Impact of brain metastasis velocity on neurologic death for brain metastasis patients experiencing distant brain failure after initial stereotactic radiosurgery

Abstract INTRODUCTION We evaluated outcomes of patients with newly diagnosed MBM treated with concurrent immune checkpoint inhibition (ICI) and stereotactic radiosurgery (SRS) (concurrentTx), defined as treatment delivery within 30 days of each other. METHODS Screening of 2,617 melanoma patients who received ICI (anti-CTLA4/anti-PD1/both) between 2011-2019 identified 151 pts who received concurrentTx for MBM. Among these, 51 had newly-diagnosed MBM and received no prior ICI or SRS, and were included in the current study. Overall survival (OS) and distant brain failure (DBF) were estimated using the Kaplan-Meier method. Incidence of radiation necrosis (RN) was captured. RESULTS Median follow up from treatment initiation (either ICI or SRS, whichever occurred first) was 37 months. Median OS was 30 months. Median interval between ICI/SRS was 12 days (range: 1-29). Twenty-two patients received ICI first and 29 received SRS first, without differences in OS (p=0.22), DBF (p=0.91), or development of RN (p=0.86). However, the interval between ICI and SRS was significant. Patients who received concurrentTx 1-11 days apart (n=25, “early”) experienced a significant improvement in OS and DBF compared to 12-29 days apart (n=26, “delayed”) (p=0.01, HR 2.8; 95%CI 1.3-6.2 for OS and p=0.02, HR 2.5; 95%CI 1.2-5.6 for DBF). OS and DBF at 36 months were 67% vs. 26% and 60% vs. 27%, respectively, for the early vs. delayed groups. Time to concurrentTx as a continuous variable was significantly associated with DBF (p=0.02), but not OS (p=0.06). Although not significant, more patients developed RN in the early (26.0%) versus delayed (3.8%) group (p=0.07). No additional patient or treatment differences were identified. CONCLUSIONS Early concurrentTx was associated with prolonged OS and improved DBF in newly diagnosed MBM patients who did not receive prior CNS-directed therapy. This finding suggests therapeutic synergism related to combined early treatment and should be validated in a prospective clinical trial.

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CD138 plasma cells may predict brain metastasis recurrence following resection and stereotactic radiosurgery

Scientific Reports ◽

10.1038/s41598-019-50298-7 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Michael H. Soike ◽

Jennifer Logue ◽

Shadi Qasem ◽

Ryan T. Hughes ◽

Emory McTyre ◽

...

Keyword(s):

Brain Metastasis ◽

Stereotactic Radiosurgery ◽

Rna Sequencing ◽

Plasma Cells ◽

Sequencing Data ◽

Tissue Samples ◽

Immunologic Markers ◽

Tumor Tissues ◽

Brain Failure ◽

Formalin Fixed

Abstract We sought to identify candidate biomarkers for early brain metastasis (BM) recurrence in patients who underwent craniotomy followed by adjuvant stereotactic radiosurgery. RNA sequencing was performed on eight resected brain metastasis tissue samples and revealed B-cell related genes to be highly expressed in patients who did not experience a distant brain failure and had prolonged overall survival. To translate the findings from RNA sequencing data, we performed immunohistochemistry to stain for B and T cell markers from formalin-fixed parffin-embedded tissue blocks on 13 patients. CD138 expressing plasma cells were identified and quantitatively assessed for each tumor sample. Patients’ tumor tissues that expressed high levels of CD138 plasma cells (N = 4) had a statistically significant improvement in OS compared to low levels of CD138 (N = 9) (p = 0.01). Although these findings are preliminary, the significance of CD138 expressing plasma cells within BM specimens should be investigated in a larger cohort. Immunologic markers based on resection cavity analysis could be predictive for determining patient outcomes following cavity-directed SRS.

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