Relationship between tumour cell in vitro radiosensitivity and clinical outcome after curative radiotherapy for squamous cell carcinoma of the head and neck

Abstract

Background and purpose: Clinically, it is recognized that individual tumours respond differently to radiation treatment. Variation in tumour cell radiosensitivity is believed to be an important underlying factor. In the current study, cellular in vitro radiosensitivity was estimated as the fraction of surviving cells after a radiation dose of 2 Gy (SF2) and related to clinical outcome after curative radiotherapy.

Patients and methods: Thirty-eight patients with squamous cell carcinoma of the head and neck were treated with curative radiotherapy alone. Pre-treatment biopsies were disaggregated to form a single-cell suspension and cells were cultured in the modified Courtenay-Mills soft agar clonogenic assay. Directly from this assay and with no respect to cell type, overall SF2 was assessed. By collecting the obtained colonies on a preparation slide using a colony-filter technique, and with immunocytochemical staining, it was possible to measure the surviving fraction of tumour cells selectively as tumour cell SF2.

Results: Experimentally, a broad inter-tumour variation was found for both tumour cell SF2 and overall SF2. Using weighted linear regression, it was demonstrated that tumour cell SF2 and overall SF2 were two independent measures of tumour radiosensitivity. In general, the measures of tumour radiosensitivity were independent of patient sex and age, T- and N-category, disease stage, tumour size and plating efficiency. Among the 38 patients grouped in loco-regional failures and patients with loco-regional control, respectively, sex, age, total radiation dose, overall treatment time and tumour grade were equally distributed. Advanced stage, lymph node involvement and tumour size correlated statistically significantly with poor loco-regional control. Neither tumour cell SF2, overall SF2, nor plating efficiency predicted loco-regional tumour control probability. In a multivariate analysis with respect to the risk of loco-regional tumour failure, only disease stage yielded independent prognostic significance. This significance suggests that this patient sample was representative for the patient population with head and neck cancer.

Conclusion: In 38 patients with squamous cell carcinoma of the head and neck, the estimated tumour radiosensitivities were not statistically related to clinical outcome after curative radiotherapy alone.