Whole brain radiotherapy for brain metastasis

Abstract

Whole brain radiotherapy (WBRT) is a mainstay of treatment in patients with both identifiable brain metastases and prophylaxis for microscopic disease. The use of WBRT has decreased somewhat in recent years due to both advances in radiation technology, allowing for a more localized delivery of radiation, and growing concerns regarding the late toxicity profile associated with WBRT. This has prompted the development of several recent and ongoing prospective studies designed to provide Level I evidence to guide optimal treatment approaches for patients with intracranial metastases. In addition to defining the role of WBRT in patients with brain metastases, identifying methods to improve WBRT is an active area of investigation, and can be classified into two general categories: Those designed to decrease the morbidity of WBRT, primarily by reducing late toxicity, and those designed to improve the efficacy of WBRT. Both of these areas of research show diversity and promise, and it seems feasible that in the near future, the efficacy/toxicity ratio may be improved, allowing for a more diverse clinical application of WBRT.

Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours

“…36,37 In contrast radiation uniformly penetrates both the brain and tumor parenchyma, engages macroscopic and microscopic disease, overcomes resistant cells, and thus is an essential therapeutic modality. 6,8 …”

“…5,46 The cognitive decline developing after 6 months is held to be progressive and irreversible and is thus of the greatest concern (Figure 2). 18,6,27 In the adult patient population, which is the focus of the present review, radiation induced neurocognitive decline follows a biphasic pattern beginning with a transient cognitive decline at approximately 4 months posttreatment, followed by an improvement, and then a progressive, irreversible deterioration in cognitive functioning at 12 months or later after irradiation. 6 However, it is important to note that tumor progression during this time period may adversely affect cognition, confounding imaging and the measurement of radiation-induced cognitive decline in many studies.…”

“…1-5 Radiation is an indispensable treatment mainstay for the majority of these brain tumors. 6-9 Brain radiotherapy is subdivided into whole brain radiotherapy (WBRT) in which the entire brain and brainstem are irradiated, and partial brain radiotherapy (PBRT) which includes treatment of the tumor or tumor bed and surrounding margin, and some healthy brain tissue subject to incidental irradiation 4,10,11 Stereotactic radiosurgery (SRS) relies on precise 3D imaging and localization to deliver ablative doses of radiation to the tumor, and can significantly reduce exposure of healthy brain tissue. 12 These modes of brain radiotherapy fulfill any of a range of clinical objectives including; (1) long term tumor control or cure as mono or combined therapy, (2) salvage treatment for slowing tumor growth or palliation, and (3) prophylaxis to kill metastatic cells that would otherwise become established in the brain.…”

“…12 These modes of brain radiotherapy fulfill any of a range of clinical objectives including; (1) long term tumor control or cure as mono or combined therapy, (2) salvage treatment for slowing tumor growth or palliation, and (3) prophylaxis to kill metastatic cells that would otherwise become established in the brain. 6,13-15 …”

Cognitive impairments following cranial irradiation can be mitigated by treatment with a tropomyosin receptor kinase B agonist

“…Prophylactic cranial irradiation has also been used successfully to reduce metastatic brain tumors and increase survival in patients with small-cell lung cancer, metastatic breast cancer, and leukemia (Bovi and White 2012, Jabbour et al 2010, Rodriguez and Lilenbaum 2010). Despite its effectiveness in cancer therapy, cranial irradiation has been shown to cause immediate and chronic defects in cognitive functions (McTyre et al 2013, Padovani et al 2012). Neurocognitive late effects, which manifest months to years after completion of cancer treatment, are common sequelae in patients undergoing cranial irradiation, and they include decreases in spatial memory, verbal memory, and short-term memory.…”