Does skin fibroblast radiosensitivity predict squamous cancer cell radiosensitivity of the same individual?

Abstract

Individualization of radiation doses is presumed to result in better radiotherapy outcome. Success rate in measuring radiosensitivity is probably the most limiting factor for present radiosensitivity assays to be introduced into clinical routine. To find a simpler predictive parameter, we compared the radiosensitivity of dermal fibroblasts and head and neck squamous cell carcinoma (SCC) cell lines established from the same individuals. The radiosensitivity was tested using the clonogenic 96-well plate assay. The surviving fraction at 2.0 Gy (SF2) was determined, as well as the mean inactivation dose (AUC) of cancer cells. SF2 of SCC cell lines and skin fibroblasts were 0.25-0.44 and 0.11-0.43, respectively. AUC of SCC cells was 1.4 -2.1 Gy. Dermal fibroblasts were more radiosensitive than SCC cells in 14 of 15 cases. In 1 patient (UT-SCC-8), cancer cells were found to be more radiosensitive than corresponding dermal fibroblasts. There was a clear tendency to a correlation between radiosensitivities of these 2 cell types, but statistical significance was reached only when the data of UT-SCC-8 was excluded. In our material, the intrinsic radiosensitivity of head and neck SCC cells could in most cases be predicted from the intrinsic radiosensitivity of dermal fibroblasts established from the same individual. Surgery and radiation therapy are the cornerstones in the treatment of head and neck squamous cell carcinoma (HNSCC). In most cases these treatment modalities are combined in order to achieve better therapy response. In practice, the given dose of radiation is, however, limited by acute and late side effects. Not only is the prescribed dose a limiting factor in the normal tissue for the treatment but also the fractionation used. In breast cancer patients, identical doses of external radiotherapy have been shown to cause a varying grade of acute and late dermal side effects, and it has been suggested that the radiosensitivity of all cells is genetically determined in each individual. 1,2 In genetic disorders, ataxiatelangiectasia, e.g., the patients are highly radiosensitive both in vitro and in vivo. In theory, in genetically sensitive individuals a lower radiation dose can be given in order to prevent side effects, but this will not necessarily result in a reduced probability of tumour control. 3 It has been estimated that a subgroup of patients with radioresistant fibroblasts might be able to tolerate perhaps up to 40% larger doses without experiencing a significant increase in severe late skin complications. 4 The in vitro radiosensitivity of skin fibroblasts has most often been regarded to correlate with the clinical expression of late skin reactions. [5][6][7][8] On the other hand, a lack of correlation between the intrinsic radiosensitivity of dermal fibroblasts and early skin reactions has been found in the majority of studies. 6,8 -11 Experimental studies have suggested that the in vitro radiosensitivity of tumour cells, estimated by the fraction of surviving cells after a radiation dose of 2.0 Gy (SF...

Pre-Clinical Characterization of Dacomitinib (PF-00299804), an Irreversible Pan-ErbB Inhibitor, Combined with Ionizing Radiation for Head and Neck Squamous Cell Carcinoma

“…Three human SCCHN cell lines were utilized: FaDu (hypopharyngeal squamous carcinoma; American Type Culture Collection), UT-SCC-8 and UT-SCC-42a (laryngeal squamous cell carcinoma); the latter two lines were a generous gift from R. Grenman (Department of Otorhinolaryntology-Head and Neck Surgery, University of Turku, Finland) [23]. FaDu cells were maintained in Minimum Essential Medium, supplemented with 10% Fetal Bovine Serum (FBS), 1.5 g/L bicarbonate, and 1 mM pyruvate.…”

What do we know about the α/β for prostate cancer?

“…In fact, the tumor heterogeneity may increase the actual a/b value, 42,131 and the use of homogeneous models overestimates its statistical significance. 132 If some studies suggest some correlation between in vitro and in vivo parameters, [133][134][135][136][137][138][139][140][141] in others little or no correspondence is achieved between in vitro predictions and relevant clinical endpoints. [141][142][143][144][145][146] This lack of correlation may be due to small patient sample sizes, unreliable radiosensitivity indicators, or uncertain relationship among in vitro indicators and in vivo endpoints.…”

Severity of oral mucositis correlates with the response of oral cancer to preoperative radiochemotherapy

“…Some of the genetic factors involved in the radiosensitivity of normal oral mucosa are likely to be shared with oral squamous cell carcinoma, as the present study showed that the response of oral cancer to radiochemotherapy correlated with the susceptibility of normal oral mucosa to the therapy in many cases. In addition, the radiosensitivity of normal skin fibroblasts is reported to correlate with that of squamous carcinoma cells in the same individual 4 .…”