Differences in microenvironment of lung cancer and pleural effusions by single-cell RNA sequencing.

BACKGROUND: Direct comparison of tumor microenvironment of matched lung cancer biopsies and pleural effusions (PE) from the same patients is critical in understanding tumor biology but has not been performed. This is the first study to compare the lung cancer and PE microenvironment by single-cell RNA sequencing (scRNA-seq). METHODS: Matched lung cancer biopsies and PE were obtained prospectively from ten patients. We isolated CD45+ cells and performed scRNA-seq to compare the biopsies and PE. RESULTS: PE had a higher proportion of CD4+ T cells but lower proportion of CD8+ T cells (False detection rate, FDR = 0.0003) compared to biopsies. There was a higher proportion of naïve CD4+ T cells (FDR = 0.04) and naïve CD8+ T cells (FDR = 0.0008) in PE vs. biopsies. On the other hand, there was a higher proportion of Tregs (FDR = 0.04), effector CD8+ (FDR = 0.006), and exhausted CD8+ T cells (FDR = 0.01) in biopsies. The expression of inflammatory genes in T cells was increased in biopsies vs. PE, including TNF, IFN-É£, IL-1R1, IL-1R2, IL-2, IL-12RB2, IL-18R1, and IL-18RAP (FDR = 0.009, 0.013, 0.029, 0.043, 0.009, 0.013, 0.004, and 0.003, respectively). The gene expression of exhaustion markers in T cells was also increased in tumor biopsies including PDCD1, CTLA4, LAG 3, HAVCR2, TIGIT, and CD160 (FDR = 0.008, 0.003, 0.002, 0.011, 0.006, and 0.049, respectively). CONCLUSIONS: There is a higher proportion of naïve T cells and lower proportion of exhausted T cells and Tregs in PE compared to lung cancer biopsies, which can be leveraged for prognostic and therapeutic applications.

Barriers and Facilitators Impacting Lung Cancer Screening Uptake Among Black Veterans: A Qualitative Study.

BACKGROUND: Racial disparities in lung cancer screening (LCS) are well established. Black Veterans are among those at the highest risk for developing lung cancer but are less likely to complete LCS. We sought to identify barriers and facilitators to LCS uptake among Black Veterans. PATIENTS AND METHODS: A qualitative study using semistructured interviews was conducted with 32 Black Veterans to assess for barriers, facilitators, and contextual factors for LCS and strategies to improve screening. Veterans were purposively sampled by age, sex, and LCS participation status (ie, patients who received a low-dose CT [LDCT], patients who contacted the screening program but did not receive an LDCT, and patients who did not connect with the screening program nor receive an LDCT). Interview guides were developed using the Theoretical Domains Framework and Health Belief Model. Data were analyzed using rapid qualitative analysis. RESULTS: Barriers of LCS uptake among Black Veterans include self-reported low LCS knowledge and poor memory, attention, and decision processes associated with the centralized LCS process. Facilitators of LCS uptake among Black Veterans include social/professional role; identity and social influences; perceived susceptibility, threat, and consequences due to smoking status and military or occupational exposures; emotion, behavioral regulation, and intentions; and high trust in providers. Environmental context and resources (eg, transportation) and race and racism serve as contextual factors that did not emerge as having a major impact on LCS uptake. Strategies to improve LCS uptake included increased social messaging surrounding LCS, various forms of information dissemination, LCS reminders, balanced and repeated shared decision-making discussions, and streamlined referrals. CONCLUSIONS: We identified addressable barriers and facilitators for LCS uptake among Black Veterans that can help focus efforts to improve disparities in screening. Future studies should explore provider perspectives and test interventions to improve equity in LCS.

Racial Disparities in Lung Cancer Screening Among Veterans, 2013 to 2021.

Importance: Racial disparities in lung cancer screening (LCS) are often ascribed to barriers such as cost, insurance status, access to care, and transportation. Because these barriers are minimized within the Veterans Affairs system, there is a question of whether similar racial disparities exist within a Veterans Affairs health care system in North Carolina. Objectives: To examine whether racial disparities in completing LCS after referral exist at the Durham Veterans Affairs Health Care System (DVAHCS) and, if so, what factors are associated with screening completion. Design, Setting, and Participants: This cross-sectional study assessed veterans referred to LCS between July 1, 2013, and August 31, 2021, at the DVAHCS. All included veterans self-identified as White or Black and met the US Preventive Services Task Force eligibility criteria as of January 1, 2021. Participants who died within 15 months of consultation or who were screened before consultation were excluded. Exposures: Self-reported race. Main Outcomes and Measures: Screening completion was defined as completing computed tomography for LCS. The associations among screening completion, race, and demographic and socioeconomic risk factors were assessed using logistic regression models. Results: A total of 4562 veterans (mean [SD] age, 65.4 [5.7] years; 4296 [94.2%] male; 1766 [38.7%] Black and 2796 [61.3%] White) were referred for LCS. Of all veterans referred, 1692 (37.1%) ultimately completed screening; 2707 (59.3%) never connected with the LCS program after referral and an informational mailer or telephone call, indicating a critical point in the LCS process. Screening rates were substantially lower among Black compared with White veterans (538 [30.5%] vs 1154 [41.3%]), with Black veterans having 0.66 times lower odds (95% CI, 0.54-0.80) of screening completion after adjusting for demographic and socioeconomic factors. Conclusions and Relevance: This cross-sectional study found that after referral for initial LCS via a centralized program, Black veterans had 34% lower odds of LCS screening completion compared with White veterans, a disparity that persisted even after accounting for numerous demographic and socioeconomic factors. A critical point in the screening process was when veterans must connect with the screening program after referral. These findings may be used to design, implement, and evaluate interventions to improve LCS rates among Black veterans.

Interventions to improve lung cancer screening among racially and ethnically minoritized groups: A scoping review.

Lung cancer screening (LCS) decreases lung cancer related mortality among high-risk people who smoke cigarettes and has been endorsed by the US Preventive Services Task Force (USPSTF) since 2013. However, adoption of LCS has been limited, and disparities in LCS among racially and ethnically minoritized groups have become apparent. While recommendations to improve disparities in LCS have been made, there is a lack of information on how these recommendations have been implemented and their relative effectiveness in improving screening disparities. This scoping review addresses this knowledge gap by examining interventions that have been implemented to improve LCS among racially and ethnically minoritized groups in the United States. A comprehensive search of MEDLINE (via PubMed), EMBASE (via Elsevier), CINAHL Complete (via EBSCO), and Scopus (via Elsevier), for articles from the period 1 January 2010 through 22 October 2021 was completed. Out of 17,045 references screened, only 11 studies describing an intervention to improve disparities in LCS were identified, underscoring the dearth of data on established interventions. The interventions discussed could be categorized into three groups -- patient level (n = 3), clinic/institution level (n = 3), and community level (n = 5) interventions. Of those studies reporting effectiveness data (n = 8), there was substantial heterogeneity in the outcomes measured and their relative effectiveness. We found that interventions which streamlined the LCS process at the level of a single clinic or institution were the most effective in improving LCS. Community-level interventions that focused on engagement and education had the greatest potential to target racially and ethnically minoritized groups. Our study underscores the need for more robust research on addressing barriers to LCS by identifying effective patient, clinic, and community-level interventions to improve LCS disparities and the need for potential standardization of intervention effectiveness outcomes.

High Yield of Pleural Cell-Free DNA for Diagnosis of Oncogenic Mutations in Lung Adenocarcinoma.

BACKGROUND: Pleural cytology is currently used to assess targetable mutations in patients with advanced lung adenocarcinoma. However, it is fraught with low diagnostic yield. RESEARCH QUESTION: Can pleural cell-free DNA (cfDNA) be used to assess targetable mutations in lung adenocarcinoma patients with malignant pleural effusions (MPE)? STUDY DESIGN AND METHODS: Patients with lung adenocarcinoma MPE were recruited prospectively between January 2017 and September 2021. Oncogenic mutations were assessed by treating providers using pleural fluid cytology or lung cancer biopsies. Pleural and plasma cfDNA were used to assess the mutations using next-generation sequencing (NGS). RESULTS: Fifty-four pleural fluid samples were collected from 42 patients. The diagnostic yield to detect oncogenic mutations for pleural cfDNA, pleural cytology, biopsy, and plasma cfDNA was 49/54 (90.7%), 16/33 (48.5%), 22/25 (88%), and 24/32 (75%), respectively, P < .001. The agreement of mutations in positive samples between pleural cfDNA and pleural cytology was 100%, whereas the agreement of pleural cfDNA with biopsies was 89.4%. The median concentration (interquartile range) of pleural cfDNA was higher than plasma: 28,444 (4,957-67,051) vs 2,966.5 (2,167-5,025) copies of amplifiable DNA per mL, P < .01. Median of 5 mL (interquartile range, 4.5-5) of pleural fluid supernatant was adequate for cfDNA testing. INTERPRETATION: The diagnostic yield of pleural cfDNA NGS for oncogenic mutations in lung adenocarcinoma patients is comparable to tumor biopsies and higher than pleural cytology and plasma cfDNA. The pleural cfDNA can be longitudinally collected, can be readily incorporated in clinical workflow, and may decrease the need for additional biopsies.

Management of Immunotherapy-Related Toxicities, Version 1.2022, NCCN Clinical Practice Guidelines in Oncology.

The aim of the NCCN Guidelines for Management of Immunotherapy-Related Toxicities is to provide guidance on the management of immune-related adverse events resulting from cancer immunotherapy. The NCCN Management of Immunotherapy-Related Toxicities Panel is an interdisciplinary group of representatives from NCCN Member Institutions, consisting of medical and hematologic oncologists with expertise across a wide range of disease sites, and experts from the areas of dermatology, gastroenterology, endocrinology, neurooncology, nephrology, cardio-oncology, ophthalmology, pulmonary medicine, and oncology nursing. The content featured in this issue is an excerpt of the recommendations for managing toxicities related to CAR T-cell therapies and a review of existing evidence. For the full version of the NCCN Guidelines, including recommendations for managing toxicities related to immune checkpoint inhibitors, visit NCCN.org.

Implementation and Effectiveness of a Veterans Affairs-Based Comprehensive Lung Cancer Survivorship Program.

PURPOSE: Few programs exist to address persistent impairment in functional status, quality of life, and mental health in lung cancer survivors. We aimed to determine whether a 12-wk multimodal survivorship program imparts clinical benefit. METHODS: Any patient at the Durham Veterans Affairs Medical Center with lung cancer and a Karnofsky score of ≥60 could participate. Chronic obstructive pulmonary disease medications were optimized at the enrollment visit. Participants with a Hospital Anxiety and Depression Scale (HADS) score of >8 were offered pharmacotherapy and mental health referral. Participants did home-based exercise with a goal of 1 hr/d, 5 d/wk. They were called weekly to assess exercise progress and review depression/anxiety symptoms. Participants were offered pharmacotherapy for smoking cessation. RESULTS: Twenty-three (50%) of the first 46 enrollees completed the full 12-wk program. Paired changes from enrollment to completion (mean ± SD) were observed in 6-min walk test (73.6 ± 96.9 m, P = .002), BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise) index (-1.45 ± 1.64 points, P < .001), Duke Activity Status Index (3.84 ± 7.12 points, P = .02), Fried Frailty Index (-0.588 ± 0.939 points, P = .02), modified Medical Research Council dyspnea scale (-0.619 ± 1.284 points, P = .04), Functional Assessment of Cancer Therapy-Lung Emotional subscale score (1.52 ± 2.96 points, P = .03), HADS total score (-2.63 ± 4.34 points, P = .02), and HADS Anxiety subscale score (-1.47 ± 2.29 points, P = .01). CONCLUSIONS: A comprehensive Lung Cancer Survivorship Program provides clinically meaningful improvements in functional status, quality of life, and mental health.

Comparison of Forceps, Cryoprobe, and Thoracoscopic Lung Biopsy for the Diagnosis of Interstitial Lung Disease - The CHILL Study.

RATIONALE: Transbronchial lung cryobiopsy (TBLC) has emerged as a less invasive method to obtain a tissue diagnosis in patients with interstitial lung disease (ILD). The diagnostic yield of TBLC compared to surgical lung biopsy (SLB) remains uncertain. OBJECTIVES: The aim of this study was to determine the diagnostic accuracy of forceps transbronchial lung biopsy (TBLB) and TBLC compared to SLB when making the final diagnosis based on multidisciplinary discussion (MDD). METHODS: Patients enrolled in the study underwent sequential TBLB and TBLC followed immediately by SLB. De-identified cases, with blinding of the biopsy method, were reviewed by a blinded pathologist and then discussed at a multidisciplinary conference. MAIN RESULTS: Between August 2013 and October 2017, we enrolled 16 patients. The raw agreement between TBLC and SLB for the MDD final diagnosis was 68.75% with a Cohen's kappa of 0.6 (95% CI 0.39, 0.81). Raw agreement and Cohen's kappa of TBLB versus TBLC and TBLB versus SLB for the MDD final diagnosis were much lower (50%, 0.21 [95% CI 0, 0.42] and 18.75%, 0.08 [95% CI -0.03, 0.19], respectively). TBLC was associated with mild bleeding (grade 1 bleeding requiring suction to clear) in 56.2% of patients. CONCLUSIONS: In patients with ILD who have an uncertain type based on clinical and radiographic data and require tissue sampling to obtain a specific diagnosis, TBLC showed moderate correlation with SLB when making the diagnosis with MDD guidance. TBLB showed poor concordance with both TBLC and SLB MDD diagnoses.

Variable Learning Curve of Basic Rigid Bronchoscopy in Trainees.

BACKGROUND: Despite increased use of rigid bronchoscopy (RB) for therapeutic indications and recommendations from professional societies to use performance-based competency, an assessment tool has not been utilized to measure the competency of trainees to perform RB in clinical settings. OBJECTIVES: The aim of the study was to evaluate a previously developed assessment tool - Rigid Bronchoscopy Tool for Assessment of Skills and Competence (RIGID-TASC) - for determining the RB learning curve of interventional pulmonary (IP) trainees in the clinical setting and explore the variability of learning curve of trainees. METHODS: IP fellows at 4 institutions were enrolled. After preclinical simulation training, all RBs performed in patients were scored by faculty using RIGID-TASC until competency threshold was achieved. Competency threshold was defined as unassisted RB intubation and navigation through the central airways on 3 consecutive patients at the first attempt with a minimum score of 89. A regression-based model was devised to construct and compare the learning curves. RESULTS: Twelve IP fellows performed 178 RBs. Trainees reached the competency threshold between 5 and 24 RBs, with a median of 15 RBs (95% CI, 6-21). There were differences among trainees in learning curve parameters including starting point, slope, and inflection point, as demonstrated by the curve-fitting model. Subtasks that required the highest number of procedures (median = 10) to gain competency included ability to intubate at the first attempt and intubation time of <60 s. CONCLUSIONS: Trainees acquire RB skills at a variable pace, and RIGID-TASC can be used to assess learning curve of IP trainees in clinical settings.

Hyperbaric oxygen therapy to prevent central airway stenosis after lung transplantation.

BACKGROUND: Central airway stenosis (CAS) is a severe airway complication after lung transplantation associated with bronchial ischemia and necrosis. We sought to determine whether hyperbaric oxygen therapy (HBOT), an established treatment for tissue ischemia, attenuates post-transplant bronchial injury. METHODS: We performed a randomized, controlled trial comparing usual care with HBOT (2 atm absolute for 2 hours × 20 sessions) in subjects with extensive airway necrosis 4 weeks after transplantation. Endobronchial biopsies were collected at 4, 7, and 10 weeks after transplantation for a quantitative polymerase chain reaction. Coprimary outcomes were incidence of airway stenting and acute cellular rejection (ACR) at 1 year. RESULTS: The trial was stopped after enrolling 20 subjects (n = 10 per group) after a pre-planned interim analysis showed no difference between usual care and HBOT groups in stenting (both 40%), ACR (70% and 40%, respectively), or CAS (40% and 60%, respectively). Time to first stent placement (median [interquartile range]) was significantly shorter in the HBOT group (150 [73-150] vs 186 [167-206] days, p < 0.05). HIF gene expression was significantly increased in donor tissues at 4, 7, and 10 weeks after transplantation but was not altered by HBOT. Subjects who developed CAS or required stenting had significantly higher HMOX1 and VEGFA expression at 4 weeks (both p < 0.05). Subjects who developed ACR had significant FLT1, TIE2, and KDR expression at 4 weeks (all p < 0.05). CONCLUSIONS: Incidence of CAS is high after severe, established airway necrosis after transplantation. HBOT does not reduce CAS severity or stenting. Elevated HMOX1 and VEGFA expressions appear to associate with airway complications.

Pilot Study of the Performance of 19-G Needle in Endobronchial Ultrasound-guided Transbronchial Aspiration for the Diagnosis and Testing of Molecular Markers in Lung Cancer.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become the standard for diagnosis and staging of lung cancer. Historically, 21- and 22-G needles have been paired with EBUS. We evaluated the performance of EBUS-TBNA using a larger 19-G needle in the assessment of tumor tissue obtained and success of testing for molecular markers. METHODS: We prospectively enrolled adult patients with lymphadenopathy concerning for metastatic lung cancer. Patients underwent diagnostic EBUS-TBNA utilizing 19-G needles. Cases of non-small cell lung cancer (NSCLC) were evaluated for programmed cell death receptor ligand (PD-L1) expression. Cases of adenocarcinoma or undifferentiated NSCLC were further evaluated for 3 molecular markers for driver mutations: epidermal growth factor receptor (EGFR), c-ros oncogene 1 (ROS-1), and anaplastic lymphoma kinase (ALK). RESULTS: Fifty patients were enrolled and underwent EBUS-TBNA using 19-G needles. PD-L1 assay was successfully performed in 90% of NSCLC cases. In adenocarcinoma or undifferentiated NSCLC cases, the success rate in testing was 90% for EGFR and 86% for ALK. ROS-1 testing had a success rate of 67%; 24% of these specimens had adequate tumor cells but there was technical difficulty with the assay. Block quality was judged by total number of tumor cells per hematoxylin and eosin-stained slide of each cell block (58% of specimens had >500 cells and 22% had 200 to 500 cells). There were no adverse events. CONCLUSION: EBUS-TBNA using 19-G needles can obtain a high number of tumor cells and has a high rate of success in performing assays for PD-L1, EGFR, and ALK in NSCLC patients without an increase in adverse events. The success rate of ROS-1 testing was lower.

Operator Perception of a Single-Use Flexible Bronchoscope: Comparison With Current Standard Bronchoscopes.

BACKGROUND: Single-use flexible bronchoscopes have gained popularity in recent years for various advantages over the traditional reusable bronchoscope. There are several commercially available disposable bronchoscopes; however, all have limitations compared to reusable bronchoscopes. The Vathin H-SteriScope is a single-use flexible bronchoscope that may have overcome some of these limitations. METHODS: We designed a survey to evaluate the performance of this new single-use bronchoscope on a bronchoscopy model with operators who are familiar with current single-use and reusable bronchoscopes. The operators were asked to rank overall assessment, scope quality, handling, maneuverability, tool interaction, and image quality of the H-SteriScope on a scale of 0-100. These operators were then asked to rank their current single-use and reusable bronchoscopes with the same scale. The results were evaluated to determine the operator perception of the H-SteriScope. RESULTS: The H-SteriScope and current reusable bronchoscopes were perceived to have significant differences compared with currently available single-use bronchoscopes in overall assessment of the scope, scope quality, handling, maneuverability, tool interaction, and image quality (P < .001). The H-SteriScope was perceived to have similar maneuverability as the reusable bronchoscope (P = .86). There were no differences among the H-SteriScope (P = .88), the current single-use bronchoscope (P = .84), and the current reusable bronchoscope (P = .89) between the training and nontraining interventional pulmonology subgroups. CONCLUSIONS: In terms of operator perception, the H-SteriScope appears to have similar maneuverability as the reusable bronchoscope. Both the H-SteriScope and the reusable bronchoscopes performed better in all measured sectors than the current single-use bronchoscope. Additional studies are required to evaluate the practicality, safety, and cost efficiency of the H-SteriScope in clinical practice.

NCCN Guidelines Insights: Management of Immunotherapy-Related Toxicities, Version 1.2020.

The NCCN Guidelines for Management of Immunotherapy-Related Toxicities provide interdisciplinary guidance on the management of immune-related adverse events (irAEs) resulting from cancer immunotherapy. These NCCN Guidelines Insights describe symptoms that may be caused by an irAE and should trigger further investigation, and summarize the NCCN Management of Immunotherapy-Related Toxicities Panel discussions for the 2020 update to the guidelines regarding immune checkpoint inhibitor-related diarrhea/colitis and cardiovascular irAEs.

Utilization of 19F MRI for Identification of Iraq-Afghanistan War Lung Injury.

INTRODUCTION: There is mounting evidence of respiratory problems related to military service in the Middle East in the past two decades due to environmental exposures during deployment (eg, sand storms and burn pits). This pilot study tests the hypothesis that regional lung function in subjects with prior deployment in Iraq and/or Afghanistan with suspected War Lung Injury (WLI) would be worse than subjects with normal lung function. MATERIALS AND METHODS: Five subjects meeting the inclusion and exclusion criteria were recruited for this pilot study. All subjects underwent spirometry, high-resolution chest computed tomography imaging, and 19F MRI. RESULTS: While the WLI subjects had normal pulmonary function tests and normal high-resolution chest computed tomography evaluations, their regional lung function from 19F MRI was abnormal with compartments with poor function showing slower filling time constants for ventilation. The scans of suspected WLI subjects show higher fractional lung volume with slow filling compartments similar to patients with chronic obstructive pulmonary disease in contrast to normal subjects. CONCLUSIONS: This is consistent with our premise that WLI results in abnormal lung function and reflects small airways dysfunction and suggests that we may be able to provide a more sensitive tool for evaluation of WLI suspected cases.

Clinical and radiographic predictors of successful therapeutic bronchoscopy for the relief of malignant central airway obstruction.

BACKGROUND: Malignant central airway obstruction (CAO) occurs in approximately 20-30% of patients with lung cancer and is associated with debilitating symptoms and poor prognosis. Multimodality therapeutic bronchoscopy can relieve malignant CAO, though carries risk. Evidence to guide clinicians regarding which patients may benefit from such interventions is sparse. We aimed to assess the clinical and radiographic predictors associated with therapeutic bronchoscopy success in relieving malignant CAO. METHODS: We reviewed all cases of therapeutic bronchoscopy performed for malignant CAO at our institution from January 2010-February 2017. Therapeutic bronchoscopy success was defined as establishing airway patency of > 50%. Patient demographics and baseline characteristics, oncology history, degree of airway obstruction, procedural interventions, and complications were compared between successful and unsuccessful groups. Univariate and multivariate logistic regression identified the significant clinical and radiographic predictors for therapeutic success. The corresponding simple and conditional odds ratio were calculated. A time-to-event analysis with Kaplan-Meier plots was performed to estimate overall survival. RESULTS: During the study period, 301 therapeutic bronchoscopies were performed; 44 (14.6%) were considered unsuccessful. Factors associated with success included never vs current smoking status (OR 5.36, 95% CI:1.45-19.74, p = 0.010), patent distal airway on CT imaging (OR 15.11, 95% CI:2.98-45.83, p < 0.0001) and patent distal airway visualized during bronchoscopy (OR 10.77, 95% CI:3.63-31.95, p < 0.001) in univariate analysis. Along with patent distal airway on CT imaging, increased time from radiographic finding to therapeutic bronchoscopy was associated with lower odds of success in multivariate analysis (OR 0.96, 95% CI:0.92-1.00, p = 0.048). Median survival was longer in the successful group (10.2 months, 95% CI:4.8-20.2) compared to the unsuccessful group (6.1 months, 95% CI:2.1-10.8, log rank p = 0.015). CONCLUSIONS: Predictors associated with successful therapeutic bronchoscopy for malignant CAO include distal patent airway visualized on CT scan and during bronchoscopy. Odds of success are higher in non-smokers, and with decreased time from radiographic finding of CAO to intervention.

Management of Immunotherapy-Related Toxicities, Version 1.2019.

The aim of the NCCN Guidelines for Management of Immunotherapy-Related Toxicities is to provide guidance on the management of immune-related adverse events resulting from cancer immunotherapy. The NCCN Management of Immunotherapy-Related Toxicities Panel is an interdisciplinary group of representatives from NCCN Member Institutions and ASCO, consisting of medical and hematologic oncologists with expertise in a wide array of disease sites, and experts from the fields of dermatology, gastroenterology, neuro-oncology, nephrology, emergency medicine, cardiology, oncology nursing, and patient advocacy. Several panel representatives are members of the Society for Immunotherapy of Cancer (SITC). The initial version of the NCCN Guidelines was designed in general alignment with recommendations published by ASCO and SITC. The content featured in this issue is an excerpt of the recommendations for managing toxicity related to immune checkpoint blockade and a review of existing evidence. For the full version of the NCCN Guidelines, including recommendations for managing toxicities related to chimeric antigen receptor T-cell therapy, visit NCCN.org.

Increasing PET Use in Small Cell Lung Cancer: Survival Improvement and Stage Migration in the VA Central Cancer Registry.

Background: Accurate staging for small cell lung cancer (SCLC) is critical for determining appropriate therapy. The clinical impact of increasing PET adoption and stage migration is well described in non-small cell lung cancer but not in SCLC. The objective of this study was to evaluate temporal trends in PET staging and survival in the Veterans Affairs Central Cancer Registry and the impact of PET on outcomes. Patients and Methods: Patients diagnosed with SCLC from 2001 to 2010 were identified. PET staging, overall survival (OS), and lung cancer-specific survival (LCSS) were assessed over time. The impact of PET staging on OS and LCSS was assessed for limited-stage (LS) and extensive-stage (ES) SCLC. Results: From 2001 to 2010, PET use in a total of 10,135 patients with SCLC increased from 1.1% to 39.2%. Median OS improved for all patients (from 6.2 to 7.9 months), those with LS-SCLC (from 10.9 to 13.2 months), and those with ES-SCLC (from 5.0 to 7.0 months). Among staged patients, the proportion of ES-SCLC increased from 63.9% to 65.7%. Among 1,536 patients with LS-SCLC treated with concurrent chemoradiotherapy, 397 were staged by PET. In these patients, PET was associated with longer OS (median, 19.8 vs 14.3 months; hazard ratio [HR], 0.78; 95% CI, 0.68-0.90; P<.0001) and LCSS (median, 22.9 vs 16.7 months; HR, 0.74; 95% CI, 0.63-0.87; P<.0001) with multivariate adjustment and propensity-matching. In the 6,143 patients with ES-SCLC, PET was also associated with improved OS and LCSS. Conclusions: From 2001 to 2010, PET staging increased in this large cohort, with a corresponding relative increase in ES-SCLC. PET was associated with greater OS and LCSS for LS-SCLC and ES-SCLC, likely reflecting stage migration and stage-appropriate therapy. These findings emphasize the importance of PET in SCLC and support its routine use.

Management of Lung Transplant Bronchial Stenosis With Mitomycin C.

BACKGROUND: Bronchial stenosis is a significant source of morbidity among lung transplant recipients, with etiologies including infection and ischemia of the airways. Current management with balloon bronchoplasty and stents is imperfect and a subset of patients requires multiple procedures to maintain airway patency. Mitomycin C (MMC) has been utilized for its antifibrotic properties in nonmalignant tracheobronchial stenosis but its application is not well studied in post-lung transplant stenosis. We performed this study to assess if MMC application decreases the need for repeated balloon bronchoplasty in lung transplant-related airway stenosis. METHODS: This is a retrospective cohort study of all lung transplant recipients who developed airway stenosis and who were treated with MMC over 4 years. MMC was injected submucosally into the stenotic airway. We compared the rate of bronchoscopic dilation at intervals of 3 and 6 months before and after MMC therapy. RESULTS: Eleven lung transplant recipients, with airway stenosis were included in our study, who required recurrent balloon dilation, despite airway stents in place in 73% of these patients. At 3 months after MMC treatment the median number of dilations decreased from 3 to 1 (P=0.023), and at 6 months from 3 to 2 dilations (P=0.004). There was a trend toward improvement in forced expiratory volume in one second and forced vital capacity, although it was not statistically significant. No adverse events related to MMC therapy was observed CONCLUSION:: Application of MMC is safe and is associated with a reduction in frequency of bronchoscopic balloon dilation in patients with post-lung transplant airway stenosis.

Yield of Malignant Pleural Effusion for Detection of Oncogenic Driver Mutations in Lung Adenocarcinoma.

BACKGROUND: Pleural fluid can be used to assess targetable mutations in patients with lung adenocarcinoma. The primary objective of this study was to assess the yield of pleural fluid cytology for targetable oncogenic mutations (EGFR, KRAS, BRAF, ALK, and ROS1 gene rearrangements). We also assessed pleural fluid volume necessary for molecular testing. METHODS: Retrospective review was performed of 134 consecutive patients with lung adenocarcinoma associated malignant pleural effusions. EGFR and KRAS testing was done using PCR amplification followed by DNA sequencing, or next generation sequencing in more recent cases that included BRAF assessment. Fluorescence in situ hybridization employing break-apart probes was used to test for ALK and ROS1 rearrangements. RESULTS: Mutation analysis on pleural fluid cell-block was performed on 56 patients. It was adequate for complete analysis ordered including EGFR, KRAS, BRAF, ALK, and ROS1 rearrangements on 40 (71.4%) samples. For individual mutations, EGFR testing was possible in 38 of 49 (77.6%); KRAS 22 of 28 (78.6%); BRAF 10 of 13 (76.9%), ALK gene rearrangement 42 of 51 (82.4%) and ROS1 gene rearrangement in 21 of 28 (75%) pleural fluid specimens. The analysis was satisfactory in 13 of 19 (68.4%) samples with ≤100 mL versus 27 of 37 (72.9%) with >100 mL of fluid tested (P-value=0.7). CONCLUSION: Genetic mutation analysis can be performed on malignant pleural effusions secondary to lung adenocarcinoma, independent of fluid volume.