When Willard "Neal" Mills suffered chest pain two years ago, his doctor at first suspected bronchitis or allergies. A scan showed something far worse: cancer in the longtime smoker's lungs.
The disease marched unchecked into his liver and bones despite months of chemotherapy, radiation and the newest treatment that stimulates the body's own immune system to fight cancer. Such progression is common with lung cancer, which kills more than 150,000 people a year nationwide.
Doctors didn't think Mills had more than six months to live.
Then a dramatic shift occurred in Mills, and now the recently retired planning director for the city of Havre de Grace is virtually cancer-free. He plans to move to his dream home in Florida and play some golf.
"Is it a miracle? Yes," said Mills, now 67. "Even the doctors say it's pretty close to a miracle."
In scientific circles it's known as the "abscopal effect," and doctors are increasingly convinced it's a real phenomenon that eventually might be induced in others. It starts with a small zap of radiation targeting one tumor and results, inexplicably, with a reduction in cancer cells throughout the body.
In Mills' case, the radiation was aimed at a tumor in his rib in hopes of diminishing its size and the pain it was causing in Mills' back. His oncologist at MedStar Franklin Square Medical Center, Dr. Suman Rao, said what happened next isn't entirely clear, though she believes the radiation kicked the immunotherapy drugs still in his system into hyperdrive.
Researchers have undertaken a number of clinical trials across the country to explore how radiation may be enhancing the positive effects of immunotherapy drugs and who may benefit.
Immunotherapy drugs have gained attention in recent years for their dramatic effects on various cancers. Former President Jimmy Carter's advanced melanoma was sent into remission after he was treated with such medications. Researchers hope to boost the benefits or extend them to more patients by coupling the medications with radiation.
While a small number of immunotherapy drugs are approved for lung cancer, for example, they have been shown to work on only about 20 percent of patients.
But the existence of an abscopal effect is hotly debated.
Some patients who have been given immunotherapy and targeted radiation have seen their condition worsen before they improve. That delay has some doctors questioning whether radiation brings on an abscopal effect, and even whether it's real, said Dr. Russell Hales, an assistant professor of radiation oncology and molecular radiation sciences at the Johns Hopkins School of Medicine.
"Would the patient be destined to have a good response anyway, or was there something about the radiation that unleashed the immune system to be more active in thwarting tumors?" Hales said. "That's the unknown."
Hales believes there is something to the radiation, but it's poorly understood. He's been looking through medical records of hundreds of lung cancer patients on immunotherapy for evidence of an abscopal effect after radiation and has found the phenomenon may have occurred in up to 10 percent of them.
It's also unclear how long the effects last. Among his patients, small cancers have appeared sometimes months after medications were stopped.
Scientists say far more study is needed to determine when to use radiation, where to aim it and how big a dose to use on patients with advanced cancers, as well as which immunotherapy drugs to use.
One such trial sponsored by the National Cancer Institute will seek to answer some of those questions by studying radiation in combination with two immunotherapy drugs that are not yet approved. Other studies underway around the world are using immunotherapy drugs to try to induce an abscopal effect in colon and breast cancer patients.
Dr. Jonathan Schoenfeld, an assistant professor of radiation oncology at Harvard Medical School and the principal investigator in the National Cancer Institute study, said radiation was once thought to suppress the immune system. Now there is general consensus among doctors that radiation stimulates it.
There are rare accounts of the abscopal effect in humans dating to the 1950s, before immunotherapy drugs were developed. Doctors believe the immunotherapy drugs simply increase the chances of inducing the effect, but Schoenfeld said more study is needed to understand how to harness the combined power of the treatments
Schoenfeld and Hales said doctors should resist zapping a tumor in each patient with advanced cancer to try to induce an abscopal effect. The radiation can have damaging side effects and put trials with more promising therapies off limits, they said.
"There is increasing recognition these abscopal effects are happening, and it's obviously stimulating a lot of excitement," Schoenfeld said. "But we need more trials that compare patients who get radiation to those who don't. ... The number of those trials is dramatically increased over the last few years. We're getting answers about which patients might benefit."
Mills' doctor, Rao, conceded that the possibility of an abscopal effect was in the back of her mind when she ordered radiation to try to reduce the size of the tumor.
His prognosis had become poor. He had become extremely fatigued and thin, and he'd lost his voice. Routine tasks such as taking out the trash had become challenging. He was relying on friends and his grown children to care for him and his mother, for whom he had been tending in her last months.
"Let's just see what happens," Rao told Mills, keeping her hopes to herself.
A week after the treatment, Mills said, his whole body felt better.
Mills said he was always eager for the next treatment option when the last one failed, a never-give-up ethos he gained in 30 years as a pilot in the Air Force. He was about to enter a trial for a drug that would target a gene mutation linked to his lung cancer and thought his improved strength would help him withstand the next round.
He went for a routine scan required by the trial, and a nurse gave him the results.
"She said the cancer is no longer officially measurable," he said. "It's disappeared or it's too small to detect. I kept saying, 'What?'"
That was more than a year ago, and Mills said he still doesn't quite understand what happened. Because the doctors can't quite explain it either, they've chosen to keep him on the immunotherapy drugs. He comes to Franklin Square every other week for about an hour and a solution is dripped into his body. Doctors have found him a hospital where he can continue treatment in Florida.
Recently, about a year after the scan found no cancer in his body, doctors found a small cancerous lesion on his spine and they decided to try radiation again to eliminate it.
"I'm going to live each day like a normal day until someone above me says I can't," Mills said just before the spot was radiated. "My message to anyone else in this situation is this is such a dynamic field. You can't quit. Don't quit."