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Title: A Voxel-Based Approach to Explore Local Dose Differences Associated With Radiation-Induced Lung Damage

Abstract

Purpose: To apply a voxel-based (VB) approach aimed at exploring local dose differences associated with late radiation-induced lung damage (RILD). Methods and Materials: An interinstitutional database of 98 patients who were Hodgkin lymphoma (HL) survivors treated with postchemotherapy supradiaphragmatic radiation therapy was analyzed in the study. Eighteen patients experienced late RILD, classified according to the Radiation Therapy Oncology Group scoring system. Each patient's computed tomographic (CT) scan was normalized to a single reference case anatomy (common coordinate system, CCS) through a log-diffeomorphic approach. The obtained deformation fields were used to map the dose of each patient into the CCS. The coregistration robustness and the dose mapping accuracy were evaluated by geometric and dose scores. Two different statistical mapping schemes for nonparametric multiple permutation inference on dose maps were applied, and the corresponding P<.05 significance lung subregions were generated. A receiver operating characteristic (ROC)-based test was performed on the mean dose extracted from each subregion. Results: The coregistration process resulted in a geometrically robust and accurate dose warping. A significantly higher dose was consistently delivered to RILD patients in voxel clusters near the peripheral medial-basal portion of the lungs. The area under the ROC curves (AUC) from the mean dose ofmore » the voxel clusters was higher than the corresponding AUC derived from the total lung mean dose. Conclusions: We implemented a framework including a robust registration process and a VB approach accounting for the multiple comparison problem in dose-response modeling, and applied it to a cohort of HL survivors to explore a local dose–RILD relationship in the lungs. Patients with RILD received a significantly greater dose in parenchymal regions where low doses (∼6 Gy) were delivered. Interestingly, the relation between differences in the high-dose range and RILD seems to lack a clear spatial signature.« less

Authors:
 [1];  [2];  [1];  [1];  [3];  [1];  [4];  [5];  [6];  [1];  [1];  [3];  [1]
  1. Institute of Biostructure and Bioimaging, National Research Council, Naples (Italy)
  2. IRCCS SDN, Naples (Italy)
  3. (Italy)
  4. Department of Health Physics, S. Camillo-Forlanini Hospital, Rome (Italy)
  5. Department of Radiation Oncology, S. Camillo-Forlanini Hospital, Rome (Italy)
  6. Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY (United States)
Publication Date:
OSTI Identifier:
22648789
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 96; Journal Issue: 1; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; COMPUTERIZED TOMOGRAPHY; DAMAGE; GY RANGE 01-10; LUNGS; MAPPING; PATIENTS; RADIATION DOSES; RADIOTHERAPY

Citation Formats

Palma, Giuseppe, Monti, Serena, D'Avino, Vittoria, Conson, Manuel, Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples, Liuzzi, Raffaele, Pressello, Maria Cristina, Donato, Vittorio, Deasy, Joseph O., Quarantelli, Mario, Pacelli, Roberto, Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples, and Cella, Laura, E-mail: laura.cella@cnr.it. A Voxel-Based Approach to Explore Local Dose Differences Associated With Radiation-Induced Lung Damage. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.04.033.
Palma, Giuseppe, Monti, Serena, D'Avino, Vittoria, Conson, Manuel, Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples, Liuzzi, Raffaele, Pressello, Maria Cristina, Donato, Vittorio, Deasy, Joseph O., Quarantelli, Mario, Pacelli, Roberto, Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples, & Cella, Laura, E-mail: laura.cella@cnr.it. A Voxel-Based Approach to Explore Local Dose Differences Associated With Radiation-Induced Lung Damage. United States. doi:10.1016/J.IJROBP.2016.04.033.
Palma, Giuseppe, Monti, Serena, D'Avino, Vittoria, Conson, Manuel, Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples, Liuzzi, Raffaele, Pressello, Maria Cristina, Donato, Vittorio, Deasy, Joseph O., Quarantelli, Mario, Pacelli, Roberto, Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples, and Cella, Laura, E-mail: laura.cella@cnr.it. 2016. "A Voxel-Based Approach to Explore Local Dose Differences Associated With Radiation-Induced Lung Damage". United States. doi:10.1016/J.IJROBP.2016.04.033.
@article{osti_22648789,
title = {A Voxel-Based Approach to Explore Local Dose Differences Associated With Radiation-Induced Lung Damage},
author = {Palma, Giuseppe and Monti, Serena and D'Avino, Vittoria and Conson, Manuel and Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples and Liuzzi, Raffaele and Pressello, Maria Cristina and Donato, Vittorio and Deasy, Joseph O. and Quarantelli, Mario and Pacelli, Roberto and Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples and Cella, Laura, E-mail: laura.cella@cnr.it},
abstractNote = {Purpose: To apply a voxel-based (VB) approach aimed at exploring local dose differences associated with late radiation-induced lung damage (RILD). Methods and Materials: An interinstitutional database of 98 patients who were Hodgkin lymphoma (HL) survivors treated with postchemotherapy supradiaphragmatic radiation therapy was analyzed in the study. Eighteen patients experienced late RILD, classified according to the Radiation Therapy Oncology Group scoring system. Each patient's computed tomographic (CT) scan was normalized to a single reference case anatomy (common coordinate system, CCS) through a log-diffeomorphic approach. The obtained deformation fields were used to map the dose of each patient into the CCS. The coregistration robustness and the dose mapping accuracy were evaluated by geometric and dose scores. Two different statistical mapping schemes for nonparametric multiple permutation inference on dose maps were applied, and the corresponding P<.05 significance lung subregions were generated. A receiver operating characteristic (ROC)-based test was performed on the mean dose extracted from each subregion. Results: The coregistration process resulted in a geometrically robust and accurate dose warping. A significantly higher dose was consistently delivered to RILD patients in voxel clusters near the peripheral medial-basal portion of the lungs. The area under the ROC curves (AUC) from the mean dose of the voxel clusters was higher than the corresponding AUC derived from the total lung mean dose. Conclusions: We implemented a framework including a robust registration process and a VB approach accounting for the multiple comparison problem in dose-response modeling, and applied it to a cohort of HL survivors to explore a local dose–RILD relationship in the lungs. Patients with RILD received a significantly greater dose in parenchymal regions where low doses (∼6 Gy) were delivered. Interestingly, the relation between differences in the high-dose range and RILD seems to lack a clear spatial signature.},
doi = {10.1016/J.IJROBP.2016.04.033},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 96,
place = {United States},
year = 2016,
month = 9
}
  • The objective of this study was to evaluate the differences in dose-volumetric data obtained using the analytical anisotropic algorithm (AAA) vs the x-ray voxel Monte Carlo (XVMC) algorithm for stereotactic body radiation therapy (SBRT) for lung cancer. Dose-volumetric data from 20 patients treated with SBRT for solitary lung cancer generated using the iPlan XVMC for the Novalis system consisting of a 6-MV linear accelerator and micro-multileaf collimators were recalculated with the AAA in Eclipse using the same monitor units and identical beam setup. The mean isocenter dose was 100.2% and 98.7% of the prescribed dose according to XVMC and AAA,more » respectively. Mean values of the maximal dose (D{sub max}), the minimal dose (D{sub min}), and dose received by 95% volume (D{sub 95}) for the planning target volume (PTV) with XVMC were 104.3%, 75.1%, and 86.2%, respectively. When recalculated with the AAA, those values were 100.8%, 77.1%, and 85.4%, respectively. Mean dose parameter values considered for the normal lung, namely the mean lung dose, V{sub 5}, and V{sub 20}, were 3.7 Gy, 19.4%, and 5.0% for XVMC and 3.6 Gy, 18.3%, and 4.7% for the AAA, respectively. All of these dose-volumetric differences between the 2 algorithms were within 5% of the prescribed dose. The effect of PTV size and tumor location, respectively, on the differences in dose parameters for the PTV between the AAA and XVMC was evaluated. A significant effect of the PTV on the difference in D{sub 95} between the AAA and XVMC was observed (p = 0.03). Differences in the marginal doses, namely D{sub min} and D{sub 95}, were statistically significant between peripherally and centrally located tumors (p = 0.04 and p = 0.02, respectively). Tumor location and volume might have an effect on the differences in dose-volumetric parameters. The differences between AAA and XVMC were considered to be within an acceptable range (<5 percentage points)« less
  • Purpose: To evaluate XVMC computed rib doses for peripherally located non-small-cell-lung tumors treated with SBRT following RTOG-0915 guidelines. Methods: Twenty patients with solitary peripherally located non-small-cell-lung tumors were treated using XVMC-based SBRT to 50–54Gy in 5−3 fractions, respectively, for PTV(V100%)=95%. Based on 4D-CT, ITV was delineated on MaximumIP images and organs-at-risk(OARs) including ribs were contoured on MeanIP images. Mean PTV(ITV+5mm uniform margin) was 46.1±38.7cc (range, 11.1–163.0cc). XVMC SBRT treatment plans were generated with a combination of non-coplanar 3D-conformal arcs/beams, and were delivered by Novalis-TX consisting of HD-MLCs and a 6MV-SRS(1000MU/min) beam, following RTOG-0915 criteria. XVMC rib maximum dose and dosemore » to <1cc, <5cc, <10cc were evaluated as a function of PTV, prescription dose and 3D-distance from tumor isocenter to the most proximal rib contour. Plans were re-computed using heterogeneity-corrected pencil-beam (PB-hete) algorithm utilizing identical beam geometry/MLC positions and MUs and subsequently compared to XVMC. Results: XVMC average maximum rib dose was 50.9±6.4Gy (range, 35.1–59.3Gy). XVMC mean rib dose to <1cc was 41.6±5.6Gy (range, 27.9–47.9Gy), <5cc was 31.2±7.3Gy (range, 10.6–43.1Gy), and <10cc was 21.2±8.7Gy (range, 1.1–36Gy), respectively. For the given prescription, correlation between PTV and rib doses to <5cc (p=0.005) and <10cc (p=0.018) was observed. 3D-distance from the tumor isocenter to the proximal rib contour strongly correlated with maximum rib dose (p=0.0001). PB-hete algorithm overestimated maximum rib dose and dose to <1cc, <5cc, and <10cc of ribs by 5%, 3%, 3%, and 3%, respectively. Conclusion: PB-hete overestimates ribs dose relative to XVMC. Since all the clinical XVMC plans were generated without compromising the target coverage (per RTOG-0915), almost all patient’s ribs doses were higher than the protocol guidelines. As expected, larger tumor size and proximity to ribs received higher absolute dose to ribs. Prospective observation is needed to determine if XVMC delivered rib doses correlates with patient symptoms including chest wall pain and/or rib fractures.« less
  • Purpose: To develop and validate a fast and accurate method that uses computed tomography (CT) voxel data to estimate absorbed radiation dose at a point of interest (POI) or series of POIs from a kilovoltage (kV) imaging procedure. Methods: The authors developed an approach that computes absorbed radiation dose at a POI by numerically evaluating the linear Boltzmann transport equation (LBTE) using a combination of deterministic and Monte Carlo (MC) techniques. This hybrid approach accounts for material heterogeneity with a level of accuracy comparable to the general MC algorithms. Also, the dose at a POI is computed within seconds usingmore » the Intel Core i7 CPU 920 2.67 GHz quad core architecture, and the calculations are performed using CT voxel data, making it flexible and feasible for clinical applications. To validate the method, the authors constructed and acquired a CT scan of a heterogeneous block phantom consisting of a succession of slab densities: Tissue (1.29 cm), bone (2.42 cm), lung (4.84 cm), bone (1.37 cm), and tissue (4.84 cm). Using the hybrid transport method, the authors computed the absorbed doses at a set of points along the central axis and x direction of the phantom for an isotropic 125 kVp photon spectral point source located along the central axis 92.7 cm above the phantom surface. The accuracy of the results was compared to those computed with MCNP, which was cross-validated with EGSnrc, and served as the benchmark for validation. Results: The error in the depth dose ranged from -1.45% to +1.39% with a mean and standard deviation of -0.12% and 0.66%, respectively. The error in the x profile ranged from -1.3% to +0.9%, with standard deviations of -0.3% and 0.5%, respectively. The number of photons required to achieve these results was 1x10{sup 6}. Conclusions: The voxel-based hybrid method evaluates the LBTE rapidly and accurately to estimate the absorbed x-ray dose at any POI or series of POIs from a kV imaging procedure.« less
  • Purpose: Optimal implementation of new radiotherapy techniques requires accurate predictive models for normal tissue complications. Since clinically used dose distributions are nonuniform, local tissue damage needs to be measured and related to local tissue dose. In lung, radiation-induced damage results in density changes that have been measured by computed tomography (CT) imaging noninvasively, but not yet on a localized scale. Therefore, the aim of the present study was to develop a method for quantification of local radiation-induced lung tissue damage using CT. Methods and Materials: CT images of the thorax were made 8 and 26 weeks after irradiation of 100%,more » 75%, 50%, and 25% lung volume of rats. Local lung tissue structure (S{sub L}) was quantified from local mean and local standard deviation of the CT density in Hounsfield units in 1-mm{sup 3} subvolumes. The relation of changes in S{sub L} (DELTAS{sub L}) to histologic changes and breathing rate was investigated. Feasibility for clinical application was tested by applying the method to CT images of a patient with non-small-cell lung carcinoma and investigating the local dose-effect relationship of DELTAS{sub L}. Results: In rats, a clear dose-response relationship of DELTAS{sub L} was observed at different time points after radiation. Furthermore, DELTAS{sub L} correlated strongly to histologic endpoints (infiltrates and inflammatory cells) and breathing rate. In the patient, progressive local dose-dependent increases in DELTAS{sub L} were observed. Conclusion: We developed a method to quantify local radiation-induced tissue damage in the lung using CT. This method can be used in the development of more accurate predictive models for normal tissue complications.« less
  • Purpose: To present a new method of evaluating the correlation between radiotherapy (RT)-induced fibrosis and the local dose delivered to non-small-cell lung cancer patients. Methods and Materials: Treatment plans were generated using the CadPlan treatment planning system (pencil beam, no heterogeneity corrections), and RT delivery was based on these plans. Retrospective Monte-Carlo dose calculations were performed, and the Monte-Carlo distributions of dose to real tissue were calculated using the planning computed tomography (CT) images and the number of monitor units actually delivered. After registration of the follow-up CT images with the planning CT images, different grades of radiologic fibrosis weremore » automatically segmented on the follow-up CT images. Subsequently, patient-specific fibrosis probabilities were studied as a function of the local dose and a function of time after RT completion. Results: A strong patient-specific variation in the fibrosis volumes was found during the follow-up period. For both lungs, the threshold dose for which the probability of fibrosis became significant coincided with the threshold dose at which significant volumes of the lung were exposed. At later stages, only fibrosis localized in the high-dose regions persisted for both lungs. Overall, the Monte-Carlo dose distributions correlated much better with the probability of RT-induced fibrosis than did the CadPlan dose distributions. Conclusion: The presented method allows for an accurate, systematic, patient-specific and post-RT time-dependent numeric study of the relationship between RT-induced fibrosis and the local dose.« less