Brain metastases from non small cell lung carcinomas (NSCLC) have a significantly higher proportion of mature blood vessels than the primary tumour, suggesting that bevacizumab may not be effective in this setting, concludes an article in the British Journal of Cancer.

Anti-angiogenic therapy with bevacizumab (Avastin®), an anti-vascular endothelial growth factor (VEGF) antibody predominantly targets immature blood vessels. While bevacizumab has shown a survival benefit NSCLC, and has recently been demonstrated to be safe in patients with brain metastases, there are questions around whether the treatment is as effective against brain metastases.

In the study Adrian Jubb from the University of Oxford and colleagues from the Catholic University (Rome, Italy) compared the relative expression of VEGF, hypoxia, proliferation, micro vessel density, vascular patterns and vascular maturity in a series of 15 formalin fixed paraffin embedded blocks derived from patients with primary NSCLC with and matched resected brain metastases from the same patients.

The results showed that the mean proportion of mature vessels was 25.7% for primary NSCLCs versus 88.9% for brain tumours (P=0.004). Furthermore, differences were also observed in vascular patterns, with a predominance of alveolar, basal and diffuse patterns in primary tumours, and a predominance of diffuse and papillary patterns in secondary tumours.

"Brain metastases of NSCLCs have a vascular phenotype that is distinct from the primary tumours. This has implications for the use of anti-VEGF therapy in this setting and should be taken into consideration when designing clinical trials to assess the efficacy of such drugs and biomarkers that may predict benefit," write the authors.

Preclinical data, they add, suggest that when endothelial regression is seen in mature vessels targeted by anti VEGF therapy a pericyte scaffold remains that permits rapid re-angiogenesis following the cessation of therapy.

Article: A Jubb, A Cesario, M Ferguson et al. Vascular phenotypes in primary non-small cell lung carcinomas and matched brain metastases. British Journal of Cancer 2011. 104: 1877-1881.