Radiation carcinogenesis modelling for risk of treatment-related second tumours following radiotherapy

Radiobiological modelling of the risk of radiation-induced tumours following high dose radiation implies a general form for the dose–response relationship. Generally, risk will rise with radiation dose at low doses, reach a maximum value and then decline with further increase in dose. The magnitude of risk and the dose at which this risk is maximum are strongly dependent on the kinetics of repopulation by surviving normal and mutant cells and on genetic factors likely to differ between tissues and between individuals. The most reliable way to reduce the risk of second tumours is to reduce radiation dose further at sites where the dose is already low. These sites are usually distant from the primary treatment volume. For illustrative purposes, we have compared the predicted relative risks of second tumours at "distant sites" for treatment plans giving similar dose distributions (dose volume histograms) at the primary site. We suggest that dose reduction to distant sites could be of significant benefit in reducing the risk of second tumours. Further improvement will require more detailed knowledge of the radiation sensitivities and mutagenicities, together with the repopulation kinetics of the various cell lineages within the treatment volume

The effect of tissue-specific growth patterns of target stem cells on the spectrum of tumours resulting from multistage tumorigenesis

A multistage mathematical model of tumorigenesis has been developed to explore the effects of target cell growth pattern on the proportions of tumours deriving from different tissues (the tumour spectrum). Analytical modelling techniques have shown that the effect of the target cell growth pattern on the tumour spectrum also depends on the number of stages (gene mutations) necessary for malignant change in cells of each tissue type. This suggests the existence of temporal “windows of opportunity” for tumours of different types in relation to stage number and growth kinetics. Models of this kind are applicable to cancer-prone transgenic (e.g. p53 deficient) mice, where homozygotes and heterozygotes differ in one carcinogenic stage, and differ also in the spectrum of tumours observed. Generally, tumours deriving from target stem cells which are developmentally short-lived will arise more frequently in homozygotes than heterozygotes. Such models may also be applicable to human syndromes (e.g. Li-Fraumeni) in which susceptibility to cancer is inherited

Laryngeal carcinoma: treatment interruption and outcome

Two patient groups have been identified from a data base of 965 patients with carcinoma of the larynx. One group of 393 patients had squamous cell carcinoma of the larynx arising in the glottis--no nodal involvement; the other group of 163 patients had tumours arising in the supraglottic region. The second group was a more heterogenous group some patients had nodal involvement at the time of presentation. All patients were treated on a linear accelerator. Patients were treated using a variety of dose-fraction-time schedules. Mathematical modelling using linear quadratic equation was carried out. This shows that a break in treatment if a week reduces the local tumour rate for glottic tumours by 12% or about 25 per day. Local tumour control rates increased as the effective dose was increased. The data for tumours arising in the supraglottic region is not so convincing though it does show that prolongation of treatment time reduces local tumour control rates. The effects of longer times can be nullified by increasing the effective dose. The supraglottic subject, however, is very heterogenous, and the groups within the subset are small