Clinicopathological characterization of next-generation sequencing detected mutations in lung cancers-a single-center experience.

Background: Despite many advances in molecular procedures many lung cancer patients do not receive full panel testing. This can limit the comprehensive understanding of their disease and potentially hinder personalized treatment options. Methods: In this retrospective analysis, we used results from next-generation sequencing (NGS) testing of 154 patients with adenocarcinoma (AC) or squamous cell carcinoma (SCC) of the lung treated at the University Hospital, Ludwig-Maximilians Universität (LMU) Munich between 2018 and 2021. We compared different clinicopathological features and patients' baseline characteristics with results of NGS testing. We used t-test and analysis of variance (ANOVA) to compare metric- and χ2-test and Fisher's exact test to compare categorical variables. Results: NGS testing found mutations in 107 (69.5%) patients; 44 patients (28.6%) had more than one mutation. The majority (79.2%) of patients had AC and 64.9% were metastasized at diagnosis. Patients with detected mutations had significantly higher PD-L1 expression than those without mutations (36.4% vs. 19.2%, P=0.005). Mean PD-L1 expression also differed between different mutations ranging from 24.0% in EGFR to 56.8% in patients with MET alterations, and increased with the number of different mutations (P=0.07). EGFR mutations were significantly more common in females compared to males (22.9% vs. 9.5%, P=0.04) and PIK3CA mutations significantly more common in SCC (21.9% vs. 2.5%, P=0.004). We found 23 different mutations in AC and 13 different gene mutations in SCC. Conclusions: Mutation profiles differed by histological type and metastases status and were significantly associated with PD-L1 expression. In the context of limited resources, our results may help prioritize patient for testing when tissue material and funding is limited.

Implications of Switching from Conventional to Electronic Cigarettes on Quality of Life and Smoking Behaviour: Results from the EQualLife Trial.

INTRODUCTION: Electronic cigarettes and "vaping" have become popular since their appearance in Europe and the USA in approximately 2006. They are often perceived as having fewer health risks than conventional cigarettes, which makes them of interest as a support tool in smoking cessation. However, its efficacy regarding cessation or reduction of smoking under real-life conditions remains controversial. Our objective was to clarify this question in an observational study of smoking habits after initiating vaping without targeted intervention, as compared to a validated cessation programme. METHODS: From October 2015 to April 2018, 80 subjects (60 in the e-cigarette group and 20 in the supervised smoking cessation group) were included in two trial visits, one at the start of the trial and the second after 3 months, plus 4 questionnaire surveys: at the start of the trial and after a 1, 2, and 3 month period. The questionnaire included a nicotine use inventory, a modified Fagerström test for nicotine dependence, and the WHO-QOL-BREF survey. RESULTS: E-cigarettes were effective, leading to a significant (p < 0.03) reduction (p < 0.03) in tobacco consumption and nicotine dependence, with an abstinence rate of 43% after 3 months. Compared to participants in the smoking cessation programme, their use was not associated with an improvement in quality of life during the quitting attempt, and there were no significant differences in clinical symptoms between groups. The reduction in nicotine dependence was more pronounced (p < 0.012) for the smoking cessation programme, with higher abstinence rates (p = 0.011 after 12 weeks) and lower (p < 0.003) remaining tobacco consumption compared to electronic cigarettes. DISCUSSION/CONCLUSIONS: The use of electronic cigarettes reduced nicotine dependence and tobacco consumption, but a supervised smoking cessation programme was superior in terms of achieved cessation in both regards. Electronic cigarettes did not improve the quality of life. Since e-cigarettes could be associated with long-term health risks, their usefulness in smoking cessation remains questionable, and a professionally guided and validated smoking cessation programme still appears to be superior and preferable, in terms of achieved cessation. Although this trial is limited regarding the number of participants and follow-up time, it highlights the need for additional, large clinical trials evaluating the efficacy of e-cigarettes for smoking cessation in comparison to a professionally guided smoking cessation programme.

Characteristics of Current Smokers versus Former Smokers with COPD and Their Associations with Smoking Cessation Within 4.5 Years: Results from COSYCONET.

Background: Many patients with chronic obstructive pulmonary disease (COPD) continue smoking. We used data from the "real-life" COSYCONET COPD cohort to evaluate whether these patients differed from patients with COPD who either had ceased smoking prior to inclusion or ceased during the follow-up time of the study. Methods: The analysis was based on data from visits 1-5 (covering 4.5 years), including all patients with the diagnosis of COPD who were either ex-smokers or smokers and categorized as GOLD 1-4 or the former GOLD 0 category. We compared the characteristics of smokers and ex-smokers at baseline (visit 1), as well as the course of lung function in the follow-up of permanent ex-smokers, permanent smokers and incident ex-smokers (smokers at visit 1 who ceased smoking before visit 5). We also identified baseline factors associated with subsequent smoking cessation. Results: Among 2500 patients who were ever-smokers, 660 were current smokers and 1840 ex-smokers at baseline. Smokers were younger than ex-smokers (mean 61.5 vs 66.0 y), had a longer duration of smoking but fewer pack-years, a lower frequency of asthma, higher forced expiratory volume in 1 sec (FEV1, 59.4 vs 55.2% predicted) and higher functional residual capacity (FRC, 147.7 vs 144.3% predicted). Similar results were obtained for the longitudinal subpopulation, comprising 713 permanent ex-smokers, 175 permanent smokers, and 55 incident ex-smokers. When analyzing the time course of lung function, higher FRC, lower FEV1 and the presence of asthma (p < 0.05 each) were associated with incident cessation prior to visit 5, while less airway obstruction was associated with smoking continuation. Conclusion: These findings, which were consistent in the cross-sectional and longitudinal analyses, suggest that lung hyperinflation was associated with being or becoming ex-smoker. Possibly, it is perceived by patients as one of the factors motivating their attempts to quit smoking, independent from airway obstruction.

Clinical factors linked to the type of respiratory medication in COPD: results from the COSYCONET cohort.

BACKGROUND: The use of maintenance medication in patients with chronic obstructive pulmonary disease (COPD) in real life is known to deviate from recommendations in guidelines, which are largely based on randomized controlled trials and selected populations. OBJECTIVES: We used the COSYCONET (COPD and Systemic Consequences - Comorbidities Network) cohort to analyze factors linked to the use of COPD drugs under non-interventional circumstances. DESIGN: COSYCONET is an ongoing, multi-center, non-interventional cohort of patients with COPD. METHODS: Patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 0-4 participating in visits 1-5 were included. Data covered the period from 2010 to 2018. Generalized linear models were used to examine the relation of COPD characteristics to different types of respiratory medication. RESULTS: A total of 1043 patients were included. The duration of observation was 4.5 years. Use of respiratory medication depended on GOLD grades 0-4 and groups A-D. Long-acting muscarinic antagonist therapy increased over time, and was associated with low carbon monoxide (CO) diffusing capacity, while inhaled corticosteroid (ICS) use decreased. Active smoking was associated with less maintenance therapy in general, and female sex with less ICS use. From the eight items of the COPD Assessment Test, only hill and stair climbing were consistently linked to treatment. CONCLUSION: Using data from a large, close to real-life observational cohort, we identified factors linked to the use of various types of respiratory COPD medication. Overall, use was consistent with GOLD recommendations. Beyond this, we identified other correlates of medication use that may help us to understand and improve therapy decisions in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT01245933.

Hyperinflation and reduced diffusing capacity predict prognosis in SCLC: value of extended pre-therapeutic lung function testing.

BACKGROUND: Small cell lung cancer (SCLC) is characterized by aggressive growth and poor prognosis. Although SCLC affects nearly exclusively heavy smokers and leads to frequent respiratory symptoms, the impact of pre-therapeutic lung function testing in SCLC is sparely investigated until now. Therefore, we sought to examine whether we could find prognostic markers in pre-therapeutic lung function testing of SCLC patients. PATIENTS AND METHODS: We retrospectively analysed a cohort of 205 patients with the diagnosis of SCLC between 2010 and 2018. Pre-therapeutic values of spirometry, body plethysmography and measurement of diffusing capacity was extracted from patients' charts. Comparisons between groups were performed using the Mann-Whitney U-test or by chi-square tests as appropriate. Kaplan-Meier analyses and COX-regression models were performed to correlate lung function parameters with patients' outcome. RESULTS: Airway obstruction itself, or the diagnosis chronic obstructive pulmonary disease (COPD) based on GOLD definitions did not correlate with survival in SCLC patients. Hyperinflation measured by increased residual volume and residual volume to total lung capacity ratio (log-rank p < 0.001) and reduced diffusing capacity (log-rank p = 0.007) were associated with reduced survival. Furthermore, patients with hyperinflation as well as impairments in gas exchange representing an emphysematic phenotype had the worst outcome (log-rank p < 0.001). CONCLUSION: We recommend including body plethysmography and measurement of diffusing capacity in the pre-therapeutic assessment of SCLC patients. Our findings suggest that reduction of hyperinflation may lead to better outcome in SCLC patients. Thus, in addition to effective tumour therapy, adequate therapy of the comorbidity of COPD should also be provided. In particular, measures to reduce hyperinflation by means of dual bronchodilation as well as respiratory physiotherapy should be further assessed in this setting.

Tumor seeding following CT- guided transthoracic needle biopsy in lung cancer. A case report.

As a result of advances in the treatment of lung cancer, the life expectancy of lung cancer patients has improved significantly, but it remains the leading cause of cancer death worldwide. For decades, most of the initial tumor biopsies have been obtained by bronchoscopy or computed tomography (CT)-guided transthoracic lung biopsy without concerning reports of cancer seeding following the latter. In this case report we discuss the patient history of a 56-year old women with low-differentiated squamous cell lung cancer who developed tumor seeding following a CT-guided transthoracic biopsy 11 months after the intervention. This is put into context reviewing former and current literature.

[Not a pneumothorax again! Birt-Hogg-Dubé syndrome: a case report]. / "Nicht schon wieder ein Pneumothorax" ­ Fallbericht Birt-Hogg-Dubé-Syndrom.

Case discussion of a 40-year-old male patient with a history of recurrent pneumothoraces due to Birt-Hogg-Dubé syndrome. In addition to conservative treatment of a pneumothorax on the left side, a subtotal parietal pleurectomy on the right side was performed after recurrence of a pneumothorax 6 years later. CT of the thorax showed high-grade structural remodelling of the lung parenchyma with cystic lung lesions on both sides with a diameter of up to 7.5 cm. After exclusion of alpha-1 antitrypsin deficiency, underlying immunological disease, unremarkable family and occupational history, Birt-Hogg-Dubé syndrome was suspected based on the morphological distribution pattern of the cystic lung lesions. Genetic examination helped detect a heterozygous pathogenic variant in the FLCN gene, namely c.1294_1298del;p.(Ser432Argfs*22). Birt-Hogg-Dubé syndrome is a rare genetic disorder clinically characterized by pulmonary cysts, fibrofolliculomas of the skin and occurrence of clustered renal tumors. In particular, the increased risk of renal malignancies and the risk of spontaneous pneumothoraces underlines the importance of early diagnosis and screening of affected patients and their families.

Comparison of the sensitivity of different criteria to select lung cancer patients for screening in a cohort of German patients.

INTRODUCTION: Trials of CT-based screening for lung cancer have shown a mortality advantage for screening in North America and Europe. Before introducing a nationwide lung cancer screening program in Germany, it is important to assess the criteria used in international trials in the German population. METHODS: We used data from 3623 lung cancer patients from the data warehouse of the German Center for Lung Research (DZL). We compared the sensitivity of the following lung cancer screening criteria overall and stratified by age and histology: the National Lung Screening Trial (NLST), the Danish Lung Cancer Screening Trial (DLCST), the 2013 and 2021 US Preventive Services Task Force (USPSTF), and an adapted version of the Prostate, Lung, Colorectal, and Ovarian no race model (adapted PLCOm2012) with 6-year risk thresholds of 1.0%/6 year and 1.7%/6 year. RESULTS: Overall, the adapted PLCOm2012 model (1%/6 years), selected the highest proportion of lung cancer patients for screening (72.4%), followed by the 2021 USPSTF (70.0%), the adapted PLCOm2012 (1.7%/6 year) (57.4%), the 2013 USPTF (57.0%), DLCST criteria (48.7%), and the NLST (48.5%). The adapted PLCOm2012 risk model (1.0%/6 year) had the highest sensitivity for all histological types except for small-cell and large-cell carcinomas (non-significant), whereas the 2021 USPTF selected a higher proportion of patients. The sensitivity levels were higher in males than in females. CONCLUSION: Using a risk-based selection score resulted in higher sensitivities compared to criteria using dichotomized age and smoking history. However, gender disparities were apparent in all studied eligibility criteria. In light of increasing lung cancer incidences in women, all selection criteria should be reviewed for ways to close this gender gap, especially when implementing a large-scale lung cancer screening program.

Gender-specific differences in COPD symptoms and their impact for the diagnosis of cardiac comorbidities.

BACKGROUND: In chronic obstructive pulmonary disease (COPD), gender-specific differences in the prevalence of symptoms and comorbidity are known. RESEARCH QUESTION: We studied whether the relationship between these characteristics depended on gender and carried diagnostic information regarding cardiac comorbidities. STUDY DESIGN AND METHODS: The analysis was based on 2046 patients (GOLD grades 1-4, 795 women; 38.8%) from the COSYCONET COPD cohort. Assessments comprised the determination of clinical history, comorbidities, lung function, COPD Assessment Test (CAT) and modified Medical Research Council dyspnea scale (mMRC). Using multivariate regression analyses, gender-specific differences in the relationship between symptoms, single CAT items, comorbidities and functional alterations were determined. To reveal the relationship to cardiac disease (myocardial infarction, or heart failure, or coronary artery disease) logistic regression analysis was performed separately in men and women. RESULTS: Most functional parameters and comorbidities, as well as CAT items 1 (cough), 2 (phlegm) and 5 (activities), differed significantly (p < 0.05) between men and women. Beyond this, the relationship between functional parameters and comorbidities versus symptoms showed gender-specific differences, especially for single CAT items. In men, item 8 (energy), mMRC, smoking status, BMI, age and spirometric lung function was related to cardiac disease, while in women primarily age was predictive. INTERPRETATION: Gender-specific differences in COPD not only comprised differences in symptoms, comorbidities and functional alterations, but also differences in their mutual relationships. This was reflected in different determinants linked to cardiac disease, thereby indicating that simple diagnostic information might be used differently in men and women. CLINICAL TRIAL REGISTRATION: The cohort study is registered on ClinicalTrials.gov with identifier NCT01245933 and on GermanCTR.de with identifier DRKS00000284, date of registration November 23, 2010. Further information can be obtained on the website http://www.asconet.net .

Changes in Behavior After Vaccination and Opinions Toward Mask Wearing: Thoracic Oncology Patient-Reported Experiences During the COVID-19 Pandemic.

Background: The COVID-19 vaccines, face masks, and social distancing are effective interventions to prevent SARS-CoV-2 infections. In this study, we aimed to determine lung cancer patients' attitudes toward vaccination, changes in behavior after vaccination, and willingness to continue mask wearing after the pandemic. Methods: We sent out questionnaires to 220 thoracic oncology patients treated at our lung cancer center in May 2021. The questionnaire focused on patients' vaccination status, self-reported experiences surrounding vaccination, and assessed changes in behaviors before and after vaccination as well as opinions toward mask wearing after the pandemic. Results are presented as absolute and relative frequencies and means with standard deviation and compared using t test, paired t test, and analysis of variance test as well as chi2 test, and Fisher exact text. Results: About 91.0% of patients reported having received at least 1 vaccination. About 73.3% of patients reported having at least 1 reaction to the vaccination. The most common reactions were pain at the injection site, fatigue, and headache. After vaccination, patients increased contact with family and friends, use of public transport, and grocery shopping. Overall, the level of willingness to wear masks beyond the end of the pandemic differed according to vaccination status. Conclusions: Acceptance of the COVID-19 vaccination among thoracic oncology patients in Germany was high. Overall, patients with thoracic malignancies tolerated the COVID-19 vaccination well. Rate of adverse reaction was not higher compared with the general population. After the vaccination, patients increased social contacts and usage of public transport. These changes suggest positive psychological effects on quality of life. While reducing social distancing can increase the risk of infection, our results indicate that an extension of mask mandates after the pandemic would likely be accepted by a majority of thoracic oncology patients, suggesting that our cohort was still aware and in support of other measure of protection.

A simple risk score for mortality including the PCR Ct value upon admission in patients hospitalized due to COVID-19.

PURPOSE: To develop a simple score for the outcomes from COVID-19 that integrates information obtained at the time of admission including the Ct value (cycle threshold) for SARS-CoV-2. METHODS: Patients with COVID-19 hospitalized from February 1st to May 31st 2021 in RoMed hospitals, Germany, were included. Clinical and laboratory parameters upon admission were recorded and patients followed until discharge or death. Logistic regression analysis was used to determine predictors of outcomes. Regression coefficients were used to develop a risk score for death. RESULTS: Of 289 patients (46% female, median age 66 years), 29% underwent high-flow nasal oxygen (HFNO) therapy, 28% were admitted to the Intensive Care Unit (ICU, 51% put on invasive ventilation, IV), and 15% died. Age > 70 years, oxygen saturation ≤ 90%, oxygen supply upon admission, eGFR ≤ 60 ml/min and Ct value ≤ 26 were significant (p < 0.05 each) predictors for death, to which 2, 2, 1, 1 and 2 score points, respectively, could be attributed. Sum scores of ≥ 4 or ≥ 5 points were associated with a sensitivity of 95.0% or 82.5%, and a specificity of 72.5% or 81.7% regarding death. The high predictive value of the score was confirmed using data obtained between December 15th 2020 and January 31st 2021 (n = 215). CONCLUSION: In COVID-19 patients, a simple scoring system based on data available shortly after hospital admission including the Ct value had a high predictive value for death. The score may also be useful to estimate the likelihood for required interventions at an early stage.

Consequences of the COVID-19 pandemic on lung cancer care and patient health in a German lung cancer center: results from a cross-sectional questionnaire.

BACKGROUND: The novel coronavirus SARS-CoV-2 has caused a global COVID-19 pandemic, leading to worldwide changes in public health measures. In addition to changes in the public sector (lockdowns, contact restrictions), hospitals modified care to minimize risk of infection and to mobilize resources for COVID-19 patients. Our study aimed to assess the impact of these measures on access to care and behaviour of patients with thoracic malignancies. METHODS: Thoracic oncology patients were surveyed in October 2020 using paper-based questionnaires to assess access to ambulatory care services and tumor-directed therapy during the COVID-19 pandemic. Additionally, behaviour regarding social distancing and wearing of face masks were assessed, as well as COVID-19 exposure, testing and vaccination. Results are presented as absolute and relative frequencies for categorical variables and means with standard deviation for numerical variables. We used t-test, and ANOVA to compare differences in metric variables and Chi2-test to compare proportions between groups. RESULTS: 93 of 245 (38%) patients surveyed completed the questionnaire. Respiration therapy and physical therapy were unavailable for 57% to 70% of patients during March/April. Appointments for tumor-directed therapy, tumor imaging, and follow-up care were postponed or cancelled for 18.9%, 13.6%, and 14.8% of patients, respectively. Patients reported their general health as mostly unaffected. The majority of patients surveyed did not report reducing their contacts with family. The majority reduced contact with friends. Most patients wore community masks, although a significant proportion reported respiratory difficulties during prolonged mask-wearing. 74 patients (80%) reported willingness to be vaccinated against SARS-CoV-2. CONCLUSIONS: This survey provides insights into the patient experience during the second wave of the COVID-19 pandemic in Munich, Germany. Most patients reported no negative changes to cancer treatments or general health; however, allied health services were greatly impacted. Patients reported gaps in social distancing, but were prepared to wear community masks. The willingness to get vaccinated against SARS-CoV-2 was high. This information is not only of high relevance to policy makers, but also to health care providers.

Reduced decline of lung diffusing capacity in COPD patients with diabetes and metformin treatment.

We studied whether in patients with COPD the use of metformin for diabetes treatment was linked to a pattern of lung function decline consistent with the hypothesis of anti-aging effects of metformin. Patients of GOLD grades 1-4 of the COSYCONET cohort with follow-up data of up to 4.5 y were included. The annual decline in lung function (FEV1, FVC) and CO diffusing capacity (KCO, TLCO) in %predicted at baseline was evaluated for associations with age, sex, BMI, pack-years, smoking status, baseline lung function, exacerbation risk, respiratory symptoms, cardiac disease, as well as metformin-containing therapy compared to patients without diabetes and metformin. Among 2741 patients, 1541 (mean age 64.4 y, 601 female) fulfilled the inclusion criteria. In the group with metformin treatment vs. non-diabetes the mean annual decline in KCO and TLCO was significantly lower (0.2 vs 2.3, 0.8 vs. 2.8%predicted, respectively; p < 0.05 each), but not the decline of FEV1 and FVC. These results were confirmed using multiple regression and propensity score analyses. Our findings demonstrate an association between the annual decline of lung diffusing capacity and the intake of metformin in patients with COPD consistent with the hypothesis of anti-aging effects of metformin as reflected in a surrogate marker of emphysema.

Quantitative proteomics of differentiated primary bronchial epithelial cells from chronic obstructive pulmonary disease and control identifies potential novel host factors post-influenza A virus infection.

Background: Chronic obstructive pulmonary disease (COPD) collectively refers to chronic and progressive lung diseases that cause irreversible limitations in airflow. Patients with COPD are at high risk for severe respiratory symptoms upon influenza virus infection. Airway epithelial cells provide the first-line antiviral defense, but whether or not their susceptibility and response to influenza virus infection changes in COPD have not been elucidated. Therefore, this study aimed to compare the susceptibility of COPD- and control-derived airway epithelium to the influenza virus and assess protein changes during influenza virus infection by quantitative proteomics. Materials and methods: The presence of human- and avian-type influenza A virus receptor was assessed in control and COPD lung sections as well as in fully differentiated primary human bronchial epithelial cells (phBECs) by lectin- or antibody-based histochemical staining. PhBECs were from COPD lungs, including cells from moderate- and severe-stage diseases, and from age-, sex-, smoking, and history-matched control lung specimens. Protein profiles pre- and post-influenza virus infection in vitro were directly compared using quantitative proteomics, and selected findings were validated by qRT-PCR and immunoblotting. Results: The human-type influenza receptor was more abundant in human airways than the avian-type influenza receptor, a property that was retained in vitro when differentiating phBECs at the air-liquid interface. Proteomics of phBECs pre- and post-influenza A virus infection with A/Puerto Rico/8/34 (PR8) revealed no significant differences between COPD and control phBECs in terms of flu receptor expression, cell type composition, virus replication, or protein profile pre- and post-infection. Independent of health state, a robust antiviral response to influenza virus infection was observed, as well as upregulation of several novel influenza virus-regulated proteins, including PLSCR1, HLA-F, CMTR1, DTX3L, and SHFL. Conclusion: COPD- and control-derived phBECs did not differ in cell type composition, susceptibility to influenza virus infection, and proteomes pre- and post-infection. Finally, we identified novel influenza A virus-regulated proteins in bronchial epithelial cells that might serve as potential targets to modulate the pathogenicity of infection and acute exacerbations.

Novel Multimodal Management of Post-Partum Synchronous Metastatic Pulmonary EBV-Associated Lymphoepithelioma-Like Carcinoma (LELC)-A Case Report.

Primary Epstein-Barr-Virus (EBV)-associated pulmonary lymphoepithelioma-like carcinoma (LELC) is an aggressive rare cancer. Higher incidences have been observed in Asian sub-populations. Multimodal treatment paradigms have emerged as promising novel strategies in the management of advanced NSCLC. In this report, we describe the case of a 34-year-old female patient of Asian origin with a post-partum initial diagnosis of pulmonary LELC. Multimodal treatment with chemoimmunotherapy and hypofractionated irradiation to the primary tumour and main metastatic sites led to a favourable response demonstrating that radiotherapy may potentially augment anti-tumour immunity. To the best of our knowledge, this is the first case report on this novel therapy strategy of multi-site hypofractionated radiotherapy and chemoimmunotherapy for metastatic pulmonary EBV-associated LELC.

Prognostic and predictive value of PD-L1 expression and tumour infiltrating lymphocytes (TiLs) in locally advanced NSCLC treated with simultaneous radiochemotherapy in the randomized, multicenter, phase III German Intergroup lung Trial (GILT).

OBJECTIVES: Immune checkpoint inhibition after radiochemotherapy (RTCT) has become a new standard of care for locally advanced non-small cell lung cancer with programmed death-ligand 1 (PD-L1) expression. However, little is known about the prognostic role of immune response markers in this setting. We analysed PD-L1 expression and tumour infiltrating lymphocytes (TiLs) in tumour biopsies from the multicenter German Intergroup Lung Trial (GILT), which previously randomised patients with stage III NSCLC to RTCT with or without consolidation chemotherapy. MATERIALS AND METHODS: We retrospectively analyzed tumour biopsies from patients treated in the GILT trial. PD-L1 expression was analysed using the Ventana SP263 assay and TiL score (low, intermediate, high) and pattern (excluded, inflamed, desert) were assessed. The primary endpoint of the biomarker analysis was PFS in patients with PD-L1 ≥ 1% vs. PD-L1 < 1% NSCLC. Secondary endpoints explored the prognostic relevance of additional PD-L1 expression levels and TiL score and pattern. RESULTS: Biopsies were available from 92 patients treated with RTCT. Patients with available tumor tissue did not differ significantly from the whole study population. PD-L1 scores from 78 samples were available for analysis. There was no difference in PFS in the PD-L1 < 1% vs. PD-L1 ≥ 1% subgroups. TiL score was available in 66 patients. Patients with high TiL score showed favourable overall survival compared to the low TiL subgroup. This trend was most pronounced in those patients treated with consolidative chemotherapy. CONCLUSION: In this analysis, PD-L1 expression did not correlate with PFS following RTCT. However, patients with TiLs > 10% were found to have longer overall survival, especially for those patients treated with consolidation chemotherapy after the end of RTCT. Further analyses to explore the prognostic and predictive relevance of TiLs in the context of consolidative checkpoint inhibition with durvalumab are required.

Osimertinib rechallenge under steroid protection following osimertinib-induced pneumonitis: three case studies.

Osimertinib is a third-generation tyrosine kinase inhibitor that became the preferred first-line treatment option for metastatic non-small cell lung cancer with sensitizing epidermal growth factor receptor mutations. Drug-induced pneumonitis is known to occur with osimertinib. In case of severe pneumonitis, discontinuation of treatment and therapy with corticosteroids is recommended, and a treatment switch is usually performed. We herein report the treatment course in three patients who were rechallenged with osimertinib under steroid protection following an osimertinib-induced pneumonitis. All our patients were initially re-exposed to a lower dose of osimertinib. Two patients were successfully rechallenged under prednisolone protection. The third patient, who was initially retreated with osimertinib without steroid protection, suffered from a recurrent pneumonitis, and was later rechallenged successfully under steroid protection. Our case series indicates that rechallenge with osimertinib following recovery from osimertinib-induced pneumonitis allows a successful rechallenge in individual cases when alternative treatment options are lacking. Concomitant steroids appear to protect against flares of pneumonitis during rechallenge.