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Abstract Objectives In this multi-center study, we proposed a structured reporting (SR) framework for non-small cell lung cancer (NSCLC) and developed a software-assisted tool to automatically translate image-based findings and annotations into TNM classifications. The aim of this study was to validate the software-assisted SR tool for NSCLC, assess its potential clinical impact in a proof-of-concept study, and evaluate current reporting standards in participating institutions. Methods A framework for SR and staging of NSCLC was developed in a multi-center collaboration. SR annotations and descriptions were used to generate semi-automated TNM classification. The SR and TNM classification tools were evaluated by nine radiologists on n = 20 representative [18F]FDG PET/CT studies and compared to the free text reporting (FTR) strategy. Results were compared to a multidisciplinary team reference using a generalized linear mixed model (GLMM). Additionally, participants were surveyed on their experience with SR and TNM classification. Results Overall, GLMM analysis revealed that readers using SR were 1.707 (CI: 1.137–2.585) times more likely to correctly classify TNM status compared to FTR strategy (p = 0.01) resulting in increased overall TNM correctness in 71.9% (128/178) of cases compared to 62.8% (113/180) FTR. The primary source of variation in classification accuracy was explained by case complexity. Participants rated the potential impact of SR and semi-automated TNM classification as positive across all categories with improved scores after template validation. Conclusion This multi-center study yielded an effective software-assisted SR framework for NSCLC. The SR and semi-automated classification tool improved TNM classification and were perceived as valuable. Critical relevance statement Software-assisted SR provides robust input for semi-automated rule-based TNM classification in non-small-cell lung carcinoma (NSCLC), improves TNM correctness compared to FTR, and was perceived as valuable by radiology physicians. Key Points SR and TNM classification are underutilized across participating centers for NSCLC staging. Software-assisted SR has emerged as a promising strategy for oncologic assessment. Software-assisted SR facilitates semi-automated TNM classification with improved staging accuracy compared to free-text reports in NSCLC. Graphical Abstract

Abstract Background Node-positive non-small cell lung cancers (NSCLCs) present a challenge for treatment decisions, particularly in patients ineligible for concurrent chemoradiotherapy (CRT) due to poor performance status and compromised lung function. We aimed to investigate the prognostic value of pretreatment positron emission tomography (PET) parameters in high-risk patients undergoing hypofractionated radiotherapy. Methods A retrospective analysis was conducted on 42 consecutive patients with inoperable node-positive NSCLC, who underwent hypofractionated radiotherapy between 2014 and 2021 at a single institution. Clinical, treatment-related, and [18F]FDG PET-based parameters were correlated with progression-free survival (PFS) and overall survival (OS). Median dichotomisation was performed to establish risk groups. Statistical analyses included univariable and multivariable Cox regression and Kaplan-Meier survival analyses. Results After a median follow-up of 47.1 months (range: 0.5-101.7), the median PFS and OS were 11.5 months (95% CI: 7.4-22.0), and 24.3 months (95% CI: 14.1-31.8). In univariable Cox regression analysis, significant predictors of PFS included receipt of salvage systemic treatment (p=0.007), SUVmax (p=0.032), and tMTV (p=0.038). Similarly, ECOG-PS (p=0.014), Histology (p=0.046), and tMTV (p=0.028) were significant predictors of OS. Multivariable Cox regression analysis (MVA) identified SUVmax as a significant predictor for PFS [HR: 2.29 (95% CI: 1.02-5.15); p=0.044]. For OS, ECOG-PS remained a significant prognosticator [HR: 3.53 (95% CI: 1.49-8.39); p=0.004], and tMTV approached significance [HR: 2.24 (95% CI: 0.95-5.26); p=0.065]. Furthermore, the high tMTV group exhibited a median PFS of 5.3 months [95% CI: 2.8-10.4], while the low tMTV group had a PFS of 15.2 months [95% CI: 10.1-33.5] (p=0.038, log-rank test). Median OS was 33.5 months [95% CI: 18.3-56.8] for tMTV ≤ 36.6 ml vs. 14.1 months [95% CI: 8.1-27.2] for tMTV > 36.6 ml (p=0.028, log-rank test). Conclusion Pretreatment PET parameters, especially tMTV, hold promise as prognostic indicators in NSCLC patients undergoing hypofractionated radiotherapy. The study highlights the potential of PET metrics as biomarkers for patient stratification.

HER2 mutation and amplification have been identified as distinct molecular targets in lung cancer with different therapeutic and prognostic values. The coexistence of HER2 and EGFR mutations is extremely rare, and therefore, no data exist on the best treatment in these cases.

Introduction: Patients with metastatic NSCLC (mNSCLC) treated with immune checkpoint inhibitors in clinical practice may often not meet the strict inclusion criteria of clinical trials. Our aim was to assess the trial eligibility of patients with mNSCLC treated with pembrolizumab monotherapy in real-world and to compare the outcome of “trial-ineligible” and “potentially trial-eligible” patients. Methods: Data from the prospective, clinical research platform CRISP were used to compare patient characteristics, treatment, and outcome of patients with programmed cell death-ligand 1 tumor proportion score greater than or equal to 50% tumors treated with pembrolizumab monotherapy who are deemed either “potentially trial-eligible” or “trial-ineligible” according to inclusion and exclusion criteria of the registrational studies (KEYNOTE-024 and -042). Results: Of 746 patients included, 343 patients (46.0%) were classified as “trial-ineligible” and had significantly worse outcomes compared with “potentially trial-eligible” patients (n = 403, 54.0%): median progression-free survival: 6.2 (95% confidence interval [CI]: 5.2–8.4) versus 10.3 (95% CI: 8.4–13.8) months, hazard ratio (trial-ineligible versus potentially trial-eligible) of 1.43 (95% CI: 1.19–1.72), p less than 0.001; median overall survival: 15.9 (95% CI: 11.4–20.3) versus 25.3 (95% CI: 19.8–30.4) months, hazard ratio of 1.36 (95% CI: 1.10–1.67), p equals 0.004. Conclusions: Our data reveal that a considerable proportion of patients with mNSCLC are not eligible to participate in a clinical trial and were found to have worse outcomes than potentially trial-eligible patients, whose outcomes were comparable with those obtained from pivotal clinical trials. This is of substantial clinical relevance for physicians discussing outcomes to be expected with their patients and stresses the need for real-world effectiveness analyses.

Abstract 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.

Background: Small-cell lung cancer (SCLC) is a highly aggressive tumor, and overall survival (OS) remains poor despite intensive efforts to develop new treatment strategies. In second line, topotecan is the only approved drug, with a median OS of 5.9 months. However, real-world SCLC patients are often in worse condition and harbor more comorbidities than study populations. Therefore, the real-world performance of topotecan may differ from that seen in studies. Here, we analyzed outcomes of SCLC patients receiving topotecan and identified predictive and prognostic markers. Patients and Methods: We retrospectively analyzed 44 consecutive SCLC patients receiving topotecan between 2015 and 2022. We analyzed baseline characteristics (age, ECOG-PS, topotecan cycles, and dosage) and pre-treatment blood values (LDH, CRP, sodium) as well as prognostic scores (neutrophil/lymphocyte ratio (NLR), thrombocyte/lymphocyte ratio (TLR), Glasgow Prognostic Score, prognostic nutritional score, systemic inflammation index (SII), and the prognostic index) extracted from electronic patients’ charts to identify predictive and prognostic markers. Results: In our cohort, mPFS and mOS were only 1.9 and 5.6 months, respectively. Gender, ECOG-PS, active brain metastases, NLR, GPS, PNI, and SII significantly influenced PFS and OS in univariate analysis. ECOG-PS (p > 0.001), active brain metastases (p = 0.001), and SII (p = 0.008) were significant independent prognostic variables in a multivariate COX regression model. Selecting patients by these three markers achieved an mPFS of 5.7 months and thus increased the mPFS three-fold. Patients not meeting all criteria had an mPFS of 1.8 months (p = 0.006). Patients identified by prognostic markers had an mOS of 9.1 months (p = 0.002). Conclusions: The efficacy of topotecan in SCLC real-world patients is poor, indicating that many patients were treated without any benefit. Easy-to-obtain markers can predict response and treatment efficacy and should therefore be validated in larger cohorts to identify patients who are more likely to benefit from topotecan.

Abstract Background Pseudoprogression (PsPD) is a rare response pattern to immune checkpoint inhibitor (ICI) therapy in oncology. This study aims to reveal imaging features of PsPD, and their association to other relevant findings. Methods Patients with PsPD who had at least three consecutive cross-sectional imaging studies at our comprehensive cancer center were retrospectively analyzed. Treatment response was assessed according to immune Response Evaluation Criteria in Solid Tumors (iRECIST). PsPD was defined as the occurrence of immune unconfirmed progressive disease (iUPD) without follow-up confirmation. Target lesions (TL), non-target lesions (NTL), new lesions (NL) were analyzed over time. Tumor markers and immune-related adverse events (irAE) were correlated. Results Thirty-two patients were included (mean age: 66.7 ± 13.6 years, 21.9% female) with mean baseline STL of 69.7 mm ± 55.6 mm. PsPD was observed in twenty-six patients (81.3%) at FU1, and no cases occurred after FU4. Patients with iUPD exhibited the following: TL increase in twelve patients, (37.5%), NTL increase in seven patients (21.9%), NL appearance in six patients (18.8%), and combinations thereof in four patients (12.5%). The mean and maximum increase for first iUPD in sum of TL was 19.8 and 96.8 mm (+ 700.8%). The mean and maximum decrease in sum of TL between iUPD and consecutive follow-up was − 19.1 mm and − 114.8 mm (-60.9%) respectively. The mean and maximum sum of new TL at first iUPD timepoint were 7.6 and 82.0 mm respectively. In two patients (10.5%), tumor-specific serologic markers were elevated at first iUPD, while the rest were stable or decreased among the other PsPD cases (89.5%). In fourteen patients (43.8%), irAE were observed. Conclusions PsPD occurred most frequently at FU1 after initiation of ICI treatment. The two most prevalent reasons for PsPD were TL und NTL progression, with an increase in TL diameter commonly below + 100%. In few cases, PsPD was observed even if tumor markers were rising compared to baseline. Our findings also suggest a correlation between PsPD and irAE. These findings may guide decision-making of ICI continuation in suspected PsPD.

Abstract 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.

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.

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

Abstract Background Lung cancers arising in never smokers have been suggested to be substantially different from lung cancers in smokers at an epidemiological, genetic and molecular level. Focusing on non-small cell lung cancer (NSCLC), we characterized lung cancer patients in China looking for demographic and clinical differences between the smoking and never-smoking subgroups. Methods In total, 891 patients with NSCLC, including 841 with adenocarcinoma and 50 with squamous cell carcinoma, were recruited in this study. Association of smoking status with demographic and clinical features of NSCLC was determined, and risk factors for lymph node metastasis and TNM stage were evaluated using Multivariate logistic regression analysis. Results In patients with adenocarcinoma, never smokers showed a younger age at diagnosis (54.2 ± 12.7vs. 59.3 ± 9.4, p adjusted

Abstract In patients with COPD, it has not been comprehensively assessed whether the predictive value of comorbidities for mortality differs between men and women. We therefore aimed to examine sex differences of COPD comorbidities in regard with prognosis by classifying comorbidities into a comorbidome related to extrapulmonary disorders and a pulmorbidome, referring to pulmonary disorders. The study population comprised 1044 women and 1531 men with the diagnosis of COPD from COSYCONET, among them 2175 of GOLD grades 1–4 and 400 at risk. Associations of comorbidities with mortality were studied using Cox regression analysis for men and women separately. During the follow-up (median 3.7 years) 59 women and 159 men died. In men, obesity, hypertension, coronary artery disease, liver cirrhosis, osteoporosis, kidney disease, anaemia and increased heart rate (HR) predict mortality, in women heart failure, hyperuricemia, mental disorders, kidney disease and increased HR (p

Abstract 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.

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 chi 2 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.

BackgroundTumor tissue as well as regional lymph nodes are removed during curative surgery for early-stage non-small cell lung cancer (NSCLC). These tissues provide a unique snapshot of the immune cell composition at the time of surgery. We investigated the immune landscape in matched tumor tissue, tumor bearing (tb) and non-tumor bearing (ntb) N1 as well as N2 lymph nodes (LNs) in patients with NSCLC and its relation to survival.MethodsInternal hospital databases were screened for surgically treated NSCLC patients for whom tumor tissue, tbLNs as well as N1 and N2 ntbLNs were available. Clinical as well as demographic data were extracted from hospital records. Expression profiling of 770 immune-related genes was performed using the PanCancer IO 360 panel by NanoString Technologies.ResultsWe identified 190 surgically treated patients of whom 16 fulfilled inclusion criteria and had sufficient archived tissue. The Tumor Immune Dysfunction and Exclusion (TIDE) score in N1 tumor-free lymph nodes was associated with OS. TIM-3 expression was inversely correlated with TIDE scores in affected LNs, N1 and N2 ntbLNs. Levels of CD8 expression were significantly higher in TIDE High compared to TIDE Low patients. TIM-3 and PD-L1 were selected for the final model for OS in multivariate regression in more than one tissue.ConclusionLevels of immune cell exhaustion markers may indicate a dysfunctional immune status and are associated with survival after curative surgery in NSCLC.

Abstract Treatment with single agent immune checkpoint inhibitors (ICIs) has tremendously changed second line therapy in NSCLC. However, there are still no reliable biomarkers predicting response and survival in this group of patients. PD-L1 revealed to be a correlating, but no perfect marker. Therefore, we sought to investigate in this prospective study, whether inflammation status and cytokine profile could serve as additional biomarkers guiding treatment decision for single agent ICIs in NSCLC. 29 stage IV NSCLC patients receiving single agent PD-1 checkpoint-inhibitor in second line were prospectively enrolled. Inflammatory scores and cytokine profiles (IL-6, IL-8, IL-10, IFN-γ and TNFα) have been obtained before treatment and at the time of the first staging. Cytokine profiles were correlated with response and survival. Patients with signs of pre-therapeutic inflammation (elevated, NLR, SII, IL-6, IL-8) showed significantly lower response to ICI treatment and reduced PFS. Contrary, elevated levels of IFN-γ revealed to characterize a subgroup of patients, who significantly benefits from ICI treatment. Furthermore, low systemic inflammation and high levels of IFN-γ characterized patients with long term-response to ICI treatment. Pre-therapeutic assessment of inflammation and cytokine profiles has the ability to predict response and survival in NSCLC patients treated with single agent ICIs.

Abstract Background Loco-regional and distant failure are common in inoperable stage III non small-cell lung cancer (NSCLC) after chemoradiotherapy (CRT). However, there is limited real-world data on failure pattern, patient prognosis and salvage options. Methods We analysed 99 consecutive patients with inoperable stage III NSCLC treated with CRT between 2011 and 2016. Follow up CT scans from date of the first-site failure were matched with the delivered radiation treatment plans. Intra-thoracic loco-regional relapse was defined as in-field (IFR) vs. out-of-field recurrence (OFR) [in- vs. outside 50Gy isodose line in the involved lung], respectively. Extracranial distant (DMs) and brain metastases (BMs) as first site of recurrence were also evaluated. Using the Kaplan-Meier method, impact of salvage surgery (sS), radiotherapy (sRT), chemotherapy (sCT) and immunotherapy (sIO) on patient survival was assessed. Results Median follow-up was 60.0 months. Median PFS from the end of CRT for the entire cohort was 7.5 (95% CI: 6.0–9.0 months) months. Twenty-six (26%) and 25 (25%) patients developed IFR and OFR. Median time to diagnosis of IFR and OFR was 7.2 and 6.2 months. In the entire cohort, onset of IFR and OFR did not influence patient outcome. However, in 73 (74%) patients who survived longer than 12 months after initial diagnosis, IFR was a significant negative prognostic factor with a median survival of 19.3 vs 40.0 months (p

Abstract Background/aim mmune checkpoint inhibition (CPI) has an increasing impact in the multimodal treatment of locally advanced non-small cell lung cancer (LA-NSCLC). Increasing evidence suggests treatment outcome depending on tumor cell PD-L1 expression. The purpose of this retrospective study was to investigate the prognostic value of PD-L1 expression on tumor cells in combination with CD8+ tumor stroma-infiltrating lymphocyte (TIL) density in inoperable LA-NSCLC treated with concurrent chemoradiotherapy (CRT). Patients and method We retrospectively assessed clinical characteristics and initial tumor biopsy samples of 31 inoperable LA-NSCLC patients treated with concurrent CRT. Prognostic impact of tumor cell PD-L1 expression (0% versus ≥1%) and CD8+ TIL density (0–40% vs. 41–100%) for local control, progression-free (PFS) and overall survival (OS) as well as correlations with clinicopathological features were evaluated. Results Median OS was 14 months (range: 3–167 months). The OS rates at 1- and 2 years were 68 and 20%. Local control of the entire cohort at 1 and 2 years were 74 and 61%. Median PFS, 1-year and 2-year PFS were 13 ± 1.4 months, 58 and 19%. PD-L1 expression

A 54-year-old patient presented with progressive pain for one month in the second finger of the right hand with an emphasis on the proximal interphalangeal (PIP) joint. Subsequent magnetic resonance imaging (MRI) showed a diffuse intraosseous lesion at the base of the middle phalanx with destruction of the cortical bone and extraosseous soft tissue. An expansively growing chondromatous bone tumor, e.g., a chondrosarcoma, was suspected. After incisional biopsy, the pathologic findings finally revealed, surprisingly, a metastasis of a poorly differentiated non-small cell adenocarcinoma of the lung. This case illustrates a rare but important differential diagnosis for painful finger lesions.

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.

Introduction: Rearranged during transfection (RET) gene fusions are rare genetic drivers in non-small cell lung cancer (NSCLC). Selective RET-inhibitors such as selpercatinib have shown therapeutic activity in early clinical trials; however, their efficacy in the real-world setting is unknown. Methods: A retrospective efficacy and safety analysis was performed on data from RET fusion-positive NSCLC patients who participated in a selpercatinib access program (named patient protocol) between August 2019 and January 2021. Results: Data from 50 patients with RET fusion-positive advanced NSCLC treated with selpercatinib at 27 centers in 12 countries was analyzed. Most patients were Non-Asian (90%), female (60%), never-smokers (74%), with a median age of 65 years (range, 38–89). 32% of the patients had known brain metastasis at the time of selpercatinib treatment. Overall, 13 patients were treatment-naïve, while 37 were pretreated with a median of three lines of therapy (range, 1–8). The objective response rate (ORR) was 68% [95% confidence interval (CI), 53–81] in the overall population. The disease control rate was 92%. The median progression-free survival was 15.6 months (95% CI, 8.8–22.4) after a median follow-up of 9 months. In patients with measurable brain metastases ( n = 8) intracranial ORR reached 100%. In total, 88% of patients experienced treatment-related adverse events (TRAEs), a large majority of them being grade 1 or 2. The most common grade ⩾ 3 TRAEs were increased liver enzyme levels (in 10% of patients), prolonged QTc time (4%), abdominal pain (4%), hypertension (4%), and fatigue/asthenia (4%). None of patients discontinued selpercatinib treatment for safety reasons. No new safety concerns were observed, nor where there any treatment-related death. Conclusions: In this real-world setting, the selective RET-inhibitor selpercatinib demonstrated durable systemic and intracranial antitumor activity in RET fusion-positive NSCLC and was well tolerated.

Background: Antiangiogenic agents have been shown to stimulate the immune system and cause synergistic effects with chemotherapy. Effects might be even stronger after immune-checkpoint-inhibitor (ICI) therapy. The purpose of this analysis was to evaluate the efficacy of ramucirumab plus docetaxel (R + D) as third-line treatment after failure of a first-line platinum-based chemotherapy and a second-line ICI treatment in patients with non-small-cell lung cancer (NSCLC) stage IV. Methods: Retrospective data were collected from 9 German thoracic oncology centers. Only patients who had received at least 1 cycle of third-line R + D were included. The numbers of cycles, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were investigated. Results: Sixty-seven patients met the criteria for inclusion. Third-line treatment with R + D achieved an ORR of 36% and a disease control rate (DCR) of 69%. Median PFS for third-line therapy was 6.8 months with a duration of response (DOR) of 10.2 months. A median OS of 29 months was observed from the start of first-line therapy with a median OS of 11.0 months from the start of third-line treatment. No unexpected toxicities occurred. Conclusion: R + D is a highly effective and safe third-line treatment after failure of second-line programmed cell death protein 1/programmed cell death-ligand 1 (PD1/PD-L1)-derived ICI therapy irrespective of NSCLC histology. As there may be synergistic effects of second- and third-line treatments, this sequence is a very suitable option for patients not treated with first-line ICI. In addition, R + D should continue to be investigated as a second-line treatment option after failure of chemotherapy plus ICI in the palliative first–line treatment.

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.

Background: Maintenance treatment with immune-checkpoint inhibition (ICI) has been shown to significantly improve patient prognosis after chemoradiotherapy (CRT) for inoperable stage III NSCLC. This survival advantage may be achieved at the expense of an increased probability for symptomatic pneumonitis as CRT as well as ICI treatment is associated with the risk of treatment-related pulmonary toxicity. Methods: We screened a prospective chemoradioimmunotherapy (CRT-IO) cohort consisting of 38 patients and identified patients with therapy-related grade 3 pneumonitis. All patients were treated with intravenous high dose corticosteroids and closely monitored by CT-scans and extended longitudinal lung function tests. We analyzed lung function parameters and CT morphological features to characterize patients’ outcome. Results: Six (16%) patients treated with CRT-IO developed grade 3 pneumonitis one to six months after completion CRT. In the CT imaging, pneumonitis was characterized by diffuse ground glass capacities and in part pulmonary consolidations within and outside the planning target volume. Onset of pneumonitis was accompanied by a reduction in diffusion capacity in all cases. The mean decline of diffusion capacity was 25.8% [6–53%]. Under treatment with corticosteroids, all patients recovered regarding symptoms and changes in CT morphology. In five out of six patients, diffusion capacity improved to at least 80% of the baseline [80–96%]. One patient showed a significant increase of diffusion capacity after treatment (from 32% to 53%) but reached only 62% of the initial value. Conclusions: Pneumonitis is a severe complication of CRT-IO. High-resolution CT imaging and extended lung function testing proved to be a suitable approach in detecting and monitoring of CRT-IO associated pneumonitis.

Stage III nonsmall cell lung cancer (NSCLC) comprises about one-third of NSCLC patients and is very heterogeneous with varying and mostly poor prognosis. It is also called “locoregionally or locally advanced disease”. Due to its heterogeneity a general schematic management approach is not appropriate. Usually a combination of local therapy (surgery or radiotherapy, depending on functional, technical and oncological operability) with systemic platinum-based doublet chemotherapy and, recently, followed by immune therapy is used. A more aggressive approach of triple agent chemotherapy or two local therapies (surgery and radiotherapy, except for specific indications) has no benefit for overall survival. Until now tumour stage and the general condition of the patient are the most relevant prognostic factors. Characterising the tumour molecularly and immunologically may lead to a more personalised and effective approach. At the moment, after an exact staging and functional evaluation, an interdisciplinary discussion amongst the tumour board is warranted and offers the best management strategy.

BackgroundAlthough lung cancer is most commonly diagnosed in elderly patients, evidence about tumor-directed therapy in elderly patients is sparse, and it is unclear to what extent this affects treatment and care. Our study aimed to discover potential disparities in care between elderly patients and those under 65 years of age.MethodsWe studied claims from 13 283 German patients diagnosed with lung cancer in 2009 who survived for at least 90 days after diagnosis. We classified patients as "non-elderly" (≤ 65), "young-old" (65-74), "middle-old" (75-84), and "old-old" (≥ 85). We compared receipt of tumor-directed therapy (6 months after diagnosis), palliative care, opioids, antidepressants, and pathologic diagnosis confirmation via logistic regression. We used generalized linear regression (gamma distribution) to compare group-specific costs of care for 3 months after diagnosis. We adjusted all models by age, nursing home residency, nursing care need, comorbidity burden, and area of residence (urban, rural). The age group "non-elderly" served as reference group.ResultsCompared with the reference group "non-elderly", the likelihood of receiving any tumor-directed treatment was significantly lower in all age groups with a decreasing gradient with advancing age. Elderly lung cancer patients received significantly fewer resections and radiotherapy than non-elderly patients. In particular, treatment with antineoplastic therapy declined with increasing age ("young-old" (OR = 0.76, CI = [0.70,0.83]), "middle-old" (OR = 0.45, CI = [0.36,0.50]), and "old-old" (OR = 0.13, CI = [0.10,0.17])). Patients in all age groups were less likely to receive structured palliative care than "non-elderly" ("young-old" (OR = 0.84, CI = [0.76,0.92]), "middle-old" (OR = 0.71, CI = [0.63,0.79]), and "old-old" (OR = 0.57, CI = [0.44,0.73])). Moreover, increased age was significantly associated with reduced quotas for outpatient treatment with opioids and antidepressants. Costs of care decreased significantly with increasing age.ConclusionThis study suggests the existence of age-dependent care disparities in lung cancer patients, where elderly patients are at risk of potential undertreatment. To support equal access to care, adjustments to public health policies seem to be urgently required.

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are an effective treatment for non-small-cell lung cancer (NSCLC) harbouring EGFR mutations. The development of isolated central nervous system (CNS) metastases is a relevant clinical problem in patients who respond well to EGFR-TKIs. Methods: We present a patient with isolated progression of brain metastases during treatment of EGFRmutated NSCLC with an EGFR-TKI and review the treatment options in this setting, including the evidence for and toxicity of treatment with high-dose TKIs. Results: Oligometastatic CNS progression during TKI therapy may be treated locally. Both whole brain radiotherapy (WBRT) and stereotactic brain irradiation are well tolerated and effective in this setting. The use of high-dose pulsed TKIs is intended to increase the concentration of TKI in the brain and has been reported to be effective and without significant toxicity in case reports and small case series. These therapeutic options are illustrated in the case of a 44-year-old NSCLC patient who developed CNS progression after WBRT during second-line erlotinib and was treated locally with stereotactic radiosurgery (SRS) and, upon further CNS progression, with high-dose pulsed erlotinib. This resulted in intracerebral response; however, significant haemorrhage also occurred. Severe haemorrhage has not previously been described as a complication of high-dose pulsed erlotinib. Conclusion: Possible explanations for isolated CNS progression during TKI treatment include inadequate dosing across the blood—brain barrier and longer survival on TKIs. The efficacy and tolerability of highdose pulsed TKIs for CNS metastases has been previously reported. None of the cases reported showed the severe haemorrhage and cerebral oedema that developed in our patient. Simultaneous anticoagulation as well as previous SRS may have predisposed our patient to haemorrhage and may prove to be relative contraindications to high-dose pulsed erlotinib. Most centres only see a few patients in this clinical situation, and co-operative efforts are needed to collect and analyse similar cases and to develop appropriate treatment strategies.