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  • 1
    Online Resource
    Online Resource
    ACTR-70. A MULTISITE CLINICAL TRIAL OF SPECTROSCOPIC MRI-GUIDED RADIATION DOSE ESCALATION IN GLIOBLASTOMA PATIENTS
    Oxford University Press (OUP) ; 2019
    In:  Neuro-Oncology Vol. 21, No. Supplement_6 ( 2019-11-11), p. vi29-vi30
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 21, No. Supplement_6 ( 2019-11-11), p. vi29-vi30
    Abstract: The standard of care for glioblastoma is neurosurgical resection followed by radiation therapy (RT) and temozolomide (TMZ) chemotherapy. Although RT is effective for glioblastoma, attempts to improve survival using RT dose escalation above 60 Gy have been largely unsuccessful. This may be because prior attempts have been targeted to resection cavity or enhancing tumor, which may not accurately predict areas at highest recurrence risk. To overcome the limitations of standard T1 and T2-weighted MRI in predicting tumor recurrence, we have shown that supplementation with 3D high-resolution spectroscopic MRI (sMRI) identifies actively proliferating tumor beyond areas of T1-enhancement by measuring endogenous metabolites and their ratios. Previously, we demonstrated that the choline to N-acetylaspartate ratio (Cho/NAA) best correlates with tumor cellularity in surgically resected tissue (ρ=0.82, p 〈 0.001) and, most importantly, areas of sMRI metabolic abnormalities predate disease recurrence in those same areas (Cordova et al, Neuro-Oncology 2016). Therefore, we seek to identify whether sMRI can be used by radiation oncologists to choose the optimal regions to target for RT dose escalation. To assess its feasibility and safety, we developed a web-based imaging platform designed specifically to incorporate sMRI into the RT planning clinical workflow and are using it in a multisite sMRI-guided dose escalation trial (NCT03137888; Emory, Johns Hopkins, U. Miami). Recently, we have completed full enrollment including 30 patients treated with sMRI-guided dose escalated RT across three institutions. We have demonstrated successful integration of sMRI into the RT planning workflow, and we have delivered sMRI-guided dose escalated RT plans to glioblastoma patients without severe adverse events to date. Follow-up data will be analyzed for overall and progression-free survival. Based on the feasibility and safety of this technique in the current trial, we plan to assess the efficacy of sMRI-guided dose-escalated RT on patient outcomes in a NCTN clinical trial.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noz175.111
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2094060-9
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  • 2
    Online Resource
    Online Resource
    SYST-07. PILOT STUDY UTILIZING THE HDAC INHIBITOR BELINOSTAT WITH CHEMORADIATION FOR NEWLY-DIAGNOSED GLIOBLASTOMA
    Oxford University Press (OUP) ; 2021
    In:  Neuro-Oncology Advances Vol. 3, No. Supplement_4 ( 2021-09-21), p. iv9-iv10
    Details
    In: Neuro-Oncology Advances, Oxford University Press (OUP), Vol. 3, No. Supplement_4 ( 2021-09-21), p. iv9-iv10
    Abstract: Glioblastomas (GBMs) are highly aggressive brain tumors with poor prognosis. Belinostat is a histone deacetylase inhibitor with blood–brain barrier permeability, anti-GBM activity, and potential to enhance chemoradiation. This clinical trial sought to determine a tolerable dose of concurrent belinostat and assess the clinical efficacy of combining this drug with standard-of-care therapy. METHODS 13 patients each were enrolled in control and belinostat cohorts. The belinostat cohort was given a belinostat regimen (500-750mg/m2 1x/day x 5 days) every 3 weeks (weeks 0, 3, and 6 of RT). All patients received standard temozolomide and radiation therapy (RT). Patient outcomes included progression-free survival, overall survival (OS), and analysis of recurrence pattern of the recurrent gross tumor volume (rGTV). RESULTS Belinostat at 750 mg/m2 produce dose-limiting toxicities (DLTs) in 2 of 3 patients while belinostat at 500 mg/m2 did not result in DLTs. Median OS was 18.5 months for the belinostat cohort and 15.8 months for the control cohort (p=0.53). The rGTVs in the control cohort occurred in areas that received higher radiation doses than that in the belinostat cohort. For those belinostat patients that experienced out-of-field recurrences, tumors were detectable by spectroscopic MRI (sMRI) before RT. In particular, one belinostat patient had an IDH-mutant GBM that had an extraordinary response to therapy with significant shrinkage of enhancing tumor much greater than expected. CONCLUSION Belinostat given concurrently at 500 mg/m2 is well-tolerated. While median OS was not significantly increased for the belinostat cohort, recurrence analysis suggests better in-field control with belinostat, suggesting a radio-sensitizing effect. This study suggests that belinostat can act as a synergistic therapeutic agent for GBMs that may be further enhanced by sMRI-guided RT and may be particularly effective against IDH mutant tumors. A trial is currently in development using belinostat with sMRI-guided RT for IDH-mutant high-grade gliomas.
    Type of Medium: Online Resource
    ISSN: 2632-2498
    URL: Article
    DOI: 10.1093/noajnl/vdab112.035
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 3009682-0
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  • 3
    Online Resource
    Online Resource
    A multisite clinical trial of spectroscopic MRI-guided radiation dose escalation for newly-diagnosed glioblastomas.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 2018-2018
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 2018-2018
    Abstract: 2018 Background: Glioblastoma (GBM) is the most common adult primary malignant brain tumor. These pts have poor outcomes [median overall survival (OS) ̃ 16 months] despite radiation therapy (RT) to 60 Gy and temozolomide (TMZ). Magnetic resonance spectroscopy (MRS) measures levels of specific metabolites in the brain including choline (Cho) and N-acetyl aspartate (NAA). Previously, we found that high Cho/NAA ratios can aid in localizing regions of brain at high risk for GBM recurrence that may not be appreciated on standard contrast-enhanced (CE) MRI. Based on this finding, we conducted a clinical trial to assess the feasibility and safety of using an advanced volumetric MRS technique termed spectroscopic MRI (sMRI) to guide RT dose escalation for newly-diagnosed GBMs. Methods: Our clinical trial (NCT03137888) funded by the NCI (RO1CA214557) enrolled pts at 3 institutions (Emory U, U Miami, Johns Hopkins U) from 5/2017 to 4/2019. This study was approved by the IRB at each respective institution. Eligibility criteria included newly-diagnosed GBM pts ≥ 18 years of age with a tumor site that could be adequately imaged by sMRI. Cho/NAA ratio was normalized to the contralateral normal appearing white matter (NAWM). For RT planning, standard gross tumor volumes (GTV1 & 2) were defined based on T2-FLAIR and T1 CE MRIs and 5 mm margins were added to generate clinical tumor volumes (CTV1 & 2). GTV3 ( = CTV3, sMRI-defined) was generated by the union of residual CE tumor and Cho/NAA ≥ 2x NAWM. To remain eligible, CTV3 was required to be ≤ 65 cc. Planning target volumes (PTVs) were generated by applying a 3 mm margin around CTVs. 50.1, 60 and 75 Gy in 30 fractions were prescribed to PTV1, PTV2 and PTV3, respectively. All pts received standard concurrent/adjuvant TMZ. Survival curves were generated by the Kaplan-Meier method. Toxicities were assessed according to CTCAE v4.0. Results: 30 pts met eligibility and were treated on study. Mean/median ages were 56.4/58.9 years. 9 pts (30%) were MGMT methylated; 2 pts (6.7%) harbored an IDH1 mutation. With median followup of 21.4 months in censored pts, median OS was 23.0 months. 11 of 30 pts were documented to have experienced grade 3 or greater toxicities that were at least possibly due to their treatment. Of the 7 pts who experienced these by 9 months post-RT, most were attributable to TMZ (thrombocytopenia x 4, thrombocytopenia/neutropenia x 1, transaminitis x 1) and only one case (headaches/fatigue x 1) could potentially be ascribed to RT. Increased risk of pseudoprogression or radiation necrosis, especially beyond 3 months post-RT, was noted but these were clinically manageable and did not result in toxicity ≥ grade 3. Conclusions: Dose-escalated RT to 75 Gy guided by sMRI appears feasible and safe for pts with newly-diagnosed GBMs. OS outcome is also quite promising and warrants additional testing. Based on these results, a phase II randomized trial is planned at ECOG-ACRIN (EAF211). Clinical trial information: NCT03137888.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.2018
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    NIMG-23. BRAIN TUMOR REPORTING AND DATA SYSTEM (BT-RADS) AND QUANTITATIVE TOOLS TO GUIDE ITS IMPLEMENTATION
    Oxford University Press (OUP) ; 2019
    In:  Neuro-Oncology Vol. 21, No. Supplement_6 ( 2019-11-11), p. vi166-vi166
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 21, No. Supplement_6 ( 2019-11-11), p. vi166-vi166
    Abstract: Glioblastoma is the most aggressive primary adult brain tumor, with median survival of 15 months despite surgery and chemoradiation. MRI is used to guide treatment decisions, but imaging interpretation is challenging because of subtle findings with overlap between treatment effect and disease progression. The most frequently used quantitative brain tumor assessment metric is the Response Assessment in Neuro-Oncology (RANO), but this scoring system requires manual delineation 2-D metrics which can be subjective and is not directly tied to patient management decisions. The Brain Tumor Reporting and Data System (BT-RADS) is a novel, management-based reporting system developed by the Emory brain tumor team to improve quantitation and reduce bias in imaging assessment. BT-RADS scoring incorporates quantitative volumetric changes in contrast-enhanced T1-weighted (CE-T1w) and fluid attenuation inversion recovery (FLAIR) MRI, patient medications, clinical outcome, and treatment dates, and has been aligned closely with management decisions. To improve repeatability and reliability of scoring, we have begun to develop a cloud platform to help physicians utilizing BT-RADS. Longitudinal MRI data from each patient are automatically co-registered using rigid registration and aligned using trilinear interpolation, enabling voxel-to-voxel comparisons across multiple scans. The platform implements a semi-automated algorithm to segment tumor volumes using curvature flow, thresholding, and morphological filtering which expedites clinical review, as physicians simply edit and confirm segmentation accuracy rather than manual segmenting and measuring 2D images. Additionally, radiation dose maps can be overlaid on clinical images to determine what may be treatment effect and in-field vs. out-of-field recurrence. A secure web interface allows easy use by the entire treatment team, e.g. in a “tumor board” setting. Future plans include incorporating clinical and genomic data and fully automating tumor segmentation. The goal of this work is to provide more quantitative and objective follow-up metrics that can guide clinical decision making in glioblastoma patients.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noz175.695
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2094060-9
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  • 5
    Online Resource
    Online Resource
    RTHP-29. A FEASIBILITY STUDY OF RADIATION THERAPY DOSE ESCALATION GUIDED BY SPECTROSCOPIC MRI IN PATIENTS WITH GLIOBLASTOMA
    Oxford University Press (OUP) ; 2018
    In:  Neuro-Oncology Vol. 20, No. suppl_6 ( 2018-11-05), p. vi231-vi231
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 20, No. suppl_6 ( 2018-11-05), p. vi231-vi231
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noy148.959
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
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  • 6
    Online Resource
    Online Resource
    CTNI-13. UPDATES ON CLINICAL OUTCOMES AND TUMOR RECURRENCE PATTERNS OF A HUMAN PILOT STUDY ASSESSING EFFICACY OF BELINOSTAT (PXD-101) COMBINING WITH CHEMORADIATION IN TREATING GLIOBLASTOMA
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii44-ii44
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii44-ii44
    Abstract: Glioblastoma (GBM) is highly aggressive with poor prognosis. Belinostat is a histone deacetylase inhibitor with blood–brain barrier permeability that has anti-GBM activity and may enhance effects of chemoradiation. Our institution conducted a clinical trial evaluating clinical efficacy of belinostat with standard-of-care therapy for GBMs. METHODS 13 and 14 patients were enrolled into cohort 1 (c1, control) or cohort 2 (c2, belinostat) with 12 in each group with sufficient follow-up MRIs for recurrence analysis. All patients received concurrent, adjuvant temozolomide and focal radiation therapy (RT). For c2 patients, the belinostat regimen (500-750mg/m2 1x/day x 5 days) was given over three cycles every 3 weeks (weeks -1, 2, and 5 of RT). RT margins of 5–10 mm and 3 mm were added to generate clinical tumor volumes and planning target volumes (PTVs). PTV1 (based on FLAIR MRI) and PTV2 (based on CE-T1w MRI) received 51 and 60 Gy, respectively, over 30 fractions. Volume at initial recurrence (rGTV) was contoured. RESULTS Mean age was 58.3 years for c1 and 51.1 years for c2. Patient/tumor characteristics were similar between cohorts. Median OS were 16.6 and 18.5 months for c1 and c2 (p=0.538), respectively. Average minimum, maximum and mean radiation dose to rGTV was 54.1 Gy, 64.2 Gy and 62 Gy, for c1, and 47.5 Gy, 57.6 Gy and 53.5 Gy, for c2 (p=0.322, 0.088 and 0.071), respectively. The mean overlap between rGTV and PTV1/PTV2 for c1 & c2 were 99.2% & 96.9%/99.8% & 78.7% (p=0.489/0.133), respectively. CONCLUSION Median OS was slightly longer for c2 though not statistically significant. rGTV in c1 received higher radiation doses and had more overlap with PTV2 than in c2. Out-of-field recurrence appears more likely in c2 suggesting better infield control with belinostat. This study highlights the potential of belinostat as a synergistic therapeutic agent for GBM treatment.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noaa215.180
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2094060-9
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