L E L Hendriks1, E F Smit2, B A H Vosse3, W W Mellema2, D A M Heideman4, G P Bootsma5, M Westenend6, C Pitz7, G J de Vries8, R Houben9, K Grünberg4, M Bendek10, E-J M Speel10, A-M C Dingemans3. 1. Department of Pulmonary Diseases, Maastricht University Medical Center+, PO Box 5800, 6202 AZ Maastricht, The Netherlands. Electronic address: lizza.hendriks@mumc.nl. 2. Department of Pulmonary Diseases, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. 3. Department of Pulmonary Diseases, Maastricht University Medical Center+, PO Box 5800, 6202 AZ Maastricht, The Netherlands. 4. Department of Pathology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. 5. Department of Pulmonary Diseases, Atrium Medical Center, H. Dunantstraat 5, 6419 PC Heerlen, The Netherlands. 6. Department of Pulmonary Diseases, VieCuri, Tegelseweg 210, 5912 BL Venlo, The Netherlands. 7. Department of Pulmonary Diseases, Laurentius Hospital, Mgr. Driessenstraat 6, 6043 CV Roermond, The Netherlands. 8. Department of Pulmonary Diseases, Orbis Medical Center, PO Box 5500, 6130 MB Sittard, The Netherlands. 9. Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, PO Box 3035, 6202 NA Maastricht, The Netherlands. 10. Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
Abstract
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.
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.
Authors: Deepa Rangachari; Norihiro Yamaguchi; Paul A VanderLaan; Erik Folch; Anand Mahadevan; Scott R Floyd; Erik J Uhlmann; Eric T Wong; Suzanne E Dahlberg; Mark S Huberman; Daniel B Costa Journal: Lung Cancer Date: 2015-02-04 Impact factor: 5.705
Authors: Kimberley S Mak; Justin F Gainor; Andrzej Niemierko; Kevin S Oh; Henning Willers; Noah C Choi; Jay S Loeffler; Lecia V Sequist; Alice T Shaw; Helen A Shih Journal: Neuro Oncol Date: 2014-07-22 Impact factor: 12.300