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New test can identify patients who may suffer serious late toxicity from radiotherapy

September 20, 2003

Radiotherapists in Switzerland have developed a fast test that can be used immediately on patients to discover whether they are likely to suffer serious late onset side effects from radiation.

Dr Mahmut Ozsahin told delegates at ECCO12 - The European Cancer Conference today (Monday 22 September) that the test was very precise. "It is capable of isolating 93% of those patients, with nearly 99% exactitude, who will suffer no increased late toxicity when using traditional doses," he said. "This means that radiotherapists can give those patients a more aggressive treatment that will be more likely to kill more cancer cells with only a slight increase in toxic side effects. This is a very significant result because it has been estimated that if you exclude 5% of the most sensitive patients, you can gain a 20% increase in the local control of many tumours in the remaining 95% of patients with only a slight increase in radiation dose."

Dr Ozsahin, a consultant radiation oncologist and associate professor at Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, and his colleagues, took blood samples from 399 cancer patients between 1998 and 2000 and irradiated the samples. They looked at two T-lymphocytes (white blood cells) - CD4 and CD8 - to see what effect radiation had on cell death (apoptosis). The process took only 48 hours. Then they correlated the results with the responses of the patients to radiotherapy.

They found that there was no correlation between the early onset of toxic side effects and T-lymphocyte apoptosis. However there was a statistically significant correlation with grade two and three late toxicity. Patients who suffered grade two and three late onset side-effects had blood samples in which radiation-induced apoptosis was below the median average. "Patients whose CD4 and CD8 T-lymphocytes suffered the least cell death were the most sensitive to late toxicity," said Dr Ozsahin.

"This is because apoptosis is the physiological cell-death of normal tissues. If a 'normal' cell sees the damage done to its DNA, it can either repair its DNA or die, and be replaced with a new fresh cell; therefore, the tissue itself will not suffer damage later on. However, if a cell does not see the damage to its DNA, as occurs in sensitive patients, it will not be replaced and, therefore, the tissue will suffer from a late reaction because a number of cells inside this tissue will not function properly."
He continued: "To our knowledge, this is the first rapid predictive test based on lymphocyte apoptosis confirmed prospectively in a large number of patients. It can predict significantly the differences in radiation-induced late toxicity between patients, and could be used as a rapid screen for genetically hypersensitive patients. It is ready to be used in the clinical setting now, and, as both CD4 and CD8 showed similar results, we need test for CD8 only.

"Furthermore, the test could be used to stratify patients in future dose escalation trials. We intend to use it for stratification in Phase III trials, and as a factor for exclusion in Phase I and II trials. A retrospective finding of our study was that patients with breast cancer who received tamoxifen during radiotherapy showed an increased proportion of subcutaneous fibrosis (tissue scarring) compared to those who did not have tamoxifen or who had it later. Now, a new multi-centre Phase III study will compare tamoxifen versus an aromatase inhibitor in breast cancer in terms of fibrosis, using our test as a stratification factor."

MR Communication and Analysis Ltd