An overview of the therapeutic strategies for neoplastic meningitis due to breast cancer: when and why?

Introduction: Neoplastic meningitis (NM), also known as leptomeningeal carcinomatosis, is characterized by the infiltration of tumor cells into the meninges, and poses a significant therapeutic challenge owing to its aggressive nature and limited treatment options. Breast cancer is a common cause of NM among solid tumors, further highlighting the urgent need to explore effective therapeutic strategies. This review aims to provide insights into the evolving landscape of NM therapy in breast cancer by collating existing research, evaluating current treatments, and identifying potential emerging therapeutic options.

Novel Therapeutic Approaches in Neoplastic Meningitis.

Central nervous system (CNS) metastasis from systemic cancers can involve the brain parenchyma, leptomeninges, or the dura. Neoplastic meningitis (NM), also known by different terms, including leptomeningeal carcinomatosis and carcinomatous meningitis, occurs due to solid tumors and hematologic malignancies and is associated with a poor prognosis. The current management paradigm entails a multimodal approach focused on palliation with surgery, radiation, and chemotherapy, which may be administered systemically or directly into the cerebrospinal fluid (CSF).

Advances in Management of Brain and Leptomeningeal Metastases.

Purpose Of Review: The management of brain and leptomeningeal metastases has changed significantly over the past decade.

Recent Findings: Historically, radiation therapy had been the mainstay of treatment. Several strategies to limit toxicities with radiation have been developed in the recent years.

Targeting Molecular Pathways in Intracranial Metastatic Disease.

The discovery and clinical application of agents targeting pivotal molecular pathways in malignancies such as lung, breast, renal cell carcinoma, and melanoma have led to impressive improvements in clinical outcomes. Mutations in epidermal growth factor receptor (), and rearrangements of anaplastic lymphoma kinase () are targetable in lung cancer, while mutations have been successfully targeted in metastatic melanoma. Targeting estrogen receptors, cyclin dependent kinases, and (Human Epidermal Receptor) have resulted in improvement in survival in breast cancer.

New molecular targets in meningiomas: the present and the future.

Purpose Of Review: Meningiomas, the most common primary brain tumor, have historically been managed with surgery and radiation. Traditional chemotherapy has not been effective. Fortunately, recent advances in genetic sequencing have led to an improved understanding of the molecular drivers in meningioma.

Novel Systemic Treatments for Brain Metastases From Lung Cancer.

Purpose Of Review: Brain metastases are frequent complication of lung cancer and are associated with poor prognosis. Patients with brain metastases secondary to lung cancer have traditionally been managed with surgery and radiation with limited role for systemic chemotherapy. In the past decade, however, this paradigm has shifted largely due to the advent of targeted therapies and immunotherapies, both of which have demonstrated efficacy in the treatment of brain metastases and extracranial disease.

Evolution of Targeted Therapy in Breast Cancer: Where Precision Medicine Began.

As we consider best practices and approaches to targeted therapy in the clinic and in terms of trial design, breast cancer can serve as a useful model for other disease types, because estrogen receptor-positive and HER2-positive breast cancer have been known entities for several decades. In this review, we provide a history of the development of anti-estrogen therapy and anti-HER2-directed therapy and we discuss our growing understanding of resistance to targeted therapy as seen through this lens. We highlight some of the recent breakthroughs that have enhanced our understanding of resistance to endocrine and anti-HER2 therapy, and we discuss some of the ongoing research in the field.

Management of Brain Metastases in the New Era of Checkpoint Inhibition.

Purpose Of The Review: Brain metastasis is a common complication of advanced malignancies, especially, lung cancer, breast cancer, renal cell carcinoma, and melanoma. Traditionally surgery, when indicated, and radiation therapy, either as whole-brain radiation therapy or stereotactic radiosurgery, constituted the major treatment options for brain metastases. Until recently, most of the systemic chemotherapy agents had limited activity for brain metastases.

Systemic therapy for brain metastases.

Central nervous system metastases cause grave morbidity in patients with advanced malignancies. Lung cancer, breast cancer, and melanoma are the three most common causes of brain metastases. Although the exact incidence of brain metastases is unclear, there appears to be an increasing incidence which has been attributed to longer survival, better control of systemic disease, and better imaging modalities.

Changing Treatment Paradigms for Brain Metastases From Melanoma-Part 2: When and How to Use the New Systemic Agents.

Until recently, therapeutic strategies for melanoma brain metastases focused on local treatments: surgery, whole-brain radiation therapy, and stereotactic radiosurgery. Historically, systemic therapy had limited utility. Immunotherapeutic drugs, such as anti-cytotoxic T-lymphocyte-associated antigen 4 and anti-programmed death 1 agents, and agents targeting the BRAF-MEK pathway have revolutionized the systemic treatment of melanoma brain metastases.

Changing Treatment Paradigms for Brain Metastases From Melanoma-Part 1: Diagnosis, Prognosis, Symptom Control, and Local Treatment.

Melanoma is the third most common cause of brain metastases, after lung and breast cancer. The management of melanoma brain metastases can be broadly divided into symptom control and therapeutic strategies. Supportive treatments include corticosteroids to reduce peritumoral edema, antiepileptics for seizure control, and medications to preserve cognitive function.

Spotlight on nivolumab in the treatment of renal cell carcinoma: design, development, and place in therapy.

Several tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptors and molecules inhibiting the mammalian target of rapamycin are being used for management of metastatic renal cell carcinoma (mRCC); however, there is still a potential for improvement. Immune checkpoint inhibitors like nivolumab and other PD-1/PD-L1 inhibitors provide an alternative approach for patients with mRCC. In this article, the authors review the safety profile and outcomes of phase 1, 2, and 3 clinical trials of nivolumab in mRCC.

Targeted Treatment of Brain Metastases.

Purpose Of Review: Brain metastases are the most common intracranial tumors in adults. Historically, the median survival after the diagnosis of brain metastases has been dismal and medical therapies had a limited role in the management of these patients.

Recent Findings: The advent of targeted therapy has ushered in an era of increased hope for patients with brain metastases.

Targeted Therapies for Brain Metastases from Breast Cancer.

The discovery of various driver pathways and targeted small molecule agents/antibodies have revolutionized the management of metastatic breast cancer. Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor, mechanistic target of rapamycin (mTOR) pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6) pathway. Brain metastasis, however, remains a thorn in the flesh, leading to morbidity, neuro-cognitive decline, and interruptions in the management of systemic disease.

Prognostic scores for brain metastasis patients: use in clinical practice and trial design.

Brain metastases (BM) are the most serious neurological complication of cancer that results in significant morbidity and mortality in these patients. The most common primary malignancies that lead to BM include lung, breast and melanoma. Until recently the outcomes of patients with BM has been dismal.

Coexistent pulmonary granular cell tumor and adenocarcinoma of the lung.

We report a case of granular cell tumor (GCT) of the lung with coexistent invasive adenocarcinoma. GCTs are rare tumors and often benign and amenable to local bronchoscopic excision. However, occasionally they are more aggressive and locally infiltrative requiring definitive surgical resection.

Bevacizumab in high-grade gliomas: past, present, and future.

The survival of patients with high-grade gliomas (anaplastic gliomas and glioblastoma) remains poor despite current treatment modalities. However, an enhanced understanding of gliomagenesis is supporting the development of targeted molecular therapies with the potential for improving clinical outcomes. Glioblastoma (GBM) is characterized by extensive microvascular proliferation and the production of large amounts of VEGF.

Current medical treatment of glioblastoma.

Glioblastoma is the most common adult malignant primary brain tumor. Despite the advances in therapeutic options, survival of patients with glioblastoma remains dismal at 15-18 months. Current standard of care for newly diagnosed glioblastoma is maximal possible safe resection consistent with the preservation of neurologic function followed by concurrent temozolomide with radiation and adjuvant.