Potential biological markers of tumour response to radiation therapy in head and neck cancers

Abstract

The rationale behind studying biological markers of tumour response to radiation therapy in head and neck cancers is to increase the individualisation of radiation therapy. This should ultimately lead to improvements in local control and survival and reduced morbidity. An evaluation was made of the theoretical and practical value of using low-dose rate irradiation to increase the resolution of clonogenic assays for radiosensitivity testing. In tumour cell lines low-dose rate irradiation improved discrimination between tumour radioresponsiveness groups. However, low-dose rate irradiation of primary human tumours followed by soft-agar clonogenic assay was impractical because it reduced the success rate for obtaining radiosensitivity data.One hundred and forty specimens of malignant head and neck tumours of different histology types were assessed for ability to grow in vitro (colony forming efficiency, CFE) and inherent tumour radiosensitivity (surviving fraction at 2 Gy, SF2) using a clonogenic soft-agar assay. The success rate for growing colonies was 74% (104/140) with a median CFE = 0.031%. SF2 was obtained for 88/140 patients (63%) with a median SF2 = 0.43. A comparison was made of SF2 values for different primary human tumour types. This showed that head and neck- (p = 0.03), cervix- (p = 0.02) and colorectal carcinomas (p = 0.003) were significantly more radioresistant than lymphomas. The relationships between proliferation, TP53 and SF2 were evaluated. No correlations were seen between SF2 and any of the parameters analysed. The study demonstrated the feasibility of obtaining parallel measurements of different biological markers in a large number of patients with head and neck cancers.A study was made of SF2 in relation to the immunohistochemical expression levels of the individual components (Ku (p70/p80) and DNA-PKcs) of the DNA double strand break repair enzyme, DNA-PK. No significant relationship was found between SF2 and the expression levels of Ku (p70/p80) or DNA-PKcs for patients with head and neck cancers.Finally, the relationship between SF2 and treatment outcome was prospectively studied in 84 patients with malignant head and neck cancers. SF2 was found to be a significant prognostic factor for local control (p = 0.036).