1. Investigational Therapies for Brain Metastases
Muhammad M. Abd-El-Barr, MD, PhD, Maryam Rahman, MD, MS, Ganesh Rao, MD 
Neurosurgery Clinics 
Volume 22, Issue 1, Pages (January 2011)
DOI: /j.nec
Copyright © 2011 Elsevier Inc. Terms and Conditions

2. Fig. 1
Pathophysiology of brain metastases. (A) A normal cell (1) undergoes multiple genetic mutations or epigenetic changes (2) to become a cancer (a melanoma as shown here) (3). It then proliferates uncontrollably and develops its own feeding vessels (4) (angiogenesis), invades the normal tissue stroma (5), and enters blood vessels or lymph channels (6). (B) The tumor gains access to the right side of the heart via the venous circulation (7). The cancer cells may be shunted to the left side of the heart via a patent foramen ovale or septal defect (8), or (C) more commonly, the cancer cells leave the heart via the pulmonary artery to reach the lung capillary bed (9), where they may either form a metastasis (9) or pass through the capillary bed to reach the left atrium (10), from where the tumor cells enter the arterial circulation and seed the brain usually at the gray matter/white matter junction. If the brain is hospitable, the tumor may leave brain capillaries and become a brain metastasis (11).
(From Gavrilovic IT, Posner JB. Brain metastases: epidemiology and pathophysiology. J Neurooncol 2005;75:5–14; with permission.)
Neurosurgery Clinics  , 87-96DOI: ( /j.nec )
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3. Fig. 2
Time to neurologic progression by treatment arm. (A) Overall—Events Review Committee. (B) Overall—investigator. (C) Lung—Events Review Committee. (D) Lung—investigator. Study time is in days (D) or months (M); median is in months. HRs were calculated using Cox proportional hazards model. Abbreviations: HR, hazard ratio; NR, not reached.
(From Mehta MP, Rodrigus P, Terhaard CH, et al. Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases. J Clin Oncol 2003;21:2529–36; with permission.)
Neurosurgery Clinics  , 87-96DOI: ( /j.nec )
Copyright © 2011 Elsevier Inc. Terms and Conditions

4. Fig. 3
The GliaSite device. The inflatable balloon catheter is sized to fit the resection cavity. The device was then filled with a radiation source (aqueous 125I radiotherapy solution). After completion of the treatment, the device was removed during a subsequent operation.
(Adapted from Rogers LR, Rock JP, Sills AK, et al. Results of a phase II trial of the GliaSite radiation therapy system for the treatment of newly diagnosed, resected single brain metastases. J Neurosurg 2006;105(3):377; with permission.)
Neurosurgery Clinics  , 87-96DOI: ( /j.nec )
Copyright © 2011 Elsevier Inc. Terms and Conditions

5. Fig. 4
Kaplan-Meier estimate of overall survival in relation to MGMT expression in brain metastases.
(Adapted from Wu PF, Kuo KT, Kuo LT, et al. O(6)-Methylguanine-DNA methyltransferase expression and prognostic value in brain metastases of lung cancers. Lung Cancer 2010;68(3):484–90; with permission.)
Neurosurgery Clinics  , 87-96DOI: ( /j.nec )
Copyright © 2011 Elsevier Inc. Terms and Conditions