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Primary CNS lymphomas

A typical MRI finding is a periventricular tumor, often multifocal. This finding should raise suspicion of PCNSL. The diagnosis can be determined in about 20% by immunocytological examination of spinal fluid. If this examination is reliable, it is sufficient to give the diagnosis of primary CNS lymphoma. 

With CNS lymphomas, it has been shown that radiation alone gives a median survival of only 12-18 months. In studies with chemotherapy and radiation therapy in combination, survival increases to 30 - 40 months. The combination of high-dose methotrexate and high-dose cytarabine appears to be better than other chemotherapy combinations. 

Treatment

Traditionally, these patients have been treated with radiation therapy to the whole brain, but with a median survival of only 12-18 months. In the 1980–90's, a series of phase III studies were conducted which combined chemotherapy and radiation therapy. The median survival times were increased to 30-40 months in the best studies. The most effective chemotherapy has been methotrexate given in high-doses. Methotrexate has a relatively high penetration of the CNS. The combination of high-dose MTX and high-dose cytarabine appears to be better than other chemotherapy combinations. However, both radiation therapy alone, and especially with combination chemotherapy (usually containing high-dose methotrexate) and radiation therapy gives a very high frequency of neurotoxicity. This applies primarily to elderly patients and is most prominent in patients over 60 years. Use of only combination chemotherapy gives very low neurotoxicity, but there are few that are cured by this treatment. Recurrences in the CNS happen within 1-2 years. Based on this, it is difficult to recommend a standard treatment for patients with PCNSL.

For patients under 60 years, the regimen from the Memorial Sloan Kettering Cancer Center is used. The regimen involves 5 courses of high-dose methotrexate every 2 weeks, where courses 1, 3, and 5 are in combination with procarbazine and vincristine. This is followed by radiation therapy to the whole brain to 45 Gy. This is then followed by two courses of high-dose cytarabine with three week intervals. Another treatment option is the Bonn regimen which will not be discussed further here.

For patients over 60 years, individualized treatment is recommended, preferably after discussion with one of the members of the Nordic CNS group.  

Experimental treatment

A Nordic phase II protocol with combination chemotherapy without radiation therapy as part of the primary regimen for all age groups started in 2006/2007.

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