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Background: A debate persists on the prognostic value of the pre-therapeutic standardized uptake value (SUV) of non-tumorous lung tissue for the risk assessment of therapy-related pneumonitis, with most studies lacking significant correlation. However, the influence of patient comorbidities on the pre-therapeutic lung SUV has not yet been systematically evaluated. Thus, we aimed to elucidate the association between comorbidities, biological variables and lung SUVs in pre-therapeutic [18F]FDG-PET/CT. Methods: In this retrospective study, the pre-therapeutic SUV in [18F]FDG-PET/CT was measured in non-tumorous areas of both lobes of the lung. SUVMEAN, SUVMAX and SUV95 were compared to a multitude of patient characteristics and comorbidities with Spearman's correlation analysis, followed by a Bonferroni correction and multilinear regression. Results: In total, 240 patients with lung cancer were analyzed. An elevated BMI was significantly associated with increased SUVMAX (β = 0.037, p < 0.001), SUVMEAN (β = 0.017, p < 0.001) and SUV95 (β = 0.028, p < 0.001). Patients with chronic obstructive pulmonary disease (COPD) showed a significantly decreased SUVMAX (β = −0.156, p = 0.001), SUVMEAN (β = −0.107, p < 0.001) and SUV95 (β = −0.134, p < 0.001). Multiple other comorbidities did not show a significant correlation with the SUV of the non-tumorous lung. Conclusions: Failure to consider the influence of BMI and COPD on the pre-therapeutic SUV measurements may lead to an erroneous interpretation of the pre-therapeutic SUV and subsequent treatment decisions in patients with lung cancer. [ABSTRACT FROM AUTHOR]

Despite therapeutic advances, early mortality in lung cancer is still prevalent. In this study, we aimed to assess risk factors for 30- and 60-day mortality in German lung cancer patients. In this retrospective cross-sectional analysis, we used data of lung cancer patients treated at LMU Hospital Munich between 2015 and 2019. We categorized patients into 30-day mortality, 60 day-mortality, and longer survival. We used Student's t-test and ANOVA to compare means and Chi2-test to compare frequencies. We used logistic regression analysis to identify factors associated with a risk for early mortality. Of the 2454 lung cancer patients, 2.0% (n = 50) died within 30 and 1.7% (n = 41) within 30 to 60 days of diagnosis. Older age and advanced stage at diagnosis were significantly associated with early mortality in the univariate and the multivariate analysis. Patients in the 30-day mortality group significantly more often did not receive tumor-directed therapy. They were also more likely to die in an acute care setting compared to the 60-day mortality group. The group of patients who died unexpectedly (12.0%) was dominantly female, with a high proportion of patients with unintentional weight loss at the time of diagnosis. Our results suggest that in the treatment of patients with lung cancer there is a need for a greater focus on older patients. Moreover, physicians should pay special attention to females with recent weight loss and patients with a comorbidity of diabetes mellitus or renal impairment. Engaging a case manager focused on detecting patients with the above characteristics could help improve overall care. [ABSTRACT FROM AUTHOR]

Purpose: Evaluating patients and treatment decisions in a multidisciplinary tumor board has led to better quality of care and longer survival in cancer patients. The aim of this study was to evaluate tumor board recommendations for thoracic oncology patients regarding guideline adherence and transferal of recommendations into clinical practice. Methods: We evaluated tumor board recommendations of the thoracic oncology tumor board at Ludwig-Maximilians University (LMU) Hospital Munich between 2014 and 2016. We compared patient characteristics between guideline-adherent and non-guideline-adherent recommendations, as well as between transferred and non-transferred recommendations. We used multivariate logistic regression models to evaluate factors associated with guideline adherence. Results: Over 90% of recommendations by the tumor board were either adherent to the guidelines (75.5%) or over fulfilling guidelines (15.6%). Almost 90% of recommendations were transferred to clinical practice. If a recommendation was not according to the guidelines, the reason was mostly associated with the general condition (age, Charlson comorbidity index, ECOG) of the patient or due to the patients' request. Surprisingly, sex also had a significant influence on the guideline adherence of recommendations, with females being more likely to get recommendations not according to the guidelines. Conclusion: In conclusion, the results of this study are promising, as the guideline adherence of recommendations as well as the transferal of recommendations into clinical practice were high. In the future, a special focus should be put on fragile patients as well as female patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Non-small-cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases and is the leading cause of cancer-related deaths. Most NSCLC patients are diagnosed with advanced disease and require systemic treatment. Despite emerging advances in chemotherapy and immunotherapy, the prognosis of stage IV patients remains poor. However, the discovery of oncogenic driver mutations including mutations in the epidermal growth factor receptor (EGFR), the anaplastic lymphoma kinase (ALK) and others, characterize a subset of patients with the opportunity of targeted therapies. Fusions between the ALK and echinoderm microtubule-associated protein-like 4 (EML4) are present in ∼ 3–5% of patients with NSCLC. Several first-, second-, and third-generation ALK tyrosine kinase inhibitors (TKIs) have been developed in the last decade and have tremendously changed treatment options and outcomes of ALK-positive NSCLC patients. With increasing treatment options, treatment sequence decisions have become more and more complex. ALK-mutations, fusion variants, or activation of by-pass pathways result in treatment resistance during the course of treatment in nearly all patients. Mutation-guided treatment sequencing can lead to better outcomes, and re-biopsy or liquid-biopsy should be performed whenever possible in case of disease progression in ALK-rearranged patients. In the future, combinational treatment of ALK TKIs with other pathway-inhibitors might further improve patients' treatment options and outcomes. Here, we review the data for currently available ALK TKIs, discuss approaches of treatment sequencing, and give an outlook on emerging developments. [ABSTRACT FROM AUTHOR]

Aims: Non-small cell lung cancer (NSCLC) patients with EGFR mutations do not respond well to checkpoint inhibitors. However, little is known about the activity of immunotherapy in NSCLC with other driver mutations. The increasing use of next-generation sequencing (NGS) leads to molecular findings that face the clinician with problems while choosing the best treatment. This study aims at analyzing response of NSCLC with driver mutations to immunotherapy. Patients and Methods: We retrospectively included 84 NSCLC patients diagnosed and treated at 2 German tertiary-care lung cancer centers using NGS and treatment with immunotherapy. Response to immunotherapy was analyzed in correlation to molecular findings. Results: 51 patients harbored at least 1 driver mutation. PIK3CA, EGFR, and STK11 mutations did not respond to immunotherapy. KRAS, TP53, and MET exon 14 skipping mutations responded well. One patient with NF-1 mutation showed durable response. Conclusions: Molecular testing may be of use in guiding treatment decision making in NSCLC. [ABSTRACT FROM AUTHOR]

Background: Generally, tyrosine kinase inhibitor (TKI) therapy is recommended in first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) harbouring a classic epidermal growth factor receptor (EGFR) mutation. However, the response of patients with rare or complex EGFR mutations to TKI treatment is not predictable, nor is the prognosis for such patients. Objectives: In cases of rare or complex EGFR mutations, the right approach to therapy remains challenging. That is why we sought to analyse the characteristics as well as the prognosis and the response to TKI treatment of patients with rare or complex EGFR mutations. Patients and Methods: 343 NSCLC patients tested for EGFR mutation at a German lung cancer centre were analysed for age, gender, and smoking status as well as for the mutation status. For 12 patients with rare and complex mutations, response to TKI treatment was described. Results: 282 of all patients had a wild-type EGFR, whereas 61 harboured an EGFR mutation. 32 of these were classic mutations, followed by 16 rare and 7 complex mutations. EGFR mutations were significantly more frequent in women. Patients with rare or complex mutations were significantly more often smokers compared to those with classic EGFR mutations. Furthermore, rare and complex mutations were less responsive to TKI therapy. Conclusion: Patients with rare or complex EGFR mutations differ from those with classic mutations in terms of smoking status and response to TKIs. As these mutations may not respond well to TKI therapy, first-line TKIs should not be automatically chosen based on the sole presence of an EGFR mutation. [ABSTRACT FROM AUTHOR]

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A correction to this paper has been published: https://doi.org/10.1007/s40265-021-01536-8 [ABSTRACT FROM AUTHOR]

a case study is presented for a 53-year-old female who was suffering from advanced nonsmall-cell lung cancer and later revealed partial tumor response after she underwent a PET-CT (Positron emission tomography-Computed tomography) scan.

This study provides comparative evidence of the selective MET inhibitor capmatinib versus standard of care (SOC) in first-line (1 L) and second-line (2 L) non-small cell lung cancer (NSCLC) patients with MET ex14 mutations in German routine care. SOC data were collected from German routine care via retrospective chart review. Analyses were conducted as naive and propensity score adjusted (PSA) comparisons to capmatinib-treated patients within the GEOMETRY mono-1 trial. Effectiveness endpoints included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), time to CNS progression (CNSprog), and exploratory safety endpoints. The SOC arm included 119 patients in 1 L and 46 in 2 L versus 60 patients in 1 L and 81 in 2 L treated with capmatinib, with balanced baseline characteristics after PSA. In 1 L, the naive comparison showed a significant benefit of capmatinib versus SOC for OS (median: 25.49 vs 14.59 months; HR 0.58; 95 % CI 0.39–0.87; P = 0.011), PFS (median: 12.45 vs 5.03 months; HR: 0.44; 95 % CI: 0.31–0.63; P < 0.001), and ORR (event rate: 68.3 vs 26.9 %; RR 2.54; 95 % CI 1.80–3.58; P < 0.001). In 2 L, OS, PFS, and ORR showed positive trends favoring capmatinib over SOC. Capmatinib treatment in the 1 L and 2 L led to significant benefit in CNSprog. PSA analyses showed consistent results to naive analysis. Exploratory safety endpoints indicated a manageable safety profile for capmatinib. The present study demonstrates the important role of capmatinib in providing robust clinically meaningful benefit to patients with NSCLC harboring MET ex14 mutations and its significant role in preventing the development of brain metastases. • RECAP study presents indirect comparison of capmatinib vs SOC in German practice. • Capmatinib shows a robust clinically meaningful benefit vs SOC in MET ex14-mutated NSCLC. • Capmatinib demonstrates significant efficacy vs SOC in preventing brain metastases. • This real-world study reinforces the high need of molecular testing in NSCLC. [ABSTRACT FROM AUTHOR]

[Display omitted] • Most genes involved in collagen metabolism are upregulated in NSCLC. • High expression of those genes is associated with poor outcome. • In vitro RAS inhibitors led to a dose dependent decrease of collagen deposition. • RAS inhibitor intake was associated with improved survival in a large NSCLC cohort. • Our results point towards collagen biosynthesis as a promising target in NSCLC. The tumor-microenvironment (TME) represents an attractive therapeutic target in NSCLC and plays an important role for efficacy of cancer therapeutics. We hypothesized that upregulation of collagen synthesis might be associated with adverse outcome in NSCLC. Literature evidence suggests that renin-angiotensin system inhibitors (RASi) decrease collagen deposition. Therefore, we aimed to explore the prognostic role of RASi intake and their influence on the TME in NSCLC. Four publicly available datasets were used to evaluate the impact of key enzymes involved in collagen biosynthesis. To investigate the influence of RASi intake on the TME and prognosis we evaluated a cohort of metastatic NSCLC patients and performed histopathological characterization of the TME. A three-dimensional microtissue in vitro model was developed to define the impact of RASi on collagen synthesis. Expression of three genes of the collagen synthesis pathway, ALDH18A1 , PLOD2 and P4HA1 , was upregulated in NSCLC compared to normal lung tissue and linked to shortened overall survival in all investigated cohorts. Together, these genes formed a 'Collagen Signature' which represents an independent unfavourable prognostic factor in two NSCLC cohorts and was linked to alterations of the extracellular matrix deposition and cell cycle pathways. In the cohort of metastatic NSCLC, RASi intake was linked to improved overall response rate and survival. Exploratory in vitro experiments revealed that RASi led to a dose dependent reduction of collagen deposition and degradation of three-dimensional lung cancer cell spheroids. We demonstrate that collagen synthesis is a key upregulated process in the NSCLC TME and its transcriptional readout, the three gene Collagen Signature is independently associated with poor outcome. Pharmacological targeting of this pathways e.g. by RASi bears potential of improving outcome in NSCLC. [ABSTRACT FROM AUTHOR]

The efficacy of checkpoint inhibitors for non-small cell lung cancer (NSCLC) with MET exon 14 skipping (METΔ14ex) remains controversial. 110 consecutive METΔ14ex NSCLC patients receiving first-line chemotherapy (CHT) and/or immunotherapy (IO) in 10 German centers between 2016–2022 were analyzed. Combined CHT-IO was given to 35/110 (32%) patients, IO alone to 43/110 (39%), and CHT to 32/110 (29%) upfront. Compared to CHT, CHT-IO showed longer progression-free survival (median PFS 6 vs. 2.5 months, p = 0.004), more objective responses (ORR 49% vs. 28%, p = 0.086) and numerically longer overall survival (OS 16 vs. 10 months, p = 0.240). For IO monotherapy, OS (14 vs. 16 months) and duration of response (26 vs. 22 months) were comparable to those of CHT-IO. Primary progressive disease (PD) was more frequent with IO compared to CHT-IO (13/43 vs. 3/35, p = 0.018), particularly for never-smokers (p = 0.041). Higher PD-L1 TPS were not associated with better IO outcomes, but TP53 mutated tumors showed numerically improved ORR (56% vs. 32%, p = 0.088) and PFS (6 vs. 3 months, p = 0.160), as well as longer OS in multivariable analysis (HR=0.54, p = 0.034) compared to their wild-type counterparts. Any second-line treatment was administered to 35/75 (47%) patients, with longer survival for capmatinib or tepotinib compared to crizotinib (PFS 10 vs. 3 months, p = 0.013; OS 16 vs. 13 months, p = 0.270). CHT-IO is superior to CHT, and IO alone also effective for METΔ14ex NSCLC, especially in the presence of TP53 mutations and independent of PD-L1 expression, but never-smokers are at higher risk of primary PD. • Chemoimmunotherapy prolongs PFS compared to chemotherapy in METΔ14ex NSCLC. • IO monotherapy confer long responses and OS similar to that of CHT-IO. • PD-L1 expression does not correlate with immunotherapeutic efficacy. • TP53 mutations are linked to better IO outcomes and may assist therapeutic decisions. • The rate of second-line treatment in the real-world setting is approximately 50%. [ABSTRACT FROM AUTHOR]