bluuebunny/crossref_metadata_2025_split huggingface dataset:
RADT-09. TYPE AND TIMING OF SYSTEMIC THERAPY USE PREDICT SURVIVAL IN PATIENTS WITH BRAIN METASTASES TREATED WITH RADIATION THERAPY
Authors: Fan Kevin , Lalani Nafisha , Levasseur Nathalie , Krauze Andra , Gondara Lovedeep , Willemsma Kaylie , Nichol Alan 
Published: December 2020

Abstract

PURPOSE
We aimed to investigate whether systemic therapy (ST) use around the time of brain radiotherapy (RT) predicts overall survival for patients with brain metastases (BM). We also aimed to validate the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) in a population-based cohort.

METHODS
We used provincial RT and pharmacy databases to retrospectively review all adult patients in British Columbia, Canada, who received a first course of RT for BMs between 2012 and 2016. We used a randomly selected subset with complete baseline data to develop a multivariate analysis (MVA)-based nomogram including ST use to predict survival after RT and to validate the DS-GPA.

RESULTS
In our 3095-patient cohort, the median overall survival (OS) of the 999 recipients of ST after RT was 5.0 months (CI 4.1-6.0) longer than the OS of the 2096 non-recipients of ST after RT (p&lt; 0.0001): targeted therapy (HR 0.42, CI 0.37-0.48), hormone therapy (HR 0.45, CI 0.36-0.55) and cytotoxic chemotherapy (HR 0.71, CI 0.64-0.79). The OS of patients who discontinued ST after RT was 0.9 months (CI 0.3-1.4) shorter than the OS of those who did not receive ST before nor after RT (p&lt; 0.0001). A MVA in the 200-patient subset demonstrated that the traditional baseline variables: cancer diagnosis, age, performance status, presence of extracranial disease, and number of BMs predicted survival, as did the novel variables: ST use before RT and ST use after RT. The MVA-based nomogram had a bootstrap-corrected Harrell’s Concordance Index of 0.70. In the 179 patients within this subset with DS-GPA-compatible diagnoses, the DS-GPA overestimated OS by 6.3 months (CI 5.3- 9.8) (p= 0.0006).

CONCLUSIONS
The type and timing of ST use around RT predict survival for patients with BMs. A novel baseline variable “ST planned after RT” should be prospectively collected to validate these findings in other cohorts.
RADT-13. EARLY CONCURRENT IMMUNOTHERAPY WITH STEREOTACTIC RADIOSURGERY IS ASSOCIATED WITH PROLONGED SURVIVAL AND DECREASED DISTANT BRAIN FAILURE IN PATIENTS WITH NEWLY DIAGNOSED MELANOMA BRAIN METASTASES (MBM)
Authors: Augustyn Alexander , Patel Roshal , Ludmir Ethan , Haydu Lauren , Guha-Thakurta Nandita , Bishop Andrew , Chung Caroline , Ghia Amol , McAleer Mary Frances , McGovern Susan , Wang Chenyang , Woodhouse Kristina , Yeboa Debra , Ferguson Sherise , Kim Betty , Glitza Isabella , Li Jing 
Published: December 2020

Abstract

INTRODUCTION
We evaluated outcomes of patients with newly diagnosed MBM treated with concurrent immune checkpoint inhibition (ICI) and stereotactic radiosurgery (SRS) (concurrentTx), defined as treatment delivery within 30 days of each other.

METHODS
Screening of 2,617 melanoma patients who received ICI (anti-CTLA4/anti-PD1/both) between 2011-2019 identified 151 pts who received concurrentTx for MBM. Among these, 51 had newly-diagnosed MBM and received no prior ICI or SRS, and were included in the current study. Overall survival (OS) and distant brain failure (DBF) were estimated using the Kaplan-Meier method. Incidence of radiation necrosis (RN) was captured.

RESULTS
Median follow up from treatment initiation (either ICI or SRS, whichever occurred first) was 37 months. Median OS was 30 months. Median interval between ICI/SRS was 12 days (range: 1-29). Twenty-two patients received ICI first and 29 received SRS first, without differences in OS (p=0.22), DBF (p=0.91), or development of RN (p=0.86). However, the interval between ICI and SRS was significant. Patients who received concurrentTx 1-11 days apart (n=25, “early”) experienced a significant improvement in OS and DBF compared to 12-29 days apart (n=26, “delayed”) (p=0.01, HR 2.8; 95%CI 1.3-6.2 for OS and p=0.02, HR 2.5; 95%CI 1.2-5.6 for DBF). OS and DBF at 36 months were 67% vs. 26% and 60% vs. 27%, respectively, for the early vs. delayed groups. Time to concurrentTx as a continuous variable was significantly associated with DBF (p=0.02), but not OS (p=0.06). Although not significant, more patients developed RN in the early (26.0%) versus delayed (3.8%) group (p=0.07). No additional patient or treatment differences were identified.

CONCLUSIONS
Early concurrentTx was associated with prolonged OS and improved DBF in newly diagnosed MBM patients who did not receive prior CNS-directed therapy. This finding suggests therapeutic synergism related to combined early treatment and should be validated in a prospective clinical trial.
RADT-17. RADIOTHERAPY IN THE MANAGEMENT OF OPTIC NERVE SHEATH MENINGIOMAS: AN INTERNATIONAL SYSTEMATIC REVIEW AND META-ANALYSIS OF EIGHTEEN STUDIES
Authors: Vaishnav Yash J , Singh Raj , Didwania Prabhanjan , Lehrer Eric J , Bakaeva Tatiana , Harris Timothy , Migliori Michael E , Trifiletti Daniel M 
Published: December 2020

Abstract

INTRODUCTION
Optic nerve sheath meningiomas (ONSMs) are often managed with radiotherapy (RT) with the goal of achieving radiographic local control (LC) to prevent further decline in visual acuity (VA); however, reports on outcomes are limited to small retrospective series. Thus, we aimed to perform a systematic review and meta-analysis of outcomes for patients with ONSM treated with RT.

METHODS
A PICOS/PRISMA/MOOSE selection criteria was utilized to identify studies for inclusion. Primary outcomes were stable or improved VA and radiographic LC at last follow-up. The secondary outcome was incidence of radiation-induced retinopathy. Weighted random effects meta-analyses using the DerSimonian and Laird methods were conducted to characterize effect sizes. Mixed effects regression models were used to examine potential correlations between gross tumor volume (GTV) and outcomes.

RESULTS
In total, 381 patients with ONSM across 18 published studies were included. Of these, 332 and 386 treated ONSMs had information on VA or LC, respectively. Median age was 46.75 (range: 9-87), median/mean GTV was 2.905cc (range: 0.28-26.3), and median follow-up was 51.15 months (range: 1-248.4 months). The estimated LC rate at last follow-up was 100% (95% CI: 98-100%), and the estimated proportion of patients with stable or improved VA at last follow-up was 89% (95% CI: 84-93%). The rate of chronic radiation retinopathy was estimated to be 7% (95% CI: 5-11%). GTV was significantly associated with VA (p=0.014) with estimated VA rates of 96.4%, 91.4%, and 80.5% for GTVs of 2.0, 3.0, and 4.0ccs, respectively.

CONCLUSIONS
RT was well-tolerated in the treatment of ONSM with excellent LC achieved. Nearly 90% of patients noted either stability or improvement in VA. Larger ONSMs were found to be associated with poorer VA. Incidences of radiation-induced retinopathy were limited and estimated to be less than 10%.
RADT-23. IMPACT OF REIRRADIATION UTILIZING STEREOTACTIC RADIOSURGERY ON RECURRENT GLIOBLASTOMA
Authors: Patrick O’Dell , Nickols H , LaRocca R , Sinicrope K , Sun D , Spalding A 
Published: December 2020

Abstract

BACKGROUND
Patients who have recurrent glioblastoma have limited treatment options. We conducted a retrospective review of patients with recurrent glioblastoma treated with standard initial radiation and temozolomide with tumor treating fields to investigate whether reirradiation using radiosurgery would be associated with improved outcomes.

METHODS
We reviewed the records of 54 consecutively treated patients with recurrent glioblastoma with ECOG 0 or 1 at recurrence and conducted Kaplan-Meier analysis with Log-rank testing to determine significance between groups.

RESULTS
We identified 24 patients who were treated without radiation therapy (control) while 30 patients underwent re-irradiation using radiosurgery (ReSRS) with a median total dose of 25Gy in five fractions. All patients had completed standard initial therapy, and there was no difference in the time to recurrence between the two groups (10 months for control, 15 months for ReSRS, [P = 0.17, HR for progression 0.65 (95% CI 0.38-1.13)]. A larger proportion of patients in the control arm (54%) had subtotal or gross total resection of the recurrence compared with the ReSRS group (44%, P &lt; 0.05). The majority of patients had recurrence confirmed with biopsy (18/22 in control group, 25/31 in the ReSRS group). MGMT methylation status did not differ between control vs ReSRS (29% vs. 27%). ReSRS was associated with improved median survival from the time of first recurrence of 11.6 months versus 3.8 months in the control arm [P&lt; 0.0001, HR for death 0.33 (95% CI 0.18-0.6)].

CONCLUSIONS
In a group of patients with high performance status diagnosed with recurrent glioblastoma, reirradiation with stereotactic radiosurgery was associated with nearly one year median survival after recurrence. Additional analyses are warranted to determine the impact of concurrent systemic therapies with irradiation and underlying tumor or patient factors to predict outcomes.
RADT-24. HIGH ABSORBED DOSES OF RHENIUM-186 NANOLIPOSOMES (RNL) IN RECURRENT GBM: A PHASE 1 STUDY
Authors: Brenner Andrew , Floyd John , Bao Ande , Phillips William , Awasthi Vibhudutta , Patel Toral , Weinberg Jeffrey 
Published: December 2020

Abstract

INTRODUCTION
While external beam radiation therapy (EBRT) remains a central component of the management of primary brain tumors, it is limited by tolerance of the surrounding normal brain tissue. Nanoliposomal BMEDA-chelated-186Rhenium (RNL™) permits the delivery of beta-emitting radiation of high specific activity with excellent retention in the tumor. We report on the phase 1 results in recurrent glioma.

METHODS
A phase 1 dose-escalation study of RNL in recurrent glioma utilizing a standard 3 + 3 design was undertaken to determine the maximum tolerated dose of RNL following stereotactic biopsy. RNL is administered with the BrainLab Flexible Catheter by convection enhanced delivery (CED) with placement guided using iPlan Flow and the Varioguide system. Infusion is followed under whole body planar imaging and SPECT/CT. Repeat SPECT/CT imaging is performed immediately following, and at 1, 3, 5, and 8 days after RNL infustion to obtain dosimetry and distribution.

RESULTS
Thirteen patients have been treated to-date, 12 were recurrent glioblastoma, and 54% failed treatment with bevacizumab. The infused dose was progressively increased from 1.0 mCi to 13.4 mCi and the volume of infusate from 1.0 mL to 5.28 mL using 1 – 2 CED catheters. The mean absorbed dose to the distribution volume was 175 Gy (CI 97 – 254). The maximum absorbed dose to the tumor volume was 593 Gy. The mean retention of the administered dose at 24 hours was 61.4% (CI 45.4 – 77.5). The therapy has been well tolerated and no dose-limiting toxicity has been observed with no treatment related adverse effects despite markedly higher absorbed doses than EBRT in patients with prior treatment. The plan is to increase the dose to 22.3 mCi and the infusate volume to 8.8 mL.

CONCLUSION
Intratumoral RNL can deliver up to twenty times the absorbed dose of radiation administered by EBRT without significant toxicity.
RADT-25. EVALUATING LYMPHOCYTE COUNTS IN NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS RECEIVING CHEMORADIATION
Authors: Hammoudeh Lubna , Lim-Fat Mary Jane , Cagney Daniel , Aizer Ayal A , Tanguturi Shyam , Arvold Nils , Mcfaline-Figueroa Jose , Chukwueke Ugonma , Reardon David , Lee Eudocia , Nayak Lakshmi , Rinne Mikael , Ligon Keith , Wen Patrick , Alexander Brian , Rahman Rifaquat 
Published: December 2020

Abstract

BACKGROUND
Glioblastoma (GBM) patients are treated with chemotherapy, radiation therapy (RT) and often corticosteroids, which can all contribute to lymphopenia. We examined lymphopenia with respect to incidence, predictors, and association with progression-free survival (PFS) and overall survival (OS).

METHODS
We reviewed 349 newly diagnosed adult GBM patients treated at our institution in the temozolomide (TMZ) era with available lymphocyte and RT records. Data was reviewed from diagnosis through the chemoradiation (CRT) phase, defined as the period upto 6 weeks after RT. Linear regression and Cox proportional hazards modeling were used to evaluate outcomes.

RESULTS
Median age was 60 years (range, 19-90); 86% had KPS ≥ 70, 30% had gross total resection (GTR), and 91% received TMZ. Prior to RT, 60% (205/341) patients had a lymphocyte measurement &lt; 1.0 x 1000 cells [K]/μL and 15% (50/341) had &lt; 0.5 K/μL. During the CRT phase of therapy, 83% (270/324) had at least one lymphocyte measurement &lt; 1.0 K/μL, 42% (135/324) &lt; 0.5 K/μL, and 5% (16/324) &lt; 0.2 K/μL. Older age was associated with lower lymphocytes pre-RT, while subtotal resection, TMZ use, and RT dose was associated with lower lymphocyte counts during CRT (p&lt; 0.05). On multivariable analysis (MVA), age (AHR 1.03, p&lt; 0.01), KPS &gt; 70 (AHR 0.35, p&lt; 0.01), MGMT status (AHR 0.47, p&lt; 0.01), GTR (AHR 0.67, p=0.03), TMZ (AHR 0.27, p&lt; 0.01) and lymphopenia during CRT (AHR 1.80, p&lt; 0.01) were significantly associated with OS. Pre-RT lymphocyte level was associated with PFS on UVA (HR 0.81, p=0.03) but not on MVA (p=0.27). Lymphocyte count during CRT was not associated with PFS (p=0.24).

CONCLUSION
Lymphopenia is common in GBM, and chemoradiation-related lymphopenia was associated with inferior OS relative to patients without lymphopenia. Further characterization of the mechanism and optimal treatment of patients with lymphopenia are warranted to improve outcomes.
RADT-38. ADJUVANT RADIOTHERAPY FOR INTRACRANIAL ATYPICAL AND MALIGNANT MENINGIOMAS IN ADULT PATIENTS
Authors: Unterberger Ansley , Kondajji Aditya , Kulinich Daniel , Duong Courtney , Yang Isaac 
Published: December 2020

Abstract

BACKGROUND
Meningiomas, the most common primary brain tumor, account for more than one third of all primary CNS tumors. High-grade meningiomas, WHO grade II and III, comprise between 16%-24% of total meningiomas and are more aggressive, recur more frequently, and portend a worse prognosis than WHO grade I meningiomas. Adjuvant radiation of high-grade meningiomas, while not uncommon, remains variably described in current literature. To assess our institution’s radiation protocol, we examined our cohort of over 200 high-grade meningiomas.

METHODS
We queried our hospital’s EHR system for surgically resected meningiomas from January 2013 to December 2019. Of 286 results identified, 24 patients met the inclusion criteria: 1) histologically confirmed WHO grade II or III meningioma, 2) primary resection coupled with adjuvant radiation therapy, and 3) no chemotherapy. Only one WHO grade III meningioma met inclusion criteria. Patients with NF2 were excluded. Patient demographics, radiation dosage, fraction number, and dates of surgery, radiation onset, recurrence, and most recent follow-up were recorded.

RESULTS
Median age at surgery was 56.2 years (± 11.1, range 37.8 – 81.7), and males comprised 70.8% (n = 17) of the population. Only FSRT or IMRT were employed. The most frequent dosage was 55.8 Gy across 31 fractions with a median time to radiation of 2.7 months (± 3.0, range 1.0 – 12.6). 5 out of 24 patients experienced recurrence, which did not include the WHO III tumor. Median time to recurrence was 3.0 years (± 2.0, range .3 – 5.8). Median follow up was 3.5 years (± 2.2, range .3 – 9.3).

CONCLUSIONS
A fraction of our population experienced recurrence, regardless of grade II or grade III pathology. FSRT remains a safe and effective adjuvant therapy for high-grade meningioma after surgical resection. Future prospective studies comparing differing radiation modalities should be conducted.
RTID-04. A RANDOMIZED PHASE II TRIAL TO COMPARE THE EFFICACY OF STANDARD VERSUS COMBINATION THERAPY (PERAMPANEL, MEMANTINE PLUS STANDARD) IN THE TREATMENT OF PATIENTS WITH NEWLY DIAGNOSED GBM-A STUDY DESIGN
Authors: Kong Xiao-Tang , Albala Bruce , Du Senxi , Kong Xiao-Tang , Bota Daniela 
Published: December 2020

Abstract

BACKGROUND
Glioblastoma (GBM) is the most aggressive malignant brain tumor in adults with poor prognosis. Effective treatment is urgently needed. Recent studies demonstrated neurogliomal synaptic communication through AMPA and NMDA receptors promotes glioma invasion and progression in vitro and in vivo. Therefore, dual blocking AMPA and NMDA receptor therapy is a potential enhancing strategy to prevent and to treat GBM progression given the two blockers act through different anti-glioma mechanisms.

OBJECTIVE/HYPOTHESIS
We hypothesize that adding AMPA blocker Perampanel (An anti-seizure medication) and NMDA blocker Memantine (An anti-dementia medication) to standard temozolomide plus radiation therapy (Stupp’s regimen) for the treatment of newly diagnosed GBM may prevent tumor progression. It may also reduce the frequency of onset/recurrence of seizure episodes and possibly improve radiation related cognition impairment.

STUDY DESIGN
This is a randomized, active controlled, open label, two arm phase II study of efficacy of treatment of GBM with combination therapy (dual AMPA and NMDA receptor blockers plus standard therapy) versus standard therapy. In the combination therapy arm, patients take Perampanel 2 mg daily and Memantine 5 mg bid, starting from -14 days to +14 days from initiation of concurrent chemo-radiation therapy. Titrating up at a 2 mg increment for Perampanel and 5 mg bid increment for Memantine until reaching MTD. If the patient has AE &gt;= grade 2, then reduce doses at a decrement of 2 mg for Perampanel and decrement of 5 mg bid for Memantine. In the standard therapy arm, the patients are treated with Stupp’s regimen.

PRIMARY AND SECONDARY ENDPOINTS
PFS, 12, 24 month survival rates and response duration. Safety will be assessed by CTCAE V5. We will use Kaplan-Meier estimates for survival data and a stratified log-rank test for the randomization strata.
RTID-05. INDIGO: A GLOBAL, RANDOMIZED, DOUBLE-BLIND, PHASE 3 STUDY OF VORASIDENIB (AG-881) VS PLACEBO IN PATIENTS WITH RESIDUAL/RECURRENT GRADE II GLIOMA WITH AN ISOCITRATE DEHYDROGENASE 1/2 (IDH1/2) MUTATION
Authors: Mellinghoff Ingo , van den Bent Martin , Clarke Jennifer , Maher Elizabeth , Peters Katherine , Touat Mehdi , de Groot John , De La Fuente Macarena , Arrillaga-Romany Isabel , Wick Wolfgang , Ellingson Benjamin , Schoenfeld Steven , Liu Hua , Le Kha , Lu Min , Steelman Lori , Hassan Islam , Pandya Shuchi , Wen Patrick , Cloughesy Timothy 
Published: December 2020

Abstract

BACKGROUND
Low-grade gliomas (LGGs; WHO grade II) are incurable and ultimately progress to high-grade gliomas. The current treatment options are surgery followed by observation (“watch and wait”) for patients with lower risk for disease progression or postoperative chemoradiotherapy (high-risk population). There are no approved targeted therapies. IDH1 and IDH2 mutations (mIDH1/2) occur in approximately 80% and 4% of LGGs, respectively, and promote tumorigenesis via neomorphic production of D-2-hydroxyglutarate. Vorasidenib, an oral, potent, reversible, brain-penetrant pan-inhibitor of mIDH1/2, was evaluated in 76 patients with glioma in two phase 1 studies (dose escalation and perioperative) and was associated with a favorable safety profile at daily doses below 100 mg. Preliminary clinical activity was observed in non-enhancing glioma patients in both studies, with an objective response rate (ORR) of 18.2% and median progression-free survival of 31.4 months in the dose escalation study.

METHODS
Approximately 366 patients will be randomized 1:1 to vorasidenib (50 mg QD) or matched placebo and stratified by 1p19q status (intact vs co-deleted). Key eligibility criteria: age ≥ 12 years; grade II oligodendroglioma or astrocytoma (per WHO 2016 criteria) not in need of immediate treatment and without high-risk features; centrally confirmed mIDH1/2 status; ≥ 1 surgery for glioma with most recent ≥ 1 year but ≤ 5 years before randomization, and no other anticancer therapy; Karnofsky performance status ≥ 80%; and centrally confirmed measurable, non-enhancing disease evaluable by magnetic resonance imaging. Crossover from placebo to the vorasidenib arm is permitted upon centrally confirmed radiographic progression per RANO-LGG criteria. Primary endpoint: progression-free survival assessed by independent review. Secondary endpoints: safety and tolerability, tumor growth rate assessed by volume, ORR, overall survival, and quality of life. Clinical data will be reviewed regularly by an independent data monitoring committee. The study is currently enrolling patients in the US, with additional countries planned (NCT04164901).
RTID-08. A PHASE 1/2 STUDY OF SELINEXOR IN COMBINATION WITH STANDARD OF CARE THERAPY FOR NEWLY DIAGNOSED OR RECURRENT GLIOBLASTOMA (ndGBM OR rGBM)
Authors: Wen Patrick , Odia Yazmin , Mehta Minesh , Goldlust Samuel , Tamir Sharon , Shacham Sharon , Wang Hongwei , Sheehan Heidi , Li Kai 
Published: December 2020

Abstract

BACKGROUND
GBM is the most common and most aggressive primary brain tumor with poor prognosis and median overall survival (mOS) of patients with ndGBM and rGBM being 15 vs 5-7 months, respectively. Selinexor is a first-in class, oral, selective nuclear export inhibitor which forces nuclear retention and reactivation of many tumor suppressor proteins. Selinexor with low dose dexamethasone was recently approved for patients with triple-class refractory multiple myeloma. Additionally, selinexor monotherapy has demonstrated broad activity in other hematologic and solid malignancies. In a Phase 2 study in rGBM (NCT01986348), selinexor demonstrated encouraging intratumoral penetration and single-agent efficacy at 80 mg once weekly with durable response and disease stabilization in heavily pretreated patients. Preclinical GBM studies showed synergy when combining selinexor with radiation, temozolomide and lomustine.

METHOD
This is a phase 1 (PH-1) dose finding study followed by a 1:1 randomized phase 2 (PH-2; n= 350) efficacy exploration trial to independently evaluate 3 different combination regimens: Arm A: radiation +/- selinexor in uMGMT ndGBM; Arm B: radiation and temozolomide +/- selinexor in MGMT ndGBM; Arm C:omustine +/- selinexor in first relapse rGBM following frontline radiation and temozolomide. The PH-1 primary endpoint is MTD/RP2D, with secondary endpoints of ORR per modified RANO, duration of response (DOR), PFS, and OS. The PH-2 primary endpoint for Arms A and B in ndGBM is PFS, with key secondary endpoints being OS, PFS6, ORR, DOR. For Arm C, the PH-2 primary endpoint is OS while key secondary endpoints are PFS, PFS6, ORR, DOR. The study has 70% power to detect a hazard ratio of 0.67 between selinexor and control for primary efficacy for arms A & B, and 80% power to detect a hazard ratio of 0.70 for arm C. We are currently enrolling patients nationwide. Clinical trial identifier: NCT04421378