Tumor response parameters for head and neck cancer derived from tumor-volume variation during radiation therapy

The main goal of this paper is to reconstruct a distribution of cell survival fractions from tumor-volume variation for a heterogeneous group of head and neck cancer patients and compare this distribution to the data from predictive assays.

To characterize the tumor-volume variation during radiation therapy treatment, the authors use a two-level tumor-volume model of cell population that separates the entire tumor cell population into two subpopulations of viable cells and lethally damaged cells. This parameterized radiobiological model is integrated with a least squares objective function and a simulated annealing optimization algorithm to describe time-dependent tumor-volume variation rates in individual patients. Several constraints have been used in the optimization problem because tumor-volume variation during radiotherapy is described by a sum of exponentials; therefore, the problem of accurately fitting a model to measured data is ill-posed. The model was applied to measured tumor-volume variation curves from a clinical study on tumor-volume variation during radiotherapy for 14 head and neck cancer patients in which an integrated CT/linear particle accelerator (LINAC) system was used for tumor-volume measurements.

The two-level cell population tumor-volume modeling is capable of describing tumor-volume variation throughout the entire treatment for 11 of the 14 patients. For three patients, the tumor-volume variation was described only during the initial part of treatment, a fact that may be related to the neglected hypoxia in the two-level approximation. The predicted probability density distribution for the survival fractions agrees with the data obtained using in vitro studies with predictive assays. The mean value 0.35 of survival fraction obtained in this study is larger than the value 0.32 from in vitro studies, which could be expected because of greater repair in vivo. The mean half-life obtained in this study for the head-and-neck squamous cell carcinoma (SCC) is equal to 3.8 mean potential doubling times, which agrees with 4.0 mean potential doubling times obtained previously for lung SCC.

The distribution of cell survival fractions obtained in this study support the hypothesis that the tumor-volume variation during radiotherapy treatment for head and neck cancer can be described by the two-level cell population tumor-volume model. This model can be used for in vivo evaluation of patient-specific radiobiological parameters that are needed for tumor-control probability evaluation.