ABSTRACT

This dissertation was based on a part of the work carried out during my appointment as research fellow at the Department of Experimental Clinical Oncology, Aarhus University Hospital.

The aim of radiotherapy is to destroy clonogenic tumour cells. Some HNSCC have the ability of accelerating this production of clonogenic cells during radiotherapy - possibly trigged by the injury produced by ionising radiation. Consequently, a significant amount of a given radiation dose may be used to sterilise cells produced during treatment, and a reduction in the overall treatment time means that fewer cell will have to be destroyed. This principle has been indirectly demonstrated in several studies and is related primarily to well-moderate differentiated tumours. However, a reduction in the overall treatment, time also increases acute morbidity. The aim of this thesis was to identify markers that characterise tumours capable of accelerated repopulation. Selected markers were the integrins β 1, β 4 and β 6, E-cadherin and EGFr. The integrins were not related to tumour cell differentiation, and further studies of these markers were not pursued. A study of the effect of EGFr, tumour differentiation and the combination of high EGFr and well-moderate differentiation versus low EGFr and/or poor differentiation showed that the prognostic value of especially the combined parameter (high EGFr and well-moderated differentiation) seemed relative and a poor prognostic factor when treatment time was long (91/2 weeks) and a positive factor, when treatment time was accelerated (51/2 weeks). No difference was seen for conventional treatment times. Similar results were obtained in a series of 803 patients treated with 61/2 or 51/2 weeks overall treatment time: High EGFr was associated with the benefit of moderate acceleration of treatment whereas low EGFr expression was not when locoregional control was used as an endpoint. Again, this effect was more pronounced, when EGFr status was combined with tumour cell differentiation. This observation indicated that other factors than EGFr are needed to identify HNSCC that benefit from a reduction in the overall treatment time of radiotherapy. Since E-cadherin was a marker of differentiation, we explored the effect of E-cadherin on the overall treatment time. Surprisingly it turned out, that tumours with low E-cadherin showed increased local control when the overall treatment time was reduced. The combination of high EGFr and low E-cadherin suggested that this combination may identify HNSCC that benefit from a reduction in the overall treatment time, whereas other combinations did not show the effect with the same magnitude. Further characterisation is necessary for a biologic understanding of this new evidence, and studies of this issue are underway.