Bronchoscopic treatment of early-stage peripheral lung cancer.

PURPOSE OF REVIEW: This review article focuses on bronchoscopic treatment of early-stage peripheral lung cancer. RECENT FINDINGS: Bronchoscopic treatment modalities have garnered considerable attention for early-stage lung cancer. Studies using photodynamic therapy, thermal vapor ablation, laser ablation, cryoablation, and intra-tumoral injection have recently been published. However, the evidence supporting these approaches largely derives from single-arm studies with small sample sizes. Based on the IDEAL-D framework, no technology has progressed passed the idea phase (1). The main weakness of these technologies to date is lack of evidence suggesting they can achieve local control. Presently, no bronchoscopic intervention for lung cancer has sufficient data to warrant its use as part of the standard of care. SUMMARY: Despite notable progress, current technologies remain suboptimal, and there is insufficient evidence to support their use outside of a research setting.

Research Priorities for Interventions to Address Health Disparities in Lung Nodule Management: An Official American Thoracic Society Research Statement.

Background: Lung nodules are common incidental findings, and timely evaluation is critical to ensure diagnosis of localized-stage and potentially curable lung cancers. Rates of guideline-concordant lung nodule evaluation are low, and the risk of delayed evaluation is higher for minoritized groups. Objectives: To summarize the existing evidence, identify knowledge gaps, and prioritize research questions related to interventions to reduce disparities in lung nodule evaluation. Methods: A multidisciplinary committee was convened to review the evidence and identify key knowledge gaps in four domains: 1) research methodology, 2) patient-level interventions, 3) clinician-level interventions, and 4) health system-level interventions. A modified Delphi approach was used to identify research priorities. Results: Key knowledge gaps included 1) a lack of standardized approaches to identify factors associated with lung nodule management disparities, 2) limited data evaluating the role of social determinants of health on disparities in lung nodule management, 3) a lack of certainty regarding the optimal strategy to improve patient-clinician communication and information transmission and/or retention, and 4) a paucity of information on the impact of patient navigators and culturally trained multidisciplinary teams. Conclusions: This statement outlines a research agenda intended to stimulate high-impact studies of interventions to mitigate disparities in lung nodule evaluation. Research questions were prioritized around the following domains: 1) need for methodologic guidelines for conducting research related to disparities in nodule management, 2) evaluating how social determinants of health influence lung nodule evaluation, 3) studying approaches to improve patient-clinician communication, and 4) evaluating the utility of patient navigators and culturally enriched multidisciplinary teams to reduce disparities.

An update on bronchopleural fistulae following cancer-related surgery.

PURPOSE OF REVIEW: Bronchopleural fistulae (BPF) are rare complications in cancer-related surgery but impart significant morbidity and mortality. BPF may be difficult to identify, with a broad differential diagnosis at presentation, so it is critical to be aware of newer diagnostic and therapeutic approaches for this disease entity. RECENT FINDINGS: Multiple novel diagnostic and therapeutic interventions are featured in this review. Reports of newer bronchoscopic techniques to localize BPF, as well as approaches for bronchoscopic management, like stent deployment, endobronchial valve placement, or alternative interventions when indicated are discussed, paying particular attention to factors that influence procedure selection. SUMMARY: Management of BPF remains highly variable, but several novel approaches have shown improved identification and outcomes. Although a multidisciplinary approach is imperative, an understanding of these newer techniques is important to provide optimal care for patients.

The Impact of Anticoagulation on Indwelling Pleural Catheter Removal due to Pleurodesis in Patients with Malignant Pleural Effusion.

BACKGROUND: A well-recognized therapy to improve the symptoms of patients with malignant pleural effusion (MPE), indwelling pleural catheters (IPCs) can also achieve spontaneous pleurodesis. Chemical pleurodesis is associated with a significant pro-coagulation and fibrinolytic environment. Hence, anticoagulation could theoretically interfere with this process. OBJECTIVE: The aim of this study was to evaluate if anticoagulation can interfere with successful spontaneous pleurodesis in patients treated with IPC. METHODS: This was a cohort study of all patients with MPE treated with IPC. The primary objective was to determine if anticoagulant use after IPC placement decreased the rate of spontaneous pleurodesis. The secondary objective was to identify other factors associated with spontaneous pleurodesis. We used a Fine-Gray subdistribution hazard model and a direct acyclic graph to identify variables associated with time to spontaneous pleurodesis. RESULTS: Of the included 410 patients, 210 patients (51.2%) achieved pleurodesis and had their IPC removed. We found no association between anticoagulation and likelihood of pleurodesis. Multivariate analyses revealed that prior chemotherapy, ECOG score of 2-4 were associated with unsuccessful pleurodesis, while chemotherapy or radiotherapy after IPC placement remained associated with increased likelihood of spontaneous pleurodesis. CONCLUSIONS: We failed to demonstrate an association between anticoagulation and pleurodesis. We found that better performance status and chemotherapy or radiotherapy after IPC placement can increase the rate of pleurodesis and catheter removal.

Malignant pleural disease: a pragmatic guide to diagnosis.

PURPOSE OF REVIEW: The diagnosis of malignant pleural disease is important in the care of patients with cancer. However, a one-size-fits-all approach to diagnosis may lead to delays in care as the sensitivity of each biopsy modality varies and can be dependent on the tumor type. We review current literature on pleural biopsy techniques and propose a diagnostic algorithm for suspected malignant pleural disease. RECENT FINDINGS: Recent literature has shown that the sensitivity of pleural fluid cytology varies based on tumor type resulting in a limited value of repeated thoracenteses in many cases. Furthermore, the ability to test for molecular biomarkers on pleural fluid samples has contributed to the recommendations to send large volumes of pleural fluid for analysis. Studies have also supported the consideration of medical thoracoscopy earlier in the diagnostic work-up of malignant pleural disease. SUMMARY: The decision to repeat a diagnostic thoracentesis when suspecting malignant pleural effusions should take into account the primary tumor type. Open pleural biopsy with medical thoracoscopy has been shown to be a relatively safe diagnostic modality with high sensitivity and should be considered in patients with a nondiagnostic thoracentesis.

Predicting malignant pleural effusion during diagnostic pleuroscopy with biopsy: A prospective multicentre study.

BACKGROUND AND OBJECTIVE: Pleuroscopy with pleural biopsy has a high sensitivity for malignant pleural effusion (MPE). Because MPEs tend to recur, concurrent diagnosis and treatment of MPE during pleuroscopy is desired. However, proceeding directly to treatment at the time of pleuroscopy requires confidence in the on-site diagnosis. The study's primary objective was to create a predictive model to estimate the probability of MPE during pleuroscopy. METHODS: A prospective observational multicentre cohort study of consecutive patients undergoing pleuroscopy was conducted. We used a logistic regression model to evaluate the probability of MPE with relation to visual assessment, rapid on-site evaluation (ROSE) of touch preparation and presence of pleural nodules/masses on computed tomography (CT). To assess the model's prediction accuracy, a bootstrapped training/testing approach was utilized to estimate the cross-validated area under the receiver operating characteristic curve. RESULTS: Of the 201 patients included in the study, 103 had MPE. Logistic regression showed that higher level of malignancy on visual assessment is associated with higher odds of MPE (OR = 34.68, 95% CI = 9.17-131.14, p < 0.001). The logistic regression also showed that higher level of malignancy on ROSE of touch preparation is associated with higher odds of MPE (OR = 11.63, 95% CI = 3.85-35.16, p < 0.001). Presence of pleural nodules/masses on CT is associated with higher odds of MPE (OR = 6.61, 95% CI = 1.97-22.1, p = 0.002). A multivariable logistic regression model of final pathologic status with relation to visual assessment, ROSE of touch preparation and presence of pleural nodules/masses on CT had a cross-validated AUC of 0.94 (95% CI = 0.91-0.97). CONCLUSION: A prediction model using visual assessment, ROSE of touch preparation and CT scan findings demonstrated excellent predictive accuracy for MPE. Further validation studies are needed to confirm our findings.

Systematic endoscopic staging of mediastinum to determine impact on radiotherapy for locally advanced lung cancer (SEISMIC): protocol for a prospective single arm multicentre interventional study.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is established as the preferred method of mediastinal lymph node (LN) staging in non-small cell lung cancer (NSCLC). Selective (targeted) LN sampling is most commonly performed however studies in early stage NSCLC and locally advanced NSCLC confirm systematic EBUS-TBNA evaluation improves accuracy of mediastinal staging. This study aims to establish the rate of detection of positron emission tomography (PET)-occult LN metastases following systematic LN staging by EBUS-TBNA, and to determine the utility of systematic mediastinal staging for accurate delineation of radiation treatment fields in patients with locally advanced NSCLC. METHODS: Consecutive patients undergoing EBUS-TBNA for diagnosis/staging of locally advanced NSCLC will be enrolled in this international multi-centre single arm study. Systematic mediastinal LN evaluation will be performed, with all LN exceeding 6 mm to be sampled by TBNA. Where feasible, endoscopic ultrasound staging (EUS-B) may also be performed. Results of minimally invasive staging will be compared to FDG-PET. The primary end-point is proportion of patients in whom systematic LN staging identified PET-occult NSCLC metastases. Secondary outcome measures include (i) rate of nodal upstaging, (ii) false positive rate of PET for mediastinal LN assessment, (iii) analysis of clinicoradiologic risk factors for presence of PET-occult LN metastases, (iv) impact of systematic LN staging in patients with discrepant findings on PET and EBUS-TBNA on target coverage and dose to organs at risk (OAR) in patients undergoing radiotherapy. DISCUSSION: With specificity of PET of 90%, guidelines recommend tissue confirmation of positive mediastinal LN to ensure potentially early stage patients are not erroneously denied potentially curative resection. However, while confirmation of pathologic LN is routinely sought, the exact extent of mediastinal LN involvement in NSCLC in patient with Stage III NSCLC is rarely established. Studies examining systematic LN staging in early stage NSCLC report a significant discordance between PET and EBUS-TBNA. In patients with locally advanced disease this has significant implications for radiation field planning, with risk of geographic miss in the event of PET-occult mediastinal LN metastases. The SEISMIC study will examine both diagnostic outcomes following systematic LN staging with EBUS-TBNA, and impact on radiation treatment planning. TRIAL REGISTRATION: ACTRN12617000333314, ANZCTR, Registered on 3 March 2017.

Understanding the patient journey to diagnosis of lung cancer.

OBJECTIVE: This research describes the clinical pathway and characteristics of two cohorts of patients. The first cohort consists of patients with a confirmed diagnosis of lung cancer while the second consists of patients with a solitary pulmonary nodule (SPN) and no evidence of lung cancer. Linked data from an electronic medical record and the Louisiana Tumor Registry were used in this investigation. MATERIALS AND METHODS: REACHnet is one of 9 clinical research networks (CRNs) in PCORnet®, the National Patient-Centered Clinical Research Network and includes electronic health records for over 8 million patients from multiple partner health systems. Data from Ochsner Health System and Tulane Medical Center were linked to Louisiana Tumor Registry (LTR), a statewide population-based cancer registry, for analysis of patient's clinical pathways between July 2013 and 2017. Patient characteristics and health services utilization rates by cancer stage were reported as frequency distributions. The Kaplan-Meier product limit method was used to estimate the time from index date to diagnosis by stage in lung cancer cohort. RESULTS: A total of 30,559 potentially eligible patients were identified and 2929 (9.58%) had primary lung cancer. Of these, 1496 (51.1%) were documented in LTR and their clinical pathway to diagnosis was further studied. Time to diagnosis varied significantly by cancer stage. A total of 24,140 patients with an SPN were identified in REACHnet and 15,978 (66.6%) had documented follow up care for 1 year. 1612 (10%) had no evidence of any work up for their SPN. The remaining 14,366 had some evidence of follow up, primarily office visits and additional chest imaging. CONCLUSION: In both cohorts multiple biopsies were evident in the clinical pathway. Despite clinical workup, 70% of patients in the lung cancer cohort had stage III or IV disease. In the SPN cohort, only 66% were identified as receiving a diagnostic work-up.

Robotic bronchoscopy for peripheral pulmonary lesions: a convergence of technologies.

PURPOSE OF REVIEW: Robotic bronchoscopy is the newest advanced diagnostic bronchoscopy technology for biopsying peripheral pulmonary lesions; sensitivity for malignancy is currently suboptimal using modalities, such as radial endobronchial ultrasound or electromagnetic navigational bronchoscopy. We review the pitfalls of prior methods and the technological advancements with robotic bronchoscopy. RECENT FINDINGS: The contributors to reduced diagnostic sensitivity with current approaches include limitations in: navigation to the target, confirmation once the target is reached, and tissue acquisition. CT to body divergence with virtual reality methods, such as with electromagnetic navigation, potential false-positive confirmation with radial endobronchial ultrasound because of intraprocedural induced atelectasis, and lack of bronchoscopic and instrument maneuverability are all limitations to improving sensitivity. Robotic bronchoscopy enhances navigation through target pathway selection, allows for further reach in the distal airways, and improves tissue acquisition with more flexible and maneuverable biopsy instruments but lacks a high-fidelity target confirmation system. SUMMARY: Robotic bronchoscopy shows promise in biopsying peripheral lesions. Current published studies focus on diagnostic yield with robotic bronchoscopy. Future studies with long-term follow-up will be needed to assess diagnostic sensitivity for lung cancer and if robotic bronchoscopy is superior to other advanced diagnostic bronchoscopic techniques for peripheral pulmonary lesions.

A Prediction Model to Help with Oncologic Mediastinal Evaluation for Radiation: HOMER.

Rationale: When stereotactic ablative radiotherapy is an option for patients with non-small cell lung cancer (NSCLC), distinguishing between N0, N1, and N2 or N3 (N2|3) disease is important.Objectives: To develop a prediction model for estimating the probability of N0, N1, and N2|3 disease.Methods: Consecutive patients with clinical-radiographic stage T1 to T3, N0 to N3, and M0 NSCLC who underwent endobronchial ultrasound-guided staging from a single center were included. Multivariate ordinal logistic regression analysis was used to predict the presence of N0, N1, or N2|3 disease. Temporal validation used consecutive patients from 3 years later at the same center. External validation used three other hospitals.Measurements and Main Results: In the model development cohort (n = 633), younger age, central location, adenocarcinoma, and higher positron emission tomography-computed tomography nodal stage were associated with a higher probability of having advanced nodal disease. Areas under the receiver operating characteristic curve (AUCs) were 0.84 and 0.86 for predicting N1 or higher (vs. N0) disease and N2|3 (vs. N0 or N1) disease, respectively. Model fit was acceptable (Hosmer-Lemeshow, P = 0.960; Brier score, 0.36). In the temporal validation cohort (n = 473), AUCs were 0.86 and 0.88. Model fit was acceptable (Hosmer-Lemeshow, P = 0.172; Brier score, 0.30). In the external validation cohort (n = 722), AUCs were 0.86 and 0.88 but required calibration (Hosmer-Lemeshow, P < 0.001; Brier score, 0.38). Calibration using the general calibration method resulted in acceptable model fit (Hosmer-Lemeshow, P = 0.094; Brier score, 0.34).Conclusions: This prediction model can estimate the probability of N0, N1, and N2|3 disease in patients with NSCLC. The model has the potential to facilitate decision-making in patients with NSCLC when stereotactic ablative radiotherapy is an option.

Shape-sensing robotic-assisted bronchoscopy for pulmonary nodules: initial multicenter experience using the Ion™ Endoluminal System.

BACKGROUND: Traditional bronchoscopy provides limited approach to peripheral nodules. Shape-sensing robotic-assisted bronchoscopy (SSRAB, Ion™ Endoluminal System) is a new tool for minimally invasive peripheral nodule biopsy. We sought to answer the research question: Does SSRAB facilitate sampling of pulmonary nodules during bronchoscopists' initial experience? METHODS: The lead-in stage of a multicenter, single-arm, prospective evaluation of the Ion Endoluminal System (PRECIsE) is described. Enrolled subjects ≥ 18 years old had recent computed tomography evidence of one or more solid or semi-solid pulmonary nodules ≥ 1.0 to ≤ 3.5 cm in greatest dimension and in any part of the lung. Subjects were followed at 10- and 30-days post-procedure. This stage provided investigators and staff their first human experience with the SSRAB system; safety and procedure outcomes were analyzed descriptively. Neither diagnostic yield nor sensitivity for malignancy were assessed in this stage. Categorical variables are summarized by percentage; continuous variables are summarized by median/interquartile range (IQR). RESULTS: Sixty subjects were enrolled across 6 hospitals; 67 nodules were targeted for biopsy. Median axial, coronal and sagittal diameters were < 18 mm with a largest cardinal diameter of 20.0 mm. Most nodules were extraluminal and distance from the outer edge of the nodule to the pleura or nearest fissure was 4.0 mm (IQR: 0.0, 15.0). Median bronchial generation count to the target location was 7.0 (IQR: 6.0, 8.0). Procedure duration (catheter-in to catheter-out) was 66.5 min (IQR: 50.0, 85.5). Distance from the catheter tip to the closest edge of the virtual nodule was 7.0 mm (IQR: 2.0, 12.0). Biopsy completion was 97.0%. No pneumothorax or airway bleeding of any grade was reported. CONCLUSIONS: Bronchoscopists leveraged the Ion SSRAB's functionality to drive the catheter safely in close proximity of the virtual target and to obtain biopsies. This initial, multicenter experience is encouraging, suggesting that SSRAB may play a role in the management of pulmonary nodules. Clinical Trial Registration identifier and date NCT03893539; 28/03/2019.

Complications following symptom-limited thoracentesis using suction.

BACKGROUND: Thoracentesis using suction is perceived to have increased risk of complications, including pneumothorax and re-expansion pulmonary oedema (REPO). Current guidelines recommend limiting drainage to 1.5 L to avoid REPO. Our purpose was to examine the incidence of complications with symptom-limited drainage of pleural fluid using suction and identify risk factors for REPO. METHODS: A retrospective cohort study of all adult patients who underwent symptom-limited thoracentesis using suction at our institution between January 1, 2004 and August 31, 2018 was performed, and a total of 10 344 thoracenteses were included. RESULTS: Pleural fluid ≥1.5 L was removed in 19% of the procedures. Thoracentesis was stopped due to chest discomfort (39%), complete drainage of fluid (37%) and persistent cough (13%). Pneumothorax based on chest radiography was detected in 3.98%, but only 0.28% required intervention. The incidence of REPO was 0.08%. The incidence of REPO increased with Eastern Cooperative Oncology Group performance status (ECOG PS) ≥3 compounded with ≥1.5 L (0.04-0.54%; 95% CI 0.13-2.06 L). Thoracentesis in those with ipsilateral mediastinal shift did not increase complications, but less fluid was removed (p<0.01). CONCLUSIONS: Symptom-limited thoracentesis using suction is safe even with large volumes. Pneumothorax requiring intervention and REPO are both rare. There were no increased procedural complications in those with ipsilateral mediastinal shift. REPO increased with poor ECOG PS and drainage ≥1.5 L. Symptom-limited drainage using suction without pleural manometry is safe.

Development and Reporting of Prediction Models: Guidance for Authors From Editors of Respiratory, Sleep, and Critical Care Journals.

Prediction models aim to use available data to predict a health state or outcome that has not yet been observed. Prediction is primarily relevant to clinical practice, but is also used in research, and administration. While prediction modeling involves estimating the relationship between patient factors and outcomes, it is distinct from casual inference. Prediction modeling thus requires unique considerations for development, validation, and updating. This document represents an effort from editors at 31 respiratory, sleep, and critical care medicine journals to consolidate contemporary best practices and recommendations related to prediction study design, conduct, and reporting. Herein, we address issues commonly encountered in submissions to our various journals. Key topics include considerations for selecting predictor variables, operationalizing variables, dealing with missing data, the importance of appropriate validation, model performance measures and their interpretation, and good reporting practices. Supplemental discussion covers emerging topics such as model fairness, competing risks, pitfalls of "modifiable risk factors", measurement error, and risk for bias. This guidance is not meant to be overly prescriptive; we acknowledge that every study is different, and no set of rules will fit all cases. Additional best practices can be found in the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines, to which we refer readers for further details.

Pulmonary cavitation in patients with thyroid cancer receiving antiangiogenic agents.

BACKGROUND: Thyroid malignancies are among the most common endocrine cancers worldwide. Owing to the angiogenic nature of these malignancies, tyrosine kinase inhibitors (TKIs) are an attractive potential treatment. However, TKIs have been associated with an increased risk of tumor cavitation, in turn linked to poor outcomes, in patients with malignancies in the lungs, where thyroid cancer commonly metastasizes. METHOD: We performe d a retrospective cohort study of patients with thyroid cancer and evidence of metastatic disease to the lung that were treated with multi-targeted antiangiogenic TKIs. The primary objective of this study was to determine the incidence of pulmonary cavitation. The secondary objective was to evaluate the effect of pulmonary cavitation on survival. RESULTS: Of the 83 patients with pulmonary nodules, 10 developed cavitation during treatment. Of these 83 patients, two patients had to stop the treatment due to pneumothorax. Additionally, cavitation did not demonstrate any significant effect on survival. CONCLUSION: In patients with thyroid cancer and evidence of metastatic disease to the chest, the use of multi-targeted TKIs led to cavitations that were not uncommon but clinical consequences were marginal. Treatment was stopped only in two patients that developed pneumothorax, however the small sample is a strong limitation of our study.

What's new in endobronchial ultrasound for mediastinal staging?

PURPOSE OF REVIEW: The essential role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in lung cancer diagnosis and staging is now well established. With a growing body of evidence seen over the last decade, the objective of this article was to review the newest findings, provide evidence-based guidance to clinicians and identify areas for future research related to EBUS-TBNA and staging in lung cancer. RECENT FINDINGS: Recent literature regarding EBUS-TBNA for lung cancer staging was reviewed, with a focus on evidence published subsequent to the 2016 guideline on technical aspects of EBUS-TBNA by the American College of Chest Physicians (ACCP). New findings were reported for the following: role of rapid on-site cytological evaluation (ROSE), needle size, lymph node ultrasound characteristics, molecular testing, as well as practice patterns and gaps in quality of care. SUMMARY: Significant advances in EBUS-TBNA have been realized since the publication of the 2016 ACCP guideline. Future areas of investigation have been identified and will require collaboration between centers of expertise. Additional work will be required to translate these technological advances into improved value-based care in the lung cancer population.

Long-term quality-adjusted survival following therapeutic bronchoscopy for malignant central airway obstruction.

BACKGROUND: While therapeutic bronchoscopy has been used to treat malignant central (CAO) airway obstruction for >25 years, there are no studies quantifying the impact of therapeutic bronchoscopy on long-term quality-adjusted survival. METHODS: We conducted a prospective observational study of consecutive patients undergoing therapeutic bronchoscopy for CAO. Patients had follow-up at 1 week and monthly thereafter until death. Outcomes included technical success (ie, relief of anatomic obstruction), dyspnoea, health-related quality of life (HRQOL) and quality-adjusted survival. RESULTS: Therapeutic bronchoscopy was performed on 102 patients with malignant CAO. Partial or complete technical success was achieved in 90% of patients. At 7 days postbronchoscopy, dyspnoea improved (mean ∆Borg-day-7=-1.8, 95% CI -2.2 to -1.3, p<0.0001) and HRQOL improved (median prebronchoscopy 0.618 utiles, 25%-75% IQR 0.569 to 0.699, mean ∆utility-day-7+0.047 utiles, 95% CI +0.023 to 0.071, p=0.0002). Improvements in dyspnoea and HRQOL were maintained long-term. Compared with the prebronchoscopy baseline, HRQOL per day of life postbronchoscopy improved (mean ∆utility-long-term+0.036 utiles, 95% CI +0.014 to 0.057, p=0.002). Median quality-adjusted survival was 109 quality-adjusted life-days (QALDs) (95% CI 74 to 201 QALDs). Factors associated with longer quality-adjusted survival included better functional status, treatment-naïve tumour, endobronchial disease, less dyspnoea, shorter time from diagnosis to bronchoscopy, absence of cardiac disease, bronchoscopic dilation and receiving chemotherapy. CONCLUSIONS: Therapeutic bronchoscopy improves HRQOL as compared with baseline, resulting in approximately a 5.8% improvement in HRQOL per day of life. The risk-benefit profile in these carefully selected patients was very favourable. TRIAL REGISTRATION NUMBER: Results; NCT03326570.

Centrally located lung cancer and risk of occult nodal disease: an objective evaluation of multiple definitions of tumour centrality with dedicated imaging software.

INTRODUCTION: Current guidelines recommend invasive mediastinal staging in patients with centrally located radiographic stage T1N0M0 nonsmall cell lung cancer (NSCLC). The lack of a specific definition of a central tumour has resulted in discrepancies among guidelines and heterogeneity in practice patterns. METHODS: Our objective was to study specific definitions of tumour centrality and their association with occult nodal disease. Pre-operative chest computed tomography scans from patients with clinical (c) T1N0M0 NSCLC were processed with a dedicated software system that divides the lungs in thirds following vertical and concentric lines. This software accurately assigns tumours to a specific third based both on the location of the centre of the tumour and its most medial aspect, creating eight possible definitions of central tumours. RESULTS: 607 patients were included in our study. Surgery was performed for 596 tumours (98%). The overall pathological (p) N disease was: 504 (83%) N0, 56 (9%) N1, 47 (8%) N2 and no N3. The prevalence of N2 disease remained relatively low regardless of tumour location. Central tumours were associated with upstaging from cN0 to any N (pN1/pN2). Two definitions were associated with upstaging to any N: concentric lines, inner one-third, centre of the tumour (OR 3.91, 95% CI 1.85-8.26; p<0.001) and concentric lines, inner two-thirds, most medial aspect of the tumour (OR 1.91, 95% CI 1.23-2.97; p=0.004). CONCLUSIONS: We objectively identified two specific definitions of central tumours. While the rate of occult mediastinal disease was relatively low regardless of tumour location, central tumours were associated with upstaging from cN0 to any N.

Management of the solitary pulmonary nodule.

PURPOSE OF REVIEW: We review the categorization and management of solitary pulmonary nodules. RECENT FINDINGS: The National Comprehensive Cancer Network guidelines were updated in 2018 and the revised Fleischner Society guidelines were published in 2017. The revised Fleischner Society guidelines published in 2017 have less frequent follow-up recommendations for incidentally detected pulmonary nodules with longer intervals between subsequent CT scans. The updated 2018 version of National Comprehensive Cancer Network lung cancer screening guidelines provide recommendations for screen-detected nodules based on a patient's risk of cancer. New molecular assays may be of use in patients with a pretest probability of malignancy less than 50%. When these tests indicate low risk, a strategy of follow-up CT imaging may be feasible, avoiding unnecessary invasive testing. However, further clinical utility studies are needed in this area. SUMMARY: Management options for pulmonary nodules include watchful waiting with follow-up CT imaging, PET imaging, or further invasive testing based on probability of malignancy. With a low estimated risk of malignancy in an incidentally detected solitary pulmonary nodule, longer intervals between follow-up CT scans are recommended for patients. For patients at high risk for malignancy or those with nodules of at least 8 mm, either incidentally, screen detected, or symptom driven, a diagnostic biopsy is necessary to establish the cause of a solitary pulmonary nodule.

Refinement of estimates of mortality risk using the Radiologic Severity Index in hematologic malignancy patients with respiratory syncytial virus infection.

BACKGROUND: Immunocompromised hematologic malignancy (HM) patients experience high mortality after respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI). We measured radiologic severity to determine whether it could improve the performance of 60-day mortality models based only upon immunodeficiency severity. METHODS: We studied 155 HM patients, including 84 hematopoietic cell transplant recipients, who developed RSV LRTI from 2001 to 2013. We measured immunodeficiency using lymphopenia (lymphocyte count <200 cells/mm3 ), Immunodeficiency Severity Index (ISI), and Severe Immunodeficiency (SID) criteria. Radiologic severity was measured by the Radiologic Severity Index (RSI, range 0-72) at time of LRTI (baseline-RSI) and peak severity (peak-RSI). Delta-RSI was defined as the difference between baseline-RSI and peak-RSI. We used logistic regression models to measure the association of immunodeficiency and RSI with 60-day all-cause mortality, and measured model discrimination using areas under the receiver-operating characteristics curves, calibration using Brier scores, and explained variance using pseudo-R2 values. RESULTS: Forty-one patients died within 60 days of RSV LRTI. Severe immunodeficiency was associated with higher mortality. Peak-RSI (odds ratio [OR] 1.06/point, 95% confidence interval [CI] 1.04-1.08), and delta-RSI (OR 1.07/point, 95% CI 1.05-1.10) were associated with 60-day mortality after RSV LRTI, but not baseline-RSI. Addition of peak-RSI or delta-RSI to baseline immunodeficiency improved the discrimination, calibration, and explained variance (P < 0.001) of 60-day mortality models. CONCLUSIONS: Although baseline immunodeficiency in HM patients helps predict 60-day mortality after RSV LRTI, mortality risk estimates can be further refined by also measuring LRTI progression using RSI. RSI is well-suited as a marker of LRTI severity in RSV infection.

PD-L1 detection in histology specimens and matched pleural fluid cell blocks of patients with NSCLC.

BACKGROUND AND OBJECTIVE: Analysis of programmed death ligand-1 (PD-L1) in tumour samples is necessary to identify candidates for anti-PD-L1/PD-L1 therapy. Because PD-L1 is evaluated by immunohistochemistry (IHC), an adequate amount of tumour tissue is a prerequisite for PD-L1 testing. To examine whether pleural fluid might be an alternative to biopsy/resection specimens for IHC evaluation of PD-L1 in patients with non-small cell lung carcinoma (NSCLC), we compared PD-L1 by IHC between histological specimens and matched pleural fluid. METHODS: A retrospective cohort study of patients with NSCLC who underwent core biopsy of a lung mass/surgical resection with PD-L1 IHC and had a pleural fluid cell block (CB) available for PD-L1 staining was conducted. PD-L1 was categorized as negative (PD-L1 in <1% of tumour cells), moderately positive (PD-L1 in ≥1% to <50%), strongly positive (PD-L1 ≥ 50) or inadequate for PD-L1 testing (<100 tumour cells in the CB). Weighted Cohen's kappa was calculated to evaluate the agreement between PD-L1 on biopsy/resection specimen and pleural fluid for variables with more than two categories. RESULTS: Of the 115 patients included in this study, 82 (71.3%) had at least 100 tumour cells and were included in the analysis. Of these, 80 (97.6%) had adenocarcinoma. For PD-L1 of histological specimens versus pleural fluid categorized as negative, moderately positive or strongly positive, the weighted kappa statistic was 0.76 (95% CI: 0.64-0.88), and the concordance was 0.78 (95% CI: 0.68-0.86). CONCLUSION: Correlation and concordance are high between PD-L1 in histological specimens and matched pleural fluid. Evaluation of PD-L1 in pleural fluid should be considered in patients unable to undergo histological biopsies.