- Email: [email protected]
CT for Radiotherapy Treatment Planning: Can Target Volumes be Changed?
I. J. Radiation Oncology d Biology d Physics
S640
Volume 78, Number 3, Supplement, 2010
Purpose/Objective(s): The spread of intensity modulated radiotherapy enabled the decrease of the delivery dose for the parotid gland in head and neck cancers. Evaluation of parotid gland function after radiotherapy has been performed using salivary gland scintigraphy. However, it uses radionuclides. The use of radionuclides obviously means that radiation exposure for human bodies is unavoidable, and making this technique unsuitable for regular evaluation of parotid gland depression caused by radiotherapy. Therefore, the safety and quantitative evaluation for the parotid gland function has not been established. We selected equivalent cross-relaxation rate imaging (ECRI) applied magnetization transfer effect using MRI as a tool for evaluating the parotid gland function. ECRI can detect minute changes in organization and molecular structure. The aim is to determine that ECRI is a feasible method for evaluating function of the parotid gland. Materials/Methods: Subjects comprised 18 patients with head and neck cancer (nasopharynx/oropharynx = 16/2). The median patient age was 53 years, ranging from 16 to 74. They underwent ECRI and salivary gland scintigraphy. As for the acquisition of ECRI, the single saturation transfer pulse frequency was employed at the frequency 7 ppm downfield from the water resonance. ECR value was defined as the percentage of signal loss between unsaturated and saturated images. ECR value shows high values by the increase of cell density or by the decrease of extracellular component. We investigated correlations between ECR and maximum uptake rate (is functional parameter obtained by salivary gland scintigraphy) at the parotid gland before and after chemoradiotherapy. Next, we investigated simple linear correlations between percentage changes in ECR and maximum uptake rate (MUR) at 3-5 months after chemoradiotherapy and median dose to the parotid gland. Results: A correlation was detected between ECR and MUR (r = 0.55, p\0.01). Moreover, a significant correlation was identified between percentage change in ECR value at 3-5 months after chemoradiotherapy and median dose (= 19.8-26.5 Gy) to the parotid gland (Pearson correlation, r = 0.62, p\0.05). These results showed the utility of the evaluation and the possibility of the forecast of the parotid gland function. ECR values (average ± SD) were 30.0±19.9 in pre-radiated parotid gland and 53.3±22.5 in post-radiated parotid gland. ECR values were elevated in the post-radiated parotid gland with significant difference (p\0.01). This result showed the decrease of extracellular component in post-radiated parotid glands. Conclusions: ECRI allowed the evaluation of the function in the parotid gland without exposure to radiation. ECRI is new imaging tool for evaluating the post-radiated parotid gland function. Author Disclosure: H. Shimizu, None; S. Matsushima, None; Y. Kinosada, None; H. Miyamura, None; T. Kodaira, None.
2978
Bioluminescence Imaging for Orthotopic Tumor Monitoring and Image Guided Radiation in a Preclinical Pancreas Cancer Mouse Model
A. J. Surmak, R. Tuli, J. Reyes, M. Armour, D. Purger, E. Ford, E. Tryggestad, J. Wong, T. L. DeWeese, J. M. Herman Johns Hopkins University School of Medicine, Baltimore, MD Purpose/Objective(s): The role of radiation therapy (RT) for pancreatic adenocarcinoma remains controversial and incrementally beneficial partly due to non-standardized and clinically unsuitable preclinical radiation models. To help bridge this translational gap, we have applied our in-house small animal radiation research platform (SARRP) to pancreas cancer using bioluminescent orthotopic xenografts in mice. Herein, we compare bioluminescence imaging (BLI) to positron emission tomography (PET) as a quantitative, non-invasive method of monitoring these tumors and as a means of delivering image guided, focal RT. Materials/Methods: We utilized a luciferase-expressing MiaPaCa-2 human pancreatic carcinoma cell line to generate orthotopic pancreatic tumors in nude mice. After seven days, BLI and PET/CT were performed to identify primary tumors, estimate largest coronal cross-sectional tumor areas and correlate to pathologic specimens at necropsy using Pearson correlation. To assess feasibility of BLI as an ‘image-guidance’ tool for focal radiation delivery, offline images were manually registered to cone beam CT images on-board the SARRP to help identify the gross tumor volume. Double exposure images were obtained to confirm the site of treatment prior to delivery of a single fraction of 10 Gy to the tumor with a beam diameter of 10 mm. One-hour post-treatment, mice were perfusion-fixed and stained with hematoxylin and eosin and gH2Ax antibodies to confirm accurate RT delivery. Results: Whole-body BLI and PET/CT correlated well with each other (p = .0004), as well as corresponding pathologic specimen (p = .02, BLI; p = .04, PET), in the quantitative assessment of tumor area. Both modalities were similarly sensitive in detecting the presence of metastatic lesions as confirmed pathologically at time of necropsy. Animal immobilization and positioning were faithfully recapitulated to allow accurate fusion of BLI and CT images. Double exposure images confirmed radiation was delivered to the site of luminescence in the abdomen. Conclusions: Our studies confirm the ability to deliver focal RT to orthotopic pancreatic tumors in mice using both molecular (BLI) and anatomic (cone-beam CT) imaging. BLI is a facile, cost-effective surrogate for PET/CT and facilitates accurate delineation of target regions and ‘image guided’ RT. It also allows for normalization of pre-treatment tumor burden and quantitative, non-invasive monitoring of tumor progression in real time. We believe this standardized, preclinical RT platform will allow us to begin to mimic contemporary human treatment. Future studies will aim for more conformal targeting of tumors. Author Disclosure: A.J. Surmak, None; R. Tuli, None; J. Reyes, None; M. Armour, None; D. Purger, None; E. Ford, None; E. Tryggestad, None; J. Wong, None; T.L. DeWeese, None; J.M. Herman, None.
2979
The Value of PET/CT for Radiotherapy Treatment Planning: Can Target Volumes be Changed?
G. N. Marta, S. A. Hanna, C. M. K. Haddad, J. F. Da Silva Hospital Sı´rio-Libaneˆs, Sa˜o Paulo, Brazil Purpose/Objective(s): PET/CT provides functional/metabolic information through a range of colors overlapping the morphologic images from tomography (CT). This information may be included in radiotherapy treatment planning since the image acquisition is in the same treatment position. The aims of this study are: (a) analyze eventual gains obtained from radiotherapy planning using PET/CT information; (b) Assess the change in target volume with the use of PET/CT when compared with CT without PET.
Proceedings of the 52nd Annual ASTRO Meeting Materials/Methods: Between July 2003 and July 2009 we retrospectively reviewed data from 105 patients who underwent simulation with PET/CT were treated with RT in a single institution. The following variables were collected: gender; tumor site; clinical target volume (CTV) defined with CT without PET and with PET/CT. Descriptive analysis were made using simple frequencies and percentages tables, with calculation of descriptive measures such as mean, standard deviation (SD), median and interquartile range (IQR). The package MedCalc, version 9.6.4.0 (Mariakerke, Belgium) was used for statistical analysis. The Kolmogorov-Smirnov test was used to verify the normality of the distribution of numerical variables. As the samples were paired comparisons between groups were made by VTC Wilcoxon test. Categorical variables were compared by chi-square test. Results: There were 46 male and 59 female patients. Treated sites were lung (n = 23), lymphoma (n = 12), head and neck (n = 30), high gastrointestinal tract (n = 11), low gastrointestinal tract (n = 9), genitourinary tract (n = 4), breast (n = 4), gynecological tract (n = 6) and others (n = 6). PET/CT changed 77.1% of the treatment plannings (39% increase and 38.1% decrease in CTV volumes) maintaining unchanged 22.9%. When analyzed the influence of PET/CT in defining the CTV according to tumor site, there were only a trend toward a significant change in the median CTVs from lung - from 65,8cm3 (IQR 23,77 - 146,02) to 54cm3 (IQR 23,47 - 93,95), p = 0,06 - and lymphoma - from 241,9cm3 (IQR 144,2 - 350,65) to 194,25cm3 (IQR 100,1 334,95), p = 0,06 - cases. However when grouped these lung and lymphoma cases plus head and neck ones the change in the CTV was significant: from 112.5 (IQR 45.6 - 205.7) cm3 to 80.7 (IQR 37.8 - 158.2) cm3, CI 95%, p = 0.0053 (Wilcoxon test). Conclusions: Target volume definitions with PET/CT may add information for radiotherapy treatment planning and should be considered mainly in head and neck, lung and lymphoma. More follow-up and prospective analysis are necessary to strength these findings. Author Disclosure: G.N. Marta, None; S.A. Hanna, None; C.M.K. Haddad, None; J.F. Da Silva, None.
2980
Dosimetric Comparison of the Simulation Treatment Planning of FLT and FDG PET-CT in Contouring the Biological Tumor Volume in Patients with Thoracic Esophageal Carcinoma
D. Han, J. Yu, G. Zhang, J. Lu, Z. Fu, W. Yang Shandong Cancer Hospital and Institute, Jinan City, China Purpose/Objective(s): Use the optimal method of 3-deoxy-3-18F-fluorothymidine (FLT) PET-CT to delineate biological tumor volume in thoracic esophageal carcinoma and make treatment planning for simulation, then compare with that of 18F-fluorodeoxyglucose(FDG) on the basis of dosimetric analysis. Materials/Methods: Twenty-two patients with esophageal squamous cell carcinoma detected by FLT and FDG PET-CT were enrolled. We used Treatment Planning System to compare the simulation treatment planning based on the optimal threshold of FLT and FDG PET-CT, respectively. According to the same standard expanded GTV to CTV and PTV. The radiation dose was prescribed as 60 Gy in 30 fractions with conformal or intensity modulated radiotherapy technique, the same patient using the same radiotherapy technique such as a five-beam CRT or seven-field IMRT. We compared parameters in dose-volume histograms of two groups planning which fields in the similar direction and ensuring prescribed dose line surround 95% target volume. SPSS 13.0 (SPSS, version 13.0; SPSS Inc.) was used for statistical analysis. The t test was used to assess the differences between groups. A p value of \0.05 was considered statistically significant. Results: GTV, CTV and PTV in FLT PET-CT imaging are less than those of FDG (All p value less than 0.05). There are no significantly difference in conformity index (CI) and homogeneity index (HI) between FLT and FDG PET-CT planning (Both p value more than 0.05). The difference in V20 of bilateral lung, V40 of heart and maximal dose received by spinal cord between FLT and FDG were not significantly (All p value more than 0.05). While, the values in MLD, V5, V10, V30, V40 and V50 of bilateral lung, MHD, and V30 of heart on FLT PET-CT based planning were significant lower than that of FDG(All p value less than 0.05). Conclusions: FLT PET-CT based treatment planning brought potential benefits to some OARs such as lungs and heart. [Key words] Esophageal neoplasms/radiotherapy; Tomography, positron emission; 3-deoxy-3-fluorothymidine; Biological tumor volumes; Dosimetry Author Disclosure: D. Han, None; J. Yu, None; G. Zhang, None; J. Lu, None; Z. Fu, None; W. Yang, None.
2981
X-ray Activated Optical Contrast Agents for Simultaneous Anatomical/Functional CT Imaging
G. Pratx, C. M. Carpenter, C. Sun, R. Rao, L. Xing Stanford University, CA, CA Purpose/Objective(s): X-ray luminescence computed tomography (XLCT) is proposed as a new molecular imaging modality for imaging X-ray-excitable phosphorescent nanoparticles three-dimensionally, in living subjects. These nano-sized tracers can be targeted to study response to radiation therapy in small animal models. In this modality, anatomical and functional information can be acquired and visualized simultaneously. Materials/Methods: The imaging mechanism used in XLCT consists in irradiating the subject using a sequence of programmed X-ray beams, while sensitive photo-detectors measure the light produced by the nanophosphors. By restricting the X-ray excitation to a single, narrow beam of radiation, the origin of the light photons can be inferred regardless of where these photons were detected, and how many times they scattered in tissue. Near-infrared (NIR) emitting phosphors are best suited for XLCT because NIR light propagates the furthest in biological tissues. By including an X-ray detector in the system, anatomical imaging is performed simultaneously with molecular imaging via standard X-ray computed tomography. The molecular and anatomical images are spatially and temporally co-registered. Simulations of an XLCT system were performed using an analytical beam model. Several real experiments were also conducted with various tissue-mimicking phantoms using a superficial
S641
S640
Volume 78, Number 3, Supplement, 2010
Purpose/Objective(s): The spread of intensity modulated radiotherapy enabled the decrease of the delivery dose for the parotid gland in head and neck cancers. Evaluation of parotid gland function after radiotherapy has been performed using salivary gland scintigraphy. However, it uses radionuclides. The use of radionuclides obviously means that radiation exposure for human bodies is unavoidable, and making this technique unsuitable for regular evaluation of parotid gland depression caused by radiotherapy. Therefore, the safety and quantitative evaluation for the parotid gland function has not been established. We selected equivalent cross-relaxation rate imaging (ECRI) applied magnetization transfer effect using MRI as a tool for evaluating the parotid gland function. ECRI can detect minute changes in organization and molecular structure. The aim is to determine that ECRI is a feasible method for evaluating function of the parotid gland. Materials/Methods: Subjects comprised 18 patients with head and neck cancer (nasopharynx/oropharynx = 16/2). The median patient age was 53 years, ranging from 16 to 74. They underwent ECRI and salivary gland scintigraphy. As for the acquisition of ECRI, the single saturation transfer pulse frequency was employed at the frequency 7 ppm downfield from the water resonance. ECR value was defined as the percentage of signal loss between unsaturated and saturated images. ECR value shows high values by the increase of cell density or by the decrease of extracellular component. We investigated correlations between ECR and maximum uptake rate (is functional parameter obtained by salivary gland scintigraphy) at the parotid gland before and after chemoradiotherapy. Next, we investigated simple linear correlations between percentage changes in ECR and maximum uptake rate (MUR) at 3-5 months after chemoradiotherapy and median dose to the parotid gland. Results: A correlation was detected between ECR and MUR (r = 0.55, p\0.01). Moreover, a significant correlation was identified between percentage change in ECR value at 3-5 months after chemoradiotherapy and median dose (= 19.8-26.5 Gy) to the parotid gland (Pearson correlation, r = 0.62, p\0.05). These results showed the utility of the evaluation and the possibility of the forecast of the parotid gland function. ECR values (average ± SD) were 30.0±19.9 in pre-radiated parotid gland and 53.3±22.5 in post-radiated parotid gland. ECR values were elevated in the post-radiated parotid gland with significant difference (p\0.01). This result showed the decrease of extracellular component in post-radiated parotid glands. Conclusions: ECRI allowed the evaluation of the function in the parotid gland without exposure to radiation. ECRI is new imaging tool for evaluating the post-radiated parotid gland function. Author Disclosure: H. Shimizu, None; S. Matsushima, None; Y. Kinosada, None; H. Miyamura, None; T. Kodaira, None.
2978
Bioluminescence Imaging for Orthotopic Tumor Monitoring and Image Guided Radiation in a Preclinical Pancreas Cancer Mouse Model
A. J. Surmak, R. Tuli, J. Reyes, M. Armour, D. Purger, E. Ford, E. Tryggestad, J. Wong, T. L. DeWeese, J. M. Herman Johns Hopkins University School of Medicine, Baltimore, MD Purpose/Objective(s): The role of radiation therapy (RT) for pancreatic adenocarcinoma remains controversial and incrementally beneficial partly due to non-standardized and clinically unsuitable preclinical radiation models. To help bridge this translational gap, we have applied our in-house small animal radiation research platform (SARRP) to pancreas cancer using bioluminescent orthotopic xenografts in mice. Herein, we compare bioluminescence imaging (BLI) to positron emission tomography (PET) as a quantitative, non-invasive method of monitoring these tumors and as a means of delivering image guided, focal RT. Materials/Methods: We utilized a luciferase-expressing MiaPaCa-2 human pancreatic carcinoma cell line to generate orthotopic pancreatic tumors in nude mice. After seven days, BLI and PET/CT were performed to identify primary tumors, estimate largest coronal cross-sectional tumor areas and correlate to pathologic specimens at necropsy using Pearson correlation. To assess feasibility of BLI as an ‘image-guidance’ tool for focal radiation delivery, offline images were manually registered to cone beam CT images on-board the SARRP to help identify the gross tumor volume. Double exposure images were obtained to confirm the site of treatment prior to delivery of a single fraction of 10 Gy to the tumor with a beam diameter of 10 mm. One-hour post-treatment, mice were perfusion-fixed and stained with hematoxylin and eosin and gH2Ax antibodies to confirm accurate RT delivery. Results: Whole-body BLI and PET/CT correlated well with each other (p = .0004), as well as corresponding pathologic specimen (p = .02, BLI; p = .04, PET), in the quantitative assessment of tumor area. Both modalities were similarly sensitive in detecting the presence of metastatic lesions as confirmed pathologically at time of necropsy. Animal immobilization and positioning were faithfully recapitulated to allow accurate fusion of BLI and CT images. Double exposure images confirmed radiation was delivered to the site of luminescence in the abdomen. Conclusions: Our studies confirm the ability to deliver focal RT to orthotopic pancreatic tumors in mice using both molecular (BLI) and anatomic (cone-beam CT) imaging. BLI is a facile, cost-effective surrogate for PET/CT and facilitates accurate delineation of target regions and ‘image guided’ RT. It also allows for normalization of pre-treatment tumor burden and quantitative, non-invasive monitoring of tumor progression in real time. We believe this standardized, preclinical RT platform will allow us to begin to mimic contemporary human treatment. Future studies will aim for more conformal targeting of tumors. Author Disclosure: A.J. Surmak, None; R. Tuli, None; J. Reyes, None; M. Armour, None; D. Purger, None; E. Ford, None; E. Tryggestad, None; J. Wong, None; T.L. DeWeese, None; J.M. Herman, None.
2979
The Value of PET/CT for Radiotherapy Treatment Planning: Can Target Volumes be Changed?
G. N. Marta, S. A. Hanna, C. M. K. Haddad, J. F. Da Silva Hospital Sı´rio-Libaneˆs, Sa˜o Paulo, Brazil Purpose/Objective(s): PET/CT provides functional/metabolic information through a range of colors overlapping the morphologic images from tomography (CT). This information may be included in radiotherapy treatment planning since the image acquisition is in the same treatment position. The aims of this study are: (a) analyze eventual gains obtained from radiotherapy planning using PET/CT information; (b) Assess the change in target volume with the use of PET/CT when compared with CT without PET.
Proceedings of the 52nd Annual ASTRO Meeting Materials/Methods: Between July 2003 and July 2009 we retrospectively reviewed data from 105 patients who underwent simulation with PET/CT were treated with RT in a single institution. The following variables were collected: gender; tumor site; clinical target volume (CTV) defined with CT without PET and with PET/CT. Descriptive analysis were made using simple frequencies and percentages tables, with calculation of descriptive measures such as mean, standard deviation (SD), median and interquartile range (IQR). The package MedCalc, version 9.6.4.0 (Mariakerke, Belgium) was used for statistical analysis. The Kolmogorov-Smirnov test was used to verify the normality of the distribution of numerical variables. As the samples were paired comparisons between groups were made by VTC Wilcoxon test. Categorical variables were compared by chi-square test. Results: There were 46 male and 59 female patients. Treated sites were lung (n = 23), lymphoma (n = 12), head and neck (n = 30), high gastrointestinal tract (n = 11), low gastrointestinal tract (n = 9), genitourinary tract (n = 4), breast (n = 4), gynecological tract (n = 6) and others (n = 6). PET/CT changed 77.1% of the treatment plannings (39% increase and 38.1% decrease in CTV volumes) maintaining unchanged 22.9%. When analyzed the influence of PET/CT in defining the CTV according to tumor site, there were only a trend toward a significant change in the median CTVs from lung - from 65,8cm3 (IQR 23,77 - 146,02) to 54cm3 (IQR 23,47 - 93,95), p = 0,06 - and lymphoma - from 241,9cm3 (IQR 144,2 - 350,65) to 194,25cm3 (IQR 100,1 334,95), p = 0,06 - cases. However when grouped these lung and lymphoma cases plus head and neck ones the change in the CTV was significant: from 112.5 (IQR 45.6 - 205.7) cm3 to 80.7 (IQR 37.8 - 158.2) cm3, CI 95%, p = 0.0053 (Wilcoxon test). Conclusions: Target volume definitions with PET/CT may add information for radiotherapy treatment planning and should be considered mainly in head and neck, lung and lymphoma. More follow-up and prospective analysis are necessary to strength these findings. Author Disclosure: G.N. Marta, None; S.A. Hanna, None; C.M.K. Haddad, None; J.F. Da Silva, None.
2980
Dosimetric Comparison of the Simulation Treatment Planning of FLT and FDG PET-CT in Contouring the Biological Tumor Volume in Patients with Thoracic Esophageal Carcinoma
D. Han, J. Yu, G. Zhang, J. Lu, Z. Fu, W. Yang Shandong Cancer Hospital and Institute, Jinan City, China Purpose/Objective(s): Use the optimal method of 3-deoxy-3-18F-fluorothymidine (FLT) PET-CT to delineate biological tumor volume in thoracic esophageal carcinoma and make treatment planning for simulation, then compare with that of 18F-fluorodeoxyglucose(FDG) on the basis of dosimetric analysis. Materials/Methods: Twenty-two patients with esophageal squamous cell carcinoma detected by FLT and FDG PET-CT were enrolled. We used Treatment Planning System to compare the simulation treatment planning based on the optimal threshold of FLT and FDG PET-CT, respectively. According to the same standard expanded GTV to CTV and PTV. The radiation dose was prescribed as 60 Gy in 30 fractions with conformal or intensity modulated radiotherapy technique, the same patient using the same radiotherapy technique such as a five-beam CRT or seven-field IMRT. We compared parameters in dose-volume histograms of two groups planning which fields in the similar direction and ensuring prescribed dose line surround 95% target volume. SPSS 13.0 (SPSS, version 13.0; SPSS Inc.) was used for statistical analysis. The t test was used to assess the differences between groups. A p value of \0.05 was considered statistically significant. Results: GTV, CTV and PTV in FLT PET-CT imaging are less than those of FDG (All p value less than 0.05). There are no significantly difference in conformity index (CI) and homogeneity index (HI) between FLT and FDG PET-CT planning (Both p value more than 0.05). The difference in V20 of bilateral lung, V40 of heart and maximal dose received by spinal cord between FLT and FDG were not significantly (All p value more than 0.05). While, the values in MLD, V5, V10, V30, V40 and V50 of bilateral lung, MHD, and V30 of heart on FLT PET-CT based planning were significant lower than that of FDG(All p value less than 0.05). Conclusions: FLT PET-CT based treatment planning brought potential benefits to some OARs such as lungs and heart. [Key words] Esophageal neoplasms/radiotherapy; Tomography, positron emission; 3-deoxy-3-fluorothymidine; Biological tumor volumes; Dosimetry Author Disclosure: D. Han, None; J. Yu, None; G. Zhang, None; J. Lu, None; Z. Fu, None; W. Yang, None.
2981
X-ray Activated Optical Contrast Agents for Simultaneous Anatomical/Functional CT Imaging
G. Pratx, C. M. Carpenter, C. Sun, R. Rao, L. Xing Stanford University, CA, CA Purpose/Objective(s): X-ray luminescence computed tomography (XLCT) is proposed as a new molecular imaging modality for imaging X-ray-excitable phosphorescent nanoparticles three-dimensionally, in living subjects. These nano-sized tracers can be targeted to study response to radiation therapy in small animal models. In this modality, anatomical and functional information can be acquired and visualized simultaneously. Materials/Methods: The imaging mechanism used in XLCT consists in irradiating the subject using a sequence of programmed X-ray beams, while sensitive photo-detectors measure the light produced by the nanophosphors. By restricting the X-ray excitation to a single, narrow beam of radiation, the origin of the light photons can be inferred regardless of where these photons were detected, and how many times they scattered in tissue. Near-infrared (NIR) emitting phosphors are best suited for XLCT because NIR light propagates the furthest in biological tissues. By including an X-ray detector in the system, anatomical imaging is performed simultaneously with molecular imaging via standard X-ray computed tomography. The molecular and anatomical images are spatially and temporally co-registered. Simulations of an XLCT system were performed using an analytical beam model. Several real experiments were also conducted with various tissue-mimicking phantoms using a superficial
S641