Modern Management of Central Nervous System Metastases in the Era of Targeted Therapy and Immune Oncology

2019 ◽  
pp. e59-e69 ◽  
Author(s):  
Priscilla Brastianos ◽  
Michael A. Davies ◽  
Kim Margolin ◽  
Helena A. Yu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
New Era ◽  
Patients With Cancer ◽  
Whole Brain Radiation ◽  
The Central Nervous System ◽  
Considerable Morbidity ◽  
Immune Oncology

Metastases to the central nervous system (CNS) are associated with considerable morbidity and mortality in patients with cancer. Historically, very few systemic therapies have shown efficacy in this patient population. Emerging data are now demonstrating that whole-brain radiation therapy, previously considered the mainstay of treatment of brain metastases, is associated with high rates of neurotoxicity. In this new era of targeted therapy and immunotherapy, clinical outcomes are improving, and patients are living longer. Despite these improvements, there is an urgent need to design central nervous system–penetrant compounds that target the genetic mutations enriched in brain metastases and to bring these to clinical trials.

scholarly journals Current management of brain metastases

2014 ◽  
Vol 33 (04) ◽  
pp. 347-351
Author(s):  
Pedro Tadao Hamamoto Filho ◽  
Vitor César Machado ◽  
Flávio Ramalho Romero ◽  
Luis Gustavo Ducati ◽  
Marco Antônio Zanini ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Metastases ◽  
Whole Brain Radiotherapy ◽  
Treatment Modalities ◽  
Current Management ◽  
Brain Radiotherapy ◽  
Recent Advances ◽  
The Central Nervous System ◽  
Treatment Surgery

AbstractBrain metastases are the most common tumors within the central nervous system. Recent advances on diagnosis and treatment modalities have allowed for longer survival. In this paper we review the indication of each modality of treatment: surgery, whole brain radiotherapy and stereotactic radiosurgery, as also recent advances on the knowledge of brain metastases biology that may improve the use of medical treatment and chemotherapy.

scholarly journals Challenges in the Treatment of Newly Diagnosed and Recurrent Primary Central Nervous System Lymphoma

2020 ◽  
Vol 18 (11) ◽  
pp. 1571-1578
Author(s):  
Matthias Holdhoff ◽  
Maciej M. Mrugala ◽  
Christian Grommes ◽  
Thomas J. Kaley ◽  
Lode J. Swinnen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Central Nervous System Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Newly Diagnosed ◽  
Phase Ii Trials ◽  
Whole Brain Radiation ◽  
The Central Nervous System

Primary central nervous system lymphomas (PCNSLs) are rare cancers of the central nervous system (CNS) and are predominantly diffuse large B-cell lymphomas of the activated B-cell (ABC) subtype. They typically present in the sixth and seventh decade of life, with the highest incidence among patients aged >75 years. Although many different regimens have demonstrated efficacy in newly diagnosed and relapsed or refractory PCNSL, there have been few randomized prospective trials, and most recommendations and treatment decisions are based on single-arm phase II trials or even retrospective studies. High-dose methotrexate (HD-MTX; 3–8 g/m2) is the backbone of preferred standard induction regimens. Various effective regimens with different toxicity profiles can be considered that combine other chemotherapies and/or rituximab with HD-MTX, but there is currently no consensus for a single preferred regimen. There is controversy about the role of various consolidation therapies for patients who respond to HD-MTX–based induction therapy. For patients with relapsed or refractory PCNSL who previously experienced response to HD-MTX, repeat treatment with HD-MTX–based therapy can be considered depending on the timing of recurrence. Other more novel and less toxic regimens have been developed that show efficacy in recurrent disease, including ibrutinib, or lenalidomide ± rituximab. There is uniform agreement to delay or avoid whole-brain radiation therapy due to concerns for significant neurotoxicity if a reasonable systemic treatment option exists. This article aims to provide a clinically practical approach to PCNSL, including special considerations for older patients and those with impaired renal function. The benefits and risks of HD-MTX or high-dose chemotherapy with autologous stem cell transplantation versus other, better tolerated strategies are also discussed. In all settings, the preferred treatment is always enrollment in a clinical trial if one is available.

scholarly journals The Biology of Brain Metastasis

2013 ◽  
Vol 59 (1) ◽  
pp. 180-189 ◽  
Author(s):  
Robert R Langley ◽  
Isaiah J Fidler
Keyword(s):  
Central Nervous System ◽  
Endothelial Cells ◽  
Nervous System ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Disease Progression ◽  
Microvascular Endothelial Cells ◽  
Number Of Patients ◽  
The Central Nervous System ◽  
Microvascular Endothelial

BACKGROUND It is estimated that at least 200 000 cases of brain metastases occur each year in the US, which is 10 times the number of patients diagnosed with primary brain tumors. Brain metastasis is associated with poor prognosis, neurological deterioration, diminished quality of life, and extremely short survival. Favorable interactions between tumor cells and cerebral microvascular endothelial cells encourage tumor growth in the central nervous system, while tumor cell interactions with astrocytes protect brain metastases from the cytotoxic effects of chemotherapy. CONTENT We review the pathogenesis of brain metastasis and emphasize the contributions of microvascular endothelial cells and astrocytes to disease progression and therapeutic resistance. Animal models used to study brain metastasis are also discussed. SUMMARY Brain metastasis has many unmet clinical needs. There are few clinically relevant tumor models and no targeted therapies specific for brain metastases, and the mean survival for untreated patients is 5 weeks. Improved clinical outcomes are dependent on an enhanced understanding of the metastasis-initiating population of cells and the identification of microenvironmental factors that encourage disease progression in the central nervous system.

scholarly journals The microenvironment of brain metastases from solid tumors

2021 ◽  
Vol 3 (Supplement_5) ◽  
pp. v121-v132
Author(s):  
Ethan S Srinivasan ◽  
Krutika Deshpande ◽  
Josh Neman ◽  
Frank Winkler ◽  
Mustafa Khasraw
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Metastases ◽  
Intracranial Tumor ◽  
Malignant Cells ◽  
Complex Interplay ◽  
Dismal Prognosis ◽  
Medical Need ◽  
Metabolic Conditions ◽  
The Central Nervous System

Abstract Brain metastasis (BrM) is an area of unmet medical need that poses unique therapeutic challenges and heralds a dismal prognosis. The intracranial tumor microenvironment (TME) presents several challenges, including the therapy-resistant blood–brain barrier, a unique immune milieu, distinct intercellular interactions, and specific metabolic conditions, that are responsible for treatment failures and poor clinical outcomes. There is a complex interplay between malignant cells that metastasize to the central nervous system (CNS) and the native TME. Cancer cells take advantage of vascular, neuronal, immune, and anatomical vulnerabilities to proliferate with mechanisms specific to the CNS. In this review, we discuss unique aspects of the TME in the context of brain metastases and pathways through which the TME may hold the key to the discovery of new and effective therapies for patients with BrM.

scholarly journals Targeted therapy of brain metastases: latest evidence and clinical implications

2017 ◽  
Vol 9 (12) ◽  
pp. 781-796 ◽  
Author(s):  
Rodica Di Lorenzo ◽  
Manmeet S. Ahluwalia
Keyword(s):  
Targeted Therapy ◽  
Brain Metastases ◽  
Survival Rates ◽  
Multimodality Treatment ◽  
Term Survival ◽  
Primary Tumors ◽  
Poor Prognostic Factor ◽  
Patients With Cancer ◽  
Whole Brain Radiation ◽  
Multiple Metastases

Brain metastases (BM) occur in 20–40% of patients with cancer and 60–75% of patients with BM become symptomatic. Due to an aging population and advances in the treatment of primary cancers, patients are living longer and are more likely to experience complications from BM. The diagnosis of BM drastically worsens long-term survival rates, with multiple metastases being a poor prognostic factor. Until recently, the mainstay of treatment consisted of stereotactic radiosurgery (SRS), surgical resection, whole brain radiation therapy (WBRT), or a combination of these modalities. Systemic chemotherapy has been felt largely ineffective in the treatment of BM due to the presence of the blood–brain barrier (BBB), which includes efflux pumps on brain capillaries. Over the past decade however, researchers have identified therapeutic agents that are able to cross the BBB. These findings could make a multimodality treatment approach possible, consisting of surgery, radiation, immunotherapy, and targeted therapy, which could lead to better disease control in this patient population and prolong survival. In this review, we discuss present evidence on available targeted therapies and their role in the treatment of BM from primary tumors with the highest prevalence of central nervous system (CNS) involvement, specifically non-small cell lung cancer (NSCLC), breast cancer melanoma, and renal cell carcinoma.

Intrathecal drug delivery for management of cancer and noncancer pain

2018 ◽  
Vol 4 (5) ◽  
pp. 293 ◽  
Author(s):  
Karen H. Simpson, FRCA ◽  
Iain Jones, FRCA
Keyword(s):  
Drug Delivery ◽  
Central Nervous System ◽  
Nervous System ◽  
Cancer Pain ◽  
Patient Selection ◽  
Medical Management ◽  
Patients With Cancer ◽  
Intrathecal Drug Delivery ◽  
The Central Nervous System ◽  
Noncancer Pain

Intrathecal drug delivery (ITDD) has been an option for the management of persistent pain since the 1980s. The discovery of opioid receptors in the central nervous system was the impetus for early attempts to deliver opioids intraspinally. Approximately, 10-20 percent patients with cancer pain get inadequate analgesia from conventional medical management; this group particularly may benefit from ITDD. However, there is also some evidence for the use of ITDD in those with noncancer pain. This review presents options for ITDD, available drugs, evidence for efficacy, principles of patient selection, and problems with the intrathecal route.

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