Selected Articles from This Issue

Metastatic spread from breast cancer is the second-leading cause of brain metastasis (BM). Preclinical and clinical evidence suggests that abemaciclib, a selective CDK4/6 inhibitor, has the ability to cross the blood-brain barrier. To assess the intracranial objective response rate (iORR) of abemaciclib in patients with breast cancer with CNS involvement, Tolaney and colleagues performed a phase 2 clinical trial of abemaciclib with or without endocrine therap. or trastuzumab. Although this study did not meet its primary endpoint, abemaciclib was associated with an intracranial clinical benefit rate of 24% in patients with HR+, HER2- disease with secondary BM. Pharmacologically relevant evidence of abemaciclib was observed in BM and CSF from treated patients. Furthermore, in patients with leptomeningeal metastases, abemaciclib treatment led to disease control and improved OS longer than expected, based on historical controls. These results suggest the need for further study of abemaciclib in breast cancer with CNS metastasis, especially in combination with other agents.

(4S)-4-(3-[¹⁸F]Fluoropropyl)-L-glutamic acid (¹⁸F-FSPG) is a radiopharmaceutical for PET imaging of system x_c⁻ activity, which can be upregulated in prostate cancer. Park and colleagues assessed ¹⁸F-FSPG PET/CT imaging of prostate cancer in a prospective multicenter study. ¹⁸F-FSPG accumulation was observed in patients with primary prostate cancer and in those with biochemical recurrence. ¹⁸F-FSPG uptake is also correlated to pathology and expression of markers of system x_c⁻, including xCT and CD44. ¹⁸F-FSPG PET/CT was able to distinguish prostate cancer from benign lesions and normal tissue as well as benign pathologies. Although this initial work is promising, additional studies are necessary to determine this agent's true clinical utility.

Glioblastoma multiforme (GBM) carries an extremely poor prognosis. Although conventional MRI has been widely adopted for examining GBM, accurate neuroimaging assessment of tumor pathology remains challenging in clinical management of GBM due to its complex tumor microenvironment and spatial heterogeneity. Ye and colleagues describe a novel diffusion histology imaging (DHI) approach, combining diffusion basis spectrum imaging (DBSI) and machine learning, to detect, differentiate, and quantify areas of high tumor cellularity, tumor necrosis, and tumor infiltration in GBM. The use of DBSI metrics as classifiers for a supervised machine learning algorithm predicted high tumor cellularity, tumor necrosis, and tumor infiltration with 87.5%, 89.0%, and 93.4% accuracy, respectively. These results suggest DHI could complement neuroimaging techniques for guiding biopsy or surgery and monitoring therapeutic response in the treatment of GBM.

Malignant pleural mesothelioma (MPM) is a rare and highly aggressive malignancy believed to have profound intra-tumor heterogeneity (ITH), making it challenging to eradicate. To explore immunogenomic ITH evolution of MPM under dasatinib treatment, Chen and colleagues delineated the genomic and T-cell repertoire ITH landscape of 69 longitudinal MPM specimens from 9 patients with resectable MPM by multiregion whole exome sequencing (WES) and T-cell receptor (TCR) sequencing. The results demonstrated that despite the homogeneous genomic landscape, the TCR repertoire is extremely heterogeneous in MPM. This heterogeneity may suppress host antitumor immune surveillance, leading to the high recurrence rate and suboptimal response to immunotherapy in MPM. However, after dasatinib treatment, patients with higher T cell clonality showed significantly longer overall survival (OS). Further study of dasatinib in MPM is warranted, especially in combination with immunotherapeutics.