[Show abstract][Hide abstract] ABSTRACT: The practice of treating a solitary pulmonary nodule (SPN) suspicious for stage I non-small cell lung cancer (NSCLC) with stereotactic ablative radiotherapy (SABR) in the absence of pathology, is growing. In the absence of randomized evidence, the appropriate prior probability threshold of lung cancer of when such a strategy is warranted can be informed using decision analysis.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to evaluate the sliced body volume (SBV) as a respiratory surrogate by comparing with the real-time position management (RPM) in phantom and patient cases. Using the SBV surrogate, breathing signals were extracted from unsorted 4D CT images of a motion phantom and 31 cancer patients (17 lung cancers, 14 abdominal cancers) and were compared to those clinically acquired using the RPM system. Correlation coefficient (R), phase difference (D), and absolute phase difference (DA) between the SBV-derived breathing signal and the RPM signal were calculated. 4D CT reconstructed based on the SBV surrogate (4D CTSBV) were compared to those clinically generated based on RPM (4D CTRPM). Image quality of the 4D CT were scored (SSBV and SRPM, respectively) from 1 to 5 (1 is the best) by experienced evaluators. The comparisons were performed for all patients, and for the lung cancer patients and the abdominal cancer patients separately. RPM box position (P), breathing period (T), amplitude (A), period variability (VT), amplitude variability (VA), and space-dependent phase shift (F) were determined and correlated to SSBV. The phantom study showed excellent match between the SBV-derived breathing signal and the RPM signal (R = 0.99, D= -3.0%, DA = 4.5%). In the patient study, the mean (± standard deviation (SD)) R, D, DA, T, VT, A, VA, and F were 0.92 (± 0.05), -3.3% (± 7.5%), 11.4% (± 4.6%), 3.6 (± 0.8) s, 0.19 (±0.10), 6.6 (± 2.8) mm, 0.20 (± 0.08), and 0.40 (± 0.18) s, respectively. Significant differences in R and DA (p = 0.04 and 0.001, respectively) were found between the lung cancer patients and the abdominal cancer patients. 4D CTRPM slightly outperformed 4D CTSBV: the mean (±SD) SRPM and SSBV were 2.6 (± 0.6) and 2.9 (± 0.8), respectively, for all patients, 2.5 (± 0.6) and 3.1 (± 0.8), respectively, for the lung cancer patients, and 2.6 (±0.7) and 2.8 (± 0.9), respectively, for the abdominal cancer patients. The difference between SRPM and SSBV was insignificant for the abdominal patients (p = 0.59). F correlated moderately with SSBV (r = 0.72). The correlation between SBV-derived breathing signal and RPM signal varied between patients and was significantly better in the abdomen than in the thorax. Space-dependent phase shift is a limiting factor of the accuracy of the SBV surrogate.
Journal of Applied Clinical Medical Physics 01/2013; 14(1):3987. · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: To investigate the necessity for adaptive radiation therapy (RT) in lung cancer IMRT treatments by quantifying tumor changes during radiotherapy and the associated impact on target, lung and esophagus. Methods: As part of an IRB-approved lung dose escalation study, contrasted CT scans were acquired on 15 patients prior to RT and in the 2nd and 5th week of treatment (total dose=58-70 Gy, 2Gy/fraction). Target, lung and esophagus volumes were segmented in all CT datasets. The original plan was recomputed on the subsequent CT sets and doses were accumulated by deformable registration to approximate the actual delivery. Five patients with the largest tumor shrinkage were selected and re-planned on the 2nd and 5th week CT sets. The plans were summed to mimic adaptive radiation therapy. Comparisons were made between the approximated actual treatment, summation of the re-optimized plans, and the original plan. Comparison metrics included QUANTEC dose parameters, equivalent uniform dose (EUD), maximum dose and target coverage (unless otherwise stated, all percentage changes in results are with respect to the original plan, averaged over all patients). Results: The approximated actual delivery had significantly increased lung dose- volume/EUD (V5 =8.19%, V20 = 4.14%, EUD = 5.95%). Tumor shrinkage- induced esophageal volume outside the originally segmented volume (3.4%-101.8%) was significant. Elevated esophagus EUD (7.27%) and spinal cord maximum dose (6.7%) were observed in most patients. PTV/GTV volumes receiving 100% of prescription dose decreased (week 2/5 PTV = -10.0%/- 6.88%, week 2/5 GTV = -6.7%/-4.1%), along with slightly increased dose to the highest 1 % of volume. Compared to the approximated actual delivery, re-optimized plans overall showed superiority in lowered dose to the esophagus (V35=-40.32%, EUD =-13.42%), lungs (V5=-4.18%, V20=- 10.66%) and spinal cord (Dmax=-22.98%). Conclusions: RT-induced esophageal volume displacement and increased lung dose during treatment are significant, warranting re-plan in cases where large tumor changes are expected.
Medical Physics 06/2012; 39(6):3986. · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine whether there is a CT dataset may be more favorable for planning and dose calculation by comparing dosimetric characteristics between treatment plans calculated using free breathing (FB), maximum and average intensity projection (MIP and AIP, respectively) CTs for lung cancer patients receiving stereotactic body radiation therapy (SBRT).
Twenty lung cancer SBRT patients, treated on a linac with 2.5 mm width multileaf-collimator (MLC), were analyzed retrospectively. Both FB helical and four-dimensional CT scans were acquired for each patient. Internal target volume (ITV) was delineated based on MIP CTs and modified based on both ten-phase datasets and FB CTs. Planning target volume (PTV) was then determined by adding additional setup margin to ITV. The PTVs and beams in the optimized treatment plan based on FB CTs were copied to MIP and AIP CTs, with the same isocenters, MLC patterns and monitor units. Mean effective depth (MED) of beams, and some dosimetric parameters for both PTVs and most important organ at risk (OAR), lung minus PTV, were compared between any two datasets using two-tail paired t test.
The MEDs in FB and AIP plans were similar but significantly smaller (Ps < 0.001) than that in MIP plans. Minimum dose, mean dose, dose covering at least 90% and 95% of PTVs in MIP plans were slightly higher than two other plans (Ps < 0.008). The absolute volume of lung minus PTV receiving greater than 5, 10, and 20 Gy in MIP plans were significantly smaller than those in both FB and AIP plans (Ps < 0.008). Conformity index for FB plans showed a small but statistically significantly higher.
Dosimetric characteristics of AIP plans are similar to those of FB plans. Slightly better target volume coverage and significantly lower low-dose region (≤30 Gy) in lung was observed in MIP plans. The decrease in low-dose region in lung was mainly caused by the change of lung volume contoured on two datasets rather than the differences of dose distribution between AIP and MIP plans. Compare with AIP datasets, FB datasets were more prone to significant image artifacts and MIP datasets may overestimate or underestimate the target volume when the target is closer to the denser tissue, so AIP seems favorable for planning and dose calculation for lung SBRT.
Medical Physics 05/2012; 39(5):2754-60. · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study the temporal nature of regional lung density changes and to assess whether the dose-dependent nature of these changes is associated with patient- and treatment-associated factors.
Between 1991 and 2004, 118 patients with interpretable pre- and post-radiation therapy (RT) chest computed tomography (CT) scans were evaluated. Changes in regional lung density were related to regional dose to define a dose-response curve (DRC) for RT-induced lung injury using three-dimensional planning tools and image fusion. Multiple post-RT follow-up CT scans were evaluated by fitting linear-quadratic models of density changes on dose with time as the covariate. Various patient- and treatment-related factors were examined as well.
There was a dose-dependent increase in regional lung density at nearly all post-RT follow-up intervals. The population volume-weighted changes evolved over the initial 6-month period after RT and reached a plateau thereafter (p < 0.001). On univariate analysis, patient age greater than 65 years (p = 0.003) and/or the use of pre-RT surgery (p < 0.001) were associated with significantly greater changes in CT density at both 6 and 12 months after RT, but the magnitude of this effect was modest.
There appears to be a temporal nature for the dose-dependent increases in lung density. Nondosimetric clinical factors tend to have no, or a modest, impact on these changes.
International journal of radiation oncology, biology, physics 04/2009; 76(1):116-22. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the association between radiotherapy (RT)-induced changes in computed tomography (CT)-defined lung tissue density and pulmonary function tests (PFTs).
Patients undergoing incidental partial lung RT were prospectively assessed for global (PFTs) and regional (CT and single photon emission CT [SPECT]) lung function before and, serially, after RT. The percent reductions in the PFT and the average changes in lung density were compared (Pearson correlations) in the overall group and subgroups stratified according to various clinical factors. Comparisons were also made between the CT- and SPECT-based computations using the Mann-Whitney U test.
Between 1991 and 2004, 343 patients were enrolled in this study. Of these, 111 patients had a total of 203 concurrent post-RT evaluations of changes in lung density and PFTs available for the analyses, and 81 patients had a total of 141 concurrent post-RT SPECT images. The average increases in lung density were related to the percent reductions in the PFTs, albeit with modest correlation coefficients (range, 0.20-0.43). The analyses also indicated that the association between lung density and PFT changes is essentially equivalent to the corresponding association with SPECT-defined lung perfusion.
We found a weak quantitative association between the degree of increase in lung density as defined by CT and the percent reduction in the PFTs.
International journal of radiation oncology, biology, physics 01/2009; 74(3):781-9. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the safety and efficacy of intensity-modulated radiotherapy (IMRT) after extrapleural pneumonectomy for malignant pleural mesothelioma.
Thirteen patients underwent IMRT after extrapleural pneumonectomy between July 2005 and February 2007 at Duke University Medical Center. The clinical target volume was defined as the entire ipsilateral hemithorax, chest wall incisions, including drain sites, and involved nodal stations. The dose prescribed to the planning target volume was 40-55 Gy (median, 45). Toxicity was graded using the modified Common Toxicity Criteria, and the lung dosimetric parameters from the subgroups with and without pneumonitis were compared. Local control and survival were assessed.
The median follow-up after IMRT was 9.5 months. Of the 13 patients, 3 (23%) developed Grade 2 or greater acute pulmonary toxicity (during or within 30 days of IMRT). The median dosimetric parameters for those with and without symptomatic pneumonitis were a mean lung dose (MLD) of 7.9 vs. 7.5 Gy (p = 0.40), percentage of lung volume receiving 20 Gy (V(20)) of 0.2% vs. 2.3% (p = 0.51), and percentage of lung volume receiving 5 Gy (V(20)) of 92% vs. 66% (p = 0.36). One patient died of fatal pulmonary toxicity. This patient received a greater MLD (11.4 vs. 7.6 Gy) and had a greater V(20) (6.9% vs. 1.9%), and V(5) (92% vs. 66%) compared with the median of those without fatal pulmonary toxicity. Local and/or distant failure occurred in 6 patients (46%), and 6 patients (46%) were alive without evidence of recurrence at last follow-up.
With limited follow-up, 45-Gy IMRT provides reasonable local control for mesothelioma after extrapleural pneumonectomy. However, treatment-related pulmonary toxicity remains a significant concern. Care should be taken to minimize the dose to the remaining lung to achieve an acceptable therapeutic ratio.
International Journal of Radiation OncologyBiologyPhysics 08/2008; 71(4):1143-50. · 4.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Radiation therapy (RT) is an important treatment modality for multiple thoracic malignancies. Incidental irradiation of the lungs, which are particularly susceptible to injury, is unavoidable and often dose-limiting. The most radiosensitive subunit of the lung is the alveolar/capillary complex, and RT-induced lung injury is often described as diffuse alveolar damage. Reactive oxygen species generated by RT are directly toxic to parenchymal cells and initiate a cascade of molecular events that alter the cytokine milieu of the microenvironment, creating a self-sustaining cycle of inflammation and chronic oxidative stress. Replacement of normal lung parenchyma by fibrosis is the culminating event. Depending on the dose and volume of lung irradiated, acute radiation pneumonitis may develop, characterized by dry cough and dyspnea. Fibrosis of the lung, which can also cause dyspnea, is the late complication. Imaging studies and pulmonary function tests can be used to quantify the extent of lung injury. While strict dose-volume constraints to minimize the risk of injury are difficult to impose, substantial data support some general guidelines. New modalities such as intensity-modulated radiation therapy and stereotactic body radiation therapy provide new treatment options but also pose new challenges in safely delivering thoracic RT.