bluuebunny/crossref_metadata_2025_split huggingface dataset:
High expression levels of CD90 to predict edema response to steroid treatment in glioblastoma multiforme (GBM) patients.
Authors: Belda-Iniesta Cristobal , Holgado Esther , Hitt Ricardo , Prat Ricardo , De Castro Javier , Ibañez de Cáceres Inmaculada , Perona Rosario , Ayuso Sacido Angel 
Published: March 2020

e13008 Background: GBM is the most aggressive brain tumour in the adult, with a median overall survival about 15 months. Patients usually present with many symptoms due to edema in addition of symptoms derived from the increasing tumour mass. Edema- dependent symptoms are currently treated with steroids. However, a number of patients do not respond to this therapy and almost all develop severe adverse effects. Currently, there is no biomarker that allows neuro-oncologists to predict edema response to steroid therapy. Methods: This is an observational study aimed to identify molecular markers based on massive expression analysis to predict edema response to steroids in patients diagnosed with GBM. Patients received dexamethasone (4mg bid) before surgery when high-grade glioma was suspected in contrast-enhanced brain MRI. 7 days later a second brain MRI was performed just before surgery to evaluate edema response according with RANO criteria. We collected neurological examinations at days -7 and -1 before surgery, surgical morbidity and time- to- recovery. Expression patterns (proliferative vs. mesenchymal) and a library of molecular markers related to both glioma-initiating cells and more differentiated cells from tumour mass were explored in tumoral and matched control samples from this cohort. Finally, we compared the expression levels of the selected molecular markers together with edema- responses after steroid therapy measured by brain MRI as well as with clinical values. Results: We recruited 54 patients and observed 32 edema- responses. We found that CD90 expression levels similar or above controls correlates with MRI response to steroids. Symptoms improvement and GBM resection without clinical worsening (p = 0.016). Nonetheless, we did not observed any association between CD90 expression level below controls and lack of response. Interestingly, we have observed that steroid responsiveness is not related with the proliferative and mesenchymal nature of the tumour. Conclusions: CD90 expression is a good predictor of edema response to dexamethasone and may be useful to identify candidates for steroid therapy.
The role of Rac proteins in glioblastoma stem cells.
Authors: Lai Yun-Ju , Yu Jei-Hwa , McFarland Braden C , Benveniste Etty N 
Published: March 2020

e13011 Background: Glioblastoma is the grade 4 astrocytoma which is notorious for its highly invasive phenotype, very low survival rate and generally poor responses to conventional therapies. Glioblastoma stem-like cells (GSC), which are usually more resistant to therapeutic treatment, may account for the poor prognosis of this disease. Rac (Ras-related C3 botulinum toxin substrate) is a subfamily of Rho small GTPase which function is regulation of actin cytoskeleton rearrangement. While Rac1 is expressed ubiquitous in different tissues and cells, Rac2 is highly expressed in the mesenchymal subtype of glioblastoma according to the TCGA (the Cancer Genome Atlas) database, and Rac3 is mainly expressed in the brain. Methods: We used Rac proteins overexpressing-glioblastoma cellines derived GSC and Rac proteins specific siRNA harboring-GSC to perform colony formation assay and migration assay. Results: Here we report that Rac proteins overexpressing glioblastoma stem-like cells derived from glioblastoma cell lines have higher proliferation rate and stronger responses to LPA-induced cell migration. Knocking-down their expression by specific siRNA reduces the proliferation and migration of these cells. Instead of Rac1, Rac2 and Rac3 are more effective on promoting proliferation and migration of glioblastoma stem-like cells. Moreover, Rac proteins promote glioblastoma progression is associated with activation of JAK-STAT and ERK pathway. Conclusions: Although Rac1 is the most studied one in the Rac family, and has also been implicated in the progression of different cancers, however, it is homogeneously expressed in all different tissues, and plays important roles in normal cellular functions involving cell movement, such as wound healing, make it not a good candidate for specific drug targeting. According to our results, Rac2 or Rac3 serve as a better potential therapeutic targets for glioblastoma treatment.
Metastatic ACTH-producing pituitary carcinoma managed with combination pasireotide and bevacizumab following failure of temozolamide therapy: A case report.
Authors: O'Riordan Lynda M. , Greally Megan , Coleman Niamh , Breathnach Oscar S. , Hennessy Bryan , Thompson Christopher J , Grogan William 
Published: March 2020

e13022 Background: ACTH-producing pituitary carcinomas (APPC) are malignant neuroendocrine tumors affecting the adenohypophysis. They are extremely rare, with a poor prognosis. They are poorly responsive to chemotherapy and radiotherapy. We report the case of a 25 year old female with a diagnosis of APPC, metastatic to bone, treated with temozolamide, followed by bevacizumab and the novel agent, pasireotide. Methods: The patient was diagnosed in 2002 with an ACTH-secreting pituitary macroadenoma causing Cushing’s disease. Despite two transphenoidal surgeries, bilateral adrenalectomies, craniotomy with excision of pituitary fossa tumour and radiotherapy she developed aggressive Nelson’s Syndrome. Following discontinuation of a somatostatin analogue in 2009 her ACTH levels rose dramatically causing progressive skin hyperpigmentation. Her disease continued to progress despite CyberKnife treatment. She was referred for temozolamide chemotherapy for treatment of the pituitary adenoma. At review, she had severe back pain. Investigations suggested metastatic disease and biopsy confirmed a diagnosis of metastatic APPC to bone.We commenced treatment with Temozolamide, however her disease progressed – ACTH levels were >200,000pmol/l in June 2012. Molecular profiling completed on the patient’s tissue was negative. Pasireotide, a novel multi-somatostatin receptor analogue, was commenced concomitantly with the anti-angiogenesis agent bevacizumab. Results: Treatment response is being assessed with imaging, serial monitoring of serum ACTH levels and skin examination. Interval imaging has shown stable disease, ACTH levels have decreased to 113,000pg/ml. Conclusions: Pituitary carcinomas are extremely rare representing 0.1-0.2% of pituitary neoplasms. To date, there is no established standard treatment, although there are reports of response to temozolamide.Our patient exhibited a clinical improvement and a reduction in ACTH levels after 6 months of combination therapy with pasireotide and bevacizumab. This combination is a possible therapeutic option in patients with metastatic ACTH-producing pituitary carcinoma.
Outcome of an advanced anaplastic astrocytoma patient treated with Newcastle disease viral (NDV) oncolytic therapy.
Authors: Freeman Arnold , Bakacs Tibor , Moss Ralph W 
Published: March 2020

e13029 Background: Oncolytic viruses are increasingly recognized for their potential promise of lasting impact on our cancer treatment repertoire. The use of attenuated Newcastle Disease Virus (NDV) against cancer was pioneered more than 40 years ago by Laszlo Csatary, a Virginia physician, who died March 20, 2012 at age 88. In 1968, Csatary used attenuated NDV as a cancer treatment. NDV, an RNA virus, shows tumor selectivity in its replication behavior in mammalian cells, including humans. Methods: A.G., a 14-year-old boy, presented in September 1994 with a large left fronto-temporal mass. The tumor was debulked and he then received 56 Gy of radiation to the brain. Pathology indicated the tumor was a glioblastoma multiforme (GBM). By November1995 there was local recurrence. Despite various chemotherapies, the cancer progressed. In May 1996 patient started on attenuated intravenous NDV in Budapest, Hungary. This was the only agent he received for the next 8 years. Results: There was progressive shrinkage of the GBM resulting in complete disappearance at 1 year. The patient remains well with no evidence of tumor 16 years after the start of NDV. Conclusions: NDV was able to eradicate GBM in this seemingly hopeless situation and merits further evaluation in this and other cancers.
Temozolomide plus interferon-β for recurrent malignant glioma patients: Experience of 28 cases.
Authors: Chen Zhong-ping , Yang Qun-ying , Guo Cheng-cheng 
Published: March 2020

e13037 Background: Previous studies showed that interferon-β may enhance chemosensitivity of temozolomide (TMZ) and nitrosoureas. The present study was to evaluate the efficiency and side effects of TMZ plus INF-β in recurrent malignant glioma patients. Methods: Patients (age≥18 years) with grade III-IV glioma that was progressive or recurrent after prior standard radiotherapy plus TMZ chemotherapy were eligible for the study. Patients were scheduled to receive INF-β 3MU subcutaneous injections on days 1, 3 and 5, while TMZ 200mg/m2orally on days 2 to 6, of a 4-week cycle until tumor progression or unacceptable toxicity. Tumor response was assessed by MRI every 8 weeks. The primary end point was objective response (complete response [CR] plus partial response [PR]) by Response Assessment in Neuro-Oncology Working Group (RANO) criterion. Secondary end points included progression free survival (PFS), overall survival (OS), and toxicity. Results: From July of 2010 to October of 2012, 28 patients were assessed (16 GBM and 12 grade III glioma). There were 22 males and 6 females, and the median age was 44.5 years (ranged from 22 to 73). The median KPS was 80 (70`100). Radiographic responses were noticed in 35.7% (10 of 28) of patients. There was none CR, but 10 PR, 14 stable disease (SD) and 4 progressive disease (PD). The median PFS was 6.0 months (95% CI 3.9-8.0),the median OS was not availability. The most common toxicities include grade±-2 neutropenia(4 cases), thrombocytopenia (3 cases), nausea and vomiting (3 case), fatigue (8 cases) and liver malfunction (3 cases). Grade III or ‡W toxicities were uncommon. Conclusions: Temozolomide plus INF-β has moderate efficacy for recurrent high grade glioma with acceptable toxicity, and thus worth further investigation.
Bevacizumab (BEV) use in disseminated choroid plexus papilloma (DCCP).
Authors: Anderson Mark Daniel , Theeler Brett James , Groves Morris D. , Penas-Prado Marta , Yung W. K. Alfred 
Published: March 2020

e13039 Background: Choroid plexus papilloma (CCP) is a rare primary neuro-ectodermal tumor of the choroid plexus, representing less than 1% of intracranial tumors in adults. The most common location in adults is the 4th ventricle and treatment is gross total resection (GTR). Leptomeningeal disease (LMD) can rarely occur, even when the tumor retains benign histology. Because of the rarity of DCCP, there is no standard treatment, with less than 20 published cases. There have no previous descriptions of the use of BEV therapy in DCCP. Methods: We present 2 patients (pts) with DCCP, who received gross total resection, radiation and chemotherapy with continued progression, who received treatment with BEV therapy. Results: Pt 1 presented with a 4th ventricular mass and evidence of LMD. GTR of the posterior fossa lesion revealed an atypical CCP. The pt received craniospinal radiation with concurrent temozolomide (TMZ) therapy. After 4 years, there was leptomeningeal disease progression and the pt developed progressive radicular pain and weakness, unresponsive to typical treatments. He was initiated on TMZ and BEV therapy, but the TMZ was discontinued due to thrombocytopenia and the pt was continued on BEV alone. While the MRI showed stable disease at, the pt had complete remission of pain and some improvement of ataxia. When BEV was held due to toxicity, the pain returned until BEV was restarted. Carboplatin was added to BEV with progression of LMD at 21 months. Pt 2 is a 58-year-old man who present with a 4th ventricular mass, shown to be CCP after gross total resection. The pt received radiotherapy for diffuse sacral recurrence. After three years of surveillance, the pt received lomustine and 6-thioguanine for disease progression, limited to 5 cycles by thrombocytopenia. After 5 years, the pt noted continued progressive radicular pain in his lower extremities. The pt completed a planned course of 10 doses of bevacizumab and had improvement in pain control and stable imaging at 11 months. Conclusions: While bevacizumab resulted in stable imaging when used in DCCP, there was significant improvement in debilitating radicular symptoms. The complications of BEV therapy must be considered with the potential benefit of symptomatic relief. Prospective studies are needed.
Phase I study of the combination of BKM120 and bevacizumab in patients with relapsed/refractory glioblastoma multiforme (GBM) or other refractory solid tumors.
Authors: Shih Kent C. , Acs Peter , Burris Howard A. , Hart Lowell L. , Kosloff Rebecca A. , Lamar Ruth E. , Hainsworth John D. 
Published: March 2020

e13045 Background: BKM120 is an oral pan-class I PI3 kinase (PI3K) inhibitor, with demonstrated CNS penetration. Enhanced PI3K signaling is common in GBM (56-75% of cases), and is associated with poor survival (Chakravarti et al, 2004). This phase I study was designed to determine the maximum tolerated dose (MTD) of BKM120 in combination with a standard dose of bevacizumab as treatment for patients with relapsed/refractory GBM or other refractory solid tumors. Methods: Patients with relapsed/refractory GBM or other refractory solid tumors for which bevacizumab was an appropriate therapy received BKM120 with bevacizumab in a standard 3+3 dose escalation design. Bevacizumab 10 mg/kg IV was administered days 1 and 15 of 28-day cycles, with escalating doses of BKM 120 self-administered daily. Patients were evaluated for response after 8 weeks; treatment continued until disease progression or unacceptable toxicity. Results: Twelve patients were treated at 2 BKM120 dose levels, DL 1 = 60 mg/day and DL 2 = 80 mg/day. DL 1 (n = 6) tumor types included: 2 GBM, 2 colorectal and 2 NSCLC with treated brain metastases. Dose-limiting toxicity (DLT) of G4 delirium was observed in 1 GBM patient. Three additional patients were enrolled, and no further DLTs occurred. DL 2 (n = 6) tumor types included: 3 GBM and 3 colorectal. DLTs were observed in 2 of 6 patients: 1 colorectal (G3 rash, G3 stomatitis, G3 dehydration, and G2 worsening vomiting), and 1 GBM (G3 ataxia and G3 mental status changes). 6 patients had CNS symptoms possibly related to treatment, including mood alteration (3 GBM and 1 colorectal), delirium, hallucinations, and mental status change (1 GBM patient each). Common treatment-related toxicities (all grades) included: dyspepsia (42%), nausea (33%), ALT elevation (25%), dehydration (25%), proteinuria (25%), rash (25%), and thrombocytopenia (25%). No objective responses were documented; however, 1 colorectal patient remains on treatment with stable disease for 8 months. Conclusions: The addition of BKM120 to standard dose bevacizumab was tolerated at a dose of 60 mg/day. A phase II study with this combination is currently underway in patients with relapsed/refractory GBM. Clinical trial information: NCT01349660.
Anaplastic gliomas: Is there a role for aggressive concomitant treatment?
Authors: Berriel Luiz Gustavo Sueth , Santos Fábio Nasser , Diniz Ana Carolina Sigolo Levy , Chinen Ludmilla Thome , da Costa Alexandre Andre Balieiro Anastacio 
Published: March 2020

e13050 Background: Anaplastic glioma is a rare type of glioma, therefore there is no standard treatment after surgery. Adjuvant treatment possibilities are monotherapy with radiotherapy or chemotherapy, or combination therapy done concomitantly or sequentialy. Methods: A comparison of adjuvant treatments in a retrospective analysis of 64 patients with the diagnosis of anaplastic glioma treated at A.C.Camargo Hospital, Sao Paulo-Brazil, from 1994 to 2012. Results: Fifty-eight percent were male, median age 42yo (16-79yo), 76,6% ECOG 0-1, Histopatology was 76,6% astrocytomas, 9,4% oligoastrocytomas and 14% oligodendrogliomas. Adjuvant treatment was concomitant radiochemotherapy in 45, 2%, sequential radiochemotherapy in 14,5%, radiotherapy-only in 16,1%, chemotherary-only in 9,7% and 14,5% received no adjuvant treatment. With a median follow up of 32,2mo (P25-P75 – 13, 3-62, 9mo), median progression free survival (mPFS) was 65mo (CI 29,2 – 100,7mo) and median overall survival (mOS) was 87mo (CI 26,3 – 147,7mo) in the whole group. There was a mOS of 31,4mo for astrocytomas, 89,2mo for oligoastrocytomas and not reached for oligodendrogliomas. Comparing with other treatments, the concomitant therapy group had a longer mPFS (124,8mo vs. 20mo, p: 0,016) and mOS (139,8mo vs. 27,9mo, p = 0.081). When only anaplastic astrocytoma where analyzed, treatment with concomitant radiochemotherapy had better mPFS (p = 0.01) and mOS (p = 0.033). On the other side, treatment with sequential radiochemotherapy didn’t have such impact in either mPFS (p: 0,22) or mOS (p: 0,27). Prognostic factors related with both mPFS and mOS in the whole group were astrocytic histology, multiple lesions and more than 50yo at diagnosis. Non-cortical lesions were also prognostic for mOS. In the multivariate analysis, treatment with concomitant radiochemotherapy had an impact at mPFS (HR 0,28, p = 0.006) and mOS (HR 0,44, p = 0.039). Conclusions: Since there is no standard adjuvant treatment for anaplastic gliomas, evidence for treatment is often taken from GBM studies. This study suggests that an aggressive strategy, like concomitant radiochemotherapy with temozolamide, is useful in grade 3 gliomas, specially in astrocystic histology.
Refining the target area in diffuse gliomas for radiation oncology based upon the location of cingulate gyrus tumors.
Authors: Hamilton Jackson , Matuschek Christiane , Boelke Edwin , Budach Wilfried , Prabhu Sujit S. , Sabel Michael , Butler Brian 
Published: March 2020

e13051 Background: Glioblastoma is a brain tumor with poor survival. Radiation therapy (RTX) is often not effective and the target volume could be improved. The aim of this study is to determine if the patterns of spread for cingulate region gliomas could be used to make rational decision for safely altering the treatment planning target volume. Methods: 69 pts. with cingulate gliomas were collected from the collaborating institutions and the patterns of spread were analyzed by serial MRI evaluation. Results: Most pts. present with seizures, one ischemic stroke and one acute hemorrhage was noted. Anterior cingulate was involved in 49 pts. The basal frontal lobe (orbitofrontal or gyrus rectus) was involved in 6 pts. and the insula in 1. There were 20 cases of posterior cingulate involvement including 1 case which wrapped posteriorly from the hippocampus to indusium griseum. None of the cases spread between the anterior and posterior cingulate. 4 had bilateral cingulate involvement. Given that the callosal fibers surround but do not enter the cingulate, the postoperative imaging were assessed which showed that often the callosum was thin and edematous, or had tumor herniate through the callosal isthmus (3 cases), rather than true callosal involvement. Additional cases outside of the 69 pts. showed callosal tumors sparing the cingulate and supra-cingulate frontal and parietal tumors which did not invade the cingulate sulcus. Conclusions: For RTX the areas of cingulate tumor spread which should be considered is the adjacent corpus callosum. There appear to be a relative functional border by the cingulate sulcus and also separating the anterior and posterior cingulate at the level of the paracentral lobules, suggesting the potential for dose deescalation, which may also help with avoiding the supra-cingulate supplemental motor area and leg motor fibers. Other areas to include are the opposite cingulate gyrus, head of the caudate nucleus and septum pellucidum. Anterior cingulate lesions near the genu should include the subcallosal (risky for deficit) and ipsilateral frontal basal areas (risks for frontal lobe syndrome). Sparing the major callosal marginal or pericallosal arteries may help to avoid stroke.
Primary glioblastoma cell lines as source for analysis of the relationship between molecular phenotype and in-vitro drug sensitivity.
Authors: Classen Carl Friedrich , Mullins Christina S , Schubert Julia , Jürgen Piek , Linnebacher Michael , Schneider Björn 
Published: March 2020

e13053 Background: Glioblastoma multiforma (GBM) still has a very poor prognosis even with today’s multimodal combination therapy of resection followed by radio-chemotherapy with temozolomide. Both new molecular inhibitors and immunotherapy may represent future therapeutical tools but due to the variability of the molecular composition in individual GBM, they probably depend on better response prediction. Methods: Based on a close cooperation and logistics between surgery, pathology, laboratory researchers and animal care facilities, we established and analysed cell lines of about 30 primary brain tumors, most of them GBM. Tumors and cell lines were characterised by morphology, growth behaviour, numerous extra- and intracellular antigens, and particularly regarding molecular features. Further, tumors were established in a subcutaneous xenograft mouse model, and growth characteristics were described. These in vitro and in vivo models represent an ideal tool for response analysis of single agent or combined treatment in early cell passages in order to predict response. Besides, relevant antigens and possible shifts of antigen-presentation in tumors can be assessed. Numerous analyses using established and new antitumor compounds – e.g. the integrin inhibitor cilengitide – were performed. Results: We found that although the specific integrin expression is individually different in the tumors analysed, cilengitide sensitivity was similar in most. Addition of temozolomide led to additional, yet not over-additive cytotoxicity. In our panel of GBM specimens we found a very heterogenous pattern of molecular alterations, going along with variations of drug sensitivity. Conclusions: This indicates that, in the future field of individualized approaches, such models are required, in order to enable future strategies to predict the efficacy of immunological, small molecular, biological-based, cytotoxic or other therapeutic strategies. The project was supported by the Förderkreis für krebskranke Kinder Rostock e.V., by a Mecklenburg-Vorpommern graduate scholarship, and by a cooperation with Merck-Serono Research and Development (gift of drug).