Merkmale von Lungenkrebs bei Patienten mit idiopathischer Lungenfibrose und interstitieller Lungenerkrankung

2019 ◽  
Vol 7 (2) ◽  
pp. 90-91
Author(s):  
Fotios Drakopanagiotakis ◽  
Andreas Günther
Keyword(s):  
Lung Cancer ◽  
Squamous Cell ◽  
Lower Lobe ◽  
Population Data ◽  
Cancer Registries ◽  
Hazard Ratio ◽  
University Of Pittsburgh ◽  
Department Of Health ◽  
Single Lung Transplant ◽  
Standard Incidence Ratio

Background: Lung Cancer is occasionally observed in patients with Idiopathic Pulmonary Fibrosis (IPF). We sought to describe the epidemiologic and clinical characteristics of lung cancer for patients with IPF and other interstitial lung disease (ILD) using institutional and statewide data registries. Methods: We conducted a retrospective analysis of IPF and non-IPF ILD patients from the ILD center registry, to compare with lung cancer registries at the University of Pittsburgh as well as with population data of lung cancer obtained from Pennsylvania Department of Health between 2000 and 2015. Results: Among 1108 IPF patients, 31 patients were identified with IPF and lung cancer. The age-adjusted standard incidence ratio of lung cancer was 3.34 (with IPF) and 2.3 (with non-IPF ILD) (between-group Hazard ratio = 1.4, p = 0.3). Lung cancer worsened the mortality of IPF (p  <  0.001). Lung cancer with IPF had higher mortality compared to lung cancer in non-IPF ILD (Hazard ratio = 6.2, p = 0.001). Lung cancer among IPF was characterized by a predilection for lower lobes (63% vs. 26% in non-IPF lung cancer, p  <  0.001) and by squamous cell histology (41% vs. 29%, p = 0.07). Increased incidence of lung cancer was observed among single lung transplant (SLT) recipients for IPF (13 out of 97, 13.4%), with increased mortality compared to SLT for IPF without lung cancer (p = 0.028) during observational period. Conclusions: Lung cancer is approximately 3.34 times more frequently diagnosed in IPF patients compared to general population, and associated with worse prognosis compared with IPF without lung cancer, with squamous cell carcinoma and lower lobe predilection. The causality between non-smoking IPF patients and lung cancer is to be determined.

Prognostic significance of α1,6-fucosyltransferase (α1,6-FT) in non-small cell lung cancers (NSCLCs).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7550-7550
Author(s):  
Rio Honma ◽  
Ichiro Kinoshita ◽  
Eiji Miyoshi ◽  
Utano Tomaru ◽  
Yoshihiro Matsuno ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell ◽  
Proportional Hazards ◽  
Egf Receptor ◽  
Proportional Hazards Model ◽  
Prognostic Significance ◽  
Multivariate Logistic Regression Analysis ◽  
Hazard Ratio ◽  
Rank Test ◽  
Low Expression

7550 Background: Lung cancer is one of the leading causes of cancer death throughout the world. A more sophisticated understanding of the pathogenesis and biology of NSCLCs could provide useful information for predicting clinical outcome and individualizing treatment. α1,6-FT is the only one enzyme responsible for the core α1,6-fucosylation of N-glycans of glycoproteins, including EGF receptor, TGF-β1 receptor, and integrin α3β1. Methods: α1,6-FT expression was studied by immunohistochemistry in a cohort of 129 surgically resected NSCLCs, classified categorically based on the proportion of positively stained cancer cells (high, > 20%; or low, < 20%), and analyzed statistically in relation to various characteristics, including histology, survival and prognosis. Results: High and low expression of α1,6-FT was found in 67 and 62 of 129 NSCLCs, respectively. Multivariate logistic regression analysis revealed a significant association between high α1,6-FT expression and non-squamous cell carcinoma (mostly adenocarcinoma), as compared with squamous cell carcinomas (odds ratio, 3.51; p = 0.008). Patients with tumors having high α1,6-FT expression had significantly shorter survival time than patients with tumors having low expression in potentially curatively resected NSCLCs (p = 0.03) and adenocarcinomas (p = 0.009), as well as in pStage I NSCLCs (p = 0.03) by the log-rank test. Surprisingly, in pStage I adenocarcinomas, 12 of 23 patients with tumors having high α1,6-FT expression died of lung cancer, although none of 15 patients with tumors having low expression died of lung cancer. High α1,6-FT expression was a significant and independent unfavorable prognostic factor in potentially curatively resected NSCLCs (hazard ratio, 1.81; p = 0.047) and adenocarcinomas (hazard ratio 2.39; p = 0.006) and in pStage I NSCLCs (hazard ratio 2.55; p = 0.03) by Cox’s proportional hazards model analysis. Conclusions: These results suggest that α1,6-FT may play a pivotal role for the biological characteristics of NSCLCs. α1,6-FT expression is associated with histology of NSCLCs, and may be a new prognostic marker for overall NSCLCs and adenocarcinomas.

scholarly journals Lung cancer in combined pulmonary fibrosis and emphysema: a large retrospective cohort analysis

2020 ◽  
Vol 6 (4) ◽  
pp. 00521-2020
Author(s):  
Faria Nasim ◽  
Teng Moua
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Pulmonary Fibrosis ◽  
Cell Carcinoma ◽  
Surgical Resection ◽  
Squamous Cell ◽  
Retrospective Cohort ◽  
Cohort Analysis ◽  
Lower Lobe ◽  
Nonsmall Cell Lung Cancer

BackgroundCombined pulmonary fibrosis and emphysema (CPFE) is characterised by upper lobe emphysema and lower lobe fibrosis. Our study aim was to determine the incident risk, presenting characteristics and outcome of lung cancer diagnoses in a cohort of CPFE patients over time.Materials and methodsWe conducted a retrospective cohort study assessing patients with radiological CPFE followed over a median of 76 months (range 1–237 months). Interval development of lung cancer and clinicopathological characteristics of those with and without lung cancer were compared and survival analysis performed.ResultsLung cancer occurred in 26 (11.6%) out of 230 CPFE patients, dominated by nonsmall cell lung cancer (88%, n=23) with squamous cell carcinoma comprising the majority (57%, n=13). There was a predominance of lower lobe (62%) and subpleural (64%) radiological presentation. Survival was reduced for the whole cohort by lung cancer even after adjusting for a priori covariables of age, sex, smoking pack-years, presenting forced vital capacity and radiological honeycombing. Univariable predictors of increased mortality after lung cancer diagnosis included honeycombing (hazard ratio (HR) 3.03, 95% CI 1.16–7.91; p=0.02) and later stage presentation (HR 4.77, 95% CI 1.8–14.94; p=0.001), with those able to undergo surgical resection having better survival (HR 0.29, 95% CI 0.09–0.87; p=0.02).ConclusionLung cancer occurred in 26 (11.6%) out of 230 CPFE patients and was dominated by squamous cell carcinoma presenting in a lower lobe peripheral distribution. Surgical resection appeared to improve survival in selected patients with earlier stage disease. Further studies are needed to develop a relevant screening programme for CPFE patients.

scholarly journals Characteristics of lung cancer in idiopathic pulmonary fibrosis with single lung transplant versus non-transplanted patients: a retrospective observational study

2020 ◽  
Vol 7 (1) ◽  
pp. e000566 ◽  
Author(s):  
Evgeni Gershman ◽  
Alona Zer ◽  
Barak Pertzov ◽  
Osnat Shtraichman ◽  
Dorit Shitenberg ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Transplantation ◽  
Lung Transplant ◽  
Lower Lobe ◽  
Smoking History ◽  
Oncological Treatment ◽  
Increased Risk ◽  
Single Lung Transplant

BackgroundPatients with idiopathic pulmonary fibrosis (IPF) have significantly higher incidence of lung cancer (LC) relative to the general population. There is a further increase in LC incidence in patients with IPF subsequent to lung transplant, specifically in patients with IPF undergoing single lung transplant.ObjectivesTo examine the incidence and characteristics of LC in patients with IPF during follow-up and after lung transplantation (LTX).MethodsWe conducted a retrospective analysis of all patients with IPF diagnosed with LC in Rabin Medical Center, Israel, over an 11-year period. We compared the characteristics of transplanted patients with IPF diagnosed with LC to patients with IPF who did not undergo lung transplant. Data were accessed from database registries using the words ‘fibrosis’, ‘lung-cancer’ and ‘lung-transplantation’. Demographic parameters included age, gender and smoking history (pack years). Clinical-pathological parameters included lapse in time from IPF diagnosis to LC, type of malignancy, affected pulmonary lobe, and stage at diagnosis, oncological treatment and survival.ResultsBetween 2008 and 2018, 205 patients with IPF underwent lung transplantation at our medical centre. Double LTX was performed in 83 and single LTX in 122 cases. Subsequently, 15 (12.3%) single LTX patients were diagnosed with LC during the study period. During the same period, of 497 non-transplanted patients with IPF followed in our centre, 45 (9.1%) were diagnosed with LC. In all 15 transplanted patients with IPF, LC was diagnosed exclusively in the native fibrotic lung. LC incidence was higher in the transplanted as compared with the non-transplanted group, but this difference did not reach statistical significance (OR=0.7, 95% CI 0.38 to 1.32, p=0.28). At LC diagnosis, the non-transplanted group was older than the transplanted group with average age of 67.7 versus 60.8 years, respectively (p=0.006). Both groups showed male predominance. In both groups, LC was primarily peripheral, lower lobe predominant and most frequently squamous cell carcinoma. The median survival time after LC diagnosis was 4 months in the transplanted group and 11 months in the non-transplanted group (p=0.19). Multivariate analysis showed improved survival in the non-transplanted group among those patients who received oncological treatment.ConclusionChest CT should be performed regularly in order to evaluate IPF patients for potential LC. Single lung transplant IPF patients face an increased risk of post-transplant LC in the native fibrotic lung. Where practicable, IPF patients should be prioritised for double lung transplant.

scholarly journals Genetically Raised Circulating Bilirubin Levels and Risk of Ten Cancers: A Mendelian Randomization Study

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 394
Author(s):  
Nazlisadat Seyed Seyed Khoei ◽  
Robert Carreras-Torres ◽  
Neil Murphy ◽  
Marc J. Gunter ◽  
Paul Brennan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Hodgkin’S Lymphoma ◽  
Mendelian Randomization ◽  
Hodgkin's Lymphoma ◽  
Squamous Cell Lung Cancer ◽  
Phenotypic Variance ◽  
A Genome

Bilirubin, an endogenous antioxidant, may play a protective role in cancer development. We applied two-sample Mendelian randomization to investigate whether genetically raised bilirubin levels are causally associated with the risk of ten cancers (pancreas, kidney, endometrium, ovary, breast, prostate, lung, Hodgkin’s lymphoma, melanoma, and neuroblastoma). The number of cases and their matched controls of European descent ranged from 122,977 and 105,974 for breast cancer to 1200 and 6417 for Hodgkin’s lymphoma, respectively. A total of 115 single-nucleotide polymorphisms (SNPs) associated (p < 5 × 10−8) with circulating total bilirubin, extracted from a genome-wide association study in the UK Biobank, were used as instrumental variables. One SNP (rs6431625) in the promoter region of the uridine-diphosphoglucuronate glucuronosyltransferase1A1 (UGT1A1) gene explained 16.9% and the remaining 114 SNPs (non-UGT1A1 SNPs) explained 3.1% of phenotypic variance in circulating bilirubin levels. A one-standarddeviation increment in circulating bilirubin (≈ 4.4 µmol/L), predicted by non-UGT1A1 SNPs, was inversely associated with risk of squamous cell lung cancer and Hodgkin’s lymphoma (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.73–0.99, P 0.04 and OR 0.64, 95% CI 0.42–0.99, p 0.04, respectively), which was confirmed after removing potential pleiotropic SNPs. In contrast, a positive association was observed with the risk of breast cancer after removing potential pleiotropic SNPs (OR 1.12, 95% CI 1.04–1.20, p 0.002). There was little evidence for robust associations with the other seven cancers investigated. Genetically raised bilirubin levels were inversely associated with risk of squamous cell lung cancer as well as Hodgkin’s lymphoma and positively associated with risk of breast cancer. Further studies are required to investigate the utility of bilirubin as a low-cost clinical marker to improve risk prediction for certain cancers.

824 Modulation of TLR3 protein in response to radiation in squamous cell lung carcinoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A874-A874
Author(s):  
Jeru Manuel ◽  
Ebru Tas ◽  
Cleopatra Rutihinda ◽  
Ayman Oweida
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Mrna Expression ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Toll Like Receptors ◽  
Small Cell Lung ◽  
Tlr3 Expression ◽  
Tlr3 Mrna

BackgroundSquamous cell lung cancer (SCLC) is the second most common type of lung cancer. Treatment is complicated due to the lack of mutated molecular targets.1 Radiotherapy (RT) is commonly used to treat SCLC, but relapse and tumor progression are common. The combination of immunotherapy (IT) with RT can enhance the effect observed with RT alone.2 Effective combination of IT and RT requires an understanding of the pathways that synergize to enhance tumor cell kill in SCLC. Our lab has identified Toll-like receptor 3 (TLR3) as a molecule that is regulated by RT and can be targeted with IT. Toll-like receptors serve a crucial role against tumor cells by activating innate and adaptive immune responses that boost antitumor immunity.3 4 TLR3 is the only receptor whose molecular mechanism functions independent of MyD88, leading to NF-κB mediated apoptosis.5 We hypothesized that increased TLR3 expression would be associated with improved response to RT. We further hypothesized that RT can downregulate TLR3 and that this effect can be reversed with TLR3 agonists leading to enhanced tumor antigen recognition. We aim to use this data to formulate further studies using combined RT and IT.MethodsMouse (KLN205) and human (SW900) squamous cell carcinoma (SCC) cell lines were used to study the effect of radiation on TLR3 expression. Irradiation was performed using the gammacell 3000 elan irradiator. Cells were irradiated with 0, 5, 10 and 20 Gy. Protein extraction was performed 48 and 72 hours after RT. Protein extracts were analyzed by Western Blot. Further, TLR3 mRNA expression and 5-year overall survival of SCLC patients was obtained from public databases. Kaplan-Meier method was used to correlate between TLR3 mRNA expression and survival.ResultsIn vitro studies and western blot analysis demonstrated a decrease of TLR3 expression in response to increasing doses of radiation. This observation was consistent in mouse and human SCC cell lines. In silico analysis of SCLC patients who received RT showed that increased TLR3 mRNA expression was associated with improved overall survival and disease-free survival.ConclusionsOur findings point to an important role for TLR3 in SCLC. Combining RT with TLR3 agonists may enhance the tumor response to RT. Several complementary experiments are underway in our lab to use the TLR3 agonist, Poly I:C, which will allow a better understanding of the effect of RT on TLR3.ReferencesGeorge J, Lim SJ, Jang SJ, et al. Comprehensive genomic profiles of small cell lung cancer. Nature 2015;524:47–53.Darragh L, Oweida A, Karam SD. Overcoming resistance to combination radiation-immunotherapy: a focus on contributing pathways withing the tumor microenvironment. Frontiers in Immunology 2019;9:3154.Shcheblyakov D, Logunov DY, Tukhvatulin AI, et al. Toll-Like Receptors (TLRs): The Role in Tumor Progression. Acta Naturae 2010;2(3):21-9.Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 2010;11:373–384.Bianchi F, Alexiadis S, Camiasaschi C, et al. TLR3 expression induces apoptosis in Human Non-Small-Cell Lung Cancer. Int J Mol Sci 2020 Feb;21(4):1440.

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