Photodynamic Therapy: A Brigh... Health Article

Robert Browning had emphysema, suffered repeated bouts of pneumonia, and began coughing up blood before he was told that he had lung cancer in 1994. James S. McCaughan, Jr., MD, director of the Grant Laser Center in Columbus, Ohio, was the light at the end of Browning’s tunnel.

The Chandlersville, Ohio, man is still alive, thanks to photodynamic therapy, or PDT, a procedure a century in the making.

McCaughan slipped a bronchoscope down Browning’s windpipe and killed 3 tumors using a laser beam directed through the end of the scope. No chemotherapy. No radiation. No surgical scar. Just a red beam of light pointed at drug-saturated tumors.

Five years later, Browning, age 70, has no signs of recurrence, says McCaughan.

For people with small early-stage lung tumors close enough to the windpipe so that the laser can reach them, PDT treatment can mean a cure. For people whose lung cancers are later stage, PDT can be used to improve the quality of life.

How Does PDT Work?

Before doing PDT, doctors use a computed tomography (CT) scan to locate the tumor. The CT scan also helps ensure that the cancer is in an early stage. That means it has not spread to distant organs, called metastasis. Nor is there cancerous fluid on the lungs, called malignant pleural effusion.

The laser used in PDT relies on a light-sensitive drug called Photofrin (porfimer sodium), which the person receives intravenously a couple of days before the procedure. The drug accumulates in tumor cells but clears from normal tissues.

With the person sedated, the doctor places a long, flexible, lighted tube called a bronchoscope through the mouth or nose and into the trachea and the lungs. The doctor then passes a fiberoptic tube, equipped with a laser, down the bronchoscope. The drug-soaked tumor reacts to the red light of the laser, which may be directed at the tumor for 15 to 20 minutes.

The light isn’t hot and doesn’t burn the tissue. “It works by what is known as the photodynamic effect,” explains Thomas Dougherty, PhD, who has perfected PDT throughout a career that began as a chemist at DuPont.  He’s now the chief of the Department of Radiation Biology and Photodynamic Therapy at Roswell Park Cancer Institute in Buffalo, N.Y. “The light is absorbed by the drug sensitizer inside the tumor. Once that happens, a photochemical reaction occurs.” Energy from the reaction is transferred into singlet oxygens, which are high-energy molecules with a short life. “That’s what attacks the cancer cell. It actually oxidizes it,” Dougherty says.

Each molecule remains stimulated as long as the laser shines on it. Dougherty, peering through the scope, can see the tumor dying. The tissue starts to blacken, indicating its blood supply is being severed. The person returns a few days later for another bronchoscopy so that the doctor can use forceps to delicately pull out the dead tumor. Doctors are currently limited to treating the tumors they can reach through a bronchoscope. Many tumors are located along the outside of the lung and cannot be reached in this way.

The Hope PDT Offers

Most lung cancers start in the lining of the bronchi, the tubes that branch into the lungs from the windpipe, or bronchus. Routine screening tests don’t exist for lung cancer as they do for cervical cancer (Pap smears) and colon cancer (fecal-occult blood tests). Thus, only about 15% of lung cancers are detected in this early stage, when PDT or other treatments have the best chance for success.

In carefully selected people whose tumors are small (less than 1 cm) and near the surface windpipe, PDT can provide 5-year survival rates comparable to those for surgery, says McCaughan.

“It works, I guarantee you, for early-stage lung cancers,” says Dougherty.

Beyond the possible cure that PDT offers for the few people whose lung cancer is found early, Dougherty says that PDT can be paired with standard treatments—including chemotherapy, radiation, or surgery—and can be used to control some of the symptoms of lung cancer. That can improve the quality of life for a person with cancer. Here are some examples.

• In cases where a person has cancer in both lungs, doctors can remove one lung. And if the remaining tumors are located close enough to the bronchus, doctors can use PDT to treat them.

• Some people who are not physically able to tolerate surgery or the loss of lung function by having a lobe removed can tolerate PDT.

• PDT can be the only hope for a person who has a tumor growing in a surgically risky spot, such as the carina, where the trachea splits into the right and left bronchi.

• PDT can help improve the quality of life for someone whose advanced tumor is so large that it interferes with breathing. The procedure can be used to reduce symptoms by shrinking the obstructive tumor. In these situations, PDT is as efficient as some other palliative methods, including electrosurgery, Nd-YAG laser, and brachytherapy.

• PDT can be used when a cancer reoccurs in the windpipe in the same place, which was previously treated with radiotherapy.

Possible Future Improvements for PDT

The main drawback of PDT is that Photofrin remains in the person’s skin for 4 to 6 weeks, which means that the person must stay totally out of the sun or risk getting a severe sunburn.

“The sun is a real problem,” says Matt Brenner, MD, a pulmonologist at the Beckman Laser Center in Irvine, Calif. People who use PDT for symptom relief may have only a few days or weeks to live. “If they have to spend 4 to 6 weeks indoors, that’s a real downside.”

He says new experimental light-sensitive medications may prove to concentrate more precisely in the tumor cells, allowing more effectiveness and fewer side effects. If drugs of the future are stronger, the laser beams may be able to penetrate more deeply. Another direction is to develop new agents that are retained in the cancer cells longer, but clear from the skin cells faster.

“The real key to the future of this field is going to be the development of a variety of dyes that can maybe allow you to tailor your therapy to the type and location of tumor,” Brenner says.

The concept of destroying cells through the use of dyes, oxygen, and light dates back to the early 1900s, according to McCaughan. Scientists discovered in 1924 that ultraviolet light could stimulate tumors to give off a red-orange fluorescence. They later used that knowledge to help detect tumors in humans.

Putting PDT to Work

The U.S. Food and Drug Administration gave approval for use of Photofrin in PDT for advanced esophageal cancers in late 1995. Three years later, the approval came for early-stage lung cancers, and Dougherty says approvals are pending for use in early-stage esophageal cancers. The method is also being tried in Barrett’s esophagus, a precancerous form of esophageal disease connected with prolonged heartburn and reflux disease.

Dougherty says that although this treatment has been evolving for decades, it has been slow to catch on. “There’s a certain reluctance from doctors who haven’t used a laser to learn how to do it.” Even so, about 100 centers in the United States offer PDT, as do several others scattered through Europe, Japan, and Canada.

People with lung cancer can locate a center by asking for a referral from their doctor. They can also find centers by searching the Internet, with assistance from a medical librarian. QLT PhotoTherapeutics of Vancouver, Canada, makes the light-sensitive drug Photofrin, and staff members know which centers it is shipped to throughout the world.

Even with the better photosensitizing drugs that the future may hold—and laser beams that penetrate more deeply—for now, PDT is a procedure that can help only a small number of people diagnosed with lung cancer. Since it is rare that people learn that they have lung cancer while the cancer is in its early stages, doctors don’t expect to make big strides in reducing cancer deaths until better screening exists.

That’s why Browning undergoes a biopsy every year. It’s not an easy procedure, but he knows it’s imperative. Since he’s already had lung cancer, he’s at a greater risk of developing it again.

He says he thinks often about PDT and how it has extended his life. It hurts him to breathe in cold weather, he gets short of breath easily, but, he says, “I don’t have cancer.”

A partial list of facilities offering PDT can be found at http://www.axcan.com/photofrin/pdtsites.php?lang=1.