Development of an inverse optimization package to plan nonuniform dose distributions based on spatially inhomogeneous radiosensitivity extracted from biological images

Abstract

An inverse optimization package which is capable of generating nonuniform dose distribution with subregional dose escalation is developed to achieve maximum equivalent uniform dose (EUD) for target while keeping the critical structure doses as low as possible. Relative cerebral blood volume (rCBV) maps obtained with a dynamic susceptibility contrast-enhanced MRI technique were used to delineate spatial radiosensitivity distributions. The voxel rCBV was converted to voxel radiosensitivity parameters (e.g., alpha and alpha/beta) based on previously reported correlations between rCBV, tumor grade, and radiosensitivity. A software package, DOSEPAINT, developed using MATLAB, optimizes the beamlet weights to achieve maximum EUD for target while limiting doses to critical structures. Using DOSEPAINT, we have generated nonuniform 3D-dose distributions for selected patient cases. Depending on the variation of the pixel radiosensitivity, the subregional dose escalation can be as high as 35% of the uniform dose as planned conventionally. The target dose escalation comes from both the inhomogeneous radiosensitivities and the elimination of integral target dose constraint. The target EUDs are found to be higher than those for the uniform dose planned ignoring the spatial inhomogeneous radiosensitivity. The EUDs for organs at risk are found to be approximately equal to or lower than those for the uniform dose plans. In conclusion, we have developed a package that is capable of generating nonuniform dose distributions optimized for spatially inhomogeneous radiosensitivity. Subregional dose escalation may lead to increased treatment effectiveness as indicated by higher EUDs. The current development will impact biological image guided radiotherapy.

Dose prescription complexity versus tumor control probability in biologically conformal radiotherapy

“…There has been much discussion in recent years of the use of deliberately non-uniform dose distributions in radiotherapy [1][2][3] , and both the technical feasibility and potential 35 benefits of "dose-painting" have been widely demonstrated [4][5][6][7][8][9][10][11][12] . There are a number of possible approaches to the incorporation of radiobiological modelling into the treatment planning process.…”

Strategies for Biologic Image-Guided Dose Escalation: A Review

“…Biologic images are used for tumor detection and delineation (21); however, such images may also contain information on the spatial distribution of factors influencing tumor radiosensitivity. Although many imaging modalities potentially offer such information (9), most studies on biologic image-guided dose escalation have used positron emission tomography (PET) with the tracers 18 F-fluorodexyoglucose (FDG), 60 Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone), 18 F-fluoromisonidazole (FMISO), and 18 F-fluoroazomycin-arabinoside (FAZA) ( Table 1; Fig. 2).…”

“…Moreover, NTCP can be calculated to ensure that normal tissue tolerance limits are not exceeded and to further distinguish between treatment plans. Alternatively, the dose distribution in the tumor or the normal tissues can be evaluated in terms of the equivalent uniform dose, which, albeit in the dose domain, relates a given nonuniform dose distribution to a uniform one with equal biologic effect (18).…”

“…Improved methods for the delivery of focal dose escalation (8), coupled with advances in biologic imaging (9) have created much interest in this potential method of increasing the therapeutic ratio. Recently, several works have been published on the subject (7,(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”

Reducing dose to the lungs through loosing target dose homogeneity requirement for radiotherapy of non small cell lung cancer

“…In addition, dose escalation strategies that involve delivery of uniform doses are typically limited by normal tissue dose tolerance. There have been studies indicating that deliberately using nonuniform radiation doses allows for dose escalation of tumor subvolumes without necessarily increasing the dose which is delivered to adjacent critical structures 22, 23…”