EGFR mutated non-small cell lung cancer patients: more prone to development of bone and brain metastases?

OBJECTIVES: Both bone and brain are frequent sites of metastasis in non-small cell lung cancer (NSCLC). Conflicting data exist whether EGFR mutant (+) patients are more prone to develop brain metastases or have a better outcome with brain metastases compared to EGFR/KRAS wildtype (WT) or KRAS+ patients. For bone metastases this has not been studied. METHODS: In this retrospective case-control study all EGFR+ (exons 19 and 21) patients diagnosed at two pathology departments were selected (2004/2008 to 2012). For every EGFR+ patient a consecutive KRAS+ and WT patient with metastatic NSCLC (mNSCLC) was identified. Patients with another malignancy within 2 years of mNSCLC diagnosis were excluded. Data regarding age, gender, performance score, histology, treatment, bone/brain metastases diagnosis, skeletal related events (SRE) and subsequent survival were collected. RESULTS: 189 patients were included: 62 EGFR+, 65 KRAS+, 62 WT. 32%, 35% and 40%, respectively, had brain metastases (p=0.645). Mean time to brain metastases was 20.8 [± 12.0], 10.8 [± 9.8], 16.4 [± 10.2] months (EGFR+-KRAS+, p = 0.020, EGFR+-WT, p = 0.321). Median post brain metastases survival was 12.1 [5.0-19.1], 7.6 [1.2-14.0], 10.7 [1.5-19.8] months (p = 0.674). 60%, 52% and 50% had metastatic bone disease (p=0.528). Mean time to development of metastatic bone disease was 13.4 [± 10.6], 23.3 [± 19.4], 16.4 [± 9.6] months (p = 0.201). Median post metastatic bone disease survival was 15.0 [10.6-20.3], 9.0 [5.2-12.9], 3.2 [0.0-6.9] months (p = 0.010). Time to 1st SRE was not significantly different. CONCLUSIONS: Incidence of brain and bone metastases was not different between EGFR+, KRAS+ and WT patients. Post brain metastases survival, time from mNSCLC diagnosis to metastatic bone disease and 1st SRE did not differ either. Post metastatic bone disease survival was significantly longer in EGFR+ patients. Although prevention of SRE's is important for all patients, the latter finding calls for a separate study for SRE preventing agents in EGFR+ patients.

Respiratory effects of coal dust exposure: clinical effects and diagnosis.

During the past two decades, growing evidence has been reported on the role of respirable inorganic dust in the development of airflow obstruction, impaired diffusion capacity, chronic bronchitis, and emphysema, irrespective of the extent of possible pneumoconiotic abnormalities. These nonpneumoconiotic effects associated with dust exposure in miners and the relationship between dust exposure and mortality are reviewed. When pneumoconiotic changes can be visualized by different radiologic techniques, including computed tomography (CT) and high-resolution CT, assessment of the respiratory impairment in coal workers at present requires evaluation of the ventilatory and gas exchange capacity.

The course of blood pressure after a meal: a difference between young and elderly subjects.

The effect of a standardized breakfast (405 kcal) on blood pressure and heart rate was studied in 25 healthy elderly subjects (mean age 79.8 +/- 5.7 years) and in 20 healthy young volunteers (mean age 31.5 +/- 4.8 years). In the elderly the maximal fall of systolic blood pressure was 7.1 +/- 1.5% and of diastolic blood pressure 14.1 +/- 1.7% at 50 min after the start of the breakfast. In the younger group, blood pressure did not change significantly after breakfast. In both groups heart rate increased significantly. The postprandial blood pressure reduction in the elderly was correlated with preprandial blood pressure. There was also a significant correlation between blood pressure reduction and age if corrected for preprandial blood pressure. In conclusion, in contrast to the younger subjects, elderly healthy subjects showed a clear blood pressure reduction after breakfast.