How many people are diagnosed with brain tumors annually. What factors influence brain tumor survival rates. How do age and tumor type affect brain tumor prognosis. What is the 5-year relative survival rate for brain tumors.

Brain Tumor Incidence: Understanding the Numbers

Brain tumors, while relatively rare, affect thousands of people each year. In 2023, an estimated 24,810 adults in the United States will be diagnosed with primary cancerous tumors of the brain and spinal cord. This breaks down to approximately 14,280 men and 10,530 women. Globally, the numbers are even more staggering, with an estimated 308,102 people diagnosed with a primary brain or spinal cord tumor in 2020.

Are brain tumors common in children? Indeed, they are a significant concern in pediatric oncology. Approximately 5,230 children under the age of 20 will be diagnosed with a central nervous system (CNS) tumor in the United States in 2023. However, this article primarily focuses on adult brain tumors.

Primary vs. Secondary Brain Tumors

It’s crucial to distinguish between primary and secondary brain tumors. Primary tumors originate in the brain or spinal cord, while secondary tumors, also known as brain metastases, start elsewhere in the body and spread to the brain. Common cancers that metastasize to the brain include breast, kidney, and lung cancers, as well as leukemia, lymphoma, and melanoma.

Brain Tumor Mortality: A Sobering Reality

Brain and other nervous system cancers represent a significant health concern, ranking as the 10th leading cause of death for both men and women. In 2023, it is estimated that 18,990 deaths (11,020 men and 7,970 women) from primary cancerous brain and CNS tumors will occur in the United States. Worldwide, the impact is even more profound, with an estimated 251,329 people succumbing to primary cancerous brain and CNS tumors in 2020.

Understanding Brain Tumor Survival Rates

Survival rates provide valuable insights into the prognosis of brain tumor patients. The relative survival rate, in particular, helps predict how a brain tumor may affect life expectancy. This statistic compares the likelihood of survival for people with brain tumors to that of similar individuals without the condition.

How is the relative survival rate calculated? Consider this example: If the 5-year relative survival rate for a specific type of cancer is 90%, it means that out of 1,000 people with this cancer, 810 (90% of 900) are expected to be alive after 5 years, compared to 900 out of 1,000 similar people without cancer.

Current Survival Statistics for Brain Tumors

• The 5-year relative survival rate for a cancerous brain or CNS tumor is nearly 36%
• The 10-year survival rate exceeds 30%
• For people younger than 15, the 5-year relative survival rate is about 75%
• For individuals aged 15 to 39, the 5-year relative survival rate approaches 72%
• For those 40 and older, the 5-year relative survival rate is 21%

Factors Influencing Brain Tumor Survival Rates

Survival rates for brain tumors are not uniform and can vary significantly based on several factors. Understanding these variables is crucial for patients and healthcare providers alike.

Tumor Grade and Prognostic Factors

The grade of a brain tumor plays a pivotal role in determining survival rates. Higher-grade tumors tend to be more aggressive and may have lower survival rates. Prognostic factors, such as the tumor’s location, size, and genetic profile, also influence outcomes.

Age and General Health

A patient’s age and overall health significantly impact their prognosis. Younger patients generally have better outcomes, as evidenced by the higher survival rates for individuals under 40. General health can affect a patient’s ability to tolerate treatments and recover from surgical interventions.

Treatment Effectiveness

The success of the treatment plan is a critical factor in determining survival rates. Advancements in surgical techniques, radiation therapy, chemotherapy, and targeted therapies have improved outcomes for many patients. However, the effectiveness of these treatments can vary depending on the specific tumor type and individual patient factors.

Brain Tumor Types and Their Impact on Prognosis

The type of brain or spinal cord tumor significantly influences survival rates and treatment approaches. Different tumor types have varying growth rates, tendencies to spread, and responses to treatment.

Common Types of Brain Tumors

• Gliomas (including astrocytomas, oligodendrogliomas, and ependymomas)
• Meningiomas
• Pituitary adenomas
• Medulloblastomas
• Schwannomas

Each of these tumor types has its own prognosis and treatment considerations. For example, low-grade gliomas generally have a better prognosis than high-grade gliomas, while meningiomas are often benign and may have excellent long-term outcomes if completely resected.

Advancements in Brain Tumor Treatment and Research

The field of neuro-oncology is rapidly evolving, with new treatments and diagnostic tools continually improving patient outcomes. Recent advancements have focused on personalized medicine approaches, targeted therapies, and immunotherapies.

Molecular Profiling and Targeted Therapies

Molecular profiling of brain tumors has revolutionized treatment approaches. By identifying specific genetic mutations and molecular markers, oncologists can tailor treatments to target the unique characteristics of each tumor. This personalized approach has led to the development of targeted therapies that can be more effective and less toxic than traditional chemotherapy.

Immunotherapy for Brain Tumors

Immunotherapy, which harnesses the power of the body’s immune system to fight cancer, has shown promise in treating certain types of brain tumors. While challenges remain due to the blood-brain barrier and the unique immune environment of the central nervous system, ongoing research is exploring novel approaches to overcome these obstacles.

Advanced Imaging Techniques

Improved imaging technologies, such as high-resolution MRI and PET scans, have enhanced the ability to detect and monitor brain tumors. These advancements allow for more precise surgical planning and better assessment of treatment response.

Living with a Brain Tumor: Quality of Life Considerations

While survival rates provide important information, they don’t tell the whole story of living with a brain tumor. Quality of life is a crucial consideration for patients and their families.

Neurological Symptoms and Management

Brain tumors can cause a wide range of neurological symptoms, including headaches, seizures, cognitive changes, and motor deficits. Effective symptom management is essential for maintaining quality of life. This may involve medications, rehabilitation therapies, and supportive care services.

Psychosocial Support

The emotional and psychological impact of a brain tumor diagnosis can be profound. Support groups, counseling services, and patient advocacy organizations play a vital role in helping patients and their families cope with the challenges of living with a brain tumor.

Long-term Survivorship

As survival rates improve, there is an increasing focus on long-term survivorship issues. This includes monitoring for late effects of treatment, addressing cognitive and functional deficits, and supporting patients in returning to work or school.

The Future of Brain Tumor Care: Hope on the Horizon

Despite the challenges posed by brain tumors, there is reason for optimism. Ongoing research and clinical trials are exploring innovative approaches to diagnosis, treatment, and supportive care.

Emerging Therapies

Several promising therapies are on the horizon, including:

• CAR T-cell therapy for brain tumors
• Nanoparticle-based drug delivery systems
• Novel combinations of existing treatments
• Precision medicine approaches based on tumor genomics

Improving Access to Care

Efforts are underway to improve access to specialized neuro-oncology care, particularly for underserved populations. Telemedicine and remote consultation services are expanding the reach of expert care, potentially improving outcomes for patients in rural or underserved areas.

Patient-Centered Research

There is a growing emphasis on patient-centered outcomes research, which focuses on aspects of care that are most important to patients and their families. This approach ensures that research priorities align with the needs and preferences of those living with brain tumors.

In conclusion, while brain tumors remain a significant health challenge, the landscape of care is rapidly evolving. Advances in understanding tumor biology, developing targeted therapies, and improving supportive care are offering new hope to patients and their families. As research continues and new treatments emerge, the outlook for those diagnosed with brain tumors is likely to improve, potentially leading to better survival rates and quality of life in the years to come.

Brain Tumor: Statistics | Cancer.Net

Approved by the Cancer.Net Editorial Board, 03/2023

ON THIS PAGE: You will find information about the estimated number of people who will diagnosed with a brain tumor each year. You will also read general information on surviving the disease. Remember, survival rates depend on several factors, and no 2 people with a tumor are the same. Use the menu to see other pages.

Every person is different, with different factors influencing their risk of being diagnosed with this tumor and the chance of recovery after a diagnosis. It is important to talk with your doctor about any questions you have around the general statistics provided below and what they may mean for you individually. The original sources for these statistics are provided at the bottom of this page.

How many people are diagnosed with a brain tumor?

A primary brain or spinal cord tumor is a tumor that starts in the brain or spinal cord. In 2023, an estimated 24,810 adults (14,280 men and 10,530 women) in the United States will be diagnosed with primary cancerous tumors of the brain and spinal cord. A person’s likelihood of developing this type of tumor in their lifetime is less than 1%. Brain tumors account for 85% to 90% of all primary central nervous system (CNS) tumors. Worldwide, an estimated 308,102 people were diagnosed with a primary brain or spinal cord tumor in 2020.

It is estimated that 5,230 children under the age of 20 will also be diagnosed with a CNS tumor in the United States in 2023. The rest of this guide deals with primary brain tumors in adults. Learn more about brain tumors in children.

In addition to primary brain tumors, there are also secondary brain tumors or brain metastases. This is when the tumor started somewhere else in the body and spread to the brain. The most common cancers that spread to the brain are breast, kidney, and lung cancers, as well as leukemia, lymphoma, and melanoma. This guide covers primary adult brain tumors only.

Brain and other nervous system cancer is the 10th leading cause of death for men and women. It is estimated that 18,990 deaths (11,020 men and 7,970 women) from primary cancerous brain and CNS tumors will occur in the United States in 2023. In 2020, an estimated 251,329 people worldwide died from primary cancerous brain and CNS tumors.

What is the survival rate for a brain tumor?

There are different types of statistics that can help doctors evaluate a person’s chance of recovery from a brain tumor. These are called survival statistics. A specific type of survival statistic is called the relative survival rate. It is often used to predict how having a tumor may affect life expectancy. Relative survival rate looks at how likely people with a brain tumor are to survive for a certain amount of time after their initial diagnosis or start of treatment compared to the expected survival of similar people without this tumor.

Example: Here is an example to help explain what a relative survival rate means. Please note this is only an example and not specific to this type of cancer. Let’s assume that the 5-year relative survival rate for a specific type of cancer is 90%. “Percent” means how many out of 100. Imagine there are 1,000 people without cancer, and based on their age and other characteristics, you expect 900 of the 1,000 to be alive in 5 years. Also imagine there are another 1,000 people similar in age and other characteristics as the first 1,000, but they all have the specific type of cancer that has a 5-year survival rate of 90%. This means it is expected that 810 of the people with the specific cancer (90% of 900) will be alive in 5 years.

It is important to remember that statistics on the survival rates for people with a brain tumor are only an estimate. They cannot tell an individual person if the tumor will or will not shorten their life. Instead, these statistics describe trends in groups of people previously diagnosed with the same disease, including specific stages of the disease.

The 5-year relative survival rate for a cancerous brain or CNS tumor is almost 36%. The 10-year survival rate is over 30%.

The survival rates for a brain tumor vary based on several factors. These include the grade and prognostic factors of a tumor, a person’s age and general health, and how well the treatment plan works. Another factor that can affect outcomes is the type of brain or spinal cord tumor (see Introduction).

The 5-year relative survival rate for people younger than age 15 is about 75%. For people age 15 to 39, the 5-year relative survival rate nears 72%. The 5-year relative survival rate for people age 40 and older is 21%.

Experts measure relative survival rate statistics for a brain tumor every 5 years. This means the estimate may not reflect the results of advancements in how a brain tumor is diagnosed or treated from the last 5 years. Talk with your doctor if you have any questions about this information. Learn more about understanding statistics.

Statistics adapted from the American Cancer Society’s publication, Cancer Facts & Figures 2023; the ACS website; the CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2015-2019, published October 2022; the International Agency for Research on Cancer website; and the National Cancer Institute website. (All sources accessed February 2023.)

The next section in this guide is Risk Factors. It describes the factors that may increase the chance of developing a brain tumor. Use the menu to choose a different section to read in this guide.

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Brain Tumor: Grades and Prognostic Factors

Approved by the Cancer.Net Editorial Board, 03/2023

ON THIS PAGE: You will learn about how doctors describe a brain tumor’s growth or spread. This is called the grade. You will also learn about the prognostic factors doctors use to help plan treatment. Use the menu to see other pages.

What is cancer staging?

For most other types of tumors in other parts of the body, a staging system is used to describe where a tumor is located, if or where it has spread, and whether it is affecting other parts of the body. However, there is no recommended systemic staging system for adult brain tumors because most primary brain tumors do not usually spread beyond the central nervous system (CNS). The grading system described below is always used instead because the specific features of a brain tumor determine how cancerous it is and how likely it is to grow.

Prognostic factors

To decide on the best treatment for a brain tumor, both the type and grade of the tumor must be determined. There are several factors that help doctors determine the appropriate brain tumor treatment plan and a patient’s prognosis, which is the chance of recovery:

• Tumor histology. As outlined in the Diagnosis section, a sample of the tumor is removed for analysis. Tumor histology includes finding out the type of tumor, the grade, and additional molecular features that predict how quickly the tumor can grow. Together, these factors will help your doctor understand how the tumor will likely behave. These factors may also help determine your treatment options.

  Prior to 2021, brain tumors were defined by grades (1 to 4) based on how the tissue looked under a microscope. This grade indicated whether a tumor was growing slowly or quickly. As described in the Introduction, in 2021 the World Health Organization released a new classification and grading system that uses specific features to describe whether a tumor will grow slowly or quickly. These features include whether there is an IDH mutation, high rate of cell division (called the mitotic index), alterations in the CDKN2A/B genes, loss of chromosome 10, gain of chromosome 7, a TERT promoter mutation, and increased number of copies of the EGFR gene.

• Age. In adults, a person’s age and level of functioning, called functional status (see below), when diagnosed is one of the best ways to predict a patient’s prognosis. In general, younger adults have a better prognosis.

• Symptoms. The symptoms a patient has and how long they last may also help determine prognosis. For example, seizures and having symptoms for a long time are linked with a better prognosis.

• Extent of tumor residual. Resection is surgery to remove a tumor. Residual refers to how much of the tumor remains in the body after surgery. A patient’s prognosis is better when all of the tumor can be surgically removed. Whenever possible, surgery to remove all or most of the tumor should be considered if the surgical team and the patient feel the risk of such a surgery is acceptable. There are 4 classifications:

  • Gross total: The entire tumor that could be seen was removed. However, microscopic cells may remain.

  • Near total or subtotal: Large portions of the tumor were removed.

  • Partial: Only part of the tumor was removed.

  • Biopsy only: Only a small portion was removed and used for diagnostic tests.

• Tumor location. A tumor can form in any part of the brain. Some tumor locations cause more damage than others, and some tumors are harder to treat because of their location.

• Molecular features. Certain genetic mutations or changes to the genes found in the tumor may help determine prognosis. These include: IDh2, IDh3, MGMT, BRAF, h4K27M, and a 1p/19q codeletion. Sometimes, whether a tumor has any of these mutations or changes determines the type of brain tumor that is diagnosed.

• Functional neurologic status. The doctor will test how well a patient is able to function and carry out everyday activities by using a functional assessment scale, such as the Karnofsky Performance Scale (KPS), outlined below. A higher score indicates a better functional status. Typically, someone who is better able to walk and care for themselves has a better prognosis.

  • 100: Normal, no complaints, no evidence of disease

  • 90: Able to carry on normal activity; minor symptoms of disease

  • 80: Normal activity with effort; some symptoms of disease

  • 70: Cares for self; unable to carry on normal activity or active work

  • 60: Requires occasional assistance but is able to care for needs

  • 50: Requires considerable assistance and frequent medical care

  • 40: Disabled, requires special care and assistance

  • 30: Severely disabled; hospitalization is indicated, but death not imminent

  • 20: Very sick, hospitalization necessary; active treatment necessary

  • 10: Approaching death, fatal processes progressing rapidly

• Metastatic spread. A tumor that starts in the brain or spinal cord, even if cancerous, rarely spreads to other parts of the body in adults, but it may grow within the CNS. For that reason, with few exceptions, tests looking at the other organs of the body are typically not needed. A tumor that does spread to other parts of the brain or spinal cord is linked with a poorer prognosis.

• Recurrent tumor. A recurrent tumor is one that has come back after treatment. If the tumor does return, there will be another round of tests to learn about the extent of the recurrence. These tests and scans are often similar to those done at the time of the original diagnosis.

Currently, the factors listed above are the best indicators of a patient’s prognosis. As discussed in Diagnosis, researchers are currently looking for biomarkers in the tumor tissue that could make a brain tumor easier to diagnose and allow for the staging of an adult brain tumor in the future. Researchers are also looking at other genetic tests that may predict a patient’s prognosis. These tools may someday help doctors predict the chance that a brain tumor will grow, develop more effective treatments, and more accurately predict prognosis.

Used with permission of the American College of Surgeons, Chicago, Illinois. The original and primary source for this information is the AJCC Cancer Staging Manual, Eighth Edition (2017), published by Springer International Publishing.

Information about the tumor’s grade, as well as the prognostic factors, will help the doctor recommend a specific treatment plan. The next section in this guide is Types of Treatment. Use the menu to choose a different section to read in this guide.

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Brain Metastases – Diseases

Gamma Knife

Modern treatment technologies prolong life for cancer patients. This leads to the fact that patients “live” to metastasize to those organs and systems that are not quite typical for this pathology.

The peculiarity of the CNS lesion is an extremely unfavorable prognosis, which forces clinicians to carry out urgent therapeutic measures because of this, even in the presence of dissemination of the process and multiple lesions of other organs and tissues. However, timely and multicomponent treatment, taking into account individual indications, can prolong the life of patients for many months and even years. At the same time, rapid diagnosis and the choice of treatment tactics – radiation and chemotherapy, targeted agents and angiogenesis inhibitors, as well as surgical intervention, if necessary, are of particular importance.

Currently, there are no standards for providing care to this category of patients, and treatment is carried out empirically, depending on the training and individual characteristics of the doctor.

The condition of this category of patients is characterized by instability, a high risk of developing cerebral edema, especially in connection with the start of radiation therapy. This requires preventive administration of glucocorticoids, usually dexamethasone at a dose of 8–36 mg/day.

With severe symptoms, the appointment of 20 mg or more, followed by a decrease to 4 mg 2 times a day, is accompanied by a regression of neurological pathology and pain. However, despite the positive effect in terms of relief of neurological symptoms, patient survival and response rates to ongoing anticancer therapy do not change.

With steroid therapy alone, life expectancy does not exceed 2 months, radiation therapy increases it to 5, and the combination of radiation and chemotherapy allows to achieve an average survival of about 6-9 months. The average life expectancy of patients with a high Karnovsky index, the absence of meningeal and extracranial spread, as well as with a limited extracerebral process amenable to antitumor therapy, can reach a year or more. Indications for surgical intervention are infratentorial lesions with signs of ataxia and large solitary metastases (especially cystic structure) located in the hemisphere. When radiation therapy is combined with excision of metastases, long-term survival rates of patients improve, which is also observed in the case of high-dose precision irradiation (gamma and cyber knife). With multiple lesions and the need to irradiate the entire volume of the brain, fractionation modes do not play a significant role.

The main approach in conventional radiotherapy for brain metastases is to irradiate the entire volume of the brain, usually in an accelerated mode, although randomized trials in this direction are ongoing. Prior to the introduction of this highly effective radiotherapy technique into everyday clinical practice at the turn of the 1950s. the median survival of this group of patients did not exceed 1-2 months. In most situations, to prevent edema during the first few days of exposure, it is necessary to prescribe dexamethasone at 12-30 mg, followed by a sharp dose reduction by half.

Two lateral opposing fields are used. Particular attention is paid to the adequacy of including the base of the skull and the posterior cranial fossa in the scope of exposure. In this case, either the eyes are shielded or the fields are unfolded in accordance with the projection of the base of the skull so that the lower boundaries are located at the level of the II cervical vertebra. The calculation is carried out on the median plane. As a rule, a pronounced regression of metastases and relief of neurological symptoms are observed. At the same time, in accordance with the recommendations of the IAEA, it is practiced to increase the ROD to 4 Gy from the point of view of economic feasibility, since the fractionation regimes do not significantly affect the long-term prognosis. It should be taken into account that a significantly accelerated fractionation, in contrast to the traditional dose of 30 Gy in 10 sessions, may be accompanied by an increased risk of new intracerebral metastases due to a lower total physical absorbed dose. However, the standard approach in most clinics remains daily irradiation of the entire volume of the brain at a dose of 3 to 30-33 Gy. The fear of long-term complications of this type of treatment is often exaggerated given the life expectancy of patients. Impairment of cognitive functions in patients with total brain irradiation is noted immediately after the start of radiation therapy. This persists after the end of treatment, but it is limited only by verbal memory and should not serve as a reason for refusing treatment.

The presence of single metastases implies a local addition directly to the lesions up to doses equivalent to 50-60 Gy, usually in an accelerated fractionation regime. With a small number of metastases (1-3), local conformal hypofractional irradiation is acceptable (ROD 5-6 Gy, SOD 18-30 Gy). Particular attention should be paid to simultaneous or synchronous chemoradiotherapy. Violation of the permeability of the hematological barrier due to tumor growth and / or surgical intervention leads to a rapid regression of metastases when cytostatics are prescribed against the background of radiation treatment. At the same time, good results are achieved with the use of drugs traditionally used for these nosological forms, despite their supposedly poor penetration through the BBB. Nitrosourea preparations – lomustine, carmustine, fotemustine (mustoforan) are actively tested within the framework of synchronous chemoradiotherapy. In recent years, encouraging results have been obtained with the use of temozolomide (Temodal), which was originally intended for the treatment of malignant gliomas.

In the case of stereotactic radiation exposure, a single irradiation of metastases is carried out at a dose of 20-30 Gy. Indications for this method are a limited number of deposits (not more than 5-10), their maximum size is not more than 3-4 cm, the absence of a pronounced mass effect and occlusive hydrocephalus. In a certain sense, stereotactic irradiation competes with surgery when these techniques are combined with total brain irradiation. The best results with stereotaxic radiosurgery are achieved in the case of small foci, whose diameter does not exceed 1.5-2 cm. In this case, an increase in indentation from the edge of the tumor over 1 mm does not lead to an increase in the effectiveness of irradiation. Such tactics can be used even with an increase in the number of metastases and their localization in vital areas – the brain stem and cavernous sinus. The median survival for irradiation with a gamma knife varies from 5-6 months for melanoma metastases to a year or more for renal cell carcinoma. Focal brain damage without a primary detected tumor is accompanied by the worst results of treatment, survival does not exceed 3 months. However, in the absence of extracranial metastases and systemic chemotherapy, acceptable rates are sometimes achieved. In some centers, surgical removal of metastases is accompanied by the installation of a system with radioactive iodine-125 (GliaSite) or a sponge with chemotherapy drugs (nitrosourea, anthracyclines) in the postoperative cavity. At the same time, a combination of these methods with total brain irradiation is very promising. The addition of irradiation of the entire brain volume with stereotactic radiosurgery and/or surgery can increase the median survival rate by 1.5-2 times. However, researchers do not stop arguing about the advisability of combining postoperative stereotaxic irradiation with a total effect on the brain. The combination of stereotactic and total brain irradiation does not greatly affect the survival of patients compared to local exposure alone, however, the frequency of detection of new foci is reduced by about 1. 5 times. Total brain irradiation is an adequate method for both independent treatment of CNS metastatic lesions and in combination with stereotactic irradiation. It is primarily indicated for multiple lesions and poor general condition of the patient. In the case of resection of single metastases or radiosurgery, total cranial irradiation is a reasonable adjunct in most clinical situations.

With the progression of the process and the appearance of new metastases in the brain, its repeated total irradiation is possible. The indications are good efficacy and tolerability of the first course, a period of at least 6 months after the previous radiation exposure and a satisfactory general condition of the patient. With repeated exposure, the frequency of complete and partial responses can reach 70%. Some authors call for wider use of stereotactic radiosurgery in these cases.

Irradiation of patients with metastatic lesions of the spinal cord and / or spine with the transition to the nervous structures is carried out according to the same principles. Usually, a posterior direct vertebral field or two paravertebral ones are used at angles with the capture of the transverse processes of the vertebrae and indents from the boundaries of the lesion in the craniocaudal direction of about 2 cm. Radiation therapy is carried out in an accelerated mode – 3 Gy × 10 times, 4-5 Gy × 4-5 times daily or (on an outpatient basis) 2-3 sessions per 1 week. Since economically feasible fractionation regimens for bone metastases have been developed, there is a clear trend towards a single irradiation of the spinal cord at a single absorbed dose of 8 Gy. At the same time, its effectiveness in terms of relief and prevention of pain and neurological (spinal cord compression) syndromes does not differ from fractionated. If necessary, repeated exposure is possible. A change in the tactics of treating this unfavorable group of patients using a combination of methods led to an increase in the average life expectancy to 1.5-2 years or more with a relatively torpid course of the underlying disease. Currently, general practitioners should consider patients with brain metastases to be actively treated, and not just symptomatic medical radiotherapy.

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Results of treatment of patients with metastatic brain lesions

intracerebral metastases, in contrast to primary brain tumors. Brain metastases account for 20–30% of all intracranial neoplasms [1]. In the United States, according to various authors, about 170,000–200,000 new cases of brain metastases are detected annually, and this figure is growing year by year [2]. This fact is associated both with the improvement of imaging methods in the form of the use of such informative studies as computed and magnetic resonance imaging (CT and MRI), and with an increase in the life expectancy of cancer patients, which provides a period of time for the development of metastatic foci. Statistical studies conducted by the United States have shown that the lifetime diagnosis of metastases in the general population of adult cancer patients is 9.6%, according to autopsies – 24-45% [2-4]. The frequency of deaths from brain metastases reaches 70,000 per year [5]. The average life expectancy of patients with brain metastases is 5-9.5 months, the number of patients who survived 1 year after the detection of brain metastases does not exceed 40%, the 5-year survival rate is 10%, complete recovery is observed in isolated cases [ 6].

60% of all metastatic tumors are diagnosed in patients aged 50-70 years, which coincides with the peak incidence of malignant neoplasms [7]. At the same time, in pediatric oncology, metastatic brain tumors occur only in 6–12.5% ​​of patients (sarcomas, neuroblastomas, and embryonic tumors metastasize most often) [8, 9].

The three most significant factors play a role in the pathogenesis of metastasis: the accumulation of changes in the metastasizing cell, the presence of a favorable microenvironment of the target organ, and the completion of a complex cascade of molecular biological events called the “metastatic cascade” [10]. Metastasis to the brain is carried out by the hematogenous route. About 20% of cardiac output enters the vessels of the brain, explaining the highest frequency of lung tumor metastasis. Most metastases occur at the border between the gray and white matter, where the diameter of the vessels is significantly narrowed, which contributes to tumor embolism (the only exception is melanoma, whose metastases develop mainly in the gray matter) [11, 12]. The cerebral blood flow washes mainly the hemispheres (80%), then the cerebellum and the brain stem. Therefore, in 85% of cases, intracerebral metastases are found in the cerebral hemispheres, 10-15% in the cerebellum, and 3% in the brain stem [11]. Extremely rarely, metastases are found in the vascular plexus, pineal gland, pituitary gland, and optic nerve. A separate problem is carcinomatosis of the meninges, when metastases develop in the meninges, are detected during routine or flowing examination of the cerebrospinal fluid and metastasize inside the central nervous system.

Intracranial metastases usually develop as well-demarcated rounded nodules, which allows for conditionally radical surgery. Activated microglial cells, tissue macrophages, form a clear border in the form of a shaft between the tumor and the brain substance [13]. Metastasis is often surrounded by a zone of edema as a result of a violation of the blood-brain barrier in the tumor. Proteins penetrate from the tumor tissue into the surrounding substance of the brain and increase its water content. Edema is promoted by increased vascular permeability as a result of the action of vasoendothelial growth factor [14].

Changes in metabolic reactions in the perifocal tissue surrounding metastases were found, which are manifested by a decrease in the concentration of antioxidants (vitamins, A and E) and an increase in the concentration of lipid peroxidation products. The depth of disturbance of the free radical metabolism of the tissue surrounding the metastasis depends on their number and the nature of the primary tumor [15].

The course of the disease in metastatic brain lesions is most often acute with a rapid onset and increase in the symptom complex of damage to cerebral structures, which is typical for a stroke-like variant of the development of brain tumors.

Differential diagnosis in metastatic brain lesions is carried out with abscesses, primary brain tumors, CNS lymphomas, demyelinating and inflammatory changes. The basis of the differential diagnosis is anamnesis (for example, a single volumetric formation in the brain in a patient with an oncological history in 95% of cases is a metastasis, and only in 5% of cases is a primary neoplasm) [7] and an MRI picture.

In MRI, metastatic foci are best visualized on T2-weighted images [16]. They have an isointense appearance in relation to the brain tissue, but in the T2 mode, the perifocal edema well outlines the affected area (Fig. 1b). On T1-weighted tomograms (Fig. 1, a), metastases are isointense or slightly hypointense in relation to the white matter of the brain and are practically not visualized. In metastatic tumors, regardless of size, central necrosis can be determined, hypointense in T1 mode and hyperintense in T2 mode. With intravenous contrast enhancement, a pronounced increase in the intensity of the signal from tumors is noted (Fig. 1c).

Rice. 1. Magnetic resonance imaging of a patient with a solitary metastatic brain lesion. a — T1-weighted image. The focus is isointense; b — T2-weighted image. The focus is isointense and surrounded by a zone of perifocal edema; c — T1-weighted image with additional contrast enhancement. Pathological tissue that accumulates a contrast agent is clearly demarcated from unaffected brain tissue.

The gold standard for diagnosing brain metastases is intravenous contrast-enhanced MRI, which assesses the location, nature, and number of both supratentorial and subtentorial lesions of the medulla.

Despite such high rates of brain metastases, there is currently no consensus on the tactics of treating these patients.

Patients with intracerebral metastases, according to the canons of oncology, belong to the group of oncological patients with distant metastases, which requires an integrated approach to their treatment. The choice of the optimal method for the treatment of tumor metastases of various histological structures, localization, and prevalence of the extracranial process is a completely unsolved problem. Improving the quality of life, rapid regression of neurological symptoms and achieving local control are the direct tasks of the neurosurgical service.

Currently, there are no factors that adversely affect the prognosis of the disease, the knowledge of which would allow us to evaluate the possible effectiveness of the planned treatment at the prehospital stage.

The aim of this work was to summarize the experience of treating patients with brain metastases and to assess the impact on overall and relapse-free survival of such factors as the histological structure of the primary tumor, the number of metastases and their localization, control of the primary focus and extracranial metastases.

Material and methods

MNIOI them. P.A. Herzen from 2007 to 2013, 268 patients with brain metastases were treated. The average age of patients was 55.8 years (from 24 to 81 years), there were 138 (51%) men and 130 (49%) women. The distribution of patients by nosology is shown in Fig. 2. Lung cancer most frequently metastasized to the brain — 90 (34%) patients, breast cancer — 71 (26%), kidney cancer — 30 (11%), colorectal cancer — 21 (7.8%) patients. Other nosologies accounted for 11% of patients.

Rice. 2. Distribution of patients by primary focus.

According to RTOG 1997, all patients with intracerebral metastases are divided into three classes [Recursive partitioning analysis (RPA) of prognostic factors] depending on the Karnofsky index, controllability of the primary disease, age, and the presence of extracranial lesions [17] (see table). In our study, 68 (25.37%) patients belonged to the 1st class, 136 (50.75%) patients to the 2nd class, and 65 (24. 25%) patients to the 3rd class.

RPA class definition

In 185 (69%) patients, metastases were found in the cerebral hemispheres, in 48 (17.9%) patients, the cerebellum was affected, and in 33 (12.3%), multiple lesions were detected.

It should be noted that in 66 (24.6%) patients there was a synchronous detection of the primary tumor and brain metastasis, i.e. the metastatic lesion was the first manifestation of the tumor process. In patients with metachronous detection of intracerebral metastasis [2 months or more – 202 (75.4%) patients], the average time since the diagnosis of the primary tumor was 39months (2–245 months).

Before starting treatment, all patients underwent a comprehensive examination. An MRI of the brain with intravenous contrast enhancement was performed (in the presence of contraindications, CT with intravenous contrast enhancement was performed). Solitary metastasis was diagnosed in 164 (61.19%) patients, oligometastases (2—3) — in 72 (26. 87%) patients, multiple metastases (more than 3) — in 32 (11.94%) patients. Extracranial metastases were detected in 162 (60.45%) patients. For 106 (39.55%) patients, brain metastasis was the only manifestation of the generalization of the process. In 17 (6.3%) patients, a primary multiplicity of tumors was noted.

All patients at the first stage underwent surgical treatment in the conditions of the neurosurgical department of the Moscow Research Institute of Optics. P.A. Herzen with the use of microsurgical technique for a metastatic intracerebral tumor.

Fluorescent diagnostics (FD) was used in 93 (34.7%) patients to control the radicalness of tumor resection. In 66 (24.6%) patients, a session of photodynamic therapy (PDT) was performed intraoperatively. In all observations for PD and PDT, the drug alasens (5-aminolevulinic acid hydrochloride – 5-ALA) was used, produced by FGU “SSC NIOPIK” according to the one developed at the Moscow Research Institute of Orthopedics. P.A. Herzen method [18]. 5-ALA is a precursor of heme, which, when excessively introduced into the patient’s body, causes the synthesis and accumulation of endogenous fluorochrome – protoporphyrin IX in tumor cells. Alasens was administered to all patients by oral administration at a dose of 20 mg/kg 2–2.5 hours before the onset of intubation anesthesia (3–4 hours before PD and PDT). For visual study of fluorescence, a D-Light AF System (Karl Storz, Germany) and a Karl Zeiss operating microscope were used. For PDT, an ALOD-01 semiconductor laser (Russia) with a wavelength of 635 nm was used.

Radical control was assessed by MRI or CT with intravenous contrast enhancement. In 212 (79.1%) patients, the removal of the metastasis was performed totally, in 55 (20.9%) — subtotally.

Results

The tactics of further treatment was developed collectively on the basis of Russian and international clinical recommendations. Patients continued treatment as in the MNIOI them. P.A. Herzen, and in other specialized institutions. The observation period for patients ranged from 3 to 79months The fate of patients was monitored by telephone messages and according to oncology dispensaries. By the time of publication, 88 (32.8%) patients are alive, 180 (67.2%) have died. In 120 (66.7%) patients, the cause of death was the generalization of the tumor process, in 25 (13.8%) – non-oncological diseases. It should be noted that 11 (6.1%) patients died from recurrence of brain metastasis and 24 (13.3%) from the appearance of new lesions in the brain.

The results were analyzed using standard statistical processing techniques (Statistica 10 software). Median overall survival in the group of patients with brain metastases was 12 months (Fig. 3).

Rice. 3. Median overall survival depending on the primary tumor (Kaplan-Meier method).

Median overall survival depended on the primary tumour. Thus, the longest survival was observed in patients with lung cancer (16 months), the results of treatment of patients with metastases of breast cancer (12 months) and kidney cancer (12. 4 months) seem to be quite good. Low overall survival rates were noted for melanoma (7 months), colorectal cancer (8.3 months), metastases from an undetected primary focus (5 months).

Overall survival significantly depended on RPA class ( p = 0.06508). So, if in the RPA of the 1st grade it was 14 months, then in the RPA of the 2nd and 3rd – 12 and 9 months, respectively (Fig. 4).

Rice. 4. Overall survival depending on the RPA class (Kaplan-Meier method).

Recurrence in the surgical area was detected in 58 (21.6%) patients. Relapse-free survival (median 11.0 months) significantly depended on the PDT used ( p = 0.00018). Dependence on PD is not significant ( p \u003d 0.14754) (Fig. 5). The median survival for synchronous detection of the primary tumor and brain metastasis was 10.5 months, for metachronous detection – 12 months.

Rice. 5. Median relapse-free survival depending on the use of PDT (Kaplan-Meier method).

We analyzed survival rates after the most common treatment options. Thus, the median overall survival of patients who did not receive any other type of therapy after surgical treatment (44 patients, 16.4%) was only 4 months. When using combined treatment (surgical treatment + radiation therapy), the median survival was 9—10.5 months (depending on the irradiation method). With drug treatment, the median overall survival was 11 months. With complex treatment, i.e. the use of chemotherapy and radiation therapy, survival rates were the highest – 12 months (Fig. 6).

Rice. 6. Median overall survival depending on the method of subsequent treatment (Kaplan-Meier method).

Relapse-free survival without additional treatment was only 3 months. After irradiation, it is significantly ( p \u003d 0.00024) increased to 7.5 months, after drug treatment – up to 11 months. With complex treatment, relapse-free survival was 9 months (Fig. 7).

Rice. 7. Median relapse-free survival depending on the method of subsequent treatment (Kaplan-Meier method).

Based on our own experience, we believe that rational surgery for brain metastases can be considered the method of choice, which allows to increase the duration and improve the quality of life of operated patients.

This allows us to treat surgical treatment as the main method in combination therapy. Undoubtedly, the problem of brain metastasis is more biological than surgical, and the total removal of the lesion does not indicate a patient’s recovery.

Factors affecting overall survival are the characteristics of the histology of the primary lesion, the multiplicity of metastatic lesions, the RPA class, and the synchronous nature of metastasis.

Only in 19.44% of cases, the cause of death of patients was an intracranial lesion. The best survival rates are observed in patients who received systemic therapy to control the extracranial process and radiation therapy to control intracerebral metastases.