bluuebunny/crossref_metadata_2025_split huggingface dataset:
QOL-18. MANAGING CANCER AND LIVING MEANINGFULLY (CALM) IN PRIMARY AND SECONDARY MALIGNANT BRAIN TUMOR PATIENTS: INTERIM ANALYSIS OF A PHASE IIC RANDOMIZED CONTROL PILOT TRIAL
Authors: Loughan Ashlee , Lanoye Autumn , Davies Alexandria , Kleva Chris , Zarrella Giuliana , Fox Amber , Rodin Gary 
Published: November 2024

Abstract

BACKGROUND
Patients with both primary and secondary brain tumors demonstrate substantial psychological distress but have been historically excluded from psychological research. Managing Cancer and Living Meaningfully (CALM), a supportive- expressive- psychotherapy, has proven to reduce depression and death-anxiety in advanced cancer patients but trials in neuro-oncology have been limited. Interim analyses (50% accrual) of the first randomized control pilot trial (RCT) of CALM in neuro-oncology are presented here.

METHODS
In this ongoing NIH ORBIT model Phase IIc pilot RCT, 60 adults with primary or secondary malignant brain tumors and heightened distress (PHQ/DADDS) are randomized (2:1) to a six-session CALM intervention or usual care. Data collection includes established feasibility and acceptability metrics, intervention satisfaction surveys and interviews, and clinically meaningful changes in distress severity scores across three timepoints (pre-, post-CALM, follow-up).

RESULTS
Of 64 patients screened, 36 were eligible and 32 enrolled (n=20 CALM, n=12 Control; 65% female; 90% White; Mage=46yrs). A multimodal recruitment model was used. Currently, assessment completion rates are: post-CALM (80%) and follow-up (67%). Reasons for withdrawal include disinterest in intervention topics (n=1) and lost to follow-up (n=1). Intervention retention is currently at 90%, with 8 participants still in active treatment. No adverse events have been documented. Perceived benefit appears high (4.1/5) and all participants report they would recommend CALM to others. Pre- to post-CALM, depression severity reductions appear equal across arms (CALM PHQ-9=30%; Control=33%) but death anxiety severity reductions appear more prevalent in the treatment group (CALM DADDS=70%; Control=50%).

CONCLUSIONS
Interim data suggests promising feasibility and acceptability results in this pilot RCT. Enrollment, retention, and assessment completion rates appear adequate. Participants are reporting high benefit and recommendation of CALM. Improvement in death anxiety appears greater in those treated with CALM compared to controls. These interim RCT findings are promising and suggest completion of the current phase.
QOL-21. PSYCHOMETRIC VALIDATION OF THE FEAR OF CANCER RECURRENCE INVENTORY FOR PRIMARY BRAIN TUMOR PATIENTS
Authors: Cheng Emilie , Mladen Samantha , Cook Sarah , Lanoye Autumn , Loughan Ashlee , Simard Sebastian , Braun Sarah 
Published: November 2024

Abstract

BACKGROUND
Fear of cancer recurrence and progression (FCR) is a significant concern among those living with primary brain tumor and may be distinct compared to FCR in other cancer populations due to poorer prognosis, neurologic symptoms, and often lifelong treatment. The gold-standard comprehensive assessment tool for FCR–the FCR Inventory (FCRI)–includes 42 items with seven subscales. Validation of the FCRI scale excluded those with primary brain tumors. The present study is the first examination of the psychometric properties of the full FCRI in a heterogeneous sample of patients with primary brain tumors.

METHODS
Adult patients with primary brain tumors (n=334) completed the FCRI, with six additional brain tumor-specific items, and psychological, medical, and demographic questionnaires. In accordance with best practices of measure development, exploratory factor analysis (EFA) was conducted on the FCRI at the subscale level. Correlations investigated construct validity.

RESULTS
EFA largely supported the overall psychometric properties of the original FCRI. Several subscales were unchanged: Psychological Distress, Functioning Impairments, Insight, and Reassurance. One brain tumor-specific item (researching treatments) exhibited good fit on the Coping Skills subscale. On the Severity subscale, one item (belief that the tumor will not return) did not fit with an otherwise strong one-factor model. Additionally, five new brain tumor-specific items demonstrated good fit with the Triggers subscale. The resultant FCRI-Brain includes 41 original FCRI items plus six new brain tumor-specific items. FCRI-Brain demonstrated good convergent validity with measures of depression (r=.72), anxiety (r=.75), and death anxiety (r=.80; ps&lt;.05).

CONCLUSIONS
This is the first validation of the comprehensive FCRI in patients with primary brain tumors. Factor analysis identified a theoretically similar and brain-tumor specific seven-factor model for the FCRI-Brain. Item-level and subscale statistics will be presented, including factor iteration and construction. Future work will use the FCRI to investigate FCR intervention efficacy in neuro-oncology.
QOL-23. MEASURING BODY FUNCTIONALITY APPRECIATION IN PATIENTS WITH PRIMARY BRAIN TUMORS
Authors: Cook Sarah , Davies Alexandria , Cheng Emilie , Lanoye Autumn , Loughan Ashlee , Braun Sarah 
Published: November 2024

Abstract

BACKGROUND
Body image is a multifaceted construct consisting of thoughts, feelings, and perceptions about one’s body and its functioning. Perception of one’s own physical functioning and capabilities may be an important consideration in neuro-oncology given the sequalae of brain tumors and associated treatment; however, it is understudied in this population. One brief measure of body image, the Functionality Appreciation Scale (FAS) is a comprehensive tool, focused on one’s perceived physical functioning and capabilities, rather than perceived appearance. We aimed to examine the psychometric properties of the recently developed Functionality Appreciation Scale (FAS) among patients with primary brain tumors.

METHODS
Adult patients with primary brain tumors (N=237) completed the FAS and other measures of psychological distress as well as medical and demographic characteristics. An exploratory variance factor analysis (EFA) using principal axis factoring and a Promax rotation was conducted. Convergent validity was examined via correlations to measures of psychological distress.

RESULTS
The EFA supported the single-factor structure, which accounted for 62.71% of the variance with all items loading significantly onto this factor. The FAS had good internal consistency (Cronbach’s a=.90). Convergent validity was demonstrated by negative associations (ps&lt;.05) with symptoms of depression (r=-.30), generalized anxiety (r=-.21), and death anxiety (r=-.17).

CONCLUSION
Results confirmed the single factor structure of the FAS in primary brain tumor patients. Furthermore, the expected negative relationships with measures of psychological distress provide evidence of convergent validity. The FAS is valid and reliable in patients with primary brain tumors. Our findings suggest that body functionality and appreciation may be important to target in psychosocial interventions for those with primary brain tumors.
RBIO-02. DEVELOPMENT OF FLASH-CAR RADIOIMMUNOTHERAPY FOR PEDIATRIC BRAIN TUMORS
Authors: Ni Haiwei , Reitman Zachary , Kirsch David , Gong Yanqing , Fan Yi 
Published: November 2024

Abstract
Pediatric brain tumors including medulloblastoma and high-grade glioma are generally refractory to T cell-based immunotherapy, largely due to an immune-hostile microenvironment infiltrated extensively with immunosuppressive macrophages. Ultra-high dose rate (FLASH) radiotherapy holds promise for treating solid tumors, given the potential lower toxicity in normal tissues and possible favorable impact on tumor immunity. Using a genetically engineered mouse model of medulloblastoma and glioma, we show that FLASH radiation stimulates pro-inflammatory polarization in tumor macrophages. Single-cell transcriptome analysis shows that FLASH proton beam radiation skews macrophages towards proinflammatory phenotypes and increases T cell infiltration in the medulloblastoma model. Further bulk transcriptome analyses reveal that FLASH radiation reduces peroxisome proliferator-activated receptor (PPAR)-γ and arginase-1 expression and inhibits immunosuppressive macrophage polarization under stimulus-inducible conditions. Mechanistically, FLASH radiation abrogates lipid oxidase expression and oxidized low-density lipid (oxLDL) generation to reduce PPARγ activity, while standard radiation induces reactive oxygen species (ROS)-dependent PPARγ activation in macrophages. Notably, FLASH radiotherapy improves infiltration and activation of chimeric antigen receptor (CAR) T cells and sensitizes tumors to GD2 CAR T immunotherapy in the autochthonous medulloblastoma and syngeneic glioma models. These findings suggest that FLASH radiotherapy may reprogram macrophage lipid metabolism to reverse tumor immunosuppression and that combination FLASH-CAR radioimmunotherapy may offer exciting opportunities for treatment of pediatric brain tumor.
RBIO-03. A SMALL ANIMAL RADIATION RESEARCH PLATFORM (FLASH-SARRP) TO MEASURE IMMUNOLOGICAL EFFECT OF ULTRA HIGH DOSE RATE (FLASH) RADIOTHERAPY
Authors: Aziz Khaled , Sforza Daniel , Tajik-Mansoury Ehsan , Rezaee Mohammad , Kleinberg Lawrence 
Published: November 2024

Abstract
Patients who undergo radiation therapy (RT), particularly fractionated courses, often develop lymphopenia. Clinical outcome for various cancer types, including brain tumors, identifies lymphopenia as a negative prognostic factor. The mechanism for RT induced lymphopenia is unclear. Simulated models suggest the volume of blood flowing through a radiation field could play a crucial role in death of radiosensitive lymphocytes. FLASH RT is ultrahigh dose rate administration of RT, &gt;100 times faster dose rate than standard RT that has been observed to improve the therapeutic ratio in preclinical models by preferential normal tissue sparing. Hypothesized mechanisms include chemical reactions depleting oxygen in well oxygenated normal cells creating radioresistance, differing pro-inflammatory signaling impacting tumor and normal tissue, and less impact on circulating immune cells consequent to decreased proportion exposed during a treatment session which may enhance antineoplastic response. We designed the novel FLASH kV x-ray cabinet system for preclinical laboratory research (FLASH-SARRP) to deliver ultra-high dose rates up to 100 Gy/s as well as conventional dose rates of 1.0 Gy/s to facilitate comparative studies. A custom designed docking system was developed to reproducibly position and immobilize mouse for stereotactic radiation of the brain. Dose and dose rate measurements were performed with calibrated Gafchromic EBT3 film in solid water with 0.025 mm additional copper filter. FLASH-SARRP system delivered kV x-rays at an average dose-rate of 79.2±2.1Gy/s corresponding to 10 mm depth in the immobilized mouse brain. For the delivery of 15 Gy, treatment duration was 0.2 seconds for FLASH RT administration whereas it was 244 seconds for conventional dose rate. We successfully designed a high-precision platform to study partial brain x-ray FLASH effects in mice and studies are ongoing to assess differential impact on normal brain tissue, circulating cytokines, and immune cell populations for single dose and fractionated administration of FLASH and standard radiotherapy.
RTID-01. ACCELERATOR-BASED BORON NEUTRON CAPTURE THERAPY, RANDOMIZED CONTROLLED TRIAL FOR RECURRENT AND REFRACTORY HIGH-GRADE MENINGIOMAS
Authors: Miyatake Shin-Ichi , Wanibuchi Masahiko , Furuse Motomasa , Nonoguchi Naosuke , Kawabata Shinji , Nihei Keiji , Ono Koji , Takeno Satoshi , Fu Naonori 
Published: November 2024

Abstract

INTRODUCTION
High-grade meningiomas (HGMs) recurred after X-ray treatment showed pessimistic prognosis. We started “A phase II investigator-lead RCT using accelerator-based BNCT system for refractory recurrent high-grade meningioma”.

MATERIALS AND METHODS
We prepared 2 study arms, BNCT test treatment arm (12 subjects) and control best supportive care arm (6 subjects) in randomized controlled trial (RCT) fashion. PFS judged by the third-party committee was primary endpoint and PFS judged by investigators themselves and OS of BNCT arm were secondary endpoints. Rescue BNCT was permitted for control group patients, if they showed progress disease (PD).

RESULTS
Three and two grade 3 subjects were included in BNCT and control arm, respectively. Others were grade 2 subjects. As of March 31, 2024, 10 out of 12 in BNCT arm and all 6 cases in control arm were judged as PD. mPFS judged by investigators showed 65 and 8 weeks for BNCT and control arm, respectively (P=0.0002, Wilcoxon). Six out of 12 in BNCT and 4 out of 6 cases in the control arm were dead. OS-2 year rates of BNCT and control arms are 91.7% and 33.3%, respectively (p=0.045, Wilcoxon). Five out of 6 cases in control arm received rescue BNCT after PD assessments. With regard to best response on MRI, PR, SD were 5 and 7 cases in treatment arms (ORR was 41.7%).

CONCLUSION
mPFS judged by third party committee is still being closed and unknown, so far. With regard to secondary endpoints, there are marked differences in both arms in mPFS judged by investigators. Recently, the results of RCT of “Trabectedine” organized by EORTC was reported. Unfortunately there was no effect of Trabectedine not only in PFS but in OS. In our current RCT results BNCT arm is extremely excellent in comparison with EORTC RCT of “Trabectedine” both in OS and PFS.
RTID-04. A MULTICENTER, RANDOMIZED, CONTROLLED PHASE 2B TRIAL OF SURVIVIN VACCINE SURVAXM PLUS ADJUVANT TEMOZOLOMIDE FOR NEWLY-DIAGNOSED GLIOBLASTOMA (SURVIVE)
Authors: Ahluwalia Manmeet , Ciesielski Michael , Abad Ajay , Reardon David , Ozair Ahmad , Khosla Atulya , Aiken Robert , Barbaro Marissa , Sinicrope Kaylyn , Peereboom David , Odia Yazmin , Brenner Andrew , Venur Vyshak , Belal Ahmed , Qiu Jingxin , Schilero Cathy , Casucci Danielle , Mechtler Laszlo , Fenstermaker Robert 
Published: November 2024

Abstract

BACKGROUND
Glioblastoma cells express high levels of survivin protein, whose presentation by MHC class I gets recognized by antibodies and cytotoxic T-lymphocytes (CTLs). A phase 2a trial (NCT02455557) demonstrated a median overall survival (OS) of 25.9 months in newly-diagnosed glioblastoma (nGBM) patients with 15-amino-acid-peptide-conjugate survivin vaccine (SurVaxM), which also stimulated production of survivin-directed antibodies and anti-tumor CTL. This phase 2b trial aims to further investigate efficacy and safety of SurVaxM plus adjuvant temozolomide (TMZ) for nGBM.

METHODS
SURVIVE is an ongoing, multicenter, randomized, placebo-controlled, investigator- and patient-blinded, phase 2b trial that randomizes nGBM patients receiving standard-of-care therapies to either SurVaxM (SurVaxM arm) or saline (control arm) in 3:2 ratio at 15 sites. Included patients have age ≥18 years, normal organ function, KPS≥70, and receive surgical resection with ≤1cm3 residual MRI contrast enhancement within 72 hours post-resection plus TMZ. Patients with recurrent, multicentric, brainstem- or cerebellar-origin GBM are excluded as well as patients on TTFields or other immunotherapies. All patients undergo 3 phases: (1) vaccine priming (VP) phase, starting ≤4 weeks after completing chemoradiation – 4 doses of SurVaxM or placebo administered q2weeks; (2) TMZ phase, started after ≥1 VP dose; and (3) vaccine maintenance phase, started 8 weeks after VP, with SurVaxM or placebo given q8weeks. TMZ phase overlaps with VP and VM phases. Primary endpoint is median OS. Assuming 1-year-OS of 75% in SurVaxM arm, based on prior trials, and 60% for control, the required sample size is N=228; 137 in SurVaxM and 91 in control arm. Accounting for dropouts, we aimed to enroll 239 patients. A log-rank test stratified by KPS (70-80 vs 90-100), MGMT methylation status, and IDH mutation status will be used for analysis. Secondary endpoints are OS and PFS at 15, 18, and 24 months, median PFS, and toxicity. A single sequential OS-driven interim analysis is planned when 50% of deaths occur. Trial is fully enrolled (NCT05163080).
SURG-08. A PHASE III RANDOMIZED TRIAL OF GROSS TOTAL RESECTION VERSUS POSSIBLE RESECTION OF FLAIR HYPERINTENSITY LESION ON MR IMAGE FOR NEWLY DIAGNOSED SUPRATENTORIAL GLIOBLASTOMA (JCOG2209)
Authors: Sonoda Yukihiko , Sekino Yuta , Mizusawa Junki , Shibahara Ichiyo , Sasaki Keita , Sekita Tetsuya , Ichikawa Mayumi , Igaki Hiroshi , Kinoshita Manabu , Shibahara Junji , Ichimura Koichi , Arakawa Yoshiki , Narita Yoshitaka 
Published: November 2024

Abstract

BACKGROUND
Complete resection of contrast-enhanced lesion (gross total resection: GTR) without severe neurological deficits has been generally accepted as the goal of surgery. However, it remains unclear if additional resection of surrounding FLAIR hyper-intense lesion combined with GTR (FLAIRectomy) has survival advantage of primary glioblastoma patients. Purpose: Multicenter, open-label, randomized phase III trial was commenced to confirm the superiority of FLAIRectomy to GTR alone followed by radiotherapy with concomitant and adjuvant temozolomide in terms of overall survival (OS) for primary glioblastoma IDH-wildtype patients. This trial investigates not only survival but also postoperative neurological and neurocognitive deficits in detail.

METHODS
We assumed a 2-year OS of 50% in the GTR arm and expected a 15% improvement in the FLAIRectomy arm. A total of 130 patients is required with a one-sided alpha of 5%, power of 70%, and will be accrued from 49 Japanese institutions in 4 years and follow-up will last 2.5 years. Patients 18-75 years of age will be registered and randomly assigned to each arm with 1:1 allocation. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, proportion of National Institutes of Health stroke scale preservation, proportion of mini-mental state examination preservation and proportion of health-related quality of life preservation. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in May 2023. Ethics approval was granted by the National Cancer Center Hospital Certified Review Board. Patient enrollment began in July 2023.

DISCUSSION
If FLAIRectomy is superior to GTR alone, aggressive surgery will become a standard surgical treatment for glioblastoma with resectable contrast-enhanced lesion. Trial registration: Registry number: jRCT1031230245. Date of registration: 19/July/2023. Date of first participant enrollment: 28/July/2023. Funding for this study is provided by National Cancer Center Research and Development Fund (2023-J-03).
SURG-22. BRAIN METASTASIS FROM ADVANCED GASTRIC CANCERS: HIGH INCIDENCE OF LEPTOMENINGEAL DISSEMINATION AND ITS CLINICAL IMPACT ON SURVIVAL
Authors: Kim Euihyun 
Published: November 2024

Abstract

OBJECTIVE
Advanced gastric cancer is one of the most common and fatal cancers worldwide, and due to its highest incidence rate in Eastern Asian, it is steadily considered important. However, brain metastasis from advanced gastric cancer is very rare, and its incidence is reported as less than 1% of patients with primary advanced gastric cancer. There have been very few studies describing on the incidence and clinical outcome of patients with brain metastasis from advanced gastric cancers.

METHOD
We retrospectively analyzed 128 patients diagnosed as brain metastasis from advanced gastric cancers, and then underwent treatment from 2005 to 2021 April in our institution. Patients’ survival and its associated prognostic factors were evaluated. Especially, subgroup analysis on patients with leptomeningeal dissemination (LMD) was performed.

RESULT
Of total 128 patients of advanced gastric cancer with brain metastasis, 74 patients (58%) were diagnosed with LMD. Overall survival of LMD group was significantly shorter than that of non-LMD group (p&lt;0.001). Patients treated with tumor removal (TR) followed by whole brain radiotherapy (WBRT) showed superior overall survival than patients with WBRT alone (p=0.002). Among 74 LMD patients, those who underwent WBRT combined with intrathecal methotrexate (IT MTX) showed better outcome than patients with WBRT alone (p=0.025). Specifically, for the 51 pure LMD patients without parenchymal brain metastasis, the superiority of adjuvant IT TMX on survival outcome was more apparent (p=0.011).

CONCLUSION
The incidence of LMD has been underestimated as 58% of patient with brain metastasis from advanced gastric cancers presented LMD on radiological and cytological studies. If the brain tumor is surgically resectable, TR followed by WBRT can be the first choice of treatment provides survival benefit. Patients with LMD are most benefited from IT MTX combined with WBRT.
SURG-25. PREOPERATIVE EMBOLIZATION IMPROVES LOCAL CONTROL AND REPROGRAMS GENE EXPRESSION IN ATYPICAL WHO GRADE 2 MENINGIOMAS
Authors: Haddad Alexander , Ramesh Rithvik , Zakimi Naomi , Quintana Daniel , Gil Eugene , Kabir Aymen , Sibih Youssef , Morales Blanca , Bhalla Shuhbhang , Morshed Ramin , Winkler Ethan , Aghi Manish , Raleigh David 
Published: November 2024

Abstract
Preoperative embolization is hypothesized to reduce blood loss and surgical time for meningioma resection, but the impact of embolization on long-term clinical outcomes and molecular profiling of meningiomas is incompletely understood. To address this, we evaluated the impact of embolization on outcomes and molecular features of WHO grade 2 meningiomas. A series of patients with grade 2 meningiomas who underwent resection at our institution from 1997 to 2021 were identified and reviewed. Available DNA methylation profiling and bulk RNA sequencing data were analyzed (n=200). Univariate and multivariate analyses, Cox proportional hazards modeling, and propensity matching (sex, age at surgery, previous surgery, extent of resection, postoperative radiation) were used. A total of 357 patients with WHO grade 2 meningiomas were included, 129 (36.1%) of which underwent preoperative embolization. Mean age at diagnosis was 53.5 years and 61.4% of patients were female. There was no significant difference in time to recurrence with or without embolization for cases with gross total resection (229/357), but embolization was independently associated with improved local control for cases with subtotal resection even after accounting for postoperative radiotherapy (HR 0.49, 95% CI 0.32-2.20 p=0.028). The average time to recurrence of atypical WHO grade 2 meningioma was 3.3 years after subtotal resection and 6.7 years after embolization and subtotal resection (p&lt;0.001, propensity matched). The distribution of Merlin-intact vs Immune-enriched vs Hypermitotic meningioma DNA methylation groups was equivalent with versus without embolization, but differential gene expression analysis of RNA sequencing data revealed enrichment of hypoxia related pathways after embolization that were unique to each DNA methylation group. In summary, these data show that preoperative embolization improves local control and reprograms gene expression in atypical WHO grade 2 meningiomas. Additional investigation into the impact of embolization on clinical outcomes and gene expression for meningiomas, especially for higher-grade tumors, is warranted.