Page 67 - Read Online

Page 12 of 16 Enrique et al. J Cancer Metastasis Treat 2019;5:54 I http://dx.doi.org/10.20517/2394-4722.2019.20

SRS TREATMENT DOSE
As described in the protocol RTOG 9005, treatment dose is inversely proportional to metastatic lesion size.
The suggested dose is 24 Gy for tumors smaller than 20 mm, 18 Gy for tumors from 21 to 30 mm, and
15 Gy for tumors from 31 to 40 mm . It is not known whether the dose used for lesions smaller than 20
[63]
mm can be safely incremented above 27 Gy; hence, the general consensus still recommends a 24 Gy dose.
However, because the organs at risk are so near, a single-dose treatment modality is associated with higher
rates of toxicity, meaning that hypofractionated treatment plans are more appropriate for local control with
acceptable toxicity .
[64]
In 2014, Minniti published results of a study of hypofractionated SRS in which lesions under 20 mm received
36 Gy in three fractions, and lesions larger than 20 mm received 27 Gy in three fractions, resulting in 2 years
of local control and an overall survival rate of 72% and 25%, respectively . In 2016, Navarria published the
[65]
results of a similar study, administering a dose of 27 Gy in three fractions to lesions of 21 to 30 mm and
a dose of 32 Gy in four fractions to lesions of 31 to 50 mm. The technique resulted in local control and an
[66]
overall survival at 2 years of 96% and 33%, respectively .

CONTOURING OF BRAIN METASTASES
Before a treatment plan is complete, an MRI with gadolinium contrast should be performed for fusion with
axial CT. GTV is defined as gadolinium enhancement, identified in MRI with a 1 mm margin. A 1-3 mm
margin is used for GTV in a geometrical form to obtain the total treatment volume (planning target volume) .
[63]

SRS boost after WBRT
Several randomized trials that employed SRS as a boost after WBRT in newly detected patients with one to
three surgically unresectable brain metastases have reported no added toxicity and improved performance
in all patients and also an important benefit in the overall survival of patients with a single metastasis [51,52,57] .
In addition, a recent review of five studies involving 2,728 patients reported a survival benefit in all patients
who received a combined modality based on prognostic criteria (RPA or DS-GPA) regardless of the number
of brain metastases .
[67]
Cavity radiation therapy
A panel of international experts has recommended the following to contour CTV in SRS for patients with
completely resected brain metastases. CTV must include the entire surgical cavity showing enhancement of
contrast, using axial images in the T1 sequence of brain MRI with gadolinium contrast, excluding edema as
determined by MRI. CTV must include the surgical path shown in the MRI or CT. If the presurgical tumor
is in contact with the dura mater, CTV must include a 5-10 mm margin, until overlap with bone structures
is achieved. If the presurgical tumor is not in contact with the dura mater, the CTV must include a 1-5 mm
margin, until contact with bone structures is achieved. If a presurgical tumor is in contact with the venous
sinus, CTV must include a 1-5 mm margin along the sinus .
[68]

Late toxicity implications: radiation cognitive syndrome
Radiation cognitive syndrome is a poorly understood entity, and currently there is no validated long-term
treatment or prevention; 50%-90% of patients who receive WBRT exhibit disabling cognitive function
including declines in learning capability, processing speed, memory, and attention. This undermines the
patient’s overall quality of life. Radiation is associated with inflammation, gliosis, demyelination, vascular
[69]
abnormalities, and necrosis, which in turn may lead to such cognitive issues .

Cognitive deterioration is usually reported 6 months to 1 year after WBRT, but may be seen as early as
1 month after treatment. In addition, cognitive decline tends to be progressive and irreversible. Many