DIFFERENTIATION STATE OF SKIN FIBROBLAST-CULTURES VERSUS RISK OF SUBCUTANEOUS FIBROSIS AFTER RADIOTHERAPY

Background and purpose: There is increasing evidence for patient-to-pa tient variation in the response of normal tissue to radiotherapy. Rece ntly, it has been suggested that accumulation of functional fibrocytes may be a key step in the development of radiation-induced fibrosis. T herefore, we have examined a possible relationship between the differe ntiation state of untreated fibroblasts and the risk of radiation-indu ced subcutaneous fibrosis in individual patients. Materials and method s: We used skin fibroblast cultures isolated from eight postmastectomy radiotherapy patients whose individual clinical radiosensitivity was assessed by the mean excess risk of fibrosis. Different types of poten tially mitotic progenitor fibroblasts (MF) and postmitotic functional fibrocytes (PMF) in the terminal differentiation lineage, MFI --> MFII --> MFIII --> PMF, were scored morphologically in clonal culture. Pro gression of differentiation was quantified by the ratio L/E of colony- forming late (MFIII and late MFII) and early (MFI and early MFII) prog enitors. Results: We observed a correlation between the ratio L/E and the mean risk of fibrosis (r(s) = 0.743, P = 0.03), indicating an appr oximately 10-fold increase in L/E with an increasing risk of fibrosis. This was paralleled by a decreasing trend in the absolute numbers of early progenitor types. By contrast, there was no significant correlat ion between the plating efficiency and the risk of fibrosis. Conclusio ns: The data suggest that the risk of fibrosis increases with the prog ression of the differentiation of untreated progenitor fibroblasts, in dicating that the progression of fibroblast differentiation may be a c o-factor in the development of radiation-induced fibrosis. Lf this hyp othesis is validated, it provides a rationale for a novel predictive r est to identify patients with an increased risk of subcutaneous fibros is. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.