General Information About Primary CNS Lymphoma
Primary central nervous system (CNS) lymphoma is a disease in
which malignant (cancer) cells form in the lymph tissue of the brain and/or
spinal cord.
Lymphoma is a disease in which malignant (cancer) cells form in the
lymph system. The lymph system is part of the immune system and is made up of the lymph, lymph vessels, lymph nodes, spleen, thymus, tonsils, and bone marrow. Lymphocytes (carried in the lymph) travel in and out of the central nervous system (CNS). It is thought that some of these lymphocytes become malignant and cause lymphoma to form in the CNS. Primary CNS lymphoma
can start in the brain,
spinal cord, or meninges (the layers that form the outer covering of the brain). Because the eye is so close to the brain, primary CNS lymphoma can also start in the eye (called ocular lymphoma).
 |
| Anatomy of the lymph system, showing the lymph vessels and lymph organs including lymph nodes, tonsils, thymus, spleen, and bone marrow. Lymph (clear fluid) and lymphocytes travel through the lymph vessels and into the lymph nodes where the lymphocytes destroy harmful substances. The lymph enters the blood through a large vein near the heart. |
Having a weakened immune system may increase the risk of
developing primary CNS lymphoma.
Anything that increases your chance of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. People who think they may be at risk should discuss this with their doctor.
Primary CNS lymphoma may occur in patients who have acquired
immunodeficiency syndrome (AIDS) or other disorders of the immune
system or who have had a kidneytransplant. For more information about lymphoma in patients with AIDS, see the PDQ summary on AIDS-Related Lymphoma Treatment.
Tests that examine the eyes, brain, and spinal cord are used to detect
(find) and diagnose primary CNS lymphoma.
The following tests and procedures may be used:
- Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
- Neurological exam: A series of questions and tests to check the brain, spinal cord, and nerve function. The exam checks a person’s mental status, coordination, ability to walk normally, and how well the muscles, senses, and reflexes work. This may also be called a neuro exam or a neurologic exam.
- Slit-lamp eye exam: An exam that uses a special microscope with a bright, narrow slit of light to check the outside and inside of the eye.
- Vitrectomy: Surgery to remove some or all of the vitreous humor (the gel-like fluid inside the eyeball). The fluid is removed through tiny incisions and then viewed under a microscope by a pathologist to check for cancer cells.
- CT scan (CAT scan):
A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. For primary CNS
lymphoma, a CT scan is done of the chest, abdomen, and pelvis (the part of the
body between the hips).
- MRI (magnetic
resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the brain and spinal cord. A substance called gadolinium is injected into the patient through a vein. The gadolinium collects around the cancer cells so they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI).
- Lumbar puncture: A procedure used to collect cerebrospinal fluid (the fluid in the spaces around the brain and spinal cord) from the spinal column. This is done by placing a needle into the spinal column. This procedure is also called an LP or spinal tap. Laboratory tests to diagnose primary CNS lymphoma may include
checking the protein level in the cerebrospinal fluid.
 |
| Lumbar puncture. A patient lies in a curled position on a table. After a small area on the lower back is numbed, a spinal needle (a long, thin needle) is inserted into the lower part of the spinal column to remove cerebrospinal fluid (CSF, shown in blue). The fluid may be sent to a laboratory for testing. |
- Stereotactic biopsy: A biopsy procedure that uses a computer and a 3-dimensional (3-D) scanning device to find a tumor site and guide the removal of tissue so it can be viewed under a microscope to check for signs of cancer.
- Complete blood count (CBC) with differential: A procedure in which a sample of blood is drawn and checked for the following:
- The number of red blood cells and platelets.
- The number and type of white blood cells.
- The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
- The portion of the blood sample made up of red blood cells.
 |
| Complete blood count (CBC). Blood is collected by inserting a needle into a vein and allowing the blood to flow into a tube. The blood sample is sent to the laboratory and the red blood cells, white blood cells, and platelets are counted. The CBC is used to test for, diagnose, and monitor many different conditions. |
- Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it.
Certain factors affect prognosis (chance
of recovery) and treatment options.
The prognosis (chance of recovery) depends on the following:
- The patient's age and
general health.
- The level of certain substances in the blood and cerebrospinal fluid (CSF).
- Where the tumor is in the central nervous system.
- Whether the patient has AIDS.
Treatment options depend
on the following:
- The stage of the cancer.
- Where the tumor is in the central nervous system.
- The patient's age and
general health.
- Whether the cancer has just been diagnosed or has recurred (come back).
Treatment of primary CNS lymphoma works best when the
tumor has not spread outside the cerebrum (the largest part of
the brain) and the patient is younger than 60 years, able to carry out most daily activities, and does not have AIDS or other diseases that weaken the immune
system.
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Staging Primary CNS Lymphoma
After primary central nervous system (CNS) lymphoma has been diagnosed, tests are done to find out if cancer cells have spread within the brain and spinal cord or to other parts of the body.
When primary CNS lymphoma continues to grow, it usually does not spread
beyond the central nervous system or the eye. The process used to find out if cancer has spread is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. The following tests and procedures may be used in the staging process:
- CT scan (CAT scan):
A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. For primary CNS
lymphoma, a CT scan is done of the chest, abdomen, and pelvis (the part of the
body between the hips).
- Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for signs of cancer.
 |
| Bone marrow aspiration and biopsy. After a small area of skin is numbed, a Jamshidi needle (a long, hollow needle) is inserted into the patient’s hip bone. Samples of blood, bone, and bone marrow are removed for examination under a microscope. |
- Slit-lamp eye exam: An exam that uses a special microscope with a bright, narrow slit of light to check the outside and inside of the eye.
- Vitrectomy: Surgery to remove some or all of the vitreous humor (the gel-like fluid inside the eyeball). The fluid is removed through tiny incisions and then viewed under a microscope by a pathologist to check for cancer cells.
There are three ways that cancer spreads in the body.
The three ways that cancer spreads in the body are:
- Through tissue. Cancer invades the surrounding normal tissue.
- Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body.
- Through the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body.
When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary (metastatic) tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone cancer.
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Recurrent Primary CNS Lymphoma
Recurrentprimary central nervous system (CNS) lymphoma is cancer that has recurred (come
back) after it has been treated. Primary CNS lymphoma commonly recurs in the
brain or the eye.
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Treatment Option Overview
There are different types of treatment for patients with
primary CNS lymphoma.
Different types of treatment are available for patients with
primary central nervous system (CNS) lymphoma. Some treatments are standard (the currently used
treatment), and some are being tested in clinical
trials. A treatment clinical trial is a research
study meant to help improve current treatments or obtain information on new
treatments for patients with cancer. When clinical trials show that a new
treatment is better than the standard
treatment, the new treatment may become the standard treatment.
Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.
Surgery is not used to treat primary CNS lymphoma.
Three standard treatments are used:
Radiation therapy
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type of cancer being treated.
High-dose
radiation therapy to the brain can damage healthy tissue and cause disorders that can affect thinking, learning, problem solving, speech, reading, writing, and memory. Clinical trials have tested the use of chemotherapy alone or before radiation therapy to reduce the damage to healthy brain
tissue that occurs with the use of radiation therapy.
Chemotherapy
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column (intrathecal chemotherapy), an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type of cancer being treated. Primary CNS lymphoma may be treated with intrathecal chemotherapy and/or intraventricular chemotherapy, in which anticancer drugs are placed into the ventricles (fluid-filled cavities) of the brain.
 |
| Intrathecal chemotherapy. Anticancer drugs are injected into the intrathecal space, which is the space that holds the cerebrospinal fluid (CSF, shown in blue). There are two different ways to do this. One way, shown in the top part of the figure, is to inject the drugs into an Ommaya reservoir (a dome-shaped container that is placed under the scalp during surgery; it holds the drugs as they flow through a small tube into the brain). The other way, shown in the bottom part of the figure, is to inject the drugs directly into the CSF in the lower part of the spinal column, after a small area on the lower back is numbed. |
A network of blood vessels and tissue, called the blood-brain barrier, protects the brain from harmful substances. This barrier can also keep anticancer drugs from reaching the brain. In order to treat CNS lymphoma, certain drugs may be used to make openings between cells in the blood-brain barrier. This is called blood-brain barrier disruption. Anticancer drugs infused into the bloodstream may then reach the brain.
Steroid therapy
Steroids are hormones made naturally in the body. They can also be made in a laboratory and used as drugs. Glucocorticoids are steroid drugs that have an anticancer effect in lymphomas.
New types of treatment are being tested in clinical trials.
This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web
site.
High-dose chemotherapy with stem cell
transplant
High-dose chemotherapy with stem cell transplant is a method of giving high doses of chemotherapy and replacing blood-forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells.
Patients may want to think about taking part in a clinical trial.
For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.
Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.
Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.
Patients can enter clinical trials before, during, or after starting their cancer treatment.
Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.
Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's clinical trials database.
Follow-up tests may be needed.
Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.
Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.
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Treatment Options for Primary CNS Lymphoma
A link to a list of current clinical trials is included for each treatment section. For some types or stages of cancer, there may not be any trials listed. Check with your doctor for clinical trials that are not listed here but may be right for you.
Primary CNS Lymphoma Not Related to AIDS
Treatment of primary central nervous system (CNS) lymphoma in patients who do not have AIDS may include the following:
- Chemotherapy.
- Chemotherapy followed by radiation therapy.
- Whole brain radiation therapy.
- A clinical trial of high-dose chemotherapy with stem cell transplant.
Primary CNS Lymphoma Related to AIDS
Treatment of primary central nervous system (CNS) lymphoma in patients who do have AIDS may include the following:
- Steroids with or without radiation therapy.
- Radiation therapy alone.
- Chemotherapy followed by radiation therapy.
Treatment of primary CNS lymphoma is different in patients with AIDS because the treatment side effects may be more severe. (See the PDQ summary on AIDS-Related Lymphoma Treatment for more
information).
Recurrent Primary CNS Lymphoma
Treatment of recurrentprimary central nervous system (CNS) lymphoma may include the following:
- Chemotherapy or radiation therapy (if not received in earlier treatment).
- A clinical trial of a new drug or treatment schedule.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with primary central nervous system lymphoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.
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To Learn More About Primary CNS Lymphoma
For more information from the National Cancer Institute about primary CNS lymphoma, see the following:
For general cancer information and other resources from the National Cancer Institute, see the following:
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This information is provided by the National Cancer Institute.
This information was last updated on June 18, 2008.
Purpose of This PDQ Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of primary CNS lymphoma. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.
Information about the following is included in this summary:
- Prognostic factors.
- Treatment options.
This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.
This summary is available in a patient version, written in less technical language, and in Spanish.
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General Information
Note: Separate PDQ summaries on Adult Hodgkin Lymphoma Treatment and Adult Non-Hodgkin Lymphoma Treatment are also available.
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
Primary central nervous system (CNS) lymphoma is defined as lymphoma limited to
the cranial-spinal axis without systemic disease. An increasing incidence of
this disease has been seen among patients with acquired immunodeficiency
syndrome (AIDS) and among other immunocompromised persons. The natural history
of this disorder differs between patients with AIDS and those without AIDS.
Computed tomographic (CT) scans may show ring enhancement in 50% of AIDS patients while patients without AIDS almost always show only homogeneous
enhancement.[1] Both groups do equally poorly without therapy (1–3 month mean
survival), but the overall survival for treated patients is much better for
patients without AIDS (18.9 months) than for those with AIDS (2.6 months).[1][2]
Poor prognostic factors include the following:[3][4][5]
- Age older than 50 years.[5]
- Performance status greater than 1 or Karnofsky performance status less than 70.[5]
- Elevated serum level of lactate dehydrogenase.
- Elevated cerebrospinal fluid protein concentration.
- Involvement of nonhemispheric areas of the brain (periventricular, basal ganglia, brainstem, and cerebellum).
When tumor progression occurs, it is usually confined to the CNS
and/or the eye. Occult systemic disease can be excluded by staging with bone
marrow biopsy and CT scans of the chest, abdomen, and pelvis.[6][7] In one prospective case series of 282 patients, 17% were found to have meningeal dissemination by cytomorphology, polymerase chain reaction of rearranged immunoglobulin heavy-chain genes, or meningeal enhancement on magnetic resonance imaging.[8] The clinical impact of meningeal involvement on prognosis and therapy remains to be evaluated. Although more than 95% of patients with primary CNS lymphoma have lymphoma of B-cell origin, 45 patients with CNS lymphoma of T-cell origin showed no difference in presentation or outcome in a retrospective series with data collected from 12 cancer centers.[9] Almost all primary CNS lymphomas are aggressive neoplasms of the diffuse large B-cell type. In a retrospective case series derived from 18 cancer centers in five countries of 40 patients with low-grade primary CNS lymphoma, a better long-term outcome was shown (7-year median survival) than is associated with the usual aggressive CNS lymphoma.[10][Level of evidence: 3iiiDiv]
References:
Fine HA, Mayer RJ: Primary central nervous system lymphoma. Ann Intern Med 119 (11): 1093-104, 1993.
Nasir S, DeAngelis LM: Update on the management of primary CNS lymphoma. Oncology (Huntingt) 14 (2): 228-34; discussion 237-42, 244, 2000.
Ferreri AJ, Blay JY, Reni M, et al.: Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience. J Clin Oncol 21 (2): 266-72, 2003.
Pollack IF, Lunsford LD, Flickinger JC, et al.: Prognostic factors in the diagnosis and treatment of primary central nervous system lymphoma. Cancer 63 (5): 939-47, 1989.
Abrey LE, Ben-Porat L, Panageas KS, et al.: Primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center prognostic model. J Clin Oncol 24 (36): 5711-5, 2006.
O'Neill BP, Dinapoli RP, Kurtin PJ, et al.: Occult systemic non-Hodgkin's lymphoma (NHL) in patients initially diagnosed as primary central nervous system lymphoma (PCNSL): how much staging is enough? J Neurooncol 25 (1): 67-71, 1995.
Abrey LE, Batchelor TT, Ferreri AJ, et al.: Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. J Clin Oncol 23 (22): 5034-43, 2005.
Fischer L, Martus P, Weller M, et al.: Meningeal dissemination in primary CNS lymphoma: prospective evaluation of 282 patients. Neurology 71 (14): 1102-8, 2008.
Shenkier TN, Blay JY, O'Neill BP, et al.: Primary CNS lymphoma of T-cell origin: a descriptive analysis from the international primary CNS lymphoma collaborative group. J Clin Oncol 23 (10): 2233-9, 2005.
Jahnke K, Korfel A, O'Neill BP, et al.: International study on low-grade primary central nervous system lymphoma. Ann Neurol 59 (5): 755-62, 2006.
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Treatment Option Overview
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
Because of the diffuse nature of central nervous system (CNS) lymphomas, aggressive surgical
decompression with partial or gross total removal of the tumor is of no benefit
to the patient. Median survival with surgery alone is in the range of only 1 to 5
months. Until recently, radiation therapy has been the standard treatment,
with doses of up to 45 Gy using standard fractionation. When the Radiation
Therapy Oncology Group (RTOG-8315) used 40 Gy whole-brain radiation therapy (WBRT) and a 20 Gy boost to
the tumor, the results were no better than had been previously reported with
a median survival of 1 year and 28% of the patients surviving 2 years.[1][2] Disease recurs in
the brain in 92% of patients despite high doses of radiation. The addition
of spinal-axis radiation does not affect survival because it does not prevent
cerebral relapse.
Two multicenter prospective trials, one of which is RTOG-8806, used preirradiation cyclophosphamide,
doxorubicin, vincristine, and dexamethasone followed by WBRT.[3][4] Median survival times were no better than for radiation
therapy alone. The failure of these and other combined modality trials [5]
has been attributed to poor penetration of standard drugs through the blood-brain barrier and to increased neurologic toxic effects.[3][5][6][7][8][9][10] A retrospective review
of 226 patients suggested improved results with the use of high-dose methotrexate or
cytarabine with radiation therapy rather than with other combination regimens.[11] A multicenter trial (RTOG-9310) of 102 patients used high-dose methotrexate (2.5 g/m2) for five cycles, intravenous vincristine, oral procarbazine, intraventricular methotrexate, and either 45 Gy of WBRT or 36 Gy in a hyperfractionated schedule.[12] Median progression-free survival (PFS) was 24 months, and median overall survival (OS) was 37 months.[13][Level of evidence: 3iiiA] Severe delayed neurologic toxic effects were seen in 15% of patients. Another multicenter trial (EORTC-20962) of 52 patients younger than 66 years used high-dose methotrexate, teniposide, carmustine, methylprednisolone, intrathecal methotrexate, cytarabine, and hydrocortisone followed by 40 Gy of radiation therapy; the median survival was 46 months, but a 10% toxic death rate occurred even in this younger patient population.[14][Level of evidence: 3iiiA] Follow-up was too short (median 27 months) to fully assess severe delayed neurologic toxic effects.
Because of unsatisfactory results of WBRT alone and the
neurologic toxic effects of chemotherapy and radiation therapy, a
major focus is now on trials with chemotherapy alone.[15] Several single-institution reports have shown that systemic chemotherapy has been employed alone or
with osmotic blood-brain barrier disruption.[8][10][16][17][18] Currently, most
regimens are employing high-dose methotrexate and require
hospitalization.[8][10][17][18][19][20] A multicenter trial (NABTT-9607) evaluated high-dose methotrexate alone (8 g/m2) for newly diagnosed patients, with whole-brain radiation therapy administered only at disease recurrence. With a median follow-up of 2 years, median PFS was 13 months and median OS had not been reached at 23-plus months.[21][Level of evidence: 3iiiA] Another multicenter trial (EORTC-26952) of 50 patients older than 60 years used high-dose methotrexate (3 g/m2/cycle), lomustine, procarbazine, methylprednisolone, and intrathecal methotrexate and cytarabine. The 1-year PFS was 40%, and the median OS was 14.3 months in this older patient group with a median age of 72 years.[22][Level of evidence: 3iiiA] Another multicenter trial of 65 patients used both high-dose methotrexate and high-dose cytarabine, including ifosfamide, cyclophosphamide, vinca alkaloids, dexamethasone, and intrathecal methotrexate, cytarabine, and prednisolone. The median time-to-treatment failure was 15 months with a median survival of 34 months.[23][Level of evidence: 3iiiA] Severe delayed neurologic toxic effects were rarely seen in these chemotherapy-only trials (in the absence of subsequent radiation therapy). Reduction of dosage for subsequent radiation to 23.4 Gy has been applied for patients who achieve clinical complete response after induction chemotherapy.[24][Level of evidence: 3iiiDiii] Intensive chemotherapy with
autologous peripheral stem cell transplantation is also under evaluation; neurologic toxic effects were not reported in the absence of radiation therapy.[25][26][27][28][29] These phase II results have never been tested in a randomized setting because of an insufficient number of patients.
Severe cognitive deficits are reported with all intensive therapies due to
iatrogenic leukoencephalopathy. Retrospective data suggest a decreased risk of
dementia when chemotherapy is employed prior to radiation therapy and even less
when radiation therapy is avoided.[11][30][31] The use of systemic chemotherapy
alone, with or without osmotic blood-brain barrier disruption, may avoid the
cognitive loss observed with radiation therapy.[11][16][17][31] Comparative trials
with validated measures of cognitive function will be necessary to determine
the value of delaying radiation therapy until relapse after high-dose
chemotherapy.[21][31][32][33][34] Glucocorticoids can also produce substantial but
short-lived remissions. Steroid efficacy may complicate the diagnostic
evaluation by obscuring the histologic findings. Other drugs that cross the
blood-brain barrier are under clinical evaluation.[35][36]
Patients with acquired immunodeficiency syndrome (AIDS) associated primary CNS lymphoma usually have very advanced
human immunodeficiency virus (HIV) infections, with CD4 counts less than 50
cells/mm3.[37] Consequently, most patients die of opportunistic
infections regardless of therapy for the lymphoma. Groups that benefit most
from radiation therapy, with or without antecedent chemotherapy, include those
HIV-seropositive patients with no prior opportunistic infections or tumors for
whom the CNS lymphoma is the AIDS-defining illness, and those patients with a
good performance status, high CD4 lymphocyte count (>100mm3), and symptoms
referable only to the CNS lymphoma.[30][38] Treatment of these patients requires
special consideration. (Refer to the PDQ summary on AIDS-Related Lymphoma
Treatment for more information.)
An international consortium performed a retrospective review of 83 HIV-negative patients with primary intraocular lymphoma.[39] In selected patients with no evidence of disseminated CNS disease, localized therapy with intraocular methotrexate or ocular radiation therapy is associated with equivalent outcomes seen with systemic chemotherapy and/or WBRT. Localized therapy with intraocular methotrexate or ocular radiation therapy did not affect relapse rate, median PFS, or median OS as compared to systemic chemotherapy and/or WBRT.[39][Level of evidence: 3iiiDiv]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with
primary central nervous system lymphoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References:
Pollack IF, Lunsford LD, Flickinger JC, et al.: Prognostic factors in the diagnosis and treatment of primary central nervous system lymphoma. Cancer 63 (5): 939-47, 1989.
Nelson DF, Martz KL, Bonner H, et al.: Non-Hodgkin's lymphoma of the brain: can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the Radiation Therapy Oncology Group (RTOG): RTOG 8315. Int J Radiat Oncol Biol Phys 23 (1): 9-17, 1992.
O'Neill BP, O'Fallon JR, Earle JD, et al.: Primary central nervous system non-Hodgkin's lymphoma: survival advantages with combined initial therapy? Int J Radiat Oncol Biol Phys 33 (3): 663-73, 1995.
Schultz C, Scott C, Sherman W, et al.: Preirradiation chemotherapy with cyclophosphamide, doxorubicin, vincristine, and dexamethasone for primary CNS lymphomas: initial report of radiation therapy oncology group protocol 88-06. J Clin Oncol 14 (2): 556-64, 1996.
Bessell EM, Graus F, López-Guillermo A, et al.: CHOD/BVAM regimen plus radiotherapy in patients with primary CNS non-Hodgkin's lymphoma. Int J Radiat Oncol Biol Phys 50 (2): 457-64, 2001 Jun 1.
Chamberlain MC, Levin VA: Primary central nervous system lymphoma: a role for adjuvant chemotherapy. J Neurooncol 14 (3): 271-5, 1992.
Fine HA: Treatment of primary central nervous system lymphoma: still more questions than answers. Blood 86 (8): 2873-5, 1995.
Blay JY, Bouhour D, Carrie C, et al.: The C5R protocol: a regimen of high-dose chemotherapy and radiotherapy in primary cerebral non-Hodgkin's lymphoma of patients with no known cause of immunosuppression. Blood 86 (8): 2922-9, 1995.
O'Brien P, Roos D, Pratt G, et al.: Phase II multicenter study of brief single-agent methotrexate followed by irradiation in primary CNS lymphoma. J Clin Oncol 18 (3): 519-26, 2000.
Gavrilovic IT, Hormigo A, Yahalom J, et al.: Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma. J Clin Oncol 24 (28): 4570-4, 2006.
Blay JY, Conroy T, Chevreau C, et al.: High-dose methotrexate for the treatment of primary cerebral lymphomas: analysis of survival and late neurologic toxicity in a retrospective series. J Clin Oncol 16 (3): 864-71, 1998.
Fisher B, Seiferheld W, Schultz C, et al.: Secondary analysis of Radiation Therapy Oncology Group study (RTOG) 9310: an intergroup phase II combined modality treatment of primary central nervous system lymphoma. J Neurooncol 74 (2): 201-5, 2005.
DeAngelis LM, Seiferheld W, Schold SC, et al.: Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol 20 (24): 4643-8, 2002.
Poortmans PM, Kluin-Nelemans HC, Haaxma-Reiche H, et al.: High-dose methotrexate-based chemotherapy followed by consolidating radiotherapy in non-AIDS-related primary central nervous system lymphoma: European Organization for Research and Treatment of Cancer Lymphoma Group Phase II Trial 20962. J Clin Oncol 21 (24): 4483-8, 2003.
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This information is provided by the National Cancer Institute.
This information was last updated on August 13, 2009.