What can you do when a lung cancer patient’s previously successful drug treatment suddenly stops working? Or a tumor mutates or cancer spreads? Is there hope when, months after radiation seemed to have wiped out a patient’s melanoma, signs of the disease reappear?
Those kinds of developments can curb enthusiasm about even the newest and most sophisticated treatment. So what can doctors do when cancer treatments that had been effective stop working?
According to Roy Decker, MD, PhD, a precise, high-dose form of radiation called stereotactic body radiotherapy (SBRT) often offers hope. Dr. Decker is the director of Yale Medicine’s Thoracic/Stereotactic Body Radiotherapy Program, among the largest in the region. SBRT is an advanced treatment that targets specific tumors, and it has a high rate of success. SBRT can help ineffectual treatments start working again, either by destroying growths that do not respond to medication or by reactivating the body’s immune system to fight the cancer.
Historically, when a patient’s cancer would reappear, options were limited, Dr. Decker says. “We would have to switch to chemotherapy or to an experimental agent.” Now, approaches such as radiosurgery, molecular profiling and immunotherapy allow oncologists to customize drugs and radiation not just to an individual patient but also to an individual tumor.
For example, one lung cancer patient, a nurse in her early 60s, came to see Dr. Decker two years ago. She had a metastatic cancer, meaning her cancer had spread from it place or origin in the body to another place or organ. Doctors found a particular mutation in her tumor and prescribed a drug (Tarceva, or erlotinib) that stifles growth in that sort of tumor. Because it was a targeted treatment that only affected the tumor, the drug did not cause side effects.
“The disease responded,” Dr. Decker says. “It shrunk down and disappeared. It stayed away for two and a half years.”
Then, during a routine monitoring scan, doctors saw that one of the lung tumors had begun to grow again. A biopsy showed that the tumor had developed a resistance to Tarceva, the drug that had previously been effective.
Normally, in a situation like this, doctors would have had to change tactics completely. The patient would have been taken off the Tarceva and put on a systemic treatment, such as chemotherapy or radiation. By definition, these treatments deliver the same toxic doses to cancer tumors as to the rest of the area or even the entire body. This is why patients suffer side effects that can disrupt everyday life.
But Yale Medicine was able to offer another option. “In fact, what we did was treat her with SBRT to this one growing tumor,” Dr. Decker says. He pointed the radiation precisely to the part of the tumor that had developed resistance to the drug.
Activating the immune system
After three 30-minute sessions, the tumor was eradicated, allowing the patient to resume taking Tarceva, which Dr. Decker said “had worked miraculously for her.” Today, it is still working, and she has required no other treatments.
While radiotherapy is known for its precision, its effects are sometimes less straightforward. One exciting but mysterious advance in the field involves the way SBRT seems to kick-start the immune system.
“There’s evidence to suggest that the use of radiation can increase your body’s immune response,” says Dr. Decker. He says immune checkpoint inhibitors, which help activate the body’s immune system to fight cancer cells, are one of the most auspicious advances in cancer treatment today.
Recently, Dr. Decker treated a woman who came to see him for her metastatic melanoma, an aggressive type of skin cancer. At first an immunotherapy drug seemed helpful and kept her cancer lesion, discovered on her leg, from spreading. But soon, as had happened to the nurse with lung cancer, the treatment stopped working and the lesions resumed their growth.
Dr. Decker again turned to SBRT and treated a spot on the patient’s foot with the targeted radiation. The treatment “persuaded” the immunotherapy to start working again—not just on the patient’s foot but throughout the area affected by the melanoma.
The radiotherapy boosted the drug’s efficacy for several months, until it failed again. Dr. Decker then treated another lesion, this one higher up the leg. That worked for a while, too.
Eventually, he treated this patient’s cancer in four specific areas. “We basically activated her immune system,” Dr. Decker says. “Perhaps we were treating lesions that had escaped immune surveillance. It could be that by destroying the tumor with high levels of radiation, we’re releasing tumor antigens into the bloodstream for the immune system to target. Or it could be more complicated.” He says there is still much to be learned.
Learning along the way
When clinical trials show evidence of promise, doctors can apply them to treatment even if they do not yet understand precisely why. This is the case with SBRT’s immune system response right now. Although doctors have known for a decade that the body can generate a strong immune response to a tumor after radiation, the exact mechanisms remain unknown. Rather than trying to answer all the questions at once, physicians refine their methods as they treat patients.
At Yale Medicine, clinical trials are under way to augment targeted cancer-treatment possibilities. That should lead to more alternatives to systematic approaches for patients at Yale Medicine and more potential applications for SBRT.
“We’re doing seminal work on higher-risk patients,” Dr. Decker says.
For Dr. Decker’s melanoma patient, the combination of immunotherapy and SBRT worked beautifully for a year. At that point, when the combined treatment stopped helping, she was able to switch to promising new medications that had just become available.