Trial design on prophylaxis and treatment of brain metastases: Lessons learned from the EORTC Brain Metastases Strategic Meeting 2012

Preusser, Matthias; Winkler, Frank; Collette, Laurence; Haller, Sven; Marréaud, Sandrine; Soffietti, Riccardo; Klein, Martin; Reijneveld, Jaap C.; Tonn, Joerg‐Christian; Baumert, Brigitta G.; Mulvenna, P.; Schadendorf, Dirk; Duchnowska, Renata; Berghoff, Anna Sophie; Lin, Nancy U.; Cameron, David; Belkacémi, Yazid; Jassem, Jacek; Weber, Damien Charles

doi:10.1016/j.ejca.2012.07.002

Cited by 38 publications

(45 citation statements)

References 52 publications

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“…Moreover, recent studies have detected relatively high frequencies of MET and FGFR gene amplifications in NSCLC BM and also inhibitors of these target aberrations should be studied in clinical investigations [15,27]. However, the design of such trials is not trivial and needs special consideration [28]. For example, centralised high-throughput analysis of tissue specimens and enrolment into specific clinical trials based on the given mutational pattern could solve the problems that rare mutations require screening of many patients to identify an adequate number of patients.…”

Section: Discussionmentioning

confidence: 99%

Spectrum of gene mutations detected by next generation exome sequencing in brain metastases of lung adenocarcinoma

Preusser¹,

Berghoff²,

Koller³

et al. 2015

European Journal of Cancer

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Section: Discussionmentioning

confidence: 99%

Spectrum of gene mutations detected by next generation exome sequencing in brain metastases of lung adenocarcinoma

Preusser¹,

Berghoff²,

Koller³

et al. 2015

European Journal of Cancer

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“…Here, the substance of interest is given before the neurosurgical resection of a BM and afterwards analyzed for the intratumoral concentration [87]. High variability was observed for the concentration of capecitabine and lapatinib, indicating that the blood-tumor barrier at least partly restricts intratumoral uptake of these drugs in BM [88].…”

Section: Challenges In the Conduction Of Clinical Trials On Targeted mentioning

confidence: 98%

“…Up to 60% of patients die from their extracranial disease, rather than due to the intracranial disease progression. The intracranial progressionfree survival was a frequently used end point in previous studies; however, the control of the (life-threating) extracranial disease is not displayed [87,97].…”

Section: • • Trial End Pointsmentioning

confidence: 99%

“…As discussed, the treatment of established BM has to overcome several obstacles, arguing that the prevention of the outgrowth from micro-to macrometastases would facilitate a feasible treatment approach [87]. Preclinical models suggested that the induction of neoangiogenesis is one of the pivotal steps of BM outgrowth and inhibition with the VEGF antibody bevacizumab resulted in reduced BM outgrowth [109].…”

Section: Review Berghoff and Preussermentioning

confidence: 99%

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The Future of Targeted Therapies for Brain Metastases

Berghoff

2015

Future Oncol.

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Brain metastases (BM) are an increasing challenge in the management of patients with advanced cancer. Treatment options for BM are limited and mainly focus on the application of local therapies. Systemic therapies including targeted therapies are only poorly investigated, as patients with BM were frequently excluded from clinical trials. Several targeted therapies have shown promising activity in patients with BM. In the present review we discuss existing and emerging targeted therapies for the most frequent BM primary tumor types. We focus on challenges in the conduction of clinical trials on targeted therapies in BM patients such as patient selection, combination with radiotherapy, the obstacles of the blood-brain barrier and the definition of study end points.

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“…Les sites anatomiques primitifs les plus fréquents sont le poumon et le sein [3]. Cependant, le méla-nome représente la tumeur qui a le plus haut pourcentage de métastases cérébrales par comparaison aux autres tumeurs primitives, avec 75 % des patients atteints d'une maladie disséminée qui verront se développer des métastases cérébrales [4,5]. Historiquement les métastases cérébrales étaient considérées comme une phase d'évolution terminale des patients atteints de cancer.…”

Section: Introductionunclassified