PREDICTIVE AND PROGNOSTIC MARKERS IN SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK

Abstract: Survival of patients with locally advanced head and neck squamous cell cancer(HNSCC)is poor, with an overall survival < 50%, despite diagnostic and therapeutic advances. The identification of prognostic and predictive markers could help optimizing treatment. From 18 patients, six tumour cell lines were established and four were xenografted to nude mice. Proliferation parameters(cell doubling time, S-phase fraction), TP53- and CCND1 status were studied in relation to cisplatin response. Metabolic activity was studied by 2-deoxy-2[18F]fluoro-D-glucose(FDG) uptake. Successful cell-line establishment was correlated to poorer survival than when cell lines failed to establish. Shorter doubling time was correlated to higher FDG uptake in vitro. Different bioassays were used to measure cisplatin sensitivity in vitro. The colony forming assay was the most effective measure of cell kill. Sequential changes in FDG uptake and in the histopathological appearance during chemotherapy were studied. FDG uptake was correlated to amount of viable tumour cells and to tumour cell viability with a decreasing uptake over time in prenecrotic cells following treatment response. A very early transient increase in FDG uptake per cell was seen in both in vivo and in vitro studies. Conclusion: Establishment of in vitro growth is an independent, negative prognostic factor. p53 mutation and cyclin D1 amplification predict a poor response to cisplatin. Early metabolic response is predictive of successful treatment effect. Uptake of FDG is mainly present in tumour cells with no interference from surrounding tissue. This is important when interpreting a metabolic tumour image(FDGPET scan).