Life after melanoma

Chuck Howard’s symptoms began around Christmas in 2009. They weren’t alarming – just some “minor discomforts” near what he assumed was his gall bladder. When the pain persisted into spring, his doctor ordered some tests.

As the technician performed an ultrasound, Howard, a 62-year-old dentist from Salem, watched for her reaction. “She tried not to tell me too much,” he says, “but it was obvious that she was concerned.” Indeed, this and other tests revealed the cause of Howard’s symptoms. His body was riddled with dozens of tumors, including one above his right kidney that was as large as a baseball.

Howard had advanced melanoma, a skin cancer that had gone undetected while it spread throughout his system. It was a devastating diagnosis. Metastatic melanoma kills 95 out of 100 patients within five years. Howard’s own niece succumbed to the disease at age 27. Still, his reaction was low-key. “I was taken aback, and I don’t really know what was going through my mind other than this could be the end and we’d better start preparing.”

He was referred to oncologist Brendan Curti, M.D., medical director of Providence Biotherapy Program. Dr. Curti specializes in immunotherapy to treat metastatic kidney cancer and melanoma. It just so happened that he and Steven Seung, M.D., Ph.D., a Providence radiation oncologist and immunologist, were studying a new treatment that pairs high-dose radiation with interleukin-2, a powerful immunotherapy.

IL-2, as it’s called, boosts the body’s immune system to seek out and kill cancer cells. It has produced remarkable results, delaying the disease’s progression and in some cases even curing the cancer. But it works for only 15 to 20 percent of patients. On his first visit with Dr. Curti, Howard had no idea if he would be one of them. He recalls Dr. Curti’s metaphor: “He said the treatment would be either a strikeout or a home run.”

Dr. Curti was concerned about his patient. Despite Howard’s optimism, his health was declining rapidly. Experience has taught Dr. Curti that the sicker the patient, the less chance of recovery.

Howard and his wife, Jo, who works in his dental office, hoped for the best, but began to think about the worst. He visited a financial consultant, began to draft his will and advertised for an associate to take over his dental practice while he was in treatment. “I was thinking that even if I recover, I’m probably going to have a shortened life expectancy.”

Dr. Curti enrolled Howard in the new study combining radiation and IL-2. Because the trial was a pilot study, Howard was one of only 12 patients given the combination therapy.

New radiation technology changes everything

Researchers have known for years that radiation affects the immune system, and in the 1980s they conducted a study combining radiation and IL-2, a treatment that they hoped would deliver the one-two punch needed to kill the cancer. The results, however, were disappointing.

“Radiation techniques were not as sophisticated as they are now,” Dr. Seung says of the early research, “and the dose intensity was less than was necessary to kill the melanoma cells.”

In early 2009, Providence acquired a state-of-the-art radiation machine that solved that problem. It could focus a radiation beam precisely on a tumor with doses 10 times stronger than traditional radiation without significantly harming surrounding healthy tissue. This technique is called stereotactic body radiotherapy, or SBRT.

Drs. Seung, Curti and Marka Crittenden, M.D., Ph.D., a Providence scientist and radiation oncologist also involved in the research, designed a study to see if SBRT might give IL-2 the boost it needed to succeed on a higher percentage of patients.

“This finding is very surprising.”

Howard’s treatment began with radiation sessions, followed by a series of IL-2 treatments. The therapy provokes a powerful immune response, with side effects ranging from drops in blood pressure to joint pain and nausea. Because of this, patients are required to be hospitalized for a week during each round.

The left scan shows melanoma tumors invading Chuck Howard’s body. After treatment, the only dark spots are a healthy brain, heart and bladder.

Howard and Jo made the best of it. Jo began referring to Providence Cancer Center as “the resort,” where happy hour began at 3 p.m. with a cocktail of IL-2. Howard celebrated his 61st birthday on the seventh floor. The staff sang “Happy Birthday,” and Howard watched the Ohio State Buckeyes trounce Miami.

Meanwhile, his immune system was finally recognizing the cancer cells and had begun waging a fierce battle against them. The worse Howard’s side effects were – at one point they even included hallucinations – the more evidence that the therapy was working.

Sure enough, the scans that followed each cycle were encouraging. Howard’s tumors were shrinking, then disappearing. The treatment was a home run. The same was happening with others enrolled in the trial; not just one patient, which would have been typical for IL-2 alone, but half the study group was seeing astonishing results.

“Factoring in that it was a small study, this finding is very, very surprising,” Dr. Curti says. “It really has not been observed in the history of interleukin-2 therapy.”

Expanding the research

The pilot study was such a success that Drs. Curti, Seung and Crittenden are testing the therapy in a larger, phase II study. Under this trial of about 40 patients, half will receive the combination therapy and half will get IL-2 alone, allowing researchers to confirm that one regimen is superior to the other.

“We’ve designed the study so that if patients do not respond to interleukin-2 alone, they can subsequently get radiation with IL-2,” Dr. Curti says.

Providence Portland Medical Foundation hopes to raise $800,000 for this research, which was the focus of a special appeal at this year’s Providence Festival of Trees. (See event photos.)

“As we move forward,” Dr. Curti says, “we want to make melanoma treatment work not just 50, 60 or 70 percent of the time, but 95 or 100 percent of the time.”

Six months after treatment, there is no evidence of cancer in Chuck Howard’s body. And given what researchers know about IL-2 successes, there’s a good chance that it won’t return. Howard has resumed the life he had before his diagnosis: He gets up each morning and he goes to work.

“My practice is still here,” he says. “I’d like to be taking more vacations and loafing more, but it’s good. I like working. I’m not ready to quit.”

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