bluuebunny/crossref_metadata_2025 huggingface dataset:
OCTS-05 BRAIN BIOMARKER ANALYSIS OF LIKELY TUMOR ORIGIN (BALTO)- A PROSPECTIVE STUDY FOR THE DETECTION/DIAGNOSIS OF CNS TUMORS FROM CSF USING THE BELAY SUMMIT™ ASSAY
Authors: Holdhoff Matthias , Kumthekar Priya , Reddi Honey , Reiners Stephanie , Bettegowda Chetan
Published: August 2024

Currently, there is a lack of adequate sensitive and specific non- or minimally invasive molecular biomarker technologies to aid in the diagnosis of Central Nervous System (CNS) cancers in patients suspected of having disease based on clinical or radiological findings. Cerebrospinal fluid (CSF) cytology has low sensitivity, necessitating tissue sampling through invasive neurosurgical procedures in most cases. Tumor-derived DNA (ctDNA) has shown potential to detect brain and spinal cord neoplasms by evaluating CSF, offering promise in monitoring dynamic changes in disease burden and evolving mechanisms of resistance in patients undergoing treatment. In this study, we aim to bridge the gap in cytology by utilizing the Belay Summit™ assay, a next generation DNA sequencing-based platform, to identify and characterize tumor derived DNA in CSF across a diverse population in comparison to the current standard of care of histopathology and CSF cytology. Our objective is to demonstrate the performance of the Belay Summit™ assay to help clinicians diagnose and manage patients with suspected or known brain cancer by characterizing the ctDNA present in CSF based on methylation, mutation, and chromosomal copy number. The primary endpoint of this study is to assess the sensitivity and specificity of this novel assay as compared to the current standard of care. This is a multi-center study in patients with known or suspected CNS tumors, with a planned enrollment of 400 individuals. CSF will be collected as part of the standard clinical care in which 2-10 ml will be sent to Belay Diagnostics for testing using the Summit™ assay. Results will be returned to the investigator, and de-identified data will be evaluated to determine the sensitivity and specificity of the assay in the detection/diagnosis of CNS tumors from CSF.
OCTS-06 A PHASE II STUDY OF NIVOLUMAB WITH IPILIMUMAB AND CABOZANTINIB IN PATIENTS WITH UNTREATED RENAL CELL CARCINOMA BRAIN METASTASES
Authors: Wang Jianbo , Campbell Matthew , Shah Amishi Y , Goswami Sangeeta , Msaouel Pavlos , Alhalabi Omar , Hahn Andrew , Kovitz Craig , Bagi Jana , Araujo John , Gao Jianjun , Lin John , Zurita Amado , Jonasch Eric , Corn Paul , Tannir Nizar
Published: August 2024

BACKGROUND

The incidence of brain metastases(mets) at the diagnosis of renal cell carcinoma (RCC) is 1.51%, and around 12% of patients(pts) with advanced RCC (aRCC) had brain mets. Brain mets confer a poor prognosis. Although systemic therapies including tyrosine kinase inhibitors and immune checkpoint inhibitors have been explored in aRCC pts with brain mets, prospective data are lacking. Cabozantinib was FDA approved for pts with aRCC and retrospective studies have suggested activity in patients with intracranial tumors. The phase III COSMIC-313 trial recently evaluated cabozantinib in combination with nivolumab and ipilimumab and demonstrated significantly improved progression-free survival (PFS) in previously untreated pts with aRCC. However, the role of this combination in aRCC pts with brain mets remains undefined. We propose a study to assess the safety and efficacy of cabozantinib in combination with nivolumab/ipilimumab in RCC pts with untreated brain mets.

METHODS

This is a phase II study to assess the safety and efficacy of the combination of nivolumab with ipilimumab and cabozantinib in pts with untreated brain mets from RCC. Planned accrual is 40 pts. Pts will receive nivolumab (3mg/kg) and ipilimumab (1mg/kg) IV every 3 weeks for 4 doses and cabozantinib 40mg daily. Then pts will be treated with nivolumab 480mg IV Q 4 weeks and cabozantinib 40mg daily. A lead-in group of 6 pts will be closely monitored for dose limiting toxicities (DLT). If stopping criteria (>3 patients develop DLTs) is met, then treatment will be switched to nivolumab plus cabozantinib omitting ipilimumab. The primary objective is intracranial progression free survival (PFS). Secondary objectives include intracranial safety, objective response rate (intracranial + extracranial) by modified RECIST v1.1 and RECIST v1.1, extracranial PFS, overall survival and correlative studies. As of 4/2024, Lead-in group has been completed with acceptable rate of DLT. Clinical trial information: NCT05048212.
OCTS-09 THE PROSPECTIVE PHASE II COG-SRS TRIAL: AN UPDATE ON COGNITIVE-SPARING STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES
Authors: Puett Connor , Hopper Austin , Connor Michael , Karunamuni Roshan , Sanghvi Parag , Kim Grace , Bruggeman Andrew , Tringale Kathryn , Moiseenko Vitali , Farid Nikdokht , McDonald Carrie , Hattangadi-Gluth Jona
Published: August 2024

Stereotactic radiosurgery (SRS) plans that respect the neural correlates of cognition should result in better post-treatment cognitive outcomes compared to standard plans. The prospective phase II COG-SRS Trial is designed to test this hypothesis. To date, 92 treatment plans that ensure standard tumor coverage but also constrain doses to selected eloquent white matter tracts and the hippocampi have been developed for 70 patients with a total of 158 brain metastases arising from various cancer types. The most common primary malignancies were lung (40%) and breast (26%). Over 90% of plans treated 3 or fewer lesions. 80% of plans successfully met the 0.03cc dose (D0.03) constraint to all white matter tracts, and 95% met the D0.03 constraint to the hippocampi. Cognitive testing of immediate and delayed recall (Hopkins Verbal Learning Test-Revised) and letter and category fluency (Controlled Oral Word Association) is available in 66% (46/70) of patients to date, 76% (35/46) of whom had received systemic therapy and 20% (9/46) surgical resection prior to SRS. Comparing pre- and 3-month post-radiotherapy performance, 52% (24/46) had a significant decline in cognitive performance, defined as a decrease of at least 1 standard deviation in the score on one or more tests. In patients for whom the D0.03 constraint could not be met in white matter tracts, 70% declined significantly. In comparison, only 47% declined when the D0.03 constraint was met. Correlating associations between specific white matter tract doses, volumetric white matter tract changes assessed by serial MRI, and performance on the full battery of neuropsychological testing will be possible when trial data are finalized. These results should help in defining the radiosensitivity of distinct neuroanatomic regions and in guiding future dose-constraint planning protocols, as this new arena of cognitive-sparing SRS continues to be explored.
OCTS-10 PREOPERATIVE TUCATINIB IN PATIENTS WITH HER2 AMPLIFIED/MUTANT BREAST OR OTHER SOLID TUMORS WHO REQUIRE BRAIN METASTASIS RESECTION: A WINDOW OF OPPORTUNITY STUDY (WINHER2 STUDY, NCT05892068)
Authors: Ferraro Emanuela , Solomon Verna , Thompson Vanessa , Pollina Rachael , Pittner Brian , Moss Nelson , Seidman Andrew D
Published: August 2024

BACKGROUND

Tucatinib is a potent and selective HER2 tyrosine kinase inhibitor currently approved for patients with metastatic HER2-positive (+) breast (BC) or colorectal cancer (CRC). In combination, it has demonstrated significant intracranial activity in both preclinical and clinical studies. However, the variability of brain metastasis (BM) tucatinib uptake, and brain-specific mechanisms of resistance are unknown.

METHODS

WinHER2 is an ongoing investigator-initiated window of opportunity study of pre-operative tucatinib for patients with HER2+ or mutant BM requiring surgery. The objective is to identify mechanisms of resistance of tucatinib in the brain. With the hypothesis that reduced tucatinib tumor penetration may limit its therapeutic efficacy, the primary endpoint is tucatinib brain drug concentration in the resected metastases, blood, and cerebrospinal fluid. The secondary objectives are the characterization of resistance mechanisms using a multi-omics approach including proteomics by immunohistochemistry and electron microscopy (efflux pump and blood brain tumor barrier analysis), genomics, and transcriptomics of the tumor and its microenvironment. The study design includes three parallel cohorts: Cohort A: patients with HER2+ BC progressing while on tucatinib (n=10); Cohort B: patients with tucatinib-naïve HER2+ BC (n=10); Cohort C: patients with HER2-mutant BC, or HER2 amplified or mutant CRC/lung/gastroesophageal cancer (n=8). The main inclusion criteria are indication for craniotomy related to radiological/clinical BM progression and history of HER2+ or mutant disease. All patients receive 4 days of tucatinib at the standard dose pre-operatively. Preoperative perfusion brain MRI is included for correlations between perfusion parameters and tumor drug levels. Additionally, CNS-specific survival outcomes will be evaluated for cohorts B and C. Differences in cohorts A and B will be assessed by descriptive statistics for primary and secondary endpoints. This study aims to provide a biological basis for innovative future strategies to improve the prognosis of patients with HER2-altered BM, which currently remains poor.
OCTS-11 PHASE 1 DOSE ESCALATION OF RHENIUM (186RE) OBISBEMEDA (RHENIUM NANOLIPOSOME,186RNL FOR THE TREATMENT OF LEPTOMENINGEAL METASTASES (LM): ONGOING CLINICAL STUDY UPDATE FOR INITIAL SAFETY AND FEASIBILITY
Authors: Brenner Andrew , Youssef Michael , Kumthekar Priya , Bao Ande , Michalek Joel , Phillips William , Patel Toral , Weinberg Jeffrey , Floyd John , Hedrick Marc , Juvierdianu Leonardo , Moore Melissa , Blouw Barbara , LaFrance Norman
Published: August 2024

BACKGROUND

Leptomeningeal metastases (LM) is a devastating systemic cancer complication most often seen with breast, lung, renal cell, and melanoma, with limited treatment options and poor survival. Rhenium (186Re) Obisbemeda (186RNL) provides the combination of effective therapeutic beta radiation, simultaneous gamma-decay for imaging, and ~89.2-hour physical half-life for optimal radiation delivery. An ongoing clinical trial update for the Phase 1 dose escalation study (Cohorts 1-5) is presented.

METHODS

ReSPECT-LM is a Phase 1 dose escalation study for patients with LM from any primary cancer. Adult patients are given a single dose of 186RNL via intraventricular catheter (Ommaya reservoir) in an outpatient setting to determine the maximum tolerated/feasible dose (MTD/MFD), safety, and tolerability. Subjects received 6.6, 13.2, 26.4, 44.10, or 66.14 mCi of 186RNL (Cohort 1-5, respectively).

RESULTS

Doses were well-tolerated with no treatment-related serious adverse events (SAEs); the majority of AEs were Grade 1 and 2. The MTD/MFD has not been reached. CSF tumor cell enumeration assays (CNSide test) were performed with a maximum reduction over baseline seen at Day28. Radiation absorbed doses were calculated for the ventricles, cranial subarachnoid space, and spinal fluid and showed a linear increase with administered dose, with liver and spleen remaining low. To date, neurological signs and symptoms from LM were reported to improve by investigators and patients. Cohort 5 is completing its enrollment and subsequent analysis.

CONCLUSION

A single dose of 186RNL for patients with LM is well tolerated, has high absorbed doses to the treatment area with low organ dose, and shows promising positive clinical improvement and reductions in tumor cell count. Enrollment to Cohort 6 (87.97 mCi) will follow Cohort 5’s data safety review; the current development status of the Phase 1 study will be reported.
RADT-04 IMPROVED SURVIVAL IN PATIENTS WITH RADIONECROSIS VS. LOCAL RECURRENCE AFTER STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES
Authors: Leng Jim , Arshad Muzamil , Carpenter David , Qazi Jamiluddin , Huang Christina , Vaios Eugene , Reitman Zachary , Floyd Scott , Kirkpatrick John , Fecci Peter , Chmura Steven , Hong Julian , Sperduto Paul , Salama Joseph , Mullikin Trey
Published: August 2024

PURPOSE: Radionecrosis (RN) is a dose-limiting toxicity after stereotactic radiosurgery (SRS) for brain metastases. How RN affects patient outcomes following SRS is not well described. Therefore, we characterized survival outcomes of patients who develop RN versus treated tumor recurrence in the absence of out-of-field intracranial progression after SRS. METHODS: This cohort study included patients completing an initial course of SRS from 2015-2020 at two institutions. Primary outcome was overall survival (OS) by presence of RN or treated tumor recurrence (LR), analyzed via the Kaplan-Meier method. Binomial logistic regression tested parameters associated with RN or LR. RESULTS: 1383 patients were included, 55% were male and median age was 63.4 years. Common primaries were lung (55%), breast (15%), and melanoma (9%). At a median follow up of 8.7 months, concern for intracranial progression was limited to irradiated sites for 143 patients (10%) - 96 with RN and 47 with LR. LR was diagnosed sooner after SRS than RN (median 5.8 vs. 8.3 months, P=0.0087), and patients with LR had significantly worse OS compared to RN (median 15.2 vs. 40.4 months, P<0.001). Patients who were symptomatic had LR and RN earlier than asymptomatic patients and had worse OS. On binomial logistic regression, RN was associated with single fraction SRS (odds ratio [OR] = 0.38, P = 0.012), receipt of immunotherapy after SRS (OR = 0.32, P < 0.014), and a longer interval from SRS (OR = 0.94, P = 0.028). CONCLUSION: In this multi-institutional cohort study of patients with brain metastasis treated with SRS, those with RN had significantly better OS vs. those with LR, with a median OS of 40.4 months vs. 15.2 months (P<0.001). This data informs the surveillance and prognosis of patients after SRS.
RADT-13 STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES SECONDARY TO PERIPHERAL NEURAL CREST TUMORS: A SINGLE INSTITUTION RETROSPECTIVE EXPERIENCE
Authors: Kattaa Ahed , Persad Amit , Park David , Hori Yusuke , Emrich Sara , Ustrzynski Louisa , Tayag Armine , Gu Xuejun , Rahimy Elham , Pollom Erqi , Soltys Scott G , Chang Steven D
Published: August 2024

BACKGROUND

Intracranial BM of peripheral neural crest tumors (PNCTs) are rare, and portent a poor prognosis. No standard treatment has been established to date, and only a few case reports describe the usage of stereotactic radiosurgery (SRS). This study aims to evaluate the efficacy of SRS for BM from PNCTs. Additionally, a comparison between SRS and other treatment modalities have been conducted.

METHODS

We retrospectively reviewed all patients diagnosed with BM from PNCTs between 2001 and 2024 at our institution. LTC was defined as a reduction/stable in tumor size, with no recurrence or hemorrhage as evidenced by radiological assessment.

RESULTS

Among the 8 patients (15 BM) identified, 3 with 6 BM underwent SRS, and 5 with 9 BM underwent other treatments (radiotherapy, craniotomy, or none). Amongst the patients treated with SRS, the median age was 4.0 years (IQR: 1.8-4.0 years) at diagnosis and 100% were male. The median follow-up was 5.5 months (IQR: 2-7 months). Amongst the patients not treated with SRS, the mean age was 2.5 years (Std. deviation: 1.4 years) at diagnosis and 60% were female. The median follow-up was 28 months (IQR: 1- 85 months). The group treated with SRS had LTC rate of 100% with no complications and a survival rate of 33.3% at one year follow up. LTC rate in the group treated with other modalities was 55.6%, with a survival rate of 60% for a one year follow up. There was no significant difference in LTC and survival between groups (p > 0.05).

CONCLUSION

SRS provides a LTC rate of 100% within one year of follow up for BM from PNCTs. We do suggest that there is similarity of outcomes between SRS and other treatment modalities. SRS may be an alternative to more invasive treatments such as craniotomy or conventional radiation in these patients.
RMTD-02 PRACTICE VARIATION AND IMPACT OF PRE-OPERATIVE AND POST-OPERATIVE DEXAMETHASONE ON PATIENT OUTCOME IN THE RESECTED BRAIN METASTASIS – INSIGHTS FROM THE CLINDEXMET MULTICENTER REGISTRY
Authors: Wasilewski David , Tommaso Araceli , Rafaelian Artem , Demetz Matthias , Asey Benedikt , Ersoy Tunc-Faik , Dauth Alice , Peukert Ricarda , Poeser Paul , Jelgersma Claudius , Früh Anton , Xu Ran , Capper David , Ehret Felix , Frost Nikolaj , Schmidt Leon , Krenzlin Harald , Ringel Florian , Meyer Hanno , Gempt Jens , Kerschbaumer Johannes , Freyschlag Christian , Thomé Claudius , Simon Matthias , Dubinski Daniel , Freiman Thomas , Schmidt Nils Ole , Proescholdt Martin , Vajkoczy Peter , Onken Julia
Published: August 2024

BACKGROUND

Patients with brain metastases that undergo brain metastasis resection regularly receive perioperative dexamethasone. We sought to evaluate variation in pre- and post-operative dexamethasone dosing and whether perioperative dexamethasone in brain metastases is linked to patient outcome.

METHODS

This was a multicenter retrospective study collecting data on daily pre- and post-operative dexamethasone dosage over a period of 27 days in patients undergoing brain metastasis resection. Non arbitrary cutpoint selection was performed using maximally selected rank statistics to dichotomize patients. Propensity score matching served to reduce bias and adjust for potential confounders including tumor and edema volume, localization of the dominant brain metastasis, disease-specifc GPA score, presence of other non-oncological diseases.

RESULTS

988 patients were included. Median follow-up time was 55,2 months [95% CI: 50.7 – 61.5]. After propensity score matching patients below the determined cutpoint of 122 mg cumulative dexamethasone showed an overall survival of 16.0 months [95% CI: 13.3 – 21] vs. patients with more than 122 mg cumulative dexamethasone with a OS of 10.6 months [9.0 – 12.7], p=0.0022. No effect on extracranial or intracranial disease progression was observed. In a multivariable model for the matched data the cumulative peri-operative dexamethasone above the cutpoint remained independently associated with overall survival (HR: 1.3 [95% CI: 1.12 – 1.6], p=0.001).

CONCLUSION

Cumulative perioperative dexamethasone is associated with decreased survival in the context of brain metastasis resection. Strict dosage, down taper or methods reducing corticosteroid dependency should be regularly evaluated in clinical practice in patients with brain metastases.
RMTD-03 USE OF A BRAIN-PENETRATING ANTHRACYCLINE IN ANTHRACYCLINE-SENSITIVE BRAIN METASTASES: THE PROMISE OF BERUBICIN
Authors: Silberman Sandra
Published: August 2024

BACKGROUND

Brain metastases are a common complication of cancer and also type of brain tumor: 10%-26% of patients develop brain metastases. Chemotherapy for these tumors is usually ineffective due to an intact blood-brain barrier (BBB). Anthracycline-sensitive cancers that metastasize to the brain do not receive anthracyclines which do not penetrate the brain. Triple-negative breast cancer (TNBC), which can be treated with doxorubicin (DOX) systemically has an incidence of brain metastases of approximately 25–46%; although lymphomas usually require an anthracycline as part of their chemotherapy, when they appear as a primary disease in the brain anthracyclines cannot be used. Berubicin is an analog of doxorubicin that appears to cross the BBB with significant central nervous system (CNS) uptake. A pivotal trial for patients with recurrent glioblastoma (GBM) after first-line therapy has finished enrollment with 252 patients in the US and Europe with evidence of efficacy and no impact on cardiac function.

METHODS

CNS Pharmaceuticals plans to evaluate Berubicin in patients with Primary CNS Lymphoma (PCNSL) who have never received an anthracycline and in TNBC with documented brain metastases. Patients will be enrolled if they have shown progression in the brain and have not undergone primary treatment. Outcome measurements will include efficacy in terms of overall response rates (ORR), progression-free survival (PFS), and overall survival (OS) as well as a continuing evaluation of Berubicin’s safety and tolerability.

CONCLUSIONS

The use of anthracyclines for the treatment of malignancy has encompassed 50 years of showing significant activity in certain diseases, however, use has been limited by both the risk of cardiotoxicity as well as the inability to penetrate the BBB, where these tumors tend to metastasize. This study offers the promise of using an anthracycline that can cross the BBB effectively for sensitive tumors and Berubicin becoming an important part of their therapy
RMTD-05 UNRAVELLING THE LANDSCAPE OF BRAIN METASTASES ACROSS PRIMARY CANCER TYPES: A PAN-CANCER STUDY UTILIZING THE SEER DATABASE
Authors: Dimou James , Stylli Stan , McCoy Patrick , Campbell Bethany , Corcoran Niall , Saunders Christobel , Drummond Kate , Hovens Christopher
Published: August 2024

INTRODUCTION

Brain metastases pose a formidable challenge in oncology. While certain cancers like lung, breast, and melanoma are known to commonly metastasize to the brain, comprehensive studies spanning cancer types that uncommonly or rarely spread to the brain are limited.

METHODS

This study employs data from the Surveillance, Epidemiology, and End Results (SEER) database to examine incidence, prevalence, and clinical characteristics of brain metastases across nearly all cancers. We conducted a detailed review of SEER-derived patient data, focusing on brain metastases. Statistical analyses, including Kaplan-Meier plots and Gehan-Breslow-Wilcoxon tests, were utilized to compare survival rates and clinical features between cancer types, integrating additional features such as staging. (i.e., T and N grades)

RESULTS

Lung cancer is the most common primary source of brain metastases. (~80.5% of cases) Furthermore, cancers traditionally associated with brain metastasis—lung, melanoma, breast, renal, and colorectal—comprise 93% of all brain metastasis cases in SEER. Further analysis showed that brain metastasis patients had worse five-year survival than patients who developed metastasis elsewhere, and those patients with high grade glioma. Recent advancements in treatment have improved survival rates for patients diagnosed with brain metastases between 2015-2019, compared to those diagnosed during 2010-2014. This improvement appears to be driven disproportionately by cancers commonly associated with brain metastasis. Moreover, it can be revealed that there are notable differences in T/N grades and clinical features of the cancers that uncommonly or rarely spread to the brain, compared to those that commonly do so.

CONCLUSIONS

This study suggests that the pattern of brain metastasis formation may differ between those primary malignancies that commonly, and uncommonly or rarely spread metastatically, highlighting the deficit of our clinical and scientific understanding of this pernicious cancer phenomenon, as well as the need to develop novel, innovative treatment paradigms for patients with brain metastases.
SPCM-02 ASSOCIATIONS BETWEEN INTRAOPERATIVE NEUROMONITORING USAGE AND CLINICAL OUTCOMES FOR SURGERIES AMONG PRIMARY NON-MALIGNANT SPINE TUMOR PATIENTS
Authors: Bishop Brandon , Woo Joshua , Rowe Dana , Luo Emily , Ndika Tobechukwu , Charles Antoinette , Arango Alissa , Yoo Seeley , Zachem Tanner , O’Callaghan Ellen , Owolo Edwin , Sperber Jacob , Crowell Kerri-Anne , Rivera Nicole , Nguyen Annee , Hockenberry Harrison , Reitz Kendall , Dalton Tara , Johnson Eli , Erickson Melissa , Goodwin C Rory
Published: August 2024

BACKGROUND

The use of intraoperative neuromonitoring (IONM) has recently increased in popularity among spinal surgery to reduce rates of postoperative neurological complications. However, its utility has been mixed, especially in elective surgeries, due to increased healthcare spending and limited guidelines. In this study, we investigated the associations between IONM and clinical outcomes, as well as both financial and demographic factors, for patients with primary non-malignant spine tumors (PNMT) undergoing surgery.

METHODS

A retrospective review was performed using the PearlDiver Patient Record Database to identify cases of PNMT patients who underwent surgery from 2011 to 2021. Rates of IONM usage were compared based on patient age, sex, family income, and region. Complications and 30-day readmissions were also assessed.

RESULTS

5,692 patients undergoing surgery with PNMTs were identified, with 1,914 (33.6%) of these utilizing IONM. Younger age (p < 0.001) and male sex (p < 0.05) were both significantly associated with IONM usage and there was significant regional variability in utilization observed (Midwest: 33.8%; Northeast: 24.6%; South: 29.0%; West: 12.6%; p < 0.001). Among clinical outcomes, nerve injury (p < 0.001), surgical complications (p < 0.001), and 30-day readmission rates (p < 0.001) were all significantly associated with IONM usage. Both mean family income (p < 0.005) and reimbursement amounts were not clinically significant in association with IONM usage.

CONCLUSIONS

Among patients with PNMTs, this study demonstrates significant differences in IONM usage across geographic regions, sex, and age as well as a positive association with 30-day readmission rates with use. While associations between IONM and family income have been observed previously, neither income nor reimbursement measures were clinically significant in our cohort. Given the growing usage of IONM in spinal surgeries, these results provide important insights into the utility of IONM among patients with non-malignant spinal tumors.
QSPC-01 INVESTIGATING DISTRESS LEVELS IN PATIENTS WITH METASTATIC SPINE DISEASE UNDERGOING SURGICAL INTERVENTION
Authors: Rowe Dana , O’Callaghan Ellen , Barrett Connor , Owolo Edwin , Charles Antoinette , Luo Emily , Arango Alissa , Bishop Brandon , Yoo Seeley , Johnson Margaret , Erickson Melissa , Goodwin C Rory
Published: August 2024

INTRODUCTION

Cancer patients often experience high levels of distress, which are particularly pronounced in the perioperative period. However, there is a dearth of research on distress rates in patients with metastatic spine disease (MSD). This study aims to assess pre-operative and post-operative distress levels in patients with MSD undergoing surgical intervention.

METHODS/STUDY POPULATION

We retrospectively queried electronic medical records from a single institution for demographic and clinical data on patients with metastatic spine disease who underwent surgical intervention between 2015 and 2023. Data also included preoperative (within 60 days of surgery) and postoperative (within 30 days of surgery) National Comprehensive Cancer Network’s Distress Thermometer (NCCN-DT) scores.

RESULTS

We identified 222 patients with complete NCCN-DT questionnaires. Nearly half (46.4%) of the patients were female, with 71.2% identifying as White, and 68.5% being married or partnered. The median age at the time of spine metastasis diagnosis was 62.5 years (IQR: 53.0; 71.5). Preoperatively, the mean distress score was 3.5 (range 0-10), with 103 (46.4%) patients reporting moderate to severe distress (DT ≥ 4). The mean distress score at 30-days postop was 3.2 (range 0-10), with 43.75% of patients reporting moderate to severe distress. At 90-days post-op, the mean distress score was 2.3 (range 0-9) with 23.8% of patients reporting moderate to severe levels.

DISCUSSION/SIGNIFICANCE OF IMPACT

Distress is a common experience among patients with metastatic spine disease undergoing surgical intervention. Preoperatively, nearly half of these patients report moderate to severe distress. While distress rates generally decline postoperatively, a considerable proportion of patients continue to experience high levels of distress. These findings underscore the significance of addressing distress in this patient population.
QSPC-09 FACTORS IMPACTING QUALITY OF LIFE AFTER BRAIN METASTASES DIAGNOSIS: A MIXED METHODS STUDY OF PATIENTS AND THEIR CAREGIVERS
Authors: Porter Kathleen , Mulligan Caroline , Fadul Camilo , Bonilla Gloribel , You Wen , Anderson Roger
Published: August 2024

To provide optimal care after the diagnosis of brain metastases (BMETS), it is crucial to understand the factors that affect quality of life (QoL) from the patient and caregiver perspectives. We conducted a mixed-methods pilot study to gain initial insight into patients’ and caregivers’ reports on factors that affect patients’ QOL following initial brain-directed treatment of brain metastases. Within 4 months of BMETS diagnosis, eligible patients completed 2 surveys ~3 months apart, while they and their caregivers completed interviews at the same timepoints. Patient demographic, diagnostic, and treatment data were abstracted from the medical record. The surveys and the semi-structured interviews assessed patients’ QoL and explored contributing factors. Median QoL change scores (Timepoint 1 minus Timepoint 2) and effect sizes (Cohen’s d) were calculated. Interviews were analyzed using directed content coding. Patients (n=8) had a median age of 69 years and had ECOG and KPS scores of ≤1 and ≥70, respectively. 25%, 75%, and 75% had received whole brain radiation therapy, stereotactic radiosurgery, and systemic medical therapy, respectively. Caregivers (n=5) had a median age of 66 years and were 60% female and 80% a patient’s spouse/partner. QoL scores decreased among the 4 patients who completed both surveys [Fact-BR: median change score = 4.5, ES=0.28; Fact-G: median change score = 4.0, ES=0.34]. Interviews identified desirable features of and changes to patient QoL across 4 domains: physical, emotional, social, and spiritual. Six factors impacting patient QoL were identified, including BMETS diagnosis, care processes, treatment, alterations to daily activities and relationships, cancer-related life strain, and positive adaptations. This pilot study revealed that patients’ QoL decreased over time at a clinically relevant magnitude and identified some of the drivers of these changes. These preliminary findings support future research to address the persistent gaps related to supporting the QoL of patients with BMETS.
TRSC-07 COMBINATION OF ENDOCRINE THERAPY WITH RADIATION DECREASES BRAIN METASTASES THROUGH REACTIVATION OF EFFECTOR IMMUNE-CELL RECRUITMENT TO THE BRAIN
Authors: Contreras-Zarate Maria Jose , Alvarez-Eraso Karen , Goodspeed Andrew , Costello James , Jaramillo-Gomez Jenny , Koliavas Stella , Fox Morgan , Ormond Ryan , Kabos Peter , Karam Sana , Cittelly Diana
Published: August 2024

Younger women with breast cancer have increased risk of development of brain metastases (BM) irrespective of the tumor subtype. We have shown that pre-menopausal levels of 17-β-Estradiol (E2) promotes BM of estrogen receptor negative (ER¯) BC cells by inducing neuroinflammatory ER+ glial cells to secrete pro-metastatic factors critical for early brain colonization. Yet, the clinical translation of endocrine therapies (ET) to the management of BM requires a better understanding of its effectiveness at late stages of metastatic progression and its interactions with current standard of care (SOC). Using scRNAseq of brain immune cells isolated from E2 or E2-suppressed mice carrying BMs we show that pre-menopausal levels of E2 suppressed immune surveillance, activation, and IRF-7/interferon-driven anti-tumoral programs in microglia. Multiparametric flow cytometry show that E2 repressed recruitment of T, B and NK cells to the brain niche from early to late stages of BM progression and ET (ovarian suppression and aromatase inhibitors) restored recruitment of these effector immune cells to the brain. ET decreased BM progression when used in combination with brain radiotherapy (RT), but not when ET was used alone or in immunocompromised mouse models, suggesting ET-induced recruitment of interferon driven T, B and NK cells to the brain synergizes with radiotherapy to promote more effective anti-tumoral immune responses. Depletion of CD4+T, CD8+T, and NK1.1+ cells in E2-suppressed mice carrying BMs showed that anti-tumoral effects of RT and ET depend on CD4T and NK cells. Suppression of CD4+ T cells further increased the effectiveness of ET and RT and improved survival, suggesting that subsets of T cells, possibly Treg cells are critical to regulate BM antitumoral responses. While ET+RT were comparable to anti-PD-1+RT in decreasing BMs, their effects were not additive. Thus, our results suggest that FDA-approved ET synergizes with RT but not PD-1 inhibitors for treatment of BMs.
Surface and interfacial sciences for future technologies
Authors: Zhou Xiong , Shen Qian , Wang Yongfeng , Dai Yafei , Chen Yongjun , Wu Kai
Published: August 2024

Physical science has undergone an evolutional transition in research focus from solid bulks to surfaces, culminating in numerous prominent achievements. Currently, it is experiencing a new exploratory phase—interfacial science. Many a technology with a tremendous impact is closely associated with a functional interface which delineates the boundary between disparate materials or phases, evokes complexities that surpass its pristine comprising surfaces, and thereby unveils a plethora of distinctive properties. Such an interface may generate completely new or significantly enhanced properties. These specific properties are closely related to the interfacial states formed at the interfaces. Therefore, establishing a quantitative relationship between the interfacial states and their functionalities has become a key scientific issue in interfacial science. However, interfacial science also faces several challenges such as invisibility in characterization, inaccuracy in calculation, and difficulty in precise construction. To tackle these challenges, people must develop new strategies for precise detection, accurate computation, and meticulous construction of functional interfaces. Such strategies are anticipated to provide a comprehensive toolbox tailored for future interfacial science explorations and thereby lay a solid scientific foundation for several key future technologies.
High sensitivity ctDNA assays in genitourinary malignancies: current evidence and future directions
Authors: Patel Kartik R , Rais-Bahrami Soroush , Basu Arnab
Published: August 2024

In the recent decade, analysis of circulating tumor DNA (ctDNA) has improved cancer care by allowing for rapid detection of actionable molecular targets. A new generation of circulating DNA tests is now becoming available commercially. These tests are characterized by a superior limit of detection of 0.01% vaF or better, allowing for the detection of radiologically occult molecular residual disease (MRD). MRD tests have the potential to revolutionize neoadjuvant and adjuvant treatment. In addition, these tests can be used as tumor markers to assess disease response. We reviewed the current evidence for the use of high-sensitivity MRD assays with particular focus on the genitourinary tumors. Multiple studies have now been reported in urothelial, renal, and recently testicular carcinoma. We find that the sensitivity varies across tumor types in the adjuvant setting and may reach a high of 100% in urothelial cancer. Specificity in tumor-informed MRD appears to be preserved across tumor types (98%-100%). Several trials are now prospectively validating MRD testing in biomarker integral studies, mainly in urothelial carcinoma.
The Age of Granulite-Facies Metamorphism in the Ivrea–Verbano Zone (NW Italy) Determined Through In Situ U–Pb Dating of Garnet
Authors: Bartoli Omar , Millonig Leo J , Carvalho Bruna B , Marschall Horst R , Gerdes Axel
Published: August 2024

Rates of melt production, extraction and crystallization, as well as scales of melt transfer and interaction with their residuum change continuously in migmatite and granulite, affecting the behavior of monazite and zircon as time capsules. Therefore, accessory mineral chronometers may be ambiguous and incomplete in providing an overview of the temperature–time evolution of high-grade metamorphic rocks. In this study, we applied the novel technique of in situ U–Pb dating of garnet to the archetypal lower continental crust of the Ivrea–Verbano Zone (IVZ), NW Italy. In the IVZ, the temporal relationship between granulite-facies metamorphism and mafic underplating has long been debated, because of the interplay between tectonic, magmatic, metamorphic and metasomatic processes over a period of more than a hundred million years. Garnet from mafic and pelitic granulites yielded U–Pb ages between 287.4 ± 4.9 Ma and 280.1 ± 12.4 Ma, overlapping within uncertainty the time proposed for the emplacement of the Mafic Complex (286–282 Ma). These results indicate that the thermal climax in granulitic rocks was caused by mafic underplating and concomitant asthenospheric upwelling, rather than being inherited from the post-Variscan Carboniferous evolution. Providing robust dating of garnet with as low as 4 ng/g U, this study demonstrates the strength of garnet petrochronology in resolving complex tectono-metamorphic histories of high-grade terranes. It also represents a further step forward towards establishing garnet as part of the in situ U–Pb geochronology repertoire.
Taxonomy and trans-Beringian biogeography of the pond snails (Gastropoda: Lymnaeidae) of East Asia: an integrative view
Authors: Aksenova Olga V , Vinarski Maxim V , Itagaki Tadashi , Ohari Yuma , Oshida Tatsuo , Kim Sang Ki , Lee Jin Hee , Kondakov Alexander V , Khrebtova Irina S , Soboleva Alena A , Travina Oksana V , Sokolova Svetlana E , Palatov Dmitry M , Bespalaya Yulia V , Vikhrev Ilya V , Gofarov Mikhail Yu , Bolotov Ivan N
Published: August 2024

In this work, we present an integrative revision of the Lymnaeidae from the northeastern margin of Asia (Far East Russia, Japan, and Korea) and Alaska. According to our results, 14 native species inhabit this region, belonging to eight genera in two subfamilies (Lymnaeinae: Dallirhytis, Galba, Walhiana, Ladislavella, and Lymnaea; and Amphipepleinae: Kamtschaticana, Orientogalba, and Radix). Four of these species are new to science and three of them are described in this paper. Additionally, three established alien species are recorded from Japan (Pseudosuccinea columella, Galba schirazensis, and Galba humilis). The Japanese Archipelago represents an evolutionary hotspot of pond snail diversity, encompassing seven native species, three of which are endemic. The faunal connections between North America and northeastern Asia are discussed in the context of historical biotic interchange across the Beringian Land Bridge. Two cold-tolerant pond snails share high-latitude but localized ranges, being endemic to the Beringian Arctic: Dallirhytis atkaensis (Chukchi Peninsula, Alaska, and Aleutian Islands) and Walhiana arctica comb. nov. (Alaska). Our findings indicate that the Beringian Land Bridge has played a role in freshwater faunal exchanges between northeastern Asia and western North America.
Deciphering the dynamics: Exploring the impact of mechanical forces on histone acetylation
Authors: Cai Jingyi , Deng Yudi , Min Ziyang , Li Chaoyuan , Zhao Zhihe , Jing Dian
Published: August 2024

Living cells navigate a complex landscape of mechanical cues that influence their behavior and fate, originating from both internal and external sources. At the molecular level, the translation of these physical stimuli into cellular responses relies on the intricate coordination of mechanosensors and transducers, ultimately impacting chromatin compaction and gene expression. Notably, epigenetic modifications on histone tails govern the accessibility of gene‐regulatory sites, thereby regulating gene expression. Among these modifications, histone acetylation emerges as particularly responsive to the mechanical microenvironment, exerting significant control over cellular activities. However, the precise role of histone acetylation in mechanosensing and transduction remains elusive due to the complexity of the acetylation network. To address this gap, our aim is to systematically explore the key regulators of histone acetylation and their multifaceted roles in response to biomechanical stimuli. In this review, we initially introduce the ubiquitous force experienced by cells and then explore the dynamic alterations in histone acetylation and its associated co‐factors, including HDACs, HATs, and acetyl‐CoA, in response to these biomechanical cues. Furthermore, we delve into the intricate interactions between histone acetylation and mechanosensors/mechanotransducers, offering a comprehensive analysis. Ultimately, this review aims to provide a holistic understanding of the nuanced interplay between histone acetylation and mechanical forces within an academic framework.
Self-reported Symptoms Associated With the Use of Printer and Photocopier Machines
Authors: Ojo Abimbola , Bello Dhimiter , Heavner Karyn , Lucas Kurt , Bello Anila
Published: August 2024

Objectives

This study aimed to document adverse health effects among office, copy, and print shop workers using the Nano-Control, International Foundation Survey.

Methods

Self-reported information on 16 health outcomes and three surrogate exposure variables were collected from 1998 individuals between 1999 and 2010. Logistic regression models, adjusted for age, gender, and smoking status, assessed the association between printer exposure and health symptoms.

Results

Among the participants, 61.9% were office workers, 5.5% were technicians, and 23.3% held other professions. Technicians had a higher risk for cancer compared to office workers (odds ratio [OR], 2.5; P < 0.01). Visible toner dust exposure was associated with chronic fatigue (OR, 9.6; P < 0.01), bronchial hyperresponsiveness (OR, 5.1; P < 0.01), cardiovascular diseases (OR, 3.6; P < 0.01), asthma, allergies, and other diseases (OR range, 1.4–3.2; P < 0.01).

Conclusions

The increased chronic and acute health risks among these workers warrant further investigations of causal associations.
Image Quality Assessment of a Deep Learning–Based Automatic Bone Removal Algorithm for Cervical CTA
Authors: Cui Yuanyuan , Fan Rongrong , Cheng Yuxin , Sun An , Xu Zhoubing , Schwier Michael , Li Linfeng , Lin Shushen , Schoebinger Max , Xiao Yi , Liu Shiyuan
Published: August 2024

Background

The present study aims to evaluate the postprocessing image quality of a deep-learning (DL)–based automatic bone removal algorithm in the real clinical practice for cervical computed tomography angiography (CTA).

Materials and Methods

A total of 100 patients (31 females, 61.4 ± 12.4 years old) who had performed cervical CTA from January 2022 to July 2022 were included retrospectively. Three different types of scanners were used. Ipsilateral cervical artery was divided into 10 segments. The performance of the DL algorithm and conventional algorithm in terms of bone removal and vascular integrity was independently evaluated by two radiologists for each segment. The difference in the performance between the two algorithms was compared. Inter- and intrarater consistency were assessed, and the correlation between the degree of carotid artery stenosis and the rank of bone removal and vascular integrity was analyzed.

Results

Significant differences were observed in the rankings of bone removal and vascular integrity between the two algorithms on most segments on both sides. Compared to DL algorithm, the conventional algorithm showed a higher correlation between the degree of carotid artery stenosis and vascular integrity (r = −0.264 vs r = −0.180). The inter- and intrarater consistency of DL algorithm were found to be higher than or equal to those of conventional algorithm.

Conclusions

The DL algorithm for bone removal in cervical CTA demonstrated significantly better performance than conventional postprocessing method, particularly in the segments with complex anatomical structures and adjacent to bone.
Iodine Density Threshold to Distinguish Between Enhancing and Nonenhancing Renal Lesions With Dual-Layer Dual-Energy CT
Authors: Margono Ezra , Qureshi Muhammad Mustafa , Gupta Avneesh
Published: August 2024

Purpose

This study aimed to determine the optimal threshold iodine density to distinguish enhancing and nonenhancing renal masses with dual-layer dual-energy CT (dlDECT).

Methods

In this retrospective, HIPAA-compliant, institutional review board–approved study, 383 consecutive renal mass dlDECT studies from September 5, 2018, through December 15, 2022, were reviewed for enhancing solid renal masses with ≥∆20 HU. Studies with simple cysts in the same interval served as controls. Lesion ROI HU measurements on unenhanced and nephrographic phases and ROI iodine density measurements of each lesion and the abdominal aorta for normalization were recorded. The mean lesion HU values and absolute and normalized iodine densities were compared with enhancing and nonenhancing renal lesions using a two-sample t test. The diagnostic accuracy of iodine thresholds was assessed by calculating sensitivity and specificity, with receiver operating characteristic curve and AUC analysis.

Results

There were 38 enhancing and 39 nonenhancing renal lesions. The mean (standard deviation [SD]) ∆HU was 73.5 (38.7) and 3.9 (5.1) HU for enhancing and nonenhancing lesions, respectively. The mean absolute iodine density was significantly different for enhancing and nonenhancing lesions (3.2 [1.7] mg/mL and 0.20 [0.22] mg/mL, respectively; P < 0.0001). Normalized mean iodine density was significantly different for enhancing and nonenhancing lesions (0.62 [0.33] mg/mL and 0.04 [0.04] mg/mL, respectively; P < 0.0001). The optimal absolute iodine density threshold of 0.70 mg/mL (AUC, 0.999) and normalized iodine density threshold of 0.11 mg/mL (AUC, 0.999) were 100% sensitive and 97.4% specific for discriminating enhancing and nonenhancing renal lesions.

Conclusions

This study provides absolute and normalized iodine density thresholds to distinguish enhancing and nonenhancing renal lesions with high sensitivity and specificity using dlDECT.
Biomimetic stimulation patterns drive natural artificial touch percepts using intracortical microstimulation in humans
Authors: Hobbs Taylor G. , Greenspon Charles M. , Verbaarschot Ceci , Valle Giacomo , Boninger Michael , Bensmaia Sliman J. , Gaunt Robert A.
Published: August 2024

Objective

Intracortical microstimulation (ICMS) of human somatosensory cortex evokes tactile percepts that people describe as originating from their own body, but are not always described as feeling natural. It remains unclear whether stimulation parameters such as amplitude, frequency, and spatiotemporal patterns across electrodes can be chosen to increase the naturalness of these artificial tactile percepts.

Approach

In this study, we investigated whether biomimetic stimulation patterns – ICMS patterns that reproduce essential features of natural neural activity – increased the perceived naturalness of ICMS-evoked sensations compared to a non-biomimetic pattern in three people with cervical spinal cord injuries. All participants had electrode arrays implanted in their somatosensory cortices. Rather than qualitatively asking which pattern felt more natural, participants directly compared natural residual percepts, delivered by mechanical indentation on a sensate region of their hand, to artificial percepts evoked by ICMS and were asked whether linear non-biomimetic or biomimetic stimulation felt most like the mechanical indentation.

Main Results

We show that simple biomimetic ICMS, which modulated the stimulation amplitude on a single electrode, was perceived as being more like a mechanical indentation reference on 32% of the electrodes. We also tested an advanced biomimetic stimulation scheme that captured more of the spatiotemporal dynamics of cortical activity using co-modulated stimulation amplitudes and frequencies across four electrodes. Here, ICMS felt more like the mechanical reference for 75% of the electrode groups. Finally, biomimetic stimulation required less stimulus charge than their non-biomimetic counterparts.

Significance

We conclude that ICMS encoding schemes that mimic naturally occurring neural spatiotemporal activation patterns in somatosensory cortex feel more like an actual touch than non-biomimetic encoding schemes. This also suggests that using key elements of neuronal activity can be a useful conceptual guide to constrain the large stimulus parameter space when designing future stimulation strategies.