Brain tumor natural history

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Brain tumor Microchapters

Patient Information

Overview

Classification

Adult brain tumors
Glioblastoma multiforme
Oligodendroglioma
Meningioma
Hemangioblastoma
Pituitary adenoma
Schwannoma
Primary CNS lymphoma
Childhood brain tumors
Pilocytic astrocytoma
Medulloblastoma
Ependymoma
Craniopharyngioma
Pinealoma
Metastasis
Lung cancer
Breast cancer
Melanoma
Gastrointestinal tract cancer
Renal cell carcinoma
Osteoblastoma
Head and neck cancer
Neuroblastoma
Lymphoma
Prostate cancer

Causes

Differentiating Brain Tumor from other Diseases

Overview

Survival rates in primary brain tumors depend on the type of tumor, age, functional status of the patient, the extent of surgical tumor removal, to mention just a few factors[1].

Patients with benign gliomas may survive for many years[2][3] while survival in most cases of glioblastoma multiforme is limited to a few months after diagnosis.

Natural History

Complications

  • Brain herniation (often fatal)
    • Uncal herniation
  • Loss of ability to interact or function
  • Permanent, worsening, and severe loss of brain function
  • Return of tumor growth
  • Side effects of medications, including chemotherapy
  • Side effects of radiation treatments

Prognosis

The main treatment option for single metastatic tumors is surgical removal, followed by radiotherapy and/or chemotherapy. Multiple metastatic tumors are generally treated with radiotherapy and chemotherapy. Stereotactic radiosurgery, such as Gamma Knife radiosurgery, remains a viable option. However, the prognosis in such cases is determined by the primary tumor, and it is generally poor.

Prognostic factors

There are several other factors that help doctors determine the appropriate brain tumor treatment plan and determine prognosis:

Tumor histology a sample of the tumor is removed for analysis. How a tumor looks under a microscope is called tumor histology.

Normal brain tissue usually has differentiated tissue (different types of cells grouped together). Brain tissue that is cancerous is usually made up of cells that look more alike. In general, the more differentiated the brain tissue (and the lower the grade), the better the prognosis.

To determine histology of a glial tumor, doctors look at several factors including, but not limited to, the following:

  • Mitosis (the number of cells dividing)
  • Hypercellularity (if the tumor contains large numbers of cells)
  • Vascular proliferation (if blood vessels in the tumor are growing)
  • Necrosis (if there is any dead tissue in the tumor)

The pathologist can determine the type of tumor and its grade. To decide on the best treatment for a brain tumor, both the type and grade of the tumor must be determined. In general, a tumor is referred to by grade. The higher the grade, the more rapidly growing the tumor is.

Specifically for glial tumors, the grade is determined by its features, as seen under a microscope, according to the following criteria:

  • Grade I is a separate group of tumors. It refers to a juvenile pilocytic astrocytoma (JPA). The term juvenile does not refer to the age of the patient, but rather the type of cell. This is a noncancerous, slow-growing tumor that can typically be cured with surgery. It is different from a low-grade astrocytoma or Grade II glioma, which are likely to recur.
  • A grade II tumor does not have mitosis, vascular proliferation, or necrosis, but shows increased cellularity.
  • A grade III tumor is hypercellular and has mitosis but no vascular proliferation and no necrosis. It is often called anaplastic astrocytoma
  • A grade IV tumor (glioblastoma, also called glioblastoma multiforme or GBM) has vascular proliferation and/or necrosis in addition to the factors common to grade II and III tumors.

Age of patient. In adults, the age of the patient (as well as his or her level of functioning, called functional status, see below) at the time of diagnosis is one of the most significant predictors of outcome. In general, the younger the adult, the better the prognosis.

Extent of tumor residual. Resection is surgery to remove a tumor, and residual refers to how much of the tumor remains in the body after surgery. Four classifications are used:

  • Gross total: The entire tumor was removed (microscopic cells may remain).
  • Subtotal: Large portions of the tumor were removed.
  • Partial: Only part of the tumor was removed.
  • Biopsy only: Only a small portion, used for a biopsy, was removed.

Prognosis is most favorable when all of the tumor can be surgically removed.

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

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, the better someone is able to walk and care for themselves indicates 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 Moribund, fatal processes progressing rapidly

0 Dead

Metastatic spread. A tumor that starts in the brain or spinal cord, if cancerous, often spreads within the CNS only and rarely metastasizes to other parts of the body in adults. 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 associated with a poorer prognosis.

Biogenetic markers. Certain molecular markers found in the tumor tissue can provide information on the tumor’s response to treatment. For instance, for oligodendroglioma, the loss of part of chromosome 1 on the p part of the chromosome, and the loss of part of chromosome 19 on the q part of the chromosome (called 1p and 19q) is associated with a much better response to chemotherapy and more successful treatment. Also, in glioblastoma, the modification of a gene called MGMT appears to be associated with improved responsiveness to treatment and better prognosis, but this is being tested in clinical trials (research studies).

Recurrent tumor. A recurrent tumor is one that comes back after treatment. If there is a recurrence, the tumor may need to be graded again using the system above.

Currently, the factors listed above are the best indicators of a patient’s prognosis. Researchers are currently looking for tumor markers in the tumor tissue that could make a brain tumor easier to diagnose and the staging of an adult brain tumor possible in the future. These tools may someday help doctors analyze the possibility that a brain tumor will grow, develop more effective treatments, and more accurately predict prognosis.

References

  1. Nicolato A, Gerosa MA, Fina P, Iuzzolino P, Giorgiutti F, Bricolo A. Prognostic factors in low-grade supratentorial astrocytomas: a uni-multivariate statistical analysis in 76 surgically treated adult patients. Surg Neurol 1995;44:208-21; discussion 221-3. PMID 8545771.
  2. Janny P, Cure H, Mohr M, Heldt N, Kwiatkowski F, Lemaire JJ, Plagne R, Rozan R. Low grade supratentorial astrocytomas. Management and prognostic factors. Cancer 1994;73:1937-45. PMID 8137221.
  3. Piepmeier J, Christopher S, Spencer D, Byrne T, Kim J, Knisel JP, Lacy J, Tsukerman L, Makuch R. Variations in the natural history and survival of patients with supratentorial low-grade astrocytomas. Neurosurgery 1996;38:872-8; discussion 878-9. PMID 8727811.

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