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Leptomeningeal Metastases from Solid Tumors: Recent Advances in Diagnosis and Molecular Approaches
Alessia Pellerino1, Priscilla K Brastianos2, Roberta Rudà1,3
1Department of Neuro-Oncology, University and City of Health and Science Hospital, 10126 Turin, Italy.
Abstract:
Leptomeningeal metastases (LM) from solid tumors represent an unmet need of increasing importance due to an early use of MRI for diagnosis and improvement of outcome of some molecular subgroups following targeted agents and immunotherapy. In this review, we first discussed factors limiting the efficacy of targeted agents in LM, such as the molecular divergence between primary tumors and CNS lesions and CNS barriers at the level of the normal brain, brain tumors and CSF. Further, we reviewed pathogenesis and experimental models and modalities, such as MRI (with RANO and ESO/ESMO criteria), CSF cytology and liquid biopsy, to improve diagnosis and monitoring following therapy. Efficacy and limitations of targeted therapies for LM from EGFR-mutant and ALK-rearranged NSCLC, HER2-positive breast cancer and BRAF-mutated melanomas are reported, including the use of intrathecal administration or modification of traditional cytotoxic compounds. The efficacy of checkpoint inhibitors in LM from non-druggable tumors, in particular triple-negative breast cancer, is discussed. Last, we focused on some recent techniques to improve drug delivery.
Insights
Leptomeningeal metastases (LM) are challenging, but advances in MRI, liquid biopsy, and targeted therapies offer new hope. This review explores current treatments and future strategies for improving outcomes in patients with LM.
Area of Science:
- Neuro-oncology
- Medical Oncology
- Radiology
Background:
- Leptomeningeal metastases (LM) from solid tumors present a significant clinical challenge with limited treatment options.
- Advances in diagnostic imaging (MRI) and molecular profiling have improved the identification and understanding of LM.
- Targeted agents and immunotherapy show promise but face challenges related to central nervous system (CNS) penetration and tumor heterogeneity.
Purpose of the Study:
- To review the current landscape of targeted therapies and immunotherapies for leptomeningeal metastases (LM).
- To discuss the factors limiting treatment efficacy, including CNS barriers and molecular divergence.
- To explore diagnostic modalities and novel drug delivery strategies for improving outcomes in LM.
Main Methods:
- Comprehensive literature review of targeted therapies and immunotherapies for LM.
- Analysis of diagnostic techniques including MRI (RANO, ESO/ESMO criteria), CSF cytology, and liquid biopsy.
- Discussion of experimental models and emerging drug delivery methods.
Main Results:
- Efficacy and limitations of targeted therapies for EGFR-mutant/ALK-rearranged NSCLC, HER2+ breast cancer, and BRAF-mutated melanoma are detailed.
- Checkpoint inhibitors show potential for LM from non-druggable tumors, including triple-negative breast cancer.
- Challenges include CNS penetration, molecular divergence between primary tumors and metastases, and resistance mechanisms.
Conclusions:
- Despite challenges, targeted agents and immunotherapy represent a growing therapeutic avenue for LM.
- Improved diagnostic tools and novel drug delivery strategies are crucial for enhancing treatment efficacy.
- Further research into overcoming CNS barriers and understanding tumor heterogeneity is essential for advancing LM care.
