by spectral shaping allows the detection and characterization of PNs with an excellent agreement with LDCT and can be proposed as a feasible approach in LCS.

Notch-Jagged1 signaling and response to bevacizumab therapy in advanced colorectal cancer: A glance to radiomics or back to physiopathology?

Introduction: The Notch intracellular domain (NICD) and its ligands Jagged-1(Jag1), Delta-like ligand (DLL-3) and DLL4 play an important role in neoangiogenesis. Previous studies suggest a correlation between the tissue levels of NICD and response to therapy with bevacizumab in colorectal cancer (CRC). Another marker that may predict outcome in CRC is radiomics of liver metastases. The aim of this study was to investigate the expression of NICD and its ligands and the role of radiomics in the selection of treatment-naive metastatic CRC patients receiving bevacizumab. Methods: Immunohistochemistry (IHC) for NICD, Jag1 and E-cadherin was performed on the tissue microarrays (TMAs) of 111 patients with metastatic CRC treated with bevacizumab and chemotherapy. Both the intensity and the percentage of stained cells were evaluated. The absolute number of CD4+ and CD8+ lymphocytes was counted in three different high-power fields and the mean values obtained were used to determine the CD4/CD8 ratio. The positivity of tumor cells to DLL3 and DLL4 was studied. The microvascular density (MVD) was assessed in fifteen cases by counting the microvessels at 20x magnification and expressed as MVD score. Abdominal CT scans were retrieved and imported into a dedicated workstation for radiomic analysis. Manually drawn regions of interest (ROI) allowed the extraction of radiomic features (RFs) from the tumor. Results: A positive association was found between NICD and Jag1 expression (p < 0.001). Median PFS was significantly shorter in patients whose tumors expressed high NICD and Jag1 (6.43 months vs 11.53 months for negative cases; p = 0.001). Those with an MVD score ≥5 (CD31-high, NICD/Jag1 positive) experienced significantly poorer survival. The radiomic model developed to predict short and long-term survival and PFS yielded a ROC-AUC of 0.709; when integrated with clinical and histopathological data, the integrated model improved the predictive score (ROC-AUC of 0.823). Discussion: These results show that high NICD and Jag1 expression are associated with progressive disease and early disease progression to anti VEGF-based therapy; the preliminary radiomic analyses show that the integration of quantitative information with clinical and histological data display the highest performance in predicting the outcome of CRC patients.

Are Interstitial Lung Abnormalities a Prognostic Factor of Worse Outcome in COVID-19 Pneumonia?

PURPOSE: To assess the association between interstitial lung abnormalities (ILAs) and worse outcome in patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19)-related pneumonia. MATERIALS AND METHODS: The study included patients older than 18 years, who were admitted at the emergency department between February 29 and April 30, 2020 with findings of COVID-19 pneumonia at chest computed tomography (CT), with positive reverse-transcription polymerase chain reaction nasal-pharyngeal swab for SARS-CoV-2, and with the availability of prepandemic chest CT. Prepandemic CTs were reviewed for the presence of ILAs, categorized as fibrotic in cases with associated architectural distortion, bronchiectasis, or honeycombing. Worse outcome was defined as intensive care unit (ICU) admission or death. Cox proportional hazards regression analysis was used to test the association between ICU admission/death and preexisting ILAs. RESULTS: The study included 147 patients (median age 73 y old; 95% CIs: 71-76-y old; 29% females). On prepandemic CTs, ILA were identified in 33/147 (22%) of the patients, 63% of which were fibrotic ILAs. Fibrotic ILAs were associated with higher risk of ICU admission or death in patients with COVID-19 pneumonia (hazard ratios: 2.73, 95% CIs: 1.50-4.97, P =0.001). CONCLUSIONS: In patients affected by COVID-19 pneumonia, preexisting fibrotic ILAs were an independent predictor of worse prognosis, with a 2.7 times increased risk of ICU admission or death. Chest CT scans obtained before the diagnosis of COVID-19 pneumonia should be carefully reviewed for the presence and characterization of ILAs.

Automated Coronary Artery Calcium and Quantitative Emphysema in Lung Cancer Screening: Association With Mortality, Lung Cancer Incidence, and Airflow Obstruction.

PURPOSE: To assess automated coronary artery calcium (CAC) and quantitative emphysema (percentage of low attenuation areas [%LAA]) for predicting mortality and lung cancer (LC) incidence in LC screening. To explore correlations between %LAA, CAC, and forced expiratory value in 1 second (FEV 1 ) and the discriminative ability of %LAA for airflow obstruction. MATERIALS AND METHODS: Baseline low-dose computed tomography scans of the BioMILD trial were analyzed using an artificial intelligence software. Univariate and multivariate analyses were performed to estimate the predictive value of %LAA and CAC. Harrell C -statistic and time-dependent area under the curve (AUC) were reported for 3 nested models (Model survey : age, sex, pack-years; Model survey-LDCT : Model survey plus %LAA plus CAC; Model final : Model survey-LDCT plus selected confounders). The correlations between %LAA, CAC, and FEV 1 and the discriminative ability of %LAA for airflow obstruction were tested using the Pearson correlation coefficient and AUC-receiver operating characteristic curve, respectively. RESULTS: A total of 4098 volunteers were enrolled. %LAA and CAC independently predicted 6-year all-cause (Model final hazard ratio [HR], 1.14 per %LAA interquartile range [IQR] increase [95% CI, 1.05-1.23], 2.13 for CAC ≥400 [95% CI, 1.36-3.28]), noncancer (Model final HR, 1.25 per %LAA IQR increase [95% CI, 1.11-1.37], 3.22 for CAC ≥400 [95%CI, 1.62-6.39]), and cardiovascular (Model final HR, 1.25 per %LAA IQR increase [95% CI, 1.00-1.46], 4.66 for CAC ≥400, [95% CI, 1.80-12.58]) mortality, with an increase in concordance probability in Model survey-LDCT compared with Model survey ( P <0.05). No significant association with LC incidence was found after adjustments. Both biomarkers negatively correlated with FEV 1 ( P <0.01). %LAA identified airflow obstruction with a moderate discriminative ability (AUC, 0.738). CONCLUSIONS: Automated CAC and %LAA added prognostic information to age, sex, and pack-years for predicting mortality but not LC incidence in an LC screening setting. Both biomarkers negatively correlated with FEV 1 , with %LAA enabling the identification of airflow obstruction with moderate discriminative ability.

MR-based simplified extraprostatic extension evaluation: comparison of performances of different predictive models.

OBJECTIVES: To test reproducibility and predictive value of a simplified score for assessment of extraprostatic tumor extension (sEPE grade). METHODS: Sixty-five patients (mean age ± SD, 67 years ± 6.3) treated with radical prostatectomy for prostate cancer who underwent 1.5-Tesla multiparametric magnetic resonance imaging (mpMRI) 6 months before surgery were enrolled. sEPE grade was derived from mpMRI metrics: curvilinear contact length > 15 mm (CCL) and capsular bulging/irregularity. The diameter of the index lesion (dIL) was also measured. Evaluations were independently performed by seven radiologists, and inter-reader agreement was tested by weighted Cohen K coefficient. A nested (two levels) Monte Carlo cross-validation was used. The best cut-off value for dIL was selected by means of the Youden J index to classify values into a binary variable termed dIL*. Logistic regression models based on sEPE grade, dIL, and clinical scores were developed to predict pathologic EPE. Results on validation set were assessed by the main metrics of the receiver operating characteristics curve (ROC) and by decision curve analysis (DCA). Based on our findings, we defined and tested an alternative sEPE grade formulation. RESULTS: Pathologic EPE was found in 31/65 (48%) patients. Average κw was 0.65 (95% CI 0.51-0.79), 0.66 (95% CI 0.48-0.84), 0.67 (95% CI 0.50-0.84), and 0.43 (95% CI 0.22-0.63) for sEPE grading, CLL ≥ 15 mm, dIL*, and capsular bulging/irregularity, respectively. The highest diagnostic yield in predicting EPE was obtained by combining both sEPE grade and dIL*(ROC-AUC 0.81). CONCLUSIONS: sEPE grade is reproducible and when combined with the dIL* accurately predicts extraprostatic tumor extension. KEY POINTS: • Simple and reproducible mpMRI semi-quantitative scoring system for extraprostatic tumor extension. • sEPE grade accurately predicts extraprostatic tumor extension regardless of reader expertise. • Accurate pre-operative staging and risk stratification for optimized patient management.

The radiological appearances of lung cancer treated with immunotherapy.

Therapy and prognosis of several solid and hematologic malignancies, including non-small cell lung cancer (NSCLC), have been favourably impacted by the introduction of immune checkpoint inhibitors (ICIs). Their mechanism of action relies on the principle that some cancers can evade immune surveillance by expressing surface inhibitor molecules, known as "immune checkpoints". ICIs aim to conceal tumoural checkpoints on the cell surface and reinvigorate the ability of the host immune system to recognize tumour cells, triggering an antitumoural immune response.In this review, we will focus on the imaging patterns of different responses occurring in patients treated by ICIs. We will also discuss imaging findings of immune-related adverse events (irAEs), along with current and future perspectives of metabolic imaging. Finally, we will explore the role of radiomics in the setting of ICI-treated patients.

Cytisine Therapy Improved Smoking Cessation in the Randomized Screening and Multiple Intervention on Lung Epidemics Lung Cancer Screening Trial.

INTRODUCTION: Cytisine, a partial agonist-binding nicotine acetylcholine receptor, is a promising cessation intervention. We conducted a single-center, randomized, controlled trial (RCT) in Italy to assess the efficacy and tolerability of cytisine as a smoking cessation therapy among lung cancer screening participants. METHODS: From July 2019 to March 2020, the Screening and Multiple Intervention on Lung Epidemics RCT enrolled 869 current heavy tobacco users in a low-dose computed tomography screening program, with a randomized comparison of pharmacologic intervention with cytisine plus counseling (N = 470) versus counseling alone (N = 399). The primary outcome was continuous smoking abstinence at 12 months, biochemically verified through carbon monoxide measurement. RESULTS: At the 12-month follow-up, the quit rate was 32.1% (151 participants) in the intervention arm and 7.3% (29 participants) in the control arm. The adjusted OR of continuous abstinence was 7.2 (95% confidence interval: 4.6-11.2). Self-reported adverse events occurred more frequently in the intervention arm (399 events among 196 participants) than in the control arm (230 events among 133 participants, p < 0.01). The most common adverse events were gastrointestinal symptoms, comprising abdominal swelling, gastritis, and constipation. CONCLUSIONS: The efficacy and safety observed in the Screening and Multiple Intervention on Lung Epidemics RCT indicate that cytisine, a very low-cost medication, is a useful treatment option for smoking cessation and a feasible strategy to improve low-dose computed tomography screening outcomes with a potential benefit for all-cause mortality.

Thoracic Ultrasound Strain Elastosonography as a Noninvasive Biomarker of Chronic Obstructive Pulmonary Disease-Associated Lung Injury: A Feasibility Study.

BACKGROUND: Transthoracic strain elastosonography (TSE) is being increasingly studied for estimating lung-pleura interface stiffness in pulmonary fibrosis. To date, no data exist on its application in chronic obstructive pulmonary disease (COPD). OBJECTIVES: The aim of this article was to describe the TSE pattern in patients with COPD and healthy subjects, either smokers or nonsmokers, and evaluate the feasibility of this technique for early detection of COPD in smokers. METHODS: Nineteen patients with COPD, twenty-one healthy smokers, and twenty healthy nonsmokers underwent spirometry and TSE. Elastosonography was performed by one ultrasound-certified operator on 12 different scans for each participant, on right and left sides, anteriorly and posteriorly, on upper and lower lobes. For each scan, lung-pleura interface stiffness index (SI) was calculated, and the average SI on all 12 scans (SI-12) and on posterior basal scans (SI-PB) was calculated and used for comparisons among groups of participants and correlations with spirometric parameters. RESULTS: Patients with lung injury (i.e., with COPD or healthy smokers) exhibited significantly increased lung-pleura interface stiffness on TSE, measured by SI-12 and SI-PB, than healthy nonsmokers (p < 0.05). Unlike SI-12, SI-PB was able to discriminate between subjects with lung injury and healthy nonsmokers on receiver operating characteristics analysis (area under the curve 0.846, 95% confidence interval 0.730-0.926, p < 0.001) and correlated with forced expiratory volume in the first second (r = -0.31, p = 0.018). CONCLUSION: The measurement of lung-pleura interface stiffness by TSE in posterior basal scans was able to discriminate patients with lung injury from healthy nonsmokers. The role of TSE for detecting early lung damage in COPD should be further investigated.

Volumetric Measurements in Lung Cancer Screening Reduces Unnecessary Low-Dose Computed Tomography Scans: Results from a Single-Center Prospective Trial on 4119 Subjects.

This study aims to compare the low-dose computed tomography (LDCT) outcome and volume-doubling time (VDT) derived from the measured volume (MV) and estimated volume (EV) of pulmonary nodules (PNs) detected in a single-center lung cancer screening trial. MV, EV and VDT were obtained for prevalent pulmonary nodules detected at the baseline round of the bioMILD trial. The LDCT outcome (based on bioMILD thresholds) and VDT categories were simulated on PN- and screenee-based analyses. A weighted Cohen's kappa test was used to assess the agreement between diagnostic categories as per MV and EV, and 1583 screenees displayed 2715 pulmonary nodules. In the PN-based analysis, 40.1% PNs were included in different LDCT categories when measured by MV or EV. The agreements between MV and EV were moderate (κ = 0.49) and fair (κ = 0.37) for the LDCT outcome and VDT categories, respectively. In the screenee-based analysis, 46% pulmonary nodules were included in different LDCT categories when measured by MV or EV. The agreements between MV and EV were moderate (κ = 0.52) and fair (κ = 0.34) for the LDCT outcome and VDT categories, respectively. Within a simulated lung cancer screening based on a recommendation by estimated volumetry, the number of LDCTs performed for the evaluation of pulmonary nodules was higher compared with in prospective volumetric management.

Interstitial lung abnormalities: new insights between theory and clinical practice.

Interstitial lung abnormalities (ILAs) represent radiologic abnormalities incidentally detected on chest computed tomography (CT) examination, potentially related to interstitial lung diseases (ILD). Numerous studies have demonstrated that ILAs are associated with increased risk of progression toward pulmonary fibrosis and mortality. Some radiological patterns have been proven to be at a higher risk of progression. In this setting, the role of radiologists in reporting these interstitial abnormalities is critical. This review aims to discuss the most recent advancements in understanding this radiological entity and the open issues that still prevent the translation from theory to practice, emphasizing the importance of ILA recognition and adequately reporting in clinical practice.

The diagnostic value of grey-scale inversion technique in chest radiography.

PURPOSE: We investigated whether the additional use of grey-scale inversion technique improves the interpretation of eight chest abnormalities, in terms of diagnostic performance and interobserver variability. MATERIAL AND METHODS: A total of 507 patients who underwent a chest computed tomography (CT) examination and a chest radiography (CXR) within 24 h were enrolled. CT was the standard of reference. Images were retrospectively reviewed for the presence of atelectasis, consolidation, interstitial abnormality, nodule, mass, pleural effusion, pneumothorax and rib fractures. Four CXR reading settings, involving 3 readers were organized: only standard; only inverted; standard followed by inverted; and inverted followed by standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy, assessed with the area under the curve (AUC), and their 95% confidence interval were calculated for each reader and setting. Interobserver agreement was tested by Cohen's K test with quadratic weights (Kw) and its 95%CI. RESULTS: CXR sensitivity % for any finding was 35.1 (95% CI: 33 to 37) for setting 1, 35.9 (95% CI: 33 to 37), for setting 2, 32.59 (95% CI: 30 to 34) for setting 3, and 35.56 (95% CI: 33 to 37) for setting 4; specificity % 93.78 (95% CI: 91 to 95), 93.92 (95% CI: 91 to 95), 94.43 (95% CI: 92 to 96), 93.86 (95% CI: 91 to 95); PPV % 56.22 (95% CI: 54.2 to 58.2), 56.49 (95% CI: 54.5 to 58.5), 57.15 (95% CI: 55 to 59), 56.75 (95% CI: 54 to 58); NPV % 85.66 (95% CI: 83 to 87), 85.74 (95% CI: 83 to 87), 85.29 (95% CI: 83 to 87), 85.73 (95% CI: 83 to 87); AUC values 0.64 (95% CI: 0.62 to 0.66), 0.65 (95% CI: 0.63 to 0.67), 0.64 (95% CI: 0.62 to 0.66), 0.65 (95% CI: 0.63 to 0.67); Kw values 0.42 (95% CI: 0.4 to 0.44), 0.40 (95% CI: 0.38 to 0.42), 0.42 (95% CI: 0.4 to 0.44), 0.41 (95% CI: 0.39 to 0.43) for settings 1, 2, 3 and 4, respectively. CONCLUSIONS: No significant advantages were observed in the use of grey-scale inversion technique neither over standard display mode nor in combination at the detection of eight chest abnormalities.

European lung cancer screening: valuable trial evidence for optimal practice implementation.

Lung cancer screening (LCS) by low-dose computed tomography is a strategy for secondary prevention of lung cancer. In the last two decades, LCS trials showed several options to practice secondary prevention in association with primary prevention, however, the translation from trial to practice is everything but simple. In 2020, the European Society of Radiology and European Respiratory Society published their joint statement paper on LCS. This commentary aims to provide the readership with detailed description about hurdles and potential solutions that could be encountered in the practice of LCS.