Dataset Information

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.

SUBMITTER: Pires da Silva I

PROVIDER: S-EPMC8258671 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Pires da Silva Ines I Glitza Isabella C IC Haydu Lauren E LE Johnpulle Romany R Banks Patricia D PD Grass George D GD Goldinger Simone M A SMA Smith Jessica L JL Everett Ashlyn S AS Koelblinger Peter P Roberts-Thomson Rachel R Millward Michael M Atkinson Victoria G VG Guminski Alexander A Kapoor Rony R Conry Robert M RM Carlino Matteo S MS Wang Wei W Shackleton Mark J MJ Eroglu Zeynep Z Lo Serigne S Hong Angela M AM Long Georgina V GV Johnson Douglas B DB Menzies Alexander M AM

Pigment cell & melanoma research 20190303 4

<h4>Background</h4>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.<h4>Methods</h4>Patients with MBM treated with radiotherapy and anti-PD-1 who survived >1 year were identified to dete ...[more]

PMID: 30767428

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Project description:IntroductionRadiation-induced brain necrosis ["radionecrosis" (rn)] is a relatively uncommon but potentially severe adverse effect of stereotactic radiosurgery (srs) for brain metastasis. Although dose, volume, and hypofractionation have been suggested to affect rn rates, patient and treatment variability in this population make it difficult to clearly delineate the risk. We set out to establish the effect of fractionation on rn rates by reviewing patients receiving simultaneous multi-fraction and single-fraction treatment at our centre.MethodsPatients receiving simultaneous (within 1 month) 1-fraction (ssrs) and 3-fraction (fsrs) radiosurgery treatments during 2012-2015 were identified in our institution's database. Serial post-srs magnetic resonance imaging (mri) was reviewed to determine rn and local recurrence. The effect of maximum dose, volume, whole-brain radiotherapy (wbrt), and fractionation on rn development was assessed using logistic regression for paired data. Results are reported using odds ratios (ors) and corresponding 95% confidence intervals (cis).ResultsOf 90 patients identified, 22 had at least a 6-month mri follow-up. Median follow-up was 320 days. The most common primary tumour type was non-small-cell lung cancer, followed by breast and rectal cancer. Radionecrosis developed in 16 patients [21 of 62 lesions (34%), with 4 being symptomatic (20%)]. Of the 21 lesions in which rn developed, 11 received 3 fractions, and 10 received 1 fraction. The or for the association between the incidence of rn and maximum dose was 1.0 (95% ci: 0.9 to 1.1); for fractionation it was 1.0 (95% ci: 0.3 to 3.6); for previous wbrt, it was 0.4 (95% ci: 0.2 to 1.2); and for a 10-unit increase in volume, it was 3.1 (95% ci: 1.0 to 9.6). Local recurrence developed in 8 patients (12%), 6 of whom belonged to the ssrs group.ConclusionsOur results indicate that patients receiving srs for multiple brain metastases experience a higher rate of rn than is reported in the literature and poorer survival despite having equivalent local control. Maximum dose did not appear to be associated with rn risk in our cohort, but volume was significantly associated with rn risk. Although fractionated treatment did not directly lower the rate of rn in this population, it might have played a role in reducing the magnitude of the rn risk in large-volume lesions. Further investigation will help to delineate optimal dose and fractionation so as to minimize rn while maintaining local control in this group.

Project description:Background and purposeDespite availability of advanced imaging, distinguishing radiation necrosis from recurrent brain tumors noninvasively is a big challenge in neuro-oncology. Our aim was to determine the feasibility of radiomic (computer-extracted texture) features in differentiating radiation necrosis from recurrent brain tumors on routine MR imaging (gadolinium T1WI, T2WI, FLAIR).Materials and methodsA retrospective study of brain tumor MR imaging performed 9 months (or later) post-radiochemotherapy was performed from 2 institutions. Fifty-eight patient studies were analyzed, consisting of a training (n = 43) cohort from one institution and an independent test (n = 15) cohort from another, with surgical histologic findings confirmed by an experienced neuropathologist at the respective institutions. Brain lesions on MR imaging were manually annotated by an expert neuroradiologist. A set of radiomic features was extracted for every lesion on each MR imaging sequence: gadolinium T1WI, T2WI, and FLAIR. Feature selection was used to identify the top 5 most discriminating features for every MR imaging sequence on the training cohort. These features were then evaluated on the test cohort by a support vector machine classifier. The classification performance was compared against diagnostic reads by 2 expert neuroradiologists who had access to the same MR imaging sequences (gadolinium T1WI, T2WI, and FLAIR) as the classifier.ResultsOn the training cohort, the area under the receiver operating characteristic curve was highest for FLAIR with 0.79; 95% CI, 0.77-0.81 for primary (n = 22); and 0.79, 95% CI, 0.75-0.83 for metastatic subgroups (n = 21). Of the 15 studies in the holdout cohort, the support vector machine classifier identified 12 of 15 studies correctly, while neuroradiologist 1 diagnosed 7 of 15 and neuroradiologist 2 diagnosed 8 of 15 studies correctly, respectively.ConclusionsOur preliminary results suggest that radiomic features may provide complementary diagnostic information on routine MR imaging sequences that may improve the distinction of radiation necrosis from recurrence for both primary and metastatic brain tumors.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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