Of the 44 subjects included, 17 subsequently received pLDR therapy concurrently with Bev. The radiation therapy was administered in 0.2 Gy pulses separated ...
Volume 90 Number 1S Supplement 2014 to 60 Gy in 30 fractions of 2 Gy followed by Bev upon imaging evidence of recurrence. Of these, 30 subjects were excluded because they had less than one cycle of Bev, were in the non-standard treatment arm of a drug study, or had incomplete treatment history. Of the 44 subjects included, 17 subsequently received pLDR therapy concurrently with Bev. The radiation therapy was administered in 0.2 Gy pulses separated by 3 min delivering 2 Gy total over 30 min. This produced an apparent dose rate of 0.0667 Gy/ min. The total prescribed dose range was 50-54 Gy (mean Z 52) delivered to the MRI FLAIR abnormality with a margin of 0.5-2 cm (mean Z 1). Brain stem and optic chiasm were limited to 50 Gy without regard to prior radiation dose. From pre-Bev initiation to last MRI exam, all available preand post-contrast T1-weighted and FLAIR images were co-registered across time. Exams were scored using a Likert system by a blinded neuroradiologist. Kaplan Meier survival curves were generated comparing overall survival (OS) in those who received Bev alone versus concurrently with pLDR. The OS was also compared in 14 concurrently treated subjects based on imaging progression following Bev and prior to pLDR initiation and also examined with respect to time between initial radiation therapy and pLDR. Results: Gender and median age were consistent across treatment groups. Those receiving concurrent pLDR and Bev had a statistically significant improvement in OS compared to patients receiving Bev alone (466 vs 222 days, p Z 0.011, HR Z 2.17). No trends were found with respect to OS based on time between initial course of radiation therapy and pLDR. Based on imaging, 11/14 patients showed progression prior to initiation of pLDR while 3 were stable. There was a non-significant trend toward improved OS if patients were treated with concurrent pLDR and Bev prior to imaging progression. Conclusions: Based on the results of this study, treatment with concurrent pLDR and Bev show significantly superior OS than Bev alone in the treatment of rGBM. A larger cohort is required to evaluate appropriate timing of pLDR initiation. Quality of life analysis of those receiving concurrent pLDR and Bev is ongoing. Advanced MRI analysis of relative cerebral blood volume as a biomarker of response to pLDR is also being investigated. Author Disclosure: J.A. Bovi: None. M. Prah: None. S.D. Rand: K. Advisory Board; Imaging Biometrics LLC. C.J. Schultz: None. K.M. Schmainda: R. Ownership Other; Imaging Biometrics LLC, Prism Clinical Imaging Inc.
2180 Extravasation Rate Constant Estimation From Pharmacokinetic First Principles to Improve Dynamic Susceptibility Contrast MRI Characterization of Brain Tumors X. Li, C.G. Varallyay, S. Gahramanov, W.D. Rooney, and E.A. Neuwelt; Oregon Health & Science University, Portland, OR Purpose/Objective(s): Proper identification of malignant CNS lesion is crucial for therapy planning. Relative cerebral blood volume (rCBV) is an important biomarker for both lesion aggressiveness classification and therapeutic response monitoring. However, rCBV derived from Dynamic Susceptibility Contrast (DSC) Magnetic Resonance Imaging (MRI) with low molecular weight Gadolinium (Gd; w600 Da) contrast agent (CA) is often confounded by CA leakage into interstitium space. We seek to correct this “leakage effect” with a new approach similar to Gjedde-Patlak linearization which uniquely identifies the leakage rate as the slope from the linear portion of the transformed data. This approach provides higher fidelity estimates of blood volume/flow and also CA extravasation rate constant. Using the high-molecular weight (w750 kDa) iron-based intravascular Ferumoxytol (Fe) DSC data, the pharmacokinetic interpretation of the new paradigm is empirically validated. Materials/Methods: Seventeen subjects with glioblastoma multiforme (GBM) were prospectively studied on institutional review board approved protocols. Subjects underwent two consecutive days of MRI scans on a 3T scanner. On the first day, DSC-MRI data were acquired using Gd CA. On
Poster Viewing Abstracts S289 the following day, the same DSC MRI protocol was acquired using the intravascular CA, Ferumoxytol. Three rCBV maps from Gd DSC are calculated for each effective transverse relaxation rate constant (R2*) timecourse: 1) without Gd leakage correction; 2) with leakage correction using a method adopted by FDA 510K cleared NordicICE; 3) with leakage correction using leakage rate determined from the new “Patlak” approach. In addition, rCBV (no leakage correction) of each R2* time-course from Fe CA is also calculated. Results: Pairing Fe rCBV with each of the three Gd rCBVs respectively, Bland-Altman plots show that the uncorrected Gd rCBV generally underestimates (mean difference -0.33), the method adopted by NordicICE often overestimates (mean difference 0.45), and the new approach (mean difference 0.09) provides the best agreement between the leakage-corrected Gd rCBV and the Fe rCBV. Conclusions: The new approach significantly simplifies rCBV quantification. A linear portion is commonly visible in the transformed data. This implies a pseudo leakage rate constant exists. Current approach predicts that pseudo leakage rate constant will depend on the pre-load dose (an addition CA injection shortly prior to DSC study) detail (CA injection time, dose, etc.). Author Disclosure: X. Li: None. C.G. Varallyay: None. S. Gahramanov: None. W.D. Rooney: None. E.A. Neuwelt: None.
2181 Dose-Escalated Intensity Modulated Radiation Therapy and Increased Radiation Doses to Subventricular Zones in Treatment Outcomes of Patients With Glioblastoma Multiforme G. Kusumawidjaja, P. Gan, D. Tan, E. Chua, C. Tham, F. Wong, and M. Chua; National Cancer Centre Singapore, Singapore Purpose/Objective(s): Despite the landmark improvement of treatment outcomes with the advent of concurrent temozolomide and radiation therapy (RT) in patients with glioblastoma multiforme (GBM), primary tumor control remains suboptimal, with recurrences mostly occurring within the high dose irradiated region (60 Gy). This study seeks to address if dose escalated RT (70 Gy), delivered using intensity modulated RT (IMRT), improves tumor control and survival outcomes in patients with GBM. Materials/Methods: Patients with surgically resected or biopsy proven GBM were eligible for dose escalated IMRT. A simultaneous boost technique was adopted to deliver 70 Gy (2.33 Gy/fraction) and 60 Gy in 30 fractions over 6 weeks to the following clinical target volumes (CTV70, CTV60). CTV70 was the tumor bed and/or contrast enhancing region with a 0.5 cm margin, while CTV60 was defined similarly, albeit with a conventional margin of 2.0 cm. A further 0.5 cm expansion of the borders of CTV70 and CTV60 derived the final treated volumes. Patients received concurrent and adjuvant TMZ with IMRT. Results: Forty-nine patients were analyzed with a median follow-up of 28.6 months for patients who remain alive. Median progression-free survival (PFS) and overall survival (OS) were 7.1 (95% CI Z 5.6-9.6) and 15.2 (11.0-18.6) months, respectively. 30.6% and 3.1% of patients remained progression free at 1 and 3 years, respectively. Primary tumor progression was definitive in 32 individuals. Among them, 68.8% (22/32) were in-field, 28.1% (9/32) marginal, and 3.1% (1/32) distal, defined as > 80%, 20-80%, and 0.05). Conclusions: This study suggests that the BED based on the LQ model may be applicable to Hypo-RT corresponding to 12 Gy/1 fx in vivo. Author Disclosure: N. Fujitani: None. T. Yoshimine: None. E. Katayama: None. N. Wakai: None. K. Inoue: None. I. Asakawa: None. T. Tamamoto: None. Y. Yoshda: None. S. Ishiuchi: None. M. Hasegawa: None.
2183 Toxicity, Hospitalization Burden, and Survival Among Glioblastoma Patients Receiving Chemoradiation R. Rahman,1 P.J. Catalano,2 A.D. Norden,2 P.Y. Wen,2 D.A. Reardon,2 E.Q. Lee,2 L. Nayak,2 R. Beroukhim,2 I.F. Dunn,2 A.J. Golby,2 M.D. Johnson,2 E.B. Claus,2 E.A. Chiocca,2 B.M. Alexander,2 and N.D. Arvold2; 1Harvard Medical School, Boston, MA, 2Dana-Farber/ Brigham & Women’s Cancer Center, Boston, MA
2184 The Battle Between Amino Acid PET and Functional MRI: Precision of Tumor Delineation Examined by Glioma Progression Pattern After Radiation Therapy C. Debus,1,2 S. Combs,1,2 R. Floca,3 K. Maier-Hein,4 M. Nolden,4 C. Schwager,1,2 A. Radbruch,1,5 K. Lutz,5 O. Ja¨kel,1,2 W. Wick,1,6 M. Bendszus,5 S. Heiland,5 U. Haberkorn,7 J. Debus,1,2 and A. Abdollahi1,2; 1German Cancer Consortium (DKTK), Heidelberg, Germany, 2Translational Radiation Oncology, Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg Institute of Radiation Oncology (HIRO), University of Heidelberg Medical School, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany, 3Software Development for Integrative Diagnostik and Therapie, German Cancer Research Center (DKFZ), Heidelberg, Germany, 4Division of Medical and Biological Informatics, German Cancer Research Center (DKFZ), Heidelberg, Germany, 5Department of
