Browse Month: October 2009

The role of chemotherapy

The role of chemotherapy as part of the initial treatment for high-grade gliomas remains somewhat of a question and problematic. This is true even though there have been more than 20 randomized trials, because if one looks at those randomized trials the data on whether chemotherapy is really effective, as far as adding something to the radiation, remains very conflicted. The brain tumor cooperative group itself has conducted three multi-center trials and their data is somewhat conflicted, even though they’ve recommended the use of chemotherapy. Why so much controversy and why are the data all over the place? One of the major reasons simply has to do with the power of randomized trials. It takes nearly 250 patients in each arm of a randomized trial in order to have a 80% probability of detecting a 20% increase in median survival. Most single institutional brain tumor trials enrolled less than 30 patients per arm, and even the large multi-institutional brain tumor trials have enrolled less than 50 patients per arm. And that most trials have not been designed to have the power to pick up potential beneficial effects from some type of therapy like chemotherapy.

Meta-analysis.

Meta-analysis is a statistical method that allows one to combine the results from multiple randomized trials in order to pick up small but potentially important clinically significant outcome differences from different therapies. The database that we used were all randomized trials, published in English between 1975 and 1990. The survivals were determined by Kaplan-Meier survival curves and the standard error of survival was determined by Greenwood’s formula.

For patients who were treated with radiation and chemotherapy, there is a higher statistically significant survival advantage compared to those that were treated with radiation alone. When we looked at the two major histology’s usually found within these randomized trials, that being glioblastoma as well as anaplastic astrocytoma, there appeared to be a survival advantage for both sets of patients.

Although a significantly greater survival advantage for anaplastic astrocytomas. So from this meta-analysis what we have concluded is that chemotherapy followed by external beam radiation is advantageous in adults with malignant glioma, although the survival advantage with anaplastic astrocytomas appears to be significantly greater than those with glioblastoma.

It appears that the relatively late survival advantage that we see in patients with glioblastoma – that meaning that if you actually look at those curves we do not begin to see a survival advantage in patients with glioblastoma treated with chemotherapy – to approximately 12-16 months. Discount levitra professional at online Canada pharmacy. a A funny finding when you consider that most patients with glioblastomas die well before that time, suggests to us that treatment with chemotherapy in patients with glioblastoma preferentially benefits patients with more favorable prognostic factors. What are those prognostic factors in glioblastoma? It’s clear that patients who are younger, who have good performance status and who have minimal postoperative residual tumor are the patients who are destined to do better. Thus, if we are going to treat patients with chemotherapy for blastomas this is the group of patients that we would recommend. Where in fact increasingly so, I’ve become less and less enthusiastic about offering standard post-radiation chemotherapy to patients with glioblastoma anyway.

High-grade astrocytomas

High-grade astrocytomas are often very heterogeneous in their histology and that there can be areas of low-grade histology immediately adjacent to areas of high-grade histology. Tumors will behave according to whatever the highest-grade histology is. One can imagine that with the small sections that are obtained via, for instance, stereotactic biopsies that one could therefore through sampling error come up with the wrong histologic grade. Thus by being able to just physically remove that mass, patients in fact often get significantly better. They are able to better tolerate radiation therapy, which has often been a problem when patients have large masses secondary to increased cerebral edema that can occur following radiation therapy. And that patients are at least palliated by removal of large masses. It probably increases survival when one looks retrospectively at the data. Again, patients who have had large resections tend to do better than patients who haven’t, but again there has been no randomized trial to prove this.

In surgery, the one thing that is clear in the treatment of high-grade astrocytoma is that radiation therapy remains the optimal and the most prudent therapy for this disease. There has been a series of randomized trials dating back to the 1970s and the 1980s that have clearly shown a significant survival advantage for patients treated with external beam standard fractionated radiation therapy. Canadian cymbalta 20 mg – effective major depressive disorder medication. Nevertheless, the role of surgery still remains somewhat limited in that although radiation therapy can nearly triple the survival of patients with high grade gliomas – in the case of glioblastoma that means going from a median survival of three months without radiation therapy to a median of nine months. So while radiation therapy clearly makes a difference, it is not optimal.

However, if one actually looks at the data from radiation therapy, one can see that there appears to be a significant dose response and dose survival curve to radiation therapy. That as those patients get treated with higher and higher doses of radiation, that one begins to see increased survival. Unfortunately, as one gets the higher doses of radiation therapy one gets into more radiation toxicity with the most worst toxicity being radiation necrosis, which in many ways is as bad as the tumor itself, causing cerebral edema and local tissue destruction which is permanent and can be permanently debilitating. There are a number of different technical ways in which we can deliver high doses of boost radiation following the standard fraction of the external beam radiation. From these techniques you’ve probably heard about that they include the things like different types of modified linear accelerators or proton beam therapy. In that sense the idea is always the same, and the idea is to be able to deliver high-dose, focal radiation to the tumor while avoiding important and eloquent intracerebral structures.

In fact most of the phase II and many of the phase II studies looking at high dose focal radiation boost, whether it is done with brachytherapy or whether it’s done with one of these external beam techniques that I’ve just talked about, have shown us what appear to be significant survival advantages in patients treated with this boost focal technology.

  • 1
  • 2