Incidence, features and management of radionecrosis in melanoma patients treated with cerebral radiotherapy and anti‐PD‐1 antibodies

Abstract

Background

Brain radiotherapy is used in the management of melanoma brain metastases (MBM), and can result in radionecrosis. Anti‐PD‐1 is active in the brain and may increase the risk of radionecrosis when combined with radiotherapy. We studied the incidence, associated factors and management of radionecrosis in longer‐term survivors with MBM treated with this combination.

Methods

Patients with MBM treated with radiotherapy and anti‐PD‐1 who survived greater than 1‐year were identified to determine radionecrosis incidence (cohort A, n=135). Cohort A plus additional radionecrosis cases were examined for factors associated with radionecrosis and management (cohort B, n=148).

Results

From Cohort A, 17% developed radionecrosis, with a cumulative incidence at 2‐years of 18%. Using Cohort B, multivariable analysis confirmed an association between radionecrosis and elevated lactate dehydrogenase (p=0.0496) and prior treatment with ipilimumab (p=0.0319). Radionecrosis was diagnosed based on MRI (100%), symptoms (69%) and pathology (56%). Treatment included corticosteroids, bevacizumab, and neurosurgery.

Conclusions

Radionecrosis is a significant toxicity in longer‐term melanoma survivors with MBM treated with anti‐PD‐1 and radiotherapy. Identification of those at risk of radionecrosis who may avoid radiotherapy is required.

Significance

Many patients with melanoma brain metastases receive radiotherapy and anti‐PD‐1 therapy, and this study demonstrates that approximately one fifth of those who survive beyond one year develop radionecrosis, which causes symptoms that can be difficult to manage. Recent data demonstrate high activity of anti‐PD‐1‐based therapy in patients with brain metastases, such that some patients may be spared radiotherapy and the risk of radionecrosis.

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