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 dose-response relationship for cancer incidence in a two-stage radiation carcinogenesis model incorporating cellular repopulation.

Purpose: To investigate the role of cellular repopulation in the dose-response relationship for radiation carcinogenesis resulting from high doses of radiation.

Method: A two-stage mathematical model of radiation carcinogenesis was developed and used to explore the effects of differing assumptions about repopulation by surviving normal stem cells and by one-stage mutants.

Results: Characteristically, cancer incidence at any fixed time after irradiation increases with radiation dose, reaches a peak and then declines with dose (the decline reflecting radiation cell-killing).

The linear-quadratic transformation of dose-volume histograms in fractionated radiotherapy.

Background And Purpose: Dose-volume histograms (DVHs) are often used in radiotherapy to provide representations of treatment dose distributions. DVHs are computed from physical dose and do not include radiobiological factors; therefore, the same DVH will be computed for a treatment plan whatever fractionation regimen is used. However, dose heterogeneity resulting from variation of daily treatment dose within the volume will have biological effects due to spatial heterogeneity of fraction size as well as total dose.

A two-stage model for childhood acute lymphoblastic leukemia: application to hereditary and nonhereditary leukemogenesis.

A differential equation model is developed to represent a two-stage mutational process leading to childhood acute lymphoblastic leukemia (ALL). Leukemogenesis is modeled as transformation of target stem cells that initially grow rapidly in the embryo but plateau and then decline in postnatal childhood. Inheritance of the first of two leukemogenic mutations is allowed as a possibility in a small minority of leukemic patients who would characteristically develop leukemia at an early age.

Alternative models for early onset of childhood leukaemia.

This paper considers theoretical models for early-onset childhood leukaemia. The major focus of attention is the two-hit mutational model. A simple mathematical representation is used to explore mechanisms which might lead to onset of leukaemia at an unusually early age.

Postvagotomy diarrhoea put into perspective.

Truncal vagotomy and drainage is still the commonest operation for duodenal ulcer in the United Kingdom, despite its known association with diarrhoea. The frequency and severity of diarrhoea were compared in 102 randomly selected men 10 or more years after truncal vagotomy and pyloroplasty (TVP) and a control group of 62 men taking long-term maintenance cimetidine treatment 2 or more years after healing of duodenal ulcer. 53% of the TVP group still had diarrhoea attacks compared with only 7% of the cimetidine group (p less than 0.

The relationship of anaemia to gastric secretion more than 15 years after vagotomy and gastro-enterostomy.

Iron deficiency anaemia is common following vagotomy and gastro-enterostomy, and this study has shown that all the anaemic patients had low gastric secretion. After correction of their anaemia, gastric secretion was increased, but was still very low, and when these levels were compared with secretion in fit non-anaemic patients it was found that the latter group had a significantly higher secretion, and that a high proportion of them showed evidence of incomplete vagotomy. These results suggest that there is a relationship between the levels of gastric secretion in patients after vagotomy and gastro-enterostomy and the development pf anaemia.