bluuebunny/crossref_metadata_2025_split huggingface dataset:
QOLP-25. PERFORMANCE STATUS OF PEDIATRIC PATIENTS WITH CENTRAL NERVOUS SYSTEM TUMORS TREATED IN A TERTIARY CENTER IN MEXICO, A SINGLE-CENTER EXPERIENCE
Authors: Madrigal-Avila Claudia , Ruvalcaba-Sanchez Rafael , Perez-Bañuelos Alfonso , Escamilla-Asiain Gabriela , Ellis Andrea , Vega-Vega Lourdes 
Published: November 2021

Abstract

BACKGROUND
Central nervous system (CNS) tumors are the most common solid neoplasms in the pediatric age. Despite this, there are no reports of results focused on the performance status of pediatric patients who are treated in a multidisciplinary setting.

OBJECTIVE
Describe the Performance Status of CNS pediatric patients after being treated with a multidisciplinary approach in a tertiary center.

METHODS
We review the chart of the pediatric patients at the Teleton Children Oncology Hospital from December 2014 to December 2019. The performance status was evaluated either using ECOG, Karnofsky, or Lansky scores. The multidisciplinary approach at our hospital includes: A Well-Equipped Diagnostic Center, integrated by a CAP-accredited laboratory, a Molecular Biology Unit, and the Imaging Unit, including a high-quality 2 tesla MRI. The surgical equipment comprises a surgical microscope, bipolar coagulation equipment, microsurgical instruments, and craniotomy equipment. For deep biopsies or functional surgery, we use Frame-Based Stereotactic Systems (FBSS) and neuronavigation systems. We provide first-line chemotherapy protocols and have a radiotherapy unit that can start treatment within a week. We have an Intensive Care Unit for oncologic patients with a 93% of overall survival. We provide ludic therapy and cognitive behavioral therapy, as well as emotional support. The Physical Rehabilitation Clinic uses the Bobath concept, proprioceptive and neuromuscular techniques as well as follow-up visits according to needs.

RESULTS
Of the 56 patients treated, 35 were evaluated with ECOG/Lansky performance status scale during the last follow up visit, resulting in 74.2% with a fully active performance, able to carry on all pre-disease activities without restriction.

CONCLUSION
A multidisciplinary approach is essential in the management of pediatric patients with CNS tumors. Efforts should be aimed at reducing post-surgical morbidity and early rehabilitation to reintegrate patients into society in the long term as we described many of them have an excellent performance status.
RBIO-02. THERAPEUTIC EFFECTS OF RADIOTHERAPY WITH CONCOMITANT IN CHILDREN WITH DIPG
Authors: Lai Mingyao , Li Shaoqun , Li Juan , Hu Qingjun , Zhen Junjie , Zhou Jiangfen , Cai Linbo , Zhou zhaoming 
Published: November 2021

Abstract

OBJECTIVE
To retrospectively analyze the therapeutic effects of radiotherapy with concomitant and adjuvant temozolomide（TMZ） versus radiotherapy with concomitant TMZ alone for pediatric diffuse intrinsic pontine glioma (DIPG), and to evaluate the value of radiotherapy and TMZ in the treatment of pediatric DIPG.

METHODS
The clinical data of children with confirmed DIPG in Guangdong Sanjiu Brain Hospital between January 1, 2010 and March 31, 2020 were collected. The inclusive criteria included (1) receiving a total radiotherapy dose of 54 Gy in 27 fractions, (2) treated with concomitant TMZ chemotherapy, and (3) with or without adjuvant TMZ chemotherapy. A total of 85 pediatric patients were eligible for the study. The Kaplan-Meier method was used for survival analysis, and a multivariable Cox proportional hazards regression model was used to assess the independent prognostic factors.

RESULTS
Among 85 cases with a median age of 7 years (range 2-16 years), the median follow-up was 9 months (range 3-28 months) and the median survival time was 9 months. The median survival time of 66 patients treated with radiotherapy with concomitant and adjuvant TMZ was 10 months, longer than 6 months of the other 19 patients treated with radiotherapy with concomitant TMZ alone, with statistical differences (p=0.002). Moreover, bevacizumab and nimotuzumab didn't bring survival benefits to patients with disease recurrence or progression. The prognosis in DIPG patients with H3K27M positive expressed is poor. Hematological toxicity (Grade IV) was not found.

CONCLUSION
Radiotherapy with concomitant and adjuvant TMZ prolongs the survival time of children with DIPG.
RBIO-03. INITIAL RESULT OF DEVELOP ROBUST DEEP LEARNING MODEL FOR DETECTING GENOMIC STATUS IN GLIOMAS AGAINST IMAGE DIFFERENCES AMONG FACILITIES
Authors: Takahashi Satoshi , Takahashi Masamichi , Kinoshita Manabu , Miyake Mototaka , Sese Jun , Kobayashi Kazuma , Ichimura Koichi , Narita Yoshitaka , Hamamoto Ryuji , glioma Consortium of Molecular Diagnosis of 
Published: November 2021

Abstract

BACKGROUND
The importance of detecting the genomic status of gliomas is increasingly recognized and IDH (isocitrate dehydrogenase) mutation and TERT (telomerase reverse transcriptase) promoter mutation have a significant impact on treatment decisions. Noninvasive prediction of these genomic statuses in gliomas is a challenging problem; however, a deep learning model using magnetic resonance imaging (MRI) can be a solution. The image differences among facilities causing performance degradation, called domain shift, have also been reported in other tasks such as brain tumor segmentation. We investigated whether a deep learning model could predict the gene status, and if so, to what extent it would be affected by domain shift.

METHOD
We used the Multimodal Brain Tumor Segmentation Challenge (BraTS) data and the Japanese cohort (JC) dataset consisted of brain tumor images collected from 544 patients in 10 facilities in Japan. We focused on IDH mutation and TERT promoter mutation. The deep learning models to predict the statuses of these genes were trained by the BraTS dataset or the training portion of the JC dataset, and the test portion of the JC dataset evaluated the accuracy of the models.

RESULTS
The IDH mutation predicting model trained by the BraTS dataset showed 80.0% accuracy for the validation portion of the BraTS dataset; however, only 67.3% for the test portion of the JC dataset. The TERT promoter mutation predicting model trained by the training portion of the JC dataset showed only 49% accuracy for the test portion of the JC dataset.

CONCLUSION
IDH mutation can be predicted by deep learning models using MRI, but the performance degeneration by domain shift was significant. On the other hand, TERT promoter mutation could not be predicted accurately enough by current deep learning techniques. In both mutations, further studies are needed.
RTID-03. DESIGN AND INITIATION OF PIVOTAL STUDIES FOR BERUBICIN, A NOVEL, POTENT TOPOISOMERASE II POISON FOR THE TREATMENT OF RECURRENT GLIOBLASTOMA MULTIFORME (GBM)
Authors: Silberman Sandra , Hsu Sigmund , Muczyczenko Zena , Picker Donald , Sipowicz Marek , Żak Ewa , Buczyńska Agnieszka , Olejniczak Mariusz , Priebe Waldemar 
Published: November 2021

Abstract
Berubicin (WP744) is a doxorubicin analog that crosses the blood-brain barrier (BBB), shows significant CNS uptake, and induces more DNA damage but lower lethality than doxorubicin at equivalent doses. Berubicin also prolongs the survival time of intracranial orthotopic glioma models in mice compared to temozolomide, currently the standard of care in GBM. A Phase 1 study at MD Anderson in patients with recurrent glioma treated with escalating doses of Berubicin administered qdx3 repeated q21 days showed that it was well tolerated, with myelosuppression (neutropenia and thrombocytopenia) as the dose-limiting toxicity. Of 25 patients evaluable for efficacy, there was 1 complete response (13+ years), 1 partial response, and 10 patients with stable disease for a clinical benefit rate of 48%. To assure a rapid and economically practicable development program, two companies have collaborated to conduct trials in the US and EU, leading to a potentially more rapid approval of Berubicin for treating GBM in patients with limited options. CNS Pharmaceuticals, Inc. has initiated a randomized, controlled clinical trial of Berubicin vs. lomustine in adults with recurrent GBM. WPD Pharmaceuticals has sub-licensed Berubicin to study recurrent GBM in adults in an open-label trial. This is a unique collaboration in which the same overall design, eligibility criteria, procedures, and database for patients receiving Berubicin are used by both companies, ensuring that there will be a more robust and substantial data set for evaluation of activity and safety. The primary endpoint of the CNS study, to be conducted in the US and Europe, is overall survival (OS). The WPD study conducted in the EU has a primary endpoint of overall response rate (ORR). The data from these two trials are expected to provide sufficient information to support a potential registration program in both the US and EU for the treatment of patients with glioblastoma.
RTID-04. GLIOTARGET: A DANISH NATIONWIDE PHASE I/II PLATFORM TRIAL FOCUSING ON INDIVIDUALIZED TARGETED TREATMENT FOR NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS BASED ON GENOMIC PROFILING
Authors: Fougner Vincent , Hasselbalch Benedikte , Urup Thomas , Lassen Ulrik , Poulsen Hans 
Published: November 2021

Abstract

INTRODUCTION
The survival in glioblastoma has been unchanged since 2005. The introduction of targeted treatments, which have improved survival in several cancers has yet to influence the treatment of glioblastoma. In Gliotarget, we will individualize the targeted treatment, and give it in the primary setting alongside standard therapy with the intention to improve the likelihood of effect.

METHODS
Gliotarget is a biomarker enriched phase I/II platform trial with initially 4 predefined biomarker selected arms, one miscellaneous biomarker arm and one control arm. All patients receive standard therapy with concomitant radiochemotherapy and adjuvant Temozolomide. The experimental treatment is given alongside the adjuvant Temozolomide. Molecular analysis, including Whole Genome Sequencing, is performed on all patients, to identify actionable biomarkers. The miscellaneous arm gathers patients with not previously defined biomarkers upon which the weekly molecular tumor board decides to treat. Gliotarget includes newly diagnosed IDH-wt glioblastoma patients. In addition, to exclude the patients where the inherent poor prognosis might conceal the drug efficacy, the patients must have a 50% probability of being alive 12 months after initial surgery, according to a prognostic model developed in our institution.
The sample size is calculated with Simon’s two-stage design using treatment effect at 9-months progression free survival (PFS9). We anticipate 9 patients for stage one and 24 in total, for each arm. Treatment effect is defined as 65% of the patients in an experimental arm reaching PFS9. For the survival analysis, supplementing the control arm data with leveraged external controls taken from our prospectively registered database will decrease the probability of false positive results.

CONCLUSION
Gliotarget complements the field of ongoing platform trials with its distinctive trial design. The chosen biomarkers and treatments will be presented at the annual meeting. Enrollment is set to open in Q4 2021.
SURG-06. THE SAFETY PROFILE OF TUMOR TREATING FIELDS (TTFIELDS; 200 KHZ) CONCOMITANT WITH VENTRICULO-PERITONEAL SHUNTS IN PATIENTS WITH GLIOBLASTOMA AND HYDROCEPHALUS
Authors: Oberheim-Bush Nancy Ann , Shi Wenyin , McDermott Michael , Grote Alexander , Stindl Julia , Lustgarten Leonardo 
Published: November 2021

Abstract

INTRODUCTION
Hydrocephalus is a common development in patients with glioblastoma (GBM) requiring treatment with ventriculo-peritoneal (VP)-shunts (programmable/non-programmable). To maximize outcomes in this high-risk population, evaluation of VP-shunt usage concomitant with GBM treatments is necessary. Tumor Treating Fields (TTFields; 200 kHz; anti-mitotic, loco-regional cancer modality) non-invasively delivers continuous, alternating electrical fields per scalp-placed arrays. TTFields treatment has obtained FDA-approval/CE-mark in adult patients with newly-diagnosed GBM (ndGBM) and recurrent GBM (rGBM). Due to insufficient TTFields/VP-shunt usage data, label does not currently advise concurrent use. We report on safety data from adult patients utilizing TTFields/VP-shunts in the real-world, clinical-setting.

METHODS
This retrospective, post-marketing, safety surveillance analysis evaluated unsolicited data from adult patients with GBM/hydrocephalus who were TTFields-treated in the presence of a VP-shunt. Available data from &gt;18,000 patients with GBM prescribed TTFields (November 1, 2012 to April 15, 2021 [cut-off date]) were screened for eligibility. Included were 156 adult patients (≥ 18 years of age) with confirmed GBM/hydrocephalus and TTFields/VP-shunt (46 programmable; 110 non-programmable/unknown) usage. Patients were further analyzed by diagnosis (ndGBM, n=92; rGBM, n=64).

RESULTS
Of 156 TTFields/VP-shunt-treated patients (median age 52), 66% were male and 81% from the United States (19%; Europe/Middle-east/Africa). Overall, no TTFields-related shunt-failures or differences by GBM diagnosis in shunt-type and TTFields-related AEs were observed. Commonly-reported TTFields-related adverse events (AEs) &gt;10% were beneath-array skin reactions (∼43%), electric sensations (∼14%; tingling), headache (∼13%), fatigue/malaise (∼12%), and heat sensation (∼11%; warmth); headache and fatigue/malaise are also associated with other concomitant treatments/disease burden. There were 5 serious AEs (all skin AEs) potentially-related to TTFields at the shunt-site (2 events, wound dehiscence; 3 events, skin erosion).

CONCLUSIONS
Adult patients with GBM/hydrocephalus treated with TTFields (200 kHz)/VP-shunts in the real-world, clinical-setting suggests feasibility and a tolerable safety profile; with no evidence of disrupted VP-shunt effectiveness. TTFields safety profile was consistent with prior-studies.
SURG-07. ERAS IN NEURO-ONCOLOGY
Authors: moro mario , Bartoletti Viola , Giordan Enrico 
Published: November 2021

Abstract

BACKGROUND
We performed a retrospective study assesses the efficacy and safety of a protocol for the enhanced clinical recovery of neuro-oncology patients undergoing surgery for supratentorial gliomas and metastasis. The protocol developed and applied to the Ca'Foncello Hospital in Treviso starts from the recommendations on the subject that the medical literature reported up to December 2018. Briefly, three main sections:1) preoperative functional status evaluation, preoperative oral carbohydrate loading; 2) minimally invasive surgery, scalp incision anesthesia, nonopioid analgesia; 3) early urinary-catheter removal, standing and feeding resumption within 3-4 hours from surgery.

METHODS
We collected and analyzed data on 28 patients operated on ERAS protocol and compared them to a control group (22 patients). The main clinical variables are: Charlson comorbidity index; times urinary-catether removal, adherence ambulation, taking food by mouth; hospital long of stay (LOS). We also collected studies from 2016 to 2020 describing data about ERAS and craniotomy and we pooled these into a meta-analysis.

RESULTS
Times urinary-catheter removal (3.1 vs 25 hours.), adherence to ambulation (4 vs 25 hours) and taking food by mouth (5.25 vs 23.72 hours) were significantly (p&lt; 0.001) reduced in the ERAS group. Median hospital LOS was 2.85 days in the ERAS group and 4.77 days in the control group (p&lt; 0.001). Our results overlapped those of the literature; the same trend was highlighted by our meta-analysis, with postoperative pain rates and hospital LOS significantly lower in ERAS patients (7.9 vs. 2.9 days, p &lt; 0.001). A further important finding was that elderly patients (≥ 65 years) got the same outcomes as younger ones.

CONCLUSIONS
Our protocol for ERAS in neuro-oncology appears to have significant benefits over conventional management: it may improve patient outcomes, accelerate functional recovery, decrease length of stay, and enable patients to begin adjuvant chemotherapy and/or radiation in a more expeditious manner.
SURG-08. SARCOPENIA IS A PROGNOSTIC FACTOR OF 90-DAY MORTALITY AND OVERALL SURVIVAL IN ELDERLY PATIENTS WITH GLIOBLASTOMA
Authors: Morshed Ramin , Young Jacob , Casey Megan , Wang Elaina , Aghi Manish K , Berger Mitchel , Hervey-Jumper Shawn 
Published: November 2021

Abstract
Elderly patients with glioblastoma (GBM) have worse overall prognosis compared to younger patients and are less likely to undergo tumor resection and adjuvant therapy. The goal of this study was to identify patient and treatment factors as well as preoperative imaging features associated with worse overall survival and death within 3 months of surgery in elderly GBM patients. A single-center retrospective study was conducted with patients who met the following inclusion criteria: 1) age ≥ 79 at surgery (past the average age of life expectancy), 2) underwent biopsy or resection of an IDH-wildtype WHO Grade IV GBM at the time of initial diagnosis, and 3) had no prior radiation or chemotherapy. Patient, imaging, and treatment data were collected retrospectively from the electronic medical record. Univariate and multivariate Cox proportional hazard and logistic regression analyses were performed to identify factors associated with overall survival and 90-day mortality. The cohort consisted of 110 patients with a mean age of 82.8 (range 79 to 94.1) at surgery and a median preoperative KPS of 80. Thirty-seven (33.6%) and 73 (66.4%) patients underwent biopsy and resection, respectively. Adjuvant chemo- and/or radiation therapy were used in 72.5% of cases. On multivariate analysis, age (HR 1.13 by year, p=0.01), increased masseter thickness (HR 0.88 by mm, p=0.049), adjuvant therapy (HR 0.05, p&lt; .0001), and surgical resection rather than biopsy (HR 0.38, p=0.0007) were associated with improved survival. Decreased masseter thickness was the only preoperative factor on analysis that predicted 90-day mortality in the cohort (p=0.038). GBM patients past the average age of life expectancy still fare better when undergoing resection followed by adjuvant chemotherapy and radiation therapy. In addition to treatment factors that predict survival, smaller masseter diameter on preoperative imaging, a marker of sarcopenia, is associated with shorter survival and death within 90 days of surgery.
TAMI-02. DEPLETION OF INTRATUMORAL TUMOR-ASSOCIATED MACROPHAGES AND MICROGLIA (TAM/M) IMPROVES CHECKPOINT-INHIBITION THERAPY FOR BRAIN METASTASIS FROM LUNG CANCER
Authors: Karschnia Philipp , Xu Tao , Fitzinger Esther , Saliger Julia C , Blobner Jens , Teske Nico , von Muecke-Heim Iven-Alex , Langer Sigrid , Konhäuser Marcel , Ishikawa-Ankerhold Hellen , Thon Niklas , Tonn Jörg-Christian , von Baumgarten Louisa 
Published: November 2021

Abstract

BACKGROUND
Brain metastases dramatically limit prognosis of lung cancer patients. Unlike systemic disease, brain metastases from lung cancer poorly respond to checkpoint-inhibition therapy. Targeting the immunosuppressive tumor-associated macrophages and microglia (TAM/M) and their receptor CSF1R may increase efficacy of checkpoint-inhibitors.

METHODS
Cranial windows were prepared in fully immunocompetent, transgenic CX3CR1GFP/wt-mice with green-fluorescent TAM/M. Intracranial injection of red-fluorescent Lewis Lung Carcinoma-cells was performed, and mice received one of the following three treatments: PD1-inhibition only (n = 8); PD1-inhibition combined with an anti-CSF1R-antibody (exhibiting limited blood-brain-barrier permeability under physiologic conditions, n = 8); or PD1-inhibition combined with a small molecular CSF1R-inhibitor (exhibiting high blood-brain-barrier permeability, n = 7). Tumor growth and TAM/M were followed by repetitive two-photon laser-scanning-microscopy over weeks.

RESULTS
Following intracranial injection, metastases were detected in all three treatment groups within eight days. In mice receiving PD1-inhibition only, metastases showed exponential growth which was paralleled by intra- and peritumoral accumulation of TAM/M. Treatment with an anti-CSF1R-antibody resulted in significantly lower numbers of intratumoral TAM/M given increased tumoral blood-brain-barrier permeability, but did not substantially affect peritumoral TAM/M or TAM/M localized in the healthy contralateral hemisphere. In contrast, treatment with a small molecular CSF1R-inhibitor not only reduced the number of intratumoral TAM/M, but also of peritumoral and contralateral TAM/M. Compared to PD1-inhibition only, the addition of either an anti-CSF1R-antibody or a small molecular CSF1R-inhibitor resulted in decreased tumor growth (tumor size on day 12: 8.3 mm2 (PD1-inhibition only) versus 0.9 mm2 (PD1-inhibition + anti-CSF1R-antibody) versus 2.5 mm2 (PD1-inhibition + small molecular CSF1R-inhibitor)) (p = 0.01). The beneficial effects of the small molecular CSF1R-inhibitor in reducing tumor growth were similar to those of the anti-CSF1R-antibody.

CONCLUSION
Targeting intratumoral TAM/M using CSF1-inhibition may increase the efficacy of checkpoint-inhibition therapy for cerebral lung cancer metastases. This approach warrants further evaluation in preclinical and clinical studies.
TAMI-06. TUMOR CELL-DERIVED CYTOKINE EXPRESSION CHANGES ASSOCIATED WITH BRAIN METASTASIS IN A SYNGENEIC MOUSE MODEL OF BREAST CANCER
Authors: Morshed Ramin , Haddad Alexander , Jain Saket , Gill Sabraj , Spatz Jordan , Aghi Manish K 
Published: November 2021

Abstract
Breast cancer is the most common malignancy in women in the United States, and brain metastases occur in almost a third of patients with metastatic dissemination. Immunoediting is a critical component of metastatic tumor cell elimination, and tumor clones that develop immune-escape mechanisms are associated with progression and metastatic dissemination. We hypothesized that breast cancer brain metastatic cells harbor immunomodulatory cytokine expression changes that promote an immunosuppressive environment to avoid immune cell-mediated elimination. To study this, a syngeneic mouse model of metastatic breast cancer was used. A brain metastatic line derived from the 4T1 breast cancer parental cell line was created by serially selecting brain metastatic populations of cells after intracardiac injection (4T1 BrM). A gene-expression analysis using an 800-gene cancer immunology-specific microarray panel was performed comparing the 4T1 parental and 4T1 BrM lines. 4T1 BrM cells demonstrate gene expression changes promoting immunosuppression including significant upregulation of IL18 and Lgals9 (Galectin-9) and downregulation of CD40, IL2rg, CCL2, and EOMES. When compared to 4T1 parental lines, the 4T1 BrM line demonstrated decreased expression of CCL2 and increased expression of GM-CSF on a cytokine array, corresponding to results obtained from gene expression analysis. These results suggest tumor-intrinsic cytokine expression changes that may mediate an immunosuppressive environment.