Radiation Therapy

A second kind of cancer treatment is radiation therapy. In this case we use high energy coming out of a radiation generator to create a release of energy within the patient’s DNA. Comparing this kind of treatment with surgery, radiation is going to give us excellent control of those microscopic margins, because we aim it in the area where the primary tumor is located, but also is going to have a wider spectrum. As opposed to surgery, radiation is not invasive and it has very few side effects and does kill cells. The problem is, though, you still need a target tumor, just as with surgery. We have to know where we are aiming it. You cannot radiate the whole body.

Also, you only get one lifetime anatomic dose. Once you have full therapeutic radiation, you can never have it again no matter how many years later. You’ve done enough damage to the blood vessels. If you radiate again on that area, probably you’ll cause death of any of the tissue you radiate.

Radiation doesn’t handle bulk very well. It needs a small amount of tumor cells, unlike surgery. It might be a good complement to surgery, however. Surgery handles the margins poorly, radiation handles them well.

The primary goal of radiation therapy is the injury to the cancer cells’ DNA. The wavelength used is such that radiation can cause a break in the DNA chain. The idea, however, is not to fry the cell. If you’re going to fry cells, you’re going to fry all the cells radiation goes through.

What we’re looking for with radiation therapy is to get the cancer cells to lose reproductive ability. We want the cell not to die because you boiled it up like an egg, but to make it so that when it tries to reproduce it just can’t. That may take several cell divisions before it falls apart, and that’s why radiation may take so long to show results. These cells have to go through a certain number of attempts to replicate before they finally die. Here we are making use of the fact that the fast-replicating cells are the cancer cells, so they are the ones dying. Most of our cells are resting, not replicating, so they are not going to feel the effect of radiation.

The dosages used are usually 5000 Rads or 50 Gray to a specific are, for example the whole breast. If you want to compare that with diagnostic radiation, a mammogram would be about 1 rad.

There are some cases of tumors induced by radiation therapy, but not nearly as many as other sources of radiation.

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Breast Cancer Surgery

Breast cancer surgery has always been the first line of treatment for this disease, and remains so today, even though is the most invasive one. Surgery is the tool with which we can remove the bulk of the tumor most easily. The good thing about surgery is that it removes the whole mass, whenever possible. A problem with it is that it requires a target. We have to know where the tumor is. This is often the case with breast cancer surgery.

Also, surgery is very invasive and we don’t get control of the microscopic margins. When we take out a cancer, it is very important that we leave no tumor cells behind at the edges. The way we do this is trying to go in and take normal tissue around the tumor as much as we can without causing destruction. In certain areas this is going to be easier than in others. For example, in breast cancer surgery we can usually take an area of normal breast tissue around the tumor, whereas in the brain everything you take will lead to destruction.

In breast cancer we have three operations we use to do. William Halsted, a very famous professor of surgery at John Hopkins, is considered the father of modern surgery. He invented rubber gloves for his girlfriend, who was a nurse allergic to disinfectants. He invented the radical mastectomy for breast cancer. With this, the entire breast was removed, and also all the pectoral muscles were removed, because he thought cancer spread through the pectoral muscles. We now know this isn’t often the case.

Around the 1960’s, doctors decided that that was too much surgery. We started removing the entire breast but leaving the pectoral muscles. After that, we moved into what is now called lumpectomy, where the tumor is removed with a little margin of normal tissue. Then, through a separate incision, we use to take out lymph nodes and do what is called a sentinel node biopsy. We inject either dye or radioactive material before the operation that will be picked up by the lymphatics and deposited in these lymph nodes. Then, we open up the axilla and we look for the dye. We take out the lymph nodes and we see if it contains metastasis. It is unusual for metastases to skip lymph nodes, so if it is clean, we consider that the tumor has not metastasized.

In order to see if this really works, surgical protocols were started about three decades ago. With many studies we found that lumpectomy with axillary dissection worked as well as the modified radical mastectomy, which worked also as well as Halsted’s radical mastectomy. Now, the lumpectomy with axillary dissection is the gold standard.

What we try to achieve surgery is to do less and less to patients in a surgical way, as it is so invasive. So far, however, we still have the need to do breast cancer surgery in a lot of cases.

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Cancer Treatment

We’ve seen what cancer is and what we think causes it. What about cancer treatment? How do we treat and cure this fearsome disease? There are three ways to treat cancer: surgery, radiation and chemotherapy. Surgery is by far the most common cancer treatment. Removal of a tumor that is localized can cure cancer. Much of cancer surgery in recent years has become conservative of the surrounding tissue.

Radiation is used in cancer treatment on localized regions that can’t be removed in surgery. This might be in a very diffuse area, for example. It also might be useful to shrink a tumor that is up against a vital organ and the surgeon is afraid of damaging that organ. Radiation damages DNA, it causes both strands of DNA to be broken. The amounts of radiation used are small from the military viewpoint, but quite large from the medical one. Let’s illustrate this. The lifetime exposure to radiation of a typical person on Earth is about 0.12 gray (a physical unit). During the course of radiation treatment, the tumor itself gets 50 gray over five weeks. That’s 400 times the lifetime dose.

The third method of cancer treatment is called chemotherapy. It is used when tumors have spread over the body, because when you put a drug in the blood system, it will be distributed everywhere. Typical chemotherapy uses drugs that kill all dividing cells, including the tumor. There are side effects to chemotherapy. Normal tissues get affected, like bone marrow, cells in the intestines and skin.

A wide array of drugs that block cell division have been isolated and are used. Some are natural products we get from plants, others we build in the laboratory.

A Real Life Case

This is a real case involving cancer treatment with chemotherapy. John first noted that he tired easily at the gym. It got worst over several weeks. When he began to have shortness of breath even when he walked from room to room, he decided to see his physician. When his doctor looked at a drop of blood under the microscope, he saw many white blood cells. A blood sample was sent to laboratory, and they confirmed that he had over 200000 white blood cells per milliliter. This is 40 times normal. An hematologist looked at bone marrow as well as the blood and found a lot of immature white blood cells. In addition, he saw an abnormality: a funny looking chromosome called the “Philadelphia chromosome”. The diagnosis: chronic myelogenous leukemia.

No one knows how, but in this disease, the DNA in two chromosomes inside an immature white blood cell is cut and spliced. Two chromosomes exchange material, so that part of two genes that are ordinarily on separate chromosomes come to be right beside one another. The shuffled chromosome that was seen in John’s white blood cells was first noticed by scientists in Philadelphia in 1960, that’s where it got its name. White blood cells carrying this strange chromosome are stimulated to divide very rapidly. This is why they found this huge number of cells in John.

John was first treated with standard chemotherapy. He was given drugs designed to kill any reproducing cell. One of the drugs bound to DNA. A second one blocked the assembly of amino-acids. A third drug blocked the mechanism that partitions chromosomes to new cells. These drugs have bad side effects on other dividing cells. Using this conventional cancer treatment, John’s white blood cell count went down from 200000 per milliliter to 80000 per milliliter. This is still 16 times normal, however.

The drugs that John took blocked cell division all over the body. They were non-specific. John’s oncologist now tried a new approach: a specific drug. In the 1990’s, the molecular biology of this type of leukemia was described in detail. The new gene found in the Philadelphia chromosome was sequenced, and its protein product was studied. The protein turned out to be a terrific cell-division stimulant. It causes cells to divide without control.

Next, chemists at a drug company went into the laboratory and designed a brand new substance: a chemical that would specifically bind to and inactivate this new gene product in the tumor cells. At the University of Oregon, Dr. Brian Druker coordinated a clinical trial in which patients with chronic myelogenous leukemia were given this drug; to test for its safety and then its effectiveness. Patients like John, whose blood concentration of white blood cells was still high, were given the new drug and the result was spectacular. In John’s case, his white blood cell count went down to a normal 5400 per milliliter. He was cured.

The development of this drug, which is called Gleevec, is a great example of a new molecular approach to cancer treatment. The aim is to find out precisely what’s going wrong in a tumor cell and design rational treatments on this basis.

Precise molecular descriptions of the chemical biology of cancer are leading to new drug treatment for cancer and targeted chemotherapies.

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