Benefit of using biologic parameters (EUD and NTCP) in IMRT optimization for treatment of intrahepatic tumors

Purpose: To investigate whether intensity-modulated radiotherapy (IMRT), optimized using the generalized equivalent uniform dose (gEUD) and normal tissue complication probability (NTCP) models, can increase the safe dose to intrahepatic tumors compared with three-dimensional conformal RT (3D-CRT). A secondary objective was to investigate the optimal beam arrangement for liver IMRT plans. Methods and Materials: Planning CT data of 15 patients with intrahepatic tumors, previously treated with 3D-CRT, were used as input. The dose delivered using 3D-CRT had been limited either by tolerance of adjacent organs, which were close to, or overlapped with, the planning target volume (PTV; overlap cases, n = 8), or liver toxicity (nonoverlap, n = 7). IMRT plans were created using the gEUD to maximize the dose across the PTV and the NTCP to maintain the organ-at-risk toxicity to that of the conformal plan. Increased heterogeneity was allowed across the PTV in overlap cases, without compromising the minimal PTV dose of the conformal plan and restricting the maximal dose to within 110% of the mean. Three different beam arrangements were used for each case: seven-field equidistant axial, six-field noncoplanar (predominantly right-sided beams), and a reproduction of the conformal gantry angles. gEUDs were also computed and used for evaluation of the plans (regardless of planning technique) to reflect the response of both high- and low-grade tumors. The IMRT plan that allowed the greatest gEUD across the PTV was used in the comparison with the 3D-CRT plan. Results: The use of IMRT significantly increased the maximal gEUD achievable across the PTV compared with the 3D-CRT plans. This was the case for the assumptions of both high- and low-grade tumors, irrespective of the tumor position within the liver. The mean gEUD increase was 11 Gy (high grade) and 18.0 Gy (low grade) for overlap cases ( p = 0.001 and p = 0.003, respectively) and 10 Gy for nonoverlap cases ( p = 0.020). When comparing the IMRT beam arrangements, gEUDs were considered equivalent if they differed by less than one fraction (1.5 Gy). In overlap cases ( n = 8), an equivalent "best" gEUD value was obtained in 3, 5, and 7 cases for the original conformal angle, seven-field axial, and six-field noncoplanar plan, respectively. The corresponding results were 5, 2, and 3 in the cases without an overlap ( n = 7). Conclusion: We have successfully used mathematical/biologic models directly as cost functions within the optimizing process to produce IMRT plans that maximize the gEUD while maintaining compliance with a well-defined protocol for the treatment of intrahepatic cancer. For both PTV-organ-at-risk overlap and nonoverlap situations, IMRT has the capacity to improve the maximal dose achievable across the PTV, expressed in terms of the gEUD. The use of multiple noncoplanar beams appears to confer an advantage over fewer beams in cases with PTV-organ-at-risk overlap. When liver toxicity is the dose-limiting factor, high gEUD values are obtained most frequently when the field arrangement is chosen to provide the shortest possible transhepatic path length.