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A complete 4DCT-ventilation functional avoidance virtual trial: Developing strategies for prospective clinical trials.

ABSTRACT: 4DCT-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.The 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.Our 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.Our 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.

SUBMITTER: Waxweiler T

PROVIDER: S-EPMC5689844 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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A complete 4DCT-ventilation functional avoidance virtual trial: Developing strategies for prospective clinical trials.

Waxweiler Timothy T Schubert Leah L Diot Quentin Q Faught Austin A Stuhr Kelly K Castillo Richard R Castillo Edward E Guerrero Thomas T Rusthoven Chad C Gaspar Laurie L Kavanagh Brian B Miften Moyed M Vinogradskiy Yevgeniy Y

Journal of applied clinical medical physics 20170424 3

<h4>Introduction</h4>4DCT-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 ...[more]

PMID: 28436107

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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.

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.

Project description:PurposeComputed tomographic (CT) ventilation imaging is a new modality that uses 4-dimensional (4D) CT information to calculate lung ventilation. Although retrospective studies have reported on the reduction in dose to functional lung, no work to our knowledge has been published in which the dosimetric improvements have been translated to a reduction in the probability of pulmonary toxicity. Our work estimates the reduction in toxicity for CT ventilation-based functional avoidance planning.Methods and materialsSeventy previously treated lung cancer patients who underwent 4DCT imaging were used for the study. CT ventilation maps were calculated with 4DCT deformable image registration and a density change-based algorithm. Pneumonitis was graded on the basis of imaging and clinical presentation. Maximum likelihood methods were used to generate normal tissue complication probability (NTCP) models predicting grade 2 or higher (2+) and grade 3+ pneumonitis as a function of dose (V5 Gy, V10 Gy, V20 Gy, V30 Gy, and mean dose) to functional lung. For 30 patients a functional plan was generated with the goal of reducing dose to the functional lung while meeting Radiation Therapy Oncology Group 0617 constraints. The NTCP models were applied to the functional plans and the clinically used plans to calculate toxicity reduction.ResultsBy the use of functional avoidance planning, absolute reductions in grade 2+ NTCP of 6.3%, 7.8%, and 4.8% were achieved based on the mean fV20 Gy, fV30 Gy, and mean dose to functional lung metrics, respectively. Absolute grade 3+ NTCP reductions of 3.6%, 4.8%, and 2.4% were achieved with fV20 Gy, fV30 Gy, and mean dose to functional lung. Maximum absolute reductions of 52.3% and 16.4% were seen for grade 2+ and grade 3+ pneumonitis for individual patients.ConclusionOur study quantifies the possible toxicity reduction from CT ventilation-based functional avoidance planning. Reductions in grades 2+ and 3+ pneumonitis were 7.1% and 4.7% based on mean dose-function metrics, with reductions as high as 52.3% for individual patients. Our work provides seminal data for determining the potential toxicity benefit from incorporating CT ventilation into thoracic treatment planning.

Project description:PurposeTo investigate the degree to which lung ventilation and gas exchange are regionally correlated, using the emerging technology of hyperpolarized (HP)-129Xe magnetic resonance imaging (MRI).Methods and materialsHyperpolarized-129Xe MRI studies were performed on 17 institutional review board-approved human subjects, including 13 healthy volunteers, 1 emphysema patient, and 3 non-small cell lung cancer patients imaged before and approximately 11 weeks after radiation therapy (RT). Subjects inhaled 1 L of HP-129Xe mixture, followed by the acquisition of interleaved ventilation and gas exchange images, from which maps were obtained of the relative HP-129Xe distribution in three states: (1) gaseous, in lung airspaces; (2) dissolved interstitially, in alveolar barrier tissue; and (3) transferred to red blood cells (RBCs), in the capillary vasculature. The relative spatial distributions of HP-129Xe in airspaces (regional ventilation) and RBCs (regional gas transfer) were compared. Further, we investigated the degree to which ventilation and RBC transfer images identified similar functional regions of interest (ROIs) suitable for functionally guided RT. For the RT patients, both ventilation and RBC functional images were used to calculate differences in the lung dose-function histogram and functional effective uniform dose.ResultsThe correlation of ventilation and RBC transfer was ρ = 0.39 ± 0.15 in healthy volunteers. For the RT patients, this correlation was ρ = 0.53 ± 0.02 before treatment and ρ = 0.39 ± 0.07 after treatment; for the emphysema patient it was ρ = 0.24. Comparing functional ROIs, ventilation and RBC transfer demonstrated poor spatial agreement: Dice similarity coefficient = 0.50 ± 0.07 and 0.26 ± 0.12 for the highest-33%- and highest-10%-function ROIs in healthy volunteers, and in RT patients (before treatment) these were 0.58 ± 0.04 and 0.40 ± 0.04. The average magnitude of the differences between RBC- and ventilation-derived functional effective uniform dose, fV20Gy, fV10Gy, and fV5Gy were 1.5 ± 1.4 Gy, 4.1% ± 3.8%, 5.0% ± 3.8%, and 5.3% ± 3.9%, respectively.ConclusionVentilation may not be an effective surrogate for true regional lung function for all patients.

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A complete 4DCT-ventilation functional avoidance virtual trial: Developing strategies for prospective clinical trials.

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A complete 4DCT-ventilation functional avoidance virtual trial: Developing strategies for prospective clinical trials.

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