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

Ines Pires da Silva; Isabella C Glitza; Lauren E Haydu; Romany Johnpulle; Patricia D Banks; George D Grass; Simone M A Goldinger; Jessica L Smith; Ashlyn S Everett; Peter Koelblinger; Rachel Roberts-Thomson; Michael Millward; Victoria G Atkinson; Alexander Guminski; Rony Kapoor; Robert M Conry; Matteo S Carlino; Wei Wang; Mark J Shackleton; Zeynep Eroglu; Serigne Lo; Angela M Hong; Georgina V Long; Douglas B Johnson; Alexander M Menzies

doi:10.1111/pcmr.12775

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

Pigment Cell Melanoma Res. 2019 Jul;32(4):553-563. doi: 10.1111/pcmr.12775. Epub 2019 Mar 3.

Authors

Ines Pires da Silva¹, Isabella C Glitza², Lauren E Haydu², Romany Johnpulle³, Patricia D Banks⁴, George D Grass⁵, Simone M A Goldinger⁶, Jessica L Smith⁷, Ashlyn S Everett⁸, Peter Koelblinger⁹, Rachel Roberts-Thomson¹⁰, Michael Millward^{11

12}, Victoria G Atkinson¹³, Alexander Guminski^{1

14}, Rony Kapoor¹, Robert M Conry⁸, Matteo S Carlino^{1

7}, Wei Wang^{1

7}, Mark J Shackleton^{4

15

16}, Zeynep Eroglu⁵, Serigne Lo¹, Angela M Hong¹, Georgina V Long^{1

14}, Douglas B Johnson³, Alexander M Menzies^{1

14}

Affiliations

¹ Melanoma Institute Australia and The University of Sydney, Sydney, New South Wales, Australia.
² The University of Texas MD Anderson Cancer Center, Houston, Texas.
³ Vanderbilt University Medical Center, Nashville, Tennessee.
⁴ Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
⁵ H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
⁶ University Hospital Zurich, Zurich, Switzerland.
⁷ Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.
⁸ University of Alabama at Birmingham, Birmingham, Alabama.
⁹ Paracelsus Medical University, Salzburg, Austria.
¹⁰ The Queen Elizabeth Hospital, Woodville South, South Australia, Australia.
¹¹ School of Medicine, University of Western Australia, Perth, Western Australia, Australia.
¹² Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
¹³ Princess Alexandra Hospital and Greenslopes Private Hospital, University of Queensland, Brisbane, Queensland, Australia.
¹⁴ Royal North Shore and Mater Hospitals, Sydney, New South Wales, Australia.
¹⁵ Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia.
¹⁶ Department of Oncology, Alfred Health, Melbourne, Victoria, Australia.

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 >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.

Keywords: brain metastases; immunotherapy; melanoma; radionecrosis; radiotherapy.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies / therapeutic use*
Brain / radiation effects*
Cohort Studies
Female
Humans
Incidence
Magnetic Resonance Imaging
Male
Melanoma / diagnostic imaging
Melanoma / immunology*
Melanoma / radiotherapy*
Middle Aged
Multivariate Analysis
Necrosis
Programmed Cell Death 1 Receptor / immunology*
Radiation Injuries / diagnostic imaging
Radiation Injuries / epidemiology*
Radiation Injuries / etiology*
Radiation Injuries / surgery
Risk Factors
Survival Analysis

Substances

Antibodies
PDCD1 protein, human
Programmed Cell Death 1 Receptor

Abstract

Publication types

MeSH terms

Substances

Grants and funding