Radiotherapy for Brain Metastases

Brain metastases affect 20% to 40% of patients with cancer and are the most common intracranial tumor in adults. The optimal treatment of brain metastases remains controversial. There are several patient- and treatment-related factors that must be considered to determine the optimal management for a given patient. At present, there is randomized control evidence supporting multiple treatment strategies incorporating radiotherapy.

The optimal treatment of brain metastases remains controversial. There are several patient- and treatment-related factors that must be considered to determine the optimal management for a given patient. At present, there is randomized control evidence supporting multiple treatment strategies incorporating radiotherapy.

Incidence

Brain metastases affect 20% to 40% of patients with cancer and are the most common intracranial tumor in adults. The incidence of metastases is thought to be increasing because of better detection and treatment of systemic malignancy. When considering various treatment approaches for brain metastases it is crucial to distinguish between single metastasis, only one lesion in the brain, regardless of extracranial status, and solitary metastasis, central nervous system (CNS) metastasis as the only site of disease, because this has disparate prognostic significance.

Prognosis

In 1997, the Radiation Therapy Oncology Group (RTOG) analyzed their database of 1200 patients with brain metastases from 3 consecutive RTOG trials conducted between 1979 and 1993 to determine the patient factors that affected overall survival (OS). This report defined 3 groups by recursive partitioning analysis (RPA): group 1, patients with Karnofsky performance score (KPS) of 70 or more, age less than 65 years, primary controlled metastasis, and no other extracranial metastases; group 2, patients with KPS of 70 or more, age of 65 years or greater, primary uncontrolled metastasis, other extracranial metastases; and group 3, patients with KPS less than 70. The median OS for these 3 cohorts was 7.1 months, 4.2 months, and 2.3 months, respectively.

Since the publication of the report, there have been 2 updates to the RTOG RPA classification. Sperduto and colleagues devised a new classification called the graded prognostic assessment (GPA) based on the RPA classification. The advantage of the GPA over the RPA classification is its ease of use and objectivity. The GPA classification is developed based on a point system and uses the following criteria: age, KPS, and cranial and extracranial metastases. Patient age is scored (0, 0.5, 1) stratified by age greater than 60 years, 50 to 59 years, or less than 50 years. KPS is scored (0, 0.5, 1) for age less than 70 years, 70 to 80 years, and 90 to 100 years. Cranial metastases are scored (0, 0.5, 1) for 3 brain metastases, 2 to 3 brain metastases, and 1 brain metastasis. Extracranial metastases are scored (0 or 1) if present or absent. The scores are summed, and OS correlates with higher score. Median OS is 2.6 months, 3.8 months, 6.9 months, and 11.0 months for a GPA score of 0 to 1, 1.5 to 2.5, 3, and 3.5 to 4, respectively.

In addition, the RTOG recently defined disease-specific GPA based on more than 4000 patients with newly diagnosed brain metastases. This study defined various prognostic factors, which were scored to categorize patients based on OS. For patients with lung cancer (both small cell lung cancer [SCLC] and non-SCLC [NSCLC]), 4 prognostic factors were included (age, KPS, extracranial metastases, and number of brain metastases). For patients with renal cell carcinoma or melanoma, 2 prognostic factors were used (KPS and number of brain metastases). For brain metastases from either a mammillary or gastrointestinal source, only KPS was required for prognostic significance. Based on these patient factors, median OS was determined ( Tables 1 and 2 ).

Table 1

GPA criteria for brain metastases

	Points
	0	0.5	1	2	3	4
NSCLC/SCLC
Age (y)	>60	59–50	<50
KPS	<70	70–80	90–100
No. of Cranial Metastases	>3	2–3	1
Extracranial Metastases	Present		Absent
Renal Cell Carcinoma/Melanoma
KPS	<70	70–80	90–100
No. of Cranial Metastases	>3	2–3	1
Breast/Gastrointestinal Tract
KPS	<70		70	80	90	100

Table 2

Median OS (in months)

GPA Score	NSCLC	SCLC	Melanoma	Renal Cell Carcinoma	Breast	Gastrointestinal Tract
0–1.0	3.0	2.8	3.4	3.3	6.1	3.1
1.5–2.5	6.5	5.3	4.7	7.3	9.4	4.4
3.0	11.3	9.6	8.8	11.3	16.9	6.9
3.5–4.0	14.8	17.0	13.2	14.8	18.7	13.5
Overall	7.0	4.9	6.7	9.6	11.9	5.4

Prognosis

In 1997, the Radiation Therapy Oncology Group (RTOG) analyzed their database of 1200 patients with brain metastases from 3 consecutive RTOG trials conducted between 1979 and 1993 to determine the patient factors that affected overall survival (OS). This report defined 3 groups by recursive partitioning analysis (RPA): group 1, patients with Karnofsky performance score (KPS) of 70 or more, age less than 65 years, primary controlled metastasis, and no other extracranial metastases; group 2, patients with KPS of 70 or more, age of 65 years or greater, primary uncontrolled metastasis, other extracranial metastases; and group 3, patients with KPS less than 70. The median OS for these 3 cohorts was 7.1 months, 4.2 months, and 2.3 months, respectively.

Since the publication of the report, there have been 2 updates to the RTOG RPA classification. Sperduto and colleagues devised a new classification called the graded prognostic assessment (GPA) based on the RPA classification. The advantage of the GPA over the RPA classification is its ease of use and objectivity. The GPA classification is developed based on a point system and uses the following criteria: age, KPS, and cranial and extracranial metastases. Patient age is scored (0, 0.5, 1) stratified by age greater than 60 years, 50 to 59 years, or less than 50 years. KPS is scored (0, 0.5, 1) for age less than 70 years, 70 to 80 years, and 90 to 100 years. Cranial metastases are scored (0, 0.5, 1) for 3 brain metastases, 2 to 3 brain metastases, and 1 brain metastasis. Extracranial metastases are scored (0 or 1) if present or absent. The scores are summed, and OS correlates with higher score. Median OS is 2.6 months, 3.8 months, 6.9 months, and 11.0 months for a GPA score of 0 to 1, 1.5 to 2.5, 3, and 3.5 to 4, respectively.

In addition, the RTOG recently defined disease-specific GPA based on more than 4000 patients with newly diagnosed brain metastases. This study defined various prognostic factors, which were scored to categorize patients based on OS. For patients with lung cancer (both small cell lung cancer [SCLC] and non-SCLC [NSCLC]), 4 prognostic factors were included (age, KPS, extracranial metastases, and number of brain metastases). For patients with renal cell carcinoma or melanoma, 2 prognostic factors were used (KPS and number of brain metastases). For brain metastases from either a mammillary or gastrointestinal source, only KPS was required for prognostic significance. Based on these patient factors, median OS was determined ( Tables 1 and 2 ).

Table 1

GPA criteria for brain metastases

	Points
	0	0.5	1	2	3	4
NSCLC/SCLC
Age (y)	>60	59–50	<50
KPS	<70	70–80	90–100
No. of Cranial Metastases	>3	2–3	1
Extracranial Metastases	Present		Absent
Renal Cell Carcinoma/Melanoma
KPS	<70	70–80	90–100
No. of Cranial Metastases	>3	2–3	1
Breast/Gastrointestinal Tract
KPS	<70		70	80	90	100