Seeking medical clues from the 'super responder'

Tony Pace and wife Dee at Universal Studios in Florida in 2011. Colon cancer had spread to his liver and bladder, but after rigorous treatment, he is cancer-free.
Tony Pace and wife Dee at Universal Studios in Florida in 2011. Colon cancer had spread to his liver and bladder, but after rigorous treatment, he is cancer-free.
Posted: February 17, 2014

'I'm pretty lucky," Tony Pace explained, which is not the reaction most people might have when hearing his story. In 2008, Pace battled colon cancer that had spread to his liver and bladder. Surgeons removed half of each organ, and had to rebuild the ureter line on the right side of his kidney. Six months of chemotherapy followed. In 2009 came a liver resection along with removal of his gallbladder. The Clifton Heights man, 53, has been cancer-free ever since.

Pace's oncologist calls him an outlier, someone whose reaction to care is so remarkable that it's unexplainable - up until now, anyway.

The National Cancer Institute and a few medical schools are investigating people such as Pace, who are also called exceptional or miracle responders. If well understood, these "miracles" could benefit all cancer patients.

"We have the technology to go deeper to find out who might respond," said Barbara A. Conley, the NCI's associate director of the Cancer Diagnosis Program.

Everyone is unique. Pace, the father of three grown sons, has been married to his soul mate, Dee, for 32 years. He works for much of the year in Orlando, Fla., for an equipment repair company. That's a thumbnail sketch, but Pace's uniqueness goes down to his DNA.

In its exceptional responders' initiative, to be launched this year, the NCI will review results from more than 200 clinical drug trials it has funded to find the 1 percent to 10 percent of patients who had a positive reaction - and to the gene mutations that caused it. Most of the drugs did not get FDA approval.

"If these people have tissues and appropriate consent, we can do massive sequencing on them," Conley said.

Better genetic tracking makes this scientifically and financially possible. The NCI will start with exome sequencing, much cheaper than whole genome sequencing and nearly as effective. It also plans RNA sequencing, a shotgun approach that takes snapshots of genes.

The NCI may then give the same drug to others with the same gene mutation in new clinical trials, regardless of what type of cancer they have. Some drugs already on the market might be included, too.

"Even with approved drugs, if that patient had a complete response, we certainly wouldn't expect that," Conley said.

A few cancer centers are also focusing on super responders, and at least one - Memorial Sloan-Kettering - is not limiting its search to patients treated with little-known therapies. Sloan-Kettering might even include super responders who have undergone surgery, like Pace.

David Solit, an oncologist leading Sloan-Kettering's effort, e-mailed that Pace is "clearly an outlier. The chemo likely contributed, but hard to know. Would be a good case to analyze in detail."

Other cancer centers pursuing super responders are Dana-Farber in Boston and MD Anderson in Houston.

Generosa Grana, director of the MD Anderson Cancer Center at Cooper University Health Care in Camden, hopes her facility might someday be involved in the Houston effort. "I think it's going to change the approach to cancer in general," she said.

There is no accepted definition of an exceptional responder. "It tends to be the person who has an unexplainably good response to whatever treatment you have given them," she said.

Conley says that for the NCI, it ranges from a tumor or tumors fully disappearing to a 30 percent shrinkage that lasts at least six months from a drug that isn't supposed to be that good. It needs to occur in at least 10 percent of patients.

Also, no one knows what exceptional responders have in common. "It's too early to say," Grana said.

The NCI isn't limiting its search to chemo. Hormone therapy is included, and "immunotherapy is not excluded," Conley said. "We want to keep it broad for now."

Chemotherapy kills cancer cells but also weakens the immune system. Immunotherapy, a newer approach, strengthens it, and that's a focus at the Abramson Cancer Center at the University of Pennsylvania.

Much of this is unexplored. One Penn patient was put on a drug that stimulates the immune system, but the drug didn't work. Doctors gave end-of-life care. "The patient had many, many metastatic lesions," recalled Chi Dang, the center's director. They disappeared after the radiation. "That's miraculous. Our doctors immunized that patient by destroying that tumor, by exposing that tumor to the immune system."

Penn began clinical trials "to use radiation therapy along with these drugs to see if we can awaken the immune system," Dang said. "We're using outliers with an understanding behind it that you can apply it more broadly."

What makes an exceptional responder might have as much to do with the immune system as with DNA, Dang said.

Meanwhile, the lucky few - whether super or miraculous - can now hope their experience may help others.

When told of the efforts ongoing to study exceptional responders, Pace said: "Long overdue."

Frank Diamond is managing editor at Managed Care magazine in Yardley.


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