bluuebunny/crossref_metadata_2025_split huggingface dataset:
RADT-24. PHASE II STUDY OF PROTON RADIATION THERAPY FOR LOWER GRADE GLIOMAS
Authors: Slater Jason , Horick Nora , Nachtigall Lisa , Parsons Michael , Zarrella Giuliana , Tritos Nicholas , Dietrich Jorg , Pursley Jennifer , Fullerton Barbara , Wang Irene , Oh Kevin , Loeffler Jay , Yeap Beow , Shih Helen 
Published: November 2022

Abstract

PURPOSE
To report preliminary results on outcomes of patients with lower grade gliomas (LGG) treated with proton therapy.

METHODS
Patients with grade II or IDH mutant grade III glioma and indications for radiation therapy were enrolled in a prospective single arm trial of proton therapy (PRT), receiving a dose of 54 Gy(RBE) or 59.4 Gy(RBE), respectively. Comprehensive baseline and regular post-treatment evaluations of neuroendocrine function, neurocognitive functions (NCF), quality of life (QOL), and progression-free survival (PFS) were performed.

RESULTS
Among 60 patients (median age 40.8) who received PRT, 28 (47%) were men, and 39 (65%) were WHO grade II. Eighteen patients (30%) were IDH mutant+1p/19q co-deleted, 36 (60%) were IDH mutant astrocytoma, and 6 (10%) were IDH wildtype. Treatment was at initial diagnosis (41; 68%) or progression (19; 32%). Median follow-up after PRT was 4.1 years. All current data are reported for 3 years from PRT. PFS at 3 years was 86% for all patients, 84% for grade II (n = 39), and 90% for favorable grade III gliomas (n = 21). PFS was 83% for IDH mutant astrocytoma, and 94% for IDH mutant+1p/19q co-deleted oligodendrogliomas. New endocrine dysfunction was detected in 3 patients (5%). There was one grade 4 case of brain necrosis (2%) but no grade 3 toxicities. NCF decline, defined by Z-score drop of &gt;/= 1SD on clinical trials battery composite, occurred in 7% (n = 3/43). QOL assessment by FACT-Brain showed 16% with decline of &gt;/= 10 points (n = 7/43).

CONCLUSIONS
At 3 years post-treatment, LGG patients receiving PRT have a high PFS, similarly to previous reports on photon therapy, few new neuroendocrine deficiencies, modest treatment toxicities, and minimal decline in NCF or QOL. These positive outcomes may be attributable to limited integral dose to the brain by use of PRT, demonstrating its value in treatment of LGG patients with long survival expectations.
RADT-25. UNDERSTANDING PATTERNS OF TUMOUR INFILTRATION IN PATIENTS WITH MULTIFOCAL GLIOBLASTOMA AND IMPACT ON SURVIVAL OUTCOMES
Authors: Back Michael , Horsley Patrick , Yim Jackie , Drummond James 
Published: November 2022

Abstract

BACKGROUND
Multifocal glioblastoma(MF-G) are often clustered with presumed uniform worse prognosis. This study explores varying patterns of infiltration of MF-G in relation to radiological features, including presence of contiguous MRI T2-weighted abnormalities and adjacent neural tract pathway involvement.

METHODS
Consecutive patients with glioblastoma from 2016-2020 managed under EORTC-NCI(Stupp60Gy) Protocol had manual tumour segmentation on T1gd and T2w sequences. Multifocal disease was defined as T1gd or solid T2w-abnormality a minimum of 10mm from the dominant lesion. Number of foci, maximum dimension, cortical/white matter site and distance from dominant lesion were recorded. Presence of contiguous T2w-abnormality was recorded, and correlated to ten major neural tract pathways. Progression-free(PFS) and overall survival(OS) were analysed.

RESULTS
Forty of 177 patients(23%) were identified with MF-G. These had less near-total resection(p = 0.001), but no difference in ECOG(p = 0.16), or MGMT-methylation(p=0.23). Foci had median size of 14.5mm (q1-3: 10-20); 73% enhancing and 58% solitary. Median distance from dominant lesion was 23mm (q1-3:15-25). Contiguous T2w abnormality and involvement of identified neural tract was evident in 78% and 83% respectively. The multifocal lesion was based in cortex in 33%, and white matter in 67%. Survival outcomes were worse with MF-G: OS (p &lt; 0.01) was 16.0 months (95%CI: 13.6-18.4) versus 19.9 months (95%CI: 17.6-22.2); and PFS (p = 0.01) was 10.8 months (95%CI: 9.9-11.7) versus 13.6 months (95%CI: 11.1-16.1). Improved PFS was associated with larger lesion size(p = 0.04), and cortical lesions(0.04). Those MF-G with contiguous T2w-abnormality(p = 0.06); identified neural tract(p = 0.07) or enhancement(p = 0.08) had trend to worse PFS. MGMT(p = 0.10), ECOG(p = 0.62) and extent of resection(p = 0.07) were not associated with PFS, nor radiological factors of foci number(p = 0.19) and lesion distance(p = 0.16).

CONCLUSIONS
Radiological pattern of infiltration in MF-G is associated with different natural history. Improved PFS was associated with cortical foci without contiguous T2 abnormality or tract involvement. Recognising infiltration patterns may impact on RT target volume delineation and understanding prognosis.
RADT-26. PATTERNS OF RECURRENCE IN PATIENTS TREATED WITH RE-IRRADIATION FOR RECURRENT HIGH-GRADE GLIOMA
Authors: Datta Debanjali , Dasgupta Archya , Meena Lilawati , Chatterjee Abhishek , Sahu Arpita , Chaudhari Amit , Joshi Kishore , Puranik Ameya , Rangarajan Venkatesh , Singh Vikas , Shetty Prakash , Moiyadi Aliasgar , Menon Nandini , Patil Vijay , Sahay Ayushi , Sridhar Epari , Kinhikar Rajesh , Gupta Tejpal 
Published: November 2022

Abstract

Purpose/Objective(s)
Re-irradiation (ReRT) is often used to treat recurrent high grade glioma (HGG). There is limited literature regarding the patterns of recurrence following ReRT, which was investigated in the current study.

Materials/METHODS
Patients with available radiation (RT) contours, dosimetry, and imaging-based evidence of recurrence were included in the retrospective study. All patients were treated with fractionated RT using conformal technique. Recurrence was documented as per decision in tumor board based on imaging with magnetic resonance imaging (MRI) or Flouroethyl-L-Tyrosine (FET) positron emission tomography (PET), which was registered with the planning CT. Failure patterns were classified as in-field, marginal, and out-field as decided by &gt;50% recurrence volume within 95%, 20-95%, and outside 20% isodose lines, respectively.

RESULTS
Study population included 37 patients treated with median dose of 54 Gy (range 50.4-54 Gy). Before ReRT, 92% patients had undergone surgery (biopsy in 3, gross total resection in 9, subtotal resection in 22), 62% received concurrent chemo with ReRT, and 49% received maintenance chemotherapy. Median time to recurrence was 9 months (7-16 months, median 10 and 8 months respectively for in-field and marginal/out-field recurrence). In-field, marginal, and out-field recurrence were seen in 24 (65%), 10 (27%), and 3 (8%), respectively. Recurrence mapping was done using MRI, PET, or both in 27, 3, and 7, respectively. Of 24 patients with in-field recurrence, 8 and 16 had disease volume within gross tumor volume and clinical target volume, respectively. 2 patients had leptomeningeal dissemination (1 with majority of recurrence volume in-field and 1 with marginal failure in addition to metastatic disease).

CONCLUSION
Following ReRT for HGG, the majority of recurrence was in the high dose region, suggesting the use of conservative target volumes. Future studies are required for feasibility of dose-escalation to improve control rates, particularly in patients with long intervals from first course of RT.
RADT-34. ANALYSIS OF A METHYLATION CLASS-GUIDED RADIOTHERAPY IN MENINGIOMA PATIENTS - AND THE PROSPECTIVE PHASE II MARCIE TRIAL WITH CARBON-ION BOOST RADIOTHERAPY
Authors: Deng Maximilian , Hinz Felix , Sievers Philipp , Eichkorn Tanja , Anna Kraemer , Eva Meixner , Elisabetta Sandrini , Juliane Hoerner-Rieber , Semi Harrabi , Katharina Seidensaal , Andreas Unterberg , Wick Antje , Wick Wolfgang , von Deimling Andreas , Combs Stephanie , Klaus Herfarth , Juergen Debus , Sahm Felix , Laila Koenig 
Published: November 2022

Abstract
Meningiomas represent the most common primary brain tumor type, with a recurrence rate of approximately 20% following resection. Classification by molecular classes was demonstrated to be more accurate in identifying patients at high risk of disease progression in meningiomas, compared to WHO grading only. Novel radiotherapeutic modalities using protons or carbon ions provide an increased relative biological effectiveness (RBE) compared to photons, enabling a higher local dose deposition while reducing the radiation dose for organs of risks. The prospective single-arm phase II - MARCIE trial investigated a bimodal radiotherapy using photons (50 Gy in 25 fractions) and a carbon-ions boost with 18 Gy (RBE) in 6 fractions. Local progression-free survival after 3 years was defined as primary endpoint. In total, 33 patients were recruited before termination of the trial. After 3 years, local progression free survival was estimated at 94.7% and overall survival at 89.8%. Serious adverse events in the form of radiation necrosis were observed in 3 cases, requiring a subsequent treatment with bevacizumab. Post-hoc DNA methylation profiling revealed that relapses occur more frequently in high-risk meningiomas following radiotherapy, compared to the intermediate risk-group, confirming the prognostic relevance of the methylation-based meningioma classifier.Subsequently, a retrospective matched-pair analysis was performed to compare irradiated (n &gt; 100) and non-irradiated meningiomas, stratified into the molecular risk groups (ben, int, high). The clinical benefit of postoperative radiotherapy and dose escalation with regard to the local control are currently being assessed for the respective molecular meningioma classes. Postoperative, bimodal radiotherapy with carbon-ion boost represent an auspicious treatment modality with an excellent local tumor control following resection. Molecular risk stratification is crucial in identifying patients who might benefit from postoperative radiotherapy.
RADT-35. A PROSPECTIVE REGISTRY STUDY OF 68GA-DOTATATE PET INCORPORATION INTO TREATMENT PLANNING OF INTRACRANIAL MENINGIOMAS
Authors: Perlow Haley , Prasad Rahul , Siedow Michael , Gokun Yevgeniya , Matsui Jennifer , Blakaj Dukagjin , Beyer Sasha , Thomas Evan , Raval Raju , Chakravarti Arnab , Prevedello Daniel , Hardesty Douglas , Elder James , Palmer Joshua 
Published: November 2022

Abstract

Introduction
The current standard for meningioma radiation planning involves MRI-based image guidance. SSTR ligands such as 68Ga-DOTATATE are being explored for meningioma radiotherapy treatment planning due to universal expression of somatostatin receptor 1/2 in meningioma tissue. We hypothesize that 68Ga-DOTATATE PET utilization can reduce the risk of local failure (LF) through precise radiation planning and may also suggest that patients who have local PET avidity after a perceived GTR may be poor observation candidates.

METHODS
A single institution prospective registry study was created and included intracranial meningioma patients who received a 68Ga-DOTATATE PET scan to assist with radiation oncologist decision-making. These were ordered for all meningioma patients as a departmental standard. Patients who received a PET scan from 1/1/2018-2/25/2022 were eligible for inclusion.

RESULTS
60 patients were treated in this prospective registry. 22%, 72%, and 7% were World Health Organization (WHO) high, intermediate, and low-risk, respectively. After completing their PET scan, 48, 11, and 1 patient(s) proceeded with RT, observation, or redo craniotomy. The median follow up was 16 months (IQR 8.3-23.1). 3 patients (5%) experienced LF between 9.2-28.5 months after diagnosis. 2 patients with LF had PET-avid disease in their post-operative cavity and elected for observation prior to recurrence, and 1 high-risk patient with multifocal disease experienced LF 2 years after a second radiation course and multiple previous recurrences. LF rates after radiation were 0%, 0%, and 8% in the low, intermediate, and high-risk cohorts, respectively. There were no Grade 3 or higher toxicities attributed to PET-guided radiation.

CONCLUSION
This is the largest known population of intracranial meningioma patients followed by physicians who utilized 68Ga-DOTATATE PET guided therapy. Only 1 patient experienced LF after receiving PET-guided radiation therapy, likely due to a radioresistant histology. Incorporating 68Ga-DOTATATE PET into future trials may assist with clinician decision-making and improve patient outcomes.
CTIM-14. COMPREHENSIVE BIOMARKER ANALYSIS OF RESPONDERS AND NON-RESPONDERS IN A PHASE IIA TRIAL OF A CMV VACCINE IMMUNOTHERAPEUTIC CANDIDATE (VBI-1901)
Authors: Wen Patrick Y , Reardon David A , Forst Deborah , Lee Eudocia , Daoud Teresa , Berthoud Tamara , Soare Catalina , Diaz-Mitoma Francisco , Anderson David E , Lassman Andrew , Iwamoto Fabio 
Published: November 2022

Abstract
Cytomegalovirus (CMV) antigens have been reported in over 90% of GBMs. CD4+ and CD8+ T cells are most frequently directed against the gB and pp65 antigens, respectively, which are immunogenic targets in a CMV-based GBM immunotherapeutic. First-recurrent GBM patients were enrolled, with Karnofsky Performance Status of at least 70, to receive VBI-1901 (a gB/pp65 enveloped virus-like particle [eVLP]) adjuvanted with GM-CSF and given intradermally (NCT03382977). Patients were vaccinated with VBI-1901 every 4 weeks, with serologic immune-monitoring 2 weeks after each vaccination and surveillance brain MRI scans every 6 weeks. Sixteen patients (8 women, 8 men) with a median age of 55 (33-67 yrs) were enrolled into the GM-CSF arm. Seven tumor responses, including two durable partial responses, were observed which led to an 18-month OS rate of 25% and mOS of 56 weeks. Detailed immunological testing was performed to identify potential correlations at baseline and after treatment between biomarkers and tumor responses. Analyses included class I and II HLA typing, modulation of plasma cytokine and chemokine responses, boosting of CMV-specific antibody and IFN-g ELISPOT responses, and modulation of CMV-specific CD4 Tem cells, of which only differential trafficking of the CD4 Tem cells appears to distinguish patients with tumor responses from those with tumor progression. Single cell, RNAseq is underway in an attempt to understand mechanistic differences in these immune cell populations in Tumor Responders vs. Non-Responders. The U.S. FDA granted Fast Track Designation to VBI-1901 adjuvanted with GM-CSF in first-recurrent GBM patients, and an expansion of the ongoing trial with this formulation in this patient population, with the addition of randomization with a contemporaneous control arm, is anticipated to begin in Q3 2022.
CTIM-20. PROSPECTIVE RANDOMIZED PHASE II PLACEBO-CONTROLLED TRIAL OF SURVAXM PLUS ADJUVANT TEMOZOLOMIDE FOR NEWLY DIAGNOSED GLIOBLASTOMA (SURVIVE)
Authors: Ahluwalia Manmeet , Ciesielski Michael J , Abad Ajay , Reardon David A , Aiken Robert , Barbaro Marissa , Sinicrope Kaylyn , Peereboom David , Odia Yazmin , Brenner Andrew , Venur Vyshak , Belal Ahmed , Qiu Jingxin , Khosla Atulya , Schilero Cathy , Casucci Danielle , Mechtler Laszlo , Fenstermaker Robert 
Published: November 2022

Abstract

BACKGROUND
Newly diagnosed glioblastoma (nGBM) has a dismal prognosis with survival of 15-18 months. Tumor associated “survivin” protein is expressed in &gt;95% of nGBM and is targetable with the use of SurVaxM, shown to be effective at generating cytotoxic T lymphocytes.

METHODS
nGBM patients are being enrolled in this randomized placebo-controlled trial phase II study. Eligibility Criteria includes age ≥ 18, KPS ≥ 70, IHC confirmed survivin-expression, and residual contrast enhancement of ≤1 cm3 by MRI, within 72 hours of surgical resection. Patients are randomized 3:2 into two arms A:B to treatment with SurVaxM in emulsion with Montanide plus sargramostim (local injection) and standard-of-care TMZ (Arm A), or placebo (saline in emulsion with Montanide) plus saline (local injection) and standard-of-care TMZ (Arm B). There are three active treatment phases in the study with vaccine priming (VP) phase; adjuvant TMZ phase; and Vaccine Maintenance (VM) phase. A total of four (4) priming doses of SurVaxM in Montanide plus sargramostim (“SurVaxM/sargramostim”) or placebo in Montanide/saline (“Placebo/Placebo”) will be administered every two weeks ( ± 3 days) during the priming phase, with subsequent dosing every 8 weeks ( ± 1 week) during the vaccine maintenance phase. After priming doses, SurVaxM/sargramostim or Placebo/Placebo will be administered every 8 weeks ( ± 1 week) until tumor progression or for a maximum of 24 months. The total sample size is of 265 patients, with 159 patients in the SurVaxM arm and 106 patients in the control arm. The primary objective is to determine the overall survival (OS), and the secondary objectives include progression-free survival (PFS), OS at pre-specified time points (OS-15, OS-18 and OS-24), PFS at pre-specified time points (PFS-3, PFS-6 and PFS-12) and evaluation of toxicities. Study duration is expected at 36 months, with enrollment ongoing at several centers and planned for total of 20 participating centers.
CTNI-05. MOLECULAR ANALYSIS OF THE PHASE I D-TERMINED TRIAL ON CONCURRENT AND ADJUVANT TEMOZOLOMIDE WITH MINOCYCLINE IN NEWLY DIAGNOSED HIGH-GRADE GLIOMA
Authors: McKean William , Boucher Kenneth , Yang Jingye , Sonty Karthik , Jensen Randy , Shrieve Dennis , Salzman Karen , Johnson Brett , Thomas Melissa , Moss Whitney , Behunin Amanda , Prystas Elizabeth , Colman Howard , Cohen Adam 
Published: November 2022

Abstract

BACKGROUND
Minocycline blocks microglial TNF signaling and downstream NF-κB activation, which reduces the mesenchymal phenotype in preclinical models of GBM. Primary analysis of the D-TERMINED trial identified a maximal tolerated dose (MTD) of oral minocycline at 150 mg BID in combination with temozolomide and radiation. In the overall population, the secondary objective of improved PFS was not met. Here, response is further stratified by biomarkers delineating mesenchymal subtype (OLIG2, CD44), microglial activation (IBA-1), and NF-κB signaling (P-p65).

METHODS
Patients with newly diagnosed high-grade glioma received continuous oral minocycline during concurrent chemoradiation and adjuvant temozolomide. Twenty patients were included in the MTD efficacy population. Within this cohort, immunohistochemistry for OLIG2, CD44, IBA-1, and P-p65 was performed on nineteen patient tumor samples. For each biomarker, the mean percent positivity or number/HPF was compared between patients who exceeded or did not exceed expected PFS. Spearman correlation coefficients were also generated for pairwise comparison of these biomarkers.

RESULTS
In patients with high PFS, 12.7% of tumor cells were positive for OLIG-2, 36.5% for CD44, and 23.9% for P-p65, with 41.7 cells/HPF positive for IBA-1. Comparatively, in patients with low PFS, 9.4% of tumor cells were positive for OLIG-2 (p = 0.59), 34.1% for CD44 (p = 0.77), and 22.3% for P-p65 (p = 0.85), with 31.1 cells/HPF positive for IBA-1 per HPF (p = 0.38). The only biomarkers demonstrating significant relationship were P-p65 and IBA-1, with a rank correlation of 0.637 (p = 0.007).

CONCLUSIONS
Exploratory analysis of D-TERMINED concludes that OLIG-2, CD44, IBA-1, and P-p65 are not predictive of improved PFS within high-grade glioma patients treated with SOC and minocycline. Concurrent use of minocycline with chemoradiation is therefore not indicated in these or unselected populations. Significant correlation is seen between IBA-1 and P-p65, biomarkers of microglial activation and NF-κB signaling. SPONSORSHIP: Funding provided by the Musella Foundation and NIH grant P30CA042014.
CTNI-46. PIVOTAL STUDY TO EVALUATE SAFETY AND EFFICACY OF EXABLATE MODEL 4000 USING MICROBUBBLE RESONATORS TO TEMPORARILY MEDIATE BLOOD-BRAIN BARRIER DISRUPTION FOR LIQUID BIOPSY IN GLIOBLASTOMA (LIBERATE)
Authors: Ahluwalia Manmeet , de Groot John , Lee John , Mogilner Alon , Schwartz Theodore H , Burns Terry , Shah Bhavya , McDermott Michael , Bettegowda Chetan , Khosla Atulya , Sahgal Arjun , Mishra Mark , Achrol Achal S , Lipsman Nir , Woodworth Graeme 
Published: November 2022

Abstract

BACKGROUND
Glioblastoma (GBM) has dismal outcome of 14-16 months. One of the challenges of drug development in GBM is lack of requisite circulating-free (cfDNA) in blood samples to develop biomarker driven targeted therapy trials. The Exablate focused ultrasound with circulating microbubble resonators uses the concept of real-time imaging to treat small target spots focusing energy in a non-invasive manner, thereby disrupting the Blood-Brain Barrier (BBBD) with potential to increase cfDNA in blood.

METHODS
LIBERATE is a prospective, multi-center, self-controlled pivotal ongoing clinical trial in subjects with suspected GBM evaluating the safety and effectiveness of Exablate Model 4000 to disrupt BBB to achieve a greater proportion of cfDNA in samples taken post-BBB disruption as compared to the sample taken before BBBD. Fifty eligible subjects with suspected GBM who are scheduled to undergo brain tumor resection or biopsy at 10 centers in the U.S. will participate in this study. The primary endpoint is defined for each subject as ratio between his/her cfDNA amount found in the blood sample 1-hour post-BBBD procedure compared to the cfDNA amount found in the blood sample collected pre-BBBD procedure. This study proposes to demonstrate that on average there is at least 2-fold increase in cfDNA (measured by central laboratory) at 1 hour post BBBD. Confirmatory secondary analysis will evaluate correlation between patterns obtained in panel of biomarkers evaluated in the resected tumor tissue and/or biopsy sample and blood sample collected 1-hour post-BBBD. Exploratory endpoints will include: (1) sensitivity of detection of known somatic mutations in the circulating blood samples (circulating tumor DNA) before and after BBBD, (2) time of greatest yield of cfDNA in the samples collected post BBBD blood samples (at 30 min, 1-hour, 2-hour and 3-hour) to determine time of greatest yield, (3) correlation of biomarkers between the imaging and the post-BBBD biomarker samples. (NCT05383872)