Clinical radiobiology of glioblastoma multiforme: estimation of tumor control probability from various radiotherapy fractionation schemes

BACKGROUND AND PURPOSE: The aim of this study was to estimate a radiobiological set of parameters from the available clinical data on glioblastoma (GB). PATIENTS AND METHODS: A number of clinical trial outcomes from patients affected by GB and treated with surgery and adjuvant radiochemotherapy were analyzed to estimate a set of radiobiological parameters for a tumor control probability (TCP) model. The analytical/graphical method employed to fit the clinical data allowed us to estimate the intrinsic tumor radiosensitivity (α), repair capability (b), and repopulation doubling time (T d ) in a first phase, and subsequently the number of clonogens (N) and kick-off time for accelerated proliferation (T(k)). The results were used to formulate a hypothesis for a schedule expected to significantly improve local control. The 95 % confidence intervals (CI(95 %)) of all parameters are also discussed. RESULTS: The pooled analysis employed to estimate the parameters summarizes the data of 559 patients, while the studies selected to verify the results summarize data of 104 patients. The best estimates and the CI(95 %) are α = 0.12 Gy⁻¹ (0.10-0.14), b = 0.015 Gy⁻² (0.013-0.020), α/b = 8 Gy (5.0-10.8), T(d)  = 15.4 days (13.2-19.5), N = 1.10⁴(1.2.10³ - 1.10⁵), and T(k)  = 37 days (29-46). The dose required to offset the repopulation occurring after 1 day (D(prolif)) and starting after T k was estimated as 0.30 Gy/day (0.22-0.39). CONCLUSION: The analysis confirms a high value for the α/b ratio. Moreover, a high intrinsic radiosensitivity together with a long kick-off time for accelerated repopulation and moderate repopulation kinetics were found. The results indicate a substantial independence of the duration of the overall treatment and an improvement in the treatment effectiveness by increasing the total dose without increasing the dose fraction.