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 Millward11,12, Victoria G Atkinson13, Alexander Guminski1,14, Rony Kapoor1, Robert M Conry8, Matteo S Carlino1,7, Wei Wang1,7, Mark J Shackleton4,15,16, Zeynep Eroglu5, Serigne Lo1, Angela M Hong1, Georgina V Long1,14, Douglas B Johnson3, Alexander M Menzies1,14. 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.
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.
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