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Title: 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 uniformmore » 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.« less

Authors:
; ; ;  [1]
  1. Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 (United States)
Publication Date:
OSTI Identifier:
20951141
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 34; Journal Issue: 4; Other Information: DOI: 10.1118/1.2710948; (c) 2007 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BLOOD; BRAIN; COMPUTER CODES; IMAGES; NEOPLASMS; NMR IMAGING; OPTIMIZATION; RADIATION DOSE DISTRIBUTIONS; RADIATION DOSES; RADIOSENSITIVITY; RADIOTHERAPY

Citation Formats

Chen, G.-P., Ahunbay, Ergun, Schultz, Christopher, and Li, X. Allen. Development of an inverse optimization package to plan nonuniform dose distributions based on spatially inhomogeneous radiosensitivity extracted from biological images. United States: N. p., 2007. Web. doi:10.1118/1.2710948.
Chen, G.-P., Ahunbay, Ergun, Schultz, Christopher, & Li, X. Allen. Development of an inverse optimization package to plan nonuniform dose distributions based on spatially inhomogeneous radiosensitivity extracted from biological images. United States. doi:10.1118/1.2710948.
Chen, G.-P., Ahunbay, Ergun, Schultz, Christopher, and Li, X. Allen. Sun . "Development of an inverse optimization package to plan nonuniform dose distributions based on spatially inhomogeneous radiosensitivity extracted from biological images". United States. doi:10.1118/1.2710948.
@article{osti_20951141,
title = {Development of an inverse optimization package to plan nonuniform dose distributions based on spatially inhomogeneous radiosensitivity extracted from biological images},
author = {Chen, G.-P. and Ahunbay, Ergun and Schultz, Christopher and Li, X. Allen},
abstractNote = {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.},
doi = {10.1118/1.2710948},
journal = {Medical Physics},
number = 4,
volume = 34,
place = {United States},
year = {Sun Apr 15 00:00:00 EDT 2007},
month = {Sun Apr 15 00:00:00 EDT 2007}
}
  • Purpose: To evaluate the advantages of anatomy-based inverse optimization (IO) in planning high-dose-rate (HDR) brachytherapy. Methods and Materials: A total of 114 patients who received HDR brachytherapy (9 Gy in two fractions) combined with hypofractionated external beam radiotherapy (EBRT) were analyzed. The dose distributions of HDR brachytherapy were optimized using geometric optimization (GO) in 70 patients and by anatomy-based IO in the remaining 44 patients. The correlation between the dose-volume histogram parameters, including the urethral dose and the incidence of acute genitourinary (GU) toxicity, was evaluated. Results: The averaged values of the percentage of volume receiving 80-150% of the prescribedmore » minimal peripheral dose (V{sub 8}-V{sub 15}) of the urethra generated by anatomy-based IO were significantly lower than the corresponding values generated by GO. Similarly, the averaged values of the minimal dose received by 5-50% of the target volume (D{sub 5}-D{sub 5}) obtained using anatomy-based IO were significantly lower than those obtained using GO. Regarding acute toxicity, Grade 2 or worse acute GU toxicity developed in 23% of all patients, but was significantly lower in patients for whom anatomy-based IO (16%) was used than in those for whom GO was used (37%), consistent with the reduced urethral dose (p <0.01). Conclusion: The results of this study suggest that anatomy-based IO is superior to GO for dose optimization in HDR brachytherapy for prostate cancer.« less
  • Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposedmore » lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. Results: IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. Conclusions: In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled.« less
  • Purpose: To perform an independent validation of an anatomy-based inverse planning simulated annealing (IPSA) algorithm in obtaining superior target coverage and reducing the dose to the organs at risk. Method and Materials: In a recent prostate high-dose-rate brachytherapy protocol study by the Radiation Therapy Oncology Group (0321), our institution treated 20 patients between June 1, 2005 and November 30, 2006. These patients had received a high-dose-rate boost dose of 19 Gy to the prostate, in addition to an external beam radiotherapy dose of 45 Gy with intensity-modulated radiotherapy. Three-dimensional dosimetry was obtained for the following optimization schemes in the Platomore » Brachytherapy Planning System, version 14.3.2, using the same dose constraints for all the patients treated during this period: anatomy-based IPSA optimization, geometric optimization, and dose point optimization. Dose-volume histograms were generated for the planning target volume and organs at risk for each optimization method, from which the volume receiving at least 75% of the dose (V{sub 75%}) for the rectum and bladder, volume receiving at least 125% of the dose (V{sub 125%}) for the urethra, and total volume receiving the reference dose (V{sub 100%}) and volume receiving 150% of the dose (V{sub 150%}) for the planning target volume were determined. The dose homogeneity index and conformal index for the planning target volume for each optimization technique were compared. Results: Despite suboptimal needle position in some implants, the IPSA algorithm was able to comply with the tight Radiation Therapy Oncology Group dose constraints for 90% of the patients in this study. In contrast, the compliance was only 30% for dose point optimization and only 5% for geometric optimization. Conclusions: Anatomy-based IPSA optimization proved to be the superior technique and also the fastest for reducing the dose to the organs at risk without compromising the target coverage.« less
  • The linear quadratic (LQ) model is applied to an organ receiving a fractionated course of radiotherapy with an inhomogeneous dose distribution. It is shown that the gradient in the extrapolated response dose (ERD) will be steeper than the gradient in the physical dose. This effect will be greatest for an organ with a small alpha/beta ratio treated with large dose fractions. Clinical implications are discussed with an emphasis on radiation myelitis.
  • High dose rate brachytherapy is a promising radiation treatment modality that uses temporarily implanted catheters to deliver the curative dose directly in the tumor. A programmable robotic device (the afterloader) moves a single tiny radioactive source (192Ir) along the catheters using a flexible cable attached to the source. With this flexible system, a wide variety of dose distributions can be generated from a given implant simply by adjusting the length of time (dwell time) that the source dwells at any location within the implanted catheters (dwell position). The challenge is to select the optimal sequence of dwell times related tomore » the unique clinical situation of each patient. This treatment-planning problem can be formalized as a combinatorial optimization problem. The optimization algorithm presented in this thesis is conceived to perform this task. An inverse planning (IP) approach has been adopted to guide the optimization process. This means that the optimization is guided by clinical objectives described by means of dose constraints specified to each digitized anatomical structure. A simulated annealing (SA) optimization engine has been designed to solve this particular problem in a short time for clinical applications (about 30 s). This inverse planning by simulated annealing (IPSA) algorithm has been successfully implanted in four institutions: UCSF(1), CHUQ(2), NIH(3), CAV(4). At the moment of writing this thesis, more than 300 patients have been treated at these institutions for a wide variety of anatomical sites. Clinical studies performed by clinicians using IPSA demonstrated that the algorithm produces superior treatment plans from a dosimetric point of view than the conventional method using geometrical optimization. IPSA improves the target dose coverage while minimizing the dose delivered to organs at risk and provides consistent results from one patient to another. Both dosimetric indices and overall procedure time were improved with the clinical introduction of IPSA.« less