Functional avoidance-based intensity modulated proton therapy with 4DCT derived ventilation imaging for lung cancer.
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ABSTRACT:
SUBMITTER: Dougherty JM
PROVIDER: S-EPMC8292710 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The principle aim of this study is to incorporate 4DCT ventilation imaging into functional treatment planning that preserves high-functioning lung with both double scattering and scanning beam techniques in proton therapy.Eight patients with locally advanced non-small-cell lung cancer were included in this study. Deformable image registration was performed for each patient on their planning 4DCTs and the resultant displacement vector field with Jacobian analysis was used to identify the high-, medium- and low-functional lung regions. Five plans were designed for each patient: a regular photon IMRT vs. anatomic proton plans without consideration of functional ventilation information using double scattering proton therapy (DSPT) and intensity modulated proton therapy (IMPT) vs. functional proton plans with avoidance of high-functional lung using both DSPT and IMPT. Dosimetric parameters were compared in terms of tumor coverage, plan heterogeneity, and avoidance of normal tissues.Our results showed that both DSPT and IMPT plans gave superior dose advantage to photon IMRTs in sparing low dose regions of the total lung in terms of V5 (volume receiving 5Gy). The functional DSPT only showed marginal benefit in sparing high-functioning lung in terms of V5 or V20 (volume receiving 20Gy) compared to anatomical plans. Yet, the functional planning in IMPT delivery, can further reduce the low dose in high-functioning lung without degrading the PTV dosimetric coverages, compared to anatomical proton planning. Although the doses to some critical organs might increase during functional planning, the necessary constraints were all met.Incorporating 4DCT ventilation imaging into functional proton therapy is feasible. The functional proton plans, in intensity modulated proton delivery, are effective to further preserve high-functioning lung regions without degrading the PTV coverage.
| S-EPMC5918906 | biostudies-literature
Project description:Introduction4DCT-ventilation is an exciting new imaging modality that uses 4DCT data to calculate lung-function maps. Because 4DCTs are acquired as standard of care for lung cancer patients undergoing radiotherapy, 4DCT-ventiltation provides functional information at no extra dosimetric or monetary cost to the patient. The development of clinical trials is underway to use 4DCT-ventilation imaging to spare functional lung in patients undergoing radiotherapy. The purpose of this work was to perform a virtual trial using retrospective data to develop the practical aspects of a 4DCT-ventilation functional avoidance clinical trial.MethodsThe study included 96 stage III lung cancer patients. A 4DCT-ventilation map was calculated using the patient's 4DCT-imaging, deformable registration, and a density-change-based algorithm. Clinical trial inclusion assessment used quantitative and qualitative metrics based on the patient's spatial ventilation profile. Clinical and functional plans were generated for 25 patients. The functional plan aimed to reduce dose to functional lung while meeting standard target and critical structure constraints. Standard and dose-function metrics were compared between the clinical and functional plans.ResultsOur data showed that 69% and 59% of stage III patients have regional variability in function based on qualitative and quantitative metrics, respectively. Functional planning demonstrated an average reduction of 2.8 Gy (maximum 8.2 Gy) in the mean dose to functional lung.ConclusionsOur work demonstrated that 60-70% of stage III patients would be eligible for functional planning and that a typical functional lung mean dose reduction of 2.8 Gy can be expected relative to standard clinical plans. These findings provide salient data for the development of functional clinical trials.
| S-EPMC5689844 | biostudies-literature
Project description:BackgroundFunctional planning based merely on 4DCT ventilation imaging has limitations. In this study, we proposed a radiotherapy planning strategy based on 4DCT ventilation imaging and CT density characteristics.Materials and methodsFor 20 stage III non-small-cell lung cancer (NSCLC) patients, clinical plans and lung-avoidance plans were generated. Through deformable image registration (DIR) and quantitative image analysis, a 4DCT ventilation map was calculated. High-, medium-, and low-ventilation regions of the lung were defined based on the ventilation value. In addition, the total lung was also divided into high-, medium-, and low-density areas according to the HU threshold. The lung-avoidance plan aimed to reduce the dose to functional and high-density lungs while meeting standard target and critical structure constraints. Standard and dose-function metrics were compared between the clinical and lung-avoidance plans.ResultsLung avoidance plans led to significant reductions in high-function and high-density lung doses, without significantly increasing other organ at risk (OAR) doses, but at the expense of a significantly degraded homogeneity index (HI) and conformity index (CI; p < 0.05) of the planning target volume (PTV) and a slight increase in monitor units (MU) as well as in the number of segments (p > 0.05). Compared with the clinical plan, the mean lung dose (MLD) in the high-function and high-density areas was reduced by 0.59 Gy and 0.57 Gy, respectively.ConclusionA lung-avoidance plan based on 4DCT ventilation imaging and CT density characteristics is feasible and implementable, with potential clinical benefits. Clinical trials will be crucial to show the clinical relevance of this lung-avoidance planning strategy.
| S-EPMC8604857 | biostudies-literature
Project description:Background and purposeIntensity modulated proton therapy (IMPT) allows for modulation parameterized for individual beamlets by position, intensity, and depth. This modulation capability is ideally suited for sparing organs at risk intermediate of the radiation target, such as hippocampal volumes within the whole brain. This work compared IMPT relative to volumetric modulated arc therapy (VMAT) during hippocampal avoidance whole brain radiation therapy (HA WBRT).Materials and methodsTen adult and ten pediatric patients previously treated for central nervous system malignancies were identified. IMPT and VMAT treatment plans employing HA WBRT were generated for each patient, delivering 30 GyE (Gray Equivalent) in 10 fractions for adults and 36 GyE in 20 fractions for pediatrics. Dose indices, including dose volume histogram metrics and homogeneity index HI = [D5% - D95%]/[Dmean] × 100, were used to assess plan quality and describe target coverage and normal-tissue sparing.ResultsIMPT offered significant benefits relative to VMAT for hippocampal sparing. Hippocampal mean dose was reduced from 13.7 ± 0.8 Gy with VMAT to 5.4 ± 0.3 GyE using IMPT for pediatrics, and was reduced from 11.7 ± 0.9 Gy with VMAT to 4.4 ± 0.2 GyE using IMPT for adults. IMPT similarly lowered left hippocampal mean dose. Dose to 95% of the clinical target volume was statistically equivalent for both groups; however IMPT reduced the homogeneity index by roughly half.ConclusionThis manuscript demonstrates that HA IMPT can match or exceed dosimetric benefits offered with modulated X-rays. Inclusion of IMPT in future prospective studies is warranted.
| S-EPMC7807533 | biostudies-literature
Project description:PurposeFunctional imaging has been proposed that uses 4DCT images to calculate 4DCT-based lung ventilation (4DCT-ventilation). We have started a 2-institution, phase 2 prospective trial evaluating the feasibility, safety, and preliminary efficacy of 4DCT-ventilation functional avoidance. The trial hypothesis is that the rate of grade ≥2 radiation pneumonitis could be reduced to 12% with functional avoidance, compared with a 25% rate of pneumonitis with a historical control. The trial employed a Simon 2-stage design with a planned futility analysis after 17 evaluable patients. The purpose of this work is to present the trial design and implementation, dosimetric data, and clinical results for the planned futility analysis.Methods and materialsEligible patients were patients with lung cancer who were prescribed doses of 45 to 75 Gy. For each patient, the 4DCT data were used to generate a 4DCT-ventilation image using the Hounsfield unit technique along with a compressible flow-based image registration algorithm. Two intensity modulated radiation therapy treatment plans were generated: (1) a standard lung plan and (2) a functional avoidance treatment plan that aimed to reduce dose to functional lung while meeting target and normal tissue constraints. Patients were treated with the functional avoidance plan and evaluated for thoracic toxicity (presented as rate and 95% confidence intervals [CI]) with a 1-year follow-up.ResultsThe V20 to functional lung was 21.6% ± 9.5% (mean ± standard deviation) with functional avoidance, representing a decrease of 3.2% (P < .01) relative to standard, nonfunctional treatment plans. The rates of grade ≥2 and grade ≥3 radiation pneumonitis were 17.6% (95% CI, 3.8%-43.4%) and 5.9% (95% CI, 0.1%-28.7%), respectively.ConclusionsDosimetrically, functional avoidance achieved reduction in doses to functional lung while meeting target and organ at risk constraints. On the basis of Simon's 2-stage design and the 17.6% grade ≥2 pneumonitis rate, the trial met its futility criteria and has continued accrual.
| S-EPMC6919556 | biostudies-literature
Project description:PurposeRadiation pneumonitis remains a major limitation in the radiation therapy treatment of patients with lung cancer. Functional avoidance radiation therapy uses functional imaging to reduce pulmonary toxic effects by designing radiation therapy plans that reduce doses to functional regions of the lung. Lung functional imaging has been developed that uses 4-dimensional computed tomography (4DCT) imaging to calculate 4DCT-based lung ventilation (4DCT-ventilation). A phase 2 multicenter study was initiated to evaluate 4DCT-ventilation functional avoidance radiation therapy. The study hypothesis was that functional avoidance radiation therapy could reduce the rate of grade ≥2 radiation pneumonitis to 12% compared with a 25% historical rate, with the trial being positive if ≤16.4% of patients experienced grade ≥2 pneumonitis.Methods and materialsLung cancer patients receiving curative-intent radiation therapy (prescription doses of 45-75 Gy) and chemotherapy were accrued. Patient 4DCT scans were used to generate 4DCT-ventilation images. The 4DCT-ventilation images were used to generate functional avoidance plans that reduced doses to functional portions of the lung while delivering the prescribed tumor dose. Pneumonitis was evaluated by a clinician at 3, 6, and 12 months after radiation therapy.ResultsSixty-seven evaluable patients were accrued between April 2015 and December 2019. The median prescription dose was 60 Gy (range, 45-66 Gy) delivered in 30 fractions (range, 15-33 fractions). The average reduction in the functional volume of lung receiving ≥20 Gy with functional avoidance was 3.5% (range, 0%-12.8%). The median follow-up was 312 days. The rate of grade ≥2 radiation pneumonitis was 10 of 67 patients (14.9%; 95% upper CI, 24.0%), meeting the phase 2 criteria.Conclusions4DCT-ventilation offers an imaging modality that is convenient and provides functional imaging without an extra procedure necessary. This first report of a multicenter study of 4DCT-ventilation functional avoidance radiation therapy provided data showing that the trial met phase 2 criteria and that evaluation in a phase 3 study is warranted.
| S-EPMC8863640 | biostudies-literature
Project description:PurposeWhole lung irradiation (WLI) is indicated for certain pediatric patients with lung metastases. This study investigated whether WLI delivered as intensity-modulated proton therapy (IMPT) could significantly spare the heart and breasts when compared with conventional WLI delivered with anteroposterior/posteroanterior photon fields and with intensity-modulated photon therapy (IMRT) WLI.Materials and methodsConventional, IMRT, and IMPT plans were generated for 5 patients (aged 5-22 years). The prescription dose was 16.5 GyRBE in 1.5-GyRBE fractions. Conventional plans used 6-MV photons prescribed to the midline and a field-in-field technique to cover the planning target volume (the internal target volume [ITV] + 1 cm). IMRT plans used 6-MV photons with a 7-beam arrangement with dose prescribed to the planning target volume. IMPT plans used scenario-based optimization with 5% range uncertainty and 5-mm positional uncertainty to cover the ITV robustly. Monte Carlo dose calculation was used for all IMPT plans. Doses were compared with paired Student t test.ResultsThe ITV Dmean was similar for the IMPT, conventional, and IMRT plans, but the IMPT plans had a lower Dmin and a higher Dmax at tissue interfaces than conventional plans (Dmean ratio: 0.96, P > .05; Dmin ratio: 0.9, P < .001; Dmax ratio: 1.1, P = .014). Dmeans for breast and heart substructures were lower with IMPT plans than with conventional/IMRT plans (heart ratios, 0.63:0.73; left ventricle ratios, 0.61:0.72; right ventricle ratios, 0.45:0.57; left atrium ratios, 0.79:0.85; right atrium ratios, 0.81:0.86; left breast ratios, 0.40:0.51; right breast ratio, 0.46:0.52; all P < .05).ConclusionsIMPT resulted in comparable ITV coverage and lower mean doses to the heart and breasts when compared with other techniques. Whole lung irradiation delivered as IMPT warrants prospective evaluation in pediatric patients.
| S-EPMC8019572 | biostudies-literature
Project description:PurposeVentilation images can be derived from four-dimensional computed tomography (4DCT) by analyzing the change in HU values and deformable vector fields between different respiration phases of computed tomography (CT). As deformable image registration (DIR) is involved, accuracy of 4DCT-derived ventilation image is sensitive to the choice of DIR algorithms. To overcome the uncertainty associated with DIR, we develop a method based on deep convolutional neural network (CNN) to derive ventilation images directly from the 4DCT without explicit image registration.MethodsA total of 82 sets of 4DCT and ventilation images from patients with lung cancer were used in this study. In the proposed CNN architecture, the CT two-channel input data consist of CT at the end of exhale and the end of inhale phases. The first convolutional layer has 32 different kernels of size 5 × 5 × 5, followed by another eight convolutional layers each of which is equipped with an activation layer (ReLU). The loss function is the mean-squared-error (MSE) to measure the intensity difference between the predicted and reference ventilation images.ResultsThe predicted images were comparable to the label images of the test data. The similarity index, correlation coefficient, and Gamma index passing rate averaged over the tenfold cross validation were 0.880 ± 0.035, 0.874 ± 0.024, and 0.806 ± 0.014, respectively.ConclusionsThe results demonstrate that deep CNN can generate ventilation imaging from 4DCT without explicit deformable image registration, reducing the associated uncertainty.
| S-EPMC7098066 | biostudies-literature
Project description:This paper presents a concept for a proton therapy system capable of delivering intensity modulated proton therapy using a fan beam of protons. This system would allow present and future gantry-based facilities to deliver state-of-the-art proton therapy with the greater normal tissue sparing made possible by intensity modulation techniques.A method for producing a divergent fan beam of protons using a pair of electromagnetic quadrupoles is described and particle transport through the quadrupole doublet is simulated using a commercially available software package. To manipulate the fan beam of protons, a modulation device is developed. This modulator inserts or retracts acrylic leaves of varying thickness from subsections of the fan beam. Each subsection, or beam channel, creates what effectively becomes a beam spot within the fan area. Each channel is able to provide 0-255 mm of range shift for its associated beam spot, or stop the beam and act as an intensity modulator. Results of particle transport simulations through the quadrupole system are incorporated into the MCNPX Monte Carlo transport code along with a model of the range and intensity modulation device. Several design parameters were investigated and optimized, culminating in the ability to create topotherapy treatment plans using distal-edge tracking on both phantom and patient datasets.Beam transport calculations show that a pair of electromagnetic quadrupoles can be used to create a divergent fan beam of 200 MeV protons over a distance of 2.1 m. The quadrupole lengths were 30 and 48 cm, respectively, with transverse field gradients less than 20 T/m, which is within the range of water-cooled magnets for the quadrupole radii used. MCNPX simulations of topotherapy treatment plans suggest that, when using the distal edge tracking delivery method, many delivery angles are more important than insisting on narrow beam channel widths in order to obtain conformal target coverage. Overall, the sharp distal falloff of a proton depth-dose distribution was found to provide sufficient control over the dose distribution to meet objectives, even with coarse lateral resolution and channel widths as large as 2 cm. Treatment plans on both phantom and patient data show that dose conformity suffers when treatments are delivered from less than approximately ten angles. Treatment time for a sample prostate delivery is estimated to be on the order of 10 min, and neutron production is estimated to be comparable to that found for existing collimated systems.Fan beam proton therapy is a method of delivering intensity modulated proton therapy which may be employed as an alternative to magnetic scanning systems. A fan beam of protons can be created by a set of quadrupole magnets and modified by a dual-purpose range and intensity modulator. This can be used to deliver inversely planned treatments, with spot intensities optimized to meet user defined dose objectives. Additionally, the ability of a fan beam delivery system to effectively treat multiple beam spots simultaneously may provide advantages as compared to spot scanning deliveries.
| S-EPMC3799727 | biostudies-other
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.
| S-EPMC3281975 | biostudies-other