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

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 ErogluSerigne Lo, Angela M. Hong, Georgina V. Long, Douglas B. Johnson, Alexander M. Menzies

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27 Citations (Scopus)

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.

Original language	English
Pages (from-to)	553-563
Number of pages	11
Journal	PIGMENT CELL & MELANOMA RESEARCH
Volume	32
Issue number	4
DOIs	https://doi.org/10.1111/pcmr.12775
Publication status	Published - Jul 2019

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10.1111/pcmr.12775

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258671

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da Silva, I. P., Glitza, I. C., Haydu, L. E., Johnpulle, R., Banks, P. D., Grass, G. D., Goldinger, S. M. A., Smith, J. L., Everett, A. S., Koelblinger, P., Roberts-Thomson, R., Millward, M., Atkinson, V. G., Guminski, A., Kapoor, R., Conry, R. M., Carlino, M. S., Wang, W., Shackleton, M. J., ... Menzies, A. M. (2019). Incidence, features and management of radionecrosis in melanoma patients treated with cerebral radiotherapy and anti-PD-1 antibodies. PIGMENT CELL & MELANOMA RESEARCH, 32(4), 553-563. https://doi.org/10.1111/pcmr.12775

@article{000a6026f28a416096ec9d1802996e62,

title = "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 > 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, BRAIN METASTASES, STEREOTACTIC RADIOSURGERY, RADIATION NECROSIS, COMBINED NIVOLUMAB, IMAGING CHANGES, OPEN-LABEL, IPILIMUMAB, SURVIVAL, RECURRENCE, MULTICENTER",

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

year = "2019",

month = jul,

doi = "10.1111/pcmr.12775",

language = "English",

volume = "32",

pages = "553--563",

journal = "PIGMENT CELL & MELANOMA RESEARCH",

issn = "1755-1471",

publisher = "Wiley-Blackwell",

number = "4",

}

da Silva, IP, Glitza, IC, Haydu, LE, Johnpulle, R, Banks, PD, Grass, GD, Goldinger, SMA, Smith, JL, Everett, AS, Koelblinger, P, Roberts-Thomson, R, Millward, M, Atkinson, VG, Guminski, A, Kapoor, R, Conry, RM, Carlino, MS, Wang, W, Shackleton, MJ, Eroglu, Z, Lo, S, Hong, AM, Long, GV, Johnson, DB & Menzies, AM 2019, 'Incidence, features and management of radionecrosis in melanoma patients treated with cerebral radiotherapy and anti-PD-1 antibodies', PIGMENT CELL & MELANOMA RESEARCH, vol. 32, no. 4, pp. 553-563. https://doi.org/10.1111/pcmr.12775

TY - JOUR

T1 - Incidence, features and management of radionecrosis in melanoma patients treated with cerebral radiotherapy and anti-PD-1 antibodies

AU - da Silva, Ines Pires

AU - Glitza, Isabella C.

AU - Haydu, Lauren E.

AU - Johnpulle, Romany

AU - Banks, Patricia D.

AU - Grass, George D.

AU - Goldinger, Simone M. A.

AU - Smith, Jessica L.

AU - Everett, Ashlyn S.

AU - Koelblinger, Peter

AU - Roberts-Thomson, Rachel

AU - Millward, Michael

AU - Atkinson, Victoria G.

AU - Guminski, Alexander

AU - Kapoor, Rony

AU - Conry, Robert M.

AU - Carlino, Matteo S.

AU - Wang, Wei

AU - Shackleton, Mark J.

AU - Eroglu, Zeynep

AU - Lo, Serigne

AU - Hong, Angela M.

AU - Long, Georgina V.

AU - Johnson, Douglas B.

AU - Menzies, Alexander M.

PY - 2019/7

Y1 - 2019/7

N2 - 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.

AB - 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.

KW - brain metastases

KW - immunotherapy

KW - melanoma

KW - radionecrosis

KW - radiotherapy

KW - BRAIN METASTASES

KW - STEREOTACTIC RADIOSURGERY

KW - RADIATION NECROSIS

KW - COMBINED NIVOLUMAB

KW - IMAGING CHANGES

KW - OPEN-LABEL

KW - IPILIMUMAB

KW - SURVIVAL

KW - RECURRENCE

KW - MULTICENTER

U2 - 10.1111/pcmr.12775

DO - 10.1111/pcmr.12775

M3 - Article

C2 - 30767428

SN - 1755-1471

VL - 32

SP - 553

EP - 563

JO - PIGMENT CELL & MELANOMA RESEARCH

JF - PIGMENT CELL & MELANOMA RESEARCH

IS - 4

ER -

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

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