Therapy management for lung cancer is entering a new era. The progress made is remarkable and sheds new light on the importance of tumor tests in diagnosis. Many insights have been gained from which, for example, patients with non-small cell lung cancer can already benefit in the early stages. Current results have also been published on the topics of treatment response and brain metastases.
Lung cancer (LC) has the highest rate of brain metastases (BM). The aim of one study was to analyze the incidence, survival and prognostic factors of LC patients with BM using a retrospective cohort [1]. The population-based study included 3952 LV patients, 15.8% of whom developed BM. By histology, BM was more common in adenocarcinoma (ADC) (21.1%), followed by small cell lung cancer (SCLC) (20.3%), not otherwise specified (NOS) (14.2%) and squamous cell carcinoma (SQ) (7.6%). Of the 625 patients with LC and BM, 72.6% were male and the average age was 63 years. Most were diagnosed at stage IV (79.8%) and 68.7% had synchronous BM. During the follow-up period, 602 patients died; the median survival time was 2.8 months. However, the median survival increased from 2.4 months in the years 2010-2014 to 3.3 months in the years 2015-2019. In multivariate analysis, histology, targeted mutant status, extracranial disease, number of BMs, BM size, BM surgery, radiotherapy and systemic treatment were statistically significant independent prognostic factors. The results show that the BM rate in LC patients is high, especially in ADC and SCLC. The data also indicate that many factors can have an influence on patient survival. Although the prognosis for patients with LC and BM remains a major challenge, there is a trend towards improvement.
HGF concentrations influence therapy response
In a pilot study, a significant association was found between high blood levels of HGF and poor response to ICI therapy in late-stage NSCLC patients. The prognostic value and role of the HGF/MET signaling pathway in first-line immunotherapy of patients with advanced NSCLC has now been investigated [2]. 82 consecutive patients were included, 49 of whom were treated with immunotherapy and 33 with chemotherapy alone as a control group. Plasma levels of HGF were analyzed by ELISA. Immunohistochemistry was used to determine the expression levels of PD-L1, MET and CD8+ T-cell infiltration. The contribution of HGF/MET to the response of NSCLC to ICIs was further investigated by culturing peripheral blood mononuclear cells (PBMC) stimulated with 10 μg/mL phytohemagglutinin (PHA) and/or pembrolizumab (20 nM). The cells were cultured with recombinant HGF or cultured with explants from NSCLC patients in the presence of the cMET inhibitors crizotinib or SGX. The immune response was quantified on the basis of CD8+ activation and INFγ production.
Correlation tests showed that lower HGF levels were associated with a good response to ICIs and low progression. Patients with low HGF levels (< Q1) at the start of treatment had a longer progression-free survival (PFS) (841 vs. 136.5 days) and a longer overall survival (OS) (median not reached vs. 489 days).
Prediction of PD-L1 expression
Advances in the treatment of early-stage NSCLC include the introduction of PD-1/PD-L1 checkpoint inhibitors. PD-L1 is an important biomarker, but its role in early NSCLC remains unclear. PD-L1 is also closely associated with the expression of glucose transporter 1 (GLUT1), and the correlation of metabolic parameters measured by [18F]FDG-PET/CT has been demonstrated in advanced disease. The aim was to investigate the relationship between [18F] FDG-PET/CT metabolic parameters and PD-L1 expression in a cohort of patients with resected early-stage NSCLC [3]. A retrospective analysis of 210 patients with node-positive, resected early-stage NSCLC was performed. DAKO 22C3 PD-L1 immunohistochemistry was performed on the primary tumor and positive nodules and evaluated according to a tumor proportion score (TPS) of <1, 1-49 or ≥50%. The [18F]FDG-PET/CT was analyzed using semi-automated techniques for standardized maximum, mean and peak uptake values (SUV), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and SUV heterogeneity index (HISUV).
The patients were predominantly male (57%), had a median age of 70 years, the majority had non-squamous NSCLC (68%) and were current smokers (89%). The disease was often at stage T2(a-b) (48%) and most had negative primary PD-L1 expression (53%). The mean SUVmaxvalues of the primary tumor and the nodes increased with PD-L1-TPS. There were similar trends in the mean SUVmean and SUVpeak values of the primary tumor and nodes in all TPS groups. SUVmax, mean and peak values were all significantly associated with PD-L1 positivity.
Congress: ESMO 2023
Literature:
- Vilá ET, et al.: Epidemiology and prognostic factors of lung cancer and brain metastases: A 10-year retrospective population cohort study in Girona, Spain. 539P. 22.10.2023. ESMO congress 2023.
- Akli A, et al.: HGF/MET pathway is associated with poor efficacy of Immune checkpoint inhibitors (ICIs) in advanced-stage NSCLC. 1498P. 23.10.2023. ESMO congress 2023.
- Hughes DJ, et al.: Predicting PD-L1 expression using [18F]FDG PET/CT in early stage non-small cell lung cancer (NSCLC). 1283P. 21.10.2023. ESMO congress 2023.
InFo ONKOLOGIE & HÄMATOLOGIE 2023; 11(6): 26
