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Impact of FACBC PET in Imaging and GTV Design of Cerebral Gliomas
S250
International Journal of Radiation Oncology Biology Physics
mm expansion was used to create both PTVs. HFSRT was delivered concomitant with temozolomide (TMZ) (75 mg/m2 daily), followed by adjuvant TMZ (150-200 mg/m2 in 5/28 days). Two patients also received additional concurrent bevacizumab (10 mg/kg every 2 weeks). Response was assessed based on the Response Assessment in Neuro-Oncology criteria. Electronic medical records were reviewed for acute toxicity, dexamethasone dosage, disease response, progression free survival (PFS) and median survival (MS). Results: Median age at diagnosis was 65 years (range, 50-82 years) and median pre-radiation KPS Z 60 (range, 40-70). The median pre-operative maximum dimension of the gross tumor on MRI was 5.4 cm (range, 1.9-8.5 cm). Three patients had gross total resection, 4 had subtotal resection, and 5 had biopsy only. The treatment was well tolerated without RTOG grade 3/4 acute toxicities. All patients were on dexamethasone at start of radiation and no increase in dosage was required in any of the patients during treatment. Three (30%) patients had dose taper during and another 3 had taper shortly after completion of radiation. Of the 8 patients with available follow-up data, 1 (13%) had partial response, 6 (75%) stable disease, and 1 (13%) progression of disease after HFSRT. With median follow-up of 8 months (range, 4-15 months), 2/8 (25%) of the patients had died. MS has not yet been reached. Median PFS was reached at 8 months from completion of HFSRT. Conclusions: The HFSRT regimen with concurrent TMZ was safe, well tolerated and convenient for patients with the poorest GBM prognosis, rendering a shorter overall treatment time with no increase in steroid requirement during treatment. Compared to the historical median survival of 5-9 months in patients with RPA class V-VI, HFSRT appeared to have done well, likely owing to the more aggressive radiation fractionation and concurrent TMZ. Further clinical trial exploring this HFRT in GBM patients with poorest prognosis is warranted. Author Disclosure: J.C. Ye: None. M. Yondorf: None. S.C. Pannullo: None. J.A. Boockvar: None. T.H. Schwartz: None. P.E. Stieg: None. B. Parashar: None. D. Nori: None. K.C. Chao: None. A. Wernicke: None.
[SUVmax/contralateral SUV mean], respectively) were determined. Tumor volumes of (a) SUV40 (BTV), (b) T2 (T2V) and (c) T1C (T1CV) were calculated. Seventeen lesions (74%) had MRI defined GTVs and Hausdorff distances (HD) were measured comparing BTV versus (v) (a) T2V and (b) T1CV. Results: Eleven males and 11 females were enrolled. Mean age was 54 years (range, 34-79 years). Pathologic distribution of lesions was: 7 LG (grade 2), and 16 HG (5 anaplastic astrocytomas and 11 glioblastomas). The mean TBRmean for HG 1.46 (range, 1.12-2.82) and LG 1.14 (range, 0.25-1.39) were compared to NB (value Z 1; p Z 0.00 and p Z 0.24, respectively). Differences were found between HG and LG in mean SUVmax (HG: 8.74; range, 4.67-13.19 vs LG 5.76; range, 1.02-9.07; p Z 0.03), mean SUV40 (HG: 3.50; range, 1.87-5.28 vs LG 2.30 (range, 0.41-3.63; p Z 0.03), and BTV (HG: 7.9 cc; range, 0-24.2 vs LG 1.6 cc; range, 0-5.1; p Z 0.01). In patients with MRI defined GTVs, BTV was smaller than T2V (BTV: 7.3 cc; range, 0-24.2 vs T2V: 119.2 cc; range, 40.9-260.3; p Z 0.00) and T1CV (BTV: 7.9 cc; range, 0-24.2 vs T1CV: 34.8 cc; range, 7.3-110.9; p Z 0.01). Mean HD between BTV vs (a) T2V and (b) T1CV was 10.8 mm (range, 1.5-19.0; p Z 0.00) and 5.5 mm (range, 0.6-13.0; p Z 0.00), respectively. Conclusions: This preliminary analysis shows that FACBC is present to a greater extent in HG and LG compared to NB, with statistically higher uptake in HG. A greater conformality of BTV is found with T1C GTV than with T2 GTV. Whether the absolute level of or a change in FACBC uptake post treatment predicts outcome of therapy remains to be determined. As well, it remains to be determined whether FACBC uptake outside of the MRI-anatomically defined GTV may identify occult tumor. Author Disclosure: D.M. Schuster: None. J. Vakili: None. J.J. Olson: None. C.G. Hadjipanayis: None. D.J. Brat: None. W.J. Curran: None. H.G. Shu: None. I.R. Crocker: K. Stock; Dr. Crocker is a shareholder in Velocity Medical Systems and subject to receiving royalties through an agreement between the Emory University Office of Technology Transfer and Velocity Medical Systems. E.M. Marchan: None. M.M. Goodman: E. Research Grant; Research sponsored by the NIH (1 R01 CA 121320-01). N. Royalty; Dr Goodman is entitled to royalty derived from sale of products related to the research described in this abstract. Terms of this arrangement have been reviewed and approved by Emory University, in accordance with its conflict of interest policies.
2120 Impact of FACBC PET in Imaging and GTV Design of Cerebral Gliomas E.M. Marchan,1 M.M. Goodman,2 D.M. Schuster,3 J. Vakili,4 J.J. Olson,5 C.G. Hadjipanayis,5 D.J. Brat,6 W.J. Curran,1 H.G. Shu,1 and I.R. Crocker1; 1Emory University School of Medicine/Radiation Oncology, Atlanta, GA, 2Emory University School of Medicine/Radiology and Imaging Sciences, Atlanta, GA, 3Emory University School of Medicine/Department of Radiology/Nuclear Medicine, Atlanta, GA, 4 Emory University Rollins School of Public Health/Biostatistics, Atlanta, GA, 5Emory University School of Medicine/Neurosurgery, Atlanta, GA, 6 Emory University School of Medicine/Pathology, Atlanta, GA Purpose/Objective(s): 18F-2-fluoro-2-deoxy-D-glucose (FDG) PET has proven valuable in both defining the extent of cancers as well as in response assessment. Because of high uptake in normal brain (NB), FDG has had limited utility in the CNS. New amino acid tracers have been designed to overcome FDG’s limitations. At our institution, a novel amino acid tracer, 1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (FACBC) has been tested in newly diagnosed low (LG) and high grade (HG) gliomas. We studied FACBC uptake in relationship to the T2 signal abnormality (T2) and the T1 contrast enhancing (T1C) volume on MRI. We also investigated differences between the FACBC PET derived biologic tumor volume (BTV) and the MRI defined GTV. Materials/Methods: Between 2008 and 2013, 22 newly diagnosed glioma patients (23 lesions) were prospectively enrolled for FACBC PET after undergoing tissue confirmation via biopsy or craniotomy. All patients had a post-operative MRI with T2 and T1 pre and post contrast sequences. Commercial software was used to co-register the MRI and PET. The ipsilateral maximum standard uptake value (SUVmax), SUV at 40% of SUVmax (SUV40), as well as mean and maximum tumor/NB ratios (TBRmean [ipsilateral SUV mean/contralateral SUV mean] and TBRmax
2121 The Development of an Unbiased, Semiautomated Method for Perioperative Tumor Volume Measurement Using VelocityAI in Glioblastoma J.S. Cordova, E. Schreibmann, C.G. Hadjipanayis, C.A. Holder, V. Bansal, J. Sepulveda, H. Danish, Y. Guo, H.G. Shu, and H. Shim; Emory University, Atlanta, GA Purpose/Objective(s): Currently, clinical glioblastoma (GBM) volume measurements rely on the product of orthogonal tumor diameters on contrast-enhanced, T1-weighted MR images. However, it is extremely difficult to consistently measure post-resection tumor size in this manner, especially when hyper-intense, non-neoplastic lesions are present. Though the desperate clinical need for objective, volumetric analysis was recently highlighted by the Neuro-Oncology Working Group, a standardized image display, processing, and analysis protocol has not been developed for a clinically-utilized volume rendering software. As such, the current work aims to standardize an MR signal-based approach for tumor segmentation using an FDA 510k-approved software package that allows for the rendering, registration, and fusion of multimodality medical images, to produce consistent and unbiased tumor volumes. Materials/Methods: As proof-of-principal, we applied our volume determination method to compare the extent of resection (EOR) using 5-aminolevulinic acid (ALA) fluorescence-guided resection to EOR of normal resections. Datasets consisted of high-resolution pre-operative and post-
International Journal of Radiation Oncology Biology Physics
mm expansion was used to create both PTVs. HFSRT was delivered concomitant with temozolomide (TMZ) (75 mg/m2 daily), followed by adjuvant TMZ (150-200 mg/m2 in 5/28 days). Two patients also received additional concurrent bevacizumab (10 mg/kg every 2 weeks). Response was assessed based on the Response Assessment in Neuro-Oncology criteria. Electronic medical records were reviewed for acute toxicity, dexamethasone dosage, disease response, progression free survival (PFS) and median survival (MS). Results: Median age at diagnosis was 65 years (range, 50-82 years) and median pre-radiation KPS Z 60 (range, 40-70). The median pre-operative maximum dimension of the gross tumor on MRI was 5.4 cm (range, 1.9-8.5 cm). Three patients had gross total resection, 4 had subtotal resection, and 5 had biopsy only. The treatment was well tolerated without RTOG grade 3/4 acute toxicities. All patients were on dexamethasone at start of radiation and no increase in dosage was required in any of the patients during treatment. Three (30%) patients had dose taper during and another 3 had taper shortly after completion of radiation. Of the 8 patients with available follow-up data, 1 (13%) had partial response, 6 (75%) stable disease, and 1 (13%) progression of disease after HFSRT. With median follow-up of 8 months (range, 4-15 months), 2/8 (25%) of the patients had died. MS has not yet been reached. Median PFS was reached at 8 months from completion of HFSRT. Conclusions: The HFSRT regimen with concurrent TMZ was safe, well tolerated and convenient for patients with the poorest GBM prognosis, rendering a shorter overall treatment time with no increase in steroid requirement during treatment. Compared to the historical median survival of 5-9 months in patients with RPA class V-VI, HFSRT appeared to have done well, likely owing to the more aggressive radiation fractionation and concurrent TMZ. Further clinical trial exploring this HFRT in GBM patients with poorest prognosis is warranted. Author Disclosure: J.C. Ye: None. M. Yondorf: None. S.C. Pannullo: None. J.A. Boockvar: None. T.H. Schwartz: None. P.E. Stieg: None. B. Parashar: None. D. Nori: None. K.C. Chao: None. A. Wernicke: None.
[SUVmax/contralateral SUV mean], respectively) were determined. Tumor volumes of (a) SUV40 (BTV), (b) T2 (T2V) and (c) T1C (T1CV) were calculated. Seventeen lesions (74%) had MRI defined GTVs and Hausdorff distances (HD) were measured comparing BTV versus (v) (a) T2V and (b) T1CV. Results: Eleven males and 11 females were enrolled. Mean age was 54 years (range, 34-79 years). Pathologic distribution of lesions was: 7 LG (grade 2), and 16 HG (5 anaplastic astrocytomas and 11 glioblastomas). The mean TBRmean for HG 1.46 (range, 1.12-2.82) and LG 1.14 (range, 0.25-1.39) were compared to NB (value Z 1; p Z 0.00 and p Z 0.24, respectively). Differences were found between HG and LG in mean SUVmax (HG: 8.74; range, 4.67-13.19 vs LG 5.76; range, 1.02-9.07; p Z 0.03), mean SUV40 (HG: 3.50; range, 1.87-5.28 vs LG 2.30 (range, 0.41-3.63; p Z 0.03), and BTV (HG: 7.9 cc; range, 0-24.2 vs LG 1.6 cc; range, 0-5.1; p Z 0.01). In patients with MRI defined GTVs, BTV was smaller than T2V (BTV: 7.3 cc; range, 0-24.2 vs T2V: 119.2 cc; range, 40.9-260.3; p Z 0.00) and T1CV (BTV: 7.9 cc; range, 0-24.2 vs T1CV: 34.8 cc; range, 7.3-110.9; p Z 0.01). Mean HD between BTV vs (a) T2V and (b) T1CV was 10.8 mm (range, 1.5-19.0; p Z 0.00) and 5.5 mm (range, 0.6-13.0; p Z 0.00), respectively. Conclusions: This preliminary analysis shows that FACBC is present to a greater extent in HG and LG compared to NB, with statistically higher uptake in HG. A greater conformality of BTV is found with T1C GTV than with T2 GTV. Whether the absolute level of or a change in FACBC uptake post treatment predicts outcome of therapy remains to be determined. As well, it remains to be determined whether FACBC uptake outside of the MRI-anatomically defined GTV may identify occult tumor. Author Disclosure: D.M. Schuster: None. J. Vakili: None. J.J. Olson: None. C.G. Hadjipanayis: None. D.J. Brat: None. W.J. Curran: None. H.G. Shu: None. I.R. Crocker: K. Stock; Dr. Crocker is a shareholder in Velocity Medical Systems and subject to receiving royalties through an agreement between the Emory University Office of Technology Transfer and Velocity Medical Systems. E.M. Marchan: None. M.M. Goodman: E. Research Grant; Research sponsored by the NIH (1 R01 CA 121320-01). N. Royalty; Dr Goodman is entitled to royalty derived from sale of products related to the research described in this abstract. Terms of this arrangement have been reviewed and approved by Emory University, in accordance with its conflict of interest policies.
2120 Impact of FACBC PET in Imaging and GTV Design of Cerebral Gliomas E.M. Marchan,1 M.M. Goodman,2 D.M. Schuster,3 J. Vakili,4 J.J. Olson,5 C.G. Hadjipanayis,5 D.J. Brat,6 W.J. Curran,1 H.G. Shu,1 and I.R. Crocker1; 1Emory University School of Medicine/Radiation Oncology, Atlanta, GA, 2Emory University School of Medicine/Radiology and Imaging Sciences, Atlanta, GA, 3Emory University School of Medicine/Department of Radiology/Nuclear Medicine, Atlanta, GA, 4 Emory University Rollins School of Public Health/Biostatistics, Atlanta, GA, 5Emory University School of Medicine/Neurosurgery, Atlanta, GA, 6 Emory University School of Medicine/Pathology, Atlanta, GA Purpose/Objective(s): 18F-2-fluoro-2-deoxy-D-glucose (FDG) PET has proven valuable in both defining the extent of cancers as well as in response assessment. Because of high uptake in normal brain (NB), FDG has had limited utility in the CNS. New amino acid tracers have been designed to overcome FDG’s limitations. At our institution, a novel amino acid tracer, 1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (FACBC) has been tested in newly diagnosed low (LG) and high grade (HG) gliomas. We studied FACBC uptake in relationship to the T2 signal abnormality (T2) and the T1 contrast enhancing (T1C) volume on MRI. We also investigated differences between the FACBC PET derived biologic tumor volume (BTV) and the MRI defined GTV. Materials/Methods: Between 2008 and 2013, 22 newly diagnosed glioma patients (23 lesions) were prospectively enrolled for FACBC PET after undergoing tissue confirmation via biopsy or craniotomy. All patients had a post-operative MRI with T2 and T1 pre and post contrast sequences. Commercial software was used to co-register the MRI and PET. The ipsilateral maximum standard uptake value (SUVmax), SUV at 40% of SUVmax (SUV40), as well as mean and maximum tumor/NB ratios (TBRmean [ipsilateral SUV mean/contralateral SUV mean] and TBRmax
2121 The Development of an Unbiased, Semiautomated Method for Perioperative Tumor Volume Measurement Using VelocityAI in Glioblastoma J.S. Cordova, E. Schreibmann, C.G. Hadjipanayis, C.A. Holder, V. Bansal, J. Sepulveda, H. Danish, Y. Guo, H.G. Shu, and H. Shim; Emory University, Atlanta, GA Purpose/Objective(s): Currently, clinical glioblastoma (GBM) volume measurements rely on the product of orthogonal tumor diameters on contrast-enhanced, T1-weighted MR images. However, it is extremely difficult to consistently measure post-resection tumor size in this manner, especially when hyper-intense, non-neoplastic lesions are present. Though the desperate clinical need for objective, volumetric analysis was recently highlighted by the Neuro-Oncology Working Group, a standardized image display, processing, and analysis protocol has not been developed for a clinically-utilized volume rendering software. As such, the current work aims to standardize an MR signal-based approach for tumor segmentation using an FDA 510k-approved software package that allows for the rendering, registration, and fusion of multimodality medical images, to produce consistent and unbiased tumor volumes. Materials/Methods: As proof-of-principal, we applied our volume determination method to compare the extent of resection (EOR) using 5-aminolevulinic acid (ALA) fluorescence-guided resection to EOR of normal resections. Datasets consisted of high-resolution pre-operative and post-