Researchers hang development of blood test on understanding genetic pathways

October 2, 2009

Clues to radiosensitivity promise personalized radiation therapy

It doesn't take much radiation to kill leukemia, but it's a different story for melanoma. Patients with this kind of cancer are excluded from radiation therapy because a clinically effective dose would likely do them more harm than good. The reason for this disparity is that cancer cells differ in their sensitivity to radiation.

People also vary in their sensitivity to radiation. And understanding why might help physicians target doses more precisely in the future.

Research presented Sept. 24 at the jointly held Congress of the European Cancer Organisation and Congress of the European Society for Medical Oncology meeting in Berlin identified a subgroup of patients who are extremely sensitive to radiation. Dr. Dirk de Ruysscher, a professor in the radiation oncology department at the Maastricht University Medical Centre in Maastricht, the Netherlands, said the work might ultimately provide the basis for personalized radiotherapy in which the use of a simple blood test would let physicians dial in the optimal radiation dose for a particular patient.

De Ruysscher's team, whose members hail from the Netherlands, Belgium, Germany, and Canada, analyzed data about patients who showed severe side effects that occurred at very low radiation levels, lasted for more than four weeks after the end of radiotherapy and/or required surgery, or persisted more than 90 days after the end of radiotherapy. From these patients they selected the most hypersensitive to radiation, a group of 11 (two male and nine female patients), whose side effects included acute skin reactions, extreme skin thickening or fibrosis, lung tissue inflammation, and blindness due to optical nerve damage.

The goal now is to launch a successor project to this research, using this subpopulation of patients to identify the genetic pathways related to radiosensitivity. The data for conducting this research may already be at hand. For their investigation, De Ruysscher and colleagues drew from the a database of some 8000 European patients who had been characterized as part of the European Union-funded genetic pathways for the prediction of the effect of irradiation (GENEPI) study, which integrates biological material with patient data and treatment specifications.

Understanding the genetic pathways responsible for radiosensitivity in the subpopulation of patients in this database, in combination with other patient information it contains, might lead to predictive models that can be used to spot patients who are most sensitive to radiation therapy and, therefore, must be treated with special care, according to de Ruysscher.

"Although radiotherapy is a highly effective way of treating cancer, it is important that we are able to identify the patients who will react badly to it and adjust their dosage accordingly," he said.

If the researchers ultimately can identify the genetic mechanism underlying radiosensitivity, they might develop a blood test that predicts the response of patients to radiotherapy. This could allow the exact targeting of dose in specific patients.

"Such personalized treatment would be a major advance, allowing us to minimize both radiotherapy doses and unpleasant side effects (in radiosensitive patients), while treating the tumor in the most effective way possible," de Ruysscher said.

By identifying patients who are the most radiosensitive, such a test conversely would allow the identification of patients who are less radiosensitive. They could then safely receive higher doses of radiation, he said, "improving control of their tumors."