Researchers from the University of Chicago Medical Center reported that targeted radiation therapy had completely controlled all signs of cancer in 21 percent of patients, who had five or fewer sites of metastatic disease, according to an ongoing trial published in the Aug. 15 issue of Clinical Cancer Research.
“This was proof of principle in patients who had failed the standard therapies and had few, if any, remaining options," said the senior author, Ralph Weichselbaum, MD, professor and chairman of radiation and cellular oncology at the University of Chicago. "We had encouraging results, including several long-term survivors, in patients with stage-IV cancers that had spread to distant sites."
In 1994, Weichselbaum and his colleague Samuel Hellman proposed that there was an intermediate state between cancer that had not spread at all and cancer that had spread extensively, calling the state oligometastases.
Recent improvements in tumor detection and precise image-guided radiation therapy have made simultaneous treatment of multiple tumor sites with radiation feasible, according to the researchers.
In 2004, Weichselbaum organized a clinical trial to test the ability of local radiation therapy to control a limited number of related tumors which his colleague Joseph Salama, MD, assistant professor of radiation oncology at the University of Chicago, has directed since 2005.
From November 2004 through February 2008, Salma and colleagues enrolled 29 patients, with a total of 56 cancerous lesions in the trial. Of the 29 patients, 24 had progressed after at least one round of systemic chemotherapy. For the other five, there was no promising choice of therapy.
Six of the 29 initial patients had lasting tumor control, with no detectable evidence of disease 15 months after treatment, according to the investigators.
The authors wrote that many patients had a complete response in at least one tumor. Thirty-one of the 56 treated tumors (55 percent) completely disappeared. Two tumors (4 percent) had a partial response, defined as reduction in tumor volume of more than 30 percent. Only three of the 56 tumors progressed (5 percent), growing in size by 20 percent or more during the treatment phase.
Tumor control improved as the radiation dose increased. Thirty-nine percent of the 31 tumors treated with 24 gray of radiation met the criteria for tumor control--a complete or partial response. That increased to 79 percent for the 19 tumors treated with 30 gray, and to 83 percent for the six tumors treated with 36 gray.
“This suggests that the initial doses were too low,” Salama said. "We have seen improved response rates with higher radiation doses without an increase in side effects yet."
The researchers said that patients tolerated the treatment with “limited difficulty.” All had some fatigue but few had serious side effects, and the most severe included one patient being treated for abdominal tumors, who were hospitalized due to vomiting. One lung cancer patient developed a severe cough. One patient had gastrointenstinal bleeding three months after treatment that required blood transfusion and laser treatment.
The investigators said that crucial to the approach is careful patient selection, distinguishing between patients who have a treatable number of tumors and those who have widespread metastasis, including multiple tumors too small to detect. Currently, they said that there are no known genetic signatures to differentiate between widespread cancer versus oligometastasis. This is one area of active research. However, only five of the 29 patients treated so far, had tumor progression in more than five sites.
The technique could also be applied after chemotherapy in cases where the drugs had eliminated most the smaller cancer, leaving only a few larger tumors behind, the authors wrote.
The trial is still underway. "We now have about 50 patients,” Weichselbaum said, “and several of them remain disease-free, one of them three years after treatment.”