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Updated: Jun 22, 2025
Modeling Brain Metastasis by Internal Carotid Artery Injection of Cancer Cells
Published on: August 2, 2022
Patterns of brain metastases response to immunotherapy with pembrolizumab
Amit Mahajan1, Sarah L Goldberg2, Sarah A Weiss3
1Department of Radiology and Biomedical Imaging, Yale University School of Medicine, Neuroradiology Section, CB 30, 333, Cedar St, New Haven, CT, 06510, USA. amit.mahajan@yale.edu.
Purpose:
Central nervous system (CNS) metastases from lung cancers and melanoma, significantly contribute to morbidity and mortality. Despite advances in local therapies, there is a need for effective systemic treatments. Pembrolizumab, a PD-1 inhibitor, has shown promise for some patients with untreated brain metastases from melanoma and non-small cell lung cancer (NSCLC). This study aims to analyze the response of brain metastasis to pembrolizumab and associate characteristics like size and location with treatment outcome.
Methods:
This retrospective study used imaging data from a phase II trial of pembrolizumab in melanoma or NSCLC patients with untreated brain metastases. MRI evaluations were conducted at 2 month intervals, with each brain metastasis treated as a distinct tumor for response assessment, based on modified RECIST criteria (maximum 5 lesions, 5 mm target lesions).
Results:
Of 130 individual target metastases (> 5 mm), in 65 patients with NSCLC (90 metastases) and Melanoma (40 metastases), 32 (24.6%) demonstrated complete resolution, 24 (18.5%) had partial resolution, 32 (24.6%) were SD and 42 (32.3%) demonstrated PD. Those smaller than 10 mm were more likely to show complete resolution (p = 0.0218), while those ≥ 10 mm were more likely to have PR. There was no significant association between size, number or location (supratentorial vs. infratentorial) and lesion progression. The median time to metastatic lesion progression in the brain was 5.7-7 weeks.
Conclusion:
Pembrolizumab is effective in brain metastases from NSCLC and melanoma, showing response (CR + PR) in 43% and progression (PD) in 32% of metastases. With the median time to CNS progression of 5.7-7 weeks, careful radiographic monitoring is essential to guide timely local treatment decisions.
Insights
Pembrolizumab effectively treats brain metastases from lung cancer and melanoma, with 43% showing response. Smaller lesions (<10 mm) had higher complete resolution rates, necessitating vigilant monitoring for treatment adjustments.
Area of Science:
- Neuro-oncology
- Medical imaging
- Immunotherapy
Background:
- Central nervous system (CNS) metastases from lung cancer and melanoma are significant causes of morbidity and mortality.
- Effective systemic treatments for brain metastases remain a critical unmet need.
- Pembrolizumab, a PD-1 inhibitor, shows potential for treating brain metastases in select cancers.
Purpose of the Study:
- To analyze the treatment response of brain metastases to pembrolizumab.
- To investigate the association between metastasis characteristics (size, location) and treatment outcomes.
- To evaluate pembrolizumab's efficacy in patients with untreated brain metastases from melanoma and non-small cell lung cancer (NSCLC).
Main Methods:
- Retrospective analysis of imaging data from a phase II trial of pembrolizumab.
- Inclusion of patients with melanoma or NSCLC and untreated brain metastases.
- Response assessment based on modified RECIST criteria, treating each metastasis as a distinct lesion.
Main Results:
- Overall response (complete + partial resolution) was observed in 43% of metastases (32% showed progressive disease).
- Metastases smaller than 10 mm were more likely to achieve complete resolution (p=0.0218).
- No significant association found between lesion size, number, or location and progression; median time to CNS progression was 5.7-7 weeks.
Conclusions:
- Pembrolizumab demonstrates efficacy against brain metastases in NSCLC and melanoma.
- Smaller metastases (<10 mm) respond better to pembrolizumab therapy.
- Close radiographic monitoring is crucial for timely intervention and treatment decisions in CNS metastases.
