Radiation cervical cancer

Anna Swoboda left my office in tears last week. Ashamed of her emotion, she would not look at me to say good-bye. Instead she rose up on her toes to give me a hug that was as shy and delicately continental as the accent in her English. She thinks I cured her cancer. In fact, I only helped aim the beam of light that did the job. But that's getting ahead of the story.

We met three years ago. Anna was then just 40 years old. She had fled to Chicago with the coming of martial law in Poland. There she had been a schoolteacher, but in this new country she had been obliged to make her living as a translator and an English tutor for other emigres. Together she and her husband earned their green cards, raised a daughter, and bought a bungalow. She had begun to believe that the American dream was within reach. Then the bleeding started.

Always full of energy, always scrimping to save, Anna--like many self-employed women--had never seen the need for extravagances like medical insurance and Pap smears. At first she tried to ignore the backache, the discharge, the spotting. Then she hemorrhaged. She paid doctors cash to diagnose her as one of the 15,000 women who develop cervical cancer each year in the United States. After that, Anna's lack of insurance proved crippling: oncologists at major medical centers gave her much sympathy but no therapy. The knowledge that her malignancy was growing while time seeped away gnawed at her courage. She lost weight, couldn't sleep, and almost lost hope. Finally she came to Cook County Hospital, where lack of health insurance never matters, and to me, the gynecologic oncologist there.

In the two weeks after our meeting, I took Anna through the tests we use to determine the size and extent of a cancer. First I gave her a pelvic examination while she lay under anesthesia, so I could feel the tumor growing into and around the ligaments that bound her cervix to the pelvic bones. The weight of the tumor on these ligaments had been the cause of Anna's back pain. And a growing tumor sprouts blood vessels to nourish it; these fragile new vessels, which break easily, were the cause of her intermittent bleeding.

Next I ordered radiographs of her chest and urinary system and inspected her rectum and bladder with special endoscopes. In the early stages, cervical cancers are confined to the cervix, burrowing into that fibrous ring designed by nature to hold in a pregnancy until labor pulls it open. Anna's cancer had grown into the tissues surrounding her pelvic bones, but it had not spread outside the pelvis. Still, it was too big for a surgical cure, and chemotherapy by itself has proved to be of little value in the treatment of cervical cancer. I told her she would have to undergo radiation.

Radiation is invisible, mysterious, and dangerous, and therefore it has become terrifying. The ghosts of Hiroshima and Nagasaki still haunt the word, and all the fear that radiation evokes was reflected in Anna's eyes when I began to explain what her treatment would entail. Radiation, like a scalpel, is not an instrument one wields cavalierly. It has taken a century to learn discrimination in its use. In 1895, Wilhelm Rontgen illuminated the bones of a hand with X-rays on a photographic plate. In 1898 the Curies discovered radium, and soon after, radiation was incorporated into cancer treatment.

Radiation is not generic. Though physicists have learned to fire neutrons and other esoteric particles at cancers, therapeutic radiation generally comes in three forms: alpha particles (helium nuclei), beta particles (electrons), and the high-energy photons that make up both gamma rays and X-rays. Of the three forms, only high-energy photons penetrate deeply into tissue.

I referred Anna to radiation oncologists, specialists in the therapeutic use of radiation. Photons were what they fired at her every day, photons like the ones that provide the light you use to read this page but endowed with such tremendous energy that they penetrate steel and fly through the body like sunlight through glass. To produce these high-energy photons, they used a device called a linear accelerator. It shoots a stream of electrons at a target; their impact releases the high-energy photons that make up X-rays.

The passage of X-rays through tissue is not uneventful, however. The treatment of cervical cancer with radiation depends on the ability of radiation to interact with the DNA of cancer cells selectively, killing them more effectively than it does normal cells. The X-ray's high-energy photons strike molecules in tissue, releasing some of their energy. That energy breaks up the molecules, stripping off electrons, which leaves free radicals, charged particles that react explosively with other molecules.

Proteins, carbohydrates, and fats that react with free radicals can be replaced or reconstructed. But when free radicals react with the cell's DNA, they can break the string of genetic information that governs fundamental life processes. Normal cells can detect the presence of many breaks in the DNA and halt cell division, providing time for repair. But in rapidly proliferating cells, like those that make up a cancer, the genetic information that controls orderly cell division has been lost. So a cancerous cell begins to divide before repair can occur. The attempt activates "suicide" enzymes, and the cancerous cell dies.

In principle, then, radiation's assault is selective: it kills only cancer cells while sparing normal ones. In practice, though, nothing is so simple. Cells in many tissues, such as bone marrow, hair follicles, or the intestinal lining, normally divide rapidly to replace cells that are sloughed or consumed. Radiation can damage these perfectly normal cells too--leading to anemia and, depending on the site of radiation, hair loss, nausea, and diarrhea.

Healthy tissues that stand in the path of the X-rays can also be scarred by the repair processes. Small arteries grow narrower. Tissues starve for oxygen. Oxygen starvation is worst inside the cancer, where blood vessels are compressed or distorted by the growing tumor. But the success of radiation depends on the presence of oxygen, because free radicals are often formed in interactions with oxygen. Thus an oxygen-poor cancer can become resistant to radiation's lethal effects.

To overcome this, medical scientists have developed drugs that form free radicals easily when radiated. By virtue of their chemistry, these drugs, called radiation sensitizers, accumulate in the acidic, oxygen-poor tissue of tumors, where they react with DNA almost as effectively as free radicals formed by interactions with oxygen. Anna Swoboda took one of these radiation sensitizers--hydroxyurea--twice a week during the five weeks of her radiation therapy.

She did relatively well. The radiation oncologists painted the skin overlying her pelvic region with indelible purple ink to mark their field. For five days each week, she lay in the beam of the linear accelerator, turning from back to front and side to side, using different angles to maximize the radiation dose to the center of her tumor while sparing other tissues. Her ovaries, exquisitely sensitive to radiation toxicity, shut down after only three weeks. The radiation had burned the ovarian follicles--the small sacs that produce the hormones eggs need to mature. As a result, Anna was entering premature menopause.

I prescribed estrogen to avoid compounding the depression that follows a cancer diagnosis with the mood swings of menopause. Her bowel, partially included in the radiation beam, grew irritable, and I gave her other drugs to quiet her nausea and diarrhea. The hydroxyurea exacerbated her anemia, and she had to be given red blood cells to promote better oxygen flow into the tumor. The more oxygen in the tumor, the better the chance that the radiation therapy would succeed. Anna came through all those side effects with the same shy smile. And most important, each week when the radiation oncologist and I examined her, we saw the cancer steadily sloughing and shrinking.

Cervical cancers lie deep within the body, and even with radiation sensitizers they are relatively resistant to treatment. Doses of radiation high enough to cure cervical cancer are easily delivered by linear accelerators. But the bladder and rectum are in intimate contact with the cervix, the former above it, the latter behind. The problem oncologists face is that radiation doses high enough to eradicate all the malignant cells in a cancer as advanced as Anna's would burn the bladder and rectum until the former became a fibrous, inelastic bag and the latter bled.