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Local Control Outcomes Using the 32P Intraoperative Brachytherapy Plaque in the Management of Malignant Lesions of the Spine Involving the Dura
S20
Abstracts / Brachytherapy 13 (2014) S15eS126
Table 1 Patient characteristics All patients (n 5 28) n Age Ethnic Status
Pathology
Grade Stage Locoregional Relapse Metastases Cause of Death Follow up
Median (Range) in years Caucasian AA Other Endometrioid Other (Mixed, Serous, Carcinosarcoma, Clear cell) I II III I II Yes No Yes No Disease Progression Medical Comorbidity Median (Range) in months
63 (44-88) 19 7 2 24 4 14 7 7 24 4 9 19 3 25 5 9 44.5 (5.3-122.1)
HDR brachytherapy (n 5 8)
%
n
67.9 25.0 7.1 85.7 14.3
64 (44-88) 5 3 8 -
50.0 25.0 25.0 85.7 14.3 32.1 67.9 10.7 89.3 35.7 64.3
6 2 8 4 4 1 7 1 3 44.5 (12.9-122.1)
HDR brachytherapy þ pelvic RT (n 5 20)
%
n
%
62.5 37.5 0 100 0
63 (51-88) 14 4 2 16 4
70 20 10 80 20
75 25 0 100 0 50.0 50.0 12.5 87.5 25.0 75.0
8 5 7 16 4 5 15 2 18 4 6 46.5 (5.3-110.7)
40 25 35 80 20 25.0 75.0 10 90 40.0 60.0
HDR: High-Dose-Rate, RT: Radiotherapy, DSS: Disease-Specific Survival, OS: Overall Survival, AA: African American
or high energy electron beams. However, there are technical drawbacks to IORT methods, such as the lack of image-based planning and the low dose delivered (5-7 Gy at 1 cm from the applicator surface). Use of high-doserate Ir-192 should show an increase in the dose at 1cm due to the higher energy of the photons used. However, this requires a shielded procedure room, which is not available at most institutions. The Image-Guided Brachytherapy Suite at the University of Virginia is such a room, which includes a sliding gantry CT scanner, an OR-type treatment couch, along with full anesthesia capabilities. Thus, all the ingredients are in place for Materials and Methods: The CT scans of 15 patients who had previously received Contura-based breast brachytherapy were used for this study (8 right breast and 7 left breast). All planning was performed on the Varian BrachyVision v. 11 treatment planning system (Varian Medical Systems, Inc., Palo Alto, CA). The treatments were optimized to delivered 10 Gy to the PTV_eval as described in the literature, with a D95 of 95% and a D150 of 28% used as the optimization parameters. Additionally, a constraining structure 3 mm around the PTV_eval was used as a further optimization to attempt to keep dose within the PTV_eval. Structures named PTV_3mm and PTV_1mm were also created by expanding the balloon three and one mm, respectively, and subtracting the balloon volume from the contour Because the dose at the surface of a structure cannot be determined directly in the treatment planning system, the PTV_1mm was used for surrogate for surface dose for comparison to published literature for 50 kV IORT. Additional structures that were contoured included the whole heart for left-sided breast patients and the ribs for all patients. Additionally, the TG-43 data for a 50 kV treatment device was loaded into the treatment planning system so that comparisons could be made between Ir-192 based brachytherapy and 50 kV electronic brachytherapy. The same volume optimization parameters were used for the 50 kV plans as for the Ir-192 plans. Results: The dosimetric results of this study are shown in Table 1. All of the dosimetric parameters showed an advantage for use of a multilumen applicator except for the heart and rib dosimetric parameters, which can be explained by the higher energy of Ir-192 treatments. However, these doses are well within tolerance. The use of volumetric optimization improved the dosimetric results for the multilumen treatment due to the
increased degrees of freedom for the optimization afforded by the multiple catheters. Conclusions: IORT may be delivered using a variety of techniques. This study shows that the use of a multilumen catheter with HDR can improve most dosimetric results when compared to a 50 kV source in a single lumen applicator. However, attention must be given to mean heart and maximum rib doses for HDR-based IORT.
MISCELLANEOUS ORAL Thursday, April 3, 2014 2:00 PM - 3:00 PM OR07
Presentation Time: 2:00 PM
Local Control Outcomes Using the 32P Intraoperative Brachytherapy Plaque in the Management of Malignant Lesions of the Spine Involving the Dura Michael R. Folkert, MD, PhD1, Mark H. Bilsky, MD2, Gil’ad N. Cohen, MS3, Marco Zaider, PhD3, Eric Lis, MD4, Ilya Laufer, MD2, Yoshiya Yamada, MD1. 1Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY; 2Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY; 3Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY; 4Radiology, Memorial Sloan Kettering Cancer Center, New York, NY. Purpose: Sterilization of surgical margins for lesions arising from or metastasizing to the spine and involving the dura may be complicated by the tolerance of the spinal cord and/or cauda equina, especially in the setting of prior radiation therapy (RT); outcomes with surgery alone are poor, with local control rates of only 31% at 1 year.1 Use of intraoperative brachytherapy at the time of salvage surgery with a shortrange, high-dose-rate source may allow local delivery of therapeutic dose without damaging sensitive structures and provide improved local control outcomes. Materials and Methods: Patients with malignant lesions arising from or metastasizing to the spine involving the dura were treated with an intraoperative brachytherapy plaque utilizing 32P following maximal
Abstracts / Brachytherapy 13 (2014) S15eS126 surgical resection of tumor, receiving 10 Gy to a prescription depth of 1mm from the treated dural surface; while the corresponding dose at the dural surface is 25 Gy, rapid falloff in dose with depth for the 32P plaque limits the dose delivered at the spinal cord surface to less than 0.5 Gy. Local control (LC) and overall survival (OS) were analyzed using Kaplan-Meier statistics; univariate analysis was performed using Cox regression. Results: Between 9/2009 and 4/2013, 68 patients with 69 lesions in the spine were treated intraoperatively with the 32P plaque, 48 (70%) metastatic lesions and 21 (30%) recurrent primary disease. Median followup was 10 months (range 0.2-44 months). Median age was 61 years (range 6-89 years). The majority of patients (n 5 59, 85.5%) had previously been treated with at least one course of prior RT to the treated site; 21 (30%) received 2 courses of prior RT to the treated site and 4 (6%) had received 3 courses of prior RT to the treated site. Thirty-eight (55%) lesions received additional postoperative hypofractionated image-guided radiation therapy with a median dose of 30 Gy (range 18-30 Gy). Overall LC at 12 months was 70% (95% CI 57-83%); OS at 12 months was 60% (95% CI 4673%). For patients who received postoperative external beam RT in addition to 32P plaque, LC at 12 months was 78% (95% CI 62-94%) compared to 59% (95% CI 49-80%) for those who were treated with the 32P plaque alone (P 5 .05). (Fig 1, below; local control for patients treated with surgery and intraoperative 32P plaque, patients receiving additional postoperative RT in green and patients treated with 32P plaque alone in blue.) No significant difference was noted on univariate analysis for LC based on recurrent primary vs. metastatic status (P 5 .16), prior RT (P 5 .25), or concurrent chemotherapy (P 5 .09). There were no acute or long-term complications from treatment observed in this cohort. Conclusions: The 32P intraoperative brachytherapy plaque is a useful adjunct to surgical intervention for primary recurrent and metastatic lesions of the spine involving the dura, and is not associated with additional toxicity. Local control outcomes using the 32P appear to be better than historical results with surgery alone, with or without additional postoperative external beam radiation therapy.
OR08 Presentation Time: 2:09 PM Yttrium-90 Microsphere Brachytherapy for Liver Metastases from Uveal Melanoma Harriet B. Eldredge-Hindy, MD1, Nitin Ohri, MD2, Rani P. Anne, MD1, David J. Eschelman, MD3, Carin Gonsalves, MD3, Charles Intenzo, MD4,
S21 1
1
1
Voichita Bar-Ad, MD , Adam Dicker, MD, PhD , Laura Doyle, MS , Jun Li, PhD1, Takami Sato, MD, PhD5. 1Radiation Oncology, Thomas Jefferson University, Philadelphia, PA; 2Radiation Oncology, Montefiore Medical Center, Bronx, NY; 3 Interventional Radiology, Thomas Jefferson University, Philadelphia, PA; 4Nuclear Medicine, Thomas Jefferson University, Philadelphia, PA; 5Medical Oncology, Thomas Jefferson University, Philadelphia, PA. Purpose: The liver is the first site of metastatic disease in 80% of patients who develop metastatic uveal melanoma (MUM). Survival of patients with MUM is poor, ranging 3-12 months. Given this remarkable predilection for the liver, liver-directed therapies are vital in the management of MUM. Yttrium-90 (Y-90) microsphere brachytherapy (MB) has emerged as a valuable therapeutic option for patients with unresectable liver metastases, but few institutions have reported on their experience with MB for MUM. We report the largest series of patients treated with Y-90 MB for liver metastases from MUM and test the hypothesis that positron emission tomography (PET)-derived functional tumor parameters are predictive for overall survival (OS) and hepatic progression free survival (PFS). Materials and Methods: Following IRB approval, a retrospective review was performed of 71 patients who were consecutively treated for unresectable liver metastases from MUM from 2007 through 2012 with Y-90 MB (SIR-Spheres; SIRTEX Medical, Sydney, Australia). Fifty patients had pre-treatment and 29 had post-treatment PET scans on which liver tumors were automatically contoured (MIM Maestro, MIM Software Inc., Cleveland, OH) using a threshold technique to obtain summative values for maximum standard uptake value (SUVmax, pre and SUVmax,post), metabolic tumor volume (MTVpre and MTVpost) and total glycolic activity (TGApre and TGApost). OS and PFS were estimated by Kaplan-Meier method. Differences in survival between subgroups were evaluated by log-rank test in univariate analysis and backwards stepwise multivariate Cox proportional hazards regression. Results: Fifty-eight patients (82%) received MB as a salvage therapy and the median time from diagnosis of liver metastases to MB was 9.8 mos.
Abstracts / Brachytherapy 13 (2014) S15eS126
Table 1 Patient characteristics All patients (n 5 28) n Age Ethnic Status
Pathology
Grade Stage Locoregional Relapse Metastases Cause of Death Follow up
Median (Range) in years Caucasian AA Other Endometrioid Other (Mixed, Serous, Carcinosarcoma, Clear cell) I II III I II Yes No Yes No Disease Progression Medical Comorbidity Median (Range) in months
63 (44-88) 19 7 2 24 4 14 7 7 24 4 9 19 3 25 5 9 44.5 (5.3-122.1)
HDR brachytherapy (n 5 8)
%
n
67.9 25.0 7.1 85.7 14.3
64 (44-88) 5 3 8 -
50.0 25.0 25.0 85.7 14.3 32.1 67.9 10.7 89.3 35.7 64.3
6 2 8 4 4 1 7 1 3 44.5 (12.9-122.1)
HDR brachytherapy þ pelvic RT (n 5 20)
%
n
%
62.5 37.5 0 100 0
63 (51-88) 14 4 2 16 4
70 20 10 80 20
75 25 0 100 0 50.0 50.0 12.5 87.5 25.0 75.0
8 5 7 16 4 5 15 2 18 4 6 46.5 (5.3-110.7)
40 25 35 80 20 25.0 75.0 10 90 40.0 60.0
HDR: High-Dose-Rate, RT: Radiotherapy, DSS: Disease-Specific Survival, OS: Overall Survival, AA: African American
or high energy electron beams. However, there are technical drawbacks to IORT methods, such as the lack of image-based planning and the low dose delivered (5-7 Gy at 1 cm from the applicator surface). Use of high-doserate Ir-192 should show an increase in the dose at 1cm due to the higher energy of the photons used. However, this requires a shielded procedure room, which is not available at most institutions. The Image-Guided Brachytherapy Suite at the University of Virginia is such a room, which includes a sliding gantry CT scanner, an OR-type treatment couch, along with full anesthesia capabilities. Thus, all the ingredients are in place for Materials and Methods: The CT scans of 15 patients who had previously received Contura-based breast brachytherapy were used for this study (8 right breast and 7 left breast). All planning was performed on the Varian BrachyVision v. 11 treatment planning system (Varian Medical Systems, Inc., Palo Alto, CA). The treatments were optimized to delivered 10 Gy to the PTV_eval as described in the literature, with a D95 of 95% and a D150 of 28% used as the optimization parameters. Additionally, a constraining structure 3 mm around the PTV_eval was used as a further optimization to attempt to keep dose within the PTV_eval. Structures named PTV_3mm and PTV_1mm were also created by expanding the balloon three and one mm, respectively, and subtracting the balloon volume from the contour Because the dose at the surface of a structure cannot be determined directly in the treatment planning system, the PTV_1mm was used for surrogate for surface dose for comparison to published literature for 50 kV IORT. Additional structures that were contoured included the whole heart for left-sided breast patients and the ribs for all patients. Additionally, the TG-43 data for a 50 kV treatment device was loaded into the treatment planning system so that comparisons could be made between Ir-192 based brachytherapy and 50 kV electronic brachytherapy. The same volume optimization parameters were used for the 50 kV plans as for the Ir-192 plans. Results: The dosimetric results of this study are shown in Table 1. All of the dosimetric parameters showed an advantage for use of a multilumen applicator except for the heart and rib dosimetric parameters, which can be explained by the higher energy of Ir-192 treatments. However, these doses are well within tolerance. The use of volumetric optimization improved the dosimetric results for the multilumen treatment due to the
increased degrees of freedom for the optimization afforded by the multiple catheters. Conclusions: IORT may be delivered using a variety of techniques. This study shows that the use of a multilumen catheter with HDR can improve most dosimetric results when compared to a 50 kV source in a single lumen applicator. However, attention must be given to mean heart and maximum rib doses for HDR-based IORT.
MISCELLANEOUS ORAL Thursday, April 3, 2014 2:00 PM - 3:00 PM OR07
Presentation Time: 2:00 PM
Local Control Outcomes Using the 32P Intraoperative Brachytherapy Plaque in the Management of Malignant Lesions of the Spine Involving the Dura Michael R. Folkert, MD, PhD1, Mark H. Bilsky, MD2, Gil’ad N. Cohen, MS3, Marco Zaider, PhD3, Eric Lis, MD4, Ilya Laufer, MD2, Yoshiya Yamada, MD1. 1Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY; 2Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY; 3Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY; 4Radiology, Memorial Sloan Kettering Cancer Center, New York, NY. Purpose: Sterilization of surgical margins for lesions arising from or metastasizing to the spine and involving the dura may be complicated by the tolerance of the spinal cord and/or cauda equina, especially in the setting of prior radiation therapy (RT); outcomes with surgery alone are poor, with local control rates of only 31% at 1 year.1 Use of intraoperative brachytherapy at the time of salvage surgery with a shortrange, high-dose-rate source may allow local delivery of therapeutic dose without damaging sensitive structures and provide improved local control outcomes. Materials and Methods: Patients with malignant lesions arising from or metastasizing to the spine involving the dura were treated with an intraoperative brachytherapy plaque utilizing 32P following maximal
Abstracts / Brachytherapy 13 (2014) S15eS126 surgical resection of tumor, receiving 10 Gy to a prescription depth of 1mm from the treated dural surface; while the corresponding dose at the dural surface is 25 Gy, rapid falloff in dose with depth for the 32P plaque limits the dose delivered at the spinal cord surface to less than 0.5 Gy. Local control (LC) and overall survival (OS) were analyzed using Kaplan-Meier statistics; univariate analysis was performed using Cox regression. Results: Between 9/2009 and 4/2013, 68 patients with 69 lesions in the spine were treated intraoperatively with the 32P plaque, 48 (70%) metastatic lesions and 21 (30%) recurrent primary disease. Median followup was 10 months (range 0.2-44 months). Median age was 61 years (range 6-89 years). The majority of patients (n 5 59, 85.5%) had previously been treated with at least one course of prior RT to the treated site; 21 (30%) received 2 courses of prior RT to the treated site and 4 (6%) had received 3 courses of prior RT to the treated site. Thirty-eight (55%) lesions received additional postoperative hypofractionated image-guided radiation therapy with a median dose of 30 Gy (range 18-30 Gy). Overall LC at 12 months was 70% (95% CI 57-83%); OS at 12 months was 60% (95% CI 4673%). For patients who received postoperative external beam RT in addition to 32P plaque, LC at 12 months was 78% (95% CI 62-94%) compared to 59% (95% CI 49-80%) for those who were treated with the 32P plaque alone (P 5 .05). (Fig 1, below; local control for patients treated with surgery and intraoperative 32P plaque, patients receiving additional postoperative RT in green and patients treated with 32P plaque alone in blue.) No significant difference was noted on univariate analysis for LC based on recurrent primary vs. metastatic status (P 5 .16), prior RT (P 5 .25), or concurrent chemotherapy (P 5 .09). There were no acute or long-term complications from treatment observed in this cohort. Conclusions: The 32P intraoperative brachytherapy plaque is a useful adjunct to surgical intervention for primary recurrent and metastatic lesions of the spine involving the dura, and is not associated with additional toxicity. Local control outcomes using the 32P appear to be better than historical results with surgery alone, with or without additional postoperative external beam radiation therapy.
OR08 Presentation Time: 2:09 PM Yttrium-90 Microsphere Brachytherapy for Liver Metastases from Uveal Melanoma Harriet B. Eldredge-Hindy, MD1, Nitin Ohri, MD2, Rani P. Anne, MD1, David J. Eschelman, MD3, Carin Gonsalves, MD3, Charles Intenzo, MD4,
S21 1
1
1
Voichita Bar-Ad, MD , Adam Dicker, MD, PhD , Laura Doyle, MS , Jun Li, PhD1, Takami Sato, MD, PhD5. 1Radiation Oncology, Thomas Jefferson University, Philadelphia, PA; 2Radiation Oncology, Montefiore Medical Center, Bronx, NY; 3 Interventional Radiology, Thomas Jefferson University, Philadelphia, PA; 4Nuclear Medicine, Thomas Jefferson University, Philadelphia, PA; 5Medical Oncology, Thomas Jefferson University, Philadelphia, PA. Purpose: The liver is the first site of metastatic disease in 80% of patients who develop metastatic uveal melanoma (MUM). Survival of patients with MUM is poor, ranging 3-12 months. Given this remarkable predilection for the liver, liver-directed therapies are vital in the management of MUM. Yttrium-90 (Y-90) microsphere brachytherapy (MB) has emerged as a valuable therapeutic option for patients with unresectable liver metastases, but few institutions have reported on their experience with MB for MUM. We report the largest series of patients treated with Y-90 MB for liver metastases from MUM and test the hypothesis that positron emission tomography (PET)-derived functional tumor parameters are predictive for overall survival (OS) and hepatic progression free survival (PFS). Materials and Methods: Following IRB approval, a retrospective review was performed of 71 patients who were consecutively treated for unresectable liver metastases from MUM from 2007 through 2012 with Y-90 MB (SIR-Spheres; SIRTEX Medical, Sydney, Australia). Fifty patients had pre-treatment and 29 had post-treatment PET scans on which liver tumors were automatically contoured (MIM Maestro, MIM Software Inc., Cleveland, OH) using a threshold technique to obtain summative values for maximum standard uptake value (SUVmax, pre and SUVmax,post), metabolic tumor volume (MTVpre and MTVpost) and total glycolic activity (TGApre and TGApost). OS and PFS were estimated by Kaplan-Meier method. Differences in survival between subgroups were evaluated by log-rank test in univariate analysis and backwards stepwise multivariate Cox proportional hazards regression. Results: Fifty-eight patients (82%) received MB as a salvage therapy and the median time from diagnosis of liver metastases to MB was 9.8 mos.