by Lynn Shapiro
, Writer | August 13, 2008
"Previous studies determined the maximal radiotherapy doses for single organs," said Salama, lead author of the study, "but this technique has not been tested for simultaneous use on multiple organs. So we designed a dose-escalation trial to determine the optimal dose, starting with fairly low levels and increasing the dose in later groups of patients."
From November 2004 through February 2008, 29 patients, with a total of 56 cancerous lesions, enrolled 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.
Many patients had a complete response in at least one tumor. Thirty-one of the 56 treated tumors (55%) completely disappeared. Two tumors (4%) had a partial response, defined as reduction in tumor volume of more than 30 percent. Only three of the 56 tumors progressed (5%), 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," said Salama. "We have seen improved response rates with higher radiation doses without an increase in side effects yet."
Typical treatment doses for a patient with breast cancer, for example, are in the range of 50 to 60 gray, spread over 20-30 sessions. The trend however, is toward delivering higher doses in fewer sessions.
Patients tolerated the treatment, the authors write, with "limited difficulty." All had some fatigue but few had serious side effects. The most severe included one patient being treated for abdominal tumors who developed vomiting that required hospitalization. One lung cancer patient developed a severe cough. One patient had gastrointenstinal bleeding three months after treatment that required blood transfusion and laser treatment.
Crucial to this 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, there are no known genetic "signatures" to differentiate between widespread cancer versus oligometastasis, the authors point out. This is one area of active research. Only five of the 29 patients treated so far, however, had tumor progression in more than five sites.