Finally, reasoning that reduced fibrosis might translate into improved survival, the investigators compared lifespans between treated and untreated mice.

They found that mice treated with the anti-integrin antibody or the soluble receptor did not live significantly longer than control mice.

"One possible explanation for this is that these mice were given whole-thorax radiation, with a large percent of the dose to both lungs and heart," Dr. Cheng said, noting that such radiation has adverse vascular effects.

"It will be interesting to repeat these experiments with more limited lung radiation fields, such as only one lung, and this will be closer to real-life clinical lung cancer radiation therapy," he said.

Paradigm shift

The results support a "paradigm shift" in our understanding of late radiation injury, Dr. Cheng concluded.

"The immediate effect at the time of radiation may not be the irreversible cause of late radiation injury," he said. "This means that if transferred to humans, these interventions may not have to be given upfront at the time of radiation but can be given later—maybe many months later, perhaps at the onset of symptoms of these injuries—and they still may be therapeutic."

At an ASTRO press conference, Dr. Cheng noted that fibrosis is a very serious side effect of radiation therapy (see box on this page).

"The toxicity of pulmonary fibrosis limits the radiation dose that can be safely given to patients," Dr. Cheng said. "Doctors may fear that the serious problems caused by fibrosis will outweigh the good done by the radiation. If further studies conclude that this drug can indeed prevent fibrosis, it could lead to more effective radiation therapies for advanced lung cancer."

A biological approach