bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II double-blind, randomized clinical trial assessing the tolerability of two different ratios of cannabis in patients with glioblastoma multiforme (GBM).
Authors: Lacey Judith , Schloss Janet Margaret , Sinclair Justin , Steel Amie , Sughrue Mike , Teo Charles , Sibbritt David 
Published: May 2020

2530 Background: Cannabis has been used for cancer-related symptoms but few trials have assessed quality of life or tolerability, and trials assessing tumour response or survival remain scarce. Treatment for recurrent glioblastoma (rGBM) remains palliative with poor prognosis. The tolerability of THC-containing cannabis products, and their effect on symptoms and quality of life in people with rGBM patients is poorly defined but is essential before efficacy trials can be conducted. Methods: We conducted a randomised double-blinded trial assessing the tolerability of two preparations of cannabis in 88 people with rGBM. The two preparations used different cannabidiol (CBD) to tetrahydrocannibidiol (THC) ratios; 1:1 (5.8mg/ml:5.6mg/ml) and 1:4 (3.8mg/ml:15mg/ml). Daily evening doses were individually monitored and titrated. Outcomes included disease response by FACT-Br, MRI imaging 12 weekly, blood pathology, NCI-CTC and clinical monitoring. Symptom assessments were performed 4 weekly for 12 weeks. Results: 921 people volunteered for screening across Australia, with 642 excluded, 92 recruited with 88 enrolled. 61 participants completed 12-week follow-up (attrition 30%). Both cannabis oils were well tolerated. Total FACT-Br was similar for both preparations, however, statistical significance was found for the physical section (p = 0.025) and functional (p = 0.014) identifying the 1:1 ratio as the more appropriate combination. Comparing groups to baseline, participants reported improvement of sleep (p = 0.009), improved energy (p = 0.015), and contentment with QoL (p = 0.006). Total cohort compared to baseline, participants reported improvement of sleep (p = 0.0001), pain (p = 0.046), nausea (p = 0.017), anxiety (p = 0.005) and seizure activity (p = 0.022). There were no major adverse events attributable to the cannabis with main side effects noted as dizziness, drowsiness, tiredness, and dry mouth. No abnormal blood pathology nor variance in NCI-CTCAE scores were observed. Conclusions: A single nightly dose of THC-containing cannabis was well tolerated in patients in both groups with rGBM and significantly improved sleep and functional wellbeing and QOL in a sample of patients compared to baseline. From this trial, the 1:1 ratio has been identified as the better tolerated product with suprerior symptom and QoL outcomes compared to the 1:4 product. Clinical trial information: ACTRN12617001287325 .
Concurrent nivolumab and ipilimumab with brain stereotactic radiosurgery for brain metastases from non-small cell lung cancer: A phase I trial.
Authors: Li Jing , Wang Yan , Tang Chad , Welsh James William , Guha- Thakurta Nandita , Carter Brett W. , Wefel Jeffrey Scott , Ghia Amol J. , Yeboa Debra , McAleer Mary Frances , Chung Caroline , Woodhouse Kristina D , Elamin Yasir , Le Xiuning , Cascone Tina , Negrao Marcelo Vailati , Skoulidis Ferdinandos , Ferrarotto Renata , Heymach John , Altan Mehmet 
Published: May 2020

2531 Background: Nivolumab (nivo) and ipilimumab (ipi) were found in the recent phase III CheckMate 227 trial to have an overall survival benefit over chemotherapy for advanced non-small cell lung cancer (NSCLC). However, patients (pts) with untreated brain metastasis (mets) were excluded from that trial. Because 30% of NSCLC pts develop brain mets, we tested nivo/ipi with concurrent stereotactic radiosurgery (SRS) for NSCLC pts with active brain mets. Methods: We report the safety data from the phase I portion of an ongoing phase I/II single-institution trial in which one treatment group was given SRS with nivo (3 mg/kg) every 2 weeks (wks) plus ipi (1 mg/kg) every 6 wks x 4 cycles, followed by maintenance nivo (480 mg) every 4 wks until disease progression, unacceptable toxicity, or withdrawal of consent. Brain SRS was delivered within 7 days of initiation of nivo/ipi. The primary endpoints were safety and 4-month (mo) intracranial progression-free survival (PFS). Dose-limiting toxicity (DLT) was defined as > 15% intracranial toxicity (>G3 hypophysitis / neurologic toxicity) or > 30% extracranial toxicity (>G3 non-dermatologic non-lab toxicity or >G4 dermatologic / lab toxicity), refractory to medical management, assessed at 8 wks after treatment initiation. Target accrual for phase I was 10 evaluable pts, with enrollment suspended after every 5 pts for DLT assessment. Results: Since June 15, 2018, 13 pts were enrolled and 10 were evaluable for DLT. The median follow-up time was 6.8 mo (range 1.2‒18). As of January 6, 2020, only 1 pt had DLT-defined toxicity and thus the predefined stopping criteria were not met. This pt had G3 seizure right after SRS that resolved within a week, and then had increased but asymptomatic CNS edema 4 wks later. Aside from DLTs, 3 pts (25%) developed treatment-related G3 (elevated liver function tests, fatigue, nausea, adrenal insufficiency, and myocarditis) or G4 events (pneumonitis/acute respiratory distress syndrome in 1 pt with confirmed influenza at 7 mos after treatment initiation). This pt subsequently died of hemophagocytic lymphohistiocytosis (considered possibly related to the study drugs). Median intracranial PFS time was 9.7 mo, and the 4-mo intracranial PFS rate was 75%. Extracranial objective response rate was 33% in the 12 evaluable pts with a median response duration of 9.1 mo. Conclusions: Concurrent SRS withnivo/ipi was safe for pts with active NSCLC brain mets. Preliminary analyses of efficacy were encouraging for durable intracranial and extracranial response. Clinical trial information: NCT02696993 .
Accelerator-based BNCT in rescue treatment of patients with recurrent GBM: A multicenter phase II study.
Authors: Miyatake Shin-Ichi , Kawabata Shinji , Goto Hiromi , Narita Yoshitaka , Suzuki Minoru , Hirose Katsumi , Takai Yoshihiro , Ono Koji , Ohnishi Takanori , Tanaka Hiroki , Kato Takahiro 
Published: May 2020

2536 Background: Boron neutron capture therapy (BNCT) is tumor-selective particle radiation and theoretically efficacious especially for tumors with infiltrative nature, such as glioblastoma (GBM). The aim of this study is to assess safety and efficacy of accelerator-based BNCT (AB-BNCT) using cyclotron-based neutron generator, BNCT30, and 10B-boronophenylalanine (borofalan(10B)) agent, SPM-011, in patients with recurrent malignant gliomas, chiefly GBM. Methods: The multi-institutional open-label, phase II clinical trial for recurrent 27 cases of malignant gliomas (MG) (24 cases were GBM) was conducted with above mentioned AB-BNCT system, using 500mg/kg of SPM-011 (study code, JG002). The patients were enrolled from February 2016 to June 2018. The inclusion criteria are bevacizumab-naïve MG, recurrent after standard treatment composed of XRT and chemotherapy with TMZ. Neutron-irradiation time were determined not to exceed to 8.5 Gy-Eq for scalp dose which was decided by preceding phase I trial. Primary endpoint was 1-year survival rate and secondary ones were median overall survival (mOS), median progression free survival (mPFS) and so on. The results were compared to previous Japanese domestic bevacizumab trial for recurrent GBM (JO22506) which had the similar inclusion criteria with JG002. Results: 1-year survival rate and mOS of recurrent GBM cases in JG002 was 79.2% (95% CI:57.0-90.8) and 18.7 months (95% CI:12.9-23.4) (data cutoff = 20 Jun 2019) respectively, while those of JO22506 was 34.5% (90% CI:20.0-49.0) and 10.5 months (95% CI:8.2-12.4), respectively. Median PFS of JG002 and JO22506 were 0.9 and 3.3 months, respectively. Most important adverse event in JG002 was brain edema. 21 out of 27 cases were treated with bevacizumab after progress disease. Conclusions: AB-BNCT demonstrated acceptable safety and prolonged survival for recurrent MG chiefly GBM. AB-BNCT might produce brain edema somewhat after the treatment, which might be the unavoidable adverse event of re-irradiation for recurrent MG, however that seemed to be controlled with bevacizumab. Clinical trial information: JapicCTI-194742 . [Table: see text]
Depatuxizumab mafodotin (Depatux-M) plus temozolomide (TMZ) in recurrent glioblastoma patients: Real-world experience from a multicenter study of Italian Association of Neuro-Oncology (AINO).
Authors: Caccese Mario , Padovan Marta , Eoli Marica , Pellerino Alessia , Rizzato Simona , Caserta Claudia , Simonelli Matteo , Michiara Maria , Zagonel Vittorina , Ruda Roberta , Lombardi Giuseppe 
Published: May 2020

2544 Background: Precision medicine is a promising tool in oncology. Depatux-M is a new antibody-drug conjugate, consisting of a specific antibody against activated EGFR and a cytotoxic agent with antimicrotubule activity. The Intellance2/EORTC 1410 phase II trial, showed interesting results for Depatux-M and TMZ combination in EGFR-amplified glioblastoma (GBM) patients (PTS) at first recurrence after RT and TMZ. In our study, we investigated clinical outcome and safety of this combination used in recurrent GBM PTS as “compassionate use”. Methods: In this prospective observational study, PTS were enrolled from 7 centres of AINO. Major inclusion criteria were: histologically confirmed diagnosis of GBM, 1 or more prior systemic therapies, ECOG PS ≤ 2 and EGFR-amplified (analyzed by FISH). According to original schedule, patients received Depatux-M 1.25 mg/kg every two weeks combined with TMZ until disease progression or unacceptable toxicity. Kaplan-Meier method was used to estimate the survival curves, RANO criteria for radiological assessment, CTCAE v5.0 for drug related adverse events. Results: From October 2018 to June 2019, we enrolled 36 PTS: median age was 57, ECOG PS 0-1 in 88% of PTS, MGMTmet in 64%, 42% received the treatment as second-line therapy and 27% underwent further chemotherapy at progression. At the time of analysis, 13 PTS (36%) had died and 27 PTS (75%) had progressed. Median OS was 8.7ms (95%CI not available), 6ms OS was 68%; median PFS was 2.3ms (95% CI 1.8 – 2.8), 6ms PFS was 37%. All PTS were evaluable for response: disease control rate was 47%: stable disease was reported in 36% and partial response in 11% of PTS. Drug-related adverse events led to dose reductions of Depatux-M in 17% of PTS, in 28% was delayed and in 8% was permanently discontinued. The most frequent grade 3-4 adverse events were ocular toxicity in 67% and haematological toxicity in 17% of PTS; no death was considered drug-related. Conclusions: We report the first “real world” experience of Depatux-M plus TMZ in recurrent GBM. We showed encouraging clinical benefit, despite most patients were treated beyond the second-line of therapy. Overall the results are closed to those reported in previous phase II trial. Although toxicity was higher than expected, it was manageable and only a small group of patients discontinued the treatment due to serious adverse events
Preliminary assessment of low-intensity transcranial magnetic stimulation (TMS) during the treatment for brain glioblastomas.
Authors: Popov Ivan A. , Kit Oleg I. , Shikhlyarova Alla I. , Frantsiyants Elena M. , Rostorguev Eduard E. , Atmachidi Dmitriy P. , Timoshkina Natalya N. , Gusareva Marina A. , Potemkin Dmitrii S. , Stasov Vitaliy V. , Arapova Yulia Yu. , Protasova Tatiana P. , Zhukova Galina V. , Kavitskiy Sergey E. , Ignatov Sergey N. , Cherkiev Islam U. , Nikitin Emzari S. , Kuznetsova Natalya S. 
Published: May 2020

2545 Background: The standard treatment of malignant brain gliomas, including surgical and radiation therapies, does not provide recovery and a long-time favorable prognosis. The development of technologies and international guidelines on the introduction of electric (TTF) and electromagnetic (TMS) fields in combination treatment for glioblastomas aims to improve immediate results, as shown in experiments on human glioblastoma cell culture. The TMS protocol requires further refinement in parameters of frequency, intensity, and exposure with an assessment of the immediate results of combined treatment. Methods: The study included 60 patients diagnosed with MBG receiving osteoplastic craniotomy with radical (within visible unchanged tissues) tumor removal. Starting from the second day after the surgery, patients of group 1 (n = 30) received 10 sessions of magnetotherapy in the double exposure mode. For the first morning exposure, we used an ultra-low-frequency magnetic field (ULFMF) (0.03 to 9.0 Hz) on the hypothalamus projection area to induce a general antistress reaction. After 2.5-3 hours, local (on the surgical site) TMS exposure with the Neuro-MSD system (Russia) was applied in the pulse algorithm, up to 1 GHz and 5 Hz, 15 mT, 3 min. The induction was reduced exponentially (C = 0.8). The control group 2 (n = 30) did not receive ULFMF or TMS. Magnetic resonance imaging (MRI) was used to determine the volume of tumors (Vt, cm3) and perifocal edema (Ve, cm3) calculated according to the Shrek’s formula for an ellipsoid (V = a×b×c×π/6). Results: Before surgery, Vt = 54.7±5.7cm3 in group 1, in group 2 - Vt = 60.9±8.5cm3 (no statistical differences). After surgery and the subsequent course of ULFMF and TMS, residual tumor volumes in group 1 were 2.5 times lower than in controls (p < 0.05). The difference between Ve values before and after treatment was on average 80.7 cm3 in group 1 and 41.8 cm3 in group 2 (p < 0.05). Conclusions: The inclusion of sequential ULFMF and TMS exposures into postoperative therapy for gliomas, taking into account various vectors of the influence on the projection of centers of homeostasis regulation and the surgical field, as well as the development of programmed modes of biotropic exposure parameters, improves antitumor and anti-edematous effects.
Genome-wide methylation analysis in long-term survivors of glioblastoma (GBM).
Authors: Chau Justin , Dhungana Neha , Kohlmeyer Jordan , Petronek Michael , Quelle Dawn , Sato Mariko , Darbro Benjamin , Jones Karra , Monga Varun 
Published: May 2020

2552 Background: Identification of tumor characteristics that may be associated with survival in patients with glioblastoma (GBM) has been largely characterized by IDH mutations and MGMT promoter methylation status. However, these genetic changes and other currently available data are not sufficient to explain the longevity experienced by a subset of long-term survivors (LTS) - patients surviving longer than 3 years past diagnosis. Methods: The study identified GBM patients established and treated at University of Iowa Holden Comprehensive Cancer Center from 2007-2017 whose disease recurred after initial resection. Patients were categorized LTS if they survived > = 3 years beyond initial definitive resection; short-term survivors (STS) if less than 3 years. Pathologic specimens at initial and repeat resection underwent genome wide methylation analysis using the Infinium EPIC microarray system. Data were analyzed to identify genes that exhibited differentially methylated CpG regions. Results: Resection specimens from GBM survivors were compared to those of STS. A total of 29 samples were analyzed and compared (15 LTS and 14 STS samples). Multidimensional scaling plots identified significant differences in genomic constitution between LTS and STS specimens. Granular analysis yielded 89 differentially methylated regions significantly associated with long-term survival (adjusted p < 0.05). PTPRN2 (p = 0.000376), PTPN11 (p = 1.38E-05), and PAX6 (p = 0.000671) were found to exhibit numerous differentially methylated CpG sites between MGMT-methylated vs. unmethylated specimens. Further notable, higher levels of differentially methylated CpG shores and open-seas regions on chromosome 12 were associated with long-term survival (p = 1.89E-08). Conclusions: Our study identified multiple significant epigenetic differences that, functionally or consequentially, may be associated with extended survival in GBM patients. The implication that CpG shores, rather than islands, are associated with long-term survival raises further intriguing questions regarding the depth of epigenetic complexity in this disease. More immediately, the surprising association of multiple protein phosphatases with LTS in our study may hint at the class’ previously unspecified, yet integral, role in delaying disease progression and identify new, novel avenues for therapy.
Role of high-dose chemotherapy with autologous stem cell transplantation for primary central nervous system lymphoma: A systematic review.
Authors: Nabeel Shaha , Ahmed Zahoor , Farooqui Arafat Ali , Shah Zunairah , Ashraf Aqsa , Imtiaz Hassan , Ashraf Rabia , Neupane Karun , Faisal Muhammad Salman , Anwer Faiz 
Published: May 2020

2562 Background: High dose chemotherapy (HDCT) followed by autologous stem cell transplant (ASCT) has shown to overcome intrinsic chemo-resistance and improve disease control in Primary Central Nervous System Lymphoma (PCNSL). Our study reviews the treatment outcome in PCNSL with sequential HDCT and ASCT. Methods: 8/34 studies were finalized after systematic search of PubMed, Cochrane, and Clinicaltrials.gov for treatment of PCNSL with HDCT followed by ASCT. Results: 251/288 patients were evaluated. Mean age was 55.5 years. 227 underwent HDCT-ASCT. 174 were newly diagnosed (ND) and 77 had relapsed refractory (R/R) PCNSL. ND patients showed superior outcomes in terms of progression free survival and overall survival. Combinations of High dose Rituximab, Busulfan and Cyclophosphamide significantly improved survival outcomes in RR patients. Significant toxicities mainly included pancytopenias and opportunistic. Conclusions: Primary CNS lymphoma treated with HDCT followed by ASCT has shown promising outcomes and has set a benchmark for future studies. [Table: see text]
Postoperative radiation therapy (PORT) impact on clinical outcomes of resected atypical meningioma: A meta-analysis.
Authors: Gallagher Kevin M. , akhtar furqan , Haddad Philip A. 
Published: May 2020

2570 Background: Although meningiomas are among the most prevalent types of brain tumors, atypical meningiomas (AM) account for around 4% of all meningiomas. AMs tend to be more aggressive with relatively higher rates of recurrence and mortality. Gross total resection (GTR) has been the standard of care when possible. However, GTR itself is not always enough to prevent recurrence of AMs. The role of PORT remains controversial in AM as the comparative studies to support its use have provided conflicting results. The purpose of this meta-analysis is to evaluate the impact of PORT on clinical outcomes in resected AMs. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of (i) AM diagnosis, (ii) English language, (iii) Simpson graded resections, and (iv) comparative studies reporting recurrence rates (RcR), Progression Free Survival (PFS), and Overall Survival (OS) with hazard ratios (HR) or Kaplan-Meier curves. A meta-analysis was conducted using an inverse variance method with random-effects model. Results: Twenty-two comparative studies with a total of 5,129 patients were included and analyzed. When GTR was attained, PORT was associated with improved RcR (HR = 0.72, 95%CI:0.59-0.86) and PFS (HR = 0.77, 95%CI:0.65-0.90), but not OS (HR = 0.93, 95%CI:0.83-1.04). When subtotal resection (STR) was attained, PORT was associated with improved PFS (HR = 0.35, 95%CI:0.26-0.48) as well as OS (HR = 0.70, 95%CI:0.54-0.89). Conclusions: This is the first meta-analysis to show that PORT is associated with PFS benefit in AMs with GTR and STR. Moreover, PORT significantly improved OS of AMs that underwent STR but had no impact on OS when GTR was achieved. In the absence of randomized clinical trials, this meta-analysis represents the most compelling data supporting the use of PORT in this patient population.
A phase I combination study of vigil and atezolizumab in recurrent/refractory advanced-stage ovarian cancer: Efficacy assessment in BRCA1/2-wt patients.
Authors: Rocconi Rodney Paul , Stevens Erin E. , Bottsford-Miller Justin N. , Ghamande Sharad A. , Aaron Phylicia , Wallraven Gladice , Bognar Ernest , Manley Meghan , Horvath Staci , Manning Luisa , Nemunaitis John J. , Herzog Thomas J , Monk Bradley J. , Coleman Robert L. ,   Vigil Team
Published: May 2020

3002 Background: Recent studies have shown poor clinical outcomes and limited survival advantage to checkpoint inhibitors (CIs) in advanced stage ovarian cancer (OvC). Vigil is a personalized precision vaccine constructed from autologous tumor tissue transfected with a DNA plasmid encoding GM-CSF and bi-shRNA-furin thereby creating TGFβ expression control and enhancing immune activation. Phase 1 and 2 trials in OvC demonstrate safety, functional immune activation and clinical response benefit. Combining Vigil with CIs may broaden responsiveness of immunotherapy in OvC. Methods: This is a randomized, 3-part safety Phase 1 study of Vigil in combination with Atezolizumab in recurrent OvC patients. Part 2 is a randomized, intra-patient crossover study of Vigil first (VF) or Atezolizumab first (AF) for two cycles followed by sequence of the combination of the two agents. Vigil (1 x 106 or 1 x 107 cells/ml) or Atezolizumab (1200mg) were administered 1x every 21 days each cycle until progression or untoward adverse event. We now report the preliminary results of part 2 of the study. Results: Twenty-one patients were randomized (1:1) to VF (n = 11) or AF (n = 10), groups were similar in demographics. Grade 3/4 toxic events occurred in 17% of AF patients compared to 3% in VF patients. Median OS of VF patients (n = 11) was not reached vs. AF (n = 10) 10.8 months suggested modest advantage to VF (HR 0.33, one-sided p 0.097). However, the subset analysis of BRCA1/2 wild type (wt) demonstrated more significant overall survival benefit in VF (n = 7) median OS not reached vs. AF (n = 7) 5.2 months (HR 0.12, one-sided p 0.015). Conclusions: The combination of Vigil immunotherapy and checkpoint inhibitor atezolizumab in recurrent OvC demonstrated safety and suggest a lower toxicity profile and a significant OS advantage in recurrent BRCA1/2-wt OvC patients treated with Vigil first followed by the combination of Vigil and Atezolizumab. Clinical trial information: NCT03073525 . [Table: see text]