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Evaluating Which Dose-Function Metrics Are Most Critical for Functional-Guided Radiation Therapy.

ABSTRACT: Four-dimensional (4D) computed tomography (CT) ventilation imaging is increasingly being used to calculate lung ventilation and implement functional-guided radiation therapy in clinical trials. There has been little exhaustive work evaluating which dose-function metrics should be used for treatment planning and plan evaluation. The purpose of our study was to evaluate which dose-function metrics best predict for radiation pneumonitis (RP).Seventy lung cancer patients who underwent 4D CT imaging and pneumonitis grading were assessed. Pretreatment 4D CT scans of each patient were used to calculate ventilation images. We evaluated 3 types of dose-function metrics that combined the patient's 4D CT ventilation image and treatment planning dose distribution: (1) structure-based approaches; (2) image-based approaches using the dose-function histogram; and (3) nonlinear weighting schemes. Log-likelihood methods were used to generate normal tissue complication probability models predicting grade 3 or higher (ie, grade 3+) pneumonitis for all dose-function schemes. The area under the curve (AUC) was used to assess the predictive power of the models. All techniques were compared with normal tissue complication probability models based on traditional, total lung dose metrics.The most predictive models were structure-based approaches that focused on the volume of functional lung receiving ?20 Gy (AUC, 0.70). Probabilities of grade 3+ RP of 20% and 10% correspond to V20 (percentage of volume receiving ?20 Gy) to the functional subvolumes of 26.8% and 9.3%, respectively. Imaging-based analysis with the dose-function histogram and nonlinear weighted ventilation values yielded AUCs of 0.66 and 0.67, respectively, when we evaluated the percentage of functionality receiving ?20 Gy. All dose-function metrics outperformed the traditional dose metrics (mean lung dose, AUC of 0.55).A full range of dose-function metrics and functional thresholds was examined. The calculated AUC values for the most predictive functional models occupied a narrow range (0.66-0.70), and all showed notable improvements over AUC from traditional lung dose metrics (0.55). Identifying the combinations most predictive of grade 3+ RP provides valuable data to inform the functional-guided radiation therapy process.

SUBMITTER: Faught AM

PROVIDER: S-EPMC5603256 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Evaluating Which Dose-Function Metrics Are Most Critical for Functional-Guided Radiation Therapy.

Faught Austin M AM Yamamoto Tokihiro T Castillo Richard R Castillo Edward E Zhang Jingjing J Miften Moyed M Vinogradskiy Yevgeniy Y

International journal of radiation oncology, biology, physics 20170408 1

<h4>Purpose</h4>Four-dimensional (4D) computed tomography (CT) ventilation imaging is increasingly being used to calculate lung ventilation and implement functional-guided radiation therapy in clinical trials. There has been little exhaustive work evaluating which dose-function metrics should be used for treatment planning and plan evaluation. The purpose of our study was to evaluate which dose-function metrics best predict for radiation pneumonitis (RP).<h4>Methods and materials</h4>Seventy lun ...[more]

PMID: 28816147

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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:PurposeDose to normal lung has commonly been linked with radiation-induced lung toxicity (RILT) risk, but incorporating functional lung metrics in treatment planning may help further optimize dose delivery and reduce RILT incidence. The purpose of this study was to investigate the impact of the dose delivered to functional lung regions by analyzing perfusion (Q), ventilation (V), and combined V/Q single-photon-emission computed tomography (SPECT) dose-function metrics with regard to RILT risk in patients with non-small cell lung cancer (NSCLC) patients who received radiation therapy (RT).Methods and materialsSPECT images acquired from 88 patients with locally advanced NSCLC before undergoing conventionally fractionated RT were retrospectively analyzed. Dose was converted to the nominal dose equivalent per 2 Gy fraction, and SPECT intensities were normalized. Regional lung segments were defined, and the average dose delivered to each lung region was quantified. Three functional categorizations were defined to represent low-, normal-, and high-functioning lungs. The percent of functional lung category receiving ≥20 Gy and mean functional intensity receiving ≥20 Gy (iV20) were calculated. RILT was defined as grade 2+ radiation pneumonitis and/or clinical radiation fibrosis. A logistic regression was used to evaluate the association between dose-function metrics and risk of RILT.ResultsBy analyzing V/Q normalized intensities and functional distributions across the population, a wide range in functional capability (especially in the ipsilateral lung) was observed in patients with NSCLC before RT. Through multivariable regression models, global lung average dose to the lower lung was found to be significantly associated with RILT, and Q and V iV20 were correlated with RILT when using ipsilateral lung metrics. Through a receiver operating characteristic analysis, combined V/Q low-function receiving ≥20 Gy (low-functioning V/Q20) in the ipsilateral lung was found to be the best predictor (area under the curce: 0.79) of RILT risk.ConclusionsIrradiation of the inferior lung appears to be a locational sensitivity for RILT risk. The multivariable correlation between ipsilateral lung iV20 and RILT, as well as the association of low-functioning V/Q20 and RILT, suggest that irradiating low-functioning regions in the lung may lead to higher toxicity rates.

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:PurposeCT ventilation image (CTVI)-guided radiotherapy that selectively avoids irradiating highly-functional lung regions has potential to reduce pulmonary toxicity. Considering Helical TomoTherapy (HT) has higher modulation capabilities, we investigated the capability and characteristic of HT at sparing functional lungs for locally advanced lung cancer.Methods and materialsPretreatment 4DCT scans were carried out for 17 patients. Local lung volume expansion (or contraction) during inspiration is related to the volume change at a given lung voxel and is used as a surrogate for ventilation. The ventilation maps were generated from two sets of CT images (peak-exhale and peak-inhale) by deformable registration and a Jacobian-based algorithm. Each ventilation map was normalized to percentile images. Six plans were designed for each patient: one anatomical plan without ventilation map and five functional plans incorporating ventilation map which designed to spare varying degrees of high-functional lungs that were defined as the top 10%, 20%, 30%, 40%, and 50% of the percentile ventilation ranges, respectively. The dosimetric and evaluation factors were recorded regarding planning target volume (PTV) and other organs at risk (OARs), with particular attention to the dose delivered to total lung and functional lungs. An established dose-function-based normal tissue complication probability (NTCP) model was used to estimate risk of radiation pneumonitis (RP) for each scenario.ResultsPatients were divided into a benefit group (8 patients) and a non-benefit group (9 patients) based on whether the RP-risk of functional plan was lower than that of anatomical plan. The distance between high-ventilated region and PTV, as well as tumor volume had significant differences between the two groups (P < 0.05). For patients in the benefit group, the mean value of fV5, fV10, fV20, and fMLD (functional V5, V10, V20, and mean lung dose, respectively) were significantly lower starting from top 30% functional plan than in anatomical plan (P < 0.05). With expand of avoidance region in functional plans, the dose coverage of PTV is not sacrificed (P > 0.05) but at the cost of increased dose received by OARs.ConclusionVentilation image-guided HT plans can reduce the dose received by highly-functional lung regions with a range up to top 50% ventilated area. The spatial distribution of ventilation and tumor size were critical factors to better select patients who could benefit from the functional plan.

Project description:Background and purposeAdjuvant whole-breast irradiation after breast-conserving surgery, typically delivered over several weeks, is the traditional standard of care for low-risk breast cancer. More recently, hypofractionated, partial-breast irradiation has increasingly become established. Neoadjuvant single-fraction radiotherapy (rt) is an uncommon approach wherein the unresected lesion is irradiated preoperatively in a single fraction. We developed the signal (Stereotactic Image-Guided Neoadjuvant Ablative Radiation Then Lumpectomy) trial, a prospective single-arm trial to test our hypothesis that, for low-risk carcinoma of the breast, the preoperative single-fraction approach would be feasible and safe.MethodsPatients presenting with early-stage (T < 3 cm), estrogen-positive, clinically node-negative invasive carcinoma of the breast with tumours at least 2 cm away from skin and chest wall were enrolled. All patients received prone breast magnetic resonance imaging (mri) and prone computed tomography simulation. Treatable patients received a single 21 Gy fraction of external-beam rt (as volumetric-modulated arc therapy) to the primary lesion in the breast, followed by definitive surgery 1 week later. The primary endpoints at 3 weeks, 6 months, and 1 year were toxicity and cosmesis (that is, safety) and feasibility (defined as the proportion of mri-appropriate patients receiving rt).ResultsOf 52 patients accrued, 27 were successfully treated. The initial dosimetric constraints resulted in a feasibility failure, because only 57% of eligible patients were successfully treated. Revised dosimetric constraints were developed, after which 100% of patients meeting mri criteria were treated according to protocol. At 3 weeks, 6 months, and 1 year after the operation, toxicity, patient- and physician-rated cosmesis, and quality of life were not significantly different from baseline.ConclusionsThe signal trial presents a feasible method of implementing single-dose preoperative rt in early-stage breast cancer. This pilot study did not identify any significant toxicity and demonstrated excellent cosmetic and quality-of-life outcomes. Future randomized multi-arm studies are required to corroborate these findings.

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Evaluating Which Dose-Function Metrics Are Most Critical for Functional-Guided Radiation Therapy.

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Evaluating Which Dose-Function Metrics Are Most Critical for Functional-Guided Radiation Therapy.

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