Convex reformulation of biologically-based multi-criteria intensity-modulated radiation therapy optimization including fractionation effects

Phys Med Biol. 2008 Nov 21;53(22):6345-62. doi: 10.1088/0031-9155/53/22/006. Epub 2008 Oct 21.

Abstract

Finding fluence maps for intensity-modulated radiation therapy (IMRT) can be formulated as a multi-criteria optimization problem for which Pareto optimal treatment plans exist. To account for the dose-per-fraction effect of fractionated IMRT, it is desirable to exploit radiobiological treatment plan evaluation criteria based on the linear-quadratic (LQ) cell survival model as a means to balance the radiation benefits and risks in terms of biologic response. Unfortunately, the LQ-model-based radiobiological criteria are nonconvex functions, which make the optimization problem hard to solve. We apply the framework proposed by Romeijn et al (2004 Phys. Med. Biol. 49 1991-2013) to find transformations of LQ-model-based radiobiological functions and establish conditions under which transformed functions result in equivalent convex criteria that do not change the set of Pareto optimal treatment plans. The functions analysed are: the LQ-Poisson-based model for tumour control probability (TCP) with and without inter-patient heterogeneity in radiation sensitivity, the LQ-Poisson-based relative seriality s-model for normal tissue complication probability (NTCP), the equivalent uniform dose (EUD) under the LQ-Poisson model and the fractionation-corrected Probit-based model for NTCP according to Lyman, Kutcher and Burman. These functions differ from those analysed before in that they cannot be decomposed into elementary EUD or generalized-EUD functions. In addition, we show that applying increasing and concave transformations to the convexified functions is beneficial for the piecewise approximation of the Pareto efficient frontier.

MeSH terms

  • Cell Survival / radiation effects
  • Dose Fractionation, Radiation*
  • Humans
  • Linear Models
  • Models, Biological
  • Neoplasms / pathology
  • Neoplasms / radiotherapy
  • Probability
  • Radiotherapy Dosage
  • Radiotherapy, Intensity-Modulated / methods*