Effectiveness of robust optimization in intensity-modulated proton therapy planning for head and neck cancers.
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ABSTRACT: Intensity-modulated proton therapy (IMPT) is highly sensitive to uncertainties in beam range and patient setup. Conventionally, these uncertainties are dealt using geometrically expanded planning target volume (PTV). In this paper, the authors evaluated a robust optimization method that deals with the uncertainties directly during the spot weight optimization to ensure clinical target volume (CTV) coverage without using PTV. The authors compared the two methods for a population of head and neck (H&N) cancer patients.Two sets of IMPT plans were generated for 14 H&N cases, one being PTV-based conventionally optimized and the other CTV-based robustly optimized. For the PTV-based conventionally optimized plans, the uncertainties are accounted for by expanding CTV to PTV via margins and delivering the prescribed dose to PTV. For the CTV-based robustly optimized plans, spot weight optimization was guided to reduce the discrepancy in doses under extreme setup and range uncertainties directly, while delivering the prescribed dose to CTV rather than PTV. For each of these plans, the authors calculated dose distributions under various uncertainty settings. The root-mean-square dose (RMSD) for each voxel was computed and the area under the RMSD-volume histogram curves (AUC) was used to relatively compare plan robustness. Data derived from the dose volume histogram in the worst-case and nominal doses were used to evaluate the plan optimality. Then the plan evaluation metrics were averaged over the 14 cases and were compared with two-sided paired t tests.CTV-based robust optimization led to more robust (i.e., smaller AUCs) plans for both targets and organs. Under the worst-case scenario and the nominal scenario, CTV-based robustly optimized plans showed better target coverage (i.e., greater D95%), improved dose homogeneity (i.e., smaller D5% - D95%), and lower or equivalent dose to organs at risk.CTV-based robust optimization provided significantly more robust dose distributions to targets and organs than PTV-based conventional optimization in H&N using IMPT. Eliminating the use of PTV and planning directly based on CTV provided better or equivalent normal tissue sparing.
Project description:Background/purposeSetup variations and anatomical changes can severely affect the quality of head and neck intensity-modulated proton therapy (IMPT) treatments. The impact of these changes can be alleviated by increasing the plan's robustness a priori, or by adapting the plan online. This work compares these approaches in the context of head and neck IMPT.Materials/methodsA representative cohort of 10 head and neck squamous cell carcinoma (HNSCC) patients with daily cone-beam computed tomography (CBCT) was evaluated. For each patient, three IMPT plans were created: 1- a classical robust optimization (cRO) plan optimized on the planning CT, 2- an anatomical robust optimization (aRO) plan additionally including the two first daily CBCTs and 3- a plan optimized without robustness constraints, but online-adapted (OA) daily, using a constrained spot intensity re-optimization technique only.ResultsThe cumulative dose following OA fulfilled the clinical objective of both the high-risk and low-risk clinical target volumes (CTV) coverage in all 10 patients, compared to 8 for aRO and 4 for cRO. aRO did not significantly increase the dose to most organs at risk compared to cRO, although the integral dose was higher. OA significantly reduced the integral dose to healthy tissues compared to both robust methods, while providing equivalent or superior target coverage.ConclusionUsing a simple spot intensity re-optimization, daily OA can achieve superior target coverage and lower dose to organs at risk than robust optimization methods.
Project description:Intensity modulated proton therapy (IMPT) is highly sensitive to range uncertainties and uncertainties caused by setup variation. The conventional inverse treatment planning of IMPT optimized based on the planning target volume (PTV) is not often sufficient to ensure robustness of treatment plans. In this paper, a method that takes the uncertainties into account during plan optimization is used to mitigate the influence of uncertainties in IMPT.The authors use the so-called "worst-case robust optimization" to render IMPT plans robust in the face of uncertainties. For each iteration, nine different dose distributions are computed-one each for ± setup uncertainties along anteroposterior (A-P), lateral (R-L) and superior-inferior (S-I) directions, for ± range uncertainty, and the nominal dose distribution. The worst-case dose distribution is obtained by assigning the lowest dose among the nine doses to each voxel in the clinical target volume (CTV) and the highest dose to each voxel outside the CTV. Conceptually, the use of worst-case dose distribution is similar to the dose distribution achieved based on the use of PTV in traditional planning. The objective function value for a given iteration is computed using this worst-case dose distribution. The objective function used has been extended to further constrain the target dose inhomogeneity.The worst-case robust optimization method is applied to a lung case, a skull base case, and a prostate case. Compared with IMPT plans optimized using conventional methods based on the PTV, our method yields plans that are considerably less sensitive to range and setup uncertainties. An interesting finding of the work presented here is that, in addition to reducing sensitivity to uncertainties, robust optimization also leads to improved optimality of treatment plans compared to the PTV-based optimization. This is reflected in reduction in plan scores and in the lower normal tissue doses for the same coverage of the target volume when subjected to uncertainties.The authors find that the worst-case robust optimization provides robust target coverage without sacrificing, and possibly even improving, the sparing of normal tissues. Our results demonstrate the importance of robust optimization. The authors assert that all IMPT plans should be robustly optimized.
Project description:PurposeWe aimed to determine whether multiple-CT (MCT) optimization of intensity-modulated proton therapy (IMPT) could improve plan robustness to anatomical changes and therefore reduce the additional need for adaptive planning.Methods and materialsTen patients with head and neck cancer who underwent IMPT were included in this retrospective study. Each patient had primary planning CT (PCT), a first adaptive planning CT (ACT1), and a second adaptive planning CT (ACT2). Selective robust IMPT plans were generated using each CT data set (PCT, ACT1, and ACT2). Moreover, a MCT optimized plan was generated using the PCT and ACT1 data sets together. Dose distributions optimized using each of the four plans (PCT, ACT1, ACT2, and MCT plans) were re-calculated on ACT2 data. The doses to the target and to organs at risk were compared between optimization strategies.ResultsMCT plans for all patients met all target dose and organs-at-risk criteria for all three CT data sets. Target dose and organs-at-risk dose for PCT and ACT1 plans re-calculated on ACT2 data set were compromised, indicating the need for adaptive planning on ACT2 if PCT or ACT1 plans were used. The D98% of CTV1 and CTV3 of MCT plan re-calculated on ACT2 were both above the coverage criteria. The CTV2 coverage of the MCT plan re-calculated on ACT2 was worse than ACT2 plan. The MCT plan re-calculated on ACT2 data set had lower chiasm, esophagus, and larynx doses than did PCT, ACT1, or ACT2 plans re-calculated on ACT2 data set.ConclusionsMCT optimization can improve plan robustness toward anatomical change and may reduce the number of plan adaptation for head and neck cancers.
Project description:PurposeThe clinical advantage of intensity modulated proton therapy (IMPT) may be diminished by range and patient setup uncertainties. We evaluated the effectiveness of robust optimization that incorporates uncertainties into the treatment planning optimization algorithm for treatment of base of skull cancers.Methods and materialsWe compared 2 IMPT planning methods for 10 patients with base of skull chordomas and chondrosarcomas: (1) conventional optimization, in which uncertainties are dealt with by creating a planning target volume (PTV); and (2) robust optimization, in which uncertainties are dealt with by optimizing individual spot weights without a PTV. We calculated root-mean-square deviation doses (RMSDs) for every voxel to generate RMSD volume histograms (RVHs). The area under the RVH curve was used for relative comparison of the 2 methods' plan robustness. Potential benefits of robust planning, in terms of target dose coverage and homogeneity and sparing of organs at risk (OARs) were evaluated using established clinical metrics. Then the plan evaluation metrics were averaged and compared with 2-sided paired t tests. The impact of tumor volume on the effectiveness of robust optimization was also analyzed.ResultsRelative to conventionally optimized plans, robustly optimized plans were less sensitive for both targets and OARs. In the nominal scenario, robust and conventional optimization resulted in similar D95% doses (D95% clinical target volume [CTV]: 63.3 and 64.8 Gy relative biologic effectiveness [RBE]), P <.01]) and D5%-D95% (D5%-D95% CTV: 8.0 and 7.1 Gy[RBE], [P <.01); irradiation of OARs was less with robust optimization (brainstem V60: 0.076 vs 0.26 cm(3) [P <.01], left temporal lobe V70: 0.22 vs 0.41 cm(3), [P = .068], right temporal lobe V70: 0.016 vs 0.11 cm(3), [P = .096], left cochlea Dmean: 28.1 vs 30.1 Gy[RBE], [P = .023], right cochlea Dmean: 23.7 vs 25.2 Gy[RBE], [P = .059]). Results in the worst-case scenario were analogous.ConclusionsRobust optimization is effective for creating clinically feasible IMPT plans for tumors of the base of skull.
Project description:PurposeTo compare the clinical benefit of robust optimized Intensity Modulated Proton Therapy (minimax IMPT) with current photon Intensity Modulated Radiation Therapy (IMRT) and PTV-based IMPT for head and neck cancer (HNC) patients. The clinical benefit is quantified in terms of both Normal Tissue Complication Probability (NTCP) and target coverage in the case of setup and range errors.Methods and materialsFor 10 HNC patients, PTV-based IMRT (7 fields), minimax and PTV-based IMPT (2, 3, 4, 5 and 7 fields) plans were tested on robustness. Robust optimized plans differed from PTV-based plans in that they target the CTV and penalize possible error scenarios, instead of using the static isotropic CTV-PTV margin. Perturbed dose distributions of all plans were acquired by simulating in total 8060 setup (±3.5 mm) and range error (±3%) combinations. NTCP models for xerostomia and dysphagia were used to predict the clinical benefit of IMPT versus IMRT.ResultsThe robustness criterion was met in the IMRT and minimax IMPT plans in all error scenarios, but this was only the case in 1 of 40 PTV-based IMPT plans. Seven (out of 10) patients had relatively large NTCP reductions in minimax IMPT plans compared to IMRT. For these patients, xerostomia and dysphagia NTCP values were reduced by 17.0% (95% CI; 13.0-21.1) and 8.1% (95% CI; 4.9-11.2) on average with minimax IMPT. Increasing the number of fields did not contribute to plan robustness, but improved organ sparing.ConclusionsThe estimated clinical benefit in terms of NTCP of robust optimized (minimax) IMPT is greater than that of IMRT and PTV-based IMPT in HNC patients. Furthermore, the target coverage of minimax IMPT plans in the presence of errors was comparable to IMRT plans.
Project description:Radiation therapy plays an integral role in the management of head and neck cancers (HNCs). While most HNC patients have historically been treated with photon-based radiation techniques such as intensity modulated radiation therapy (IMRT), there is a growing awareness of the potential clinical benefits of proton therapy over IMRT in the definitive, postoperative and reirradiation settings given the unique physical properties of protons. Intensity modulated proton therapy (IMPT), also known as "pencil beam proton therapy," is a sophisticated mode of proton therapy that is analogous to IMRT and an active area of investigation in cancer care. Multifield optimization IMPT allows for high quality plans that can target superficially located HNCs as well as large neck volumes while significantly reducing integral doses. Several dosimetric studies have demonstrated the superiority of IMPT over IMRT to improve dose sparing of nearby organs such as the larynx, salivary glands, and esophagus. Evidence of the clinical translation of these dosimetric advantages has been demonstrated with documented toxicity reductions (such as decreased feeding tube dependency) after IMPT for patients with HNCs. While there are relative challenges to IMPT planning that exist today such as particle range uncertainties and high sensitivity to anatomical changes, ongoing investigations in image-guidance techniques and robust optimization methods are promising. A systematic approach towards utilizing IMPT and additional prospective studies are necessary in order to more accurately estimate the clinical benefit of IMPT over IMRT and passive proton therapy on a case-by-case basis for patients with sub-site specific HNCs.
Project description:The distal edge tracking (DET) technique in intensity-modulated proton therapy (IMPT) allows for high energy efficiency, fast and simple delivery, and simple inverse treatment planning; however, it is highly sensitive to uncertainties. In this study, the authors explored the application of DET in IMPT (IMPT-DET) and conducted robust optimization of IMPT-DET to see if the planning technique's sensitivity to uncertainties was reduced. They also compared conventional and robust optimization of IMPT-DET with three-dimensional IMPT (IMPT-3D) to gain understanding about how plan robustness is achieved.They compared the robustness of IMPT-DET and IMPT-3D plans to uncertainties by analyzing plans created for a typical prostate cancer case and a base of skull (BOS) cancer case (using data for patients who had undergone proton therapy at our institution). Spots with the highest and second highest energy layers were chosen so that the Bragg peak would be at the distal edge of the targets in IMPT-DET using 36 equally spaced angle beams; in IMPT-3D, 3 beams with angles chosen by a beam angle optimization algorithm were planned. Dose contributions for a number of range and setup uncertainties were calculated, and a worst-case robust optimization was performed. A robust quantification technique was used to evaluate the plans' sensitivity to uncertainties.With no uncertainties considered, the DET is less robust to uncertainties than is the 3D method but offers better normal tissue protection. With robust optimization to account for range and setup uncertainties, robust optimization can improve the robustness of IMPT plans to uncertainties; however, our findings show the extent of improvement varies.IMPT's sensitivity to uncertainties can be improved by using robust optimization. They found two possible mechanisms that made improvements possible: (1) a localized single-field uniform dose distribution (LSFUD) mechanism, in which the optimization algorithm attempts to produce a single-field uniform dose distribution while minimizing the patching field as much as possible; and (2) perturbed dose distribution, which follows the change in anatomical geometry. Multiple-instance optimization has more knowledge of the influence matrices; this greater knowledge improves IMPT plans' ability to retain robustness despite the presence of uncertainties.
Project description:This study aimed to assess the impact of the margin applied to the clinical target volume, to create the planning target volume, on plan quality of a novel dysphagia-optimised intensity modulated radiotherapy technique developed within a head and neck cancer multicentre randomised controlled trial. Protocol compliant plans were used for a single benchmark planning case. Larger margins were associated with higher doses to adjacent organs at risk, particularly the inferior pharyngeal constrictor muscle, but coincided with some improved low dose target coverage. A 3 mm margin is recommended for this technique if local practices allow.
Project description:PurposeTo design and commission a head and neck (H&N) anthropomorphic phantom that the Imaging and Radiation Oncology Core Houston (IROC-H) can use to verify the quality of intensity-modulated proton therapy H&N treatments for institutions participating in National Cancer Institute-sponsored clinical trials.Materials and methodsThe phantom design was based on a generalized oropharyngeal tumor, including critical H&N structures (parotid glands and spinal cord). Radiochromic film and thermoluminescent dosimeter (TLD)-100 capsules were embedded in the phantom and used to evaluate dose delivery. A spot-scanning treatment plan with typical clinical constraints for H&N cancer was created by using the Eclipse analytic algorithm. The treatment plan was approved by a radiation oncologist and the phantom was irradiated 4 times. The measured dose distribution using a ±7%/4 mm gamma analysis (85% of pixels passing) and point doses were compared with the treatment planning system calculations. The prescribed target dose was 6 Gy (RBE) with 646.2 cGy (RBE) and 648.6 cGy (RBE) planned to the superior and inferior TLD, respectively.ResultsFor point dosimetry, the average measured-to-calculated dose ratios were 0.984 and 0.986 for the superior and inferior target TLD, respectively. Dose values for the superior and inferior target TLDs were 636.1 cGy and 639.6 cGy, respectively. For the relative dose comparison, the pixel passing rates for the axial and sagittal films, respectively, were 95.5% and 94.2% for trial 1, 97.3% and 93.2% for trial 2, 93.4% and 90.0% for trial 3, and 96.2% and 92.7% for trial 4.ConclusionThe anthropomorphic H&N phantom was successfully designed so that TLD measured-to-calculated ratios were within IROC-H's 7% acceptance criteria, 1.6% and 1.4% lower than expected for the superior and inferior target TLDs, respectively. All trials passed the 85% pixel passing criteria established at IROC-H for the relative dose comparison performed when using a gamma index of ±7%/4 mm.
Project description:Background and purposeRobust optimization for IMPT takes setup and range uncertainties into account during plan optimization. However, anatomical changes were not prospectively included. The purpose of this study was to examine robustness and dose variation due to setup uncertainty and anatomical change in IMPT of lung cancer.Material and methodsPlans were generated with multi-field optimization based on planning target volume (MFO-PTV) and worst-case robust optimization (MFO-RO) on simulation computed tomography scans (CT0) for nine patients. Robustness was evaluated on the CT0 by computing the standard deviation of DVH (SD-DVH). Dose variations calculated on weekly CTs were compared with SD-DVH. Equivalent uniform dose (EUD) change from the original plan on weekly dose was also calculated for both plans.ResultsSD-DVH and dose variation on weekly CTs were both significantly lower in the MFO-RO plans than in the MFO-PTV plans for targets, lungs, and the esophagus (p<0.05). When comparing EUD for ITV between weekly and planned dose distributions, three patients and 28% of repeated CTs for MFO-RO plans, and six patients and 44% of repeated CTs for MFO-PTV plans, respectively, showed an EUD change of >5%.ConclusionsRO in IMPT reduces the dose variation due to setup uncertainty and anatomy changes during treatment compared with PTV-based planning. However, dose variation could still be substantial; repeated imaging and adaptive planning as needed are highly recommended for IMPT of lung tumors.