The long term objective is to improve the treatment of cancer by radiation using modified fractional schedules, with carefully selected doses per fraction, total doses and overall time. Recent and emerging clinical results are correlating well with radiobiological predictions, quantitatively for dose per fraction and qualitatively for cell population kinetics. Such correlations were not seen or methods of dealing with hypoxic cells or for high LET radiation, probably because of reoxygenation. It is proposed to exploit those good correlations found in fractionated radiotherapy to search for better radiobiological values for proliferation in tumors (and some normal tissues) in the head, neck and thorax. The linear quadratic (LG) model will be used, with selected comparison with Curtis's LPL model; and the newly formulated time factor representing cellular proliferation will be used. The strategy will be to analyze published and emerging clinical results with the following aims: 1. In tumors of brain, head, throat, esophagus, spinal cord and lung, taking account of site, stage, size, histology and any adjuvant therapy, to extract data on: a) Time dependence (e.g. rate of proliferation and time of achieving accelerated proliferation) where overall time was varied; b) Dose-per-fraction dependence (e.g. alpha/beta) where size of fraction was varied. The primary aim is 1(a) because of a number of new fractionation protocols are using accelerated fractionation and it is a matter of current importance to determine how worthwhile that is, or not, in certain circumstances. 2. In normal tissues in the head, neck and thorax to determine by analysis of clinical data: a) Time dependence (if any in late-reacting tissues) where overall time was varied. b) Dose-per-fraction dependence (e.g. alpha/beta) where size of fraction was varied. The emphasis will be on late complications. The selection of data will depend upon sufficient details being available in a given set. Proliferation data cannot be obtained by conventional cell kinetic methods, including flow cytometry, in non-equilibrium situations such as during treatment. The approach proposed in the present application will, however, enable data about time dependence to be obtained that cannot be obtained in any other way than by appropriate analysis of real clinical results.
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| Fowler, J F (1991) Apparent rates of proliferation of acutely responding normal tissues during radiotherapy of head and neck cancer. Int J Radiat Oncol Biol Phys 21:1451-6 |
| Fowler, J F; Tanner, M A; Bataini, J P et al. (1990) Further analysis of the time factor in squamous cell carcinoma of the tonsillar region. Radiother Oncol 19:237-44 |
