Radiotherapy in the management of advanced melanoma patient with brain metastases
When is radiotherapy indicated for patients with distant brain metastases?
Systematic review evidence
Clinical trials evaluating the use of radiotherapy (RT) in the management of metastatic malignancy have predominantly included multiple histological tumour types, including melanoma. The systematic review for these guidelines focused on studies that included patients with melanoma only.
The role of RT alone or in combination with other modalities in the management of brain metastases is complex, in view of the recent advances in systemic therapies that are effective in patients with brain metastases. Multidisciplinary team input is therefore required (see Treatment approaches to brain metastases).
There have been numerous studies on the role of RT in the management of melanoma brain metastases. Whilst there have been several randomised trials evaluating the role of stereotactic radiosurgery (SRS) and whole brain RT (WBRT) in the management of brain metastases, the number of patients with melanoma brain metastases in these studies was generally small. The systematic review focused on studies that included melanoma only (or mainly melanoma). The studies were all non-randomised and mostly retrospective series. For melanoma patients with single or a small number of brain metastases, SRS provides a high rate of local control, as for other malignancies. At 6 and 12 months, the local control rates are about 80% and 60%, respectively, and the overall survival (OS) rates 70% and 15%. The dose of SRS is dependent on the size of the metastasis and should be prescribed as per published protocols. The addition of WBRT after SRS may improve intracranial control, but with no OS benefit. For patients with multiple brain metastases, WBRT may provide some benefit but its role has not been directly compared with systemic therapy or supportive care alone.
Non-systematic review evidence
Adjuvant whole brain radiotherapy after local treatment of single or oligo brain metastases
A total of four randomised trials reported results for selected patients with up to four brain metastases (any histologies) treated with SRS alone versus WBRT and SRS. The addition of WBRT to SRS significantly improved local control of the SRS-treated lesions as well as distant brain control. However, WBRT did not provide an OS benefit and was associated with a decline in neurocognitive function. In a randomised, phase III trial of SRS to the surgical cavity versus WBRT in patients with one resected brain metastasis, SRS was associated with a significantly shorter time to intracranial progression than WBRT (6.4 months vs 27.5 months, HR 2.45, p<0.001). The cognitive deterioration-free survival was better with SRS to the cavity (3.7 months vs 3.0 months, p<0.001) and there was no difference in the OS between the 2 groups. Hippocampal avoidance WBRT using intensity modulated RT has been shown in one phase II study to lessen the effect of WBRT on neurocognitive function.
Adjuvant stereotactic radiosurgery to surgical cavity
In a randomised, phase III study it was shown that the addition of a SRS boost to the surgical cavity significantly improved the 12-month freedom from local recurrence rate compared with observation in patients with 1–3 completely resected brain metastases (72% vs 43%, HR=0.46, p<0.015). The benefit was seen in all histologies including melanoma. There was no difference in OS between the two groups. Multiple retrospective studies of SRS to the surgical cavity after resection of melanoma metastases have shown local control rates exceeding 70%, which is similar to surgery with postoperative WBRT.
Evidence summary and recommendations
|Stereotactic radiosurgery (SRS) for melanoma brain metastases achieves a high rate of local control.||III-2||, , , , |
|Stereotactic radiosurgery (SRS) may be considered for patients with single or a small number of brain metastases to maximise local control.||C|
|For patients with multiple brain metastases, whole brain radiation therapy may provide some palliative benefits.||C|
All melanoma patients with brain metastases should be reviewed by a multidisciplinary team to ensure optimal combination and sequencing of systemic drug therapy, surgery and RT treatments.
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