Bronchoscopically-visible massive central airway cancer cavitation is associated with metastatic disease, lack of actionable mutations and poor prognosis: a case series.

Cavitating lung tumors occur in approximately 10-15% of the patients, are more commonly associated with squamous histology, and are typically located in the lung parenchyma. Herein we describe an exceedingly rare series of 5 patients, 4 of whom treatment-naïve, whose tumor caused the disruption of the normal airway anatomy at the level of lobar or segmental bronchi, leading to the formation of an endoscopically-visible cavity which ended up in the lung parenchyma or even into the pleural space. Sex (3 males, 2 females), smoking habit (2 never smokers, 2 former smokers, 1 current smoker), and histology (3 adenocarcinoma, 2 squamous cell carcinoma) were heterogeneous, but the 4 patients treatment-naïve presented with metastatic disease, poor ECOG performance status, similar clinical complaints of long duration, and lack of actionable mutations. The only patient who exhibited a meaningful response to treatment had the lowest symptoms' duration, the smallest size of the cavitated mass, and the best performance status at the time of diagnosis. This series provides the first comprehensive description of a rare presentation of lung cancer characterized by similar clinical complaints, delayed diagnosis and poor prognosis.

Thirty-Day Complications, Unplanned Hospital Encounters, and Mortality after Endosonography and/or Guided Bronchoscopy: A Prospective Study.

BACKGROUND AND OBJECTIVE: Limited data exist regarding the adverse events of advanced diagnostic bronchoscopy, with most of the available information derived from retrospective datasets that primarily focus on early complications. METHODS: We conducted a 15-month prospective cohort study among consecutive patients undergoing endosonography and/or guided bronchoscopy under general anesthesia. We evaluated the 30-day incidence of severe complications, any complication, unplanned hospital encounters, and deaths. Additionally, we analyzed the time of onset (immediate, within 1 h of the procedure; early, 1 h-24 h; late, 24 h-30 days) and identified risk factors associated with these events. RESULTS: Thirty-day data were available for 697 out of 701 (99.4%) enrolled patients, with 85.6% having suspected malignancy and multiple comorbidities (median Charlson Comorbidity Index (IQR): 4 (2-5)). Severe complications occurred in only 17 (2.4%) patients, but among them, 10 (58.8%) had unplanned hospital encounters and 2 (11.7%) died within 30 days. A significant proportion of procedure-related severe complications (8/17, 47.1%); unplanned hospital encounters (8/11, 72.7%); and the two deaths occurred days or weeks after the procedure. Low-dose attenuation in the biopsy site on computed tomography was independently associated with any complication (OR: 1.87; 95% CI 1.13-3.09); unplanned hospital encounters (OR: 2.17; 95% CI 1.10-4.30); and mortality (OR: 4.19; 95% CI 1.74-10.11). CONCLUSIONS: Severe complications arising from endosonography and guided bronchoscopy, although uncommon, have significant clinical consequences. A substantial proportion of adverse events occur days after the procedure, potentially going unnoticed and exerting a negative clinical impact if a proactive surveillance program is not implemented.

Lung cancer multi-omics digital human avatars for integrating precision medicine into clinical practice: the LANTERN study.

BACKGROUND: The current management of lung cancer patients has reached a high level of complexity. Indeed, besides the traditional clinical variables (e.g., age, sex, TNM stage), new omics data have recently been introduced in clinical practice, thereby making more complex the decision-making process. With the advent of Artificial intelligence (AI) techniques, various omics datasets may be used to create more accurate predictive models paving the way for a better care in lung cancer patients. METHODS: The LANTERN study is a multi-center observational clinical trial involving a multidisciplinary consortium of five institutions from different European countries. The aim of this trial is to develop accurate several predictive models for lung cancer patients, through the creation of Digital Human Avatars (DHA), defined as digital representations of patients using various omics-based variables and integrating well-established clinical factors with genomic data, quantitative imaging data etc. A total of 600 lung cancer patients will be prospectively enrolled by the recruiting centers and multi-omics data will be collected. Data will then be modelled and parameterized in an experimental context of cutting-edge big data analysis. All data variables will be recorded according to a shared common ontology based on variable-specific domains in order to enhance their direct actionability. An exploratory analysis will then initiate the biomarker identification process. The second phase of the project will focus on creating multiple multivariate models trained though advanced machine learning (ML) and AI techniques for the specific areas of interest. Finally, the developed models will be validated in order to test their robustness, transferability and generalizability, leading to the development of the DHA. All the potential clinical and scientific stakeholders will be involved in the DHA development process. The main goals aim of LANTERN project are: i) To develop predictive models for lung cancer diagnosis and histological characterization; (ii) to set up personalized predictive models for individual-specific treatments; iii) to enable feedback data loops for preventive healthcare strategies and quality of life management. DISCUSSION: The LANTERN project will develop a predictive platform based on integration of multi-omics data. This will enhance the generation of important and valuable information assets, in order to identify new biomarkers that can be used for early detection, improved tumor diagnosis and personalization of treatment protocols. ETHICS COMMITTEE APPROVAL NUMBER: 5420 - 0002485/23 from Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore Ethics Committee. TRIAL REGISTRATION: clinicaltrial.gov - NCT05802771.

Reducing Post-Operative Alveolo-Pleural Fistula by Applying PGA-Sheets (Neoveil) after Major Lung Resection: A Historical Case-Control Study.

Alveolo-pleural fistula remains a serious post-operative complication in lung cancer patients after surgery, which is associated with prolonged hospital stay and higher healthcare costs. The aim of this study is to evaluate the efficacy of a polyglycol acid (PGA)-sheet known as Neoveil in preventing post-operative air-leak in cases of detected intra-operative air-leak after lung resection. Between 11/2021 and 7/2022, a total of 329 non-small cell lung cancer (NSCLC) patients were surgically treated in two institutions. Major lung resections were performed in 251 cases. Among them, 44 patients with significant intra-operative air-leak at surgery were treated by reinforcing staple lines with Neoveil (study group). On the other hand, a historical group (selected by propensity score matched analysis) consisting of 44 lung cancer patients with significant intra-operative air leak treated by methods other than the application of sealant patches were considered as the control group. The presence of prolonged air-leak (primary endpoint), pleural drainage duration, hospital stay, and post-operative complication rates were evaluated. The results showed that prolonged air-leak (>5 days after surgery) was not observed in study group, while this event occurred in four patients (9.1%) in the control group. Additionally, a substantial reduction (despite not statistically significant) in the chest tube removal was noted in the study group with respect to the control group (3.5 vs. 4.5, p = 0.189). In addition, a significant decrease in hospital stay (4 vs. 6 days, p = 0.045) and a reduction in post-operative complications (2 vs. 10, p = 0.015) were observed in the study group when compared with the control group. Therefore, in cases associated with intra-operative air-leak after major lung resection, Neoveil was considered a safer and more effective aerostatic tool and represents a viable option during surgical procedures.

Rate and Predictors of Unforeseen PN1/PN2-Disease in Surgically Treated cN0 NSCLC-Patients with Primary Tumor > 3 cm: Nationwide Results from Italian VATS-Group Database.

Background. Since no robust data are available on the real rate of unforeseen N1-N2 disease (uN) and the relative predictive factors in clinical-N0 NSCLC with peripheral tumours > 3 cm, the usefulness of performing a (mini)invasive mediastinal staging in this setting is debated. Herein, we investigated these issues in a nationwide database. Methods. From 01/2014 to 06/2020, 15,784 thoracoscopic major lung resections were prospectively recorded in the "Italian VATS-Group" database. Among them, 1982 clinical-N0 peripheral solid-type NSCLC > 3 cm were identified, and information was retrospectively reviewed. A mean comparison of more than two groups was made by ANOVA (Bonferroni correction for multiple comparisons), while associations between the categorical variables were estimated with a Chi-square test. The multivariate logistic regression model and Kaplan-Meyer method were used to identify the independent predictors of nodal upstaging and survival results, respectively. Results. At pathological staging, 229 patients had N1-involvement (11.6%), and 169 had uN2 disease (8.5%). Independent predictors of uN1 were SUVmax (OR: 1.98; CI 95: 1.44-2.73, p = 0.0001) and tumour-size (OR: 1.52; CI: 1.11-2.10, p = 0.01), while independent predictors of uN2 were age (OR: 0.98; CI 95: 0.96-0.99, p = 0.039), histology (OR: 0.48; CI 95: 0.30-0.78, p = 0.003), SUVmax (OR: 2.07; CI 95: 1.15-3.72, p = 0.015), and the number of resected lymph nodes (OR: 1.03; CI 95: 1.01-1.05, p = 0.002). Conclusions. The unforeseen N1-N2 disease in cN0/NSCLCs > 3 cm undergoing VATS resection is observable in between 12 and 8% of all cases. We have identified predictors that could guide physicians in selecting the best candidate for (mini)invasive mediastinal staging.

Ultrasound-Guided Needle Aspiration Biopsy of Superficial Metastasis of Lung Cancer with and without Rapid On-Site Evaluation: A Randomized Trial.

BACKGROUND AND OBJECTIVE: Studies which evaluated the role of an ultrasound-guided needle aspiration biopsy (US-NAB) of metastases from lung cancer located in "superficial" organs/tissues are scant, and none of them assessed the possible impact of rapid on-site evaluation (ROSE) on diagnostic accuracy and safety outcomes. METHODS: Consecutive patients with suspected superficial metastases from lung cancer were randomized 1:1 to US-NAB without (US-NAB group) or with ROSE (ROSE group). The diagnostic yield for a tissue diagnosis was the primary outcome. Secondary outcomes included the diagnostic yield for cancer genotyping, the diagnostic yield for PD-L1 testing, and safety. RESULTS: During the study period, 136 patients were randomized to receive an US-NAB with (n = 68) or without ROSE (n = 68). We found no significant differences between the ROSE group and the US-NAB group in terms of the diagnostic yields for tissue diagnosis (94.1% vs. 97%, respectively; p = 0.68), cancer genotyping (88% vs. 91.8%, respectively; p = 0.56), and PD-L1 testing (93.5% vs. 90.6%, respectively; p = 0.60). Compared to the diagnostic US-NAB procedures, the non-diagnostic procedures were characterized by less common use of a cutting needle (66.6% vs. 96.9%, respectively; p = 0.0004) and less common retrieval of a tissue core (37.5% vs. 98.5%; p = 0.0001). Only one adverse event (vasovagal syncope) was recorded. CONCLUSION: US-NAB of superficial metastases is safe and has an excellent diagnostic success regardless of the availability of ROSE. These findings provide a strong rationale for using US-NAB as the first-step method for tissue acquisition whenever a suspected superficial metastatic lesion is identified in patients with suspected lung cancer.

Pattern of cancer patient referral and organisational model of an interventional pulmonology programme during the COVID-19 pandemic.

An interventional pulmonary programme can be carried out safely for both cancer patients and HCWs during the #COVID19 pandemic. However, a worrisome reduction of new cancer patient referral occurs during periods of high community spread of the virus. https://bit.ly/2PRWNXo.

Accuracy and Reproducibility of Endoscopic Ultrasound B-Mode Features for Observer-Based Lymph Nodal Malignancy Prediction.

BACKGROUND: Endoscopic ultrasound routinely guides lymph node evaluation for the staging of a known or suspected lung cancer. Characteristics seen on B-mode imaging might help the observer decide on the lymph nodes of risk. The influence of nodal size on the predictivity of these characteristics and the agreement with which operators can combine these for malignancy risk prediction is to be determined. OBJECTIVES: We evaluated (1) if prospectively scored individual B-mode ultrasound features predict malignancy when further divided by size and (2) assessed if observers were able to reproducibly agree on still lymph node image malignancy risk. METHODS: Lymph nodes as visualized by EBUS were prospectively scored for B-mode characteristics. Still B-mode images were furthermore collected. After collection, a repeated scoring of a subset of lymph nodes was retrospectively performed (n = 11 observers). RESULTS: Analysis of 490 lymph nodes revealed the short axis size is an objective measure for stratifying risk of malignancy (ROC area under the curve 0.78). With ≥8-mm size, 210/237 malignant lymph nodes were correctly identified (89% sensitivity, 46% specificity, 61% PPV, and 81% NPV). Secondary addition of B-mode features in <8-mm nodes had limited value. Retrospective analysis of intra- and interobserver scoring furthermore revealed significant disagreement. CONCLUSIONS: Lymph nodes of ≥8-mm size and preferably even smaller should be aspirated regardless of other B-mode features. Observer disagreement in scoring both small and large lymph nodes suggests it is infeasible to include subjective features for stratification. Future research should focus on (integrating) other (semi)quantitative values for improving prediction.

Predictive Value of Endobronchial Ultrasound Strain Elastography in Mediastinal Lymph Node Staging: The E-Predict Multicenter Study Results.

BACKGROUND: Systematic assessment of lymph node status by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is indicated in (suspected) lung cancer. Sampling is herein guided by nodal size and FDG-PET characteristics. Ultrasound strain elastography (SE) might further improve risk stratification. By imaging tissue deformation over time, SE computes relative tissue strain. In several tissues, a lower strain (deformation) has been associated with a higher likelihood of malignancy. OBJECTIVES: To assess if EBUS-SE can independently help predict malignancy, and when combined with size and FDG uptake information. METHODS: This multicenter (n = 5 centers) prospective trial included patients with suspected or proven lung cancer using a standardized measurement protocol. Cytopathology combined with surgery or follow-up imaging (>6 months) were used as reference standard. RESULTS: Between June 2016 and July 2018, 327 patients and 525 lymph nodes were included (mean size 12.3 mm, malignancy prevalence 0.48). EBUS-SE had an overall AUC of 0.77. A mean strain <115 (range 0-255) showed 90% sensitivity, 43% specificity, 60% positive predictive value, and 82% negative predictive value. Combining EBUS-SE (<115) with size (<8 mm) and FDG-PET information into a risk stratification algorithm increased the accuracy. Combining size and SE showed that the 48% a priori chance of malignancy changed to 11 and 70% in double negative or positive nodes, respectively. In the subset where FDG-PET was available (n = 370), triple negative and positive nodes went from a 42% a priori chance of malignancy to 9 and 73%, respectively. CONCLUSIONS: EBUS-SE can help predict lymph node malignancy and may be useful for risk stratification when combined with size and PET information.

Endobronchial Ultrasound for the Diagnosis of Centrally Located Lung Tumors: A Systematic Review and Meta-Analysis.

INTRODUCTION: Obtaining a tissue diagnosis of centrally located lung tumors in patients presenting without endobronchial abnormalities is challenging, and therefore a considerable diagnostic problem. OBJECTIVE: The objective of this study was to evaluate the performance of linear endobronchial ultrasound guided-transbronchial-needle aspiration (EBUS-TBNA) for the diagnosis of centrally located lung tumors. METHODS: We performed a systematic review (PROSPERO, CRD42017080968) and searched MEDLINE, Embase, BIOSIS Previews, and Web of Science till November 18, 2018 for studies that evaluated the yield and/or sensitivity of EBUS-TBNA for diagnosing centrally located lung tumors. We assessed the study quality using QUADAS-2 and performed random-effects meta-analysis. RESULTS: A total of 5,657 manuscripts were identified; of these 14 were considered for the study, including 1,175 patients who underwent EBUS-TBNA for diagnosing an intrapulmonary tumor. All studies had a high risk of bias or applicability concerns, predominately regarding patient selection. The average yield of EBUS-TBNA for diagnosing centrally located lung tumors was 0.89 (95% CI 0.84-0.92) and average sensitivity for diagnosing malignant tumors was 0.91 (95% CI 0.88-0.94). Among studies reporting this information, EBUS-related complications occurred in 5.4% of patients (42/721). CONCLUSION: EBUS-TBNA has a high yield and sensitivity for diagnosing centrally located lung tumors and is safe in selected patients. Prospective studies are recommended to evaluate the routine use of this procedure for diagnosing intrapulmonary tumors.

Competence in endosonographic techniques.

Endobronchial ultrasound (EBUS) has revolutionized the field of bronchoscopy because it allows to observe peribronchial structures and distal peripheral lung lesions. The use of EBUS was first described by Hurte and Hanrath in 1992. EBUS technology exists in two forms: radial and convex transducer probes. The radial EBUS probe has a 20-MHZ (12-30 MHz available) rotating transducer that can be inserted together with or without a guide sheath through the working channel (2.0-2.8 mm) of a standard flexible bronchoscope. The transducer rotates and produces a 360-degree circular image around the central position of the probe. There are two types of radial EBUS probes: "peripheral" probes, used to identify parenchymal lung lesions, and "central" probes, with balloon sheaths, used for the assessment of airway walls and peribronchial lymph nodes.