ABSTRACT
Brain metastases are frequent in patients with lung cancer and a major cause of morbidity and mortality. Finding a biomarker predicting brain metastases could facilitate early start of treatment and thereby reduce morbidity and possibly improve overall survival. Previous studies suggest S100B as a possible biomarker for this purpose. This prospective study enrolled 185 patients with newly diagnosed stage IV non-small cell lung cancer (NSCLC). A total of 22 patients had brain metastases verified by magnetic resonance imaging or computed tomography at the time of enrollment. Serum S100B levels were measured in blood samples collected prior to any treatment from 22 patients who had brain metastases at enrollment and from 50 patients randomly selected from the remaining 163 patients without brain metastases at enrollment. No statistically significant difference was found in the levels of serum S100B between patients with and without brain metastases [range 0.018-0.209 µg/l, mean 0.049 µg/l, 95% confidence interval (CI), 0.032-0.061 µg/l] and (range 0.016-0.130 µg/i, mean 0.044 µg/l, 95% CI, 0.037-0.051 µg/l), respectively, (P=0.852). Univariate analysis of prognostic factors for S100B indicated a correlation (P<0.2) with sex (P=0.088) and histology (adenocarcinoma vs. squamous cell carcinoma/others) (P=0.028). In the multivariate analysis only histology (P=0.029) remained statistically significant. Conclusion: The present study found no significant correlation between the level of serum S100B and the presence of brain metastases in patients with advanced NSCLC. The clear cut-off of S100B in patients with and without brain metastases reported in other studies could not be verified in this study. Further studies investigating the role of S100B as a biomarker for brain metastases in non-small cell lung cancer are warranted.
ABSTRACT
BACKGROUND: Lung cancer is one of the most common malignant diseases worldwide and associated with considerable morbidity and mortality. New agents targeting the epidermal growth factor system are emerging, but only a subgroup of the patients will benefit from the therapy. Cell free DNA (cfDNA) in the blood allows for tumour specific analyses, including KRAS-mutations, and the aim of the study was to investigate the possible prognostic value of plasma mutated KRAS (pmKRAS) in patients with non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Patients with newly diagnosed, advanced NSCLC eligible for chemotherapy were enrolled in a prospective biomarker trial. A pre-treatment blood sample was drawn and subsequently DNA was extracted and pmKRAS analysed. The patients received carboplatin (AUC5) i.v. day 1 and vinorelbine (30mg/m(2) i.v. day 1 and 60mg/m(2) p.o. day 8) for a maximum of six cycles. Response to chemotherapy was evaluated according to RECIST v.1.0 by CT scans of the chest and upper abdomen. The presence of pmKRAS at baseline was assessed by an in-house qPCR method. The primary endpoint was overall survival (OS). Secondary end-points were progression free survival (PFS) and overall response rate. RESULTS: The study included 246 patients receiving a minimum of 1 treatment cycle, and all but four were evaluable for response according to RECIST. Forty-three patients (17.5%) presented with a KRAS mutation. OS was 8.9 months and PFS by intention to treat 5.4 months. Patients with a detectable plasma-KRAS mutation had a significantly shorter OS and PFS compared to the wild type (WT) patients (median OS 4.8 months versus 9.5 months, HR 1.87, 95% CI 1.23-2.84, p=0.0002 and median PFS 3.0 months versus 5.6 months, HR 1.60, 95% CI 1.09-2.37, p=0.0043). A multivariate Cox regression analysis confirmed the independent prognostic value of pmKRAS in OS but not in PFS. The response rate to chemotherapy was significantly lower in the group of patients with a mutation compared to WT (p<0.0001). CONCLUSION: The presence of KRAS mutations in plasma may be a marker of poor prognosis and may also hold predictive value. Further validation in an independent cohort is highly needed.
