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Qiuwen Wu

Publications and source records attributed to Qiuwen Wu.

At least 19 recordsLinked to original sources

Geometric and dosimetric evaluations of an online image-guidance strategy for 3D-CRT of prostate cancer.

PURPOSE: To evaluate an online image-guidance strategy for conformal treatment of prostate cancer and to estimate margin-reduction benefits. METHODS AND MATERIALS: Twenty-eight patients with at least 16 helical computed tomography scans were each used in this study. Two prostate soft-tissue registration methods, including sagittal rotation, were evaluated. Setup errors and rigid organ motion were corrected online; non-rigid and intrafraction motion were included in offline analysis. Various clinical target volume-planning target volume (CTV-PTV) margins were applied. Geometrical evaluations included analyses of isocenter shifts and rotations and overlap index. Dosimetric evaluations included minimum dose and equivalent uniform dose (EUD) for prostate and gEUD for rectum. RESULTS: Average isocenter shift and rotation were (dX,dY,dZ,theta) = (0.0 +/- 0.7,-1.1 +/- 4.0,-0.1 +/- 2.5,0.7 degrees +/- 2.0 degrees ) mm. Prostate motion in anterior-posterior (AP) direction was significantly higher than superior-inferior and left-right (LR) directions. This observation was confirmed by isocenter shift in perspectives AP (1.8 +/- 1.8 mm) and RL (3.7 +/- 3.0 mm). Organ motion degrades target coverage and reduces doses to rectum. If 2% dose reduction on prostate D(99) is allowed for 90% patients, then minimum 3 mm margins are necessary with ideal image registration. CONCLUSIONS: Significant margin reduction can be achieved through online image guidance. Certain margins are still required for nonrigid and intrafraction motion. To further reduce margin, a strategy that combines online geometric intervention and offline dose replanning is necessary.

Algorithms↗

Monte Carlo-based dosimetry of head-and-neck patients treated with SIB-IMRT.

PURPOSE: To evaluate the accuracy of previously reported superposition/convolution (SC) dosimetric results by comparing with Monte Carlo (MC) dose calculations for head-and-neck intensity-modulated radiation therapy (IMRT) patients treated with the simultaneous integrated boost technique. METHODS AND MATERIALS: Thirty-one plans from 24 patients previously treated on a phase I/II head-and-neck squamous cell carcinoma simultaneous integrated boost IMRT protocol were used. Clinical dose distributions, computed with an SC algorithm, were recomputed using an EGS4-based MC algorithm. Phantom-based dosimetry quantified the fluence prediction accuracy of each algorithm. Dose-volume indices were used to compare patient dose distributions. RESULTS AND DISCUSSION: The MC algorithm predicts flat-phantom measurements better than the SC algorithm. Average patient dose indices agreed within 2.5% of the local dose for targets; 5.0% for parotids; and 1.9% for cord and brainstem. However, only 1 of 31 plans agreed within 3% for all indices; 4 of 31 agreed within 5%. In terms of the prescription dose, 4 of 31 plans agreed within 3% for all indices, whereas 28 of 31 agreed within 5%. CONCLUSIONS: Average SC-computed doses agreed with MC results in the patient geometry; however deviations >5% were common. The fluence modulation prediction is likely the major source of the dose discrepancy. The observed dose deviations can impact dose escalation protocols, because they would result in shifting patients to higher dose levels.

Algorithms↗

Application of dose compensation in image-guided radiotherapy of prostate cancer.

In image-guided radiation therapy (IGRT), volumetric information on patient anatomy at treatment conditions is made available with in-room imaging devices capable of cone-beam CT. Setup error and inter-fraction rigid motion can be corrected online. The planning margin can therefore be reduced significantly. However, to compensate for uncertainties including organ deformation and intra-fraction motion, offline evaluation and replanning are necessary. The purpose of this study is to investigate the use of an offline dose compensation technique to further reduce the margin safely. In IGRT, online CT scan, rigid image registration and setup correction are performed at each fraction. Later the regions of interest are registered offline between treatment and planning CTs using a finite element method to account for non-rigid organ motion. Cumulative dose distribution is calculated and compared with the prescription dose. The discrepancy, if found significant, is repaired using the dose compensation technique, in which the cumulative dose distribution is incorporated in adaptive IMRT planning for future fractions. Two compensation schedules were tested in this study: single compensation at the end of the treatment course and compensation performed weekly. One patient with one planning CT and 16 treatment CTs were used in this simulation study. Due to the aggressive smaller planning margin used, severe underdose was observed in the clinical target volume. The size and magnitude of the underdose were reduced substantially with online guidance but were still significant. Both dose compensation strategies were able to reduce the dose deficit to an acceptable level without additional planning margin. Weekly compensation is more biologically beneficial and can spread the execution error into multiple fractions. The offline dose compensation technique allows further margin reduction and can complement the online guidance by compensating for uncertainties that cannot be reduced online, thereby increasing the confidence in IGRT delivery.

Dose-Response Relationship, Radiation↗

Effect of patient setup errors on simultaneously integrated boost head and neck IMRT treatment plans.

PURPOSE: The purpose of this study is to determine dose delivery errors that could result from random and systematic setup errors for head-and-neck patients treated using the simultaneous integrated boost (SIB)-intensity-modulated radiation therapy (IMRT) technique. METHODS AND MATERIALS: Twenty-four patients who participated in an intramural Phase I/II parotid-sparing IMRT dose-escalation protocol using the SIB treatment technique had their dose distributions reevaluated to assess the impact of random and systematic setup errors. The dosimetric effect of random setup error was simulated by convolving the two-dimensional fluence distribution of each beam with the random setup error probability density distribution. Random setup errors of sigma = 1, 3, and 5 mm were simulated. Systematic setup errors were simulated by randomly shifting the patient isocenter along each of the three Cartesian axes, with each shift selected from a normal distribution. Systematic setup error distributions with Sigma = 1.5 and 3.0 mm along each axis were simulated. Combined systematic and random setup errors were simulated for sigma = Sigma = 1.5 and 3.0 mm along each axis. For each dose calculation, the gross tumor volume (GTV) received by 98% of the volume (D(98)), clinical target volume (CTV) D(90), nodes D(90), cord D(2), and parotid D(50) and parotid mean dose were evaluated with respect to the plan used for treatment for the structure dose and for an effective planning target volume (PTV) with a 3-mm margin. RESULTS: Simultaneous integrated boost-IMRT head-and-neck treatment plans were found to be less sensitive to random setup errors than to systematic setup errors. For random-only errors, errors exceeded 3% only when the random setup error sigma exceeded 3 mm. Simulated systematic setup errors with Sigma = 1.5 mm resulted in approximately 10% of plan having more than a 3% dose error, whereas a Sigma = 3.0 mm resulted in half of the plans having more than a 3% dose error and 28% with a 5% dose error. Combined random and systematic dose errors with sigma = Sigma = 3.0 mm resulted in more than 50% of plans having at least a 3% dose error and 38% of the plans having at least a 5% dose error. Evaluation with respect to a 3-mm expanded PTV reduced the observed dose deviations greater than 5% for the sigma = Sigma = 3.0 mm simulations to 5.4% of the plans simulated. CONCLUSIONS: Head-and-neck SIB-IMRT dosimetric accuracy would benefit from methods to reduce patient systematic setup errors. When GTV, CTV, or nodal volumes are used for dose evaluation, plans simulated including the effects of random and systematic errors deviate substantially from the nominal plan. The use of PTVs for dose evaluation in the nominal plan improves agreement with evaluated GTV, CTV, and nodal dose values under simulated setup errors. PTV concepts should be used for SIB-IMRT head-and-neck squamous cell carcinoma patients, although the size of the margins may be less than those used with three-dimensional conformal radiation therapy.

Algorithms↗

Dose sculpting with generalized equivalent uniform dose.

With intensity-modulated radiotherapy (IMRT), a variety of user-defined dose distribution can be produced using inverse planning. The generalized equivalent uniform dose (gEUD) has been used in IMRT optimization as an alternative objective function to the conventional dose-volume-based criteria. The purpose of this study was to investigate the effectiveness of gEUD optimization to fine tune the dose distributions of IMRT plans. We analyzed the effect of gEUD-based optimization parameters on plan quality. The objective was to determine whether dose distribution to selected structures could be improved using gEUD optimization without adversely altering the doses delivered to other structures, as in sculpting. We hypothesized that by carefully defining gEUD parameters (EUD0 and n) based on the current dose distributions, the optimization system could be instructed to search for alternative solutions in the neighborhood, and we could maintain the dose distributions for structures already satisfactory and improve dose for structures that need enhancement. We started with an already acceptable IMRT plan optimized with any objective function. The dose distribution was analyzed first. For structures that dose should not be changed, a higher value of n was used and EUD0 was set slightly higher/lower than the EUD value at the current dose distribution for critical structures/targets. For structures that needed improvement in dose, a higher to medium value of n was used, and EUD0 was set to the EUD value or slightly lower/higher for the critical structure/target at the current dose distribution. We evaluated this method in one clinical case each of head and neck, lung and prostate cancer. Dose volume histograms, isodose distributions, and relevant tolerance doses for critical structures were used for the assessment. We found that by adjusting gEUD optimization parameters, the dose distribution could be improved with only a few iterations. A larger value of n could lead to faster convergence and a medium value of n could result in a search in a broader area. Such improvement could also be achieved by optimization based on other criteria, but the gEUD-based method has the advantage of efficiency and flexibility. Therefore, gEUD-based optimization can be used as a tool to improve IMRT plans by adjusting the planning parameters, thereby making dose sculpting feasible.

Algorithms↗

Development of methods for beam angle optimization for IMRT using an accelerated exhaustive search strategy.

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.

Algorithms↗

A dose calculation method including scatter for IMRT optimization.

IMRT optimization is an iterative process in which many dose calculations may be necessary. A fast and accurate dose calculation engine is essential for the optimization program to converge to a reliable solution in a reasonable time. Previously we developed a fast dose calculation method for IMRT optimization based on the table lookup (TLP). The TLP kernel is constructed from the dose distributions computed from an accurate superposition/convolution (SC) algorithm at the beginning. Dose calculations at subsequent iterations are performed by looking up the kernel in memory, therefore are very fast. However, it is assumed by the TLP that the beamlet only deposits doses to the voxels on its path. In this paper, we propose an improved table lookup based dose calculation method that includes the scatter contribution (TLPS). The intensity map for each beam is decomposed into an even and an odd checkbox-type pattern for the construction of the kernel for primary and scatter components. The performance of this algorithm is compared with the methods of SC only and TLP without scatter on a few clinical cases and the advantages of speed and accuracy are demonstrated. This method is especially useful for those optimizations that utilize the IMRT optimization as an inner loop, such as the beam angle optimization.

Algorithms↗

Simultaneous integrated boost intensity-modulated radiotherapy for locally advanced head-and-neck squamous cell carcinomas: II--clinical results.

PURPOSE: To perform a Phase I radiation dose-escalation trial to determine the maximal tolerable dose (MTD) deliverable to the gross tumor volume (GTV) using an accelerated fractionation with simultaneous integrated boost intensity-modulated radiotherapy regimen with parotid gland sparing as the sole therapy in the treatment of locally advanced head-and-neck squamous cell carcinoma. The primary objective was the definition of the MTD using established criteria of quantifying acute dose-limiting toxicity (DLT). Secondary objectives included analysis of failure patterns, tumor control rates, and toxicity. METHODS AND MATERIALS: Between July 1999 and June 2002, eligible patients with bulky Stage II to Stage IVB head-and-neck squamous cell carcinoma, excluding laryngeal primaries, were enrolled. Intensity-modulated radiotherapy was delivered with 6-MV photons using a "sliding-window" technique. Enrollment of 6 patients for each dose level was planned; if DLTs were seen in >2 of 6 patients, the previous dose was to be expanded by an additional 6 patients to confirm that dose level as the MTD. All schedules administered a total of 30 fractions, but with escalating doses per fraction (2.27, 2.36, and 2.46 Gy) to achieve a total dose to the GTV of 68.1, 70.8, and 73.8 Gy, respectively. The remaining target tissues were constrained to receive the same dose in all patients regardless of the GTV dose level. The clinical target volume, defined as tissue within 1 cm around the GTV (at high risk of subclinical disease), received 60 Gy in 30 fractions of 2.0 Gy. The electively irradiated target volume, defined as the clinically uninvolved lymph node-bearing tissues, received 54 Gy in 30 fractions of 1.8 Gy. The parotid glands were spared to the degree possible without compromising target coverage. Acute toxicity was scored weekly using National Cancer Institute Common Toxicity Criteria. DLT was defined as any Grade 4 acute toxicity or any acute toxicity requiring either a dose reduction or a treatment break of >5 treatment days. RESULTS: Of 18 men and 2 women (average age, 57 years; range, 37-80 years), 17 presented with oropharyngeal primary tumors, and 1 each with squamous cell carcinoma of the oral cavity, nasopharynx, and hypopharynx. None of the 6 patients at dose level 1, and 2 of the 6 patients initially enrolled at dose level 2, developed DLT. Both patients treated at dose level 3 required a 3-day treatment break and dose reduction after rapid development of Grade 3 toxicity (by Day 15). Six additional confirmatory patients subsequently enrolled at dose level 2 completed treatment without DLT. At least 50% of the total parotid gland volume received <30 Gy in 14 patients (average, 54% of volume), with an average mean dose of 32 Gy. In contrast, >/=50% of the distal parotid gland volume received <25 Gy in 15 patients (average, 63% of volume), with an average mean dose of 24 Gy. With a median follow-up of 20 months from the date of enrollment and 28 months for surviving patients, the actuarial 2-year local control (primary site), regional control (nodal sites), and distant control rate was 76.3%, 66.7%, and 71.8%, respectively. CONCLUSION: Dose level 2, 70.8 Gy in 30 fractions of 2.36 Gy, was defined as the MTD deliverable to the GTV using this accelerated fractionation with simultaneous integrated boost intensity-modulated radiotherapy regimen with parotid gland sparing as the sole treatment for locally advanced head-and-neck squamous cell carcinoma. Adequate parotid sparing was achievable in most cases. Early toxicity, tumor control, and survival rates compared favorably with the outcomes after other accelerated regimens.

Adult↗

Feasibility of sparing lung and other thoracic structures with intensity-modulated radiotherapy for non-small-cell lung cancer.

PURPOSE: To investigate the possibility of using intensity-modulated radiotherapy (IMRT) to reduce the irradiated volumes of the normal lung and other critical structures in the treatment of non-small-cell lung cancer (NSCLC) and to investigate the effect of IMRT on the potential of spreading low doses to large volumes of normal tissues in such treatment. METHODS AND MATERIALS: A retrospective treatment planning study was performed to compare IMRT and conventional three-dimensional conformal radiation therapy (3D-CRT) for 10 NSCLC patients (Stage I-IIIB). In the IMRT plans, three to nine coplanar beams were designed to treat 95% of the planning target volume with 63 Gy and to minimize the volumes of the normal lung, esophagus, heart, and spinal cord irradiated above their tolerance doses. The two types of plans were compared with respect to the planning target volume coverage, dose-volume histograms, and other dosimetric indexes of the normal structures. RESULTS: Comparing the nine-beam IMRT plan with the 3D-CRT plan, the percentage of lung volume that received >20 Gy and the mean lung dose were reduced for all cases, with a median reduction of 8% and 2 Gy, respectively. An additional reduction of the >5-Gy volume and >10-Gy volume for the lung and thoracic tissue was more difficult with IMRT, although still possible using fewer beams in IMRT. The integral dose to the entire thorax was equivalent and even reduced for 8 of 10 cases using IMRT. CONCLUSION: It is possible to reduce the volumes of low doses (such as the >10-Gy volume and >20-Gy volume) for thoracic normal tissues using IMRT. The increased integral dose and low-dose volumes can be avoided for IMRT if such concerns are addressed carefully in the inverse planning process and with optimization of the IMRT beam configuration.

Carcinoma, Non-Small-Cell Lung↗

Speed and convergence properties of gradient algorithms for optimization of IMRT.

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.

Algorithms↗

Potential of intensity-modulated radiotherapy to escalate doses to head-and-neck cancers: what is the maximal dose?

PURPOSE: To investigate the potential of intensity-modulated radiotherapy (IMRT) to escalate doses to head-and-neck cancer and find the maximal dose that could be prescribed to the target volume with IMRT while doses to critical organs were maintained at their currently acceptable levels. The secondary goal was to search for limits in current IMRT technology. METHODS AND MATERIALS: For a group of 12 head-and-neck cancer patients with different tumor locations and shapes, we performed IMRT planning using a simultaneous integrated boost strategy, that is, the gross tumor volume (GTV), clinical target volume (CTV), and electively treated nodes were treated simultaneously at different dose levels. The critical structures involved in the treatment field that needed to be spared included the brainstem, spinal cord, and parotid glands, depending on the disease site. Nine coplanar 6-MV photon beams were used for planning with the IMRT system developed at our institution, and dose-volume criteria were used for optimization. By varying the optimization parameters, we gradually increased the dose to the GTV while keeping the dose to the critical structures at less than the acceptable tolerance level. The criteria for accepting the plan included the following: (1) the prescription dose to the GTV had to cover 99% of the volume, and the dose homogeneity of the GTV needed to be <10%; (2) the prescription to the CTV (which was set either at 60 Gy or 10 Gy less than that of the GTV) had to cover 95% of the volume, and the same amount of normal tissue outside the CTV received the CTV prescription dose as in the current acceptable plan; (3) the prescription to the electively treated lymph nodes needed to cover 90% of the volume; and (4) the maximal dose to the brainstem and spinal cord had to be <55 Gy and 45 Gy, respectively. For parotid glands, the dose needed to be as low as possible without compromising the target doses. The deliverable plans as determined by the actual multileaf collimator leaf sequences were used for the final evaluation. To verify that the acceptable plans were deliverable, the experimental measurements of planar dose distribution were performed in phantom with film. RESULTS: The maximal dose to the GTV varied from 86 to 176 Gy if the CTV dose increased with the GTV dose. It was reduced to 76-82 Gy if the CTV dose was kept at 60 Gy. The competing criteria usually are the requirements of the tolerance doses to the critical organs and target dose homogeneity, not the target prescription dose. Using more beams only increased the dose marginally. The results could change significantly if a different set of criteria for the plan evaluation were used. Dosimetric measurements confirmed that such a high dose and dose gradient could be delivered accurately with dynamic multileaf collimators. Statistical analyses showed no significant correlations between the maximal doses and the number of GTVs and volume of GTVs and CTVs. CONCLUSION: Doses to head-and-neck cancers with simultaneous integrated boost IMRT can be escalated to a greater level than currently prescribed clinically. The limit of IMRT in head-and-neck cancer has not been reached at the current prescription level of 70 Gy. Such high total and fractionated doses should be carefully evaluated before being prescribed clinically.

Adult↗

Algorithm and performance of a clinical IMRT beam-angle optimization system.

This paper describes the algorithm and examines the performance of an intensity-modulated radiation therapy (IMRT) beam-angle optimization (BAO) system. In this algorithm successive sets of beam angles are selected from a set of predefined directions using a fast simulated annealing (FSA) algorithm. An IMRT beam-profile optimization is performed on each generated set of beams. The IMRT optimization is accelerated by using a fast dose calculation method that utilizes a precomputed dose kernel. A compact kernel is constructed for each of the predefined beams prior to starting the FSA algorithm. The IMRT optimizations during the BAO are then performed using these kernels in a fast dose calculation engine. This technique allows the IMRT optimization to be performed more than two orders of magnitude faster than a similar optimization that uses a convolution dose calculation engine. Any type of optimization criterion present in the IMRT system can be used in this BAO system. An objective function based on clinically-relevant dose-volume (DV) criteria is used in this study. This facilitates the comparison between a BAO plan and the corresponding plan produced by a planner since the latter is usually optimized using a DV-based objective function. A simple prostate case and a complex head-and-neck (HN) case were used to evaluate the usefulness and performance of this BAO method. For the prostate case we compared the BAO results for three, five and seven coplanar beams with those of the same number of equispaced coplanar beams. For the HN case we compare the BAO results for seven and nine non-coplanar beams with that for nine equispaced coplanar beams. In each case the BAO algorithm was allowed to search up to 1000 different sets of beams. The BAO for the prostate cases were finished in about 1-2 h on a moderate 400 MHz workstation while that for the head-and-neck cases were completed in 13-17 h on a 750 MHz machine. No a priori beam-selection criteria have been used in achieving this performance. In both the prostate and the head-and-neck cases, BAO is shown to provide improvements in plan quality over that of the equispaced beams. The use of DV-based objective function also allows us to study the dependence of the improvement of plan quality offered by BAO on the DV criteria used in the optimization. We found that BAO is especially useful for cases that require strong DV criteria. The main advantages of this BAO system are its speed and its direct link to a clinical IMRT system.

Algorithms↗

A fast dose calculation method based on table lookup for IMRT optimization.

This note describes a fast dose calculation method that can be used to speed up the optimization process in intensity-modulated radiotherapy (IMRT). Most iterative optimization algorithms in IMRT require a large number of dose calculations to achieve convergence and therefore the total amount of time needed for the IMRT planning can be substantially reduced by using a faster dose calculation method. The method that is described in this note relies on an accurate dose calculation engine that is used to calculate an approximate dose kernel for each beam used in the treatment plan. Once the kernel is computed and saved, subsequent dose calculations can be done rapidly by looking up this kernel. Inaccuracies due to the approximate nature of the kernel in this method can be reduced by performing scheduled kernel updates. This fast dose calculation method can be performed more than two orders of magnitude faster than the typical superposition/convolution methods and therefore is suitable for applications in which speed is critical, e.g., in an IMRT optimization that requires a simulated annealing optimization algorithm or in a practical IMRT beam-angle optimization system.

Algorithms↗

Simultaneous integrated boost intensity-modulated radiotherapy for locally advanced head-and-neck squamous cell carcinomas. I: dosimetric results.

PURPOSE: This report describes the dosimetric analyses of a Phase I/II protocol, designed to examine the capabilities of an institutionally developed intensity-modulated radiotherapy (IMRT) system with respect to dose escalation. The protocol employed stringent dosimetric guidelines in the treatment of locally advanced head-and-neck squamous cell carcinomas (HNSCC) with radiotherapy alone using IMRT and the simultaneous integrated boost (SIB) technique. METHODS AND MATERIALS: The first 14 patients enrolled on the protocol were included in this analysis. Escalating doses of 68.1 Gy (6 patients), 70.8 Gy (6 patients), and 73.8 Gy (2 patients) were delivered to the gross tumor volume (GTV) in 30 fractions. Simultaneously, constant dose coverage was given to the subclinical disease and the electively treated nodal regions, which received 60 Gy and 54 Gy, respectively, in all three cohorts. Parotid glands were spared to the degree possible without compromising target coverage. The following indices are reported for the GTV: (1) dose to specified percent volumes (e.g., D(98) and D(2)); (2) homogeneity index defined as the ratio (D(2) - D(98))/D(prescription); (3) biologically equivalent uniform dose (EUD); and (4) an index of conformality, PITV, defined as the ratio of volume enclosed within the prescribed isodose surface to the target volume. Treatments were planned and delivered with nine 6-MV photon beams using the multileaf collimator (MLC) "sliding window" technique. RESULTS: Mean doses to 98% of GTV were 68.4 Gy, 70.5 Gy, and 70.8 Gy, and average GTV dose homogeneity was 6.7%, 7.6%, and 8.8% for the three cohorts. The average doses to the parotid gland proximal to and distant from GTV were 41.3 Gy and 25.7 Gy, respectively. Dose distributions measured in phantom showed good agreement with calculations. CONCLUSIONS: Treatment of locally advanced HNSCC using SIB-IMRT as described is feasible. Treatment planning and delivery are safer and more efficient than with conventional three-dimensional processes. Predicted dose distributions can be accurately delivered with excellent conformality using dynamic MLC. At least one of the parotid glands can be adequately spared. Patient follow-up continues and will allow eventual quantitative correlation of delivered dose distributions with clinical outcomes.

Carcinoma, Squamous Cell↗

Intensity-modulated radiotherapy optimization with gEUD-guided dose-volume objectives.

Currently, most intensity-modulated radiation therapy systems use dose-volume (DV)-based objectives. Although acceptable plans can be generated using these objectives, much trial and error is necessary to plan complex cases with many structures because numerous parameters need to be adjusted. An objective function that makes use of a generalized equivalent uniform dose (gEUD) was developed recently that has the advantage of involving simple formulae and fewer parameters. In addition, not only does the gEUD-based optimization provide the same coverage of the target, it provides significantly better protection of critical structures. However, gEUD-based optimization may not be superior once dose distributions and dose-volume histograms (DVHs) are used to evaluate the plan. Moreover, it is difficult to fine-tune the DVH with gEUD-based optimization. In this paper, we propose a method for combining the gEUD-based and DV-based optimization approaches to overcome these limitations. In this method, the gEUD optimization is performed initially to search for a solution that meets or exceeds most of the treatment objectives. Depending on the requirements, DV-based optimization with a gradient technique is then used to fine-tune the DVHs. The DV constraints are specified according to the gEUD plan, and the initial intensities are obtained from the gEUD plan as well. We demonstrated this technique in two clinical cases: aprostate cancer and ahead and neck cancer case. Compared with the DV-optimized plan, the gEUD plan provided better protection of critical structures and the target coverage was similar. However, homogeneities were slightly poorer. The gEUD plan was then fine-tuned with DV constraints, and the resulting plan was superior to the other plans in terms of the dose distributions. The planning time was significantly reduced as well. This technique is an effective means of optimizing individualized treatment plans.

Adenocarcinoma↗

Optimization of intensity-modulated radiotherapy plans based on the equivalent uniform dose.

PURPOSE: The equivalent uniform dose (EUD) for tumors is defined as the biologically equivalent dose that, if given uniformly, will lead to the same cell kill in the tumor volume as the actual nonuniform dose distribution. Recently, a new formulation of EUD was introduced that applies to normal tissues as well. EUD can be a useful end point in evaluating treatment plans with nonuniform dose distributions for three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. In this study, we introduce an objective function based on the EUD and investigate the feasibility and usefulness of using it for intensity-modulated radiotherapy optimization. METHODS AND MATERIALS: We applied the EUD-based optimization to obtain intensity-modulated radiotherapy plans for prostate and head-and-neck cancer patients and compared them with the corresponding plans optimized with dose-volume-based criteria. RESULTS: We found that, for the same or better target coverage, EUD-based optimization is capable of improving the sparing of critical structures beyond the specified requirements. We also found that, in the absence of constraints on the maximal target dose, the target dose distributions are more inhomogeneous, with significant hot spots within the target volume. This is an obvious consequence of unrestricted maximization target cell kill and, although this may be considered beneficial for some cases, it is generally not desirable. To minimize the magnitude of hot spots, we applied dose inhomogeneity constraints to the target by treating it as a "virtual" normal structure as well. This led to much-improved target dose homogeneity, with a small, but expected, degradation in normal structure sparing. We also found that, in principle, the dose-volume objective function may be able to arrive at similar optimum dose distributions by using multiple dose-volume constraints for each anatomic structure and with considerably greater trial-and-error to adjust a large number of objective function parameters. CONCLUSION: The general inference drawn from our investigation is that the EUD-based objective function has the advantages that it needs only a small number of parameters and allows exploration of a much larger universe of solutions, making it easier for the optimization system to balance competing requirements in search of a better solution.

Algorithms↗

Technical considerations in the application of intensity-modulated radiotherapy as a concomitant integrated boost for locally-advanced cervix cancer.

The technical aspects of IMRT applied to cervix cancer are discussed in this paper, as well as issues related to tumor delineation, target volume definitions, inverse planning, and IMRT delivery. A theoretical example illustrating how IMRT can accurately mimic dose distributions obtained using conventional planning plus HDR brachytherapy is also shown. The notion of clinical optimization parameters is introduced to account for the radiation delivery variables, which affect the overall treatment time. This is especially relevant to the possible introduction of intrafractional movement and resulting inaccuracy, as well as facility efficiency.

Brachytherapy↗

Clinical application of intensity-modulated radiotherapy for locally advanced cervical cancer.

Intensity-modulated radiotherapy (IMRT) offers technical advantages over conventional external beam radiotherapy (CXRT) that might prove clinically advantageous in the management of gynecologic malignancies. Especially in the case of locally advanced cervical cancer, IMRT provides an opportunity to improve the therapeutic ratio by allowing a selective combination of normal tissue dose reduction and/or concomitant integrated boost dose to the tumor. The clinical and biologic rationale for IMRT in this setting is presented here, and pertinent technical considerations such as the delineation of relevant clinical and planning target volumes are discussed. The capacity for IMRT-mediated normal tissue sparing is illustrated by example and review of the literature. Furthermore, for a small cohort of patients with locally advanced or recurrent cervical cancer treated with concomitant integrated boost IMRT and concurrent chemotherapy, preliminary clinical observations of toxicity and tumor response are presented. Concomitant integrated boost IMRT appears clinically tolerable and efficacious in this setting, and formal clinical investigation is warranted as a means of exploiting the fraction-size dependence of radiosensitizers in common clinical use.

Female↗