Case Study 3 Cns Cancer

Case presentation – A five-year survival of the patient with glioblastoma brain tumor

Hubert Urbańczyk,a,Anita Strączyńska-Niemiec,bGrzegorz Głowacki,aDariusz Lange,b and Leszek Miszczyka

aCentrum Onkologii, Instytut im. Marii Skłodowskiej-Curie, Oddział w Gliwicach, Zakład Radioterapii, Poland

bCentrum Onkologii, Instytut im. Marii Skłodowskiej-Curie, Oddział w Gliwicach, Zakład Patologii Nowotworów, Poland

Hubert Urbańczyk: lp.eciwilg.oi@trebuh: moc.liamg@kyzcnabru.a.trebuh

Corresponding author at: Centrum Onkologii, Instytut im. Marii Skłodowskiej-Curie, Oddział w Gliwicach, Zakład Radioterapii, 44-101 Gliwice, ul. Wybrzeże Armii Krajowej 15, Poland. Tel.: +48 609 139840. lp.eciwilg.oi@trebuh, moc.liamg@kyzcnabru.a.trebuh

Author information ►Article notes ►Copyright and License information ►

Received 2013 Jan 31; Revised 2014 Feb 27; Accepted 2014 Apr 5.

Copyright © 2014 Greater Poland Cancer Centre. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

This article has been cited by other articles in PMC.

Abstract

This paper presents an atypical case of a patient with brain tumor of the glioblastoma multiforme (GBM) type who achieved a 5-year survival. Some general information is provided including epidemiology, diagnostic and treatment procedures (surgery and radio-chemo-therapy), and prognosis of survival related to GBM. The course of the disease, including its main symptoms, individual reasons for the delay of adjuvant treatment, after the primary surgical treatment, 37-month period of the decease free survival, as well as comprehensive management after the tumor recurrence are also presented. Histopathology confirming the clinical diagnosis is discussed in a separate chapter.

Keywords: Glioblastoma, Survival, Brain tumors, Treatment, Radiotherapy

1. Background

Primary brain tumors account for about 2% of all malignant neoplasms in adults. Approximately a half of them represent gliomas, derived from neuroepithelial cells, among which glioblastoma (GBM) is the most common type.

GBM cases represent about 20% of all primary brain tumors in the adult population, and about 75% of all the anaplastic gliomas.1 The prevalence of GBM is about 2–4 cases per 100,000. It is more common in men than in women, and its incidence increases with age.2 Only sporadically, GBM can be found in individuals younger than 20 years of age, and its frequency rapidly increases, starting from the 5-th decade of life.

The treatment results of patients diagnosed with GBM are often unsatisfactory, and the outcome is usually poor. Currently, the main standard therapeutic methods include a radical surgical procedure, combined with radio-chemo-therapy. Some innovative methods of radiotherapy based on the application of novel radiosensitizers of corpuscular irradiation or radio-immune-therapy are now being investigated. A median survival time of patients diagnosed with GBM, treated only with the use of neurosurgical procedures are 3–5 months. The application of conventional adjuvant radiotherapy prolongs this average time about 3-fold, with a three-year survival for only about 6% of patients.

The post-treatment survival time depends on many clinical factors, such as general patient condition, age, and histopathological type of the tumor. Simson et al. demonstrated statistically significant longer survival periods among patients in whom the primary tumor location was in the frontal lobe, in comparison to the ones in whom it was located in the parietal or temporal cerebral region (11.4 months vs. 9.6 months vs. 9.1 months, respectively; p = 0.01).3 Severity of neurological symptoms, limits of the performed surgical procedures, and response to the applied therapy, based on imaging tests, also represent prognostic factors.

Etiology of malignant neoplasms of the central nervous system (CNS) is still unknown. The most common of many probable carcinogens include: nitrosamines, pesticides, herbicides, petrochemical substances, polyvinyl chloride, and electromagnetic irradiation. However, the role of these pro-carcinogenic factors has not been unequivocally proven.4,5 In contrast, it has been documented that patients exposed to ionizing irradiation have an increased risk of the CNS malignant gliomas. According to the current state of knowledge in the field of molecular biology and genetics of these malignancies, two main hypotheses related to their development have been proposed. The first one includes de novo creation which is related to the loss of heterozygotic properties in chromosomes 9p, 10, 17p, and with the amplification of genes for the EGFR and CDK4 (this type of malignant growth occurs more often in older patients). The second one involves the creation of anaplastic gliomas, through the progression of gliomas with a lower malignancy grade (encountered more often in younger patients).6,7

Currently, a required standard of therapy for patients with GBM is a combined treatment, including tumor resection, with following concomitant radio-chemo-therapy, and adjuvant chemo-therapy, based on Temozolomide. In patients who undergo non-radical surgery, or who are not treated surgically, the palliative whole brain radiotherapy (WBRT), stereotactic radiation surgery (SRS), or combination of both of these therapeutic methods are used. Also, the application of palliative chemotherapy and symptomatic treatment remain important. In addition, alternatively fractionated radiotherapy, brachytherapy, targeted molecular therapy, radio-immune-therapy, hadrone therapy, or radio-sensitizers can be considered in individual cases.

In 2005, Stupp et al. presented results of a randomized study conducted by EORTC (European Organization for Research and Treatment of Cancer) and NCIC (National Cancer Institute of Canada), comparing the application of combined radio-chemo-therapy based on Temozolomide and radical radiotherapy alone. The combined management in a statistically significant manner prolonged the total survival time from 12.1 to 14.6 months, and the rate of 2-year survival was 26.5%, compared to 10.4% for radiotherapy alone.8 The follow-up results, after a longer period of observation, confirmed the previous reports. The 2-, 3-, and 4-year survival rates were 27.3%, 16.7%, and 12.9%, respectively (p < 0.0001) in the patients’ group treated with a combined therapy, and 11.2%, 4.3%, and 3.8%, in the patients’ group treated with radiotherapy only.9

Unfortunately, despite the use of Temozolomide, the results are unsatisfactory. The reason for this therapeutic failure is the GBM resistance to most chemotherapeutic agents or rapid development of the GBM as a result of genetic transformations within the tumor cells. The main mechanism of the GBM resistance to alkylating agents, such as temozolomide, procarbazine, or nitrogen mustard derivatives, is the repair of damages caused by these drugs with involvement of protein coded by MGMT (O6-methyl-guanine-DNA methyl-transferase) gene.

A degree of methylation of the promoter's region of MGMT gene appears to be closely correlated with a therapeutic response of the glioma cells. Hypermethylation of this part of the gene significantly increases treatment efficacy among patients treated with Temozolomide,10 influencing their survival period, as well.9

2. Case presentation

The patient is a 38 year old Caucasian male, smoker (about 10–15 cigarettes per day for 20 years), without other relevant family or personal risk factors for neoplasic disease who had suffered from severe headaches and nausea (his first disease symptoms) since August of 2005. He did not seek any medical help until November of 2005, when he presented to his doctor, due to exacerbation of those symptoms. No abnormalities on both physical and neurological examinations were detected at that time.

On December 30th of 2005, the CT scan of his brain was remarkable for the following findings: “An expansive lesion of approximately 5 cm × 3 cm in size, located in the right temporal lobe, with nonhomogenic, post-contrast signal amplification. A large edema surrounding the lesion. A compression of the occipital corner of the right lateral ventricle. A slight enlargement of the supratentorial ventricular system, shifting to the left.”

On January 25th of 2006, the patient underwent surgical therapy, including right temporal craniotomy, with total resection of the tumor. On February 7th of 2006, a histopathology examination (identification number 475,958; Info-Pat, Poznań, Poland), confirmed a diagnosis of the GBM IV stage (according to WHO classification). Microscopic images of the tumor are presented (Figs. 1–5).

Fig. 1

Microscopic image of patient's tumor.

Fig. 2

Microscopic image of patient's tumor.

Fig. 3

Microscopic image of patient's tumor.

Fig. 4

Microscopic image of patient's tumor.

Fig. 5

Microscopic image of patient's tumor.

After the surgery, the patient was referred to the Institute of Radiation Oncology in Gliwice, Poland, for the post-operative radiotherapy. Although the patient was qualified for this treatment, he did not arrive to the Institute of Radiation Oncology on the day of the scheduled preparatory procedures. The reason for his absence was a simultaneous diagnostic finding of the left lung's tumor, for which the patient underwent a thoracotomy with the wedge tumor resection (for diagnostic purposes). On June 12th of 2006, based on the histopathological examination results, which showed post-tuberculosis lesions, the patient's pulmonary treatment was completed.

In February 2007, approximately 13 months after his brain tumor surgery, the patient again presented to the Institute of Oncology, and according to the follow-up diagnostic work-up, no brain tumor recurrence was found. Due to the absence of tumor, no radiotherapy was considered, and “watchful waiting” was recommended including brain imaging studies (CT or MRI) to be repeated every 3 months. In the face of the atypical disease course, an additional verification of the histopathological diagnosis was also performed, confirming the original findings of the GBM. The patient had remained under close control until February 2009 (37 months from his initial brain tumor surgery), and at that time the brain tumor recurrence was found. His recurrent tumor was located in the primary tumor's bed, and its size was 4 cm × 5.3 cm × 3.5 cm (Fig. 6). However, those findings were not associated with any particular symptoms or abnormalities on subsequent physical or neurological examinations of the patient. On March 16th 2009, the patient underwent another craniotomy with the subtotal tumor resection. (MRI scans after the second craniotomy are shown in Figs. 7 and 8.) The histopathology examination was again consistent with GBM. During the period from May 11th to June 19th of 2009, the patient received the radiotherapy dose of 60 Gy/30 fractions to the tumor lodge, including the residual tumor, with 2.5 cm of tissue margin. Due to the lack of the patient's consent, no chemotherapy was implemented. During the irradiation period, he had the first seizure episode, and was started on antiepileptic therapy (Depakine 200 mg a day). He continued this therapy for the rest of his life. After the radiotherapy, diagnostic follow-up examinations were conducted every 3 months. At the beginning of March 2010, another recurrence was found, and the tumor was localized in an upper part of the tumor bed, within the previously irradiated area (its size was 3.7 cm × 2.6 cm × 2.3 cm). Surprisingly, the patient had not experienced any symptoms, and his physical and neurological examinations were unremarkable. On March 13th of 2010, the stereotactic radiotherapy, using a single dose of 8 Gy applied to the area of recurrent tumor was performed. Unfortunately, on the control examination, on July 6th of 2010, further progression of the GBM was found. The patient expired on November 15th of 2010, in the local hospital (Zawiercie, Poland), due to the tumor expansion, resulting in cerebral edema, herniation, and multi-organ failure.

Fig. 6

CT scan of recurrence tumor.

Fig. 7

MRI scan after the second craniotomy.

Fig. 8

MRI scan after the second craniotomy.

3. Histopathology examination

On a histopathology specimen, the large areas of thrombotic necrosis, most probably caused by a large tumor size (5 cm × 3 cm) were found. In contrast, no “palisade” necrosis (with the characteristic palisade-like cell arrangements), typical for this type of tumor, was found.

Within vital tumor structures, a high cellular polymorphism was found. Besides some small calls (with hyperchromatic nucleus and scarce amount of cytoplasm), mostly atypical cells (giant, multisided or oval, with numerous nuclei with abnormal shapes, and visible nucleoli) were present. The cells revealed a strongly positive GFAP reaction that can be indicative of their glioma-type origin. Also, some distinctive GBM features, including proliferation of vascular endothelium (focal areas of numerous mitotic figures, in high power field – HPF), were visible. The described microscopic images are presented in Figs. 1–5 (the images of primary and recurrent tumors appear identical).

4. Summary

In this paper, we presented a remarkably long survival period (63 months since the initial onset of symptoms, and 58 months since the primary surgical treatment) of the GBM patient. An important message from our case study that could be useful in the management of many other GBM cases is that the initial complete resection suggests a beneficial role of radical neurosurgery in the early GBM treatment and potential survival period.

Unfortunately, we are unable to indicate the specific reasons for such a long survival of our relatively asymptomatic patient who experienced some disadvantages, including the second malignancy, which caused the delay in the application of his radiotherapy.

Nevertheless, it should be emphasized that personalized, patient-centered approach, using comprehensive diagnostic and therapeutic strategies, as well as vigilant, multi-level follow-up care, should be helpful in explaining different factors, contributing to overall survival. In addition, our single case presentation illustrates several challenges that are common to many GBM patients, and merit further, more individualized research on this devastating disease.

Conflict of interest

None declared.

Financial disclosure

None declared.

References

1. DeAngelis L. Anaplastic glioma how to prognosticate outcome and choose a treatment strategy. J Clin Oncol. 2009;27:5861–5862. [Editorial] [PubMed]

2. Klonowicz M., Spych M., Fijuth J. Postoperative radiochemotherapy – a new standard in treatment for glioblastoma? Onkol Prakt Klin. 2007;3:28–31.

3. Simpson J., Horton J., Scott C. Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials. Int J Radiat Oncol Biol Phys. 1993;26:239–244.[PubMed]

4. Thomas T., Steward P., Stemhagen A. Risk of astrocytic brain tumors associated with occupational chemical exposures: a case-referent study. Scand J Work Environ Health. 1987;13:417–423.[PubMed]

5. Wrensch M., Minn Y., Chew T. Epidemiology of primary brain tumors: current concepts and review of the literature. Neurooncology. 2002;4:278–299.[PMC free article][PubMed]

6. Van Meyel D., Ramsey D., Cassone A. p53 mutation, expression, and DNA ploidy in evolving gliomas: evidence for two pathways of progression. J Natl Cancer Inst. 1994;86:1011.[PubMed]

7. Lang F., Miller D., Koslov M. Pathways leading to glioblastoma multiforme. A molecular analysis of genetic alternations in 65 astrocytic tumors. J Neurosurg. 1994;81:427.[PubMed]

8. Stupp R., Mason W., van den Bent M. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–996.[PubMed]

9. Mirimanoff R., Mason W., Stupp R. Is long-term survival in glioblastoma possible? Updated results of the EORTC/NCIC Phase III Randomized Trial on radiotherapy (RT) and concomitant and adjuvant Temozolomide (TMZ) versus RT alone. Rad Oncol Biol Phys. 2007;69:S2.

10. Hegi M., Diserens A., Gorlia T. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352:997–1003.[PubMed]

Articles from Reports of Practical Oncology and Radiotherapy are provided here courtesy of Elsevier

World Health Organization (WHO) Updates Official Classification of Tumors of the Central Nervous System

On May 9, 2016, the World Health Organization (WHO) published an official reclassification of Tumor Types of the Central Nervous System, which has moved the greater neuro-oncology field toward a more precise and accurate system of brain tumor classification. Based on information from expert neuropathologists and neuro-oncologists, the result of the updated WHO classifications, which integrate molecular information with histology, is that doctors will be better able to more accurately diagnose, make prognoses, plan treatment, and predict therapeutic response for patients. A more precise diagnosis and treatment plan is a win for patients.

Since the advent of new technology and capabilities for genomic sequencing, and in particular the seminal Cancer Genome Atlas project funded by the National Institutes of Health, recent molecular studies on brain tumors have begun to reveal the vast diversity of genetic and epigenetic alterations that exist between brain tumors. This biological heterogeneity often means tumors that may, at first blush, appear to be the same, may actually require a different approach to treatment – as well as the converse (i.e. tumors that may look different under the microscope may have common molecular alterations). Further studies have also shown that molecular signatures in tumor cells can define different groups of brain tumor types with distinctive characteristics, and that analyzing a tumor for mutations or deletions in certain genes or regions of chromosomes, can provide a deeper level of understanding of each tumor’s make-up.

Thus, it was critical that molecular data be integrated into traditional histopathology approaches to reclassify brain tumor types more effectively.

New integrated classifications will also improve future research and the development of new treatments by ensuring that patients participating in clinical trials are comparable within and across trials, and patients in clinical trials are correctly stratified based on their molecular signatures with targeted therapies most likely to benefit them. Additionally, the updated classifications will help provide more accurate analysis and understanding of experimental studies in the lab, as well as better interpretation of population-based disease trends that may help identify causes and risk factors. In short, this move away from traditional histopathology alone, to integrated classification with molecular characteristics, moves the brain tumor field further into the era of medicines that are highly targeted for a particular brain tumor patient.

You can access the reclassification document HERE.

There are more than 120 types of brain and central nervous system (CNS) tumors. Today, most medical institutions use the World Health Organization (WHO) classification system to identify brain tumors. The WHO classifies brain tumors by cell origin and how the cells behave, from the least aggressive (benign) to the most aggressive (malignant). Some tumor types are assigned a grade, ranging from Grade I (least malignant) to Grade IV (most malignant), which signifies the rate of growth. There are variations in grading systems, depending on the tumor type. The classification and grade of an individual tumor help predict its likely behavior. This section describes the most frequently diagnosed types.

Click on the links below for more information on specific tumor types.

The following tumor types are more common in children than in adults:

Keep in mind that many tumors have different subtypes; for example, an astrocytoma can be a juvenile pilocytic astrocytoma, an anaplastic astrocytoma or a glioblastoma. In addition, the same tumors sometimes have different names; even pathologists are not always consistent in what they call them. Finally, it is important to note that nonmalignant, or benign, brain tumors can be just as difficult to treat as malignant brain tumors.

Acoustic Neuroma

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An acoustic neuroma is also known as a schwannoma, vestibular schwannoma, or neurilemmoma.

Characteristics

  • Arises from cells that form a protective sheath around nerve fibers
  • Typically grows around the eighth cranial nerve, but can be found around other cranial or spinal nerves

Symptoms

  • Hearing loss in one ear
  • Dizziness or vertigo
  • Tinnitus (ringing in the ear)
  • Tingling or numbness in the face
  • Walking and balance problems
  • Lack of coordination

Treatment

An acoustic neuroma may be observed in order to monitor its growth, or surgery may be performed. The goal of surgery is the complete removal of the tumor without harming the seventh cranial nerve (which controls facial movement) or causing hearing loss. Radiosurgery can be a viable option for many patients. This focused, high-energy radiation prevents the growth of acoustic neuromas, but actual shrinkage of the tumor may never occur or may take several months.

Grade I – Pilocytic Astrocytoma

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Also called Juvenile Pilocytic Astrocytoma (JPA)

Characteristics

  • Slow growing, with relatively well-defined borders
  • Grows in the cerebrum, optic nerve pathways, brain stem and cerebellum
  • Occurs most often in children and teens
  • Accounts for two percent of all brain tumors

Treatment

Surgery is the standard treatment. If the tumor cannot be completely resected, radiation or chemotherapy may be given. Chemotherapy may be given to very young children instead of radiation therapy to avoid damage to the developing brain. Some of these tumors can progress to a higher grade, so it is important to be diligent about following up with the medical team after treatment.

Grade II – Low-grade Astrocytoma

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An astrocytoma is a type of glioma that develops from star-shaped cells (astrocytes) that support nerve cells. The WHO classifies a low-grade astrocytoma as a grade II tumor.

Characteristics

  • Slow growing
  • Rarely spreads to other parts of the CNS
  • Borders not well defined
  • Common among men and women in their 20s-50s

Treatment

Treatment depends on the size and location of the tumor. The doctor will most likely perform a biopsy or surgery to remove the tumor. Partial resections or inoperable tumors may be treated with radiation. Recurring tumors may require additional surgery, radiation and/or chemotherapy.

Grade III – Anaplastic Astrocytoma

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An astrocytoma is a glioma that develops from star-shaped glial cells (astrocytes) that support nerve cells.  An anaplastic astrocytoma is classified as a grade III tumor.

Characteristics

  • Grows faster and more aggressively than grade II astrocytomas
  • Tumor cells are not uniform in appearance
  • Invades neighboring tissue
  • Common among men and women in their 30s-50s
  • More common in men than women
  • Accounts for two percent of all brain tumors

Treatment

Treatment depends on the location of the tumor and how far it has progressed. Surgery and radiation therapy, with chemotherapy during or following radiation, are the standard treatments. If surgery is not an option, then the doctor may recommend radiation and/or chemotherapy. Many clinical trials (experimental treatments) using radiation, chemotherapy, or a combination are available for initial and recurrent anaplastic astrocytomas.

Grade IV – Glioblastoma (GBM)

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Description and Location

Glioblastoma multiforme (GBM) is the most common and deadliest of malignant primary brain tumors in adults and is one of a group of tumors referred to as gliomas.

Classified as a Grade IV (most serious) astrocytoma, GBM develops from the lineage of star-shaped glial cells, called astrocytes, that support nerve cells.

GBM develops primarily in the cerebral hemispheres but can develop in other parts of the brain, brainstem, or spinal cord.

Because of its lethalness, GBM was selected as the first brain tumor to be sequenced as part of The Cancer Genome Atlas (TCGA Website), a national effort to map the genomes of the many types of cancer. In this effort, researchers discovered that GBM has four distinct genetic subtypes that respond differently to aggressive therapies, making treatment extremely difficult and challenging. Parallel research Parallel research at Johns Hopkins University also contributed to the expansion of genomic information on GBM.

 Characteristics:

  • Can be composed of several different cell types
  • Can develop directly or evolve from lower grade astrocytoma or oligodendroglioma
  • Most common in older individuals and more common in men than women
  • Less common in children
  • Median survival rate of ~15 months; 5-year survival rate of ~4%
  • The cause is unknown, but increasingly research is pointing toward genetic mutations

Incidence

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The incidence, or the number of new diagnoses made annually is 2 to 3 per 100,000 people in the United States and Europe. GBM accounts for 12% to 15% of all intracranial tumors and 50% to 60% of astrocytic tumors.

Treatment

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Standard treatment is surgery, followed by radiation therapy or combined radiation therapy and chemotherapy. If inoperable, then radiation or radiation/chemotherapy can be administered.

Treatment requires effective teamwork from neurosurgeons, neuro-oncologists, radiation oncologists, physician assistants, social workers, psychologists, and nurses. A supportive family environment is also helpful.

Surgery

GBM’s capacity to wildly invade and infiltrate normal surrounding brain tissue makes complete resection impossible. However, improvements in neuroimaging have helped to make better distinctions between tumor types and between tumor and normal cells.

Radiation

After surgery, radiation therapy is used to kill leftover tumor cells and try and prevent recurrence.

Chemotherapies, an Alkylating Agent, and a Medical Device

(identified by generic names)

Temozolomide

FDA-approved in 2005 for treatment of adult patients with newly diagnosed GBM

Bevacizumab

FDA-approved in 2009 for treatment of patients with recurrent GBM and prior treatment

Polifeprosan 20 with Carmustine Implant

FDA-approved in 1997 for treatment of initial occurrence GBM, an alkylating agent that is surgically implanted as a wafer after surgical resection and allows for drug delivery directly to the tumor site

TTF Device

FDA-approved in 2011 approved as a medical device for adult patients with recurrent GBM after surgery and chemotherapy treatment to deliver electric tumor-treating fields to the brain to physically break up the tumor cell membranes

Ongoing Research and Clinical Trials

Clinical Trials

A number of clinical trials are being conducted to search for GBM treatments. The National Cancer Institute maintains a website that lists these trials:

GBM Clinical Trials

The trials involve many types of therapy, including immunotherapy, antiangiogenic therapy, gene and viral therapy, cancer stem cell therapy, and targeted therapy (personalized medicine).

Chordoma

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Characteristics

  • Rare and low grade
  • Occurs at the sacrum, near the lower tip of the spine, or at the base of the skull
  • Originates from cells left over from early fetal development
  • Invades the bone and soft tissues but rarely the brain tissue
  • Can block the ventricles, causing hydrocephalus (water on the brain)
  • Can metastasize (spread) or recur

Symptoms

Treatment

Surgery and radiation therapy are the common forms of treatment. Chordomas at the base of the skull can be difficult to remove. Surgical resection may be possible if the tumor is located in the spine.

CNS Lymphoma

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CNS Lymphoma is a type of cancer that develops in the lymphatic system. The lymphatic system is a network of small organs called lymph nodes and vessels (similar to blood vessels) that carry a clear, watery fluid called lymph throughout the body. This fluid supplies cells called lymphocytes that fight disease and infection. To correctly diagnose primary CNS Lymphoma, staging must be done. Staging is the process of using CT scanning to examine many parts of the body. Staging helps to confirm where the cancer originated and how far it has spread.

Characteristics

  • Very aggressive
  • Usually involves multiple tumors throughout the central nervous system (CNS)
  • More common in people whose immune systems are compromised
  • Often develops in the brain, commonly in the areas adjacent to the ventricles
  • Can be primary (originating in the brain) or secondary
  • Most common among men and women in their 60s-80s, but incidence is increasing in young adults
  • More common in men than women
  • Accounts for about two percent of all brain tumors

Symptoms

  • Headaches
  • Partial paralysis on one side of the body
  • Seizures
  • Cognitive or speech disorders
  • Vision problems

Treatment

Radiation therapy, chemotherapy, and steroids are the most common forms of treatment. Surgery is rarely an option because there are usually multiple lesions. However, a biopsy at the start of steroid treatment can be critical to ensure the correct diagnosis.

Craniopharyngioma

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Characteristics

  • Most common in the parasellar region, an area at the base of the brain and near the optic nerves
  • Also grows in the regions of the optic nerves and the hypothalamus, near the pituitary gland
  • Tends to be low grade
  • Often accompanied by a cyst
  • Originates in cells left over from early fetal development
  • Occurs in children and men and women in their 50s and 60s

Symptoms

  • Headaches
  • Visual changes
  • Weight gain
  • Delayed development in children

Treatment

Surgery is the most common treatment. Radiation therapy may be used.

Brain Stem Glioma

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Characteristics

  • Named for its location at the base of the brain
  • Can range from low grade to high grade
  • Occurs most often in children between three and ten years of age, but can occur in adults

Symptoms

  • Headaches
  • Nausea
  • Speech or balance abnormalities
  • Difficulty swallowing
  • Weakness or numbness of the arms and/or legs
  • Facial weakness
  • Double vision

Symptoms can develop slowly and subtly and may go unnoticed for months. In other cases, the symptoms may arise abruptly. A sudden onset of symptoms tends to occur with rapidly growing, high-grade tumors.

Treatment

Surgery may not be an option because the brain stem controls vital life functions and can easily be damaged. Radiation therapy can reduce symptoms and help slow the tumor’s growth. Low-grade brain stem gliomas can have very long periods of remission.

Ependymoma

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Ependymal tumors begin in the ependyma, cells that line the passageways in the brain where cerebrospinal fluid (CSF) is produced and stored. Ependymomas are classified as either supratentorial (in the cerebral hemispheres) or infratentorial (in the back of the brain). Variations of this tumor type include subependymoma, subependymal giant-cell astrocytoma, and malignant ependymoma. Ependymoblastoma, which occurs in infants and children under three years, is no longer considered a subtype of ependymoma. For ependymoblastoma, see primitive neuroectodermal tumor (PNET) in the Non-glial Tumors section.

Characteristics

  • Usually localized to one area of the brain
  • Develops from cells that line the hollow cavities at the bottom of the brain and the canal containing the spinal cord
  • Can be slow growing or fast growing
  • May be located in the ventricles (cavities in the center of the brain)
  • May block the ventricles, causing hydrocephalus (water on the brain)
  • Sometimes extends to the spinal cord
  • Common in children, and among men and women in their 40s and 50s
  • Occurrence peaks at age five and again at age 34
  • Accounts for two percent of all brain tumors

Symptoms

  • Severe headaches
  • Nausea and vomiting
  • Difficulty walking
  • Fatigue and sleepiness
  • Problems with coordination
  • Neck pain or stiffness
  • Visual problems

Treatment

The doctor will perform tests to determine if it has spread to the spinal cord. Surgery followed by radiation therapy is the usual course of treatment. A shunt may be needed to treat hydrocephalus caused by blockage of the ventricles.

Additional Resources

Mixed Glioma

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A mixed glioma is often a combination of an astrocytoma and an oligodendroglioma (see oligodendroglioma for more).

Characteristics

  • Composed of two or more types of glioma cells
  • Graded according to the most aggressive type of tumor cells
  • Common among men and women in their 20s-50s
  • Accounts for one percent of all brain tumors

Symptoms

  • Headaches
  • Seizures
  • Weakness or paralysis
  • Nausea and vomiting
  • Visual problems
  • Behavioral and cognitive changes

Treatment

Mixed gliomas are generally treated for the most anaplastic (cancerous) type of cell found in the tumor. For example, in the case of a tumor composed of an anaplastic astrocytoma and a low-grade oligodendroglioma, the treatment would be based on the anaplastic astrocytoma – the more aggressive of the two cell types.

Optic Nerve Glioma

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Characteristics

  • Named for its location on or near the nerve pathways between the eyes and the brain
  • Can range from low grade to high grade
  • Occurs most often in infants and children, but can occur in adults
  • Symptoms
  • Headaches
  • Progressive loss of vision
  • Double vision

Treatment

Surgery is standard treatment, usually followed by radiation therapy or chemotherapy. Chemotherapy may be given to very young children instead of radiation therapy to avoid damage to the developing brain.

Subependymoma

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This tumor forms from ependymal cells, and is a variation of an ependymoma. Ependymal cells are cells line the passageway in the brain where cerebral spinal fluid (CSF) is produced and stored. Ependymal tumors are classified as either supratentorial (in the cerebral hemispheres) or infratentorial (in the back of the brain). See “Ependymoma” for more information.

Characteristics

  • Slow growing
  • Usually located in the fourth and lateral ventricles
  • More common in men than in women

Symptoms

  • Headaches
  • Nausea
  • Loss of balance
  • Sometimes no symptoms occur and tumor is detected incidentally

Treatment

Surgery will be performed when possible. Radiation therapy may be used if the tumor progresses or recurs. A shunt may be needed to treat hydrocephalus (water on the brain).

Medulloblastoma

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Characteristics

  • A type of primitive neuroectodermal tumor (PNET) (see below)
  • Often located in the cerebellum or near the brain stem
  • Can spread to the spinal cord through the cerebrospinal fluid (CSF)
  • May obstruct the fourth ventricle, causing hydrocephalus (water on the brain)
  • Occurs most often in children under the age of ten, but may occur in adults
  • Slightly more common in males than females

Symptoms

  • Headaches
  • Early morning vomiting
  • Lethargy or sleepiness
  • Lack of coordination
  • Double vision
  • Behavioral or personality changes
  • Signs of pressure seen behind the eye when examined with an ophthalmoscope

Treatment

Surgery is the standard treatment when possible. Chemotherapy is usually part of the treatment plan. Radiation of the brain and spine is often recommended in adults and children over three years of age. A shunt may be needed to treat hydrocephalus. This tumor may recur years later if not totally resected.

Meningioma

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These tumors grow from the meninges, the layers of tissue covering the brain and spinal cord. As they grow, meningiomas compress adjacent brain tissue. Symptoms are often related to this compression of brain tissue, which can also affect cranial nerves and blood vessels. In some cases, meningioma growth can also extend into the bones of the head and face, which may produce visible changes. Most meningiomas are considered nonmalignant or low grade tumors. However, unlike nonmalignant tumors elsewhere in the body, some of these brain tumors can cause disability and may sometimes be life threatening. In many cases, meningiomas grow slowly. Other meningiomas grow more rapidly or have sudden growth spurts. There is no way to predict the rate of growth of a meningioma or to know for certain how long a specific tumor was growing before diagnosis. Meningiomas are graded from low to high. The lower the grade, the lower the risk of recurrence and aggressive growth.

The WHO classification divides meningiomas into three grades:

Grade I: Benign Meningioma

Grade II: Atypical Meningioma

Grade III: Malignant (Anaplastic) Meningioma

Characteristics

  • May arise after previous treatment from ionizing radiation or excessive x-ray exposure
  • Common among women and men in their 40s-50s, but can occur at any age
  • Twice as common in women as in men
  • Accounts for 34 percent of all primary brain tumors
  • In very rare cases, can invade the skull or metastasize to the skin or lungs
  • Women with meningiomas can experience tumor growth during pregnancy
  • In rare cases, multiple meningiomas can develop at the same time in different parts of the brain and/or spinal cord

Symptoms

  • Seizures
  • Headaches
  • Nausea and vomiting
  • Vision changes
  • Behavioral and cognitive changes
  • Sometimes no symptoms occur and tumor is detected incidentally

Treatment

If there are no symptoms, the doctor may monitor the tumor with MRIs. Otherwise, surgery is the standard treatment. If the tumor cannot be completely resected or if it recurs, radiation therapy may be given as well. Chemotherapy for unresectable, aggressive, atypical, or recurrent meningiomas is being tested through clinical trials. Follow-up scans are needed indefinitely, because meningiomas can recur years or even decades after treatment.

Oligodendroglioma

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This tumor type develops from glial cells called oligodendrocytes.

Characteristics

  • Occurs frequently in the frontal or temporal lobes
  • Can be classified as low grade or high grade
  • Common among men and women in their 20s-40s, but can occur in children
  • More common in men than women
  • Accounts for two percent of all brain tumors
  • May be associated with 1p or 19q chromosomal losses

Symptoms

  • Seizures
  • Headaches
  • Behavioral and cognitive changes
  • Weakness or paralysis

Treatment

Treatment options depend on the grade of the tumor. If the tumor is low grade and symptoms are not severe, the doctor may decide to perform surgery, then “watch and wait” and evaluate tumor growth through MRIs. There is a malignant form called anaplastic oligodendroglioma and a mixed malignant astrocytoma-oligodendroglioma. The common treatment for these high-grade tumors is surgery followed by radiation therapy and/or chemotherapy. Both low- and high-grade oligodendrogliomas can recur. If a tumor recurs, the doctor will evaluate it for a second surgical procedure, radiation, and/or chemotherapy. Gene expression studies are used to classify gliomas based on certain characteristics, or genetic profiles. Oligodendrogliomas can be identified by deficiencies in certain chromosomes named 1p and 19q. Genetic profiling of oligodendrogliomas provides a more accurate predictor of prognosis and treatment options than does standard pathology.

Pituitary Tumors

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The pituitary gland produces hormones that affect growth and the functions of other glands in the body. Certain pituitary tumors secrete abnormally high amounts of their respective hormones and cause related symptoms. Other pituitary tumors do not secrete hormones, but grow and compress brain tissue, causing other symptoms.

Characteristics

  • Named for its location on or near the pituitary gland, located at the center of the brain behind and above the nose
  • Can range from low grade to high grade
  • May cause excessive secretion of hormones
  • Common among men and women in their 50s-80s
  • Accounts for about 13 percent of all brain tumors

Symptoms

  • Headache
  • Depression
  • Vision loss
  • Nausea or vomiting
  • Behavioral and cognitive changes
  • Cessation of menstrual periods (amenorrhea)
  • Leaking of fluid from the breasts (galactorrhea)
  • Hair growth in women
  • Impotence in men
  • Abnormal growth of hands and feet
  • Abnormal weight gain

Treatment

If the tumor is large or compressing the optic nerve, standard treatment is surgery. This can be transphenoidal surgery, which gets access to the tumor by entering through the nasal passage. Radiation therapy may also be used. Some pituitary tumors may be treated with medication, and/or observed with MRI scans. Certain drugs can block the pituitary gland from making too many hormones. Follow up with an endocrinologist may be necessary to manage hormonal changes.

Primitive Neuroectodermal (PNET)

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There are several tumor types in this category. Names of specific PNETs may be based on the tumor location. Examples include pineoblastoma (located in the pineal region, a form of pineal tumor), medulloblastoma (located in the cerebellum), and cerebral cortex PNET (located in the cerebral cortex).

Characteristics

  • Highly aggressive and tend to spread throughout the CNS
  • Grow from undeveloped brain cells
  • Commonly include cysts and calcification (calcium deposits)
  • Tend to be large

Symptoms

  • Can vary depending on location of tumor
  • Weakness or change in sensation on one side of the body
  • Morning headache or headache that goes away after vomiting
  • Nausea and vomiting
  • Seizures
  • Unusual sleepiness or lethargy
  • Behavioral or personality changes
  • Unexplained weight loss or weight gain

Treatment

Surgery is the standard treatment when possible. In adults and children over three years of age, surgery may be followed by radiation therapy to the whole brain and spinal cord, and chemotherapy. In children under three years of age, surgery may be followed by chemotherapy or a clinical trial of chemotherapy to delay or reduce the need for radiation therapy.

Other Brain-Related Conditions

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Cysts

A cyst is a fluid-filled sac that may encapsulate (surround) or be located next to a tumor. Based on its location in the brain, a cyst can cause symptoms such as headache, pain, seizures, or a neurological deficit. Cysts can be surgically removed or drained. If a cyst is not causing neurological difficulties, the doctor will conduct ongoing MRI and CT scans to observe its growth pattern.

Neurofibromatosis

Neurofibromatosis is a genetic disorder that can cause tumors in various parts of the central nervous system (CNS). There are two types of neurofibromatosis. Type 1, the more common kind, usually occurs outside of the CNS. Type 2 occurs within the CNS. Type 2 neurofibromatosis causes multiple CNS tumors, including neurofibromas, multiple meningiomas, bilateral vestibular schwannomas, optic nerve gliomas, and spinal cord tumors. Symptoms include loss of balance, tinnitus, total hearing loss, facial pain or numbness, and headache. Surgery is the standard treatment.

Pseudotumor Cerebri

This condition is not a brain tumor, but its symptoms mimic a brain tumor. Pseudotumor Cerebri most commonly afflicts obese adolescent girls and young women. Symptoms include headaches, blurred vision, dizziness, and a slight numbness of the face. The symptoms are caused by a buildup of cerebrospinal fluid (CSF). Treatment is given to relieve the symptoms, particularly visual impairment. Treatment may include repeated lumbar punctures or medications to decrease CSF. In severe cases, a shunt may be needed.

Tuberous Sclerosis

Tuberous Sclerosis is a genetic disorder that causes numerous neurological and physical symptoms, including tumors of the CNS, eyes, and kidneys. Most cases occur in children under 20 years of age. About fifty percent of tuberous sclerosis patients develop brain tumors. Subependymal giant-cell astrocytomas are the most common type, but other tumor types are also associated with this condition. Most patients suffer from seizures. Treatment may involve inserting a shunt to prevent hydrocephalus (water on the brain). Surgery is another treatment option.

Schwannoma

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Also known as vestibular schwannoma, neurilemmoma and acoustic neuroma (see acoustic neuroma).

Characteristics

  • Arises from cells that form a protective sheath around nerve fibers
  • Typically grows around the eighth cranial nerve, but can be found around other cranial or spinal nerves

Symptoms

  • Reduced hearing in the ear on the side of the tumor when eighth cranial nerve is involved Tinnitus (ringing in the ear)
  • Balance problems
  • Deficits depend on the nerve that is affected

Treatment

Surgery and radiotherapy are the most common forms of treatment. If the tumor is not completely removed, recurrence is likely.

Brain Stem Glioma

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Characteristics

  • Named for its location at the base of the brain
  • Can range from low grade to high grade
  • Occurs most often in children between three and ten years of age, but can occur in adults

Symptoms

  • Headaches
  • Nausea
  • Speech or balance abnormalities
  • Difficulty swallowing
  • Weakness or numbness of the arms and/or legs
  • Facial weakness
  • Double vision

Symptoms can develop slowly and subtly and may go unnoticed for months. In other cases, the symptoms may arise abruptly. A sudden onset of symptoms tends to occur with rapidly growing, high-grade tumors.

Treatment

Surgery may not be an option because the brain stem controls vital life functions and can easily be damaged. Radiation therapy can reduce symptoms and help slow the tumor’s growth. Low-grade brain stem gliomas can have very long periods of remission.

Craniopharyngioma

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Characteristics

  • Most common in the parasellar region, an area at the base of the brain and near the optic nerves
  • Also grows in the regions of the optic nerves and the hypothalamus, near the pituitary gland
  • Tends to be low grade
  • Often accompanied by a cyst
  • Originates in cells left over from early fetal development
  • Occurs in children and men and women in their 50s and 60s

Symptoms

  • Headaches
  • Visual changes
  • Weight gain
  • Delayed development in children

Treatment

Surgery is the most common treatment. Radiation therapy may be used.

Ependymoma

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Ependymal tumors begin in the ependyma, cells that line the passageways in the brain where cerebrospinal fluid (CSF) is produced and stored. Ependymomas are classified as either supratentorial (in the cerebral hemispheres) or infratentorial (in the back of the brain). Variations of this tumor type include subependymoma, subependymal giant-cell astrocytoma, and malignant ependymoma. Ependymoblastoma, which occurs in infants and children under three years, is no longer considered a subtype of ependymoma. For ependymoblastoma, see primitive neuroectodermal tumor (PNET) in the Non-glial Tumors section.

Characteristics

  • Usually localized to one area of the brain
  • Develops from cells that line the hollow cavities at the bottom of the brain and the canal containing the spinal cord
  • Can be slow growing or fast growing
  • May be located in the ventricles (cavities in the center of the brain)
  • May block the ventricles, causing hydrocephalus (water on the brain)
  • Sometimes extends to the spinal cord
  • Common in children, and among men and women in their 40s and 50s
  • Occurrence peaks at age five and again at age 34
  • Accounts for two percent of all brain tumors

Symptoms

  • Severe headaches
  • Nausea and vomiting
  • Difficulty walking
  • Fatigue and sleepiness
  • Problems with coordination
  • Neck pain or stiffness
  • Visual problems

Treatment

The doctor will perform tests to determine if it has spread to the spinal cord. Surgery followed by radiation therapy is the usual course of treatment. A shunt may be needed to treat hydrocephalus caused by blockage of the ventricles.

Additional Resources

  • Watch videos by the Collaborative Ependymoma Research Network (CERN) Foundation.

Juvenile Pilocytic Astrocytoma (JPA)

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Also called Juvenile Pilocytic Astrocytoma (JPA)

Characteristics

  • Slow growing, with relatively well-defined borders
  • Grows in the cerebrum, optic nerve pathways, brain stem and cerebellum
  • Occurs most often in children and teens
  • Accounts for two percent of all brain tumors

Treatment

Surgery is the standard treatment. If the tumor cannot be completely resected, radiation or chemotherapy may be given. Chemotherapy may be given to very young children instead of radiation therapy to avoid damage to the developing brain. Some of these tumors can progress to a higher grade, so it is important to be diligent about following up with the medical team after treatment.

Medulloblastoma

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Characteristics

  • A type of primitive neuroectodermal tumor (PNET) (see below)
  • Often located in the cerebellum or near the brain stem
  • Can spread to the spinal cord through the cerebrospinal fluid (CSF)
  • May obstruct the fourth ventricle, causing hydrocephalus (water on the brain)
  • Occurs most often in children under the age of ten, but may occur in adults
  • Slightly more common in males than females

Symptoms

  • Headaches
  • Early morning vomiting
  • Lethargy or sleepiness
  • Lack of coordination
  • Double vision
  • Behavioral or personality changes
  • Signs of pressure seen behind the eye when examined with an ophthalmoscope

Treatment

Surgery is the standard treatment when possible. Chemotherapy is usually part of the treatment plan. Radiation of the brain and spine is often recommended in adults and children over three years of age. A shunt may be needed to treat hydrocephalus. This tumor may recur years later if not totally resected.

Optic Nerve Glioma

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Characteristics

  • Named for its location on or near the nerve pathways between the eyes and the brain
  • Can range from low grade to high grade
  • Occurs most often in infants and children, but can occur in adults
  • Symptoms
  • Headaches
  • Progressive loss of vision
  • Double vision

Treatment

Surgery is standard treatment, usually followed by radiation therapy or chemotherapy. Chemotherapy may be given to very young children instead of radiation therapy to avoid damage to the developing brain.

Pineal Tumor

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A malignant form of pineal tumor is called pineoblastoma.

Characteristics

  • Named for its location in or around the pineal gland (near the center of the brain)
  • Can range from low grade to high grade
  • Can produce an excess of melatonin, a hormone that controls the sleep/wake cycle
  • Can block the ventricles, causing hydrocephalus
  • High-grade pineal tumors can spread to the spinal cord through the CSF
  • Common types include germ cell tumors, pineal parenchymal tumors, and gliomas
  • Occurs most often in children and young adults

Symptoms

  • Headaches
  • Nausea and vomiting
  • Fatigue
  • Double vision
  • Memory problems

Treatment

Surgery is standard treatment when possible. Radiation therapy may be used as primary treatment in adults and children above age three. Chemotherapy may be given to delay the use of radiation therapy in very young patients. A shunt may be needed to treat hydrocephalus (water on the brain) caused by blockage of the ventricles. Treatment for high-grade (malignant) pineal tumors such as a pineoblastoma may involve radiation to the brain and spine to control spread through the CSF. Clinical trials using chemotherapy or biological therapy following radiation therapy are being investigated.

Primitive Neuroectodermal Tumors (PNET)

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There are several tumor types in this category. Names of specific PNETs may be based on the tumor location. Examples include pineoblastoma (located in the pineal region, a form of pineal tumor), medulloblastoma (located in the cerebellum), and cerebral cortex PNET (located in the cerebral cortex).

Characteristics

  • Highly aggressive and tend to spread throughout the CNS
  • Grow from undeveloped brain cells
  • Commonly include cysts and calcification (calcium deposits)
  • Tend to be large

Symptoms

  • Can vary depending on location of tumor
  • Weakness or change in sensation on one side of the body
  • Morning headache or headache that goes away after vomiting
  • Nausea and vomiting
  • Seizures
  • Unusual sleepiness or lethargy
  • Behavioral or personality changes
  • Unexplained weight loss or weight gain

Treatment

Surgery is the standard treatment when possible. In adults and children over three years of age, surgery may be followed by radiation therapy to the whole brain and spinal cord, and chemotherapy. In children under three years of age, surgery may be followed by chemotherapy or a clinical trial of chemotherapy to delay or reduce the need for radiation therapy.

Rhabdoid Tumor

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Characteristics

  • Rare
  • Highly aggressive and tends to spread throughout the CNS
  • Often appears in multiple sites in the body, especially the kidneys
  • Difficult to classify; may be confused with medulloblastoma or PNETs
  • Occurs most often in young children but can also occur in adults

Symptoms

  • Vary depending on location of tumor in the brain or body
  • An orbital tumor may cause the eye to protrude
  • Balance problems may occur
  • External tumors cause noticeable lumps; internal tumor symptoms vary based on location

Treatment

Whenever possible, surgery is performed to remove as much of the tumor as possible. This is usually followed by chemotherapy and radiation therapy. In children under three years of age, surgery may be followed by chemotherapy alone. Clinical trials are being studied using autologous bone marrow transplantation after high-dose chemotherapy for recurrent or multiple rhabdoid tumors.

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