Doctors freezing away tumors

Doctors freezing away tumors

Cryoablation put to the test as scar-free breast cancer therapy

ASSOCIATED PRESS WASHINGTON, Sept. 9 — Robin Imhof watched, fascinated, as her doctor stuck a needle into the dime-sized lump in her breast and pumped freezing gas through it. On a nearby ultrasound monitor, a round image gradually turned lighter and lighter - her noncancerous but extremely painful tumor being encased in a ball of ice.

IT DIDN’T HURT

- the cold itself was anesthetic even as it froze the growth to death. No hospital stay, stitches or scar. An hour later, the Ferndale, Wash., woman headed home to wait for the lump to shrink over the next few months, her body slowly absorbing the destroyed cells.

Doctors have long attacked tumors with heat. Now a few clinics around the country are turning to cold. Called cryoablation, it’s being used to extend the lives of people dying from liver cancer, to treat prostate cancer, and as the first nonsurgical alternative for the half-million women who have benign breast tumors removed each year. Doctors have just begun testing it as a possible scar-free way to remove early breast cancer, and as an alternative to open surgery for kidney cancer.

It’s catching on slowly - the delicate technique requires special training to avoid serious side effects from accidentally freezing healthy tissue, and it has a controversial history. But “it made perfect sense,” says Imhof, explaining why she chose cryoablation over standard breast surgery. “I thought, ‘Yeah, the simple science of stuff in your freezer decaying ... that makes really good sense.”’

Cryoablation, which destroys cells by shattering their outer walls during freeze-and-thaw cycles, actually was first hailed in the 1960s. But it proved too risky for much deep-body use - doctors couldn’t see what they were aiming to freeze and thus had high complication rates. Dermatologists and gynecologists continued to freeze away easy-to-see skin or cervical growths, but other uses of cryoablation faded away.

CRYOABLATION COMEBACK

Today it’s making a slow comeback thanks to improved medical imaging that allows doctors to see deep in the body while they work. They can place a needle that emits freezing gas - argon is used primarily - in a tumor or organ and literally watch until ice encases it.



“You could see it so exquisitely under ultrasound,” said Dr. Gary Onik, who pioneered cryoablation’s return. The first approved use is in patients whose colorectal cancer had spread to the liver and become inoperable. Cryoablation offers the hope of buying them some time; Onik says about 20 percent of his patients survive five years.



For prostate cancer, cryoablation proved more difficult. Bad aim causes serious side effects in the bladder or rectum; inconsistent freezing can miss cancer. But after years of research - and bad publicity from what Onik says were poorly trained doctors and technology companies rushing the procedure - a recent study published in the journal Urology suggests a careful cryoablation technique may be as effective as a widely used treatment, radioactive seed implants.

Like other prostate treatments, however, cryoablation can cause impotence. So Onik, at Florida Hospital/Celebration Health, is experimenting with a nerve-sparing version in hopes of reducing that risk.

On to the breast: Sanarus Medical Inc. recently won federal approval of its cryoablation system to destroy fibroadenomas, benign breast tumors like Imhof’s.

The weapons are changing in the war on cancer. Some cases of breast cancer may be prevented with a pill; better scanning techniques are diagnosing prostate cancer with a precision never before possible. Most exciting, scientists say, are new drugs that target the disease’s genetic roots, seeking out and destroying cancerous cells while leaving healthy ones unscathed.

Select from the Prevention, Testing or Treatment tabs above to find out more about new approaches as well as some in the pipeline.

Designer anti-estrogens

Taking advantage of the fact that the female hormone estrogen fuels the growth of breast cancer, scientists have developed anti-estrogen drugs that block the action of estrogens and thereby interfere with, or even prevent, the proliferation of breast and uterine cancer cells.

About five years ago, researchers reported that tamoxifen -- a designer anti-estrogen that has been used for years to treat breast cancer -- also prevents the disease in high-risk women. Then came reports that its cousin raloxifene, already on the market for osteoporosis, reduces such risk by two-thirds. Both drugs bind to estrogen receptors in the breast and prevent the hormone itself from binding to the receptors and contributing to the growth of cancer. A big plus: Both can be given in pill form.

One of the most exciting developments in this area is an experimental class of drugs called aromatase inhibitors, which block the action of an enzyme women need to produce estrogen. New research indicates that these experimental hormone-blocking drugs work better than standard tamoxifen in preventing women with early-stage breast cancer from developing tumors in the healthy breast.

Vitamins

Evidence is accumulating that antioxidant vitamins, such as C and E, may lower the risk of a variety of cancers by sopping up so-called oxygen-free radicals that can damage DNA. In one study, daily supplements of vitamin E cut the risk of prostate cancer by about one-third; in another, lycopene, which has the distinction of being both an antioxidant and the stuff that makes tomatoes red, also appeared to ward off prostate cancer.

The vitamins may also enhance the disease-fighting abilities of the immune system.

The B vitamin folic acid also appears to have tumor-fighting properties; in one study, women with family history of colon cancer lowered their risk by taking vitamins containing folic acid. And vitamin D may help prevent colon cancer by detoxifying one of the body’s most toxic digestive byproducts, although scientists warn that high doses can do more harm than good.

Other new research suggests that eating even moderate amounts of oily fish like salmon, mackerel or sardines that are rich in omega-3 fatty acids may cut the risk of prostate cancer in half.



Prophylactic Surgery

In the strongest study yet to show that the controversial strategy works, Dutch researchers recently reported that removing the healthy breasts of women with genetic mutations that often trigger breast cancer can save their lives. And new work suggests that removal of the ovaries is an effective option for women with so-called breast cancer genes BRCA1 and BRCA2.



Scanning techniques

A new imaging device is diagnosing prostate cancer with a precision never before possible, guiding doctors in choosing the best treatment. The device: a standard MRI, or magnetic resonance imaging, machine attached to equipment that measures chemical activity inside prostate tissue, showing exactly where the cancer is and how far it has spread.

Early detection in lung cancer can be lifesaving, but it extremely difficult. Now researchers report that spiral CT scans are proving three to 10 times more effective at detecting malignant lung disease than traditional chest x-rays. The multi slice-low dose spiral CT scanner improves on the regular CT scanner by offering faster scanning, and is able to achieve better resolution and more diagnostic detail.

Genetic testing

In the past few years, it has become clear that cancer is a disease of good genes gone bad, due to both inherited mutations and errors in DNA accumulated over a lifetime. This new understanding is leading to tests that can home in on faulty genes years before cancer symptoms ever develop.

One gene, known as p53, that normally puts the brakes on out-of-control cell growth is thought to be damaged in over half of all cancers. While p53 testing is still controversial, it is frequently performed in clinical trials. And checking for the so-called breast-cancer genes BRCA1 and BRCA2 in high-risk women is now offered nationwide.

And a new screening test that detects extremely small traces of a cancer gene called APC in patients’ stool appears to find colon cancer in its early, curable stage. Though still years away from routine use, the experimental test could offer an entirely new approach to mass screening for colon cancer.

Artificial intelligence

Government researchers recently announced that they have discovered a highly accurate blood test for ovarian cancer, dubbed the “silent killer” because until now there was no way to detect it early. The experimental computer-assisted blood test showed an amazing 100 percent accuracy in detecting 50 cases of ovarian cancer, even at the earliest stages.

The researchers already are testing the same early-detection concept for proteins associated with prostate, colon, breast and many other cancers. Stay tuned.

Smart drugs

Scientists are discovering the genes and chemical signals that make cancer cells grow out of control — and then figuring out exactly how to turn them off. The so-called targeted therapies that are growing out of this new understanding of cancer’s molecular roots are widely considered the most exciting advance is the field today.

A monoclonal antibody that seeks out and destroys cancerous cells in some women with advanced breast cancer was the field’s first success story. Called Herceptin, the drug targets the so-called HER-2 gene, which encodes for a growth factor receptor that fuels a particularly aggressive form of the disease in about one-third of women with breast cancer. More recently, Gleevac, which blocks another growth factor receptor that promotes the growth of cancer, was approved for a type of leukemia as well as a rare form of stomach tumor. Hundreds of similar drugs that work against signals that are present in breast cancer, colon cancer and prostate cancer among other forms of the disease are in clinical trials.

Designer anti-estrogens A novel class of drugs known as aromatase inhibitors that cut the body’s production of estrogen appear to work better than the standard anti-estrogen tamoxifen in the treatment of breast cancer — and with fewer side effects. Doctors say it’s too soon to know if the new drugs should replace tamoxifen as a favored drug, but in clinical trials they shrank tumors better and helped more women survive.

Gene therapy

Despite a major setback when an experiment killed a teen-ager at the University of Pennsylvania in 1999, gene therapy continues to show promise in lab animals and small trials of cancer patients. One technique under study involves replacing the defective genes that cause cancer with healthy genes; another injects cancer cells with a gene that makes them more sensitive to treatment with an anti-cancer drug. The hope is that when the anti-cancer drug is given, only the cells that contain the drug-sensitive gene will be killed, leaving healthy tissue unscathed.

Immune vaccines

These novel strategies involve using genetically engineered vaccines to activate cancer patients’ own immune systems to recognize cancer cells as foreign and attack them. While the immune system exists, in essence, to recognize outside invaders and attack them, it often has trouble distinguishing normal cells from cancerous ones. But in recent years, researchers realized that they could take advantage of genetic engineering to wake up a slumbering immune system to the fact that tumor cells have invaded the body. Once they recognized the cancer cells as the enemy, the immune system’s disease-fighting T cells would do their job — and attack, they reasoned. And early studies are bearing that out.

One such vaccine, called GVAX, has demonstrated anti-tumor effects in clinical trials of prostate, pancreatic, lung, renal and skin cancers. And another approach, called a dendritic vaccine, is showing similarly encouraging results in colorectal, lung and prostate cancers.

Anti-angiogenesis agents

Reports that a combination of anti-angiogenesis agents -- drugs that block the growth of blood vessels that feed tumors, choking off their nutrient supply and killing them -- completely cured tumors in mice set off a media furor in 1998. Researchers were quick to temper enthusiasm with caution, and rightly so: Since then, results of clinical trials have been a mixed bag. The experimental drug Neovastat, derived from shark cartilage, appears effective in patients with kidney cancer, and the nose drop IM-862 appears to stabilize ovarian cancers.

But a study of 19 patients with advanced colon, breast, ovarian and head and neck cancer given angiostatin showed tumors did not shrink, although they stopped growing for six months in three of them. And tumors grew in 15 patients given endostatin, although the drug temporarily helped some. Clinical trials continue.

Antisense therapies

A relatively new class of compounds called antisense work at the genetic level to interrupt the production of cancer-causing proteins. The antisense molecule incorporates itself into a gene responsible for key functions of the cancer cell, essentially disabling it and preventing it from operating properly. Researchers recently reported that they had been able to produce a complete response — total disappearance of the tumor — in advanced melanoma, a difficult to treat, fatal disease. The 14-patient study also established safety.

Freeze therapy

Freezing cancer cells and then bombarding them with a toxic drug could be a new weapon in the war against cancer, scientists say. Called cryochemotherapy, the technique involves inserting icy needle-like metallic probes into a tumor, which kill most of the cancerous cells, and then using a potent anti-cancer drug like bleomycin to finish the job. So far, the approach has only been tested in the lab on melanoma cells, though researchers say it could prove effective for most types of solid tumors.

Targeted radiation

Recently, the government approved a drug that uses a “smart bomb” approach to bring radiation directly to cancer cells as a long-awaited treatment for lymphoma. Called Zevalin, the novel approach attaches radiation to antibodies that seek out a protein called CD20 found on lymphoma cells. The antibodies latch onto the cells, flagging them for attack by the immune system.

Another approach, targeted internal radiation, is being used to treat prostate and breast cancers. Called brachytherapy by doctors, the technique delivers radiation seeds just to the tumor site instead of the whole organ, thereby minimizing side effects.

TWO TESTS UNDER WAY

Now the company is conducting two pilot studies to test whether cryoablation might treat breast cancer, too. In one study, 25 women will have small cancers frozen. Three weeks later, they’ll undergo a lumpectomy - standard surgery - so scientists can examine the lump for any cancer cells left lurking around the edges. The hope is that cryoablation might someday replace lumpectomies for certain women.

In the second study, another 25 women will undergo cryo-assisted lumpectomy, as scientists test whether freezing tumors that are hard for surgeons to feel can help them remove all the cancer on the first try.

“There’s tempered enthusiasm,” said study investigator Dr. J. Stanley Smith of the Pennsylvania State College of Medicine, cautioning that it will take years to prove whether the technique works. Other scientists are testing freezing for kidney cancer patients who are poor candidates for grueling open surgery.

Experiments aside, patients considering even approved uses of cryoablation should pick an experienced cryosurgeon, warns Dr. LaMar McGinnis of the American Cancer Society: It takes lots of training and practice to avoid complications.

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