Incorporating biologic measurements (SF₂, CFE) into a tumor control probability model increases their prognostic significance: a study in cervical carcinoma treated with radiation therapy☆

Abstract 

To assess whether incorporation of measurements of surviving fraction at 2 Gy (SF₂) and colony-forming efficiency (CFE) into a tumor control probability (tcp) model increases their prognostic significance.

Measurements of SF₂ and CFE were available from a study on carcinoma of the cervix treated with radiation alone. These measurements, as well as tumor volume, dose, and treatment time, were incorporated into a Poisson tcp model (tcp_α,ρ). Regression analysis was performed to assess the prognostic power of tcp_α,ρ vs. the use of either tcp models with biologic parameters fixed to best-fit estimates (but incorporating individual dose, volume, and treatment time) or the use of SF₂ and CFE measurements alone.

In a univariate regression analysis of 44 patients, tcp_α,ρ was a better prognostic factor for both local control and survival (p < 0.001 and p = 0.049, respectively) than SF₂ alone (p = 0.009 for local control, p = 0.29 for survival) or CFE alone (p = 0.015 for local control, p = 0.38 for survival). In multivariate analysis, tcp_α,ρ emerged as the most important prognostic factor for local control (p < 0.001, relative risk of 2.81). After allowing for tcp_α,ρ, CFE was still a significant independent prognostic factor for local control, whereas SF₂ was not. The sensitivities of tcp_α,ρ and SF₂ as predictive tests for local control were 87% and 65%, respectively. Specificities were 70% and 77%, respectively.

A Poisson tcp model incorporating individual SF₂, CFE, dose, tumor volume, and treatment time was found to be the best independent prognostic factor for local control and survival in cervical carcinoma patients.

Keywords:  Radiobiologic models, Radiosensitivity, SF₂, Predictive assays, Tumor control probability