bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTIM-30. PHASE II TRIAL OF PEMBROLIZUMAB IN RECURRENT AND RESIDUAL HIGH-GRADE MENINGIOMAS
Authors: Brastianos Priscilla , Kim Albert , Giobbie-Hurder Anita , Lee Eudocia Quant , Wang Nancy , Eichler April , Chukwueke Ugonma , Forst Deborah , Arrillaga-Romany Isabel , Dietrich Jorg , Lou Kevin , Larson Juliana , Mora Joana , Nayyar Naema , Loeffler Jay , Oh Kevin , Shih Helen , Curry William , Cahill Daniel , Barker Fred , Gerstner Elizabeth , Santagata Sandro 
Published: November 2021

Abstract

INTRODUCTION
High-grade meningiomas are associated with significant neuro-cognitive morbidity and a poor prognosis. Systemic therapies, to date, have demonstrated minimal efficacy. We recently found that high-grade meningiomas harbor an immunosuppressive tumor microenvironment and that programmed cell death-ligand 1 (PD-L1) expression may contribute to the aggressive phenotype of these tumors. Therefore, we conducted a single-arm, open-label phase II trial evaluating efficacy of pembrolizumab, a PD-1 inhibitor, in a cohort of 24 patients with recurrent and progressive grade II and III meningiomas.

METHODS
The primary endpoint was the rate of progression-free survival at 6 months. The trial distinguished between 6-month PFS (PFS-6) rates of 26% vs. 52%. If at least 10 patients demonstrated a 6-month PFS, among the 24 patients, the agent would be considered worthy of further study. This design has at least 88% power using an exact binomial test with a one-sided significance level of 0.1.

RESULTS
Between November 2017 to December 2019, twenty-four patients were enrolled. The majority of the patients in our cohort were heavily pre-treated; prior to enrolling to the study, twenty patients underwent more than one surgical resection and twelve patients had received more than one round of radiotherapy. Our study met its primary endpoint and achieved a 6-month progression-free survival rate of 0.50 (90% exact CI: 0.32-0.68) and a median PFS of 8.3 months (90% CI: 4.1-12.9 months). For the twelve patients who achieved the PFS-6 primary endpoint, median PFS from the start of treatment was 17.3 months (90% CI: 9.7 – 24.3 months). Four patients had grade-3 or higher adverse events that were at least possibly treatment-related, including colitis, skin infection, encephalopathy and transaminitis.

CONCLUSION
Our study achieved its primary endpoint. These results suggest that pembrolizumab exerts promising activity on these tumors and results in prolonged PFS compared to historical controls.
CTIM-31. A PHASE II, OPEN-LABEL, SINGLE ARM TRIAL OF PEMBROLIZUMAB FOR REFRACTORY ATYPICAL AND ANAPLASTIC MENINGIOMA AND HEMANGIOPERICYTOMA
Authors: Yust-Katz Shlomit , Amiel Alexandra , Yust-Katz Shlomit , Limon Dror 
Published: November 2021

Abstract

BACKGROUND
Grade II and III meningiomas are invasive tumors which tend to recur following initial treatment and are associated with shorter survival (relative to grade I). Hemangiopericytoma (HPC) is a dural based tumor that originates in the pericytes. Treatment options for these tumors include surgical resection and radiation. There are no defined standard treatments after failure these modalities, and effective systemic treatments are lacking. This trial concept was developed following previous reports of high PD-L1 levels in anaplastic meningioma. We currently report our initial experience with pembrolizumab for refractory atypical/anaplastic meningioma (RAM) and HPC patients.

METHODS
This is a single arm, single institute, phase 2 trial. Inclusion criteria included patients with RAM or HPC whose all previous lines of treatment were exhausted. All patients were treated with pembrolizumab (200mg every 3 weeks) until disease progression. Primary endpoint was 6- and 12-months progression free survival (PFS). The study was planned for 25 patients and we report here preliminary results.

RESULTS
Through February 2021, 12 patients were enrolled to this study (two with HPC, 10 with RAM). After a median follow up of 18.5 months, the 6 and 12 months PFS were 25% and 16.7% respectively, with a median PFS of 2.75 months. Two patients had a partial response while all others progressed, making the overall response rate 16.7%. One of the responders had HPC and has been stable for 30 months, while the second had atypical meningioma and was stable for 13 months. Median survival has not been reached yet; 1 year survival rate was 82.5%. Grade 3 toxicities included hyperglycemia, elevated liver enzymes and fatigue, with no grade 4 or 5 toxicities.

CONCLUSIONS
Pembrolizumab induced a low response rate for RAM and HPC. However, a subset of patients might benefit from this treatment with a prolonged response period.
CTNI-09. TRIDENT PHASE 3 TRIAL (EF-32): FIRST-LINE TUMOR TREATING FIELDS (TTFields; 200 KHZ) CONCOMITANT WITH CHEMO-RADIATION, FOLLOWED BY MAINTENANCE TTFIELDS/TEMOZOLOMIDE IN NEWLY-DIAGNOSED GLIOBLASTOMA
Authors: Shi Wenyin , Kleinberg Lawrence , Jeyapalan Suriya , Goldlust Samuel , Nagpal Seema , Combs Stephanie , Roberge David , Nishikawa Ryo , Reardon David , Grossman Rachel , Glas Martin 
Published: November 2021

Abstract

INTRODUCTION
Tumor Treating Fields (TTFields; 200 kHz; non-invasive, loco-regional antimitotic treatment) is approved for newly-diagnosed glioblastoma (ndGBM). In the Phase 3 EF-14 trial, post-surgical radiotherapy/temozolomide, followed by maintenance TTFields/temozolomide significantly increased overall survival (OS) and progression-free survival (PFS) in patients with ndGBM versus TMZ alone. Addition of maintenance TTFields did not increase systemic toxicity; and related adverse events (AEs) were mainly dermatological. In preclinical models, addition of TTFields increased the benefit of radiotherapy. Two pilot studies showed that TTFields concomitant with radiotherapy/temozolomide is feasible and well-tolerated. The benefit of TTFields concomitant with radiotherapy/temozolomide will be investigated in the TRIDENT trial.

METHODS
TRIDENT (EF-32; NCT04471844) is an international, pivotal, phase 3 randomized trial comparing triple-combination of TTFields/radiotherapy/temozolomide versus standard radiotherapy/temozolomide. Patients in both arms will receive maintenance TTFields/TMZ. Arrays of the Optune® System will be used to deliver TTFields (200 KHz) for ≥18 hours/day concomitant with radiotherapy. TTFields treatment will be continued until second disease progression (RANO) or 24 months, whichever occurs first. Patients with pathologically-confirmed ndGBM, ≥ 18 years of age (≥ 22 years of age; US), KPS ≥ 70, post-surgery/biopsy, and amenable for radiotherapy/temozolomide will be stratified by extent-of-resection and MGMT promoter methylation status. The primary endpoint is median OS. Secondary endpoints include median PFS (RANO), 1-year and 2-year survival rates, overall radiological response (ORR; RANO), PFS (PFS-6M, PFS-12M, PFS-2Y), severity and frequency of AEs (CTCAE V5.0), pathological post-treatment changes in resected GBM tumors, quality-of-life (EORTC QLQ-C30), and OS correlation to TTFields duration-of-usage. The hypothesis is that first-line TTFields/RT/TMZ triple-combination will significantly improve OS compared to radiotherapy/temozolomide; each followed by maintenance TTFields/temozolomide. Sample size (N=950; 475/arm) was powered for a HR &lt; 0.8 with 5% type I error. Survival will be measured from time-of-randomization. The TRIDENT trial is currently enrolling patients.

RESULTS/CONCLUSIONS
N/A TiP.
CTNI-10. ADVANCES IN MANAGEMENT OF LOW-GRADE GLIOMAS
Authors: Raval Ruchi , Pandya Aadi , Behl Jaspreet , Raval Sumul 
Published: November 2021

Abstract

BACKGROUND
Low-grade gliomas (LGGs) are common benign brain tumors that arise from glial cells of the brain. The complex and variable backgrounds of LGGs cause difficulties in assigning therapies. In this report, we compile findings relating to LGG genetics and treatment options in order to create a coherent summary for referential use.

METHODS
We compiled 70 articles from the past ten years that cover a broad range of topics pertaining to LGGs, including molecular, genetic, epigenetic, morphological, and other diagnostic factors, as well as prognosis and treatment options.

RESULTS
In order to provide proper treatment, the molecular basis and histology of the tumor must be addressed. The 1p/19q co-deletion indicator has been considered the gold standard of glioma diagnosis, but oft-sighted mutations in the IDH1 and IDH2 genes have given rise to three subgroups of 1p/19q co-deleted tumors, each associated with specific patterns of nervous cells. Other molecular markers and microRNA expression patterns have been studied for possible diagnostic and prognostic methods. Microsurgical resection is the singular treatment with highest overall survival (OS) and quality of life (QOL). Total gross resection is optimal, with patients having a 5-year OS of 100% with 90% tumor resection. Low doses of radiation are as effective as high doses and are better tolerated (with less cognitive deficits). Chemotherapy, specifically temozolomide, offers a favorable toxicity profile and QOL; additionally, seizure reduction is an early and consistent prognostic marker for survival after treatment with temozolomide.

CONCLUSIONS
The “wait and see” approach for treatment is no longer the standard for LGGs. Immediate treatment after diagnosis is recommended. Gross total resection (if achievable) is the most favorable treatment, with the highest OS and QOL. The use of temozolomide and radiotherapy is recommended. Histological background and genetic markers are vital for determining a treatment plan.
CTNI-28. VOLUMETRIC AND DOSIMETRIC PATTERNS OF FAILURE ANALYSIS OF A PHASE II CLINICAL TRIAL OF 18F-DOPA-PET DIRECTED DOSE ESCALATED RADIOTHERAPY FOR GLIOBLASTOMA
Authors: Breen William , Anderson S Keith , Pafundi Deanna , Kaufmann Timothy , Hunt Christopher , Lowe Val , Vogen Diane , Yan Elizabeth , Sarkaria Jann , Brown Paul , Kizilbash Sani , Uhm Joon , Ruff Michael , Zakhary Mark , Zhang Yan , Seaberg Maasa , Rehim Abdou Abdel , Tseung Hok Seum Wan Chan , Qian Jing , Kabat Brian , Kemp Bradley , Laack Nadia , Brinkmann Debra 
Published: November 2021

Abstract
While dose escalation of radiotherapy (DERT) has failed to improve overall survival (OS) or progression-free survival (PFS) for glioblastoma in previous studies, a recent phase II clinical trial utilizing 18F-DOPA-PET-directed DERT demonstrated improved PFS in MGMT-unmethylated patients and OS in MGMT-methylated patients compared to historical controls. This planned secondary analysis sought to determine 1) how 18F-DOPA-PET changes RT volumes beyond standard MRI-planning, 2) which patients benefit most and least from this protocol, 3) which are mostly likely to experience clinically significant radionecrosis after DERT, and 4) patterns of failure after DERT. For 69 evaluable patients, median MRI-defined, PET-defined, and combined low-dose gross tumor volumes (GTV51) were 54 cc (range 9-248), 23 cc (0.4-179), and 62 cc (10-260), respectively. Median MRI-defined, PET-defined, and combined high-dose GTVs (GTV76) were 32 cc (range 4-136), 6 cc (0.1-138), and 34 cc (4-162), respectively. 18F-DOPA-PET resulted in a median volumetric expansion of 13% (0-243%) and 5% (0-217%) from MRI-defined low-dose and high-dose GTV’s, respectively. Central failures ( &gt;95% of recurrence tumor volume) occurred within the 76 Gy, 60 Gy, and 51 Gy isodose lines in 32 (46%), 60 (87%), and 64 (93%) patients, respectively. Recursive partitioning analysis stratified patients by OS and PFS. Patients with 18F-DOPA-PET-defined GTV76 &gt; 7.8cc, MRI-defined GTV76 &gt; 42.7cc, and MGMT promotor-unmethylated tumors had the shortest OS, while patients with smaller PET and MRI-defined tumors had the longest OS (median 10.4 vs. 64.6 months, p&lt; 0.001). Similarly, PFS was worst in patients with 18F-DOPA-PET-defined GTV76 &gt; 2.17 cc who had biopsy only (median PFS 3.2 months, p&lt; 0.001). Patients with 18F-DOPA-PET-defined GTV51 &gt; 50 cc had the highest risk of grade 3+ radionecrosis (p&lt; 0.001). In conclusion, larger 18F-DOPA-PET and MRI-defined tumor volumes were associated with worse outcomes, and 18F-DOPA-PET-directed DERT appears to reduce risk of central recurrence in high-dose volumes.
CTNI-30. A SNAPSHOT OF “REAL WORLD” CURRENT NEURO-ONCOLOGY PRACTICE IN TEN UK CENTRES AND RATIONALE FOR THE TESSA JOWELL BRAIN MATRIX (TJBM) PLATFORM STUDY
Authors: Wykes Victoria , Apps John , Savage Joshua , Meade Sara , Pohl Ute , Sawlani Vijay , Patel Amit , Billingham Lucinda , Thompson Gerard , Waldman Adam , Ansorge Olaf , Watts Colin 
Published: November 2021

Abstract

OVERVIEW
The TJBM Platform Study (https://www.birmingham.ac.uk/research/crctu/trials/brain-matrix) is a programme of work aimed at improving the knowledge of, and treatment for, glioma. We present the feasibility data collected from the initial ten UK centres.

METHOD
The UK TJBM centres completed a multi-disciplinary feasibility questionnaire to facilitate participation and collaboration across centres. Data were collected from hospital electronic board review records, clinic letters, operative and imaging notes, MDT or personal experience.

RESULTS
Work load: Between 2016-2018 service provision redistribution reflects a trend towards higher volume centres. Overall, glioma workload within ten TJBM centres has remained stable. Imaging: All TJBM centres have good access to imaging techniques and neuroradiology expertise, including relevant ‘advanced’ imaging. All have RANO capability, although not widely used clinically. Neurosurgery: All centres have access to 5 ALA, perform awake craniotomy for language assessment and motor/sensory mapping are typically performed asleep, with subtle variation in techniques. Pathology: Despite molecular analysis advances, current practice is limited to the evaluation of formalin embedded tissue by traditional morphology/ immunohistochemically staining, with limited targeted testing of specific genetic changes. Clinical oncology: Oncology treatments for glioma were as per NICE guidance with some minor local variation. A relative lack of linking treatments to detailed clinical, treatment, toxicity, and quality of life data making communication of significance of findings to patients challenging.

CONCLUSION
Through systematic real-world data collection the TJBM platform study will provide a detailed understanding of practice within the UK, linked to molecular tumour genotype, treatment response outcome measures, and regular quality of life assessments. This infrastructure will help establish a trial-competent network for future collaborative research. Academic and industry partners will be able to use the TJBM platform through collaboration, overseen by a strong governance framework. This will maximise the opportunities and abilities to translate advances into trials and patient benefit.
CTNI-31. RESECTION AND SURGICALLY TARGETED RADIATION THERAPY FOR TREATMENT OF LOCALLY RECURRENT GBM IN 28 PROSPECTIVELY TREATED PATIENTS
Authors: Smith Kris , Nakaji Peter , Thomas Theresa , Pinnaduwage Dilini , Wallstrom Garrick , Brachman David 
Published: November 2021

Abstract

INTRODUCTION
Recurrent GBM is a diffuse disease and resection (R) alone does not routinely provide durable local control (LC) or prolonged overall survival (OS). We hypothesized R plus immediate radiation (RT) utilizing a novel brachytherapy device might achieve more durable LC and thereby secondarily improve OS.

METHODS
From 2/2013-2/2018, locally recurrent GBM were treated in a single arm trial (ClinicalTrials.gov, NCT#03088579) of R plus immediate implantation of a surgically targeted radiation therapy (STaRT) device utilizing Cs-131 in bioresorbable collagen tiles (GammaTile, GT Medical Technologies, Tempe AZ USA).

RESULTS
28 patients (pts) were treated, 20 at first recurrence (range 1-3). Median age 58 (range 21-80), KPS 80 (60-100), female:male ratio 10:18. Median OS was 10.7 mo., radiographic LC 8.8 mo., and no first failure was local. MGMT, KPS, and sex were non-predictive. Post hoc analysis disclosed after R+STaRT, 17 pts (54%) received &gt; 1 cycle of Sys (“Sys+”) and 13 (46%) did not (“Sys- “). Sys was given as adjuvant, salvage, or both, either alone or in combination. 15 pts received bevacizumab (BEV), 12 temozolomide (TMZ) and 8 lomustine (CCNU). Median OS (mo.) for Sys+ vs. Sys- was 15.1/6.5 (hazard ratio (HR) .38, p=.017); OS for BEV+ vs. BEV- was 16.7/4.5 (HR .38, p=.017), TMZ+ vs. TMZ- 17.5/6.7 (HR .40, p=.025) and for CCNU+ vs. CCNU- 17.5/7.9 (HR .61, p=.25), respectively. LC was 11.4 mo. for Sys+ vs. 2.1 mo. for Sys- (HR .44; p=.16). Three attributed AE occurred, 1 wound infection requiring surgery and 2 radiation brain effects, managed medically.

CONCLUSION
Post hoc analysis suggests R+STaRT+Sys may have the potential to impact OS in locally recurrent GBM, possibly by allowing sufficient time for effective but biologically slower treatments to have an impact. FDA clearance was received in 2018 for recurrent intracranial neoplasms and in 2020 for newly-diagnosed malignant brain tumors.
CTNI-33. METRONOMIC TEMOZOLOMIDE THERAPY IN HEAVILY PRETREATED PATIENTS WITH RECURRENT GLIOBLASTOMA: A LARGE MONO-INSTITUTIONAL RETROSPECTIVE STUDY
Authors: Bosio Alberto , Cerretti Giulia , Padovan Marta , Caccese Mario , Guarneri Valentina , Zagonel Vittorina , Lombardi Giuseppe 
Published: November 2021

Abstract

BACKGROUND
Despite advances in surgical and first-line treatment, all glioblastoma pts relapse. The aim of this study is to evaluate the benefit of metronomic temozolomide (mTMZ) for recurrent glioblastoma.

METHODS
120 pts treated at Veneto Institute of Oncology from September 2013 to March 2021 were retrospectively reviewed. Major inclusion criteria were: first-line therapy with Stupp protocol, relapse after first or subsequent line of therapy, treatment with mTMZ schedule (50mg/m2 continuously), hystologically confirmed diagnosis.

RESULTS
mFollow-up was 15.6ms, mAge 59ys (range 18-81), ECOG PS 0-2 in 107pts (89%) and 3 in 11 (9%). MGMT was methylated in 66 of 105 (62%) evaluable pts, IDH mutated in 9 of 106 (8%). mNumber of prior lines of treatment was 2 (range 1-7); 41% of pts received mTMZ beyond the third line. mTime between last standard TMZ (sTMZ) cycle and mTMZ administration was 6ms (range 1-50); 40% of pts started mTMZ after 3ms from sTMZ. All pts were evaluable for response: 3 (2%) and 48 (40%) showed PR and SD. mOS from the start of mTMZ was 5.4ms (95% CI 4.3-6.4), mPFS 2.6ms (95% CI 2.3-2.8). On univariate analysis, MGMTmet and MGMTunmet pts had a mOS of 5.6 and 4.4ms (p= 0.03); mOS for pts with ECOG PS &gt; or ≤ 2 was 2.3 and 6.0ms (p&lt; 0.001). On multivariate analysis, MGMTmet status (HR= 2.3, 95% CI, p= 0.004) and ECOG PS (HR= 0.5, 95% CI, p= 0.017) remained significant for PFS; ECOG PS (HR= 0.4, 95% CI, p= 0.001) was the only factor significantly associated with OS. The most common grade 3-4 hematologic toxicities were lymphopenia (10%) and thrombocytopenia (3%). Grade 3-4 nonhematologic toxicities were uncommon.

CONCLUSIONS
Rechallenge with mTMZ can be a well tolerated treatment option for recurrent glioblastoma, even in heavily pretreated pts. Pts with MGMTmet and good ECOG PS might report the major benefit.
CTNI-34. TOXICITY PROFILE AND COMPLIANCE OF PATIENTS WITH HIGH RISK GRADE 2 OR GRADE 3 GLIOMAS RECEIVING ADJUVANT PCV VERSUS ADJUVANT TEMOZOLOMIDE
Authors: Menon Nandini , Chatterjee Abhishek , Gupta Tejpal , Goda Jayant Sastri , Sridhar Epari , Sahay Ayushi , Janu Amit , Mahajan Abhishek , Puranik Ameya , Moiyadi Aliasgar , Shetty Prakash , Singh Vikas , Jalali Rakesh , Patil Vijay 
Published: November 2021

Abstract

INTRODUCTION
The NCCN recommends either PCV (Procarbazine, CCNU and vincristine) or Temozolomide (TMZ) as adjuvant therapy in high-risk grade 2 & grade 3 gliomas. In this ongoing study we are comparing PCV with TMZ as adjuvant therapy in this setting.

METHODS
This is a randomised phase 3 study that includes patients with high risk (as per RTOG) grade 2 gliomas and grade 3 gliomas after surgery. Patient are randomly assigned in 1: 2 to receive either adjuvant PCV or TMZ after adjuvant RT. The primary end-point is progression-free survival & key secondary end points are overall survival, toxicity and quality of life. The current analysis focuses on the compliance and adverse events seen in patients enrolled till 30th April 2020.

RESULTS
46 patients were enrolled, with 30 patients in TMZ arm. The median age of patients was 37 years (range 23-64). The ECOG PS was 1 in 45 (97.8%) patients and 2 in 1(2.2%) patient at enrolment. The number of patients who have completed all planned cycles of chemotherapy in the PCV arm is 62.5% (10, n=16) as compared to 90% (27, n=30) in the TMZ arm (P=0.047). The incidence of grade 3 or higher adverse events is 68.8% (n=11) in the PCV arm and 16.7% (n=5) in the TMZ arm (P=0.001). The most common grade 3 or higher toxicities noted are lymphopenia in 50% (n=8), neutropenia in 37.5% (n=6), and thrombocytopenia in 25% (n=4) in the PCV arm; while the corresponding numbers in the TMZ arm are 13.3% (n=4), 3.3% (n=1) and 10% (n=3) respectively.

CONCLUSION
In the current study the chemotherapy completion rates are higher with TMZ and it is associated with lower grade 3-4 events, whether this will lead to an improvement in outcomes remains to be seen.
CTNI-35. UPDATE ON THE FEASIBILITY STUDY OF OKN-007 IN COMBINATION WITH TEMOZOLOMIDE AND RADIATION IN NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Battiste James , Wright Deborah , Glenn Chad , Dunn Ian , Algan Ozer , Gunter Tyler , Zhao Daniel , Cohoon Andrew , Sung Sarah , Towner Rheal , Kim Hyon sook 
Published: November 2021

Abstract

BACKGROUND
Temozolomide (TMZ) with concurrent radiation is the traditional standard of care for newly diagnosed glioblastoma. Unfortunately, this combination has limited efficacy and resistance can render TMZ ineffective. The novel anti-cancer agent OKN-007 plus TMZ increased survival in preclinical studies. Therefore, we initiated a phase Ib/feasibility clinical trial (NCT03587038) of OKN-007 in combination with TMZ and radiation therapy (RT). We report the safety and tolerability findings of this trial in-progress.

METHODS
Adults with newly-diagnosed GBM were eligible. OKN-007 was administered by IV at 60 mg/kg. There were three treatment phases: Concomitant, Pre-Maintenance, and Maintenance. In the Concomitant Phase, patients received OKN-007 three times per week (Cohort A) or five times per week (Cohort B); all patients receive TMZ at 75 mg/m2 daily and RT at 60 Gy over 30 fractions. In the 28-day Pre-Maintenance Phase, all patients receive OKN-007 thrice weekly. In the Maintenance Phase (MP), comprising up to eighteen 28-day cycles, TMZ was dosed at 150-200 mg/m2 on days 1-5 of each cycle for six cycles. OKN-007 was administered thrice weekly for six cycles, then twice weekly for three cycles, then once weekly for nine cycles. Each cohort was evaluated for safety with 3-6 patients followed by an expansion of cohorts if safety parameters were met.

RESULTS
Three patients completed Cohort A without dose-limiting toxicity (DLT). In Cohort B, two DLT’s (hematologic toxicities deemed to be related to TMZ) occurred, and this cohort was stopped. Currently, median PFS and OS have not been reached due to lack of events, but preliminary data indicate improved median PFS and OS compared to standard of care.

CONCLUSIONS
The treatment plan appears safe and well-tolerated at the Cohort A combination dosing level and may increase favorable treatment outcomes suggesting that the OKN-007 warrants further study.