Current Treatment Strategies for Brain Metastasis and Complications From Therapeutic Techniques

Abstract

Each year approximately 170,000 patients are diagnosed with brain metastasis in the United States, making this the most common intracranial tumor in adults. Historically, treatment strategies focused on the use of whole brain radiation therapy (WBRT) for palliation, yielding a median survival time of only 3 to 6 months. The possible effect of WBRT on cognitive function has generated much concern and debate regarding the use of this modality. Thus, the use of WBRT alone, or in conjunction with other treatment modalities should take into account both risks and benefits, to ensure the best patient outcome with regard to disease state and functional status. The advent of technologies permitting local dose-escalation have clearly increased local control rates, and in select patients, even survival, thereby, further intensifying the debate regarding the use of WBRT. Here, we review the use of WBRT, radiosurgery, and resection for the treatment of brain metastases. Further, we will review the use of radiation sensitizers and blood-brain barrier penetrating cytotoxics such as temozolomide. Finally, we will discuss current treatment strategies for possibly maintaining and improving cognitive function for these patients.

The Sun Has Not Yet Set on WBRT

“…With a predilection for the grey-white matter junction adjacent to the cerebral vasculature, brain metastases are found in the cerebral hemispheres 85% of the time [2]. Over 2/3 of cases result from a primary lung cancer, breast cancer, or melanoma [3]. Whole brain radiation therapy (WBRT) was first used in 1954 to treat brain metastases [4].…”

Deterioro cognitivo asociado a radioterapia en tumores cerebrales

“…Independientemente de la dosis empleada, los diferentes estudios relacionados encuentran evidencia de afectación cognitiva que la RT causa en los pacientes (4) en los que se emplea. Estos efectos negativos sobre la cognición parecen localizar su origen en lesiones vasculares por daños en la sustancia blanca, desmielinización y necrosis (12) . Tres son los núcleos temáticos que jalonan la esfera cognitiva en la literatura revisada: a) alteraciones cognitivas debidas a la RT, b) factores de riesgo para el desarrollo de deterioro cognitivo inducido por la RT y c) tiempo transcurrido desde la aplicación de la RT hasta la aparición de las alteraciones cognitivas.…”

“…Platta et al (12) , afirman que los efectos negativos sobre la cognición aparecen a partir de los seis meses. Sin embargo, Lawrence et al (3) advierten que pocos estudios han seguido a los pacientes el tiempo suficiente para detectar las alteraciones cognitivas.…”

Does overall treatment time impact on survival after whole-brain radiotherapy for brain metastases?

“…Administration of 10 fractions of 3 Gy over 2 weeks is one of the commonly used fractionation regimens [3]. Treatment interruption, irrespective of the underlying cause, increases the overall treatment time (OTT).…”