Induction and concurrent taxanes enhance both the pulmonary metabolic radiation response and the radiation pneumonitis response in patients with esophagus cancer.

PURPOSE: The primary aim of this study was to assess pulmonary radiation toxicity quantitatively in patients who received thoracic radiotherapy combined with induction and/or concurrent chemotherapy with or without taxanes for esophageal cancer. METHODS AND MATERIALS: The study subjects were 139 patients treated at the University of Texas M.D. Anderson Cancer Center for esophageal cancer and who had undergone [(18)F]-fluorodeoxyglucose positron emission tomography/computed tomography between November 1, 2003 and December 15, 2007 for disease restaging after chemoradiotherapy. The patients were grouped into those who had not received taxanes (Group 1), those who had received induction or concurrent taxanes (Group 2), and those who had received both induction and concurrent taxanes (Group 3). Clinical pulmonary toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. Linear regression was applied to the fluorodeoxyglucose uptake vs. radiation dose to determine the pulmonary metabolic radiation response (PMRR) for each case. The clinical toxicity scores and PMRR among the groups were evaluated for significance differences. RESULTS: The crude rate of pneumonitis symptoms was 46%, 62%, and 74% for Group 1, 2, and 3, respectively. The analysis of variance test of log(PMRR) by treatment was significant (p = .0046). Group 3 had a 61% greater PMRR compared with Group 1 (p = .002). Group 2 had a 38% greater PMRR compared with Group 1 (p = .015). Finally, Group 3 had a 17% greater PMRR compared with Group 2 (p = .31). A PMRR enhancement ratio of 1.60 (95% confidence interval, 1.19-2.14) was observed for Group 3 vs. Group 1. CONCLUSION: Patients given induction and concurrent taxane chemotherapy had a significantly greater PMRR and clinical pneumonitis symptoms compared with the patients whose chemotherapy regimen did not include taxanes.

Determination of patient-specific internal gross tumor volumes for lung cancer using four-dimensional computed tomography.

BACKGROUND: To determine the optimal approach to delineating patient-specific internal gross target volumes (IGTV) from four-dimensional (4-D) computed tomography (CT) image data sets used in the planning of radiation treatment for lung cancers. METHODS: We analyzed 4D-CT image data sets of 27 consecutive patients with non-small-cell lung cancer (stage I: 17, stage III: 10). The IGTV, defined to be the envelope of respiratory motion of the gross tumor volume in each 4D-CT data set was delineated manually using four techniques: (1) combining the gross tumor volume (GTV) contours from ten respiratory phases (IGTVAllPhases); (2) combining the GTV contours from two extreme respiratory phases (0% and 50%) (IGTV2Phases); (3) defining the GTV contour using the maximum intensity projection (MIP) (IGTVMIP); and (4) defining the GTV contour using the MIP with modification based on visual verification of contours in individual respiratory phase (IGTVMIP-Modified). Using the IGTVAllPhases as the optimum IGTV, we compared volumes, matching indices, and extent of target missing using the IGTVs based on the other three approaches. RESULTS: The IGTVMIP and IGTV2Phases were significantly smaller than the IGTVAllPhases (p < 0.006 for stage I and p < 0.002 for stage III). However, the values of the IGTVMIP-Modified were close to those determined from IGTVAllPhases (p = 0.08). IGTVMIP-Modified also matched the best with IGTVAllPhases. CONCLUSION: IGTVMIP and IGTV2Phases underestimate IGTVs. IGTVMIP-Modified is recommended to improve IGTV delineation in lung cancer.

Consequences of anatomic changes and respiratory motion on radiation dose distributions in conformal radiotherapy for locally advanced non-small-cell lung cancer.

PURPOSE: To determine the effect of interfractional changes in anatomy on the target and normal tissue dose distributions during course of radiotherapy in non-small-cell lung cancer patients. METHODS AND MATERIALS: Weekly respiration-correlated four-dimensional computed tomography scans were acquired for 10 patients. Original beam arrangements from conventional and inverse treatment plans were transferred into each of the weekly four-dimensional computed tomography data sets, and the dose distributions were recalculated. Dosimetric changes to the target volumes and relevant normal structures relative to the baseline treatment plans were analyzed by dose-volume histograms. RESULTS: The overall difference in the mean +/- standard deviation of the doses to 95% of the planning target volume and internal target volume between the initial and weekly treatment plans was -11.9% +/- 12.1% and -2.5% +/- 3.9%, respectively. The mean +/- standard deviation change in the internal target volume receiving 95% of the prescribed dose was -2.3% +/- 4.1%. The overall differences in the mean +/- standard deviation between the initial and weekly treatment plans was 3.1% +/- 6.8% for the total lung volume exceeding 20 Gy, 2.2% +/- 4.8% for mean total lung dose, and 34.3% +/- 43.0% for the spinal cord maximal dose. CONCLUSION: Serial four-dimensional computed tomography scans provided useful anatomic information and dosimetric changes during radiotherapy. Although the observed dosimetric variations were small, on average, the interfractional changes in tumor volume, mobility, and patient setup was sometimes associated with dramatic dosimetric consequences. Therefore, for locally advanced lung cancer patients, efforts to include image-guided treatment and to perform repeated imaging during the treatment course are recommended.

Validation of a model-based segmentation approach to propagating normal anatomic regions of interest through the 10 phases of respiration.

PURPOSE: To validate a model-based segmentation (MBS) algorithm in a commercial radiation treatment planning system for use in propagating the contours of normal anatomic regions of interest (ROIs) through the respiratory phases that constitute a four-dimensional (4D) computed tomography (CT) image data set. METHODS AND MATERIALS: The 4D CT data sets for 12 patients treated for non-small-cell lung cancer were acquired. Five ROIs were selected for delineation: right and left lungs, spinal cord, heart, and esophagus. These ROIs were manually delineated on the CT data set corresponding to the end-inspiration respiratory phase (0%). An MBS algorithm implemented on the treatment planning system propagated the ROIs sequentially through the respiratory phases that constituted the 4D CT data sets, concluding with the 0% phase data set, which was propagated from the 90% phase data set. The propagated ROIs on the 0% phase were compared with the original ROIs on that phase by using visual assessment and a quantitative measure of coincidence. RESULTS: Acceptable propagation accuracy within 1 mm of uncertainty was achieved for lungs and spinal cord. Propagation of the heart produced slightly larger contours that were similar to interphysician variations in contouring the heart. The esophagus was poorly propagated because of lack of tissue contrast and definitive shape. CONCLUSIONS: The MBS propagation is a promising tool for efficiently propagating contours through the different phases of respiration. However, propagating the esophagus through this technique may be difficult because of the lack of definitive shape and clearer boundaries from surrounding tissue.

Radiation pneumonitis: correlation of toxicity with pulmonary metabolic radiation response.

PURPOSE: To characterize the relationship between radiation pneumonitis (RP) clinical symptoms and pulmonary metabolic activity on post-treatment [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET). PATIENTS AND METHODS: We retrospectively studied 101 esophageal cancer patients who underwent restaging FDG-PET/computed tomography imaging 3-12 weeks after completing thoracic radiotherapy. The National Institutes of Health Common Toxicity Criteria, version 3, was used to score the RP clinical symptoms. Linear regression was applied to the FDG-PET/computed tomography images to determine the normalized FDG uptake vs. radiation dose. The pulmonary metabolic radiation response (PMRR) was quantified as this slope. Modeling was performed to determine the interaction of PMRR, mean lung dose (MLD), and the percentage of lung receiving >20 Gy with RP outcomes. RESULTS: Of the 101 patients, 25 had Grade 0, 10 had Grade 1, 60 had Grade 2, 5 had Grade 3, and 1 had Grade 5 RP symptoms. Logistic regression analysis demonstrated that increased values of both MLD and PMRR were associated with a greater probability of RP clinical symptoms (p = 0.032 and p = 0.033, respectively). Spearman's rank correlation found no association between the PMRR and the dosimetric parameters (planning target volume, MLD, percentage of lung receiving >5-30 Gy). Twofold cross-validation demonstrated that the combination of MLD and PMRR was superior to either alone for assessing the development of clinical RP symptoms. The combined MLD (or percentage of lung receiving >20 Gy) and PMRR had a greater sensitivity and accuracy (53.3% and 62.5%, respectively) than either alone. CONCLUSION: The results of this study have demonstrated a significant correlation between RP clinical symptoms and the PMRR measured by FDG-PET/computed tomography after thoracic radiotherapy.

Comparison of rigid and adaptive methods of propagating gross tumor volume through respiratory phases of four-dimensional computed tomography image data set.

PURPOSE: To compare three different methods of propagating the gross tumor volume (GTV) through the respiratory phases that constitute a four-dimensional computed tomography image data set. METHODS AND MATERIALS: Four-dimensional computed tomography data sets of 20 patients who had undergone definitive hypofractionated radiotherapy to the lung were acquired. The GTV regions of interest (ROIs) were manually delineated on each phase of the four-dimensional computed tomography data set. The ROI from the end-expiration phase was propagated to the remaining nine phases of respiration using the following three techniques: (1) rigid-image registration using in-house software, (2) rigid image registration using research software from a commercial radiotherapy planning system vendor, and (3) rigid-image registration followed by deformable adaptation originally intended for organ-at-risk delineation using the same software. The internal GTVs generated from the various propagation methods were compared with the manual internal GTV using the normalized Dice similarity coefficient (DSC) index. RESULTS: The normalized DSC index of 1.01 +/- 0.06 (SD) for rigid propagation using the in-house software program was identical to the normalized DSC index of 1.01 +/- 0.06 for rigid propagation achieved with the vendor's research software. Adaptive propagation yielded poorer results, with a normalized DSC index of 0.89 +/- 0.10 (paired t test, p <0.001). CONCLUSION: Propagation of the GTV ROIs through the respiratory phases using rigid- body registration is an acceptable method within a 1-mm margin of uncertainty. The adaptive organ-at-risk propagation method was not applicable to propagating GTV ROIs, resulting in an unacceptable reduction of the volume and distortion of the ROIs.