Glioblastoma Grade IV

I will be starting my therapy soon and it looks like I have quite a fight ahead of me. It parallels the old wagon train approach of putting the wagons in a circle to fight off the Indian attack. I don't know how well they succeeded in their method, but there is nothing more serious in my coming life.

I've done a significant amount of reading and research, and I can only hope that health technology makes a breakthrough fast. What I read does not look very promising. I have done what I can to prepare so far, and I am leaving no stone unturned in my quest to find some magic that'll turn this whole thing around, but short of the miracle of miracles, the long term prognosis is a dark fog.

This is what I learned so far:

The only therapy(ies) that could possibly cure primary brain tumors must:
1. Treat the whole brain
2. Cross the Blood:Brain barrier
3. Get to each and every tumor cell
4. Kill all cell types within the tumor
5. Spare the remaining normal brain.

Using the Glioblastoma Multiforme (GBM) as an example, the physician needs to consider the following factors:

GROWTH DYNAMICS (GBM)

Growth Fraction = 20 % (Only a percentage of the tumor is growing at any one time)
Cell Cycle Time = 2 - 5 Days (This is how long it takes a growing cell to reproduce)
Cell Loss = 80 - 90 % (A high percentage of cells spontaneously die off)
Doubling Time = Around 7 Days

Therefore, any therapy aimed at controlling the growth of this tumor must recognize the above dynamics. Therapy must catch the cells at the appropriate phase of the cell cycle (when they are sensitive to treatment), take into account tumor doubling time, and acknowlege that the growth fraction is relatively small.

There are other problems to take into account as well:

Many cells live in a low oxygen environment (hypoxic). These hypoxic cells are:

• * radio-resistant
• * often chemotherapy resistant
• * far from the blood supply

The blood supply to the tumor is quite peripheral, surrounding rather than entering it. The center of the tumor (necrotic center) contains living tumor cells. Therefore, much of the tumor is virtually unavailable to chemotherapy, radiation therapy, immunotherapy or any other therapy.

Standard Therapy

To date, the best treatment for the malignant astrocytoma and GBM is a combination of:

• * Surgery (Gross total removal, i.e. 80 - 99 %)
• * Radiotherapy (5,000 - 6,000 Rads)
• * Chemotherapy (BCNU)

This combination is now "standard therapy", and has been the benchmark to which all other therapies have been compared. Unfortunately, this protocol represents only a single month of improvement over surgery alone! In other words, in over thirty years of clinical research, very little has been done with any outstanding success! (The newly formed Foundation for Neuosurgical Research, however, is dedicated to changing this track record. It will be focused specifically on brain tumor patient improvement alone!)

"Standard therapy" in this country has failed to alleviate, despite spawning 400-plus new, different protocols. This presents a mind-boggling problem for patients and their families, especially when ofttimes they don't even know what a brain tumor really is! Added to the confusion is the enormous proliferation of new technologies becoming available to treat these tumors: lasers, stereotactic computers, cryosurgery, thermal killing machines, ultrasound, radiosurgery, the Gamma Knife, the X-Knife, photoirradiation, blood:brain barrier disruption, boron neutron capture, etc.

Where do science and technology meet the logic of brain tumor biology? What is purely experimental? What is logically worth the effort? What are the numbers? Where does a therapist's enthusiasm for new technology or protocol end, and logical approach to these tumors begin? These are just some of the newer questions which arise during the first weeks after coming in contact with the problem of a malignant brain tumor.

A Guide to the Perplexed

Considering all of the above, the following is a suggested method for approaching the therapy of malignant primary brain tumors. Be logical.

Imagine that a particular tumor weighs about 100 grams. Consider the following:

100 gm of tumor = 100 billion cells, approximately.

If a tumor size can double in volume in a matter of weeks, it would make sense to decrease the size of the mass of the tumor right away. Otherwise, a patient could not make it through a treatment course. Surgery is the way to radically reduce the volume of a tumor, removing anywhere from 80 to 99% of the tumor mass. Recent advances in surgical technologies have aided in the removal of brain tumor tissue with a newer, higher net percentage tumor reduction of 90-99%. These include computer assisted stereotactic surgery, laser instrumentation (carbon dioxide, argon, and Yag), ultrasonic aspiration, operative phototherapy, etc.

Consider the following:

• 90% removal of tumor (100,000,000,000 cells), leaves 10 billion cells
• 99% removal of tumor (100,000,000,000 cells), leaves 1 billion cells

Thus, no matter how good the local surgical therapy is, the patient is still left with at least 1 billion tumor cells!

There now remains the combination of therapies: follow up the initial volume reduction therapy with something else. The usual choices are radiotherapy or chemotherapy. In the best of circumstances, one could expect another 90-99% reduction in tumor cell number. Another 90-99.9 % cell reduction still leaves 1 million to 100 million cells.

The logical procedure now would be to hit the tumor again with yet something else, (usually radiation or chemotherapy) that might attack the remaining cell population.

If left without treating a third time, it is possible that the tumor could return to its original size in as few as 6 weeks, factoring in the numbers mentioned above.

This is not encouraging news, but Sue and I are committed to battle this thing with all the fight we have in us. Feel free to send any positive vibes our way. We're going to need them.