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Correlation of Regional Lung Ventilation and Gas Transfer to Red Blood Cells: Implications for Functional-Avoidance Radiation Therapy Planning.

ABSTRACT: PURPOSE:To 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 MATERIALS:Hyperpolarized-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. RESULTS:The correlation of ventilation and RBC transfer was ? = 0.39 ± 0.15 in healthy volunteers. For the RT patients, this correlation was ? = 0.53 ± 0.02 before treatment and ? = 0.39 ± 0.07 after treatment; for the emphysema patient it was ? = 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. CONCLUSION:Ventilation may not be an effective surrogate for true regional lung function for all patients.

SUBMITTER: Rankine LJ

PROVIDER: S-EPMC6689416 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Correlation of Regional Lung Ventilation and Gas Transfer to Red Blood Cells: Implications for Functional-Avoidance Radiation Therapy Planning.

Rankine Leith J LJ Wang Ziyi Z Driehuys Bastiaan B Marks Lawrence B LB Kelsey Chris R CR Das Shiva K SK

International journal of radiation oncology, biology, physics 20180414 5

<h4>Purpose</h4>To investigate the degree to which lung ventilation and gas exchange are regionally correlated, using the emerging technology of hyperpolarized (HP)-<sup>129</sup>Xe magnetic resonance imaging (MRI).<h4>Methods and materials</h4>Hyperpolarized-<sup>129</sup>Xe 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 a ...[more]

PMID: 29907488

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Project description:PurposeTo present a methodology to use pulmonary gas exchange maps to guide functional avoidance treatment planning in radiation therapy (RT) and evaluate its efficacy compared with ventilation-guided treatment planning.Methods and materialsBefore receiving conventional RT for non-small cell lung cancer, 11 patients underwent hyperpolarized 129Xe gas exchange magnetic resonance imaging to map the distribution of xenon in its gas phase (ventilation) and transiently bound to red blood cells in the alveolar capillaries (gas exchange). Both ventilation and gas exchange maps were independently used to guide development of new functional avoidance treatment plans for every patient, while adhering to institutional dose-volume constraints for normal tissues and target coverage. Furthermore, dose-volume histogram (DVH)-based reoptimizations of the clinical plan, with reductions in mean lung dose (MLD) equal to the functional avoidance plans, were created to serve as the control group. To evaluate each plan (regardless of type), gas exchange maps, representing end-to-end lung function, were used to calculate gas exchange-weighted MLD (fMLD), gas exchange-weighted volume receiving ≥20 Gy (fV20), and mean dose in the highest gas exchanging 33% and 50% volumes of lung (MLD-f33% and MLD-f50%). Using each clinically approved plan as a baseline, the reductions in functional metrics were compared for ventilation-optimization, gas exchange optimization, and DVH-based reoptimization. Statistical significance was determined using the Freidman test, with subsequent subdivision when indicated by P values less than .10 and post hoc testing with Wilcoxon signed rank tests to determine significant differences (P < .05). Toxicity modeling was performed using an established function-based model to estimate clinical significance of the results.ResultsCompared with DVH-based reoptimization of the clinically approved plans, gas exchange-guided functional avoidance planning more effectively reduced the gas exchange-weighted metrics fMLD (average ± SD, -78 ± 79 cGy, compared with -45 ± 34 cGy; P = .03), MLD-f33% (-135 ± 136 cGy, compared with -52 ± 47 cGy; P = .004), and MLD-f50% (-96 ± 95 cGy, compared with -47 ± 40 cGy; P = .01). Comparing the 2 functional planning types, Gas Exchange-Guided planning more effectively reduced MLD-f33% compared with ventilation-guided planning (-64 ± 95; P = .009). For some patients, Gas Exchange-Guided functional avoidance plans demonstrated clinically significant reductions in model-predicted toxicity, more so than the accompanying ventilation-guided plans and DVH-based reoptimizations.ConclusionGas Exchange-Guided planning effectively reduced dose to high gas exchanging regions of lung while maintaining clinically acceptable plan quality. In many patients, ventilation-guided planning incidentally reduced dose to higher gas exchange regions, to a lesser extent. This methodology enables future prospective trials to examine patient outcomes.

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: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:PurposeCurrently, several active clinical trials of functional lung avoidance radiation therapy using different imaging modalities for ventilation or perfusion are underway. Patients with lung cancer often show ventilation-perfusion mismatch, whereas the significance of dose-function metric remains unclear. The aim of the present study was to compare dose-ventilation metrics with dose-perfusion metrics for radiation therapy plan evaluation.Methods and materialsPretreatment 4-dimensional computed tomography and 99mTc-macroaggregated albumin single-photon emission computed tomography perfusion images of 60 patients with lung cancer treated with radiation therapy were analyzed. Ventilation images were created using the deformable image registration of 4-dimensional computed tomography image sets and image analysis for regional volume changes as a surrogate for ventilation. Ventilation and perfusion images were converted into percentile distribution images. Analyses included Pearson's correlation coefficient and comparison of agreements between the following dose-ventilation and dose-perfusion metrics: functional mean lung dose and functional percent lung function receiving 5, 10, 20, 30, and 40 Gy (fV5, fV10, fV20, fV30, and fV40, respectively).ResultsOverall, the dose-ventilation metrics were greater than the dose-perfusion metrics (ie, fV20, 26.3% ± 9.9% vs 23.9% ± 9.8%). Correlations between the dose-ventilation and dose-perfusion metrics were strong (range, r = 0.94-0.97), whereas the agreements widely varied among patients, with differences as large as 6.6 Gy for functional mean lung dose and 11.1% for fV20. Paired t test indicated that the dose-ventilation and dose-perfusion metrics were significantly different.ConclusionsStrong correlations were present between the dose-ventilation and dose-perfusion metrics. However, the agreement between the dose-ventilation and dose-perfusion metrics widely varied among patients, suggesting that ventilation-based radiation therapy plan evaluation may not be comparable to that based on perfusion. Future studies should elucidate the correlation of dose-function metrics with clinical pulmonary toxicity metrics.

Project description:PurposeLung functional image guided radiation therapy (RT) that avoids irradiating highly functional regions has potential to reduce pulmonary toxicity following RT. Tumor regression during RT is common, leading to recovery of lung function. We hypothesized that computed tomography (CT) ventilation image-guided treatment planning reduces the functional lung dose compared to standard anatomic image-guided planning in 2 different scenarios with or without plan adaptation.Methods and materialsCT scans were acquired before RT and during RT at 2 time points (16-20 Gy and 30-34 Gy) for 14 patients with locally advanced lung cancer. Ventilation images were calculated by deformable image registration of four-dimensional CT image data sets and image analysis. We created 4 treatment plans at each time point for each patient: functional adapted, anatomic adapted, functional unadapted, and anatomic unadapted plans. Adaptation was performed at 2 time points. Deformable image registration was used for accumulating dose and calculating a composite of dose-weighted ventilation used to quantify the lung accumulated dose-function metrics. The functional plans were compared with the anatomic plans for each scenario separately to investigate the hypothesis at a significance level of 0.05.ResultsTumor volume was significantly reduced by 20% after 16 to 20 Gy (P = .02) and by 32% after 30 to 34 Gy (P < .01) on average. In both scenarios, the lung accumulated dose-function metrics were significantly lower in the functional plans than in the anatomic plans without compromising target volume coverage and adherence to constraints to critical structures. For example, functional planning significantly reduced the functional mean lung dose by 5.0% (P < .01) compared to anatomic planning in the adapted scenario and by 3.6% (P = .03) in the unadapted scenario.ConclusionsThis study demonstrated significant reductions in the accumulated dose to the functional lung with CT ventilation image-guided planning compared to anatomic image-guided planning for patients showing tumor regression and changes in regional ventilation during RT.

Dataset Information

Correlation of Regional Lung Ventilation and Gas Transfer to Red Blood Cells: Implications for Functional-Avoidance Radiation Therapy Planning.

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Correlation of Regional Lung Ventilation and Gas Transfer to Red Blood Cells: Implications for Functional-Avoidance Radiation Therapy Planning.

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