title: A Voxel-Based Approach to Explore Local Dose Differences Associated With Radiation-Induced Lung Damage.
abstract: To apply a voxel-based (VB) approach aimed at exploring local dose differences associated with late radiation-induced lung damage (RILD).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy.
authors: Giuseppe
authors: G
authors: Palma
authors: IRCCS SDN, Naples, Italy.
authors: Serena
authors: S
authors: Monti
authors: Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy.
authors: Vittoria
authors: V
authors: D'Avino
authors: Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy; Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples, Italy.
authors: Manuel
authors: M
authors: Conson
authors: Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy.
authors: Raffaele
authors: R
authors: Liuzzi
authors: Department of Health Physics, S. Camillo-Forlanini Hospital, Rome, Italy.
authors: Maria Cristina
authors: MC
authors: Pressello
authors: Department of Radiation Oncology, S. Camillo-Forlanini Hospital, Rome, Italy.
authors: Vittorio
authors: V
authors: Donato
authors: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY.
authors: Joseph O
authors: JO
authors: Deasy
authors: Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy.
authors: Mario
authors: M
authors: Quarantelli
authors: Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy; Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples, Italy.
authors: Roberto
authors: R
authors: Pacelli
authors: Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy. Electronic address: laura.cella@cnr.it.
authors: Laura
authors: L
authors: Cella
mesh_terms: D000328:Adult; D000368:Aged; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D055370:Lung Injury / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017564:Radiation Pneumonitis / Q000000981:diagnostic imaging* / Q000209:etiology / Q000473:pathology; D011857:Radiographic Image Interpretation, Computer-Assisted / Q000379:methods*; D011874:Radiometry / Q000379:methods*; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed / Q000379:methods*; D016896:Treatment Outcome