Theory and practice of predictive assays in radiation therapy.

PURPOSE: An overview of the field of predictive assays is presented. It has been written with the many clinicians and scientists in mind who would like to become better acquainted with the general scope, principles and themes in the field. RESULTS: Predictive assays have yielded much valuable information about the radiobiology of tumors e.g. the overall treatment time for rapidly proliferating tumors should be kept to a minimum. However, alteration of current treatment protocols based on results from predictive assays is still a matter of debate. What justification do we have to change established treatment protocols? A necessary and sufficient justification would be when the test value indicated an alternative treatment producing a better outcome, i.e. higher survival, improved local control, etc. Necessary but not always sufficient justification is correlation between the parameter measured and clinical outcome, if insufficient clinical benefit can be derived even when this is known. It is not sufficient that a test be demonstrated to be discriminatory. It must discriminate a sufficient number of patients, and its use must provide the patient with useful therapeutic alternatives. These parameters measured by predictive assays may well interact radiobiologically, and restricting observations to just one assay is probably insufficient for reliable indications. In the future, it is more likely that a panel of tests will be performed, and clinical decisions based on multi-parametric analysis of biopsy material. CONCLUSION: In the following overview general predictive assay theory is presented followed by a brief introduction to some of the more established assays and finally some guidelines are suggested for the development of new assays

Single nucleotide polymorphisms, apoptosis, and the development of severe late adverse effects after radiotherapy.

PURPOSE: Evidence has accumulated in recent years suggestive of a genetic basis for a susceptibility to the development of radiation injury after cancer radiotherapy. The purpose of this study was to assess whether patients with severe radiation-induced sequelae (RIS; i.e., National Cancer Institute/CTCv3.0 grade, > or =3) display both a low capacity of radiation-induced CD8 lymphocyte apoptosis (RILA) in vitro and possess certain single nucleotide polymorphisms (SNP) located in candidate genes associated with the response of cells to radiation. EXPERIMENTAL DESIGN: DNA was isolated from blood samples obtained from patients (n = 399) included in the Swiss prospective study evaluating the predictive effect of in vitro RILA and RIS. SNPs in the ATM, SOD2, XRCC1, XRCC3, TGFB1, and RAD21 genes were screened in patients who experienced severe RIS (group A, n = 16) and control subjects who did not manifest any evidence of RIS (group B, n = 18). RESULTS: Overall, 13 and 21 patients were found to possess a total of <4 and > or =4 SNPs in the candidate genes. The median (range) RILA in group A was 9.4% (5.3-16.5) and 94% (95% confidence interval, 70-100) of the patients (15 of 16) had > or =4 SNPs. In group B, median (range) RILA was 25.7% (20.2-43.2) and 33% (95% confidence interval, 13-59) of patients (6 of 18) had > or =4 SNPs (P < 0.001). CONCLUSIONS: The results of this study suggest that patients with severe RIS possess 4 or more SNPs in candidate genes and low radiation-induced CD8 lymphocyte apoptosis in vitro