CNS metastasis

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Brain CT scan showing CNS metastasis from the breast, the primary source. Cerebral Metastasis Breast Cancer.jpg
Brain CT scan showing CNS metastasis from the breast, the primary source.

CNS metastasis is the spread and proliferation of cancer cells from their original tumour to form secondary tumours in portions of the central nervous system. [1]

Contents

The process of tumour cells invading distant tissue is complex and obscure, but modern technology has permitted an enhanced detection of metastasis. Currently, the diagnosis of central nervous system, or CNS, metastasis involves high-scale imaging to produce high-definition images of internal organs for analysis. This aids doctors and clinicians in prescribing suitable therapeutic methods, though there is yet to be a perfect treatment or preventative measure.

Mechanism

Cancer cells spread by intravasation. Diagram showing cancer cells spreading into the blood stream CRUK 448.svg
Cancer cells spread by intravasation.

CNS metastasis is the spread and proliferation of cancer cells from their original tumour to form secondary tumours in portions of the CNS. [1] Typically, this progression initiates when tumour cells separate from the primary tumour and insert into the bloodstream or the lymph system via intravasation. [2] Intravasation into the circulatory system allows the tumour cells to travel and colonise distant sites such as the brain, a major structure of the CNS, forming a  secondary brain tumour. [2] However, CNS metastasis only occurs when genetically unstable cancers can adapt to foreign tissue native to the CNS environments, but dissimilar from the original tumour. [3] Subsequently, metastasised cells assume new genomic phenotypes, while dropping unfavourable characteristics, once cells disassociate from the primary lesion. [4] This is particularly crucial for the formation of CNS metastasis, as the tumour cells require characteristics favourable for the disruption of the blood-brain barrier, allowing them to transverse. [5] [6]

Recent evidence demonstrates that the dissemination of cells from the primary tumour is not sequential but consists of overlapping processes and routes. [4] This includes the tumour cells invading and colluding with tissue stroma while adapting to evade immune surveillance by suppressive inhibition of regular cellular anti-tumourigenic properties. [4] These cancerous cells modulate the foreign tissue environment while evolving to adapt to therapeutic intervention. [4]

Any systemic tumour can progress towards CNS metastasis. [7] Up to 30% of adult cancer cases harbour CNS metastasis, although this statistic is reportedly underdiagnosed because of the fallibility of medical diagnostic methods. [7] Clinically, the majority of diagnosed CNS metastasis are derived from well-known primary tumours, while still, about 5-10% are from unknown sources. [8] Since most cancers can progress towards CNS metastasis despite multimodal treatments, it is a significant risk for patients with systemic cancer.

Symptoms

Metastasis occurrence indicates stage 4 cancer progression and carries a poor prognosis. [7] Cancer usually causes numerous and varying symptoms at this stage depending on the underlying cancer and metastasis location. [7] Importantly for diagnosis, a symptomatic primary lesion is localised through either surgery or radiation. [7] Notably, CNS metastasis may occur in the brain, spinal cord, leptomeninges, epidural space, or even the dura singly or in combination. [7] Patients are often asymptomatic with several neurological manifestations depending on tumour size and location. [9] Clinically, CNS metastasis is known to cause haemorrhage or obstruction in the cranial portion of the CNS leading to hydrocephalus. [9]

Additionally, metastatic lesions are usually discrete within the brain and appear as spherical masses that displace the brain parenchyma rather than invading the tissues. [10] Generally, other symptoms include cystic degeneration, necrosis, as well as CNS haemorrhage commonly within the brain. [10] These conditions lead to the long-term degradation of neurocognition, speech, coordination, and behaviour, altering the quality of life of patients. [1]

Risk factors

Since CNS metastasis is the pathway of the natural progression of primary cancers, hence, main risk factors include modifiers of cancer risk. These modifiers include the accumulation of genetic, epigenetic, and environmental factors resulting in chromosomal and genomic aberrations and instability. [11] Research has demonstrated that 80-90% of malignant tumours are caused by external environmental factors such as carcinogens. [11]

Clinically, research evidence demonstrated that the primary tumours that have the greatest association with brain metastasis consist of lung, breast, melanoma, and colon cancers. [1] [5] Despite the knowledge of sources, there is a lack of understanding regarding why these sources have increased predilection, nor an understanding of the mechanism difference behind each metastasis process. [1]

Diagnosis

CNS metastases can be diagnosed through various imaging approaches and clinical manifestations. These techniques allow doctors to detect abnormalities and identify the location and extent of the metastatic spread. [12]

Imaging technology: MRI and CT scans

CNS metastases are diagnosed through imaging techniques that produce detailed images of the inside of the body, including parts such as the bones, organs, muscles, and nerves. [13] Magnetic resonance imaging (MRI) and computed tomography (CT) are two representative imaging procedures for this purpose. [12]

Brain MRI of a patient diagnosed with primary cardiac angiosarcoma that metastasised to the brain. Metastatic angiosarcoma in the brain.jpg
Brain MRI of a patient diagnosed with primary cardiac angiosarcoma that metastasised to the brain.

MRI scans use strong magnetic fields and radio waves to create an image, while CT scans use X-rays. MRI scans produce more detailed images of bodily structures, particularly soft tissues including the brain, [13] and are better at detecting CNS metastases than CT scans. However, CT scans are sometimes used for the initial imaging modality due to their lower cost and efficiency in screening for multiple conditions. [14]

Alternative techniques

When a lesion is suspected of having CNS metastases and its primary site is unknown, additional imaging and biopsies maybe necessary for an accurate diagnosis. [14] These procedures allow medical practitioners to examine and evaluate the histology, or micro-anatomy, of the suspected tissue. [15]

MR spectroscopy (MRS) of the brain to identify different chemical components based on their unique resonant frequencies. MRS 112040.png
MR spectroscopy (MRS) of the brain to identify different chemical components based on their unique resonant frequencies.

Biopsies involve surgical removal of the suspected tissue but can be invasive. They warrant a thorough evaluation of their necessity and the patient’s capability to withstand the side effects.

A less intrusive alternative imaging technique is magnetic resonance spectroscopy (MRS), which is used to determine the chemical compositions of cells. However, it is not as reliable as biopsies. [12]

These techniques are also relevant if a singular metastasis site is inadequate to explain the patient symptoms. In this case, additional screenings would be warranted to locate the other lesions and the tumour source. With this information, doctors aim to determine the metastasis lineage and accurately identify the underlying cancer. Modern clinical screening allows the detection of numerous serum levels of circulating tumour cells. However, a disproportionate amount of metastasis is still undetectable, causing under-diagnosis. [4]

Therapeutic methods

The best treatment approach for patients depends on a comprehensive assessment of several factors, including the primary cancer type, tumour location, prognosis, and patient preference, among others. Some of the main treatment methods are surgery, radiotherapy, chemotherapy, immunotherapy, and other system-targeting therapies. [14]

Surgery and Radiotherapy

The typical treatment pathway is receiving surgical resection to remove the CNS metastases, then undergo postoperative radiotherapy. [14] Radiation therapy can be delivered through stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT), or a combination of the two. In SRS, a high dose of radiation is delivered to the tumour site while sparing the surrounding healthy tissues. This is particularly useful for small CNS metastases. WBRT is, as the name suggests, delivered to the entire brain, and is preferred in cases with a risk of developing metastases or having multiple metastases. [15]

Medication

Other methods of management are mostly in the form of drugs. These medications can be employed to target specific systems in patients, or the cancer cells themselves. The wide variety of available drugs have varying impacts and side effects on a per-patient basis. [14] One of the most popular examples of drug-based management is immunotherapy, which bolsters the patient’s immune system to fight cancer. Since this process is less intrusive and more varied than traditional chemotherapy or surgery, it is preferred for patients with lower tolerability, such as the elderly. [16]

If cancer recurs or progresses, the therapeutic methods are adjusted, and varying combinations of all available options are explored. Coping with successive disease progression can be challenging due to the taxing side effects, which can take a physical and mental toll on patients. Consequently, the prognosis for further attempts may not be as promising as it was initially. [17]

Recent development

Diagnostic techniques for CNS metastasis are a major area of ongoing research, as detecting metastatic lesions early is crucial for timely treatment and better patient outcomes. [14]

One promising field is the use of biomarkers- proteins, genes, or other molecules associated with a specific condition. These are used to indicate normal or abnormal conditions of the body. [18] Early research suggests screening for biomarkers could facilitate easier diagnosis and have predictive applications. [19] Biomarkers need to be uniquely representative of CNS metastasis. Otherwise, there could be high incidences of false-positive results, rendering the method less precise. [18]

Another rising approach is chimeric antigen receptor (CAR) T cells. [14] This is a type of immunotherapy that involves engineering a patient’s T cells, a type of white blood cell, to identify and attack cancerous cells. [18]

Both methods require a better understanding of the molecular determinants of CNS metastasis. Knowing these biomolecular factors could also lead to the development of preventative methods, a heavily underdeveloped area in CNS metastasis. [20]

Related Research Articles

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A brain tumor occurs when abnormal cells form within the brain. There are two main types of tumors: malignant tumors and benign (non-cancerous) tumors. These can be further classified as primary tumors, which start within the brain, and secondary tumors, which most commonly have spread from tumors located outside the brain, known as brain metastasis tumors. All types of brain tumors may produce symptoms that vary depending on the size of the tumor and the part of the brain that is involved. Where symptoms exist, they may include headaches, seizures, problems with vision, vomiting and mental changes. Other symptoms may include difficulty walking, speaking, with sensations, or unconsciousness.

<span class="mw-page-title-main">Metastasis</span> Spread of a disease inside a body

Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, are metastases (mets). It is generally distinguished from cancer invasion, which is the direct extension and penetration by cancer cells into neighboring tissues.

<span class="mw-page-title-main">Bone tumor</span> Medical condition

A bone tumor is an abnormal growth of tissue in bone, traditionally classified as noncancerous (benign) or cancerous (malignant). Cancerous bone tumors usually originate from a cancer in another part of the body such as from lung, breast, thyroid, kidney and prostate. There may be a lump, pain, or neurological signs from pressure. A bone tumor might present with a pathologic fracture. Other symptoms may include fatigue, fever, weight loss, anemia and nausea. Sometimes there are no symptoms and the tumour is found when investigating another problem.

<span class="mw-page-title-main">Biopsy</span> Medical test involving extraction of sample cells or tissues for examination

A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a disease. The tissue is then fixed, dehydrated, embedded, sectioned, stained and mounted before it is generally examined under a microscope by a pathologist; it may also be analyzed chemically. When an entire lump or suspicious area is removed, the procedure is called an excisional biopsy. An incisional biopsy or core biopsy samples a portion of the abnormal tissue without attempting to remove the entire lesion or tumor. When a sample of tissue or fluid is removed with a needle in such a way that cells are removed without preserving the histological architecture of the tissue cells, the procedure is called a needle aspiration biopsy. Biopsies are most commonly performed for insight into possible cancerous or inflammatory conditions.

<span class="mw-page-title-main">Renal cell carcinoma</span> Medical condition

Renal cell carcinoma (RCC) is a kidney cancer that originates in the lining of the proximal convoluted tubule, a part of the very small tubes in the kidney that transport primary urine. RCC is the most common type of kidney cancer in adults, responsible for approximately 90–95% of cases. RCC occurrence shows a male predominance over women with a ratio of 1.5:1. RCC most commonly occurs between 6th and 7th decade of life.

Spinal tumors are neoplasms located in either the vertebral column or the spinal cord. There are three main types of spinal tumors classified based on their location: extradural and intradural. Extradural tumors are located outside the dura mater lining and are most commonly metastatic. Intradural tumors are located inside the dura mater lining and are further subdivided into intramedullary and extramedullary tumors. Intradural-intramedullary tumors are located within the dura and spinal cord parenchyma, while intradural-extramedullary tumors are located within the dura but outside the spinal cord parenchyma. The most common presenting symptom of spinal tumors is nocturnal back pain. Other common symptoms include muscle weakness, sensory loss, and difficulty walking. Loss of bowel and bladder control may occur during the later stages of the disease.

<span class="mw-page-title-main">Dermatofibrosarcoma protuberans</span> Medical condition

Dermatofibrosarcoma protuberans (DFSP) is a rare locally aggressive malignant cutaneous soft-tissue sarcoma. DFSP develops in the connective tissue cells in the middle layer of the skin (dermis). Estimates of the overall occurrence of DFSP in the United States are 0.8 to 4.5 cases per million persons per year. In the United States, DFSP accounts for between 1 and 6 percent of all soft tissue sarcomas and 18 percent of all cutaneous soft tissue sarcomas. In the Surveillance, Epidemiology and End Results (SEER) tumor registry from 1992 through 2004, DFSP was second only to Kaposi sarcoma.

<span class="mw-page-title-main">Invasive carcinoma of no special type</span> Medical condition

Invasive carcinoma of no special type (NST) is also referred to as invasive ductal carcinoma or infiltrating ductal carcinoma(IDC) and invasive ductal carcinoma, not otherwise specified (NOS). Each of these terms represents to the same disease entity, but for international audiences this article will use invasive carcinoma NST because it is the preferred term of the World Health Organization (WHO).

<span class="mw-page-title-main">Primary central nervous system lymphoma</span> Medical condition

Primary central nervous system lymphoma (PCNSL), also termed primary diffuse large B-cell lymphoma of the central nervous system (DLBCL-CNS), is a primary intracranial tumor appearing mostly in patients with severe immunodeficiency. It is a subtype and one of the most aggressive of the diffuse large B-cell lymphomas.

<span class="mw-page-title-main">Neuroendocrine tumor</span> Medical condition

Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. They most commonly occur in the intestine, where they are often called carcinoid tumors, but they are also found in the pancreas, lung, and the rest of the body.

<span class="mw-page-title-main">Atypical teratoid rhabdoid tumor</span> Medical condition

An atypical teratoid rhabdoid tumor (AT/RT) is a rare tumor usually diagnosed in childhood. Although usually a brain tumor, AT/RT can occur anywhere in the central nervous system (CNS), including the spinal cord. About 60% will be in the posterior cranial fossa. One review estimated 52% in the posterior fossa, 39% are supratentorial primitive neuroectodermal tumors (sPNET), 5% are in the pineal, 2% are spinal, and 2% are multifocal.

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<span class="mw-page-title-main">Leptomeningeal cancer</span> Medical condition

Leptomeningeal cancer is a rare complication of cancer in which the disease spreads from the original tumor site to the meninges surrounding the brain and spinal cord. This leads to an inflammatory response, hence the alternative names neoplastic meningitis (NM), malignant meningitis, or carcinomatous meningitis. The term leptomeningeal describes the thin meninges, the arachnoid and the pia mater, between which the cerebrospinal fluid is located. The disorder was originally reported by Eberth in 1870.

In oncology, metastasectomy is the surgical removal of metastases, which are secondary cancerous growths that have spread from cancer originating in another organ in the body.

<span class="mw-page-title-main">Bone metastasis</span> Medical condition

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<span class="mw-page-title-main">Brain metastasis</span> Cancer that has metastasized (spread) to the brain from another location in the body

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References

  1. 1 2 3 4 5 Aragon-Ching JB, Zujewski JA (March 2007). "CNS metastasis: an old problem in a new guise". Clinical Cancer Research. 13 (6): 1644–1647. doi:10.1158/1078-0432.CCR-07-0096. PMID   17363516. S2CID   16496891.
  2. 1 2 Zeeshan R, Mutahir Z (August 2017). "Cancer metastasis - tricks of the trade". Bosnian Journal of Basic Medical Sciences. 17 (3): 172–182. doi:10.17305/bjbms.2017.1908. PMC   5581965 . PMID   28278128.
  3. ↑ Gupta GP, Massagué J (November 2006). "Cancer metastasis: building a framework". Cell. 127 (4): 679–695. doi:10.1016/j.cell.2006.11.001. PMID   17110329. S2CID   7362869.
  4. 1 2 3 4 5 Suhail Y, Cain MP, Vanaja K, Kurywchak PA, Levchenko A, Kalluri R (August 2019). "Systems Biology of Cancer Metastasis". Cell Systems. 9 (2): 109–127. doi:10.1016/j.cels.2019.07.003. PMC   6716621 . PMID   31465728.
  5. 1 2 Achrol AS, Rennert RC, Anders C, Soffietti R, Ahluwalia MS, Nayak L, et al. (January 2019). "Brain metastases". Nature Reviews. Disease Primers. 5 (1): 5. doi:10.1038/s41572-018-0055-y. PMID   30655533.
  6. ↑ Steindl A, Brastianos PK, Preusser M, Berghoff AS (November 2021). "Precision medicine biomarkers in brain metastases: applications, discordances, and obstacles". Neuro-Oncology Advances. 3 (Suppl 5): v35–v42. doi:10.1093/noajnl/vdab105. PMC   8633753 . PMID   34859231.
  7. 1 2 3 4 5 6 Boire A (December 2020). "Metastasis to the Central Nervous System". Continuum. 26 (6): 1584–1601. doi:10.1212/CON.0000000000000939. PMC   9924436 . PMID   33273173.
  8. ↑ Lopes MB (2018). "Metastatic diseases of the central nervous system – neuropathologic aspects". Handbook of Clinical Neurology. Metastatic Disease of the Nervous System. Vol. 149. Elsevier. pp. 67–73. doi:10.1016/b978-0-12-811161-1.00005-0. ISBN   978-0-12-811161-1. PMID   29307362 . Retrieved 2023-04-08.
  9. 1 2 Nieblas-Bedolla E, Zuccato J, Kluger H, Zadeh G, Brastianos PK (February 2022). "Central Nervous System Metastases". Hematology/Oncology Clinics of North America. Central Nervous System Malignancies. 36 (1): 161–188. doi:10.1016/j.hoc.2021.08.004. PMID   34711458. S2CID   239978410.
  10. 1 2 Lopes MB (2018). Schiff D, van den Bent MJ (eds.). "Metastatic diseases of the central nervous system - neuropathologic aspects". Handbook of Clinical Neurology. Metastatic Disease of the Nervous System=. Elsevier. 149: 67–73. doi:10.1016/B978-0-12-811161-1.00005-0. ISBN   9780128111611. PMID   29307362.
  11. 1 2 Lewandowska AM, Rudzki M, Rudzki S, Lewandowski T, Laskowska B (March 2019). "Environmental risk factors for cancer - review paper". Annals of Agricultural and Environmental Medicine. 26 (1): 1–7. doi:10.26444/aaem/94299. PMID   30922021. S2CID   81923271.
  12. 1 2 3 Wanleenuwat P, Iwanowski P (May 2020). "Metastases to the central nervous system: Molecular basis and clinical considerations". Journal of the Neurological Sciences. 412: 116755. doi:10.1016/j.jns.2020.116755. PMID   32120132. S2CID   211221479.
  13. 1 2 Pope WB (1 January 2018). "Chapter 7 - Brain metastases: neuroimaging". Handbook of Clinical Neurology. Metastatic Disease of the Nervous System. Vol. 149. Elsevier. pp. 89–112. doi:10.1016/B978-0-12-811161-1.00007-4. ISBN   9780128111611. PMC   6118134 . PMID   29307364.
  14. 1 2 3 4 5 6 7 Nieblas-Bedolla E, Zuccato J, Kluger H, Zadeh G, Brastianos PK (February 2022). "Central Nervous System Metastases". Hematology/Oncology Clinics of North America. 36 (1): 161–188. doi:10.1016/j.hoc.2021.08.004. PMID   34711458. S2CID   239978410.
  15. 1 2 Khan M, Arooj S, Li R, Tian Y, Zhang J, Lin J, et al. (7 July 2020). "Tumor Primary Site and Histology Subtypes Role in Radiotherapeutic Management of Brain Metastases". Frontiers in Oncology. 10: 781. doi: 10.3389/fonc.2020.00781 . PMC   7358601 . PMID   32733787.
  16. ↑ Hu H, Xu ZY, Zhu Q, Liu X, Jiang SC, Zheng JH (14 July 2021). "Brain Metastases Status and Immunotherapy Efficacy in Advanced Lung Cancer: A Systematic Review and Meta-Analysis". Frontiers in Immunology. 12: 669398. doi: 10.3389/fimmu.2021.669398 . PMC   8316922 . PMID   34335570.
  17. ↑ Tan XL, Le A, Scherrer E, Tang H, Kiehl N, Han J, et al. (8 December 2022). "Systematic literature review and meta-analysis of clinical outcomes and prognostic factors for melanoma brain metastases". Frontiers in Oncology. 12: 1025664. doi: 10.3389/fonc.2022.1025664 . PMC   9773194 . PMID   36568199.
  18. 1 2 3 Kalita-de Croft P, Joshi V, Saunus JM, Lakhani SR (February 2022). "Emerging Biomarkers for Diagnosis, Prevention and Treatment of Brain Metastases-From Biology to Clinical Utility". Diseases. 10 (1): 11. doi: 10.3390/diseases10010011 . PMC   8884016 . PMID   35225863.
  19. ↑ Steindl A, Brastianos PK, Preusser M, Berghoff AS (November 2021). "Precision medicine biomarkers in brain metastases: applications, discordances, and obstacles". Neuro-Oncology Advances. 3 (Suppl 5): v35–v42. doi:10.1093/noajnl/vdab105. PMC   8633753 . PMID   34859231.
  20. ↑ Achrol AS, Rennert RC, Anders C, Soffietti R, Ahluwalia MS, Nayak L, et al. (January 2019). "Brain metastases". Nature Reviews. Disease Primers. 5 (1): 5. doi:10.1038/s41572-018-0055-y. PMID   30655533.
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