bluuebunny/crossref_metadata_2025_split huggingface dataset:
LOCL-08 SAFETY AND FEASIBILITY OF RHENIUM-186 NANOLIPOSOME (186RNL) IN RECURRENT GLIOMA: THE RESPECT™ PHASE 1 TRIAL
Authors: Brenner Andrew , Hedrick Marc , LaFrance Norman , Bao Ande , Ohillips William , Patel Torel , Weinberg Jeffrey , Floyd John 
Published: August 2022

Abstract

BACKGROUND
Liposomal rhenium-186 (186RNL) is a potent source of electrons with short path length, low dose rate, high radiation density and gamma emission. Preclinically, 186RNL via convection enhanced delivery (CED) achieves very high doses of targeted radiation and a wide therapeutic index. We report the updated results of ReSPECT, the first in man, dose escalation phase 1 trial of 186RNL in recurrent glioma.

METHODS
Following computer assisted treatment planning and placement of intracranial catheter(s), we performed a single administration of 186RNL by CED. Whole body planar and SPECT/CT imaging was obtained on days 1-8 following treatment for dosimetry and distribution. Patients were followed for safety, progression and survival.

RESULTS
Twenty-one patients across 7 cohorts received 1.0-22.3mCi in a tumor volume of 0.6-8.80mL. Mean tumor volume was 8.3mL (0.9-22.8mL). Patients had a mean of 1.7 recurrences, 5 with prior bevacizumab. 19 (91%) were grade 4 gliomas, and 100% were after cohort 4. We used a CED rate of 5-20µl/min per catheter, with 1-4 catheters per patient. Tumor mean absorbed radiation dose was 255Gy (8.9-740Gy) while exposure outside the brain was negligible. The mean percentage tumor in the treated volume (Tu/Tv) was 60.3% (19.8%-100%). Thus far, we have observed no dose limiting toxicities, one grade 3 treatment related adverse event (AEs), and the majority of AEs were mild in intensity. The incidence and severity of AEs did not correlate with increasing dose. Mean Tu/Tv in patients not receiving prior bevacizumab was 75% vs. 48% in those that had. Thus far, overall survival (OS) in 16 bevacizumab naïve patient is 49 weeks with 7 patients still alive and a positive correlation of OS to Tu/Tv.

CONCLUSIONS
186RNL achieves high absorbed doses without significant toxicity with favorable overall survival. Updated delivery feasibility, safety and overall survival will be presented.
LOCL-13 SURGICAL RESECTION PLUS STEREOTACTIC RADIOSURGERY (SRS) VERSUS SRS ALONE FOR LARGE POSTERIOR FOSSA BRAIN METASTASES: OUTCOMES AND FACTORS GUIDING THE DECISION OF TREATMENT MODALITY
Authors: Lau-Rodriguez Ruth , Kalyvas Aristotelis , Gutierrez-Valencia Enrique , Weiss Jessica , Conrad Tatiana , Millar Barbara-Ann , Laperriere Normand , Berlin Alejandro , Bernstein Mark , Zadeh Gelareh , Schultz David , Kongkham Paul 
Published: August 2022

Abstract

INTRODUCTION
Approximately 20% of brain metastases (BM) occur in the posterior fossa (PF). However, the criteria to treat large PF BM with surgery (S) followed by stereotactic radiosurgery (SRS) or SRS alone are still unclear. We aim to identify parameters that can help in the decision of treating PF BM with S+SRS or SRS and to compare outcomes between the two groups.

METHODOLOGY
We reviewed a prospective registry database (2009 to 2020) and identified all patients with PF BM (≥4cc in volume) treated with SRS or S+SRS. Clinical and radiological, parameters were analyzed. We examined two endpoints: Overall Survival (OS) and Local Failure (LF).

RESULTS
64 patients were identified; 30 were treated with S+ SRS and 34 with SRS. Gait imbalance and Intracranial pressure symptoms were significantly different between the groups; 97% and 80% for S+SRS vs 47% and 35% for SRS, respectively. Radiologically, there were significant differences in the mean volume of the lesions [6.7 cm3 in SRS vs 29.8cm3 in S+SRS cohort] (p&lt;0.001), compression of the IV ventricle (47% in SRS vs 96% in S+SRS cohort, (p&lt;0.001)) and hydrocephalus (0% in SRS vs 29% in S+SRS cohort, (p&lt;0.001)). One surgical patient required salvage SRS and two SRS patients required salvage S. Patients with S+SRS (HR 0.35, p&lt;0.001) and higher GPA scores (HR 0.62, p=0.007) correlated with better OS. There was no significant difference in rates of LF between the 2 groups.

CONCLUSIONS
Patients treated with S+SRS were more likely to be symptomatic, have larger tumors, and have compression of the IV ventricle with hydrocephalus. Non-symptomatic patients with moderately sized lesions were safely managed with SRS. S+SRS treatment and higher GPA were associated with improved OS.
MMAP-06 INTEGRATED TEAM-BASED BRAIN METASTASIS CARE REDUCES PATIENT VISITS AND SHORTENS TIME TO ADJUVANT IRRADIATION
Authors: Moss Nelson S , El Ahmadieh Tarek Y , Brown Samantha , Chen Justin , Imber Brandon S , Pike Luke , Reiner Anne S , Panageas Katherine S , Brennan Cameron , Tabar Viviane , Beal Kathryn 
Published: August 2022

Abstract

PURPOSE
Timely surgical cavity stereotactic radiosurgery (SRS) is an important adjuvant to brain metastasis resection, with earlier treatment associated with less frequent recurrence. The logistical complexity of treatment organization, however, has resulted in suboptimal start times post-surgically. We implemented a team-based process improvement approach to reduce the time from surgery to adjuvant irradiation of resected brain metastases.

METHODS
A multidisciplinary working group used process-mapping to identify opportunities to reduce visits and shorten treatment times. The care delivery process was modified to streamline perioperative SRS preparation with (1) early patient identification, (2) preoperative intra-team communication, and (3) consolidation of required steps. Plan-Do-Study-Act cycles were used for process improvement. The surgery-to-SRS initiation time interval was the primary outcome. Secondary outcomes included the number of associated patient encounters.

RESULTS
Following implementation, the median (IQR) interval from surgery to SRS was reduced 48% from 27 (21,34) to 14 (13,17) days (p&lt;0.001). The rate of surgical-cavity SRS within 30 days increased from 64% (n=63/98) to 97% (n=60/62; p&lt;0.001). The median (IQR) number of CNS-associated encounters between resection and SRS decreased from 5 (4,6) to 4 (3,5; p&lt;0.001). The proportion of patients who had &gt;1 MRI/CT between surgery and SRS decreased from 45% (44/98) to 13% (8/62; p&lt;0.001). The time from surgery to systemic therapy resumption/initiation among patients treated within 90 days post-operatively decreased from 35 (24,48) to 32 days (23,40; p=0.074). There were no wound complications in either group.

CONCLUSION
Adjuvant SRS latency and treatment-associated encounters were significantly reduced after care-coordination implementation. This approach reduces patient and healthcare system burden and can be applied to other scenarios where early post-operative SRS administration is critical.
MMAP-07 IMPACT OF SINGLE AND DUAL IMMUNE CHECKPOINT BLOCKADE ON RISK OF RADIATION NECROSIS AMONG PATIENTS WITH BRAIN METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY
Authors: Vaios Eugene , Shenker Rachel , Hendrickson Peter , D’Anna Rachel , Niedzwiecki Donna , Carpenter David , Floyd Warren , Winter Sebastian , Dietrich Jorg , Floyd Scott , Kirkpatrick John , Mullikin Trey , Allen Karen , Salama April , Clarke Jeffrey , Reitman Zachary 
Published: August 2022

Abstract

PURPOSE
While stereotactic radiosurgery (SRS) is often an efficacious treatment for brain metastases, it carries a significant risk of radionecrosis (RN). Single and dual immune checkpoint inhibition (ICPI) have emerged as common treatment options for many patients, particularly those with melanoma and non-small cell lung cancer (NSCLC). While data suggest a cancer control benefit of combining SRS and ICPI, we hypothesized that concurrent receipt of dual ICPI with SRS increases the risk for RN.

METHODS
We performed a retrospective review of serial patients with metastatic melanoma or NSCLC treated with SRS for intact brain metastases from 2014-2020 at our single institution. Patients were stratified by receipt of dual vs. single ICPI vs. SRS alone. RN was biopsy confirmed or determined radiographically, in combination with clinical assessment and steroid use. Kaplan-Meier estimates were used to compare rates of RN between cohorts.

RESULTS
673 brain lesions from 93 patients met inclusion criteria [median (Q1, Q3): 5.0 (2.0-10.0) lesions per patient]. Median follow-up of lesions was 8.1 months (95% CI: 7.3, 8.7). Most (82.8%) lesions were supratentorial and histologies included melanoma (53.5%), adenocarcinoma NSCLC (27.3%), squamous cell NSCLC (6.1%), and NSCLC NOS (6.1%). In the entire cohort, 88 lesions from 25 patients (27%) developed RN. 77 (87%) lesions were diagnosed clinico-radiographically and 11 (13%) were biopsy-proven. ICPI use was highly enriched among lesions that developed RN (85.2%) versus those that did not (19.8%). Freedom from RN at 6 months was 80% for dual ICPI, 82% for single ICPI, and 97% for SRS alone; 12 month rates were 78% in each of the ICPI cohorts and 95% with SRS alone (P=0.0002).

CONCLUSIONS
In a large cohort of SRS-treated brain metastases, we observed an increased risk of RN among patients who received either dual or single ICPI concurrently with SRS.
MMAP-09 CHARACTERISTICS CORRELATING WITH SURVIVAL IN PATIENTS TREATED FOR LARGE BRAIN METASTASES
Authors: Gutierrez-Valencia Enrique , Kalyvas Aristotelis , Millar Barbara-Ann , Laperriere Normand , Conrad Tatiana , Berlin Alejandro , Weiss Jessica , Zadeh Gelareh , Bernstein Mark , Kongkham Paul , Shultz David B 
Published: August 2022

Abstract

BACKGROUND
We aimed to identify factors predicting survival following treatment to large (&gt;4cc) BrM.

METHODS
From a prospective registry database, we identified 364 adult patients treated for brain metastases (BrM) or surgical cavities larger than &gt;4 cc: 127 and 237 treated with surgery plus stereotactic radiosurgery (S+SRS) and SRS alone, respectively. We compared the 2 treatment arms using propensity score-matched (PSMA) and multivariate analyses (MVA). P values &lt;0.05 were considered statistically significant.

RESULTS
Median target volume was 6.6cc (4-36.9cc) for intact BrM and 15cc (4-54) for cavities. Median OS was 19 and 12 months for the S+SRS and SRS groups, respectively [HR 1.73 (1.35-2.22) (P&lt;0.001)]. On UVA, number of BrM [HR 1.13 (1.06-1.22) (P&lt;0.001)], ECOG 3-4 [HR 2.78 (1.73-4.46) (P&lt;0.001)], and extracranial disease (ECD) at BrM treatment [HR 1.82 (1.37,2.40) (P&lt;0.001)], correlated inversely with OS. GPA [HR 0.61 (0.52,0.70) (P&lt;0.001)] and receipt of systemic therapy after BrM treatment[HR 0.58 (0.45-0.75) (P&lt;0.001)] correlated to improved OS. On MVA, S+SRS [HR 1.81 (1.19,2.74) (P&lt;0.0054)], reduced target volume [HR 1.03 (1.01,1.06) (P&lt;0.0042)], and receipt of immune/targeted therapy [HR 0.68 (0.50,0.93) (P&lt;0.015)] correlated with OS. PSMA comparing the treatment arms matched by ECD, number of BrM, ECOG, and SRS target volume, demonstrated that treatment arm remained correlated to OS [HR 1.62 (1.20-2.19) (P=0.0015)]. The cumulative incidence (CI) of LF requiring surgical resection at 12 months was 3% versus 7% for S+SRS and SRS groups, respectively [(HR 2.04 (0.89-4.69) (P =0.091)]. CI of PMD at 12 months was 16% versus 0% for S+SRS and SRS groups, respectively.

CONCLUSION
Reduced SRS target volume, treatment with systemic therapy following BrM treatment, and surgical resection prior to SRS correlate with survival in patients with large BrM. PMSA supports the hypothesis that surgery prior to SRS improves survival in patients with large BrM.
MMAP-11 VOLUMETRIC STUDY OF BRAIN METASTASES IN EGFR-POSITIVE NSCLC TREATED WITH OSIMERTINIB WITH OR WITHOUT CNS-DIRECTED RADIATION THERAPY
Authors: Ni Lisa , Phuong Christina , Chen Jie Jane , Chen William , Daras Mariza , Raleigh David , Nakamura Jean , Boreta Lauren , Sneed Penny , Braunstein Steve 
Published: August 2022

Abstract

BACKGROUND
In patients with brain metastases (BM) from EGFR-positive non-small cell lung cancer (NSCLC), recent data indicated that treating with CNS-penetrant tyrosine kinase inhibitors such as osimertinib may enable deferring radiotherapy (RT) in select patients. The purpose of this study was to describe the radiographic response of newly diagnosed BM to osimertinib with or without stereotactic radiosurgery or whole brain radiotherapy, to identify parameters that may guide early versus delayed salvage RT.

METHODS
In this single-institution retrospective study, 35 patients with 186 newly diagnosed BM started on osimertinib between 2014 and 2020 were reviewed. BM with tumor volume ≥ 0.1 cm3 were included in the volumetric analyses (N=106 BM). Survival was estimated with the Kaplan-Meier method, and univariable analysis was performed using log-rank tests. Cox proportional hazards was used for multivariable analyses for local control (LC), distant brain failure (DBF), and overall survival (OS).

RESULTS
Of the 35 patients, 8 (23%) received osimertinib alone. Median follow-up was 29 months. The 1- and 2-year LC rates were 94% and 86%. The 1- and 2-year OS rates were 89% and 66%. Median time to DBF was 24 months. Patients treated with osimertinib and RT were more likely to have a significant radiographic volumetric response at early follow-up (4-12 weeks after treatment initiation) compared to osimertinib alone (median volumetric response of –80% vs. –41%, p=0.05). On per lesion analysis, early volumetric response of ≥ 80% was associated with improved LC (3-year LC 98% vs 72%, p=0.04).

CONCLUSIONS
The combination of osimertinib and CNS RT is associated with greater early volumetric response in patients with BM from EGFR-positive NSCLC compared to osimertinib alone. BM with significant initial radiographic response remain well-controlled in the long term. Patients whose BM demonstrate limited initial volumetric response may benefit from targeted RT to provide long term control.
SPCR-02 NEUROCOGNITIVE FUNCTION IN PATIENTS WITH LEPTOMENINGEAL METASTASIS TREATED WITH PROTON CRANIOSPINAL IRRADIATION
Authors: Correa Denise , Koch Adrian , Baser Raymond , Pentsova Elena , Wolden Suzanne , Imber Brandon , Boire Adrienne , Yang Jonathan 
Published: August 2022

Abstract

BACKGROUND
Proton craniospinal irradiation (pCSI) as a potential treatment for patients with solid tumor leptomeningeal metastasis (LM) is being assessed in a phase II randomized study comparing it with photon involved-field radiotherapy (RT). We report the preliminary results of prospective neurocognitive function in a subset of patients treated with pCSI.

METHODS
Patients with LM and without evidence of CNS disease progression completed standardized neurocognitive tests of attention and working memory, executive function, and verbal memory at baseline (pre-pCSI), and 3 and 6 months post-pCSI. All patients received chemotherapy (baseline and follow up) and memantine (follow up). Means across the three timepoints were estimated for each neurocognitive test score using a linear mixed model (LMM) predicting the score by timepoint. Mean changes between pairs of timepoints were similarly estimated from the LMMs and tested for statistical significance using model-based contrasts.

RESULTS
Baseline, 3-month and 6-month neurocognitive data were available for 12, 11, and 8 patients, respectively. Linear mixed model analyses showed a significant decline in graphomotor speed (Trails A, p=0.03), verbal learning (HVLT-R Total Learning, p&lt;0.001), and verbal recognition memory (HVLT-R Discrimination, p=0.03) from baseline to 3 months post-pCSI, with scores remaining stable at 6 months post-pCSI. There was a significant decline in timed set-shifting (Trails B, p=0.04) from baseline to 6 months post-pCSI. There were no significant changes in attention and working memory over the follow-up period.

CONCLUSION
Preliminary results in a subset of patients showed a decline in graphomotor speed and verbal memory at 3 months and executive function at 6 months post-pCSI, possibly related to the early adverse effects of RT. These results are overall consistent with findings in other populations treated with whole-brain RT. However, there was no change in attention and working memory and most cognitive domains remained stable at six months with pCSI.
SPCR-03 NEUROCOGNITIVE OUTCOMES FROM PHASE 1 TRIAL OF BMX-001 IN COMBINATION WITH CONCURRENT RADIATION THERAPY AND TEMOZOLOMIDE IN NEWLY DIAGNOSED HIGH-GRADE GLIOMA PATIENTS
Authors: Peters Katherine , Kirkpatrick John , Batinic-Haberle Ines , Affronti Mary Lou , Woodring Sarah , Lipp Eric , Herndon James , Boyd Kendra , Spasojevic Ivan , Penchev Sara , Gad Shayne , Silberstein David , Johnson Margaret , Desjardins Annick , Friedman Henry , Ashley David , Crapo James 
Published: August 2022

Abstract

INTRODUCTION
Neurocognitive dysfunction can result from radiation therapy which is the mainstay of treatment for high-grade glioma, particularly glioblastoma. Preclinical observations found that BMX-001, a novel metalloporphyrin, acts as a radioprotectant for normal CNS cells yet as a radiosensitizer to cancer cells in human GBM xenograft experiments. In a phase 1 study evaluating the safety of BMX-001 in combination with concurrent radiation therapy and temozolomide, we further studied neurocognitive function before and after concurrent radiation therapy and temozolomide in newly diagnosed high-grade glioma patients.

METHODS
We performed a phase 1 study of BMX-001 combined with radiation therapy (6-week total of 59.4-60 Gy) and temozolomide (75 mg/m2/day for 42 days). We administered BMX-001 as a subcutaneous injection at a loading dose before radiation therapy and temozolomide and then subsequent doses twice weekly for eight weeks. A key secondary endpoint was the evaluation of neurocognition. We performed neurocognitive testing with the computerized program CNS Vital Signsâ. This battery consists of seven tests: verbal memory, visual memory, finger tapping, symbol digit coding, the Stroop Test, a test of shifting attention, and a continuous performance test. We defined neurocognitive impairment at baseline as a z-score ≥ 1.5 SDs below the normative mean. We described improvements or declines in neurocognition at 2 and 6 months from baseline.

RESULTS
Fifteen patients (age 19-80 years) enrolled and underwent neurocognitive testing before and after RT. All patients had WHO grade 4 glioblastoma. Most subjects had neurocognitive impairment ranging from 46.7-to 80% on specific neurocognitive tests. At two months (N=15) and six months (N=9), most testing demonstrated improved neurocognitive performance.

CONCLUSIONS
Neurocognitive function is maintained and can improve after concurrent radiation therapy and temozolomide in this high-grade glioma cohort treated with BMX-001 during concurrent radiation therapy and temozolomide.
SYST-02 PHASE ⅡB CLINICAL TRIAL OF NEOADJUVANT CHEMOTHERAPY REVERSING GLIOMA STEM CELLS CHEMORESISTANCE IN NEWLY DIAGNOSED GBM WITH MGMT PROMOTER UNMETHYLATION
Authors: Dong Jun , Wang Liping , Chen Yanming 
Published: August 2022

Abstract

PURPOSE
To evaluate clinical efficacy and safety of combination of nicardipine and valproic acid on temozolomide (TMZ) neoadjuvant chemotherapy targeting on glioma stem cells (GSCs) in newly diagnosed glioblastoma multiforme (GBM) patients with O6-methylguanine-DNA-methyltransferase (MGMT) promoter unmethylation.

METHODS
From June 2018 to April 2021, newly diagnosed GBM patients after tumor surgical removal and concurrent radio-chemotherapy with TMZ, with MGMT promoter unmethylation were randomly assigned to two groups. The control group was applied standard TMZ regimen. The trial group was administered standard TMZ regimen, plus nicardipine(20mg/d) and valproic acid (1.2g/d) as neoadjuvant treatment against GSCs chemoresistance. The relevant treatment data and adverse reactions of the patients were collected, Karnofsky performance status (KPS) score, progression-free survival (PFS) and overall survival (OS) were evaluated during patient follow-up.

RESULTS
33 patients were enrolled in this study, eighteen patients were randomly assigned in the trial group and 15 patients were in the control group. There was no statistical difference in gender composition, age, degree of surgical resection, or KPS score before treatment between the two groups. The median progression-free survival (mPFS) in the trial group was 10.8 months (95%CI 5.81-15.79 month), and the mPFS in the control group was 7.1 months (95%CI 5.12-9.08 month), which was a statistically difference (Log-Rank test P=0.033). The median overall survival (mOS) increased from 12.1 months (95%CI 9.18-15.00 month) in the control group to 15.7 months (95%CI 7.67-23.73 month) in the trial group (Log-Rank test P=0.015). There was no statistically significant difference in the incidence of adverse reactions between the two groups, and there were no treatment regimen related deaths.

CONCLUSIONS
TMZ combined with neoadjuvant of nicardipine and valproic acid against GSCs chemoresistance can prolong the survival time of patients who was newly diagnosed glioblastoma with MGMT promoter unmethylation. The preferred regimen can be applied safely without serious adverse events, which deserved further multi-center clinical investigations.
Multiscale dynamical cross-talk in zeolite-catalyzed methanol and dimethyl ether conversions
Authors: Lin Shanfan , Zhi Yuchun , Liu Zhiqiang , Yuan Jiamin , Liu Wenjuan , Zhang Wenna , Xu Zhaochao , Zheng Anmin , Wei Yingxu , Liu Zhongmin 
Published: August 2022

AbstractEstablishing a comprehensive understanding of the dynamical multiscale diffusion and reaction process is crucial for zeolite shape-selective catalysis and is urgently demanded in academia and industry. So far, diffusion and reaction for methanol and dimethyl ether (DME) conversions have usually been studied separately and focused on a single scale. Herein, we decipher the dynamical molecular diffusion and reaction process for methanol and DME conversions within the zeolite material evolving with time, at multiple scales, from the scale of molecules to single catalyst crystal and catalyst ensemble. Microscopic intracrystalline diffusivity is successfully decoupled from the macroscopic experiments and verified by molecular dynamics simulation. Spatiotemporal analyses of the confined carbonaceous species allow us to track the migratory reaction fronts in a single catalyst crystal and the catalyst ensemble. The constrained diffusion of DME relative to methanol alleviates the high local chemical potential of the reactant by attenuating its local enrichment, enhancing the utilization efficiency of the inner active sites of the catalyst crystal. In this context, the dynamical cross-talk behaviors of material, diffusion and reaction occurring at multiple scales is uncovered. Zeolite catalysis not only reflects the reaction characteristics of heterogeneous catalysis, but also provides enhanced, moderate or suppressed local reaction kinetics through the special catalytic micro-environment, which leads to the heterogeneity of diffusion and reaction at multiple scales, thereby realizing efficient and shape-selective catalysis.