MRI radiomic features are associated with survival in melanoma brain metastases treated with immune checkpoint inhibitors

Abstract

Background: Melanoma brain metastases historically portend a dismal prognosis, but recent advances in immune checkpoint inhibitors (ICIs) have been associated with durable responses in some patients. There are no validated imaging biomarkers associated with outcomes in patients with melanoma brain metastases receiving ICIs. We hypothesized that radiomic analysis of magnetic resonance images (MRIs) could identify higher-order features associated with survival.

Methods: Between 2010 and 2019, we retrospectively reviewed patients with melanoma brain metastases who received ICI. After volumes of interest were drawn, several texture and edge descriptors, including first-order, Haralick, Gabor, Sobel, and Laplacian of Gaussian (LoG) features were extracted. Progression was determined using Response Assessment in Neuro-Oncology Brain Metastases. Univariate Cox regression was performed for each radiomic feature with adjustment for multiple comparisons followed by Lasso regression and multivariate analysis.

Results: Eighty-eight patients with 196 total brain metastases were identified. Median age was 63.5 years (range, 19-91 y). Ninety percent of patients had Eastern Cooperative Oncology Group performance status of 0 or 1 and 35% had elevated lactate dehydrogenase. Sixty-three patients (72%) received ipilimumab, 11 patients (13%) received programmed cell death protein 1 blockade, and 14 patients (16%) received nivolumab plus ipilimumab. Multiple features were associated with increased overall survival (OS), and LoG edge features best explained the variation in outcome (hazard ratio: 0.68, P = 0.001). In multivariate analysis, a similar trend with LoG was seen, but no longer significant with OS. Findings were confirmed in an independent cohort.

Conclusion: Higher-order MRI radiomic features in patients with melanoma brain metastases receiving ICI were associated with a trend toward improved OS.

Keywords: MRI radiomic features; brain metastases; imaging biomarkers; immune checkpoint inhibitors; intratumoral heterogeneity.

Fig. 1

CONSORT diagram.

Fig. 2

MR images of a 56-year-old female patient with a left frontotemporal lobe melanoma brain metastasis that did not respond to ipilimumab and required unplanned radiation (upper panel), and a 75-year-old male patient with a right frontal lobe melanoma brain metastasis that had a complete response to ipilimumab (lower panel). Pretreatment post-contrast imaging is shown in (A) and (D) for each patient, respectively. Edge-filtered images for each metastatic lesion show that the LoG edges are more complex in the metastasis that progressed (B) compared with the metastasis that responded (E). Additionally, a representation of the extracted entropy feature shows there is higher entropy, highlighted by the increase in variation as well as disorder in the gray level distribution, in the progressing metastatic lesion (C) in comparison with the responding metastatic lesion (F).