Adherence to STIKO recommendations in patients with pulmonary disease in southeast Germany.

BACKGROUND: Vaccinations are among the most effective preventative healthcare measures. The aim of this cross-sectional study was to evaluate the adherence of adults with pre-existing pulmonary conditions to the national vaccination schedule and to identify reasons for poor adherence. METHODS: All patients with an appointment at Donaustauf hospital between October 2019 and April 2020 were asked to bring their vaccination certificates for evaluation and to compete a questionnaire. To determine the adherence vaccination certificates and patients' comorbidities were correlated with the national recommendations of the German Standing Committee on Vaccination (STIKO). RESULTS: 571 (65.6%) of all patients believed that their vaccination status was up-to-date. An appropriate vaccination status according to national recommendations (STIKO) was documented as follows: tetanus 56.4% (375/665), diphtheria 43.2% (292/676), poliomyelitis 28.5% (189/662), tick-borne encephalitis 45.4% (300/659), hepatitis A 31.0% (18/58), hepatitis B 34.6% (27/78), shingles 1.2% (6/489), influenza 21.0% (125/596, season 2019/2020), measles 38.3% (31/81), rubella 33.3% (7/21), pneumococcal disease 29.5% (175/593), pertussis 54.2% (365/674) and haemophilus influenza type b 100% (1/1). Adherence to rabies (0/2), varicella (0/28), meningococcal type ACWY (0/36) and type b (0/36) was 0%. 72% of patients would follow a physician's recommendation to get vaccinated. CONCLUSION: Adherence to STIKO recommendations was poor. However, patients are willing to follow a physician's recommendation for vaccination.

Outcome of First-Line Treatment With Pembrolizumab According to KRAS/TP53 Mutational Status for Nonsquamous Programmed Death-Ligand 1-High (≥50%) NSCLC in the German National Network Genomic Medicine Lung Cancer.

INTRODUCTION: Programmed death-ligand 1 expression currently represents the only validated predictive biomarker for immune checkpoint inhibition in metastatic NSCLC in the clinical routine, but it has limited value in distinguishing responses. Assessment of KRAS and TP53 mutations (mut) as surrogate for an immunosupportive tumor microenvironment (TME) might help to close this gap. METHODS: A total of 696 consecutive patients with programmed death-ligand 1-high (≥50%), nonsquamous NSCLC, having received molecular testing within the German National Network Genomic Medicine Lung Cancer between 2017 and 2020, with Eastern Cooperative Oncology Group performance status less than or equal to 1 and pembrolizumab as first-line palliative treatment, were included into this retrospective cohort analysis. Treatment efficacy and outcome according to KRAS/TP53 status were correlated with TME composition and gene expression analysis of The Cancer Genome Atlas lung adenocarcinoma cohort. RESULTS: Proportion of KRASmut and TP53mut was 53% (G12C 25%, non-G12C 28%) and 51%, respectively. In KRASmut patients, TP53 comutations increased response rates (G12C: 69.7% versus 46.5% [TP53mut versus wild-type (wt)], p = 0.004; non-G12C: 55.4% versus 39.5%, p = 0.03), progression-free survival (G12C: hazard ratio [HR] = 0.59, p = 0.009, non-G12C: HR = 0.7, p = 0.047), and overall survival (G12C: HR = 0.72, p = 0.16, non-G12C: HR = 0.56, p = 0.002), whereas no differences were observed in KRASwt patients. After a median follow-up of 41 months, G12C/TP53mut patients experienced the longest progression-free survival and overall survival (33.7 and 65.3 mo), which correlated with high tumor-infiltrating lymphocyte densities in the TME and up-regulation of interferon gamma target genes. Proinflammatory pathways according to TP53 status (mut versus wt) were less enhanced and not different in non-G12C and KRASwt, respectively. CONCLUSIONS: G12C/TP53 comutations identify a subset of patients with a very favorable long-term survival with immune checkpoint inhibitor monotherapy, mediated by highly active interferon gamma signaling in a proinflammatory TME.

Gender Differences in Symptom Burden, Functional Performance and Global Quality of Life of Lung Cancer Patients Receiving Inpatient versus Outpatient Treatment.

Background: Lung cancer may cause severe impairment of quality of life. An increasing number of lung cancer patients are receiving outpatient chemotherapy. However, little is known about gender aspects in the areas of impaired QoL in outpatient versus inpatient lung cancer patients. The aim of the study was to investigate this. Methods: We report from a prospective, multicenter study to analyze the EORTC QLQ-LC29, a new designed module to assess the QoL of lung cancer patients. The participants filled out the EORTC QLQ-C30 and the recently updated lung cancer module QLQ-LC29. Results: A total of 198 lung cancer patients (73 female and 125 male, mean 64.5 age years) during first-line therapy were enrolled in this study by completing the both questionnaires. Women showed higher symptom scores, when being inpatient. Significant results were found regarding nausea/vomiting (mean women = 17.6 and mean men = 9.3, p = 0.037) and hair loss (mean women = 40.0 and mean men = 21.7, p = 0.010), although women received fewer chemotherapy treatments than their male counterparts (women n = 47, 64.4% and men n = 86, 68.8%). When it comes to global QoL, men report a significant worse QoL than women (mean women = 57.5 and mean men = 46.1, p = 0.016), when being inpatient. As outpatients, men report significant results regarding sore mouth and tongue (mean women = 1.2 and mean men = 13.5, p = 0.012). Conclusion: This study adds to the literature in showing the typical gender difference effect on QoL, suggesting men suffer less than women, is not a universal phenomenon irrespective of being inpatient or outpatient. It also confirms the hypothesis that the symptom burden is higher with inpatients than outpatients.

Management, risk factors and prognostic impact of checkpoint-inhibitor pneumonitis (CIP) in lung cancer - A multicenter observational analysis.

INTRODUCTION: Checkpoint-inhibitor pneumonitis (CIP) represents a major immune-related adverse event (irAE) in patients with lung cancer. We aimed for the clinical characterization, diagnostics, risk factors, treatment and outcome in a large cohort of patients from everyday clinical practice. PATIENTS AND METHODS: For this retrospective analysis, 1,376 patients having received checkpoint inhibitors (CPI) in any line of therapy from June 2015 until February 2020 from three large-volume lung cancer centers in Berlin, Germany were included and analyzed. RESULTS: With a median follow-up of 35 months, all-grade, high-grade (CTCAE ≥ 3) and fatal CIP were observed in 83 (6.0%), 37 (2.7%) and 12 (0.9%) patients, respectively, with a median onset 4 months after initiation of CPI therapy. The most common radiologic patterns were organizing pneumonia (OP) and non-specific interstitial pneumonia (NSIP) (37% and 31%). All except 7 patients with G1-2 CIP interrupted treatment. Corticosteroids were administered to 74 patients with a median starting dose of 0.75 mg/kg. After complete restitution (n = 67), re-exposure to CPI (n = 14) led to additional irAE in 43% of the cases. Thoracic radiotherapy targeting the lung was the only independent risk factor for CIP (odds ratio 2.8, p < 0.001) and pretherapeutic diffusing capacity for carbon monoxide inversely correlated with CIP severity. Compared with patients without CIP and non-CIP irAE, CIP was associated with impaired overall survival (hazard ratios 1.23, p = 0.24 and 2.01, p = 0.005). CONCLUSIONS: High-grade CIP accounts for almost half of all CIP cases in an allcomer lung cancer population. A continuous vigilance, rapid diagnostics and adequate treatment are key to prevent disease progression associated with impaired survival.

Gender Differences in Quality of Life of Metastatic Lung Cancer Patients.

Background: Gender aspects in lung cancer patients are a topic of growing interest. But little is known about gender aspects affecting the quality of life (QoL) for those with this life-threatening disease. The aim of the following study was to investigate how gender differences affect QoL in metastatic lung cancer patients. Methods: In a prospective, multicenter study patients filled out the EORTC QLQ-C30 questionnaire and the recently updated lung cancer module QLQ-LC29 at an undefined point in time during first-line therapy. Gender differences were calculated for all QoL scores using ANCOVAs, which controlled for confounders. Results: A total of 130 patients with metastatic lung cancer (UICC stage IV) (46 female and 84 male, mean age 66 years) were enrolled in this study by completing the questionnaires. The only significant gender difference in QoL was found regarding hair loss (mean women= 42.498, mean men=25.490, p-value= 0.010), although women received fewer chemotherapy treatments than men (women n=34, 74% and men n=68, 84%). Conclusion: This study provides evidence that the typical cancer related gender difference effect on QoL, suggesting that men suffer less than women, cannot be found in metastatic tumor stages of lung cancer patients.

Chronic Cough.

BACKGROUND: Chronic cough, i.e., cough lasting longer than eight weeks, affects approximately 10% of the population and is a common reason for outpatient medical consultation. Its differential diagnosis is extensive, and it is generally evaluated in poorly structured fashion with a variety of diagnostic techniques. The German Clinical Practice Guideline on Acute and Chronic Cough was updated in 2021 and contains a description of the recommended stepwise, patient-centered, and evidencebased procedure for the management of chronic cough. METHODS: The guideline has been updated in accordance with the findings of a systematic search of the literature for international guidelines and systematic reviews. All recommendations were developed in an interdisciplinary manner and agreed upon by formal consensus. The target group consists of adult patients with cough. RESULTS: History-taking, after the exclusion of red flags, should include questioning about smoking status, medications, and relevant present and past illnesses (COPD, asthma). Subsequent diagnostic testing should include a chest x-ray and pulmonary function tests. If the patient is taking an ACE inhibitor, a test of drug discontinuation can be carried out first. Radiologically detected pulmonary masses or evidence of rare diseases (interstitial lung diseases, bronchiectasis) are an indication for chest CT or for direct referral to an appropriate specialist. If the imaging studies and pulmonary function tests are normal, the patient is most likely suffering from a disease entity that can be treated empirically, such as upper airway cough syndrome or cough variant asthma. Any patient with an unexplained or refractory cough must receive proper patient education; individual therapeutic trials of physiotherapeutic or speech-therapeutic methods are possible, as is the off-label use of gabapentin or morphine. CONCLUSION: Chronic cough should be evaluated according to an established diagnostic algorithm in collaboration with specialists. Treatments such as inhaled corticosteroids should be tested exhaustively in accordance with the guidelines, and the possibility of multiple causes as well as the role of patient compliance should be kept in mind before a diagnosis of unexplained or intractable cough is assigned.

Low Adherence to Pneumococcal Vaccination in Lung Cancer Patients in a Tertiary Care University Hospital in Southern Germany.

INTRODUCTION: The aim of this study was to investigate the adherence to vaccinations, especially pneumococcal vaccinations, in lung cancer patients. METHODS: the study was performed at the University Hospital Regensburg, Germany. All patients with a regular appointment scheduled between 1 December 2020 and 29 April 2021 and who provided informed consent were included. Available medical records, vaccination certificates, and a questionnaire were analyzed. RESULTS: we included 136 lung cancer patients (NSCLC n = 113, 83.1%, SCLC n = 23, 16.9%). A correct pneumococcal vaccination according to national recommendations was performed in 9.4% (12/127) of the patients. A correct vaccination was performed for tetanus in 50.4% (66/131), diphtheria in 34.4% (44/128), poliomyelitis in 25.8% (33/128), tick-borne encephalitis in 40.7% (24/59), hepatitis A in 45.5% (7/11), hepatitis B in 38.5% (5/13), shingles in 3.0% (3/101), measles in 50.0% (3/6), pertussis in 47.7% (62/130), influenza in 54.4% (74/136), and meningococcal meningitis in 0% (0/2) of the patients. CONCLUSION: adherence to pneumococcal vaccinations, as well as to other vaccinations, is low in lung cancer patients.

Psychosocial Burden and Quality of Life of Lung Cancer Patients: Results of the EORTC QLQ-C30/QLQ-LC29 Questionnaire and Hornheide Screening Instrument.

BACKGROUND: Overall survival is the ultimate criterion for the therapy of lung cancer, but psychosocial care, which helps the patient to cope with the disease, becomes a more and more important issue in the treatment of this life-threatening disease. METHODS: We report the satellite project within a prospective, international, cross-cultural, multicenter study to validate the EORTC QLQ-LC29, a new designed module to assess the quality of life of lung cancer patients. The participants filled in the EORTC QLQ-C30, the recently updated lung cancer module QLQ-LC29 and the Hornheide questionnaire (HSI). RESULTS: A total of 81 patients (32 female and 49 male, mean age 65.2 years, SD = 9.7) were enrolled in this study by completing the questionnaires. Fatigue (mean 55.4, SD = 26.3) and dyspnea (mean 46.3, SD = 36.2) were the most prominent symptoms. Thirty-nine patients (48.1%) according to the HSI needed psychosocial support. When using the EORTC questionnaires as screening instrument with 50 as cut-off in contrast only 29.5% of our patients needed psychosocial support. The need for psychosocial support according to the HSI correlated most with the EORTC scales "fatigue" (38.3% overlap between the two questionnaires), "existential fear" (38.3% overlap between the two questionnaires) and worse "global quality of life" (27.2% overlap between the two questionnaires). CONCLUSION: If psychosocial distress is at the core, the HSI is a suitable instrument for quick screening. The EORTC measures help to specify impaired quality of life areas and also cover somatic symptoms that are specific for cancer patients. Once psychosocial distress has been ascertained, clinicians should be particularly aware of specific problems regarding "fatigue", "existential fear" and diminished "global quality of life". TRIAL REGISTRATION: clinicaltrials.gov, reference number NCT02745691. Registered 20 April 2016.

Cardiopulmonary exercise pattern in patients with persistent dyspnoea after recovery from COVID-19.

Cause and mechanisms of persistent dyspnoea after recovery from COVID-19 are not well described. The objective is to describe causal factors for persistent dyspnoea in patients after COVID-19. We examined patients reporting dyspnoea after recovery from COVID-19 by cardiopulmonary exercise testing. After exclusion of patients with pre-existing lung diseases, ten patients (mean age 50±13.1 years) were retrospectively analysed between May 14th and September 15th, 2020. On chest computed tomography, five patients showed residual ground glass opacities, and one patient showed streaky residua. A slight reduction of the mean diffusion capacity of the lung for carbon monoxide was noted in the cohort. Mean peak oxygen uptake was reduced with 1512±232 ml/min (72.7% predicted), while mean peak work rate was preserved with 131±29 W (92.4% predicted). Mean alveolar-arterial oxygen gradient (AaDO2) at peak exercise was 25.6±11.8 mmHg. Mean value of lactate post exercise was 5.6±1.8 mmol/l. A gap between peak work rate in (92.4% predicted) to peak oxygen uptake (72.3% pred.) was detected in our study cohort. Mean value of lactate post exercise was high in our study population and even higher (n.s.) compared to the subgroup of patients with reduced peak oxygen uptake and other obvious reason for limitation. Both observations support the hypothesis of anaerobic metabolism. The main reason for dyspnoea may therefore be muscular.

HPV and lung cancer: A systematic review and meta-analysis.

BACKGROUND: Lung cancer has emerged as a global public health problem and is the most common cause of cancer deaths by absolute cases globally. Besides tobacco, smoke infectious diseases such as human papillomavirus (HPV) might be involved in the pathogenesis of lung cancer. However, data are inconsistent due to differences in study design and HPV detection methods. AIM: A systematic meta-analysis was performed to examine the presence of HPV-infection with lung cancer. METHODS AND RESULTS: All studies in all languages were considered for the search concepts "lung cancer" and "HPV" if data specific to HPV prevalence in lung cancer tissue were given. This included Journal articles as well as abstracts and conference reports. As detection method, only HPV PCR results from fresh frozen and paraffin-embedded tissue were included. Five bibliographic databases and three registers of clinical trials including MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov were searched through February 2020. A total 4298 publications were identified, and 78 publications were selected, resulting in 9385 included lung cancer patients. A meta-analysis of 15 case-control studies with n = 2504 patients showed a weighted overall prevalence difference of 22% (95% CI: 12%-33%; P < .001) and a weighted overall 4.7-fold (95% CI: 2.7-8.4; P < .001) increase of HPV prevalence in lung cancer patients compared to controls. Overall, HPV prevalence amounted to 13.5% being highest in Asia (16.6%), followed by America (12.8%), and Europe (7.0%). A higher HPV prevalence was found in squamous cell carcinoma (17.9%) compared to adenocarcinoma (P < .01) with significant differences in geographic patterns. HPV genotypes 16 and 18 were the most prevalent high-risk genotypes identified. CONCLUSION: In conclusion, our review provides convincing evidence that HPV infection increases the risk of developing lung cancer.

Gender effects on quality of life and symptom burden in patients with lung cancer: results from a prospective, cross-cultural, multi-center study.

BACKGROUND: Lung cancer causes impairment of health-related quality of life (QoL), but little is known about gender aspects in QoL and symptom burden of lung cancer patients. The aim of this study was to investigate gender differences in QoL as assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the updated lung cancer module. METHODS: In a prospective, international, cross-cultural, multicenter study that was undertaken to update the lung cancer-specific module EORTC QLQ-LC13, patients filled in the core questionnaire EORTC QLQ-C30 and the updated lung cancer module. Gender differences were calculated for all QoL scores using ANCOVAs that controlled for known and suspected confounders. Comparisons with historic data were drawn. RESULTS: A total of 200 patients (82 female and 118 male, median age 65 years) were recruited. With the exception of coughing (estimated marginal means: women 33.86 and men 43.52, P=0.022) and diarrhea (estimated marginal means: women 26.01 and men 17.93, P=0.038) there were no significant QoL gender differences. Fatigue was the most pronounced symptom in both, men and women, outpacing typical respiratory symptoms. Quite generally, our sample of lung cancer patients showed considerably worse QoL in all scores when compared to EORTC reference data (lung cancer and combined cancer diagnoses, mean differences up to 13.70 and 21.54 score points, respectively) and to a German norm reference sample (up to 35.37 score points). CONCLUSIONS: This study adds to the literature in showing that the typical QoL gender difference effect (women doing worse than men) may not be generalizable across all patient samples.