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Publications and source records attributed to Helen Liu.
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AIM: To evaluate the dosimetry, efficacy and toxicity of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with locally advanced cervical and upper thoracic esophageal cancer. METHODS: A retrospective study was performed on 7 patients who were definitively treated with IMRT and concurrent chemotherapy. Patients who did not receive IMRT radiation and concurrent chemotherapy were not included in this analysis. IMRT plans were evaluated to assess the tumor coverage and normal tissue avoidance. Treatment response was evaluated and toxicities were assessed. RESULTS: Five- to nine-beam IMRT were used to deliver a total dose of 59.4-66 Gy (median: 64.8 Gy) to the primary tumor with 6-MV photons. The minimum dose received by the planning tumor volume (PTV) of the gross tumor volume boost was 91.2%-98.2% of the prescription dose (standard deviation [SD]: 3.7%-5.7%). The minimum dose received by the PTV of the clinical tumor volume was 93.8%-104.8% (SD: 4.3%-11.1%) of the prescribed dose. With a median follow-up of 15 mo (range: 3-21 mo), all 6 evaluable patients achieved complete response. Of them, 2 developed local recurrences and 2 had distant metastases, 3 survived with no evidence of disease. After treatment, 2 patients developed esophageal stricture requiring frequent dilation and 1 patient developed tracheal-esophageal fistula. CONCLUSION: Concurrent IMRT and chemotherapy resulted in an excellent early response in patients with locally advanced cervical and upper thoracic esophageal cancer. However, local and distant recurrence and toxicity remain to be a problem. Innovative approaches are needed to improve the outcome.
Optimizing intensity-modulated radiotherapy (IMRT) plans involves tradeoffs that balance normal-tissue objectives against each other and against tumor objectives. Adjusting the parameters that determine the appropriate contributions of individual anatomic structures to the objective functions through trial and error is time consuming and may not produce the best achievable plans. We have developed a sensitivity-guided parameter optimization (SGPO) method to assist in the automatic determination of parameters to drive the IMRT optimization to better achieve, or even exceed, specified planning goals. The method is based on the trade-off relationships among multiple objectives: In a globally optimal plan (or within a convex subspace of the plan objectives), any attempt to improve the achievement of goals for a structure will result in sacrificing the goals for at least one other structure. However, different objectives may have different sensitivities to the overall goal of an IMRT plan. For instance, changes in dose distribution, hence the subscore corresponding to an objective for a given normal structure, may minimally impact the target dose distribution. Stated differently, the target coverage is insensitive to the changes in dose distribution of the specific normal structure. A lung cancer treatment plan designed with the SGPO method was used to demonstrate that IMRT plans could be designed to favor a structure with the highest target sensitivity and spare the structures with the least target sensitivity without compromising the target coverage. Using one case each of prostate and paranasal sinus cancers, we also demonstrated that several alternative optimal solutions could be designed with the SGPO algorithm favoring different structures. Finally, we applied the method to eight oropharyngeal cancer cases to obtain objective function parameters that satisfied the Radiation Therapy Oncology Group RTOG-H-0022 protocol. The eight plans optimized using the computer-generated objective function parameters met the protocol's scoring criteria with no or only minor protocol violations. Our preliminary study indicates that the SGPO method may be an effective and practical way to improve IMRT planning.
Optical motion analysis techniques have been widely used in biomechanics for measuring large-scale motions such as gait, but have not yet been significantly explored for measuring smaller movements such as the tooth displacements under load. In principle, very accurate measurements could be possible and this could provide a valuable tool in many engineering applications. The aim of this study was to evaluate accuracy and repeatability of the Qualisys ProReflex-MCU120 system when measuring small displacements, as a step towards measuring tooth displacements to characterise the properties of the periodontal ligament. Accuracy and repeatability of the system was evaluated using a wedge comparator with a resolution of 0.25 microm to provide measured marker displacements in three orthogonal directions. The marker was moved in ten steps in each direction, for each of seven step sizes (0.5, 1, 2, 3, 5, 10, and 20 microm), repeated five times. Spherical and diamond markers were tested. The system accuracy (i.e. percentage of maximum absolute error in range/measurement range), in the 20-200 microm ranges, was +/-1.17%, +/-1.67% and +/-1.31% for the diamond marker in x, y and z directions, while the system accuracy for the spherical marker was +/-1.81%, +/-2.37% and +/-1.39%. The system repeatability (i.e. maximum standard deviation in the measurement range) measured under the different days, light intensity and temperatures for five times, carried out step up and then step down measurements for the same step size, was +/-1.7, +/-2.3 and +/-1.9 microm for the diamond marker, and +/-2.6, +/-3.9 and +/-1.9 microm for the spherical marker in x, y and z directions, respectively. These results demonstrate that the system suffices accuracy for measuring tooth displacements and could potentially be useful in many other applications.
PURPOSE: To assess the association of clinical and especially dosimetric factors with the incidence of postoperative pulmonary complications among esophageal cancer patients treated with concurrent chemoradiation therapy followed by surgery. METHOD AND MATERIALS: Data from 110 esophageal cancer patients treated between January 1998 and December 2003 were analyzed retrospectively. All patients received concurrent chemoradiotherapy followed by surgery; 72 patients also received irinotecan-based induction chemotherapy. Concurrent chemotherapy was 5-fluorouracil-based and in 97 cases included taxanes. Radiotherapy was delivered to a total dose of 41.4-50.4 Gy at 1.8-2.0 Gy per fraction with a three-dimensional conformal technique. Surgery (three-field, Ivor-Lewis, or transhiatal esophagectomy) was performed 27-123 days (median, 45 days) after completion of radiotherapy. The following dosimetric parameters were generated from the dose-volume histogram (DVH) for total lung: lung volume, mean dose to lung, relative and absolute volumes of lung receiving more than a threshold dose (relative V(dose) and absolute V(dose)), and absolute volume of lung receiving less than a threshold dose (volume spared, or VS(dose)). Occurrence of postoperative pulmonary complications, defined as pneumonia or acute respiratory distress syndrome (ARDS) within 30 days after surgery, was the endpoint for all analyses. Fisher's exact test was used to investigate the relationship between categorical factors and incidence of postoperative pulmonary complications. Logistic analysis was used to analyze the relationship between continuous factors (e.g., V(dose) or VS(dose)) and complication rate. Logistic regression with forward stepwise inclusion of factors was used to perform multivariate analysis of those factors having univariate significance (p < 0.05). The Mann-Whitney test was used to compare length of hospital stay in patients with and without lung complications and to compare lung volumes, VS5 values, and absolute and relative V5 values in male vs. female patients. Pearson correlation analysis was used to determine correlations between dosimetric factors. RESULTS: Eighteen (16.4%) of the 110 patients developed postoperative pulmonary complications. Two of these died of progressive pneumonia. Hospitalizations were significantly longer for patients with postoperative pulmonary complications than for those without (median, 15 days vs. 11 days, p = 0.003). On univariate analysis, female gender (p = 0.017), higher mean lung dose (p = 0.036), higher relative volume of lung receiving > or = 5 Gy (V5) (p = 0.023), and smaller volumes of lung spared from doses > or = 5-35 Gy (VS5-VS35) (p < 0.05) were all significantly associated with an increased incidence of postoperative pulmonary complications. No other clinical factors were significantly associated with the incidence of postoperative pulmonary complications in this cohort. On multivariate analysis, the volume of lung spared from doses > or = 5 Gy (VS5) was the only significant independent factor associated with postoperative pulmonary complications (p = 0.005). CONCLUSIONS: Dosimetric factors but not clinical factors were found to be strongly associated with the incidence of postoperative pulmonary complications in this cohort of esophageal cancer patients treated with concurrent chemoradiation plus surgery. The volume of the lung spared from doses of > or = 5 Gy was the only independent dosimetric factor in multivariate analysis. This suggests that ensuring an adequate volume of lung unexposed to radiation might reduce the incidence of postoperative pulmonary complications.
PURPOSE: To determine the effectiveness of noncoplanar beam configurations and the benefit of plans using fewer but optimally placed beams designed by a parallelized multiple-resolution beam angle optimization (PMBAO) approach. METHODS AND MATERIALS: The PMBAO approach uses a combination of coplanar and noncoplanar beam configurations for intensity-modulated radiation therapy (IMRT) treatment planning of paranasal sinus cancers. A smaller number of beams (e.g. 3) are first used to explore the solution space to determine the best and worst beam directions. The results of this exploration are then used as a starting point for determining an optimum beam orientation configuration with more beams (e.g. 5). This process is parallelized using a message passing interface, which greatly reduces the overall computation time for routine clinical practice. To test this approach, treatment for 10 patients with paranasal sinus cancer was planned using a total of 5 beams from a pool of 46 possible beam angles. The PMBAO treatment plans were also compared with IMRT plans designed using 9 equally spaced coplanar beams, which is the standard approach in our clinic. Plans with these two different beam configurations were compared with respect to dose conformity, dose heterogeneity, dose-volume histograms, and doses to organs at risk (i.e., eyes, optic nerve, optic chiasm, and brain). RESULTS: The noncoplanar beam configuration was superior in most paranasal sinus carcinoma cases. The target dose homogeneity was better using a PMBAO 5-beam configuration. However, the dose conformity using PMBAO was not improved and was case dependent. Compared with the 9-beam configuration, the PMBAO configuration significantly reduced the mean dose to the eyes and optic nerves and the maximum dose to the contralateral optical path (e.g. the contralateral eye and optic nerve). The maximum dose to the ipsilateral eye and optic nerve was also lower using the PMBAO configuration than using the 9-beam configuration, although this difference was not significant. The mean doses to the optic chiasm and brain are marginally lower using the PMBAO configuration than using 9-beam configuration. The maximum doses to the optic chiasm and brain are the same with the PMBAO configuration and the 9-beam configuration. CONCLUSION: Parallelized multiple-resolution beam angle optimization with an optimized noncoplanar beam configuration is an effective and practical approach for IMRT treatment planning. Five-beam treatment plans optimized using the PMBAO are at least equivalent to, and overall better than, the plans using 9 equally spaced coplanar beams.
PURPOSE: Recent imaging studies have demonstrated that there can be significant changes in anatomy from day to day and over the course of radiotherapy as a result of daily positioning uncertainties and physiologic and clinical factors. There are a number of strategies to minimize such changes, reduce their impact, or correct for them. Measures to date have included improved immobilization of external and internal anatomy or adjustment of positions based on portal or ultrasound images. Perhaps the most accurate way is to use CT image-guided radiotherapy, for which the possibilities range from simple correction of setup based on daily CT images to on-line near real-time intensity modulated radiotherapy (IMRT) replanning. In addition, there are numerous intermediate possibilities. In this paper, we report the development of one such intermediate method that takes into account anatomic changes by deforming the intensity distributions of each beam based on deformations of anatomy as seen in the beam's-eye-view. METHODS AND MATERIALS: The intensity distribution deformations are computed based on anatomy deformations discerned from the changes in the current image relative to a reference image (e.g., the pretreatment CT scan). First, a reference IMRT plan is generated based on the reference CT image. A new CT image is acquired using an in-room CT for every fraction. The anatomic structure contours are obtained for the new image. (For this article, these contours were manually drawn. When image guided IMRT methods are implemented, anatomic structure contours on subsequent images will likely be obtained with automatic or semiautomatic means. This could be achieved by, for example, first deforming the original CT image to match today's image, and then using the same deformation transformation to map original contours to today's image.) The reference intensity distributions for each beam are then deformed so that the projected geometric relationship within the beam's-eye-view between the anatomy (both target and normal tissues) extracted from the reference image and the reference intensity distribution is the same as (or as close as possible to) the corresponding relationship between anatomy derived from today's image and the newly deformed intensity distributions. To verify whether the dose distributions calculated using the deformed intensity distributions are acceptable for treatment as compared to the original intensity distributions, the deformed intensities are transformed into leaf sequences, which are then used to compute intensity and dose distributions expected to be delivered. The corresponding dose-volume histograms and dose-volume and dose-response indices are also computed. These data are compared with the corresponding data derived (a) from the original treatment plan applied to the original image, (b) from the original treatment plan applied to today's image, and (c) from a new full-fledged IMRT plan designed based on today's image. RESULTS: Depending on the degree of anatomic changes, the use of an IMRT plan designed based on the original planning CT for the treatment of the current fraction could lead to significant differences compared to the intended dose distributions. CT-guided setup compared to the setup based on skin marks or bony landmarks may improve dose distributions somewhat. Replanning IMRT based on the current fraction's image yields the best physically deliverable plan (the "gold standard"). For the prostate and head-and-neck examples studied as proof of principle, the results of deforming intensities within each beam based on the anatomy seen in the beam's-eye-view are a good approximation of full-fledged replanning compared with other alternatives. CONCLUSIONS: Our preliminary results encourage us to believe that deforming intensities taking into account deformation in the anatomy may be a rapid way to produce new treatment plans on-line in near real-time based on daily CT images. The methods we have developed need to be applied to a group of patients for both prostate and head-and-neck cases to confirm the validity of our approach.
PURPOSE: The purpose of this article is to explore the use of the accelerated exhaustive search strategy for developing and validating methods for optimizing beam orientations for intensity-modulated radiation therapy (IMRT). Combining beam-angle optimization (BAO) with intensity distribution optimization is expected to improve the quality of IMRT treatment plans. However, BAO is one of the most difficult problems to solve adequately because of the huge hyperspace of possible beam configurations (e.g., selecting 7 of 36 uniformly spaced coplanar beams would require the intercomparison of 8,347,680 IMRT plans). METHODS AND MATERIALS: An "influence vector" (IV) approximation technique for high-speed estimation of IMRT dose distributions was used in combination with a fast gradient search algorithm (Newton's method) for IMRT optimization. In the IV approximation, it is assumed that the change in intensity of a ray (or bixel) proportionately changes dose along the ray. Evidence is presented that the IV approximation is valid for BAO. The scatter contribution at points away from the ray is accounted for fully in IMRT optimization after the optimum beam orientation has been determined. IVs for all candidate beam angles are generated before the start of optimization. For all subsets of beams selected from a given pool of beams (e.g., 5 of 24 uniformly spaced beams), the distribution of planning scores for the best and the worst plans, optimum angle distributions, dose distributions, and dose-volume histograms (DVH) were analyzed for one prostate and two lung cancer cases. The results of the exhaustive search technique were used to develop a "multiresolution" search strategy. In this approach, a smaller number of beams (e.g., three) is first used to explore the hyperspace of solutions to determine the most preferred and the least preferred directions. The results of such exploration are then used as a starting point for determining an optimum configuration comprising a larger number of beams (e.g., seven). This two-step process is considerably faster than full exhaustive search. The question to be answered was whether the two methods lead to the same or similar solutions. The results of exhaustive search and multiresolution approaches were also compared with a previously published approach that used beam's-eye-view dosimetrics (BEVD). RESULTS: The relative ranks of plans optimized by an accurate dose calculation method were highly correlated with those of the plans optimized by the fast calculation method (i.e., using the IV approximation), which suggests that an approximate dose calculation algorithm can be used effectively for ranking of plans during BAO. We found that dose distributions and DVH of many beam configurations within a specified subset from a given pool of beams (e.g., 5 of 18) may be clinically indistinguishable and acceptable. Their optimized IMRT scores fall in a narrow range, although beam configurations and dose distributions may be different. We used the frequency distributions as a function of beam angles for the best 100 and the worst 100 plans to determine the most and the least preferred beam angles. We found that the most and the least preferred angle distributions for 3 of 18 configurations were very similar to those for 5, 6, 7, or 8 of 18 or 24 configurations, but the size of the search space was much smaller for the 3 of 18 case. Using fewer than three beams was discovered to be inadequate. This information was used to select the most preferred angles and eliminate the least preferred ones before searching for the optimum angles for the remaining beams. For the cases we studies, the multiresolution strategy produced very similar results to the full exhaustive search. Based on the observation that the worst plans had at least one parallel-opposed pair of beams and virtually all of the best plans had none, we were able to further reduce the size of the search space dramatically by using a pool of only nonparallel-opposed equispaced beams (i.e., 7 of 19 instead of 7 of 36). Another observation was that the probability of finding an optimum configuration in a smaller beam pool is substantially lower than in a larger pool (e.g., 5 of 18 vs. 5 of 24). The implication of this BAO is not very important when a large number of beams (nine or more) is used and vice versa. Our results showed that the plans with fewer but optimally placed beams could be as good as or better than plans using a larger number of unoptimized or uniformly placed beams. CONCLUSION: Exhaustive search with fast IMRT algorithms provides a novel and realistic approach to study the characteristics of IMRT dose distributions as a function of beam angles and to design practical BAO strategies for IMRT planning.
PURPOSE: Conformal radiotherapy (RT) has allowed radiation dose escalation to improve the outcome of prostate cancer. With higher doses, concern exists that rectal injury may increase. This study analyzed the utility and limitations of the widely used Lyman-Kutcher- Burman (LKB) normal tissue complication probability model in projecting the hazards of rectal complication with high-dose RT. METHODS AND MATERIALS: A total of 128 patients were included in this study. These patients were treated with three-dimensional conformal RT alone at the University of Texas M.D. Anderson Cancer Center between 1992 and 1999. Patients were treated to 46 Gy with a four-field box technique followed by a six-field arrangement to boost the total dose to 78 Gy. All doses were delivered at 2 Gy/fraction to the isocenter. The minimal follow-up was 2 years. The end point for analysis was Grade 2 or worse rectal bleeding by 2 years. The LKB model was fitted to the data using the maximal likelihood method. RESULTS: Of the 128 patients, 29 experienced Grade 2 or worse rectal bleeding by 2 years. For the entire cohort, the parameters obtained from the fit of the LKB model were as follows: the volume factor was n = 3.91 (95% confidence interval [CI] 0.031 to infinity ), dose associated with 50% chance of complication for uniform whole rectal irradiation [TD50(1)] was 53.6 Gy (95% CI 50.0-75.1), and a determinant of the steepness of the dose-response curve, (m), was 0.156 (95% CI 0.036-0.271). A statistically significant difference was found in the rate of postradiation rectal bleeding in patients with hemorrhoids vs. those without hemorrhoids. The parameters obtained for the patients without hemorrhoids were as follows: n = 0.746 (95% CI 0.026 to infinity ), TD50(1) 56.7 Gy (95% CI 49.9-75.2), and m 0.092 (95% CI 0.019-0.189). CONCLUSION: Our analysis suggests a dose response for rectal bleeding probability along with a volume effect. We found that the LKB model might have limited utility in determining a large volume effect. We further suggest that LKB model should be used with caution in clinical practice.
PURPOSE: This study describes a new intensity-modulated radiation therapy (IMRT) delivery method that utilizes a single modulator to deliver multiple fields ("multifield modulator"). This technique reduces the treatment time and manufacturing costs typically associated with modulator-IMRT. Technical feasibility was evaluated for treating paranasal sinus cancers. METHODS AND MATERIALS: Technical feasibility was measured by three criteria: The dose distributions of the multifield modulator-IMRT plans should offer improvements over those produced by 3D conformal plans and be equivalent to those of step-and-shoot multileaf collimator (MLC) IMRT plans, the manufactured modulators should meet quality assurance specifications, and the effort required to use this technology should not substantially exceed the effort required for current IMRT practice. Seven paranasal cancer cases were examined. The Wilcoxon signed rank test was used for statistical analysis. RESULTS: Multifield modulator-IMRT plans can improve target coverage while reducing critical structure doses compared to 3D conformal plans. Multifield modulator-IMRT plans are at least equivalent to the corresponding step-and-shoot MLC-IMRT plans. Multifield modulators can be constructed to meet design specifications in quality assurance tests. The time required for manufacturing, quality assurance, and treatment delivery using multifield modulators was measured and found to be only slightly greater than that for current IMRT treatment methods. CONCLUSIONS: IMRT treatments using multifield modulators for paranasal sinus tumors are feasible. Clinics may find it worthwhile to commit the minimal extra time for quality assurance and treatment to benefit from the improved dose distribution and lack of interplay between MLC leaf motion and internal target motion.
Gradient algorithms are the most commonly employed search methods in the routine optimization of IMRT plans. It is well known that local minima can exist for dose-volume-based and biology-based objective functions. The purpose of this paper is to compare the relative speed of different gradient algorithms, to investigate the strategies for accelerating the optimization process, to assess the validity of these strategies, and to study the convergence properties of these algorithms for dose-volume and biological objective functions. With these aims in mind, we implemented Newton's, conjugate gradient (CG), and the steepest decent (SD) algorithms for dose-volume- and EUD-based objective functions. Our implementation of Newton's algorithm approximates the second derivative matrix (Hessian) by its diagonal. The standard SD algorithm and the CG algorithm with "line minimization" were also implemented. In addition, we investigated the use of a variation of the CG algorithm, called the "scaled conjugate gradient" (SCG) algorithm. To accelerate the optimization process, we investigated the validity of the use of a "hybrid optimization" strategy, in which approximations to calculated dose distributions are used during most of the iterations. Published studies have indicated that getting trapped in local minima is not a significant problem. To investigate this issue further, we first obtained, by trial and error, and starting with uniform intensity distributions, the parameters of the dose-volume- or EUD-based objective functions which produced IMRT plans that satisfied the clinical requirements. Using the resulting optimized intensity distributions as the initial guess, we investigated the possibility of getting trapped in a local minimum. For most of the results presented, we used a lung cancer case. To illustrate the generality of our methods, the results for a prostate case are also presented. For both dose-volume and EUD based objective functions, Newton's method far outperforms other algorithms in terms of speed. The SCG algorithm, which avoids expensive "line minimization," can speed up the standard CG algorithm by at least a factor of 2. For the same initial conditions, all algorithms converge essentially to the same plan. However, we demonstrate that for any of the algorithms studied, starting with previously optimized intensity distributions as the initial guess but for different objective function parameters, the solution frequently gets trapped in local minima. We found that the initial intensity distribution obtained from IMRT optimization utilizing objective function parameters, which favor a specific anatomic structure, would lead to a local minimum corresponding to that structure. Our results indicate that from among the gradient algorithms tested, Newton's method appears to be the fastest by far. Different gradient algorithms have the same convergence properties for dose-volume- and EUD-based objective functions. The hybrid dose calculation strategy is valid and can significantly accelerate the optimization process. The degree of acceleration achieved depends on the type of optimization problem being addressed (e.g., IMRT optimization, intensity modulated beam configuration optimization, or objective function parameter optimization). Under special conditions, gradient algorithms will get trapped in local minima, and reoptimization, starting with the results of previous optimization, will lead to solutions that are generally not significantly different from the local minimum.