- Email: [email protected]
Results of the Phase III ENRICH (RT-016) Study of Efaproxiral Administered Concurrent with Whole Brain Radiation Therapy (WBRT) in Women with Brain Metastases from Breast Cancer
I. J. Radiation Oncology d Biology d Physics
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delivery. Three patient setup methods are commonly used in clinic, which include marker based, kV-image based, and cone-beam CT (CBCT) based alignments. In this work, we retrospectively calculated and compared the accumulated dose over the whole treatment course for each setup scenario. Materials/Methods: Five patients who underwent lung SBRT were selected for this study. At each fraction, patients were immobilized using a vacuum cushion and CT scanned. They were moved to treatment room within their immobilization devices. Treatment plans were performed on free-breathing CT by following the RTOG 0236 protocol with the assumption of homogeneous patient geometry. All plans were normalized such that 60 Gy (3 fractions) was prescribed to the 85% isodose line. PTV was created by adding a 5 mm uniform margin to the internal target volume (ITV), which is a union of GTVs at different respiration phases. The plan parameters were copied onto each CT to recalculate the dose with heterogeneity correction under 3 setup scenarios: marker based (setup 1), bony structure based (setup 2), and soft tissue based alignments (setup 3). Meanwhile, each CT was registered to the simulation CT using B-Spline based deformable registration algorithm. The resultant registration field provided the trajectory of voxel motion over the treatment course. The recalculated dose at each fraction was summed along voxel trajectories to generate the accumulated dose, which is the total dose delivered to the patient. The accumulated doses were compared using parameters such as mean dose, V20, and biologically effective dose (BED). Results: Tumor BED averaged over the 5 patients was 206.60 ± 24.67, 119.94 ± 45.88, and 249.21 ± 14.93 Gy for setup 1, 2, and 3 respectively. The corresponding tumor V60 was 56.59 ± 16.15%, 14.98 ± 24.89%, and 98.42 ± 2.16%, respectively. The isodose line covering 100% of the GTV was 41.97 ± 3.71, 23.53 ± 12.03, and 59.23 ± 10.19 Gy, covering 100% of the ITV was 38.03 ± 0.55, 22.67 ± 13.22, and 57.23 ± 12.51 Gy, covering 95% of the PTV was 31.63 ± 5.20, 19.53 ± 12.03, and 45.97 ± 13.93 Gy, respectively, for setup 1, 2, and 3. The corresponding lung mean dose was 2.91 ± 0.32, 3.05 ± 0.32, and 2.64 ± 0.37 Gy, lung BED was 5.69 ± 0.82, 5.75 ± 0.92, and 5.16 ± 0.78 Gy, and lung V20 was 4.24 ± 1.26%, 4.36 ± 1.22%, and 3.76 ± 1.09%, respectively, for setup 1, 2 and 3. Conclusions: Marker based and bony structure (kV-image) based patient alignments are inaccurate for aligning patients in lung SBRT. Soft tissue (e.g., CBCT) based alignment is necessary to match the prescribed dose delivered to the tumors. Author Disclosure: J. Wu, None; M. Fuss, None; W.D. D’Souza, None.
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Comparison of Liver Tumor Motion with and without Abdominal Compression using Cine-MRI
C. L. Eccles1,2, R. Patel2, G. Lockwood1, T. Purdie1,2, A. Kirilova1, M. Haider1, L. A. Dawson1,2 1
Princess Margaret Hospital, Toronto, ON, Canada, 2University of Toronto, Toronto, ON, Canada
Purpose/Objective(s): For patients receiving liver stereotactic body radiotherapy (SBRT), abdominal compression (AC) has been used to reduce liver motion due to breathing. The purpose of this study is to measure the change in 3D liver tumor motion with AC using cine-magnetic resonance imaging (MRI). Materials/Methods: Forty-nine patients treated on an institutional research ethics board approved liver SBRT protocol were evaluated at treatment planning. Patients underwent T2-weighted cineMRI through the centroid of the liver tumor in the coronal and sagittal planes. 182 cineMR sequences acquired at a rate of 1-3 images/second over 30 - 60 seconds were evaluated using motiontrack, an in-house template matching tool (based on coefficient correlation) to measure the magnitude of motion of tumor edges in each direction. Average tumor edge displacements were used to determine the change in tumor motion with abdominal compression in the superior-inferior (SI), anterior-posterior (AP), and medial-lateral (ML) directions. Results: The mean (range) of tumor breathing motion without abdominal compression was 15.1 (6.6, 38.7), 6.9 (1.5, 15.5), and 4.7 (0, 12.6) mm in SI, AP, and ML directions, respectively. With abdominal compression, the mean (range) tumor motion was significantly reduced to 12.1 (3.1, 40.8), 5.6 (1.6, 17.9), and 3.6 (0, 9.4) mm in the SI, AP, and ML directions, respectively (p\0.01 in all directions). Abdominal compression reduced tumor motion in all directions in 22 of 49 patients, and in two directions in 17 patients. In these patients, the mean (range) reduction in liver tumour motion using abdominal compression was 3.7 (0.3, 10.8), 2.6 (0.7, 7.7), and 2.7 (0.7, 7.5) mm in the SI, AP, and ML directions, respectively. There was a significant positive correlation between breathing motion amplitude and magnitude of motion reduction with compression (r2 = 0.4, 0.52, and 0.68 in SI, AP, and ML directions, respectively). Repeat single observer measurements using the automated software resulted in intraobserver variability \2mm in 89% of observations. Reduction in tumor motion by $2mm was seen in all directions in 7 patients, in two directions in 11 patients, and in only one direction in 15 patients. Increases in tumour motion using abdominal compression were seen in 5, 10, and 9 patients in the SI, AP, and ML directions, respectively; the mean (range) increase in tumour motion was 2.4 (0.3, 8.2), 2.5 (0.7, 4.5), and 2.3 (0.9, 3.8) mm in the SI, AP, and ML directions, respectively. Seven patients (14%) had an increase in motion in at least one direction by $2mm with compression. Conclusions: Abdominal compression significantly reduces 3D liver tumour motion in the majority of patients. The magnitude of motion reduction varies between patients, and increases in motion can be seen in up to 20% of patients. Author Disclosure: C.L. Eccles, None; R. Patel, None; G. Lockwood, None; T. Purdie, None; A. Kirilova, None; M. Haider, None; L.A. Dawson, Elekta, B. Research Grant.
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Results of the Phase III ENRICH (RT-016) Study of Efaproxiral Administered Concurrent with Whole Brain Radiation Therapy (WBRT) in Women with Brain Metastases from Breast Cancer
J. H. Suh1, B. Stea2, K. Tankel3, H. Marsiglia4, Y. Belkacemi5, H. Gomez6, S. Falcone-Lizaraso7, J. May8, M. Saunders8 1 Cleveland Clinic, Cleveland, OH, 2University of Arizona, Tucson, AZ, 3Cross Cancer Institute, Edmonton, AB, Canada, 4 Institut Gustave-Roussy, Villejuif, France, 5Centre Oscar Lambert, Lille, France, 6Instituto de Enfermerdades Neoplasicas, Lima, Peru, 7Hospital Edgardo Rebagliati, Lima, Peru, 8Allos Therapeutics, Westminster, CO Purpose/Objective(s): RT-016 (ENRICH) was a Phase III, randomized, open-label study of whole brain radiation therapy (WBRT) with supplemental oxygen, with or without concurrent efaproxiral, in women with brain metastases from breast cancer to determine if the addition of efaproxiral to WBRT prolongs survival and increases tumor response. Materials/Methods: Key eligibility criteria included breast cancer with brain metastases, Karnofsky performance status (KPS) $70, and no other active concurrent malignancy. All pts received WBRT (30 Gray [Gy] over 2 weeks at 3.0 Gy per fraction). Pts were
Proceedings of the 50th Annual ASTRO Meeting randomized 1:1 to the Efaproxiral Arm or Control Arm. Pts randomized to the Efaproxiral Arm received efaproxiral and supplemental oxygen within 30 minutes prior to daily WBRT. Pts randomized to the Control Arm received supplemental oxygen and WBRT. The planned sample size was 360 patients (180 pts/Arm). Pts were stratified for KPS (70-80 and 90-100) and known liver metastases (presence or absence), for a total of 4 strata. The primary endpoint was overall survival. The final analysis occurred at 281 deaths. Results: From Feb/04-Sep/06, 368 pts were randomized at 78 sites in 15 countries. Efficacy analyses were conducted on 365 eligible pts (n = 182 Efaproxiral Arm, n = 183 Control Arm). No statistically significant difference in survival was detected between the two arms using the stratified log-rank test (hazard ratio [HR] = 0.87, p = 0.233). The median survival time (MST) was 8.5 months in the Efaproxiral Arm compared to 7.5 months in the Control Arm. Secondary efficacy endpoints of response rate in the brain at 3 months (confirmed complete response [CR] plus partial response [PR] = 31% in the Efaproxiral Arm and 27% in the Control Arm), KPS, and neurological signs and symptoms improvement also failed to achieve statistical significance. Nausea and headache were the most frequent adverse events (AE). Conclusion: The addition of efaproxiral to WBRT failed to improve overall survival in women with brain metastases originating from breast cancer. Survival for the WBRT only arm was greater than predicted. No significant impact was observed in any of the pre-specified secondary endpoints. Author Disclosure: J.H. Suh, Schering Plough, D. Speakers Bureau/Honoraria; B. Stea, None; K. Tankel, None; H. Marsiglia, None; Y. Belkacemi, None; H. Gomez, None; S. Falcone-Lizaraso, None; J. May, Allos Therapeutics, A. Employment; M. Saunders, Allos Therapeutics, A. Employment; Stock ownership, E. Ownership Interest.
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A Multi-institutional Validation Study of a New Prognostic Index (Graded Prognostic Assessment, GPA) for Patients with Brain Metastases
P. Sperduto1, P. Sneed2, A. Bhatt3, A. Schwer4, J. Fiveash5, V. Chiang6, J. Knisely6, Y. Zhu7, L. E. Gaspar4, M. Mehta3 1 Minneapolis Radiation Oncology, Minneapolis, MN, 2University of California, San Francisco, San Francisco, CA, 3University of Wisconsin, Madison, WI, 4University of Colorado, Denver, CO, 5University of Alabama, Birmingham, AL, 6Yale University, New Haven, CT, 7School of Public Health, Univ. of Minnesota, Minneapolis, MN
Purpose/Objective(s): A new prognostic index for patients with brain metastases was recently published (Int J Radiat Oncol Biol Phys 70:510-514; 2008), based on an analysis of 1,960 patients in the Radiation Therapy Oncology Group (RTOG) database. This index, the Graded Prognostic Assessment (GPA) uses four criteria (age, KPS, number of brain metastases, and whether extracranial metastases are present or absent) and scores each with a 0, 0.5, or 1.0 value. The patient with the best prognosis would have a GPA of 4.0. The purpose of this study is to validate the GPA by retrospectively correlating the GPA with median survival time (MST) at multiple institutions. A secondary objective was to determine if there is a difference in survival in patients treated with: a) Whole Brain Radiation (WBRT) alone; b) Stereotactic Radiosurgery (SRS) alone; c) WBRT + SRS. Materials/Methods: A database of 1880 patients treated between July 1985 and August 2007 was created retrospectively from raw data submitted by six institutions. Survival time was calculated from the date treatment began for the brain metastases. The GPA score was calculated for each patient in the group overall (1880), the group without surgery (1598), and the group without salvage therapy or surgery (1201). Salvage therapy was defined as any treatment .2 months from the start of brain metastasis treatment. The GPA was correlated with survival via the log-rank test and the multivariate Cox regression model. These findings were compared with the results from the RTOG database. Survival by initial treatment was assessed. Results: The MST for the RTOG data (n = 1960), the validation data without salvage therapy or surgery (n = 1201), and the validation data overall (n = 1880) was 11.0, 14.3, and 18.2 mo for GPA 3.5-4.0; 8.9, 13.3, and 14.9 mo for GPA 3.0; 3.8, 7.1, and 10.1 mo for GPA 1.5-2.5; and 2.6, 3.0, and 4.3 mo for GPA 0-1.0, respectively. There was a significant difference in survival between each GPA group in the validation data (p\0.0001). In the non-surgical group (1598), MST for WBRT + SRS, SRS alone, and WBRT alone was 14.8, 8.4, and 2.9 months, respectively. WBRT + SRS was significantly better than SRS alone (p \ 0.0001) or WBRT alone (p \ 0.0001). Conclusions: 1) The validation data agree with the RTOG data in that the higher the GPA, the longer the survival. 2) There are significant differences in survival between each GPA group (p \ 0.0001). 3) The improvement in survival between the RTOG database and the validation database is probably attributable to selection bias and advances in treatment. 4) For the non-surgical group, WBRT + SRS as initial treatment was superior to SRS alone or WBRT alone. 5) This study validates the GPA as a useful prognostic index for future clinical trials and for clinical decision-making regarding which patients warrant aggressive treatment. Author Disclosure: P. Sperduto, Minneapolis Radiation Oncology, E. Ownership Interest; P. Sneed, None; A. Bhatt, None; A. Schwer, None; J. Fiveash, None; V. Chiang, None; J. Knisely, None; Y. Zhu, None; L.E. Gaspar, None; M. Mehta, None.
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Stereotactic Body Radiosurgery for 121 Cases of Spinal Metastases Treated at M.D. Anderson Cancer Center
E. L. Chang, A. S. Shiu, P. Grossman, P. K. Allen, X. S. Wang, A. Mahajan, T. Mendoza, C. Cleeland, S. Y. Woo, L. D. Rhines M.D. Anderson Cancer Center, Houston, TX Purpose/Objective(s): To report on outcomes for patients undergoing stereotactic body radiosurgery (SBRS) for spinal metastases. Materials/Methods: Patients were enrolled on an IRB-approved prospective protocol involving SBRS for spinal metastases using CT-on-rails image guidance. Spinal metastases were treated ever other day using IMRT, initially to 30 Gy in 5 fractions, and later to 27 Gy in 3 fractions. Progression free survival (PFS) was determined by spinal MRI. Follow-ups including neurological exam were conducted at 3-mo follow-up intervals in the first year, and every 6 mos thereafter. The Brief Pain Inventory (BPI) and the M. D. Anderson Symptom Inventory (MDASI) were administered at baseline, and at each follow-up to assess pain control and symptom interference respectively. Acute toxicity was assessed using the NCI Toxicity Scale version 2.0. Results: From Nov 2002 to Dec 2007, 121 cases were evaluable in which 136 spinal metastases were treated with SBRS. The median age of the study cohort was 60 yrs (range, 22-88). Prior therapy could be categorized as previous irradiation (n = 27), previous surgery (n = 17), previous surgery and irradiation (n = 37). Tumor histology was characterized as lung (n = 16), breast (n = 12), melanoma (n = 2), renal (n = 43), colon (n = 4), sarcoma (n = 16), other (n = 26), and unknown primary (n = 2). Median tumor volume was 40.6 cc (range, 1.6 - 357.9). Median follow-up was 13.0 mos (range, 1.0 - 54.5). The 6-mo and 1-yr spinal
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delivery. Three patient setup methods are commonly used in clinic, which include marker based, kV-image based, and cone-beam CT (CBCT) based alignments. In this work, we retrospectively calculated and compared the accumulated dose over the whole treatment course for each setup scenario. Materials/Methods: Five patients who underwent lung SBRT were selected for this study. At each fraction, patients were immobilized using a vacuum cushion and CT scanned. They were moved to treatment room within their immobilization devices. Treatment plans were performed on free-breathing CT by following the RTOG 0236 protocol with the assumption of homogeneous patient geometry. All plans were normalized such that 60 Gy (3 fractions) was prescribed to the 85% isodose line. PTV was created by adding a 5 mm uniform margin to the internal target volume (ITV), which is a union of GTVs at different respiration phases. The plan parameters were copied onto each CT to recalculate the dose with heterogeneity correction under 3 setup scenarios: marker based (setup 1), bony structure based (setup 2), and soft tissue based alignments (setup 3). Meanwhile, each CT was registered to the simulation CT using B-Spline based deformable registration algorithm. The resultant registration field provided the trajectory of voxel motion over the treatment course. The recalculated dose at each fraction was summed along voxel trajectories to generate the accumulated dose, which is the total dose delivered to the patient. The accumulated doses were compared using parameters such as mean dose, V20, and biologically effective dose (BED). Results: Tumor BED averaged over the 5 patients was 206.60 ± 24.67, 119.94 ± 45.88, and 249.21 ± 14.93 Gy for setup 1, 2, and 3 respectively. The corresponding tumor V60 was 56.59 ± 16.15%, 14.98 ± 24.89%, and 98.42 ± 2.16%, respectively. The isodose line covering 100% of the GTV was 41.97 ± 3.71, 23.53 ± 12.03, and 59.23 ± 10.19 Gy, covering 100% of the ITV was 38.03 ± 0.55, 22.67 ± 13.22, and 57.23 ± 12.51 Gy, covering 95% of the PTV was 31.63 ± 5.20, 19.53 ± 12.03, and 45.97 ± 13.93 Gy, respectively, for setup 1, 2, and 3. The corresponding lung mean dose was 2.91 ± 0.32, 3.05 ± 0.32, and 2.64 ± 0.37 Gy, lung BED was 5.69 ± 0.82, 5.75 ± 0.92, and 5.16 ± 0.78 Gy, and lung V20 was 4.24 ± 1.26%, 4.36 ± 1.22%, and 3.76 ± 1.09%, respectively, for setup 1, 2 and 3. Conclusions: Marker based and bony structure (kV-image) based patient alignments are inaccurate for aligning patients in lung SBRT. Soft tissue (e.g., CBCT) based alignment is necessary to match the prescribed dose delivered to the tumors. Author Disclosure: J. Wu, None; M. Fuss, None; W.D. D’Souza, None.
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Comparison of Liver Tumor Motion with and without Abdominal Compression using Cine-MRI
C. L. Eccles1,2, R. Patel2, G. Lockwood1, T. Purdie1,2, A. Kirilova1, M. Haider1, L. A. Dawson1,2 1
Princess Margaret Hospital, Toronto, ON, Canada, 2University of Toronto, Toronto, ON, Canada
Purpose/Objective(s): For patients receiving liver stereotactic body radiotherapy (SBRT), abdominal compression (AC) has been used to reduce liver motion due to breathing. The purpose of this study is to measure the change in 3D liver tumor motion with AC using cine-magnetic resonance imaging (MRI). Materials/Methods: Forty-nine patients treated on an institutional research ethics board approved liver SBRT protocol were evaluated at treatment planning. Patients underwent T2-weighted cineMRI through the centroid of the liver tumor in the coronal and sagittal planes. 182 cineMR sequences acquired at a rate of 1-3 images/second over 30 - 60 seconds were evaluated using motiontrack, an in-house template matching tool (based on coefficient correlation) to measure the magnitude of motion of tumor edges in each direction. Average tumor edge displacements were used to determine the change in tumor motion with abdominal compression in the superior-inferior (SI), anterior-posterior (AP), and medial-lateral (ML) directions. Results: The mean (range) of tumor breathing motion without abdominal compression was 15.1 (6.6, 38.7), 6.9 (1.5, 15.5), and 4.7 (0, 12.6) mm in SI, AP, and ML directions, respectively. With abdominal compression, the mean (range) tumor motion was significantly reduced to 12.1 (3.1, 40.8), 5.6 (1.6, 17.9), and 3.6 (0, 9.4) mm in the SI, AP, and ML directions, respectively (p\0.01 in all directions). Abdominal compression reduced tumor motion in all directions in 22 of 49 patients, and in two directions in 17 patients. In these patients, the mean (range) reduction in liver tumour motion using abdominal compression was 3.7 (0.3, 10.8), 2.6 (0.7, 7.7), and 2.7 (0.7, 7.5) mm in the SI, AP, and ML directions, respectively. There was a significant positive correlation between breathing motion amplitude and magnitude of motion reduction with compression (r2 = 0.4, 0.52, and 0.68 in SI, AP, and ML directions, respectively). Repeat single observer measurements using the automated software resulted in intraobserver variability \2mm in 89% of observations. Reduction in tumor motion by $2mm was seen in all directions in 7 patients, in two directions in 11 patients, and in only one direction in 15 patients. Increases in tumour motion using abdominal compression were seen in 5, 10, and 9 patients in the SI, AP, and ML directions, respectively; the mean (range) increase in tumour motion was 2.4 (0.3, 8.2), 2.5 (0.7, 4.5), and 2.3 (0.9, 3.8) mm in the SI, AP, and ML directions, respectively. Seven patients (14%) had an increase in motion in at least one direction by $2mm with compression. Conclusions: Abdominal compression significantly reduces 3D liver tumour motion in the majority of patients. The magnitude of motion reduction varies between patients, and increases in motion can be seen in up to 20% of patients. Author Disclosure: C.L. Eccles, None; R. Patel, None; G. Lockwood, None; T. Purdie, None; A. Kirilova, None; M. Haider, None; L.A. Dawson, Elekta, B. Research Grant.
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Results of the Phase III ENRICH (RT-016) Study of Efaproxiral Administered Concurrent with Whole Brain Radiation Therapy (WBRT) in Women with Brain Metastases from Breast Cancer
J. H. Suh1, B. Stea2, K. Tankel3, H. Marsiglia4, Y. Belkacemi5, H. Gomez6, S. Falcone-Lizaraso7, J. May8, M. Saunders8 1 Cleveland Clinic, Cleveland, OH, 2University of Arizona, Tucson, AZ, 3Cross Cancer Institute, Edmonton, AB, Canada, 4 Institut Gustave-Roussy, Villejuif, France, 5Centre Oscar Lambert, Lille, France, 6Instituto de Enfermerdades Neoplasicas, Lima, Peru, 7Hospital Edgardo Rebagliati, Lima, Peru, 8Allos Therapeutics, Westminster, CO Purpose/Objective(s): RT-016 (ENRICH) was a Phase III, randomized, open-label study of whole brain radiation therapy (WBRT) with supplemental oxygen, with or without concurrent efaproxiral, in women with brain metastases from breast cancer to determine if the addition of efaproxiral to WBRT prolongs survival and increases tumor response. Materials/Methods: Key eligibility criteria included breast cancer with brain metastases, Karnofsky performance status (KPS) $70, and no other active concurrent malignancy. All pts received WBRT (30 Gray [Gy] over 2 weeks at 3.0 Gy per fraction). Pts were
Proceedings of the 50th Annual ASTRO Meeting randomized 1:1 to the Efaproxiral Arm or Control Arm. Pts randomized to the Efaproxiral Arm received efaproxiral and supplemental oxygen within 30 minutes prior to daily WBRT. Pts randomized to the Control Arm received supplemental oxygen and WBRT. The planned sample size was 360 patients (180 pts/Arm). Pts were stratified for KPS (70-80 and 90-100) and known liver metastases (presence or absence), for a total of 4 strata. The primary endpoint was overall survival. The final analysis occurred at 281 deaths. Results: From Feb/04-Sep/06, 368 pts were randomized at 78 sites in 15 countries. Efficacy analyses were conducted on 365 eligible pts (n = 182 Efaproxiral Arm, n = 183 Control Arm). No statistically significant difference in survival was detected between the two arms using the stratified log-rank test (hazard ratio [HR] = 0.87, p = 0.233). The median survival time (MST) was 8.5 months in the Efaproxiral Arm compared to 7.5 months in the Control Arm. Secondary efficacy endpoints of response rate in the brain at 3 months (confirmed complete response [CR] plus partial response [PR] = 31% in the Efaproxiral Arm and 27% in the Control Arm), KPS, and neurological signs and symptoms improvement also failed to achieve statistical significance. Nausea and headache were the most frequent adverse events (AE). Conclusion: The addition of efaproxiral to WBRT failed to improve overall survival in women with brain metastases originating from breast cancer. Survival for the WBRT only arm was greater than predicted. No significant impact was observed in any of the pre-specified secondary endpoints. Author Disclosure: J.H. Suh, Schering Plough, D. Speakers Bureau/Honoraria; B. Stea, None; K. Tankel, None; H. Marsiglia, None; Y. Belkacemi, None; H. Gomez, None; S. Falcone-Lizaraso, None; J. May, Allos Therapeutics, A. Employment; M. Saunders, Allos Therapeutics, A. Employment; Stock ownership, E. Ownership Interest.
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A Multi-institutional Validation Study of a New Prognostic Index (Graded Prognostic Assessment, GPA) for Patients with Brain Metastases
P. Sperduto1, P. Sneed2, A. Bhatt3, A. Schwer4, J. Fiveash5, V. Chiang6, J. Knisely6, Y. Zhu7, L. E. Gaspar4, M. Mehta3 1 Minneapolis Radiation Oncology, Minneapolis, MN, 2University of California, San Francisco, San Francisco, CA, 3University of Wisconsin, Madison, WI, 4University of Colorado, Denver, CO, 5University of Alabama, Birmingham, AL, 6Yale University, New Haven, CT, 7School of Public Health, Univ. of Minnesota, Minneapolis, MN
Purpose/Objective(s): A new prognostic index for patients with brain metastases was recently published (Int J Radiat Oncol Biol Phys 70:510-514; 2008), based on an analysis of 1,960 patients in the Radiation Therapy Oncology Group (RTOG) database. This index, the Graded Prognostic Assessment (GPA) uses four criteria (age, KPS, number of brain metastases, and whether extracranial metastases are present or absent) and scores each with a 0, 0.5, or 1.0 value. The patient with the best prognosis would have a GPA of 4.0. The purpose of this study is to validate the GPA by retrospectively correlating the GPA with median survival time (MST) at multiple institutions. A secondary objective was to determine if there is a difference in survival in patients treated with: a) Whole Brain Radiation (WBRT) alone; b) Stereotactic Radiosurgery (SRS) alone; c) WBRT + SRS. Materials/Methods: A database of 1880 patients treated between July 1985 and August 2007 was created retrospectively from raw data submitted by six institutions. Survival time was calculated from the date treatment began for the brain metastases. The GPA score was calculated for each patient in the group overall (1880), the group without surgery (1598), and the group without salvage therapy or surgery (1201). Salvage therapy was defined as any treatment .2 months from the start of brain metastasis treatment. The GPA was correlated with survival via the log-rank test and the multivariate Cox regression model. These findings were compared with the results from the RTOG database. Survival by initial treatment was assessed. Results: The MST for the RTOG data (n = 1960), the validation data without salvage therapy or surgery (n = 1201), and the validation data overall (n = 1880) was 11.0, 14.3, and 18.2 mo for GPA 3.5-4.0; 8.9, 13.3, and 14.9 mo for GPA 3.0; 3.8, 7.1, and 10.1 mo for GPA 1.5-2.5; and 2.6, 3.0, and 4.3 mo for GPA 0-1.0, respectively. There was a significant difference in survival between each GPA group in the validation data (p\0.0001). In the non-surgical group (1598), MST for WBRT + SRS, SRS alone, and WBRT alone was 14.8, 8.4, and 2.9 months, respectively. WBRT + SRS was significantly better than SRS alone (p \ 0.0001) or WBRT alone (p \ 0.0001). Conclusions: 1) The validation data agree with the RTOG data in that the higher the GPA, the longer the survival. 2) There are significant differences in survival between each GPA group (p \ 0.0001). 3) The improvement in survival between the RTOG database and the validation database is probably attributable to selection bias and advances in treatment. 4) For the non-surgical group, WBRT + SRS as initial treatment was superior to SRS alone or WBRT alone. 5) This study validates the GPA as a useful prognostic index for future clinical trials and for clinical decision-making regarding which patients warrant aggressive treatment. Author Disclosure: P. Sperduto, Minneapolis Radiation Oncology, E. Ownership Interest; P. Sneed, None; A. Bhatt, None; A. Schwer, None; J. Fiveash, None; V. Chiang, None; J. Knisely, None; Y. Zhu, None; L.E. Gaspar, None; M. Mehta, None.
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Stereotactic Body Radiosurgery for 121 Cases of Spinal Metastases Treated at M.D. Anderson Cancer Center
E. L. Chang, A. S. Shiu, P. Grossman, P. K. Allen, X. S. Wang, A. Mahajan, T. Mendoza, C. Cleeland, S. Y. Woo, L. D. Rhines M.D. Anderson Cancer Center, Houston, TX Purpose/Objective(s): To report on outcomes for patients undergoing stereotactic body radiosurgery (SBRS) for spinal metastases. Materials/Methods: Patients were enrolled on an IRB-approved prospective protocol involving SBRS for spinal metastases using CT-on-rails image guidance. Spinal metastases were treated ever other day using IMRT, initially to 30 Gy in 5 fractions, and later to 27 Gy in 3 fractions. Progression free survival (PFS) was determined by spinal MRI. Follow-ups including neurological exam were conducted at 3-mo follow-up intervals in the first year, and every 6 mos thereafter. The Brief Pain Inventory (BPI) and the M. D. Anderson Symptom Inventory (MDASI) were administered at baseline, and at each follow-up to assess pain control and symptom interference respectively. Acute toxicity was assessed using the NCI Toxicity Scale version 2.0. Results: From Nov 2002 to Dec 2007, 121 cases were evaluable in which 136 spinal metastases were treated with SBRS. The median age of the study cohort was 60 yrs (range, 22-88). Prior therapy could be categorized as previous irradiation (n = 27), previous surgery (n = 17), previous surgery and irradiation (n = 37). Tumor histology was characterized as lung (n = 16), breast (n = 12), melanoma (n = 2), renal (n = 43), colon (n = 4), sarcoma (n = 16), other (n = 26), and unknown primary (n = 2). Median tumor volume was 40.6 cc (range, 1.6 - 357.9). Median follow-up was 13.0 mos (range, 1.0 - 54.5). The 6-mo and 1-yr spinal
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