BackgroundThe brain represents a frequent progression site in lung adenocarcinoma. This study was designed to analyse the association between the epidermal growth factor receptor (EGFR) mutation status and the frequency of brain metastases (BM) and survival in routine clinical practice.Patients and methodsWe retrospectively analysed the medical records of 629 patients with adenocarcinoma in Slovenia who were tested for EGFR mutations in order to analyse the cumulative incidence of BM, the time from the diagnosis to the development of BM (TDBM), the time from BM to death (TTD) and the median survival.ResultsOut of 629 patients, 168 (27%) had BM, 90 patients already at the time of diagnosis. Additional 78 patients developed BM after a median interval of 14.3 months; 25.8 months in EGFR positive and 11.8 months in EGFR negative patients, respectively (p = 0.002). EGFR mutations were present in 47 (28%) patients with BM. The curves for cumulative incidence of BM in EGFR positive and negative patients demonstrate a trend for a higher incidence of BM in EGFR mutant patients at diagnosis (19% vs. 13%, p = 0.078), but no difference later during the course of the disease. The patients with BM at diagnosis had a statistically longer TTD (7.3 months) than patients who developed BM later (3.1 months). The TTD in EGFR positive patients with BM at diagnosis was longer than in EGFR negative patients (12.6 vs. 6.8, p = 0.005), while there was no impact of EGFR status on the TTD of patients who developed BM later.ConclusionsExcept for a non-significant increase of frequency of BM at diagnosis in EGFR positive patients, EGFR status had no influence upon the cumulative incidence of BM. EGFR positive patients had a longer time to CNS progression. While EGFR positive patients with BM at diagnosis had a longer survival, EGFR status had no influence on TTD in patients who developed BM later during the course of disease.

Background Expression of PD-L1 is the most investigated predictor of benefit from immune checkpoint blockade in advanced NSCLC but little is known about the association of PD-L1 expression and clinicopathological parameters of patients with unresectable stage III NSCLC. Methods National registry data was searched for medical records of consecutive inoperable stage III NSCLC patients treated with ChT and RT from January 2012 to December 2017. Totally 249 patients were identified that met inclusion criteria and of those 117 patients had sufficient tissue for PD-L1 immunohistochemical staining. Results Eighty patients (68.4%) expressed PD-L1 of ≥ 1% and 29.9% of more than 50%. Median PFS was 15.9 months in PD-L1 negative patients and 16.1 months in patients with PD-L1 expression ≥ 1% (p = 0.696). Median OS in PD-L1 negative patients was 29.9 months compared to 28.5 months in patients with PD-L1 expression ≥ % (p = 0.888). There was no difference in median OS in patients with high PD-L1 expression (≥ 50%) with 29.8 months compared to 29.9 months in those with low (1–49%) or no PD-L1 expression (p = 0.694). We found that patients who received a total dose of 60 Gy or more had significantly better median OS (32 months vs. 17.5 months, p < 0.001) as well as patients with PS 0 (33.2 vs. 20.3 months, p = 0.005). Conclusions In our patients PD-L1 expression had no prognostic value regarding PFS and OS. Patients with good performance status and those who received a total radiation dose of more than 60 Gy had significantly better mOS.

Inoperable locally advanced non-small cell lung cancer (LA NSCLC) is treated with concurrent or sequential chemotherapy (ChT) and radiation therapy (RT). Survival rates with this treatment remains poor, reported 5-year survival is about 15%. New treatment strategies, including immunotherapy with programmed death ligand-1 (PD-L1) check point inhibitors are being investigated. The clinical significance of PD-L1 expression in tumor samples from patients with inoperable LA NSCLC who underwent concurrent chemoradiotherapy (CRT) in our institution between 2005 and 2010 was evaluated. The expression of PD-L1 was correlated with clinical and pathological parameters and outcome of treatment. We analysed 107 patients treated with concurrent CRT. Only 43 patients (36 males and 7 females) had sufficient tissue for immunohistochemical (IHC) staining. PD-L1 expression was demonstrated in 7 tumors. No statistical significant differences in patient characteristics, including age, smoking status and gender, were found according to the PD-L1 expression. After a median follow up of 103.6 months, median progression free survival (PFS) was 19.9 months in patients without and 10.1 months in patients with PD-L1 expression (p=0.006). Median overall survival (OS) was 28.4 and 12.1 months for PD-L1 negative and PD-L1 positive patients, respectively (p=0.012).In conclusions, PD-L1 expression was negative prognostic factor for PFS and OS after concurrent CRT in LA NSCLC. As only small number of patients had enough tissue for the IHC testing, no firm conclusions could be made and further investigation is warranted.

BackgroundProphylactic cranial irradiation (PCI) has been used in patients with small-cell lung cancer (SCLC) to reduce the incidence of brain metastases (BM) and thus increase overall survival. The aim of this retrospective study was to analyze the characteristics of patients with SCLC referred to the Institute of Oncology Ljubljana, their eligibility for PCI, patterns of dissemination, and survival.Patients and methodsMedical charts of 357 patients with SCLC, referred to the Institute of Oncology Ljubljana between January 2004 and December 2006, were reviewed to determine characteristics of patients chosen for PCI. The following data were collected: age, gender, performance status (PS), extent of the disease, smoking status, type of primary treatment with outcome, haematological and biochemical parameters, PCI use, and finally brain metastases (BM) status at diagnoses and after treatment.ResultsPCI was performed in 24 (6.7%) of all patients. Six (25%) patients developed brain metastases after they were treated with PCI. Brain was the only site of metastases in 4 patients, two progressed to multiple organs. Median overall survival of patients with PCI was 21.9 months, without PCI 12.13 months (p = 0.004). From the collected data there were good prognostic factors: age under 65 years, limited disease (LD), performance status, normal levels of lactate dehydrogenase (LDH) and normal levels of C-reactive protein levels (CRP). Other prognostic factors did not show statistical significant values.ConclusionsSurvival of patients with LD, who have had PCI, was significantly better than those who had not. We decided to perform PCI in patients with LD, in those with complete or near complete response, and those with good performance status (≥ 80). We did not use PCI in extended disease (ED). The reason for that shall be addressed in the future. Doses for PCI were not uniform, therefore more standard approach should be considered.