The Risks and Advantages of Whole Brain Radiation Therapy in Patients with Brain Metastases

Brain Metastasis Overview

Clinical Presentation

Brain metastasis occurs in approximately 25% of all cancer patients. The most common primary cancers include lung and breast cancers ( Table 14.1 ) ( ). Brain metastasis incidence has been rising and this may be attributed to systemic therapy advancements as well as accessibility to imaging tests such as magnetic resonance imaging (MRI). Headaches, mental problems, focal weaknesses are just a few of the commonly reported complications in patients with brain metastasis ( Table 14.2 ) ( ). These neurological symptoms should prompt the clinician to suspect brain metastasis in patients with known cancer although abscess or stroke should also be in the differential.

Table 14.1

Epidemiology of Brain Metastasis ( )

PRIMARY SITE
Lung	50%
Breast	15–20%
Other known primary	10–15%
Unknown primary	10–15%
Melanoma	10%
Colon	5%
RELEVANT FACTS
Median survival	<1 year
Mean age	60 years
Annual US incidence	>400,000
Autopsy incidence	10–30%
Clinical incidence	15–30%
Metastatic/primary ratio	10:1

Table 14.2

Clinical Presentation of Brain Metastasis ( )

Symptom	Percent of patients	Sign	Percent of patients
Headache	49	Hemiparesis	59
Mental problems	32	Cognitive deficits	58
Focal weakness	30	Sensory deficits	21
Ataxia	21	Papilledema	20
Seizures	18	Ataxia	19
Speech problems	12	Apraxia	18

Diagnosis/Prognosis

Initially, computed tomography (CT) scan is typically performed to detect brain metastasis. However, MRI is considered the standard of care due to its high resolution, accuracy and ability to detect small lesions in the brain which can often be undetectable on the CT scan. Positron emission tomography and CT scan are valuable tests used in a full work-up for brain metastasis.

The prognosis varies depending on the Karnofsky Performance Status (KPS) and extracranial disease status of patients. A study of 1200 patients by the Radiation Oncology Therapy Group (RTOG) reveals the median survival rates of patients in three recursive partitioning analysis (RPA) classes ( Table 14.3 ) ( ). Patients with RPA class I (KPS ≥ 70, Age <65 years, controlled primary, brain metastasis only) had a median survival of 7.1 months while RPA class III (KPS < 70) had a median survival of only 2.3 months. It is important to note that the Grade Prognostic Assessment (GPA) plays a significant role in assessing the prognosis of various cancers. It is a complicated system based on different prognostic factors such as age, KPS, number of metastatic lesions, and presence of extracranial metastases. Different cancers have different prognostic factors which determine the specific treatments that will benefit patients with intracranial metastasis ( ).

Table 14.3

RTOG Recursive Partitioning Analysis ( )

	KPS	Other criteria	Average survival
RPA class I	>70	Age <65 Controlled Primary Brain Mets only	7.1 months
RPA class II	Not meeting criteria of class I or class III		4.2 months
RPA class III	<70		2.3 months

RTOG, Radiation Therapy Oncology Group; RPA, Recursive Partitioning Analysis.

Medical Symptom Management

Corticosteroids

Symptomatic patients who are newly diagnosed with brain metastases should undergo initial therapy with corticosteroids such as dexamethasone. This can decrease inflammation and resultant peritumoral edema. Further, it can prevent serious complications such as brain herniation due to mass effect. Because of these antiinflammatory properties, corticosteroids have shown to improve performance status. Vecht and colleagues randomized two groups to two different doses of dexamethasone ( ). Both groups were evaluated with different doses of dexamethasone: the first group ( n =47) with 8 mg/day versus 16 mg/day initial dexamethasone doses, with tapering schedules over 4 weeks; the second group ( n =49) with 4 mg/day versus 16 mg/day over a 28-day period before tapering. KPS improvements at 7 days and 28 days were 54–70% and 50–81%, respectively. While all arms were statistically equivalent, this study suggested that the higher initial doses resulted in greater KPS improvements. Based on this study dexamethasone should be started at 2–4 mg every 6–8 h before tapering in a judicious manner. Corticosteroids should not be in asymptomatic patients.

Anticonvulsants

While still commonly used, no randomized trial has ever demonstrated an advantage to starting anticonvulsant therapy to prevent a seizure in someone who has never experienced one. Based on four negative randomized trials as well as serious side-effects associated with this class of medications, the American Academy of Neurology first published a consensus statement in 2000 that advises against the use of prophylactic anticonvulsants with patients newly diagnosed with brain tumor who have not experienced seizures ( ). It is safe to taper off this medication if the patient has not experienced a seizure.

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