Thomas Guerrero | University of Texas M. D. Anderson Cancer Center (original) (raw)

Papers by Thomas Guerrero

Physics in Medicine and Biology, 2004

The purpose of this work was to develop and validate an automated method for intrathoracic tumour... more The purpose of this work was to develop and validate an automated method for intrathoracic tumour motion estimation from breath-hold computed tomography (BH CT) imaging using the three-dimensional optical flow method (3D OFM). A modified 3D OFM algorithm provided 3D displacement vectors for each voxel which were used to map tumour voxels on expiration BH CT onto inspiration BH CT images. A thoracic phantom and simulated expiration/inspiration BH CT pairs were used for validation. The 3D OFM was applied to the measured inspiration and expiration BH CT images from one lung cancer and one oesophageal cancer patient. The resulting displacements were plotted in histogram format and analysed to provide insight regarding the tumour motion. The phantom tumour displacement was measured as 1.20 and 2.40 cm with full-width at tenth maximum (FWTM) for the distribution of displacement estimates of 0.008 and 0.006 cm, respectively. The maximum error of any single voxel's motion estimate was 1.1 mm along the z-dimension or approximately one-third of the z-dimension voxel size. The simulated BH CT pairs revealed an rms error of less than 0.25 mm. The displacement of the oesophageal tumours was nonuniform and up to 1.4 cm, this was a new finding. A lung tumour maximum displacement of 2.4 cm was found in the case evaluated. In conclusion, 3D OFM provided an accurate estimation of intrathoracic tumour motion, with estimated errors less than the voxel dimension in a simulated motion phantom study. Surprisingly, oesophageal tumour motion was large and nonuniform, with greatest motion occurring at the gastro-oesophageal junction.

Physics in Medicine and Biology, 2010

Two calculation methods to produce ventilation images from four-dimensional computed tomography (... more Two calculation methods to produce ventilation images from four-dimensional computed tomography (4DCT) acquired without added contrast have been reported. We reported a method to obtain ventilation images using deformable image registration (DIR) and the underlying CT density information. A second method performs the ventilation image calculation from the DIR result alone, using the Jacobian determinant of the deformation field to estimate the local volume changes resulting from ventilation. For each of these two approaches, there are variations on their implementation. In this study, two implementations of the Jacobian-based methodology are evaluated, as well as a single density change-based model for calculating the physiologic specific ventilation from 4DCT. In clinical practice, 99mTc-labeled aerosol single photon emission computed tomography (SPECT) is the standard method used to obtain ventilation images in patients. In this study, the distributions of ventilation obtained from the CT-based ventilation image calculation methods are compared with those obtained from the clinical standard SPECT ventilation imaging. Seven patients with 4DCT imaging and standard 99mTc-labeled aerosol SPECT/CT ventilation imaging obtained on the same day as part of a prospective validation study were selected. The results of this work demonstrate the equivalence of the Jacobian-based methodologies for quantifying the specific ventilation on a voxel scale. Additionally, we found that both Jacobian- and density-change-based methods correlate well with global measurements of the resting tidal volume. Finally, correlation with the clinical SPECT was assessed using the Dice similarity coefficient, which showed statistically higher (p-value < 10-4) correlation between density-change-based specific ventilation and the clinical reference than did either Jacobian-based implementation.

International Journal of Radiation Oncology Biology Physics, 2005

Purpose: We describe a method of quantifying regional ventilation from the radiotherapy treatment... more Purpose: We describe a method of quantifying regional ventilation from the radiotherapy treatment planning computed tomography (CT) images, with the goal of developing functional images for treatment planning and optimization. Methods and Materials: A series of exhalation breath-hold (eBH-CT) and inhalation breath-hold (iBH-CT) CT images obtained using a feedback-guided breath-hold technique for radiotherapy treatment planning was selected. The eBH-CT was mapped on a voxel-by-voxel basis to the iBH-CT using a deformable image registration algorithm. By using the average CT number over a 3 mm 3 region surrounding each pair of mapped voxels, the change in fraction of air per voxel (i.e., regional ventilation) was calculated. This methodology was applied to a series of 22 patients. The calculated total ventilation was compared to the change in contoured lung volumes between the exhalation and inhalation CTs (measured tidal volume). Results: A significant correlation was found between the calculated and measured tidal volumes for the left (R ‫؍‬ 0.982) and right (R ‫؍‬ 0.985), and for both lungs combined (R ‫؍‬ 0.985). In the resulting images, the regional ventilation was highly variable and corresponded with the spatial distribution of differences in the CT values (Hounsfield units) between the eBH-CT and the iBH-CT images. Conclusions: A method of quantifying regional ventilation from radiotherapy treatment planning CT data sets was demonstrated. The ventilation images can be used in plan optimization to minimize injury to functioning lung.

International Journal of Radiation Oncology Biology Physics, 2007

Purpose: To retrospectively compare outcomes for patients with unresectable locally advanced non-... more Purpose: To retrospectively compare outcomes for patients with unresectable locally advanced non-small-cell lung cancer (NSCLC) treated at our institution with concurrent chemoradiation with or without induction chemotherapy. Methods and Materials: We retrospectively analyzed 265 consecutive patients who received definitive treatment with three-dimensional conformal radiation and concurrent chemotherapy. Of these, 127 patients received induction chemotherapy before concurrent chemoradiation. Results: The two groups of patients (with induction vs. without induction chemotherapy) were similar in age, performance status, weight loss, histology, grade, and stage. Patients who received induction chemotherapy had better overall survival (median, 1.9 vs. 1.4 years; 5-year rate, 25% vs. 12%; p < 0.001) and distant metastasis-free survival (5-year rate, 42% vs. 23%; p ‫؍‬ 0.021). Locoregional control was not significantly different between the two groups. Multivariate analysis showed that induction chemotherapy was the most significant factor affecting overall survival, with a hazard ratio of 0.55 (95% confidence interval 0.40 -0.75; p < 0.001). A planned subgroup analysis showed that induction chemotherapy was associated with a significant overall survival benefit for patients with adenocarcinoma or large-cell carcinoma (5-year rate, 24% vs. 8%; p ‫؍‬ 0.003) but not for those with squamous cell carcinoma. A multivariate analysis of patients with adenocarcinoma or large-cell carcinoma confirmed that induction chemotherapy was the most significant factor associated with better overall survival, with a hazard ratio of 0.47 (95% confidence interval, 0.28 -0.78; p ‫؍‬ 0.003). Conclusion: Our retrospective analysis suggests that in combination with concurrent chemoradiation, induction chemotherapy may provide a small but significant survival benefit for patients with unresectable locally advanced adenocarcinoma or large-cell carcinoma of the lung.

International Journal of Radiation Oncology Biology Physics, 2005

Stage II-III unresectable esophageal cancer treated with concurrent chemotherapy and radiotherapy... more Stage II-III unresectable esophageal cancer treated with concurrent chemotherapy and radiotherapy. Methods and Materials: The medical records of 69 consecutive patients with clinical Stage II or III esophageal cancer treated with definitive chemoradiotherapy at the University of Texas M. D. Anderson Cancer Center between 1990 and 1998 were retrospectively reviewed. Of the 69 patients, 43 had received <51 Gy (lower dose group) and 26 >51 Gy (higher dose group). The median dose in the lower and higher dose groups was 30 Gy (range, 30 -51 Gy) and 59.4 Gy (range, 54 -64.8 Gy), respectively. Two fractionation schedules were used: rapid fractionation, delivering 30 Gy at 3 Gy/fraction within 2 weeks, and standard fractionation, delivering >45 Gy at 1.8 -2 Gy/fraction daily. Total doses of <50 Gy were usually given with rapid fractionation. Cisplatin and 5-fluorouracil were administrated to 93% of the patients. Results: The patient characteristic that differed between the two groups was that patients in the lower dose group were more likely to have had weight loss >5% (46.2% vs. 23.3%). The lower dose group had more N1 tumors, but the tumor classification and stage grouping were similar in the two groups. The median follow-up time for all patients was 22 months (range, 2-56 months). Patients in the higher dose group had a statistically significant better 3-year local control rate (36% vs. 19%, p ‫؍‬ 0.011), disease-free survival rate (25% vs. 10%, p ‫؍‬ 0.004), and overall survival rate (13% vs. 3%, p ‫؍‬ 0.054). A trend toward a better distant-metastasis-free survival rate was noted in the higher dose group (72% vs. 59%, p ‫؍‬ 0.12). The complete clinical response rate was significantly greater in the higher dose group (46% vs. 23%, p ‫؍‬ 0.048). In both groups, the most common type of first failure was persistence of the primary tumor. Significantly fewer patients in the higher dose group had tumor persistence after treatment (p ‫؍‬ 0.02). No statistically significant difference was found between the two groups in the pattern of locoregional or distant failure. The long-term side effects of chemoradiotherapy were similar in the two groups, although it was difficult to assess the side effects accurately in a retrospective fashion. On multivariate analysis, Stage II (vs. III) disease and radiation dose >51 Gy were independent predictors of improved LRC, and locoregional failure was an independent predictor of worse overall survival. Conclusion: Our data suggested a positive correlation between radiation dose and LRC in the population studied. A higher radiation dose was associated with increased LRC and survival in the dose range studied. The data also suggested that better LRC was associated with a lower rate of distant metastasis. A threshold of tumor response to radiation dose might be present, as suggested by the flattened slope in the high-dose area on the dose-response curve. A carefully designed dose-escalation study is required to confirm this assumption.

International Journal of Radiation Oncology Biology Physics, 2006

Purpose: This retrospective analysis was performed to assess the outcomes of three-dimensional (3... more Purpose: This retrospective analysis was performed to assess the outcomes of three-dimensional (3D) conformal radiotherapy and two-dimensional (2D) planning. Methods and Materials: Between 1978 and 2003, 200 patients with Stage I non-small-cell lung cancer (NSCLC) were treated with radiotherapy alone at M.D. Anderson Cancer Center. Eighty-five patients were treated with 3D conformal radiotherapy. For the 3D group, median age, radiation dose, and follow-up was 73 (range, 50 -92), 66 Gy (range, 45-90.3 Gy), and 19 months (range, 3-77 months), respectively; and for the 2D group, 69 (range, 44 -88), 64 Gy (range, 20 -74 Gy), 20 months (range, 1-173 months), respectively. Overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control (LRC), and distant metastasisfree survival (DMFS) rates were analyzed.

Computer Methods and Programs in Biomedicine, 2006

c o m p u t e r m e t h o d s a n d p r o g r a m s i n b i o m e d i c i n e 8 4 ( 2 0 0 6 ) 124... more c o m p u t e r m e t h o d s a n d p r o g r a m s i n b i o m e d i c i n e 8 4 ( 2 0 0 6 ) 124-134 Deformable image registration Optical flow Fourier interpolation a b s t r a c t

Medical Physics, 2005

The purpose of this work is to demonstrate a proof of feasibility of the application of a commerc... more The purpose of this work is to demonstrate a proof of feasibility of the application of a commercial prototype deformable model algorithm to the problem of delineation of anatomic structures on four-dimensional (4D) computed tomography (CT) image data sets. We acquired a 4D CT image data set of a patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s thorax that consisted of three-dimensional (3D) image data sets from eight phases in the respiratory cycle. The contours of the right and left lungs, cord, heart, and esophagus were manually delineated on the end inspiration data set. An interactive deformable model algorithm, originally intended for deforming an atlas-based model surface to a 3D CT image data set, was applied in an automated fashion. Triangulations based on the contours generated on each phase were deformed to the CT data set on the succeeding phase to generate the contours on that phase. Deformation was propagated through the eight phases, and the contours obtained on the end inspiration data set were compared with the original manually delineated contours. Structures defined by high-density gradients, such as lungs, cord, and heart, were accurately reproduced, except in regions where other gradient boundaries may have confused the algorithm, such as near bronchi. The algorithm failed to accurately contour the esophagus, a soft-tissue structure completely surrounded by tissue of similar density, without manual interaction. This technique has the potential to facilitate contour delineation in 4D CT image data sets; and future evolution of the software is expected to improve the process.

Physics in Medicine and Biology, 2010

A four-dimensional deformable image registration (4D DIR) algorithm, referred to as 4D local traj... more A four-dimensional deformable image registration (4D DIR) algorithm, referred to as 4D local trajectory modeling (4DLTM), is presented and applied to thoracic 4D computed tomography (4DCT) image sets. The theoretical framework on which this algorithm is built exploits the incremental continuity present in 4DCT component images to calculate a dense set of parameterized voxel trajectories through space as functions of time. The spatial accuracy of the 4DLTM algorithm is compared with an alternative registration approach in which component phase to phase (CPP) DIR is utilized to determine the full displacement between maximum inhale and exhale images. A publically available DIR reference database (http://www.dir-lab.com) is utilized for the spatial accuracy assessment. The database consists of ten 4DCT image sets and corresponding manually identified landmark points between the maximum phases. A subset of points are propagated through the expiratory 4DCT component images. Cubic polynomials were found to provide sufficient flexibility and spatial accuracy for describing the point trajectories through the expiratory phases. The resulting average spatial error between the maximum phases was 1.25 mm for the 4DLTM and 1.44 mm for the CPP. The 4DLTM method captures the long-range motion between 4DCT extremes with high spatial accuracy.

Purpose: To investigate the effect of induction chemotherapy (CHT) before trimodality therapy on ... more Purpose: To investigate the effect of induction chemotherapy (CHT) before trimodality therapy on the outcome of patients with resectable cancer of the esophagus. Methods and Materials: This retrospective study included 81 consecutive patients with resectable cancer of the esophagus who received neoadjuvant chemoradiotherapy followed by esophagectomy between January 1990 and December 1998 (inclusive). Thirty-nine patients underwent chemoradiotherapy followed by esophagectomy (CHT/RT؉S), 42 received additional induction CHT followed by CHT/RT؉S (CHT؉CHT/RT؉S). Of the 81 patients, 47 were entered in institutional or national prospective trials (6 in the CHT/RT؉S and 41 in the CHT؉CHT/RT؉S group). Induction CHT consisted of three courses of 5-fluorouracil (5-FU), cisplatin, and paclitaxel given in 28-day cycles in 37 patients (88.1%). Concurrent CHT was 5-FU and platinum based. The median radiation dose for patients treated with CHT/RT؉S was 30 Gy (range, 30 -50.4 Gy) delivered in a median of 10 fractions (range, 10 -28 fractions) and 45 Gy (range, 30 -45 Gy) in a median of 25 fractions (range, 10 -25 fractions) for patients treated with CHT؉CHT/RT؉S. Esophagectomy was performed 6 -8 weeks after completion of concurrent chemoradiotherapy. Most patients underwent transthoracic esophagectomy (n ‫؍‬ 66, 82.5%). Results: The pretreatment characteristics were well balanced between the two groups except for age. The median follow-up time was 29 months (22 months for the CHT/RT؉S group and 38.5 months for the CHT؉CHT/RT؉S group) for all patients and 49 months for living patients. The actuarial overall survival (OS), disease-free survival (DFS), locoregional control (LRC), and distant metastasis-free survival (DMFS) rate at 5 years for the entire group was 46%, 36.6%, 70.7%, and 53.2%, respectively. Statistically significant differences in the OS, DFS, and LRC rates between the two groups were detected. Specifically, the 5-year OS rate was 22.8% and 71.1% in the CHT/RT؉S and CHT؉CHT/RT؉S group (p ‫؍‬ 0.0001), respectively. The 5-year DFS rate was 27.6% and 56.6% in the CHT/RT؉S and CHT؉CHT/RT؉S group (p ‫؍‬ 0.003), respectively. The 5-year LRC rate was 64.2% and 85.6% in the CHT/RT؉S and CHT؉CHT/RT؉S group (p ‫؍‬ 0.007), respectively. The difference in the DMFS rate between the two groups was statistically significant, with a 2-and 5-year actuarial rate of 63.9% and 51.9%, respectively, in the CHT/RT؉S group and 76.9% and 74.1%, respectively, in the CHT؉CHT/RT؉S group (p ‫؍‬ 0.04). The statistically significant differences persisted when patients who received >45 Gy in each group were compared. Among those patients, the 5-year OS, DFS, LRC, and DMFS rates were 23.1%, 15.4%, 58.6%, and 39.2%, respectively, for those receiving CHT/RT؉S, and 71.4% (p ‫؍‬ 0.001), 55.8% (p ‫؍‬ 0.0008), 84.6% (p ‫؍‬ 0.005), and 77.3% (p ‫؍‬ 0.009), respectively, for those receiving CHT؉CHT/RT؉S. The pathologic complete response (pCR) rate was greater in the CHT؉CHT/RT؉S group compared with in the CHT/RT؉S group (p ‫؍‬ 0.008). In univariate analysis, young age, good Karnofsky performance status, Stage II disease, total radiation dose, multiple drug regimen for concurrent CHT, pCR, R0 resection, distant disease progression, and Reprint requests to: Zhongxing Liao, MD., CHT؉CHT/RT؉S treatment proved to be prognostic factors for OS. Lower esophageal/gastroesophageal junction tumor location, pCR, R0 resection, and CHT؉CHT/RT؉S treatment were favorable prognostic factors for LRC. Neither the total radiation dose nor multiple drugs for concurrent CHT were negative prognostic factors for LRC. In multivariate analysis, pCR, R0 resection, and treatment with CHT؉CHT/RT؉S were independent positive predictive factors for OS, and distant recurrences were negative predictive factors for OS. R0 resection, CHT؉CHT/RT؉S treatment, and lower esophageal/gastroesophageal junction tumor location were positive predictive factors for LRC. The radiation dose was not identified as an independent prognostic factor for either OS or LRC in the multivariate analysis. Meaningful multivariate analysis could not be performed when the multiple drug variable was included in the model because of the small number of patients. Conclusion: Significantly greater LRC, DFS, OS, and DMFS were found in patients treated with CHT؉CHT/ RT؉S compared with those treated with CHT/RT؉S. The pCR rate was significantly higher in the CHT؉CHT/ RT؉S group. Induction CHT was an independent favorable prognostic factor for both LRC and OS for the population included in this study. Our data suggest that a randomized trial comparing CHT؉CHT/RT؉S and CHT/RT؉S is warranted to assess further the merits of this treatment in patients with this currently very lethal cancer.

Physics in Medicine and Biology, 2006

A novel method for dynamic ventilation imaging of the full respiratory cycle from four-dimensiona... more A novel method for dynamic ventilation imaging of the full respiratory cycle from four-dimensional computed tomography (4D CT) acquired without added contrast is presented. Three cases with 4D CT images obtained with respiratory gated acquisition for radiotherapy treatment planning were selected. Each of the 4D CT data sets was acquired during resting tidal breathing. A deformable image registration algorithm mapped each (voxel) corresponding tissue element across the 4D CT data set. From local average CT values, the change in fraction of air per voxel (i.e. local ventilation) was calculated. A 4D ventilation image set was calculated using pairs formed with the maximum expiration image volume, first the exhalation then the inhalation phases representing a complete breath cycle. A preliminary validation using manually determined lung volumes was performed. The calculated total ventilation was compared to the change in contoured lung volumes between the CT pairs (measured volume). A linear regression resulted in a slope of 1.01 and a correlation coefficient of 0.984 for the ventilation images. The spatial distribution of ventilation was found to be case specific and a 30% difference in mass-specific ventilation between the lower and upper lung halves was found. These images may be useful in radiotherapy planning.

Cancer Journal, 2003

Malignant pleural mesothelioma often recurs locally in spite of aggressive resection by extrapleu... more Malignant pleural mesothelioma often recurs locally in spite of aggressive resection by extrapleural pneumonectomy and conventional radiotherapy. This may be due to failure to recognize the extent of clinical target volume (CTV) or suboptimal dose delivery to a target that abuts the heart, esophagus, liver, lung, kidney, and spinal cord. We report how these geometric/dosimetric constraints were overcome by exploiting intensity-modulated radiotherapy in the first cohort patient. Twenty-eight patients who had undergone extrapleural pneumonectomy were treated with intensity-modulated radiotherapy. The CTV included the surgically violated inner chest wall, insertion of diaphragm, pleural reflections, and deep margin of the incision. CTV delineation was facilitated by intraoperative radio-opaque marking. Motion was assessed. CTV doses were 45-50 Gy with boosts taken to 60 Gy. Despite the large, irregular CTV (median, 4151 cc; range, 2667-7286 cc), an average of 97% of the CTV was covered to the target dose (range, 92%-100%). Respiratory motion was minimal because of immobility of the prosthetic diaphragm. Normal tissue dose constraints were met. The commonest effects were nausea/vomiting (89%) and dyspnea (80%). Esophagitis was absent (59% of patients) or mild (34% grade 1/2). At median follow-up of 9 months (range, 5-27 months), local control within the contoured target was 100%. One-year survival, disease-specific survival, and disease-free survival are 65%, 91%, and 88%, respectively. Intensity-modulated radiotherapy after extrapleural pneumonectomy is tolerable and seems effective, at least at this early point. As local control improves, systemic metastases become more common, and it may be appropriate to add novel agents to further improve the therapeutic ratio.

International Journal of Radiation Oncology Biology Physics, 2008

To characterize the relationship between radiation pneumonitis (RP) clinical symptoms and pulmona... more 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). 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;20 Gy with RP outcomes. 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s rank correlation found no association between the PMRR and the dosimetric parameters (planning target volume, MLD, percentage of lung receiving &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;20 Gy) and PMRR had a greater sensitivity and accuracy (53.3% and 62.5%, respectively) than either alone. 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.

Computer Methods and Programs in Biomedicine, 2008

c o m p u t e r m e t h o d s a n d p r o g r a m s i n b i o m e d i c i n e 9 0 ( 2 0 0 8 ) 25-... more c o m p u t e r m e t h o d s a n d p r o g r a m s i n b i o m e d i c i n e 9 0 ( 2 0 0 8 ) 25-37 (G.G. Zhang).

International Journal of Radiation Oncology Biology Physics, 2004

Purpose: To investigate dosimetric improvements with respect to tumor-dose conformity and normal ... more Purpose: To investigate dosimetric improvements with respect to tumor-dose conformity and normal tissue sparing using intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3D-CRT) for advanced-stage non-small-cell lung cancer (NSCLC). Methods and Materials: Forty-one patients with Stage III-IV and recurrent NSCLC who previously underwent 3D-CRT were included. IMRT plans were designed to deliver 63 Gy to 95% of the planning target volume using nine equidistant coplanar 6-MV beams. Inverse planning was performed to minimize the volumes of normal lung, heart, esophagus, and spinal cord irradiated above their tolerance doses. Dose distributions and dosimetric indexes for the tumors and critical structures in both plans were computed and compared. Results: Using IMRT, the median absolute reduction in the percentage of lung volume irradiated to >10 and >20 Gy was 7% and 10%, respectively. This corresponded to a decrease of >2 Gy in the total lung mean dose and of 10% in the risk of radiation pneumonitis. The volumes of the heart and esophagus irradiated to >40 -50 Gy and normal thoracic tissue volume irradiated to >10 -40 Gy were reduced using the IMRT plans. A marginal increase occurred in the spinal cord maximal dose and lung volume >5 Gy in the IMRT plans, which could be have resulted from the significant increase in monitor units and thus leakage dose in IMRT. Conclusion: IMRT planning significantly improved target coverage and reduced the volume of normal lung irradiated above low doses. The spread of low doses to normal tissues can be controlled in IMRT with appropriately selected planning parameters. The dosimetric benefits of IMRT for advanced-stage non-small-cell lung cancer must be evaluated further in clinical trials.

Physics in Medicine and Biology, 2010

Online adaptive radiation therapy (ART) promises the ability to deliver an 20 optimal treatment i... more Online adaptive radiation therapy (ART) promises the ability to deliver an 20 optimal treatment in response to daily patient anatomic variation. A major technical barrier for the clinical implementation of online ART is the requirement of rapid image segmentation. Deformable image registration (DIR) has been used as an automated segmentation method to transfer tumor/organ contours from the planning image to daily images. However, the current 25 computational time of DIR is insufficient for online ART. In this work, this issue is addressed by using computer graphics processing units (GPUs). A greyscale based DIR algorithm called demons and five of its variants were implemented on GPUs using the Compute Unified Device Architecture (CUDA) programming environment. The spatial accuracy of these algorithms was 30 evaluated over five sets of pulmonary 4DCT images with an average size of 256×256×100 and more than 1,100 expert-determined landmark point pairs each. For all the testing scenarios presented in this paper, the GPU-based DIR computation required around 7 to 11 seconds to yield an average 3D error ranging from 1.5 to 1.8 mm. It is interesting to find out that the original passive 35 force demons algorithms outperform subsequently proposed variants based on the combination of accuracy, efficiency, and ease of implementation. 2 X. Gu et al.

International Journal of Radiation Oncology Biology Physics, 2004

To compare the outcome of induction chemotherapy followed by surgery (C/S) and concurrent chemora... more To compare the outcome of induction chemotherapy followed by surgery (C/S) and concurrent chemoradiotherapy (CRT) for clinical Stage IIIA non-small-cell lung cancer (NSCLC). Between 1990 and 2000, 107 patients underwent either induction C/S (n = 55) or concurrent CRT (n = 52) for clinical Stage IIIA NSCLC at The University of Texas M. D. Anderson Cancer Center. Patient and tumor characteristics were balanced in the two treatment groups with respect to T and N stage, race, median age, performance status, weight loss, and histologic findings. In the C/S group, induction chemotherapy included two to four cycles of cisplatin-based chemotherapy followed by lobectomy and mediastinal lymph node dissection. Postoperative RT was delivered in 35 patients, with referral for RT made at the discretion of the treating physician. CRT consisted of three cycles of cisplatin-based chemotherapy given every 3 weeks concurrent with RT to 60-63 Gy in 30-35 fractions in 27 patients and 69.6 Gy in 58 fractions (b.i.d.) in 25 patients. Local control, overall disease-free survival, and distant metastasis-free survival rates were calculated using the Kaplan-Meier method. The median follow-up duration was 20 months in all patients and 32 months in surviving patients. No statistically significant differences were found in the end points measured in the two treatment groups. Specifically, the median survival time was 31 and 27 months and the 5-year overall survival rate was 33% and 30% in the C/S and CRT groups, respectively. Likewise, the 5-year local control (58% vs. 61%), disease-free (24% vs. 23%), and distant metastasis-free (44% vs. 36%) survival rates in the two groups were not significantly different. In the C/S group, postoperative RT significantly improved the 5-year local control rate from 33.8% to 81.5% (p = 0.007) but did not significantly improve overall survival. Additionally, patients in the C/S group whose disease responded to induction chemotherapy had a significantly improved 5-year overall survival rate (50%) compared with those who had stable or progressive disease (16%, p = 0001). Treatment of Stage IIIA NSCLC using either induction C/S or CRT resulted in similar outcomes in terms of local control and median overall, 5-year overall, distant metastasis-free, and disease-free survival. However, patients undergoing induction C/S often needed postoperative RT to achieve local control equivalent to that achieved with concurrent CRT. Advances in radiation-based treatment as reflected in this study have resulted in similar outcomes compared with modern induction C/S. To improve survival, however, newer systemic agents that reduce and control distant metastasis are required.

International Journal of Radiation Oncology Biology Physics, 2008

Purpose-To compare three-dimensional (3D) and 4D computed tomography (CT)-based treatment plans f... more Purpose-To compare three-dimensional (3D) and 4D computed tomography (CT)-based treatment plans for proton therapy or intensity-modulated radiation therapy (IMRT) for esophageal cancer in terms of doses to the lung, heart, and spinal cord and variations in target coverage and normal tissue sparing.

International Journal of Radiation Oncology Biology Physics, 2008

Purpose: To investigate the motion characteristics of distal esophagus cancer primary tumors usin... more Purpose: To investigate the motion characteristics of distal esophagus cancer primary tumors using four-dimensional computed tomography (4D CT). Methods and Materials: Thirty-one consecutive patients treated for esophagus cancer who received respiratorygated 4D CT imaging for treatment planning were selected. Deformable image registration was used to map the full expiratory motion gross tumor volume (GTV) to the full-inspiratory CT image, allowing quantitative assessment of each voxel's displacement. These displacements were correlated with patient tumor and respiratory characteristics. Results: The mean (SE) tidal volume was 608 (73) mL. The mean GTV volume was 64.3 (10.7) mL on expiration and 64.1 (10.7) mL on inspiration (no significant difference). The mean tumor motion in the x-direction was 0.13 (0.006) cm (average of absolute values), in the y-direction 0.23 (0.01) cm (anteriorly), and in the z-direction 0.71 (0.02) cm (inferiorly). Tumor motion correlated with tidal volume. Comparison of tumor motion above vs. below the diaphragm was significant for the average net displacement (p = 0.014), motion below the diaphragm was greater than above. From the cumulative distribution 95% of the tumors moved less than 0.80 cm radially and 1.75 cm inferiorly. Conclusions: Primary esophagus tumor motion was evaluated with 4D CT. According to the results of this study, when 4D CT is not available, a radial margin of 0.8 cm and axial margin of ±1.8 cm would provide tumor motion coverage for 95% of the cases in our study population. Ó

International Journal of Radiation Oncology Biology Physics, 2005

To compare treatment plans for multileaf collimators (MLCs) with different leaf widths and differ... more To compare treatment plans for multileaf collimators (MLCs) with different leaf widths and different finite pencil beam (FPB) sizes, to determine the planning quality and delivery efficiency of segmented MLC (SMLC) delivery of intensity-modulated radiation therapy (IMRT) for malignant pleural mesothelioma (MPM). Computerized tomography images of 10 right-side MPM patients were used for this planning study on a CORVUS treatment-planning system (NOMOS Corporation, Sewickley, PA) for a Varian Millennium 120-MLC (Varian Medical Systems, Palo Alto, CA). Three beam models were used. The first model forced two 0.5-cm MLC leaves to move in tandem to simulate a 1-cm leaf-width MLC and a FPB size of 1 x 1 cm2. The second model used 0.5-cm leaves with a FPB size of 0.5 x 1 cm2 (1 cm in the direction of leaf movement). The third model used 0.5-cm leaves, with a FPB size of 0.5 x 0.5 cm2. For optimization, the same dose constraints and beam parameters were used for each data set. Tissue heterogeneity corrections were used during optimization and dose calculation. Plans were optimized such that the clinical target volume received 50 Gy in 25 fractions. Dose distributions to the target and normal structures were evaluated. The number of monitor units, the number of segments, and delivery times were used to evaluate delivery efficiency. All three beam models could be used for IMRT planning for MPM. The doses to clinical target volume, spinal cord, lung, liver, heart, and contralateral kidney were acceptable with all three beam models. The 0.5 x 0.5-cm2 beam model used the most monitor units (6883 +/- 974 vs. 3332 +/- 406 and 3407 +/- 443 for the 1 x 1-cm2 and 0.5 x 1-cm2 models, respectively) and treated the most segments (4297 +/- 802 vs. 1357 +/- 156 and 1767 +/- 212 for the 1 x 1-cm2 and 0.5 x 1-cm2 models, respectively). The plan generated with the 1 x 1-cm2 model required the least amount of time to deliver. The quality of the MPM IMRT plans generated with the three beam models presented here was similar; however, the 1 x 1-cm2 model provided the most efficient delivery of MPM IMRT with the CORVUS planning system.

Physics in Medicine and Biology, 2004

The purpose of this work was to develop and validate an automated method for intrathoracic tumour... more The purpose of this work was to develop and validate an automated method for intrathoracic tumour motion estimation from breath-hold computed tomography (BH CT) imaging using the three-dimensional optical flow method (3D OFM). A modified 3D OFM algorithm provided 3D displacement vectors for each voxel which were used to map tumour voxels on expiration BH CT onto inspiration BH CT images. A thoracic phantom and simulated expiration/inspiration BH CT pairs were used for validation. The 3D OFM was applied to the measured inspiration and expiration BH CT images from one lung cancer and one oesophageal cancer patient. The resulting displacements were plotted in histogram format and analysed to provide insight regarding the tumour motion. The phantom tumour displacement was measured as 1.20 and 2.40 cm with full-width at tenth maximum (FWTM) for the distribution of displacement estimates of 0.008 and 0.006 cm, respectively. The maximum error of any single voxel&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s motion estimate was 1.1 mm along the z-dimension or approximately one-third of the z-dimension voxel size. The simulated BH CT pairs revealed an rms error of less than 0.25 mm. The displacement of the oesophageal tumours was nonuniform and up to 1.4 cm, this was a new finding. A lung tumour maximum displacement of 2.4 cm was found in the case evaluated. In conclusion, 3D OFM provided an accurate estimation of intrathoracic tumour motion, with estimated errors less than the voxel dimension in a simulated motion phantom study. Surprisingly, oesophageal tumour motion was large and nonuniform, with greatest motion occurring at the gastro-oesophageal junction.

Physics in Medicine and Biology, 2010

Two calculation methods to produce ventilation images from four-dimensional computed tomography (... more Two calculation methods to produce ventilation images from four-dimensional computed tomography (4DCT) acquired without added contrast have been reported. We reported a method to obtain ventilation images using deformable image registration (DIR) and the underlying CT density information. A second method performs the ventilation image calculation from the DIR result alone, using the Jacobian determinant of the deformation field to estimate the local volume changes resulting from ventilation. For each of these two approaches, there are variations on their implementation. In this study, two implementations of the Jacobian-based methodology are evaluated, as well as a single density change-based model for calculating the physiologic specific ventilation from 4DCT. In clinical practice, 99mTc-labeled aerosol single photon emission computed tomography (SPECT) is the standard method used to obtain ventilation images in patients. In this study, the distributions of ventilation obtained from the CT-based ventilation image calculation methods are compared with those obtained from the clinical standard SPECT ventilation imaging. Seven patients with 4DCT imaging and standard 99mTc-labeled aerosol SPECT/CT ventilation imaging obtained on the same day as part of a prospective validation study were selected. The results of this work demonstrate the equivalence of the Jacobian-based methodologies for quantifying the specific ventilation on a voxel scale. Additionally, we found that both Jacobian- and density-change-based methods correlate well with global measurements of the resting tidal volume. Finally, correlation with the clinical SPECT was assessed using the Dice similarity coefficient, which showed statistically higher (p-value < 10-4) correlation between density-change-based specific ventilation and the clinical reference than did either Jacobian-based implementation.

International Journal of Radiation Oncology Biology Physics, 2005

Purpose: We describe a method of quantifying regional ventilation from the radiotherapy treatment... more Purpose: We describe a method of quantifying regional ventilation from the radiotherapy treatment planning computed tomography (CT) images, with the goal of developing functional images for treatment planning and optimization. Methods and Materials: A series of exhalation breath-hold (eBH-CT) and inhalation breath-hold (iBH-CT) CT images obtained using a feedback-guided breath-hold technique for radiotherapy treatment planning was selected. The eBH-CT was mapped on a voxel-by-voxel basis to the iBH-CT using a deformable image registration algorithm. By using the average CT number over a 3 mm 3 region surrounding each pair of mapped voxels, the change in fraction of air per voxel (i.e., regional ventilation) was calculated. This methodology was applied to a series of 22 patients. The calculated total ventilation was compared to the change in contoured lung volumes between the exhalation and inhalation CTs (measured tidal volume). Results: A significant correlation was found between the calculated and measured tidal volumes for the left (R ‫؍‬ 0.982) and right (R ‫؍‬ 0.985), and for both lungs combined (R ‫؍‬ 0.985). In the resulting images, the regional ventilation was highly variable and corresponded with the spatial distribution of differences in the CT values (Hounsfield units) between the eBH-CT and the iBH-CT images. Conclusions: A method of quantifying regional ventilation from radiotherapy treatment planning CT data sets was demonstrated. The ventilation images can be used in plan optimization to minimize injury to functioning lung.

International Journal of Radiation Oncology Biology Physics, 2007

Purpose: To retrospectively compare outcomes for patients with unresectable locally advanced non-... more Purpose: To retrospectively compare outcomes for patients with unresectable locally advanced non-small-cell lung cancer (NSCLC) treated at our institution with concurrent chemoradiation with or without induction chemotherapy. Methods and Materials: We retrospectively analyzed 265 consecutive patients who received definitive treatment with three-dimensional conformal radiation and concurrent chemotherapy. Of these, 127 patients received induction chemotherapy before concurrent chemoradiation. Results: The two groups of patients (with induction vs. without induction chemotherapy) were similar in age, performance status, weight loss, histology, grade, and stage. Patients who received induction chemotherapy had better overall survival (median, 1.9 vs. 1.4 years; 5-year rate, 25% vs. 12%; p < 0.001) and distant metastasis-free survival (5-year rate, 42% vs. 23%; p ‫؍‬ 0.021). Locoregional control was not significantly different between the two groups. Multivariate analysis showed that induction chemotherapy was the most significant factor affecting overall survival, with a hazard ratio of 0.55 (95% confidence interval 0.40 -0.75; p < 0.001). A planned subgroup analysis showed that induction chemotherapy was associated with a significant overall survival benefit for patients with adenocarcinoma or large-cell carcinoma (5-year rate, 24% vs. 8%; p ‫؍‬ 0.003) but not for those with squamous cell carcinoma. A multivariate analysis of patients with adenocarcinoma or large-cell carcinoma confirmed that induction chemotherapy was the most significant factor associated with better overall survival, with a hazard ratio of 0.47 (95% confidence interval, 0.28 -0.78; p ‫؍‬ 0.003). Conclusion: Our retrospective analysis suggests that in combination with concurrent chemoradiation, induction chemotherapy may provide a small but significant survival benefit for patients with unresectable locally advanced adenocarcinoma or large-cell carcinoma of the lung.

International Journal of Radiation Oncology Biology Physics, 2005

Stage II-III unresectable esophageal cancer treated with concurrent chemotherapy and radiotherapy... more Stage II-III unresectable esophageal cancer treated with concurrent chemotherapy and radiotherapy. Methods and Materials: The medical records of 69 consecutive patients with clinical Stage II or III esophageal cancer treated with definitive chemoradiotherapy at the University of Texas M. D. Anderson Cancer Center between 1990 and 1998 were retrospectively reviewed. Of the 69 patients, 43 had received <51 Gy (lower dose group) and 26 >51 Gy (higher dose group). The median dose in the lower and higher dose groups was 30 Gy (range, 30 -51 Gy) and 59.4 Gy (range, 54 -64.8 Gy), respectively. Two fractionation schedules were used: rapid fractionation, delivering 30 Gy at 3 Gy/fraction within 2 weeks, and standard fractionation, delivering >45 Gy at 1.8 -2 Gy/fraction daily. Total doses of <50 Gy were usually given with rapid fractionation. Cisplatin and 5-fluorouracil were administrated to 93% of the patients. Results: The patient characteristic that differed between the two groups was that patients in the lower dose group were more likely to have had weight loss >5% (46.2% vs. 23.3%). The lower dose group had more N1 tumors, but the tumor classification and stage grouping were similar in the two groups. The median follow-up time for all patients was 22 months (range, 2-56 months). Patients in the higher dose group had a statistically significant better 3-year local control rate (36% vs. 19%, p ‫؍‬ 0.011), disease-free survival rate (25% vs. 10%, p ‫؍‬ 0.004), and overall survival rate (13% vs. 3%, p ‫؍‬ 0.054). A trend toward a better distant-metastasis-free survival rate was noted in the higher dose group (72% vs. 59%, p ‫؍‬ 0.12). The complete clinical response rate was significantly greater in the higher dose group (46% vs. 23%, p ‫؍‬ 0.048). In both groups, the most common type of first failure was persistence of the primary tumor. Significantly fewer patients in the higher dose group had tumor persistence after treatment (p ‫؍‬ 0.02). No statistically significant difference was found between the two groups in the pattern of locoregional or distant failure. The long-term side effects of chemoradiotherapy were similar in the two groups, although it was difficult to assess the side effects accurately in a retrospective fashion. On multivariate analysis, Stage II (vs. III) disease and radiation dose >51 Gy were independent predictors of improved LRC, and locoregional failure was an independent predictor of worse overall survival. Conclusion: Our data suggested a positive correlation between radiation dose and LRC in the population studied. A higher radiation dose was associated with increased LRC and survival in the dose range studied. The data also suggested that better LRC was associated with a lower rate of distant metastasis. A threshold of tumor response to radiation dose might be present, as suggested by the flattened slope in the high-dose area on the dose-response curve. A carefully designed dose-escalation study is required to confirm this assumption.

International Journal of Radiation Oncology Biology Physics, 2006

Purpose: This retrospective analysis was performed to assess the outcomes of three-dimensional (3... more Purpose: This retrospective analysis was performed to assess the outcomes of three-dimensional (3D) conformal radiotherapy and two-dimensional (2D) planning. Methods and Materials: Between 1978 and 2003, 200 patients with Stage I non-small-cell lung cancer (NSCLC) were treated with radiotherapy alone at M.D. Anderson Cancer Center. Eighty-five patients were treated with 3D conformal radiotherapy. For the 3D group, median age, radiation dose, and follow-up was 73 (range, 50 -92), 66 Gy (range, 45-90.3 Gy), and 19 months (range, 3-77 months), respectively; and for the 2D group, 69 (range, 44 -88), 64 Gy (range, 20 -74 Gy), 20 months (range, 1-173 months), respectively. Overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control (LRC), and distant metastasisfree survival (DMFS) rates were analyzed.

Computer Methods and Programs in Biomedicine, 2006

c o m p u t e r m e t h o d s a n d p r o g r a m s i n b i o m e d i c i n e 8 4 ( 2 0 0 6 ) 124... more c o m p u t e r m e t h o d s a n d p r o g r a m s i n b i o m e d i c i n e 8 4 ( 2 0 0 6 ) 124-134 Deformable image registration Optical flow Fourier interpolation a b s t r a c t

Medical Physics, 2005

The purpose of this work is to demonstrate a proof of feasibility of the application of a commerc... more The purpose of this work is to demonstrate a proof of feasibility of the application of a commercial prototype deformable model algorithm to the problem of delineation of anatomic structures on four-dimensional (4D) computed tomography (CT) image data sets. We acquired a 4D CT image data set of a patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s thorax that consisted of three-dimensional (3D) image data sets from eight phases in the respiratory cycle. The contours of the right and left lungs, cord, heart, and esophagus were manually delineated on the end inspiration data set. An interactive deformable model algorithm, originally intended for deforming an atlas-based model surface to a 3D CT image data set, was applied in an automated fashion. Triangulations based on the contours generated on each phase were deformed to the CT data set on the succeeding phase to generate the contours on that phase. Deformation was propagated through the eight phases, and the contours obtained on the end inspiration data set were compared with the original manually delineated contours. Structures defined by high-density gradients, such as lungs, cord, and heart, were accurately reproduced, except in regions where other gradient boundaries may have confused the algorithm, such as near bronchi. The algorithm failed to accurately contour the esophagus, a soft-tissue structure completely surrounded by tissue of similar density, without manual interaction. This technique has the potential to facilitate contour delineation in 4D CT image data sets; and future evolution of the software is expected to improve the process.

Physics in Medicine and Biology, 2010

A four-dimensional deformable image registration (4D DIR) algorithm, referred to as 4D local traj... more A four-dimensional deformable image registration (4D DIR) algorithm, referred to as 4D local trajectory modeling (4DLTM), is presented and applied to thoracic 4D computed tomography (4DCT) image sets. The theoretical framework on which this algorithm is built exploits the incremental continuity present in 4DCT component images to calculate a dense set of parameterized voxel trajectories through space as functions of time. The spatial accuracy of the 4DLTM algorithm is compared with an alternative registration approach in which component phase to phase (CPP) DIR is utilized to determine the full displacement between maximum inhale and exhale images. A publically available DIR reference database (http://www.dir-lab.com) is utilized for the spatial accuracy assessment. The database consists of ten 4DCT image sets and corresponding manually identified landmark points between the maximum phases. A subset of points are propagated through the expiratory 4DCT component images. Cubic polynomials were found to provide sufficient flexibility and spatial accuracy for describing the point trajectories through the expiratory phases. The resulting average spatial error between the maximum phases was 1.25 mm for the 4DLTM and 1.44 mm for the CPP. The 4DLTM method captures the long-range motion between 4DCT extremes with high spatial accuracy.

Purpose: To investigate the effect of induction chemotherapy (CHT) before trimodality therapy on ... more Purpose: To investigate the effect of induction chemotherapy (CHT) before trimodality therapy on the outcome of patients with resectable cancer of the esophagus. Methods and Materials: This retrospective study included 81 consecutive patients with resectable cancer of the esophagus who received neoadjuvant chemoradiotherapy followed by esophagectomy between January 1990 and December 1998 (inclusive). Thirty-nine patients underwent chemoradiotherapy followed by esophagectomy (CHT/RT؉S), 42 received additional induction CHT followed by CHT/RT؉S (CHT؉CHT/RT؉S). Of the 81 patients, 47 were entered in institutional or national prospective trials (6 in the CHT/RT؉S and 41 in the CHT؉CHT/RT؉S group). Induction CHT consisted of three courses of 5-fluorouracil (5-FU), cisplatin, and paclitaxel given in 28-day cycles in 37 patients (88.1%). Concurrent CHT was 5-FU and platinum based. The median radiation dose for patients treated with CHT/RT؉S was 30 Gy (range, 30 -50.4 Gy) delivered in a median of 10 fractions (range, 10 -28 fractions) and 45 Gy (range, 30 -45 Gy) in a median of 25 fractions (range, 10 -25 fractions) for patients treated with CHT؉CHT/RT؉S. Esophagectomy was performed 6 -8 weeks after completion of concurrent chemoradiotherapy. Most patients underwent transthoracic esophagectomy (n ‫؍‬ 66, 82.5%). Results: The pretreatment characteristics were well balanced between the two groups except for age. The median follow-up time was 29 months (22 months for the CHT/RT؉S group and 38.5 months for the CHT؉CHT/RT؉S group) for all patients and 49 months for living patients. The actuarial overall survival (OS), disease-free survival (DFS), locoregional control (LRC), and distant metastasis-free survival (DMFS) rate at 5 years for the entire group was 46%, 36.6%, 70.7%, and 53.2%, respectively. Statistically significant differences in the OS, DFS, and LRC rates between the two groups were detected. Specifically, the 5-year OS rate was 22.8% and 71.1% in the CHT/RT؉S and CHT؉CHT/RT؉S group (p ‫؍‬ 0.0001), respectively. The 5-year DFS rate was 27.6% and 56.6% in the CHT/RT؉S and CHT؉CHT/RT؉S group (p ‫؍‬ 0.003), respectively. The 5-year LRC rate was 64.2% and 85.6% in the CHT/RT؉S and CHT؉CHT/RT؉S group (p ‫؍‬ 0.007), respectively. The difference in the DMFS rate between the two groups was statistically significant, with a 2-and 5-year actuarial rate of 63.9% and 51.9%, respectively, in the CHT/RT؉S group and 76.9% and 74.1%, respectively, in the CHT؉CHT/RT؉S group (p ‫؍‬ 0.04). The statistically significant differences persisted when patients who received >45 Gy in each group were compared. Among those patients, the 5-year OS, DFS, LRC, and DMFS rates were 23.1%, 15.4%, 58.6%, and 39.2%, respectively, for those receiving CHT/RT؉S, and 71.4% (p ‫؍‬ 0.001), 55.8% (p ‫؍‬ 0.0008), 84.6% (p ‫؍‬ 0.005), and 77.3% (p ‫؍‬ 0.009), respectively, for those receiving CHT؉CHT/RT؉S. The pathologic complete response (pCR) rate was greater in the CHT؉CHT/RT؉S group compared with in the CHT/RT؉S group (p ‫؍‬ 0.008). In univariate analysis, young age, good Karnofsky performance status, Stage II disease, total radiation dose, multiple drug regimen for concurrent CHT, pCR, R0 resection, distant disease progression, and Reprint requests to: Zhongxing Liao, MD., CHT؉CHT/RT؉S treatment proved to be prognostic factors for OS. Lower esophageal/gastroesophageal junction tumor location, pCR, R0 resection, and CHT؉CHT/RT؉S treatment were favorable prognostic factors for LRC. Neither the total radiation dose nor multiple drugs for concurrent CHT were negative prognostic factors for LRC. In multivariate analysis, pCR, R0 resection, and treatment with CHT؉CHT/RT؉S were independent positive predictive factors for OS, and distant recurrences were negative predictive factors for OS. R0 resection, CHT؉CHT/RT؉S treatment, and lower esophageal/gastroesophageal junction tumor location were positive predictive factors for LRC. The radiation dose was not identified as an independent prognostic factor for either OS or LRC in the multivariate analysis. Meaningful multivariate analysis could not be performed when the multiple drug variable was included in the model because of the small number of patients. Conclusion: Significantly greater LRC, DFS, OS, and DMFS were found in patients treated with CHT؉CHT/ RT؉S compared with those treated with CHT/RT؉S. The pCR rate was significantly higher in the CHT؉CHT/ RT؉S group. Induction CHT was an independent favorable prognostic factor for both LRC and OS for the population included in this study. Our data suggest that a randomized trial comparing CHT؉CHT/RT؉S and CHT/RT؉S is warranted to assess further the merits of this treatment in patients with this currently very lethal cancer.

Physics in Medicine and Biology, 2006

A novel method for dynamic ventilation imaging of the full respiratory cycle from four-dimensiona... more A novel method for dynamic ventilation imaging of the full respiratory cycle from four-dimensional computed tomography (4D CT) acquired without added contrast is presented. Three cases with 4D CT images obtained with respiratory gated acquisition for radiotherapy treatment planning were selected. Each of the 4D CT data sets was acquired during resting tidal breathing. A deformable image registration algorithm mapped each (voxel) corresponding tissue element across the 4D CT data set. From local average CT values, the change in fraction of air per voxel (i.e. local ventilation) was calculated. A 4D ventilation image set was calculated using pairs formed with the maximum expiration image volume, first the exhalation then the inhalation phases representing a complete breath cycle. A preliminary validation using manually determined lung volumes was performed. The calculated total ventilation was compared to the change in contoured lung volumes between the CT pairs (measured volume). A linear regression resulted in a slope of 1.01 and a correlation coefficient of 0.984 for the ventilation images. The spatial distribution of ventilation was found to be case specific and a 30% difference in mass-specific ventilation between the lower and upper lung halves was found. These images may be useful in radiotherapy planning.

Cancer Journal, 2003

Malignant pleural mesothelioma often recurs locally in spite of aggressive resection by extrapleu... more Malignant pleural mesothelioma often recurs locally in spite of aggressive resection by extrapleural pneumonectomy and conventional radiotherapy. This may be due to failure to recognize the extent of clinical target volume (CTV) or suboptimal dose delivery to a target that abuts the heart, esophagus, liver, lung, kidney, and spinal cord. We report how these geometric/dosimetric constraints were overcome by exploiting intensity-modulated radiotherapy in the first cohort patient. Twenty-eight patients who had undergone extrapleural pneumonectomy were treated with intensity-modulated radiotherapy. The CTV included the surgically violated inner chest wall, insertion of diaphragm, pleural reflections, and deep margin of the incision. CTV delineation was facilitated by intraoperative radio-opaque marking. Motion was assessed. CTV doses were 45-50 Gy with boosts taken to 60 Gy. Despite the large, irregular CTV (median, 4151 cc; range, 2667-7286 cc), an average of 97% of the CTV was covered to the target dose (range, 92%-100%). Respiratory motion was minimal because of immobility of the prosthetic diaphragm. Normal tissue dose constraints were met. The commonest effects were nausea/vomiting (89%) and dyspnea (80%). Esophagitis was absent (59% of patients) or mild (34% grade 1/2). At median follow-up of 9 months (range, 5-27 months), local control within the contoured target was 100%. One-year survival, disease-specific survival, and disease-free survival are 65%, 91%, and 88%, respectively. Intensity-modulated radiotherapy after extrapleural pneumonectomy is tolerable and seems effective, at least at this early point. As local control improves, systemic metastases become more common, and it may be appropriate to add novel agents to further improve the therapeutic ratio.

International Journal of Radiation Oncology Biology Physics, 2008

To characterize the relationship between radiation pneumonitis (RP) clinical symptoms and pulmona... more 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). 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;20 Gy with RP outcomes. 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s rank correlation found no association between the PMRR and the dosimetric parameters (planning target volume, MLD, percentage of lung receiving &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;20 Gy) and PMRR had a greater sensitivity and accuracy (53.3% and 62.5%, respectively) than either alone. 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.

Computer Methods and Programs in Biomedicine, 2008

c o m p u t e r m e t h o d s a n d p r o g r a m s i n b i o m e d i c i n e 9 0 ( 2 0 0 8 ) 25-... more c o m p u t e r m e t h o d s a n d p r o g r a m s i n b i o m e d i c i n e 9 0 ( 2 0 0 8 ) 25-37 (G.G. Zhang).

International Journal of Radiation Oncology Biology Physics, 2004

Purpose: To investigate dosimetric improvements with respect to tumor-dose conformity and normal ... more Purpose: To investigate dosimetric improvements with respect to tumor-dose conformity and normal tissue sparing using intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3D-CRT) for advanced-stage non-small-cell lung cancer (NSCLC). Methods and Materials: Forty-one patients with Stage III-IV and recurrent NSCLC who previously underwent 3D-CRT were included. IMRT plans were designed to deliver 63 Gy to 95% of the planning target volume using nine equidistant coplanar 6-MV beams. Inverse planning was performed to minimize the volumes of normal lung, heart, esophagus, and spinal cord irradiated above their tolerance doses. Dose distributions and dosimetric indexes for the tumors and critical structures in both plans were computed and compared. Results: Using IMRT, the median absolute reduction in the percentage of lung volume irradiated to >10 and >20 Gy was 7% and 10%, respectively. This corresponded to a decrease of >2 Gy in the total lung mean dose and of 10% in the risk of radiation pneumonitis. The volumes of the heart and esophagus irradiated to >40 -50 Gy and normal thoracic tissue volume irradiated to >10 -40 Gy were reduced using the IMRT plans. A marginal increase occurred in the spinal cord maximal dose and lung volume >5 Gy in the IMRT plans, which could be have resulted from the significant increase in monitor units and thus leakage dose in IMRT. Conclusion: IMRT planning significantly improved target coverage and reduced the volume of normal lung irradiated above low doses. The spread of low doses to normal tissues can be controlled in IMRT with appropriately selected planning parameters. The dosimetric benefits of IMRT for advanced-stage non-small-cell lung cancer must be evaluated further in clinical trials.

Physics in Medicine and Biology, 2010

Online adaptive radiation therapy (ART) promises the ability to deliver an 20 optimal treatment i... more Online adaptive radiation therapy (ART) promises the ability to deliver an 20 optimal treatment in response to daily patient anatomic variation. A major technical barrier for the clinical implementation of online ART is the requirement of rapid image segmentation. Deformable image registration (DIR) has been used as an automated segmentation method to transfer tumor/organ contours from the planning image to daily images. However, the current 25 computational time of DIR is insufficient for online ART. In this work, this issue is addressed by using computer graphics processing units (GPUs). A greyscale based DIR algorithm called demons and five of its variants were implemented on GPUs using the Compute Unified Device Architecture (CUDA) programming environment. The spatial accuracy of these algorithms was 30 evaluated over five sets of pulmonary 4DCT images with an average size of 256×256×100 and more than 1,100 expert-determined landmark point pairs each. For all the testing scenarios presented in this paper, the GPU-based DIR computation required around 7 to 11 seconds to yield an average 3D error ranging from 1.5 to 1.8 mm. It is interesting to find out that the original passive 35 force demons algorithms outperform subsequently proposed variants based on the combination of accuracy, efficiency, and ease of implementation. 2 X. Gu et al.

International Journal of Radiation Oncology Biology Physics, 2004

To compare the outcome of induction chemotherapy followed by surgery (C/S) and concurrent chemora... more To compare the outcome of induction chemotherapy followed by surgery (C/S) and concurrent chemoradiotherapy (CRT) for clinical Stage IIIA non-small-cell lung cancer (NSCLC). Between 1990 and 2000, 107 patients underwent either induction C/S (n = 55) or concurrent CRT (n = 52) for clinical Stage IIIA NSCLC at The University of Texas M. D. Anderson Cancer Center. Patient and tumor characteristics were balanced in the two treatment groups with respect to T and N stage, race, median age, performance status, weight loss, and histologic findings. In the C/S group, induction chemotherapy included two to four cycles of cisplatin-based chemotherapy followed by lobectomy and mediastinal lymph node dissection. Postoperative RT was delivered in 35 patients, with referral for RT made at the discretion of the treating physician. CRT consisted of three cycles of cisplatin-based chemotherapy given every 3 weeks concurrent with RT to 60-63 Gy in 30-35 fractions in 27 patients and 69.6 Gy in 58 fractions (b.i.d.) in 25 patients. Local control, overall disease-free survival, and distant metastasis-free survival rates were calculated using the Kaplan-Meier method. The median follow-up duration was 20 months in all patients and 32 months in surviving patients. No statistically significant differences were found in the end points measured in the two treatment groups. Specifically, the median survival time was 31 and 27 months and the 5-year overall survival rate was 33% and 30% in the C/S and CRT groups, respectively. Likewise, the 5-year local control (58% vs. 61%), disease-free (24% vs. 23%), and distant metastasis-free (44% vs. 36%) survival rates in the two groups were not significantly different. In the C/S group, postoperative RT significantly improved the 5-year local control rate from 33.8% to 81.5% (p = 0.007) but did not significantly improve overall survival. Additionally, patients in the C/S group whose disease responded to induction chemotherapy had a significantly improved 5-year overall survival rate (50%) compared with those who had stable or progressive disease (16%, p = 0001). Treatment of Stage IIIA NSCLC using either induction C/S or CRT resulted in similar outcomes in terms of local control and median overall, 5-year overall, distant metastasis-free, and disease-free survival. However, patients undergoing induction C/S often needed postoperative RT to achieve local control equivalent to that achieved with concurrent CRT. Advances in radiation-based treatment as reflected in this study have resulted in similar outcomes compared with modern induction C/S. To improve survival, however, newer systemic agents that reduce and control distant metastasis are required.

International Journal of Radiation Oncology Biology Physics, 2008

Purpose-To compare three-dimensional (3D) and 4D computed tomography (CT)-based treatment plans f... more Purpose-To compare three-dimensional (3D) and 4D computed tomography (CT)-based treatment plans for proton therapy or intensity-modulated radiation therapy (IMRT) for esophageal cancer in terms of doses to the lung, heart, and spinal cord and variations in target coverage and normal tissue sparing.

International Journal of Radiation Oncology Biology Physics, 2008

Purpose: To investigate the motion characteristics of distal esophagus cancer primary tumors usin... more Purpose: To investigate the motion characteristics of distal esophagus cancer primary tumors using four-dimensional computed tomography (4D CT). Methods and Materials: Thirty-one consecutive patients treated for esophagus cancer who received respiratorygated 4D CT imaging for treatment planning were selected. Deformable image registration was used to map the full expiratory motion gross tumor volume (GTV) to the full-inspiratory CT image, allowing quantitative assessment of each voxel's displacement. These displacements were correlated with patient tumor and respiratory characteristics. Results: The mean (SE) tidal volume was 608 (73) mL. The mean GTV volume was 64.3 (10.7) mL on expiration and 64.1 (10.7) mL on inspiration (no significant difference). The mean tumor motion in the x-direction was 0.13 (0.006) cm (average of absolute values), in the y-direction 0.23 (0.01) cm (anteriorly), and in the z-direction 0.71 (0.02) cm (inferiorly). Tumor motion correlated with tidal volume. Comparison of tumor motion above vs. below the diaphragm was significant for the average net displacement (p = 0.014), motion below the diaphragm was greater than above. From the cumulative distribution 95% of the tumors moved less than 0.80 cm radially and 1.75 cm inferiorly. Conclusions: Primary esophagus tumor motion was evaluated with 4D CT. According to the results of this study, when 4D CT is not available, a radial margin of 0.8 cm and axial margin of ±1.8 cm would provide tumor motion coverage for 95% of the cases in our study population. Ó

International Journal of Radiation Oncology Biology Physics, 2005

To compare treatment plans for multileaf collimators (MLCs) with different leaf widths and differ... more To compare treatment plans for multileaf collimators (MLCs) with different leaf widths and different finite pencil beam (FPB) sizes, to determine the planning quality and delivery efficiency of segmented MLC (SMLC) delivery of intensity-modulated radiation therapy (IMRT) for malignant pleural mesothelioma (MPM). Computerized tomography images of 10 right-side MPM patients were used for this planning study on a CORVUS treatment-planning system (NOMOS Corporation, Sewickley, PA) for a Varian Millennium 120-MLC (Varian Medical Systems, Palo Alto, CA). Three beam models were used. The first model forced two 0.5-cm MLC leaves to move in tandem to simulate a 1-cm leaf-width MLC and a FPB size of 1 x 1 cm2. The second model used 0.5-cm leaves with a FPB size of 0.5 x 1 cm2 (1 cm in the direction of leaf movement). The third model used 0.5-cm leaves, with a FPB size of 0.5 x 0.5 cm2. For optimization, the same dose constraints and beam parameters were used for each data set. Tissue heterogeneity corrections were used during optimization and dose calculation. Plans were optimized such that the clinical target volume received 50 Gy in 25 fractions. Dose distributions to the target and normal structures were evaluated. The number of monitor units, the number of segments, and delivery times were used to evaluate delivery efficiency. All three beam models could be used for IMRT planning for MPM. The doses to clinical target volume, spinal cord, lung, liver, heart, and contralateral kidney were acceptable with all three beam models. The 0.5 x 0.5-cm2 beam model used the most monitor units (6883 +/- 974 vs. 3332 +/- 406 and 3407 +/- 443 for the 1 x 1-cm2 and 0.5 x 1-cm2 models, respectively) and treated the most segments (4297 +/- 802 vs. 1357 +/- 156 and 1767 +/- 212 for the 1 x 1-cm2 and 0.5 x 1-cm2 models, respectively). The plan generated with the 1 x 1-cm2 model required the least amount of time to deliver. The quality of the MPM IMRT plans generated with the three beam models presented here was similar; however, the 1 x 1-cm2 model provided the most efficient delivery of MPM IMRT with the CORVUS planning system.