- Email: [email protected]
Contrast-enhanced Synchrotron Stereotactic Radiotherapy Clinical Trials from a Medical Physicist Point of View
S16
International Journal of Radiation Oncology Biology Physics
QC, Canada, 6CHR Trois-Rivie`res, Trois-Rivie`res, QC, Canada, 7Centre de Sante´ et Services Sociaux de Chicoutimi, Chicoutimi, QC, Canada, 8 Hoˆpital Ge´ne´ral Juif de Montre´al, Montre´al, QC, Canada, 9Hoˆpital de Gatineau, Gatineau, QC, Canada, 10Hoˆpital Maisonneuve-Rosemont de Montre´al, Montre´al, QC, Canada
contrast agents. The radiation dose enhancement depends on the amount of iodine in the tumor and its time course. Quantitative, post-infusion iodine bio-distribution and associated brain perfusion parameters were studied in human brain metastasis as key parameters for treatment feasibility and quality. The reproducibility of iodine concentrations between the recruitment day and the treatment day was assessed in order to predict dose errors. Materials/Methods: Twelve patients received an intravenous bolus of iodinated contrast agent (40 mL, 4 mL/s), followed by a steady-state infusion (160 mL, 0.5 mL/s) in order to ensure stable intratumoral amounts of iodine during the treatment. Absolute iodine concentrations and quantitative perfusion maps were derived from 40 multi-slice dynamic conventional CT images of the brain (recruitment day) or from quantitative synchrotron radiation CT (treatment day). For three of these patients, iodine concentrations reached in the tumor were compared between the recruitment day and the treatment day (w10 days interval). Results: The post-infusion mean intratumoral iodine concentration (over thirty minutes) reached 1.94 0.12 mg/mL. Reasonable correlations were obtained between these concentrations and the permeability surface area product and the cerebral blood volume. Iodine concentrations were reproducible leading to dose errors in the radiotherapy standards. Conclusions: To our knowledge, this is the first quantitative study of contrast agent biodistribution versus time in brain metastasis. The study demonstrates that suitable and stable amounts of iodine can be reached in brain metastasis for SSRT treatment. Moreover, the associated perfusion measurements provide useful information for the patient recruitment and management processes. Author Disclosure: L. Obeid: None. P. Deman: None. T. Alexandre: None. J. Balosso: None. F. Este`ve: None. J.F. Adam: None.
Purpose/Objective(s): In a previous report from a randomized trial, we showed that 18 months of androgen deprivation therapy (18 mos ADT) appears to be equally effective as 36 months (36 mos ADT) in high risk prostate cancer (HRPC) patients. This current analysis was performed to evaluate quality of life (QOL) after testosterone recovery in patients treated in that multicentric randomized phase III trial (PCS IV clinical trials, Gov. # NCT 00223171). Materials/Methods: Patients were randomized to radiotherapy (RT) plus either 36 mos ADT or 18 mos ADT. QOL was assessed by two validated tools: EORTC30 (30 items) and PR25 (25 items). The 55 items were regrouped into 21 scales. All items and scales scores were linearly transformed to a 0-100 points scale. Serum testosterone was measured at baseline then at each visit. Abnormal testosterone was defined as below the normal level. Time to testosterone recovery between arms was compared with Kaplan-Meier and log-rank test. All items and scales scores were analyzed with general linear model and repeated measures to evaluate changes between patients who did versus those who did not recover normal levels of testosterone over time. P-value < 0.01 was considered statistically significant and a difference in mean scores of 10 points was considered clinically relevant. Patient-reported outcomes were filled out before treatments, every 6 months during ADT, 4 months after ADT and then once a year for 5 years. For patients who developed biochemical failure, QOL evaluation ceased at the time of a new course of ADT. Results: Five hundred sixty-one patients were retained for the analysis (69 patients excluded: 46 no baseline testosterone and 23 only baseline testosterone). With a median follow-up of 84 months, 283/561 (50.9%) patients recovered normal testosterone level: 161/289 (55.7%) in 18 mos ADT and 122/272 (44.9%) in 36 mos ADT, p Z 0.01. The median time to testosterone recovery is shorter in 18 mos ADT than 36 mos ADT: 47.2 (40.1-54.3) vs 73.2 (58.3-88.2) months, p < 0.001.The global adherence to QOL questionnaires was 72.3% (10172/14062) and was similar between arms. When comparing QOL between patients who recovered with those who did not recover normal testosterone, patients with testosterone recovery had a better QOL: 26/55 items and 12/21 scales were statistically significant. Similarly, 5/26 items and 1/21 scales which reached statistical significance, were also clinically relevant. Conclusions: In HRPC treated with RT and ADT, patients who recover a normal testosterone level have a significantly better quality of life. There is a major advantage for the use of 18 mos ADT vs 36 mos ADT since a higher proportion of patients recover a normal testosterone level in a much shorter time without apparent detriment in long term outcomes. Acknowledgment: This research was supported by AstraZeneca Pharmaceuticals. Author Disclosure: A. Nabid: E. Research Grant; AstraZeneca. F. Honoraria; Sanofi. I. Travel Expenses; Sanofi. N. Carrier: None. A. Martin: None. J. Bahary: None. L. Souhami: None. M. Duclos: None. F. Vincent: None. S. Vass: None. B. Bahoric: None. R. Archambault: None. C. Lemaire: None.
25 Iodinated Contrast Agent Time Course In Human Brain Metastasis: A Study For Synchrotron Stereotactic Radiotherapy Clinical Trials L. Obeid,1,2 P. Deman,1,2 T. Alexandre,3 J. Balosso,3,2 F. Este`ve,3,1 and J.F. Adam1,2; 1INSERM U836, Grenoble-Institut des Neurosciences, Grenoble, France, 2Universite´ Joseph Fourier, Grenoble, France, 3Centre Hospitalier Universitaire, Grenoble, France Purpose/Objective(s): Synchrotron stereotactic radiotherapy (SSRT) is an innovative treatment combining the selective accumulation of heavy elements in tumors with stereotactic irradiations using monochromatic medium energy x-rays from a synchrotron source. Phase I/II clinical trials on brain metastasis are underway using venous infusion of iodinated
26 Contrast-enhanced Synchrotron Stereotactic Radiotherapy Clinical Trials from a Medical Physicist Point of View J. Adam,1,2 M. Vautrin,1 L. Obeid,1 A. Tessier,3 Y. Prezado,4 M. Renier,5 C. Nemoz,5 T. Brochard,5 A. Bravin,5 J. Le Bas,1,2 H. Elleaume,1 P. Berkvens,5 J. Balosso,1,2 and F. Este`ve1,2; 1Grenoble Institute des Neurosciences - Universite´ Joseph Fourier - INSERM U836-6, Grenoble, France, 2Centre Hospitalier Universitaire de Grenoble, Grenoble, France, 3 Centre Hospitalier Re´gional d’Annecy, Annecy, France, 4Unite´ Imagerie et Mode´lisation en Neurobiologie et Cance´rologie, UMR 8165, CNRS, Orsay, France, 5European Synchrotron Radiation Facility, France Purpose/Objective(s): The first clinical study of therapeutic applications of Synchrotron Stereotactic Radiation Therapy (SSRT) is underway since June 2012 at the European Synchrotron Radiation Facility (ESRF) and at the University Hospital (CHU) in Grenoble (France). This phase I-II clinical trial is designed to test the feasibility and safety of SSRT through a series of steps of increasing complexity. The treatment is based on stereotactic irradiations using high-flux quasi-parallel monochromatic medium energy x-ray beams (80 keV), in presence of heavy atoms, previously introduced in the tumor. At these energies, a localized dose enhancement occurs in the target, due to increased photoelectric absorption. The moderate kinetic energy photoelectrons deposit their energy over a submillimetric distance, in the close vicinity to the heavy atoms; whereas Compton scattering predominates in the surrounding healthy tissues. Consequently, the radiation becomes more penetrating, and hence interesting, for treating deep-seated tumors. The medical physics developments required by this innovative technique will be discussed in this presentation. Materials/Methods: A dedicated treatment room has been built at the ESRF medical beamline. The patient is seating on an armchair with his head tightly maintained by the same stereotactic frame used at the CHU for complimentary irradiations. A dedicated treatment planning system was adapted to SSRT specificities. The synchrotron beamline geometry was modeled. The dosimetry is based on parallelized Monte Carlo simulations of low-medium energy electrons and polarized photons transport in presence of high-Z material. Dedicated quality assurance protocols were implemented. The treatments plans and absolute dosimetry are validated
Volume 90 Number 1S Supplement 2014
Oral Scientific Sessions
with measurements performed in a dedicated water tank as well as in solid water with and without bone slabs. A 3D dosimetry technique is being developed in anthropomorphic phantoms. Results: The SSRT procedure includes the i.v. injection of iodinated contrast agent (400 mg/ml nominal concentration) followed by the monochromatic irradiation in the next minutes, with 4 to 10 beams. At the end of 2013, this study has already included six patients suffering from few brain metastases of medium-to-small volume. In this first clinical trial phase, the patients receive a fraction of the treatment by SSRT (5 Gy), while the remaining of the treatment is delivered by standard stereotactic irradiation at the CHU (6 Gy and 2 x 11 Gy). All patients were in good general condition. Conclusions: The technical feasibility and safety of treating brain metastasis with SSRT has been successfully initiated. The protocol now enters its dose escalation phase. Author Disclosure: J. Adam: None. M. Vautrin: None. L. Obeid: None. A. Tessier: None. Y. Prezado: None. M. Renier: None. C. Nemoz: None. T. Brochard: None. A. Bravin: None. J. Le Bas: None. H. Elleaume: None. P. Berkvens: None. J. Balosso: None. F. Este`ve: None.
27 A Dosimetric Comparison of a Novel Breast Stereotactic Radiotherapy Device for the Delivery of Partial Breast Irradiation (PBI) Versus Intensity Modulated Radiotherapy (IMRT) PBI J.W. Snider III, E.M. Nichols, S.J. Feigenberg, A. Hall, P. Vadnais, W.F. Regine, and Y.D. Mutaf; University of Maryland Medical Center, Baltimore, MD Purpose/Objective(s): A breast cancer specific stereotactic delivery device has been developed which has 2 unique components which allow sparing of surrounding critical structures. A hemispherical carrier is utilized containing 36 Cobalt-60 sources that rotate around a single isocenter. A dynamic treatment table allows dose distributions similar to stereotactic radiosurgery systems in the brain. The BSRT-device also makes use of a custom patient prone-position support table and vacuum-assisted breast immobilization cups which provide a stereotactic coordinate system with an accuracy of < 3 mm. This approach allows for highly focused radiation with fewer hot spots, as compared to the sphere packing approach, with a rapid dose fall-off outside the target. This study was designed to directly compare dosimetric parameters of the BSRT-device-based PBI versus IMRT PBI. Materials/Methods: CT simulations of 7 previously treated breast cancer patients were completed in prone position with the BSRT-device immobilization system. Normal tissue structures and volumes including the CTV, PTV, and PTV-eval were generated in accordance with those used in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39 PBI study. All planning utilized these volumes for direct comparison. IMRT PBI plans were similarly generated using up to 5 noncoplanar, unopposed beams as a rigorous comparison of conformality. Plans were also comparatively evaluated using previously validated parameters for cosmetic and clinical toxicity based upon percentage of total dose delivered to each of these structures (Vx). Results: With the BSRT-device, dose to the uninvolved, ipsilateral breast was statistically significantly reduced by means of: V20 -30.3% (p < 0.001); V50 -36.5% (p < 0.001); V80 -36.2% (p < 0.001); and V100 -41.6%
Oral Scientific Abstract 27; Table BSRT
Dosimetric Comparison of IMRT PBI and
IMRT PBI BSRT Relative Reduction p-value V20% ipsilateral breast V50% ipsilateral breast V80% ipsilateral breast V100% ipsilateral breast V15% ipsilateral breast skin V40% ipsilateral breast skin V15% ipsilateral chest wall V15% ipsilateral lung
60.3% 42.5% 26.3% 11.1% 54.2% 34.5% 29.0% 11.8%
42.0% 27.0% 16.8% 6.5% 39.5% 22.0% 21.6% 1.8%
30.3% 36.5% 36.2% 41.6% 27.0% 36.2% 25.4% 84.8%
< 0.001 < 0.001 < 0.001 0.04 < 0.001 < 0.001 0.01 0.05
S17
(p Z 0.04). The V15 and V40 of the ipsilateral breast skin, V15 of the ipsilateral chest wall, and V15 of the ipsilateral lung were also significantly decreased. Maximum dose points were each approximately 10% higher. Conclusions: The BSRT-device achieved comparable coverage of the identical target volumes to those utilized for IMRT PBI planning. It did so while significantly reducing the dose to surrounding critical structures. This novel BSRT-device could further improve the conformality, normal tissue dose reduction, and patient cosmetic outcomes associated with PBI compared to IMRT PBI, and it warrants further clinical investigation. A first of its kind multi-institutional study utilizing the BSRT-device will be activated in 2014. Author Disclosure: J.W. Snider III: None. E.M. Nichols: None. S.J. Feigenberg: None. A. Hall: None. P. Vadnais: None. W.F. Regine: None. Y.D. Mutaf: None.
28 Predicting Dose Distributions in Spinal SBRT Plans Using An Active Appearance Model (AAM) J. Liu,1 Q. Wu,2 F. Yin,2 J.P. Kirkpatrick,3 A.R. Cabrera,2 and Y. Ge4; 1 Department of Radiation Oncology, Duke University, Durham, NC, 2Duke University Medical Center, Durham, NC, 3Duke University, Durham, NC, 4 University of North Carolina at Charlotte, Charlotte, NC Purpose/Objective(s): To estimate dose distribution in spinal SBRT plans by understanding the influence of shape variation between spinal cords and PTVs on dose distributions using clinically accepted plans. Materials/Methods: Thirty plans were evenly divided into training and testing datasets. Among them were 4 C-spine, 20 T-spine, and 6 L-spine SBRT plans, with PTV volume ranging 13.2-982.8 cm3 (mean std: 116.7 175.3 cm3), and the affected cord 0.6-16.0 cm3 (4.5 4.1 cm3). The prescription dose range was 14.25-25 Gy (18 3 Gy) in 2-5 fractions. Our method for modeling the relationship between shape variation and dose distribution consists of six steps. 1) Collect paired sets of dose and structure regions containing spinal cord and PTV from each image of each scan in the training datasets. 2) Subdivide structure regions into four groups based on PTV location in relation to the spinal cord, (“top,” “bottom,” “left,” and “right.”) The dose regions are assigned accordingly. 3) Randomly choose a dose region as the reference for each group, and match all others to it using the optical flow method, which estimates relative displacements between two dose regions. 4) Perform principal component analysis of the flow vectors and dose values to yield the AAM that describes dose variations in a group. 5) Compute the PTV’s skeleton, a smoothed curve that characterizes shape relationship between PTV and spinal cord in a structure region. The principal component analysis computes skeleton variations. 6) Assess the correlation between AAM and the skeleton variations via linear regression modeling. To predict the dose distribution of a new case, we 1) assign it to a group based on its PTV location; 2) compute the PTV’s skeleton and decompose it by principal components of the skeleton variations within the group, and 3) estimate the dose distribution using the regression model. The Gamma index was chosen to evaluate dose difference and distance-to-agreement distributions between the clinically accepted and predicted dose regions. The dose difference threshold is set to 5% and the distance-to-agreement threshold is 2 mm. We also compared DVHs of two dose regions. Results: The Gamma index achieved up to 98% of the “top” group and 83% in the training and testing datasets. It dropped to 3% of the “left” group and 25% of the “right” group due to insufficient training samples. DVH comparisons also confirmed that predicted dose distributions were more accurate in the “top” group due to a higher number of training samples. Conclusions: An AAM-based approach was developed to model the relationship between PTV and spinal cord shape variations and dose distributions. AAM can automatically estimate dose distributions of spinal cords. The experimental results were promising in groups with more training samples. Further work is underway to collect more training samples, refine the models and evaluate the dose to adjacent critical organs.
International Journal of Radiation Oncology Biology Physics
QC, Canada, 6CHR Trois-Rivie`res, Trois-Rivie`res, QC, Canada, 7Centre de Sante´ et Services Sociaux de Chicoutimi, Chicoutimi, QC, Canada, 8 Hoˆpital Ge´ne´ral Juif de Montre´al, Montre´al, QC, Canada, 9Hoˆpital de Gatineau, Gatineau, QC, Canada, 10Hoˆpital Maisonneuve-Rosemont de Montre´al, Montre´al, QC, Canada
contrast agents. The radiation dose enhancement depends on the amount of iodine in the tumor and its time course. Quantitative, post-infusion iodine bio-distribution and associated brain perfusion parameters were studied in human brain metastasis as key parameters for treatment feasibility and quality. The reproducibility of iodine concentrations between the recruitment day and the treatment day was assessed in order to predict dose errors. Materials/Methods: Twelve patients received an intravenous bolus of iodinated contrast agent (40 mL, 4 mL/s), followed by a steady-state infusion (160 mL, 0.5 mL/s) in order to ensure stable intratumoral amounts of iodine during the treatment. Absolute iodine concentrations and quantitative perfusion maps were derived from 40 multi-slice dynamic conventional CT images of the brain (recruitment day) or from quantitative synchrotron radiation CT (treatment day). For three of these patients, iodine concentrations reached in the tumor were compared between the recruitment day and the treatment day (w10 days interval). Results: The post-infusion mean intratumoral iodine concentration (over thirty minutes) reached 1.94 0.12 mg/mL. Reasonable correlations were obtained between these concentrations and the permeability surface area product and the cerebral blood volume. Iodine concentrations were reproducible leading to dose errors in the radiotherapy standards. Conclusions: To our knowledge, this is the first quantitative study of contrast agent biodistribution versus time in brain metastasis. The study demonstrates that suitable and stable amounts of iodine can be reached in brain metastasis for SSRT treatment. Moreover, the associated perfusion measurements provide useful information for the patient recruitment and management processes. Author Disclosure: L. Obeid: None. P. Deman: None. T. Alexandre: None. J. Balosso: None. F. Este`ve: None. J.F. Adam: None.
Purpose/Objective(s): In a previous report from a randomized trial, we showed that 18 months of androgen deprivation therapy (18 mos ADT) appears to be equally effective as 36 months (36 mos ADT) in high risk prostate cancer (HRPC) patients. This current analysis was performed to evaluate quality of life (QOL) after testosterone recovery in patients treated in that multicentric randomized phase III trial (PCS IV clinical trials, Gov. # NCT 00223171). Materials/Methods: Patients were randomized to radiotherapy (RT) plus either 36 mos ADT or 18 mos ADT. QOL was assessed by two validated tools: EORTC30 (30 items) and PR25 (25 items). The 55 items were regrouped into 21 scales. All items and scales scores were linearly transformed to a 0-100 points scale. Serum testosterone was measured at baseline then at each visit. Abnormal testosterone was defined as below the normal level. Time to testosterone recovery between arms was compared with Kaplan-Meier and log-rank test. All items and scales scores were analyzed with general linear model and repeated measures to evaluate changes between patients who did versus those who did not recover normal levels of testosterone over time. P-value < 0.01 was considered statistically significant and a difference in mean scores of 10 points was considered clinically relevant. Patient-reported outcomes were filled out before treatments, every 6 months during ADT, 4 months after ADT and then once a year for 5 years. For patients who developed biochemical failure, QOL evaluation ceased at the time of a new course of ADT. Results: Five hundred sixty-one patients were retained for the analysis (69 patients excluded: 46 no baseline testosterone and 23 only baseline testosterone). With a median follow-up of 84 months, 283/561 (50.9%) patients recovered normal testosterone level: 161/289 (55.7%) in 18 mos ADT and 122/272 (44.9%) in 36 mos ADT, p Z 0.01. The median time to testosterone recovery is shorter in 18 mos ADT than 36 mos ADT: 47.2 (40.1-54.3) vs 73.2 (58.3-88.2) months, p < 0.001.The global adherence to QOL questionnaires was 72.3% (10172/14062) and was similar between arms. When comparing QOL between patients who recovered with those who did not recover normal testosterone, patients with testosterone recovery had a better QOL: 26/55 items and 12/21 scales were statistically significant. Similarly, 5/26 items and 1/21 scales which reached statistical significance, were also clinically relevant. Conclusions: In HRPC treated with RT and ADT, patients who recover a normal testosterone level have a significantly better quality of life. There is a major advantage for the use of 18 mos ADT vs 36 mos ADT since a higher proportion of patients recover a normal testosterone level in a much shorter time without apparent detriment in long term outcomes. Acknowledgment: This research was supported by AstraZeneca Pharmaceuticals. Author Disclosure: A. Nabid: E. Research Grant; AstraZeneca. F. Honoraria; Sanofi. I. Travel Expenses; Sanofi. N. Carrier: None. A. Martin: None. J. Bahary: None. L. Souhami: None. M. Duclos: None. F. Vincent: None. S. Vass: None. B. Bahoric: None. R. Archambault: None. C. Lemaire: None.
25 Iodinated Contrast Agent Time Course In Human Brain Metastasis: A Study For Synchrotron Stereotactic Radiotherapy Clinical Trials L. Obeid,1,2 P. Deman,1,2 T. Alexandre,3 J. Balosso,3,2 F. Este`ve,3,1 and J.F. Adam1,2; 1INSERM U836, Grenoble-Institut des Neurosciences, Grenoble, France, 2Universite´ Joseph Fourier, Grenoble, France, 3Centre Hospitalier Universitaire, Grenoble, France Purpose/Objective(s): Synchrotron stereotactic radiotherapy (SSRT) is an innovative treatment combining the selective accumulation of heavy elements in tumors with stereotactic irradiations using monochromatic medium energy x-rays from a synchrotron source. Phase I/II clinical trials on brain metastasis are underway using venous infusion of iodinated
26 Contrast-enhanced Synchrotron Stereotactic Radiotherapy Clinical Trials from a Medical Physicist Point of View J. Adam,1,2 M. Vautrin,1 L. Obeid,1 A. Tessier,3 Y. Prezado,4 M. Renier,5 C. Nemoz,5 T. Brochard,5 A. Bravin,5 J. Le Bas,1,2 H. Elleaume,1 P. Berkvens,5 J. Balosso,1,2 and F. Este`ve1,2; 1Grenoble Institute des Neurosciences - Universite´ Joseph Fourier - INSERM U836-6, Grenoble, France, 2Centre Hospitalier Universitaire de Grenoble, Grenoble, France, 3 Centre Hospitalier Re´gional d’Annecy, Annecy, France, 4Unite´ Imagerie et Mode´lisation en Neurobiologie et Cance´rologie, UMR 8165, CNRS, Orsay, France, 5European Synchrotron Radiation Facility, France Purpose/Objective(s): The first clinical study of therapeutic applications of Synchrotron Stereotactic Radiation Therapy (SSRT) is underway since June 2012 at the European Synchrotron Radiation Facility (ESRF) and at the University Hospital (CHU) in Grenoble (France). This phase I-II clinical trial is designed to test the feasibility and safety of SSRT through a series of steps of increasing complexity. The treatment is based on stereotactic irradiations using high-flux quasi-parallel monochromatic medium energy x-ray beams (80 keV), in presence of heavy atoms, previously introduced in the tumor. At these energies, a localized dose enhancement occurs in the target, due to increased photoelectric absorption. The moderate kinetic energy photoelectrons deposit their energy over a submillimetric distance, in the close vicinity to the heavy atoms; whereas Compton scattering predominates in the surrounding healthy tissues. Consequently, the radiation becomes more penetrating, and hence interesting, for treating deep-seated tumors. The medical physics developments required by this innovative technique will be discussed in this presentation. Materials/Methods: A dedicated treatment room has been built at the ESRF medical beamline. The patient is seating on an armchair with his head tightly maintained by the same stereotactic frame used at the CHU for complimentary irradiations. A dedicated treatment planning system was adapted to SSRT specificities. The synchrotron beamline geometry was modeled. The dosimetry is based on parallelized Monte Carlo simulations of low-medium energy electrons and polarized photons transport in presence of high-Z material. Dedicated quality assurance protocols were implemented. The treatments plans and absolute dosimetry are validated
Volume 90 Number 1S Supplement 2014
Oral Scientific Sessions
with measurements performed in a dedicated water tank as well as in solid water with and without bone slabs. A 3D dosimetry technique is being developed in anthropomorphic phantoms. Results: The SSRT procedure includes the i.v. injection of iodinated contrast agent (400 mg/ml nominal concentration) followed by the monochromatic irradiation in the next minutes, with 4 to 10 beams. At the end of 2013, this study has already included six patients suffering from few brain metastases of medium-to-small volume. In this first clinical trial phase, the patients receive a fraction of the treatment by SSRT (5 Gy), while the remaining of the treatment is delivered by standard stereotactic irradiation at the CHU (6 Gy and 2 x 11 Gy). All patients were in good general condition. Conclusions: The technical feasibility and safety of treating brain metastasis with SSRT has been successfully initiated. The protocol now enters its dose escalation phase. Author Disclosure: J. Adam: None. M. Vautrin: None. L. Obeid: None. A. Tessier: None. Y. Prezado: None. M. Renier: None. C. Nemoz: None. T. Brochard: None. A. Bravin: None. J. Le Bas: None. H. Elleaume: None. P. Berkvens: None. J. Balosso: None. F. Este`ve: None.
27 A Dosimetric Comparison of a Novel Breast Stereotactic Radiotherapy Device for the Delivery of Partial Breast Irradiation (PBI) Versus Intensity Modulated Radiotherapy (IMRT) PBI J.W. Snider III, E.M. Nichols, S.J. Feigenberg, A. Hall, P. Vadnais, W.F. Regine, and Y.D. Mutaf; University of Maryland Medical Center, Baltimore, MD Purpose/Objective(s): A breast cancer specific stereotactic delivery device has been developed which has 2 unique components which allow sparing of surrounding critical structures. A hemispherical carrier is utilized containing 36 Cobalt-60 sources that rotate around a single isocenter. A dynamic treatment table allows dose distributions similar to stereotactic radiosurgery systems in the brain. The BSRT-device also makes use of a custom patient prone-position support table and vacuum-assisted breast immobilization cups which provide a stereotactic coordinate system with an accuracy of < 3 mm. This approach allows for highly focused radiation with fewer hot spots, as compared to the sphere packing approach, with a rapid dose fall-off outside the target. This study was designed to directly compare dosimetric parameters of the BSRT-device-based PBI versus IMRT PBI. Materials/Methods: CT simulations of 7 previously treated breast cancer patients were completed in prone position with the BSRT-device immobilization system. Normal tissue structures and volumes including the CTV, PTV, and PTV-eval were generated in accordance with those used in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39 PBI study. All planning utilized these volumes for direct comparison. IMRT PBI plans were similarly generated using up to 5 noncoplanar, unopposed beams as a rigorous comparison of conformality. Plans were also comparatively evaluated using previously validated parameters for cosmetic and clinical toxicity based upon percentage of total dose delivered to each of these structures (Vx). Results: With the BSRT-device, dose to the uninvolved, ipsilateral breast was statistically significantly reduced by means of: V20 -30.3% (p < 0.001); V50 -36.5% (p < 0.001); V80 -36.2% (p < 0.001); and V100 -41.6%
Oral Scientific Abstract 27; Table BSRT
Dosimetric Comparison of IMRT PBI and
IMRT PBI BSRT Relative Reduction p-value V20% ipsilateral breast V50% ipsilateral breast V80% ipsilateral breast V100% ipsilateral breast V15% ipsilateral breast skin V40% ipsilateral breast skin V15% ipsilateral chest wall V15% ipsilateral lung
60.3% 42.5% 26.3% 11.1% 54.2% 34.5% 29.0% 11.8%
42.0% 27.0% 16.8% 6.5% 39.5% 22.0% 21.6% 1.8%
30.3% 36.5% 36.2% 41.6% 27.0% 36.2% 25.4% 84.8%
< 0.001 < 0.001 < 0.001 0.04 < 0.001 < 0.001 0.01 0.05
S17
(p Z 0.04). The V15 and V40 of the ipsilateral breast skin, V15 of the ipsilateral chest wall, and V15 of the ipsilateral lung were also significantly decreased. Maximum dose points were each approximately 10% higher. Conclusions: The BSRT-device achieved comparable coverage of the identical target volumes to those utilized for IMRT PBI planning. It did so while significantly reducing the dose to surrounding critical structures. This novel BSRT-device could further improve the conformality, normal tissue dose reduction, and patient cosmetic outcomes associated with PBI compared to IMRT PBI, and it warrants further clinical investigation. A first of its kind multi-institutional study utilizing the BSRT-device will be activated in 2014. Author Disclosure: J.W. Snider III: None. E.M. Nichols: None. S.J. Feigenberg: None. A. Hall: None. P. Vadnais: None. W.F. Regine: None. Y.D. Mutaf: None.
28 Predicting Dose Distributions in Spinal SBRT Plans Using An Active Appearance Model (AAM) J. Liu,1 Q. Wu,2 F. Yin,2 J.P. Kirkpatrick,3 A.R. Cabrera,2 and Y. Ge4; 1 Department of Radiation Oncology, Duke University, Durham, NC, 2Duke University Medical Center, Durham, NC, 3Duke University, Durham, NC, 4 University of North Carolina at Charlotte, Charlotte, NC Purpose/Objective(s): To estimate dose distribution in spinal SBRT plans by understanding the influence of shape variation between spinal cords and PTVs on dose distributions using clinically accepted plans. Materials/Methods: Thirty plans were evenly divided into training and testing datasets. Among them were 4 C-spine, 20 T-spine, and 6 L-spine SBRT plans, with PTV volume ranging 13.2-982.8 cm3 (mean std: 116.7 175.3 cm3), and the affected cord 0.6-16.0 cm3 (4.5 4.1 cm3). The prescription dose range was 14.25-25 Gy (18 3 Gy) in 2-5 fractions. Our method for modeling the relationship between shape variation and dose distribution consists of six steps. 1) Collect paired sets of dose and structure regions containing spinal cord and PTV from each image of each scan in the training datasets. 2) Subdivide structure regions into four groups based on PTV location in relation to the spinal cord, (“top,” “bottom,” “left,” and “right.”) The dose regions are assigned accordingly. 3) Randomly choose a dose region as the reference for each group, and match all others to it using the optical flow method, which estimates relative displacements between two dose regions. 4) Perform principal component analysis of the flow vectors and dose values to yield the AAM that describes dose variations in a group. 5) Compute the PTV’s skeleton, a smoothed curve that characterizes shape relationship between PTV and spinal cord in a structure region. The principal component analysis computes skeleton variations. 6) Assess the correlation between AAM and the skeleton variations via linear regression modeling. To predict the dose distribution of a new case, we 1) assign it to a group based on its PTV location; 2) compute the PTV’s skeleton and decompose it by principal components of the skeleton variations within the group, and 3) estimate the dose distribution using the regression model. The Gamma index was chosen to evaluate dose difference and distance-to-agreement distributions between the clinically accepted and predicted dose regions. The dose difference threshold is set to 5% and the distance-to-agreement threshold is 2 mm. We also compared DVHs of two dose regions. Results: The Gamma index achieved up to 98% of the “top” group and 83% in the training and testing datasets. It dropped to 3% of the “left” group and 25% of the “right” group due to insufficient training samples. DVH comparisons also confirmed that predicted dose distributions were more accurate in the “top” group due to a higher number of training samples. Conclusions: An AAM-based approach was developed to model the relationship between PTV and spinal cord shape variations and dose distributions. AAM can automatically estimate dose distributions of spinal cords. The experimental results were promising in groups with more training samples. Further work is underway to collect more training samples, refine the models and evaluate the dose to adjacent critical organs.