WEDNESDAY, April 11, 2001

When and Why is Radiation Helpful?

Radiation was one of the first non-surgical treatments for cancer. If the body could tolerate radiation, it would be curative; as at very high doses it kills cancer. Certainly in breast cancer radiation has been found to lower the risk of local recurrence in the breast after lumpectomy. There is new evidence from clinical trials that it may also stop the spread of cancer. Radiation depends on energy high enough to break the DNA bonds, and new forms are being developed. The questions that need study are how to use radiation safely and properly, and when does it improve outcome, what are the long and short term side effects, and how can they be minimized.

Lawrence Margolis, M.D., a longtime member of the Department of Radiation Oncology will be our guest tonight. Historically, the first patient treated with radiation was in 1899. The first patient to be treated with a positive response was Babe Ruth who had head/neck cancer in 1947. Evidence from over 20,000 women with breast cancer has indicated that radiation definitely improves local control, the question is whether or not it improves survival. Data from the 1940ís-1960ís does not show evidence of increased survival. More recently, with the addition of chemotherapy, which prevents cancer from entering the bloodstream, radiation is showing improvement in survival.

Should radiation be given before or after chemotherapy? This is controversial, but the general feeling is to give the chemotherapy first. It is first important to clear out anything that might be in the bloodstream. CALGB studies with various types of chemotherapy that varied the time that radiation was given did not seem to show a difference in outcome based on delays in radiation.

How about hormonal therapy? The research group NSABP tends to give the hormonal therapy all during the chemo and radiation. The research group associated with UCSF (CALGB) gives Tamoxifen after both chemotherapy and radiation. This is because it is easier to sort out side effects that might develop from the different treatments. Hormonal therapy can be given at the same time as the radiation. This has shown a significant improvement in overall survival in prostate cancer.

In the 1960ís physicians radiated the whole breast without removing the tumor. This was done with high dose for about 10 weeks, and achieved about 50% control. In the 1980ís, with the advent of lumpectomy, physicians could decrease the radiation dose to the entire breast by about 40% because the mass had been removed. When mastectomy was compared to lumpectomy and radiation, identical survival was found. Now with mammography, smaller and smaller cancers are discovered which can be treated with small amounts of radiation, or none at all. About 1/3 of cancers discovered today are DCIS, which may not even be a true cancer.

Is incidence of recurrence comparable between lumpectomy with radiation and mastectomy? Recurrence varies considerably by size of tumor and surgical skill, but the NSABP-06 study compared three groups: lumpectomy alone, lumpectomy plus radiation, and mastectomy. After eight years the recurrence rate for mastectomy was 8%, lumpectomy plus radiation was 10%, and lumpectomy alone was 53%.

What about nerve and cardiac damage due to radiation? In the early days when massive doses were given routinely nerve damage was fairly common. Now it is extremely rare. Dr. Margolis has not had one case out of 7000. Until about 1980, the lymph nodes along the sternum were radiated. The beam went straight into the heart, damaging the heart muscle. There are centers all over the world that do still use this technique, but here at UCSF, this technique has not been used for 20 years, and we have had no problems with cardiac damage. Techniques that have contributed to minimizing this problem include high energy beams which eliminate damaging penetration; dosimetry (careful calculation of the amount of energy absorbed); and treatment planning and shielding (using CT scans to figure out how dose is delivered and how to adequately shield vital organs).

What would be the long terms side effects of radiation therapy? It is harder to quantify the long term side effects because we donít tend to ask patients quality of life questions twenty years after their treatment. The effects of radiation occur exclusively where the beam is directed. Skin lesions used to be a problem but newer machines are skin sparing and donít cause permanent damage. Treatment planning is now done exclusively by computer and is much more sophisticated. Some people experience a small amount of radiation pneumonia. Other problems, which have now been eliminated, are rib fractures and cardiac problems.

How do you treat skull (bony) metastases with radiation? First we obtain a CT scan of the skull and measure the thickness. Then we use an electron beam, which can be set to the exact thickness of the lesion without giving any radiation to the underlying brain. It is possible to somewhat relieve bone pain at least 80-90% of the time, with complete relief about 50% of the time.

What types of symptoms do women suffer during or after radiation therapy? Treatments are five days a week for five to six weeks with mastectomy and six to seven weeks following lumpectomy. The treatments take about 15 minutes and are totally painless. Most women suffer some fatigue, but many are able to work right through their treatments with a small adjustment for some extra sleep. Local skin reactions will happen to different degrees, depending on sensitivity to radiation and the amount of skin fold present (under the breast, the axilla, etc.). Some degree of redness usually will have occurred by the end of treatment. Patients are told to avoid alcohol-based deodorants during treatment because this can be irritating to the skin. Aloe vera can be very soothing to the skin.

What exactly is radiation doing to the lesion? Radiation is preventing the DNA from dividing within the cell. Cancer cells are more sensitive than normal cells and small doses of radiation will tend to kill cancer cells permanently while allowing the normal cells to recover. After numerous small doses you have hopefully eliminated the tumor while preserving the normal tissue.

If you radiate one metastasis do you prevent another metastasis in another part of the body? This is not generally thought to be the case. Most metastatic conditions have been present for some time before they are discovered, so radiation is unlikely to have an effect. With very slow progression, say in the bone, radiation may slow down progression in other bone sites.

What is the difference between cobalt radiation and linear accelerator treatment? They are biologically equivalent although the linear accelerator has higher energy. There are no cobalt radiation machines left in the Bay Area.

What causes a physician to order a bone scan? It is usually a symptom like pain that prompts the physician to order the scan. When some is totally asymptomatic bone scans are usually not ordered, unless there is a new metastasis. Timing in metastatic cancer is not as critical as in early stage breast cancer. Rather it is the response to the treatment that is important.

What is the relationship between radiation and chemotherapy? The medical oncologist and the radiation oncologist work together to control the spread of disease. Radiation is usually recommended after any lumpectomy. After mastectomy, radiation is only used routinely if the tumor is large (over five centimeters), if the skin or chest wall is involved, or if there are many (over four) positive lymph nodes. It is up to the chemotherapy to treat any spread of disease through the bloodstream (micrometastases), so that radiation can target the tumor and bring local control. Trials that show that radiation can control distant spread are trials in which chemotherapy is also being used.

Whatís new in radiation therapy? Now that we have been able to make a diagnosis based on just a few flecks of calcium, the future plan is to try to identify the patients who might not need radiation therapy. Currently the local control rate for women with small tumors who do not have radiation is 70%. This means that 70 out of 100 women may be getting radiation therapy that donít need it. We cannot determine now whom these women are today, but within ten years we should be able to.

Is there a difference in the positivity of nodes or are all positive nodes the same? The number of tumor cells in the lymph node seems to matter. A micrometastasis would be less of a long-term risk than a regular metastasis. Lymph nodes higher up in the axilla seem to present a higher risk than those found lower in the axilla.

Does the radiation following lumpectomy include radiating the lymph nodes? This is controversial, about 50% of radiologists do and 50% donít. Many things need to be taken into consideration: what is the denominator (1 out of 2 or 2 out of 22 nodes?); what is the grade of the tumor, etc. It is important to individualize care. We cannot even be certain that radiation of the nodes is beneficial. One older U.S. study (30 years ago) showed that there was only a 15% recurrence rate whether or not patients had a lymph node dissection. Patients who later recurred had a delayed dissection, but this did not seem to affect survival. One reason for this may be that surgeons at the time were taking larger amount of tissue from the breast and may have inadvertently been taking out nodes without knowing it.

What is the sentinel node? Blue dye or radioactive tracer is injected in the area of the tumor. The sentinel node is the first node that the tumor drains to, although there can be more than one. This node can then be tested for cancer cells. If that node is negative, the likelihood of other nodes being involved is very low. If the sentinel node were positive, then the surgeon would proceed with a full lymph node dissection. This procedure has a 95-98% accuracy rate in centers that do a lot of these procedures.

If you have had chemotherapy before surgery and no cancer shows in the nodes, could it have been killed by the chemotherapy? Yes, sometimes you can see some scar tissue in the node. In a large randomized study comparing patients who received chemotherapy first to those who received surgery first, the surgery first group had about twice the number of positive nodes. Using neoadjuvant (before surgery) chemotherapy gives us a lot of information about the response of the tumor and prognosis, but we lose information about the status of the lymph nodes.

Do you always recommend radiation for tumors over a certain size? The last overview analysis of over 19,000 women worldwide has shown that women with four or more positive nodes or a tumor of five centimeters or greater, the chest wall recurrence rate was very high, 25-30% with radiation, cut down to just a few percent with chemotherapy. The current controversy is about women with one to three nodes.

What about interoperative radiation? This is radiation during surgery and is being done in Milan. The problem with this procedure is it requires a very large incision to introduce the beam into the tumor, and gives a less satisfactory cosmetic result.