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Poster: "ECR 2012 / C-0808 / Cystic fibrosis (CF) in adult patients: correlation of lung function test results and pathologic lung morphology as expressed by the Brody score" by: "U. Mueller-Lisse, M. Schmitz, N. Ashoori,... more
Poster: "ECR 2012 / C-0808 / Cystic fibrosis (CF) in adult patients: correlation of lung function test results and pathologic lung morphology as expressed by the Brody score" by: "U. Mueller-Lisse, M. Schmitz, N. Ashoori, S. Allert, I. Mindiuk, J. Pichler, R. Fischer, R. Huber, M. F. Reiser; Munich/DE"
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Background: COPD is a common chronic condition in adulthood that has many systemic effects apart pulmonary impairment. While severe COPD has substantial economic consequences, little is known about resource use and costs in early stages.... more
Background: COPD is a common chronic condition in adulthood that has many systemic effects apart pulmonary impairment. While severe COPD has substantial economic consequences, little is known about resource use and costs in early stages. Methods: Data from the population-based KORA F4 and KORA Age study (Southern Germany) were used to calculate excess costs of early stages of COPD. Diagnosis and staging of COPD for 2252 participants aged 41 to 89 was based on pre-bronchodilator spirometry according to GOLD standards. Resource use with regard to physician visits, hospital stays, and drug consumption was compared between participants with COPD stage I, stage II+ (stage II or higher), and subjects with normal lung function. Costs per year were calculated from utilization by applying national unit costs. To control for confounders such as age, sex and education, two-part generalized regression analyses were used to account for the skewed distribution of costs and the high proportion of ...
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7075 Background: In NSCLC simultaneous or induction radiochemotherapy is superior to chemo- or radiotherapy alone. Our study proves, weather after induction chemotherapy simultaneous radiochemotherapy is superior to radiotherapy alone.... more
7075 Background: In NSCLC simultaneous or induction radiochemotherapy is superior to chemo- or radiotherapy alone. Our study proves, weather after induction chemotherapy simultaneous radiochemotherapy is superior to radiotherapy alone. METHODS Patients (pts) with inoperable NSCLC IIIA/B are included. They get 2 cycles q3w of Paclitaxel 200mg/m2 and Carboplatinum AUC 6. If the tumor is not progressive the pts are randomized to radiotherapy alone (total dose at least 60 Gy per fraction) or simultaneous chemotherapy with weekly Paclitaxel 60mg/m2 and the same radiotherapy. Primary objective is survival; secondary endpoints are time to progression, response and toxicity. RESULTS Inclusion ended 05/02. The last follow-up was 11/03. As planned, 303 pts are included in the trial. 275 pts finished induction-therapy. 219 pts could be randomized: radiotherapy 115 pts, simultaneous radiochemotherapy 104 pts. Median survival is higher in the simultaneous arm: 18.67 months (95%CI 14.05-23.29) versus 14.1 months (95%CI 11.64-16.56). Progression free survival is statistically superior (log rank: p=0.0003) in the simultaneous arm: median 11.43 months (95%CI 7.88-14.98) versus 5.57 months (95%CI 3.88-7.25). In the simultaneous arm there are also statistically less recurrences (Pearson Chi-Square: p<0.001): 62.1% vs. 83.8%. The reduction on recurrences can be seen in local as in distant relapses. Toxicities are not statistically different. CONCLUSIONS The combination of induction chemotherapy and then simultaneous radiochemotherapy with weekly Paclitaxel is superior to induction alone regarding progression-free survival, without increased toxicities. Also the survival seems to be better (not yet statistically significant). [Table: see text].
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Erkrankungen des Respirationstrakts gehören zu den häufigsten chronischen Krankheiten. In diesem Kapitel werden Erkrankungen der oberen Atemwege, des Bronchialsystems, des Lungeninterstitiums sowie Infektionen und bösartige Neubildungen... more
Erkrankungen des Respirationstrakts gehören zu den häufigsten chronischen Krankheiten. In diesem Kapitel werden Erkrankungen der oberen Atemwege, des Bronchialsystems, des Lungeninterstitiums sowie Infektionen und bösartige Neubildungen der Lunge hinsichtlich ihrer vielfältigen klinischen Erscheinungsformen und ihrer eingehenden Diagnostik und Zusammenhangsbeurteilung dargestellt. Eine besondere Bedeutung kommt hierbei den Aspekten des sozialen Entschädigungsrechts, z. B. bei Berufskrankheiten, unter Berücksichtung des aktuellen klinisch-wissenschaftlichen Kenntnisstandes und der rechtlichen Rahmenbedingungen, zu.
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TPS7617 Background: Patients with non-small cell lung cancer (NSCLC) who respond to treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) seem to be at increased risk of central nervous system relapse, and... more
TPS7617 Background: Patients with non-small cell lung cancer (NSCLC) who respond to treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) seem to be at increased risk of central nervous system relapse, and may benefit from prophylactic cranial irradiation (PCI) more than other NSCLC patients. Methods: This study investigates the safety and efficacy of combining PCI with EGFR TKIs in stage IV NSCLC. Patients with stage IV NSCLC, no evidence of brain metastases, and an indication for first or later line therapy with an EGFR TKI will be enrolled. Those with complete response (CR), partial response (PR), or stable disease (SD) following 6 weeks of therapy and no evidence of brain metastases on MRI will be treated with PCI. Neurocognitive function, depression indices, quality of life, symptoms, and ability to function independantly will be assessed at baseline, before PCI, and at 6 week and then 3 month intervals following PCI. MRI will be repeated 6 week...
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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)... more
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 ther...
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Purpose: Non–small cell lung cancer (NSCLC) is a fatal disease with poor prognosis. A membrane-bound form of Hsp70 (mHsp70) which is selectively expressed on high-risk tumors serves as a target for mHsp70-targeting natural killer (NK)... more
Purpose: Non–small cell lung cancer (NSCLC) is a fatal disease with poor prognosis. A membrane-bound form of Hsp70 (mHsp70) which is selectively expressed on high-risk tumors serves as a target for mHsp70-targeting natural killer (NK) cells. Patients with advanced mHsp70-positive NSCLC may therefore benefit from a therapeutic intervention involving mHsp70-targeting NK cells. The randomized phase II clinical trial (EudraCT2008-002130-30) explores tolerability and efficacy of ex vivo–activated NK cells in patients with NSCLC after radiochemotherapy (RCT). Patients and Methods: Patients with unresectable, mHsp70-positive NSCLC (stage IIIa/b) received 4 cycles of autologous NK cells activated ex vivo with TKD/IL2 [interventional arm (INT)] after RCT (60–70 Gy, platinum-based chemotherapy) or RCT alone [control arm (CTRL)]. The primary objective was progression-free survival (PFS), and secondary objectives were the assessment of quality of life (QoL, QLQ-LC13), toxicity, and immunobiolog...
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7001 Background: Concurrent chemo-radiotherapy (CT-RT) is considered as a standard in st III NSCLC. Published trials with C after CT-RT show encouraging but discordant results. This ph III was set up to assess C in st III NSCLC. Methods:... more
7001 Background: Concurrent chemo-radiotherapy (CT-RT) is considered as a standard in st III NSCLC. Published trials with C after CT-RT show encouraging but discordant results. This ph III was set up to assess C in st III NSCLC. Methods: Patients (pts) received NVBo 50 mg/m² D1, D8, D15 + P 20 mg/m² D1-D4 q4w / 2 cycles (cy) + RT (66 Gy / 33 Fr). C for OR+SD pts: NVBo 60-80 mg/m² D1D8 + P 80 mg/m² D1 q3w / 2 cy + BSC (Arm A) or BSC (Arm B). PFS was the primary endpoint. Results: From 07/05 to 05/09, 279 pts received CT/RT and 201 pts (72%) were randomised to receive CT+BSC or BSC as C. Toxicity (tox) G3-4 (% pt) CT-RT/ C (Arm A/B): anaemia 3.2/3.5/1.1; thrombopenia 2.5/1.2/0.6; neutropenia (N) 11.2/11.7/5.7; febrile N 1.4/1.0/0; nausea (G3) 5.0/4.7/2.9; vomiting (G3) 3.9/3.5/2.0; anorexia 3.6/1.2/3.0; dysphagia 1.8/2.3/1.0; fatigue 3.3/ 2.3/1.0; pneumonia/ pneumonitis 2.6/0/2.0; CT-RT pain 2.2; CT-RT oesophagitis 8.6; 3 toxic deaths. Conclusions: In this ph III, NVBo+P+RT reports a ...
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Medicine and Lung Cancer
9007Background: We report the first results of a pivotal ph 2 trial of BRG in pts with ALK+ NSCLC. BRG, an investigational oral tyrosine kinase inhibitor (TKI) with preclinical activity against rea...
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Immune checkpoint inhibitors (ICIs) may cause immune-related adverse events (IRAEs). Characterisation and data on treatment of musculoskeletal IRAEs are scarce. In this cohort study, patients receiving ICI therapy who experienced... more
Immune checkpoint inhibitors (ICIs) may cause immune-related adverse events (IRAEs). Characterisation and data on treatment of musculoskeletal IRAEs are scarce. In this cohort study, patients receiving ICI therapy who experienced arthralgia were evaluated for the presence of synovitis. Data on demographics, ICI regime, time of onset, imaging and response to therapy of synovitis were prospectively collected. Arthritis was demonstrated in 14 of 16 patients of whom 7 showed monarthritis, 5 had oligoarthritis and 2 had polyarthritis. Patients with ICI-induced arthritis were predominantly male (57%) and seronegative (69%). Regarding the detection of synovitis in staging imaging, moderate sensitivity for contrast-enhanced CT with PET-CT as reference was observed. Disease burden at baseline was high and was significantly reduced after anti-inflammatory treatment. Nine patients were treated with systemic and eight patients with intra-articular glucocorticoids. Six patients who flared on glu...
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Background: Despite initial response to chemotherapy, the prognosis of small cell lung cancer (SCLC) patients is limited. Following first-line therapy, the strongest predictor of durable progression-free survival (PFS) is remission... more
Background: Despite initial response to chemotherapy, the prognosis of small cell lung cancer (SCLC) patients is limited. Following first-line therapy, the strongest predictor of durable progression-free survival (PFS) is remission quality. Febrile neutropenia (FN) is a frequent complication after chemotherapy, and its prevention could improve treatment density and degree of remission. Patients and Methods: We retrospectively analyzed 39 SCLC patients treated at a German tertiary care lung cancer center between 2013 and 2016. We extracted data sets from electronic records and analyzed anthropometric data, pretherapeutic blood values, and prognostic scores. Discriminant analysis was performed to predict FN. Results: PFS after first-line chemotherapy was significantly shorter in patients with FN (p = 0.003). Pretherapeutic albumin (p = 0.019), C-reactive protein (CRP; p < 0.001), lactate dehydrogenase (p = 0.041), neutrophil-to-lymphocyte ratio (p = 0.009), prognostic nutritional i...
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Afatinib has demonstrated clinical benefit in patients with non-small-cell lung cancer progressing after treatment with erlotinib/gefitinib. This phase III trial prospectively assessed whether continued irreversible ErbB-family blockade... more
Afatinib has demonstrated clinical benefit in patients with non-small-cell lung cancer progressing after treatment with erlotinib/gefitinib. This phase III trial prospectively assessed whether continued irreversible ErbB-family blockade with afatinib plus paclitaxel has superior outcomes versus switching to chemotherapy alone in patients acquiring resistance to erlotinib/gefitinib and afatinib monotherapy. Patients with relapsed/refractory disease following ≥1 line of chemotherapy, and whose tumors had progressed following initial disease control (≥12 weeks) with erlotinib/gefitinib and thereafter afatinib (50 mg/day), were randomized 2:1 to receive afatinib plus paclitaxel (40 mg/day; 80 mg/m(2)/week) or investigator's choice of single-agent chemotherapy. The primary end point was progression-free survival (PFS). Other end points included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes. Two hundred and two patients with progressive di...
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Anthropometry, Adolescent, Medicine, Lung Function, Humans, and 15 moreFemale, Male, Clinical Sciences, Aged, Middle Aged, Adult, Multiple regression analysis, Body Weight, Pulmonary Function, Healthy Subjects, Cohort Studies, prediction equation, Inspiratory capacity, Cardiovascular medicine and haematology, and Percentile
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Genetics, Genomics, Medicine, Lung Cancer, EGFR, and 15 moreHumans, Internal Medicine, Female, Male, Clinical Sciences, Aged, Epidermal Growth Factor Receptor, Adult, Brain Metastases, Disease Progression, Brain Neoplasms, Afatinib, Brain Metastasis, Cardiovascular medicine and haematology, and lung neoplasms
Background We report an analysis of Asian vs non-Asian pts with CRZ-refractory, ALK+ NSCLC from ALTA (NCT02094573). Methods Pts were stratified by presence of baseline (BL) CNS metastases and best response to prior CRZ and randomized 1:1... more
Background We report an analysis of Asian vs non-Asian pts with CRZ-refractory, ALK+ NSCLC from ALTA (NCT02094573). Methods Pts were stratified by presence of baseline (BL) CNS metastases and best response to prior CRZ and randomized 1:1 to BRG 90 mg qd (arm A) or 180 mg qd with a 7-day lead-in at 90 mg (arm B). Primary endpoint: Investigator-assessed confirmed ORR by RECIST v1.1. Results 222 pts were randomized; 69 Asian (A/B, n = 39/30), 153 non-Asian (n = 73/80); median age: Asian, 50/56 y; non-Asian, 51/57 y; 85/70% vs 64/66% had BL CNS metastases. As of Sep 2017, median follow-up was 18.4/22.5 mo (A/B) in Asians vs 22.3/24.5 mo in non-Asians. In Asians, median IRC-assessed PFS (mo) was 9.1 (95% CI 5.6–18.2) in A vs 15.6 (9.2–21.2) in B (HR 0.88 [95% CI 0.48–1.62]; P = 0.6808); in non-Asians, PFS (A/B) was 9.9 (9.0–26.3) vs 17.9 (11.6–23.9; HR 0.72 [0.45–1.13]; P = 0.1510) (Table). Of 7/2 (A/B) Asian pts with measurable BL CNS metastases, 3/1 had confirmed intracranial objective...
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9036 Background: Seribantumab (MM-121) is a human monoclonal IgG2 antibody that blocks the HRG domain of HER3. Preclinical data suggest that seribantumab reverses HRG mediated drug resistance across multiple cancer models. In prior... more
9036 Background: Seribantumab (MM-121) is a human monoclonal IgG2 antibody that blocks the HRG domain of HER3. Preclinical data suggest that seribantumab reverses HRG mediated drug resistance across multiple cancer models. In prior retrospective analyses, addition of seribantumab to standard of care (SOC) appeared to improve outcomes in pts with HRG+ tumors. Here we tested if seribantumab plus SOC improved progression-free survival (PFS) in pts with HRG+ lung adenocarcinoma who had received prior platinum-based therapy. Methods: SHERLOC was a randomized, open-label, multicenter, Phase 2 study in pts with advanced HRG+ adenocarcinoma of the lung. Archival or pre-treatment tumor samples were assessed for HRG+ by RNA in situ hybridization. Eligibility criteria included prior platinum-based therapy for advanced disease with ≤ 2 total prior lines of therapy (prior IO was allowed) and no EGFR or ALK mutations. Pts were randomized 2:1 to receive seribantumab 3000 mg/docetaxel 75 mg IV q3w ...
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Medicine and Pneumologie
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SummaryBackgroundTreatment of advanced EML4-ALK-translocation-positive non-small-cell lung cancer (NSCLC) with an ALK tyrosine kinase inhibitor (TKI) is now standard of care. Since EML4-ALK gene fusion is rare in NSCLC and testing... more
SummaryBackgroundTreatment of advanced EML4-ALK-translocation-positive non-small-cell lung cancer (NSCLC) with an ALK tyrosine kinase inhibitor (TKI) is now standard of care. Since EML4-ALK gene fusion is rare in NSCLC and testing depletes both tissue samples and health care funds, deciding who to screen is critical. CT features associated with EML4-ALK-positive cases may help prioritize individual patients for ALK testing in settings where biopsy size or health care factors make ubiquitous testing difficult.MethodsWe used well-described computed tomography (CT) lung tumor features to distinguish EML4-ALK-translocation-positive from ALK-negative European patients with advanced NSCLC. CT scans were evaluated for lung tumor location (either central or peripheral versus combined), growth pattern (focal versus diffuse), array (single versus multiple lesions), delineation (infiltrative versus circumscribed), composition (solid only versus nonsolid parts), site-specific blood vessel appearance (normal versus altered), and air inclusions (present versus absent). Two-tailed statistical tests (Fisher exact/Student-T) were used to compare ALK-positive and ALK-negative tumors. The analyses took potential confounders into account including patient age, gender, previous NSCLC therapy, UICC stage, and smoking status.ResultsTen of 39 adult European Caucasian patients (age 57 ± 10 years, 17 female) were ALK positive. Diffuse tumor growth (ALK positive 9, ALK negative 7/5, p < 0.0005/p < 0.0001, agreement 95%), multiple lung lesion arrays (ALK positive 9, ALK negative 6, p < 0.0002, agreement 82%), and combined central/peripheral tumor location (ALK positive 9, ALK negative 12/7, p < 0.01/p < 0.0005, agreement 82%) each were associated with ALK-positive cases.ConclusionsDiffuse tumor growth, multiple lung lesion arrays, and combined central/peripheral tumor location are CT features that may prove useful in prioritizing NSCLC samples for ALK testing in this setting.
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Neuroendocrine tumors (NETs; syn. carcinoid tumors) are highly or moderately differentiated neoplasms. They comprise a large variety of rare and heterogeneous tumors with an estimated incidence of 3-5/100,000/year. They can arise in... more
Neuroendocrine tumors (NETs; syn. carcinoid tumors) are highly or moderately differentiated neoplasms. They comprise a large variety of rare and heterogeneous tumors with an estimated incidence of 3-5/100,000/year. They can arise in virtually every internal organ, but mainly occur in the gastroenteropancreatic and bronchopulmonary systems. Around 25% of the NETs are localized in the bronchopulmonary system. Approximately 2% of all lung tumors are NETs. According to the World Health Organization (WHO) classification of lung tumors, bronchopulmonary NETs are subdivided into typical carcinoids (TCs) and atypical carcinoids (ACs). The parameter with the highest impact on NET behavior and prognosis is the histological classification and staging according to the tumor/node/metastasis (TNM) system. The diagnosis of NETs is established by histological examination and the immunohistochemical detection of general neuroendocrine markers, such as chromogranin A (CgA) and synaptophysin. Serum ma...