Kezdeti tapasztalatok a HUNCHEST – alacsony dózisú CT-tüdőrákszűrési pilotprogrammal = First experiences with HUNCHEST – low-dose CT lung cancer screening programme

Absztrakt: Bevezetés: A tüdőrák évente átlagosan több mint 8000 beteg halálát okozza hazánkban. Célkitűzés: Nemzetközi vizsgálatok alapján az alacsony dózisú CT-vizsgálattal (LDCT) végzett szűrés igazoltan csökkenti a rizikócsoportba tartozó személyek tüdőrák-mortalitását. A 2014-ben indított HUNCHEST pilotprojekt során azt vizsgáljuk, hogy a szűrés milyen módon kivitelezhető hazánkban, illetve a krónikus obstruktív tüdőbetegség (COPD) anamnézisű személyek körében magasabb lesz-e a kiemelt tüdőrákok aránya. Módszer: 50–79 éves korcsoportban alacsony dózisú CT-vizsgálat készül dohányos és nem dohányos, COPD-s és nem COPD-s csoportokban. Eredmények és következtetés: A vizsgálat jelenleg is a betegbevonás szakaszában tart, de az Országos Korányi Pulmonológiai Intézetben rendelkezésre álló első eredmények tükrében röviden ismertetjük a vizsgálat alapelveit. Orv Hetil. 2018; 159(43): 1741–1746. | Abstract: Introduction: Lung cancer is the cause of death of around 8000 Hungarians each year. Aim: International studies have proved that low-dose CT (LDCT) screening lowers the lung cancer mortality of high risk patients. The HUNCHEST pilot study launched in 2014 studies the possibilities of a lung cancer screening programme in Hungary. The study is also aimed at showing whether there is an increased number of detected lung cancer in the subgroup with chronic obstructive pulmonary disease (COPD). Method: COPD and nonCOPD subjects, smokers and non-smokers are screened with low-dose CT in the 50–79 age group. Results and conclusion: The study is still undergoing recruitement, but in the light of the first results, the principles of the screening programme at the National Korányi Institute of Pulmonology are also presented. Orv Hetil. 2018; 159(43): 1741–1746

Nationwide lung cancer screening with low-dose computed tomography: implementation and first results of the HUNCHEST screening program

Lung cancer (LC) kills more people than any other cancer in Hungary. Hence, there is a clear rationale for considering a national screening program. The HUNCHEST pilot program primarily aimed to investigate the feasibility of a population-based LC screening in Hungary, and determine the incidence and LC probability of solitary pulmonary nodules.A total of 1890 participants were assigned to undergo low-dose CT (LDCT) screening, with intervals of 1 year between procedures. Depending on the volume, growth, and volume doubling time (VDT), screenings were defined as negative, indeterminate, or positive. Non-calcified lung nodules with a volume > 500 mm3 and/or a VDT < 400 days were considered positive. LC diagnosis was based on histology.At baseline, the percentage of negative, indeterminate, and positive tests was 81.2%, 15.1%, and 3.7%, respectively. The frequency of positive and indeterminate LDCT results was significantly higher in current smokers (vs. non-smokers or former smokers; p < 0.0001) and in individuals with COPD (vs. those without COPD, p < 0.001). In the first screening round, 1.2% (n = 23) of the participants had a malignant lesion, whereas altogether 1.5% (n = 29) of the individuals were diagnosed with LC. The overall positive predictive value of the positive tests was 31.6%. Most lung malignancies were diagnosed at an early stage (86.2% of all cases).In terms of key characteristics, our prospective cohort study appears consistent to that of comparable studies. Altogether, the results of the HUNCHEST pilot program suggest that LDCT screening may facilitate early diagnosis and thus curative-intent treatment in LC.• The HUNCHEST pilot study is the first nationwide low-dose CT screening program in Hungary. • In the first screening round, 1.2% of the participants had a malignant lesion, whereas altogether 1.5% of the individuals were diagnosed with lung cancer. • The overall positive predictive value of the positive tests in the HUNCHEST screening program was 31.6%

Chemotherapy treatment is associated with altered PD-L1 expression in lung cancer patients

OBJECTIVES: While the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression is unknown. The aim of this study was to determine the changes in PD-L1 expression of tumor cells (TC) and immune cells (IC), in PD-1 expression of IC, and in the amount of stromal mononuclear cell infiltration after platinum-based chemotherapy in patients with lung cancer. MATERIALS AND METHODS: We determined the amount of stromal mononuclear cells and PD-L1/PD-1 expressions by immunohistochemistry in bronchoscopic biopsy samples including 20 adenocarcinomas (ADC), 15 squamous cell carcinomas (SCC), 2 other types of non-small cell lung cancer, and 4 small cell lung cancers together with their corresponding surgical resection tissues after platinum-based chemotherapy. RESULTS: PD-L1 expression of TC decreased in ten patients (24.4%) and increased in three patients (7.32%) after neoadjuvant chemotherapy (p = 0.051). The decrease in PD-L1 expression, however, was significant only in patients who received cisplatin-gemcitabine combination (p = 0.020), while in the carboplatin-paclitaxel group, no similar tendency could be observed (p = 0.432). There was no difference between ADC and SCC groups. Neither PD-1 expression nor the amount of stromal IC infiltration showed significant changes after chemotherapy. CONCLUSIONS: This is the first study, in which both PD-L1 and PD-1 expression were analyzed together with the amount of stromal IC infiltration in different histological subtypes of lung cancer before and after platinum-based chemotherapy. Our results confirm that chemotherapy decreases PD-L1 expression of TC in a subset of patients, therefore, rebiopsy and re-evaluation of PD-L1 expression may be necessary for the indication of immune checkpoint inhibitor therapy

EPOR is expressed in human lung ADC cell lines but exogenous rHuEPOα does not modify ADC cell proliferation in vitro.

<p>(A) Real-time qRT-PCR demonstrating the expression of EPOR mRNA in human lung ADC cell lines and K562 and HUVEC cells as control. The highest EPOR expression level was detected in the H1975 ADC cell line. H1975 (B), H1650 (C) and H358 (D) cells were treated with rHuEPOα at different concentrations (1, 3 IU/ml) with or without gemcitabine (1, 10 µg/ml). Cell numbers were estimated at 48 hours by sulforhodamine B colorimetric assay. Although gemcitabine significantly decreased the proliferation of ADC cells (<i>p</i> < 0.001), rHuEPO treatment (either alone or in combination with gemcitabine) did not modify ADC cell proliferation in vitro. </p