CLINICAL IMPACT OF PREDICTIVE ASSAYS FOR ACUTE AND LATE RADIATION MORBIDITY

Background: Clinically reliable predictive assays for normal tissue ra diation sensitivity would help to avoid severe radiation induced morbi dity and result in individualized dose prescriptions. Profound differe nces of individual fibroblast and lymphocyte radiation sensitivity in vitro have been documented in patients with certain genetic syndromes but also in patients without known genetic disorders. The following re view evaluates whether fibroblast or lymphocyte radiation sensitivity measured in vitro correlates with the degree of acute and late radiati on induced morbidity. Results: Acute radiation side effects and lympho cyte sensitivity has been investigated in 2 studies. One of them repor ted an insecure correlation, the other no correlation at all. Fibrobla st radiation sensitivity and the extent of acute radiation induced sid e effects on skin and mucosal sites has been compared in a total of 5 studies. None of these studies found a consistent significant correlat ion Lymphocyte radiation sensitivity and late effects have been studie d by 2 institutions. Late radiation induced skin and mucosal changes d id not correlate with lymphocyte sensitivity in head and neck cancer p atients, whereas in breast cancer patients a weak (R-2 = 0.06) correla tion between the degree of late skin reactions and lymphocyte sensitiv ity was observed. Late skin or mucosal radiation reactions and fibrobl ast sensitivity were examined by 5 research groups. Data analysis reve aled significant correlations or at least a trend towards a significan t correlation in all studies. The quality of the reported correlations expressed as R-2 ranged from 0.13 to 0.60, indicating a low predictiv e value. Conclusions: Lymphocyte radiation sensitivity as measured by currently available assays does not or only poorly correlate with acut e and late effects of radiation in patients, precluding predictive tes ts based on lymphocyte sensitivity. Fibroblast radiation sensitivity d oes not correlate with acute but generally correlates with late radiat ion morbidity. The quality of the later correlation is insufficient fo r a reliable predictive lest with currently available methods to deter mine cellular radiation sensitivity.