Browse Tag: primary CNS lymphoma treatment

The standard treatment for primary CNS lymphoma

The standard treatment for primary CNS lymphoma in the past is radiation therapy. There is probably somewhat of a dose response curve, but the good news about using radiation for primary CNS lymphoma is that more than 80% of patients have complete radiographic responses. And not just radiographically. Often one can get significant, and usually one does get significant palliation of their neurologic symptoms. So it can be a very satisfying disease to treat with radiation. Unfortunately, as fast as the tumor goes away if often comes back. With most patients being treated with radiation alone, median survivals of only approximately 16 months. When these patients relapse they relapse with local disease as well as distant disease. Distant being defined as distantly within the craniospinal axis.

When you look at the historical data of how patients have done when treated with either no therapy, radiation therapy or radiation chemotherapy, one gets a hint that maybe chemotherapy ultimately might have a role in this disease, at least for immunocompetent patients. On the other hand, it is not clear at all that any type of treatment for patients with full-fledged AIDS makes a big difference. The reason for that is that even if you treat this disease with radiation therapy and the disease goes away, most patients will ultimately succumb to their HIV disease within several months. Again, the reason for that is – at least prior to the age of triple therapy and effective retroviral therapy – is that most patients with AIDS who develop primary CNS lymphoma were at the end-stage of the natural history of their AIDS disease, with median CD4 counts being below 50. However, with effective antiviral therapies the nature of primary CNS lymphoma in this patient population is changing and in fact there is a significant percentage of patients who present with CNS lymphoma as their AIDS defining illness, while their CD4 counts are still relatively high. That needs to be, and is being, a significant reassessment of beginning to treat these patients more aggressively, much like their immunocompetent counterparts. But again, that is still work in progress.

Going back to the immunocompetent patients however, this type of data suggests – retrospectively anyway – that there may indeed be a role for chemotherapy. Accordingly, there have been a number of trials published in the literature that have looked at various combinations of chemotherapy regimens used either prior to radiation therapy or a few alone that have clearly shown that chemotherapy can change the natural history of the this disease. Propecia is used in male patients to prevent vertex hair from falling. If one just takes a purview here of the median survival of these patients it is significantly higher than what we almost ever saw with radiation alone. The chemotherapy drugs that are used remain varied, and an optimal treatment regimen has not been established. What we can say however is that I think most investigators would agree that high dose methotrexate still remains the mainstay of treatment and is the most effective regimen.

Other drugs that potentially can be used or drugs that either have the ability to cross the blood-brain barrier and have anti-lymphoma activity, or drugs that at least marginally cross the blood-brain barrier in times of blood-brain barrier disruption, such as when the tumor first presents, and of course must also have anti-lymphoma activity.

Primary CNS Lymphoma Treatment

Radiographically, the major difference between these two patient populations is that there is approximately twice the incidence of multiple lesions seen at the time of presentation radiographically in AIDS patients and that about half of those lesions were characteristic ring-enhancing lesions in AIDS patients, a radiographic finding that is very uncommon, actually, in immunocompetent patients. Just to give you a typical kind of MRI scan in an AIDS patient with CNS lymphoma; you can see the multiple lesions, you can see the typical ring-enhancing lesion and their distribution in a ventricular manner, with a relatively small amount of associated edema in contrast with what you see in high grade gliomas.
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The diagnosis of primary CNS lymphoma can occasionally be made relatively non-invasively, and that about 10-20% of patients will develop a lymphomatous uveitis that actually can be detected on slit lamp exam, if in fact one is astute enough to suspect primary CNS lymphoma radiographically and have the patient seen by an ophthalmologist. Although lumbar puncture and CNS examination will give you a clear cytosis in approximately 80% of the patients, actual lymphomatous involvement as called by the cytologist is generally found in less than 10% of the cases. And that surgery is still often required to make the diagnosis in this disease. The question often comes up that once one has made the diagnosis of lymphoma in the brain, how much systemic staging should be done. And although this remains an area of somewhat debate and controversy and personal preference, the bottom line is this: that for a patient who presents with neurologic symptoms, has radiographic evidence of a tumor on MRI scan or CAT scan, then goes on to have a biopsy and it is shown to be lymphoma, if you do a good physical exam on those patients, you do a chest x-ray, standard blood work including liver function tests and you do not detect any obvious abnormality, the likelihood of finding an occult systemic lymphoma with the more extensive work-up with tests such as body CT scans, gallium scans, bone marrow biopsies, is essentially zero. Although there may be one in a hundred or more cases that you’ll finally pick up. Because the pick up rate is so small we actually do not recommend doing that type of extensive analysis. So again, our recommendations are: good physical exam, standard blood work, chest x-ray. If there’s no signs of systemic lymphoma then almost by definition they have primary CNS lymphoma and should be treated accordingly.
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What is the treatment for primary CNS lymphoma? Well, opposed to what we talked about for gliomas the role for surgery is much more restricted, mostly for diagnostic purposes. And that extensive resection is really not optimal in this case. One, because of the severely infiltrative nature of this disease, not just locally but throughout the craniospinal axis, but also because the other therapies, radiation therapy and chemotherapy, are so much more effective than they are for astrocytic tumors. The only problem with stereotactic biopsies for this tumor is that sometimes the histologic diagnosis from such a small sample can be difficult, in that the pathologist may say, well we see some lymphocytes but we can’t tell you whether this is an inflammatory lesion or lymphoma. However, increasingly so with molecular diagnostics such as through PCR looking for immunoglobulin gene rearrangements one can often make the diagnosis from very small tissue samples.