bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adoption of behavioral restrictions as anti-infective measures: A survey among solid tumor patients.
Authors: Shachar Eliya , Ferro Leora , Peleg Hasson Shira , Emmanuel Waller , Wolf Ido 
Published: May 2020

2081 Background: Despite lack of evidence, a wide range of rigorous behavioral and social restrictions are recommended in various guidelines and websites in an attempt to mitigate infections. These include patient guided sites. We aimed to study the practices of patients with solid tumors treated with active therapy. Methods: We conducted an anonymous survey among cancer patients treated at a tertiary care center, addressing behavioral approach to infection prevention, by assessing adopted social (seven items), environmental (five items), and dietary (eight items) limitations, as well as compliance to influenza vaccinations. Clinical data included neutropenic fever (NF), and therapy myelosuppressive potential. Multivariable Poisson regression adjusted for sex, age, disease status, therapy to estimate the impact of these restrictions. Results: 214 patients with solid tumors responded to the survey, the majority female (59%), with a median age of 63. The most common tumor types included breast (28%), lung (14%), and colon (9.3%). Most (68%) were treated with chemotherapy, 17% with immunotherapy, 11% with biologicals and 3% with chemo-immunotherapy. Only 6% were admitted for NF. Sources of information regarding restrictions included physicians (4%), nurses (32.9%), and internet (9.8%); the majority were self-imposed. 53% maintained environmental limitations (traveling, sun exposure, hair dying), 37% adopted social restrictions (abstained from children, public places), and 21% affirmed dietary constraints (raw vegetables, tap water consumption). Females practiced stricter environmental and dietary restraint (p < 0.05), with a numerical trend reflecting stricter female social measures (p < 0.4). With no difference in practices among patients treated for a malignant disease and curative intent, and no difference in practice across therapies, in those treated with chemotherapy and immuno-therapy. 37% affirmed difficulty in adherence to these limitations. Conclusions: Our findings indicate that despite lack of evidence, cancer patients adopt anti-infective behavioral measures, which have a deleterious impact on quality of life. These practices are being used even among patients at low or no risk of NF. These findings call for implementation of an education program and development of practical instructions enabling patients to resume their normal life
MGMT methylation as a prognostic factor in IDH wild type anaplastic gliomas.
Authors: Franceschi Enrico , Tosoni Alicia , Di Nunno Vincenzo , Mura Antonella , Asioli Sofia , Pession Annalisa , Agati Raffaele , Paccapelo Alexandro , Bartolini Stefania , Brandes Alba Ariela 
Published: May 2020

2523 Background: Anaplastic gliomas are classified according to the presence of IDH-mutation. IDH wild type (IDH wt) is associated with poor prognosis and limited effectiveness of treatments.The aim of this study was to find out if MGMT methylation represents a prognostic factor in this setting. Methods: Anaplastic gliomas are classified according to the presence of IDH-mutation. IDH wild type (IDH wt) is associated with poor prognosis and limited effectiveness of treatments.The aim of this study was to find out if MGMT methylation represents a prognostic factor in this setting. Results: The analysis included 73 pts with grade III, IDH wt (19.3%) gliomas. Median follow-up time was 69.9 months. Median age was 50 (Range: 18-75), M/F ratio was 40(54.8%)/33(45.2%).MGMT promoter was methylated in 34 pts (46.6%) and unmethylated in 39 pts (53.4%). After surgery, 9 pts (12.3%) received RT alone, 57 pts (78.1%) received both RT and CT (sequential, concomitant or both). Median survival was 26.2 months. In multivariate analysis age (HR = 1.064, 95%CI: 1.030-1.099; P < 0.001) and MGMT methylation (HR = 0.422, 95%CI: 0.210-0.848; P = 0.015) were independently associated with risk for death. Conclusions: IDH wild type confers a dismal prognosis in patients with grade III gliomas. MGMT methylation, as was demonstrated in glioblastoma, represents a prognostic factor that correlated with lower risk for death. Further studies will investigate potential correlations with treatments.
Leptomeningeal disease after surgical resection and radiosurgery for brain metastases and neurologic death: A multi-institutional analysis.
Authors: Prabhu Roshan Sudhir , Turner Brandon E , Asher Anthony L , Marcrom Samuel , Fiveash John B. , Foreman Paul M , Press Robert H. , Buchwald Zachary , Curran Walter J , Patel Kirtesh R. , Breen William , Brown Paul D. , Jethwa Krishan , Grills Inga S. , Arden Jessica , Foster Lauren M , Manning Matthew A. , Vaslow Zachary , Burri Stuart , Soltys Scott G. 
Published: May 2020

2524 Background: Postoperative radiosurgery (SRS) has been associated with up to 30% risk of subsequent leptomeningeal disease (LMD). We previously demonstrated that radiographic pattern of LMD (classical “sugarcoating” [cLMD] vs. nodular [nLMD]) in this setting is prognostic. The association between radiographic pattern of LMD, type of salvage treatment (tx), and neurologic death (ND) has not been well described. Methods: The records of patients (pts) with brain metastases (BM), of which 1 was resected and treated with adjunctive SRS, and who subsequently developed LMD were combined from 7 tertiary care centers. Pts with classically radiosensitive tumors or prior or planned whole brain radiotherapy (WBRT) were excluded. ND was defined as symptomatic CNS progression around the time of death without life threatening systemic symptoms or progression. Salvage radiotherapy (RT) for LMD was categorized according to use of WBRT vs. focal cranial RT. Results: The study cohort consisted of 147 pts, of which 125 had died with known cause, 107 also received LMD salvage tx, and 82 also had cranial MRI follow-up. The ND rate in the 125 pts who died with known cause was 79%; the rate in pts who underwent LMD salvage tx (n = 107) was 76%. Univariate logistic regression demonstrated radiographic pattern of LMD (cLMD vs. nLMD, odds ratio [OR] 2.9, p = 0.04) and 2nd LMD failure after salvage tx (OR 3.9, p = 0.02) as significantly associated with ND. The ND rate was 86% for cLMD vs. 68% for nLMD pattern. WBRT was used in 95% of pts with cLMD vs. 52% of pts with nLMD. In the nLMD cohort (n = 58), there was no difference in ND rate based on type of salvage RT (WBRT: 67% vs. focal cranial RT: 68%, p = 0.92). Second LMD failure (vs. not) was associated with higher ND in the nLMD cohort (77% vs. 52%, p = 0.02). Of the 26 pts with nLMD who experienced 2nd LMD failure, 7 had classical 2nd LMD, of which 100% experienced ND, and 19 had nodular 2nd LMD, of which 68% experienced ND (p = 0.09). Conclusions: LMD after surgery and SRS for brain metastases is a clinically significant event with high rates of neurologic death. Classical LMD pattern (vs. nodular) and 2nd LMD failure after salvage tx were significantly associated with higher risk of neurologic death. In the nodular LMD cohort, radiographic pattern of 2nd LMD may be associated with risk of subsequent neurologic death. Pts with nodular LMD treated with salvage focal cranial RT or WBRT had similar risk of neurologic death. Methods to decrease LMD and the subsequent high risk of neurologic death in this setting warrant investigation.
Genomic profiling of breast cancer brain metastases reveals targetable alterations.
Authors: Kabraji Sheheryar Kairas , Spurr Liam F. , Hughes Melissa E , Li Yvonne Y. , Leone Jose Pablo , Garrido-Castro Ana Christina , Barroso-Sousa Romualdo , Files Janet , Kirkner Gregory , Johnson Bruce E. , Winer Eric P. , Cherniack Andrew D. , Lin Nancy U. 
Published: May 2020

2525 Background: Genomic characterization of breast cancer brain metastases (BCBMs) has thus far been limited. The objective of this study was to describe the landscape of genomic alterations in patients (pts) with BCBMs. Methods: Targeted next-generation DNA sequencing of > 300 cancer-related genes (OncoPanel) was prospectively performed on primary and metastatic (met) tumors in 321 pts with a diagnosis of BCBM between August 2016 and April 2019 at Dana-Farber Cancer Institute (table). Enrichment analysis of genomic alterations was performed using a two-sided Fisher exact test and differences in tumor mutation burden (TMB) between groups were assessed using two-sided Mann-Whitney U test. Multiple comparison correction was performed using the Benjamini-Hochberg procedure. Results: All subtypes were represented in BCBM (25 HR+/HER2-; 24 HR+/HER2+; 27 HR-/HER2+; 18 TNBC; 5 unknown; n = 99) and extracranial (EC) samples: (96 HR+/HER2-; 32 HR+/HER2+; 22 HR-/HER2+; 41 TNBC; 31 unknown; n = 222). BCBMs were found most commonly to have mutations or copy number alterations in TP53, ERBB2, PIK3CA, GATA3, PTEN, ESR1, CDH1, BRCA2, ARID1A, BRCA1 (>5% frequency, table). Two pts acquired ERBB2 amplification (amp) between the matched primary breast sample and brain met. In pair-wise comparisons of BCBMs to unmatched primaries or EC mets, only ERBB2 amp was significantly enriched (table, † = adjusted p < 0.05). There was no significant difference in TMB between BCBM and EC mets (median 9.12 vs 7.26, p = 0.15). In contrast, TMB was significantly higher in BCBMs compared to unmatched primaries (median 9.12 vs 7.26, p=0.005). Conclusions: BCBMs display similar mutations and copy number alterations compared to primary tumors and EC mets in pts with BCBM. These data suggest that BCBMs contain actionable genomic alterations that are most often also reflected in EC disease. Alterations in ERBB2, PIK3CA/PTEN, and BRCA1/2 represent potentially targetable alterations in pts with BCBM. [Table: see text]
A phase I clinical trial on intratumoral and intracavitary administration of ipilimumab and nivolumab in patients with recurrent glioblastoma.
Authors: Schwarze Julia Katharina , Duerinck Johnny , Dufait Ines , Awada Gil , Klein Samuel , Fischbuch Lydia , Seynaeve Laura , Vaeyens Freya , Rogiers Anne , Everaert Hendrik , Vanbinst Anne-Marie , Michotte Alex , Neyns Bart 
Published: May 2020

2534 Background: Intravenous (IV) administration of ipilimumab (IPI) and nivolumab (NIVO) has low activity in recurrent glioblastoma (rGB). Intratumoral (IT) and intracavitary (IC) administration of IPI and NIVO is under evaluation in the GlITIpNi phase I clinical trial. Methods: Patients (pts) with resectable rGB were recruited to cohorts C1, C2 and C4; pts with non-resectable rGB were recruited in C3 (biopsy only). IT administration (brain tissue lining the resection cavity during surgery) of IPI (10 mg)(C1), or IPI (5 mg) plus NIVO (10 mg)(C2, C3 and C4), was followed by IC administration of NIVO at escalating doses of 1, 5 or 10 mg Q2w in both C3 and C4 (via an Ommaya reservoir). In all cohorts, pts received 10 mg NIVO IV Q2w (6x in C1/C2, and 12x in C3/C4). Corticosteroids were contraindicated. Results: Forty-six pts (31 male; median age 56y (38-74); IDH1 R132H mutation in 2 pts in C1/C2; NGS somatic mutation analysis for C3/C4 ongoing) with rGB following resection, RT and temozolomide were enrolled (3, 24, 13 and 6 pts in C1, C2, C3 and C4, respectively). All pts received IT administrations. Pts in C1/C2 received a median of 5 IV NIVO administrations. Study treatment has been completed in all pts in C1/C2, in 9 pts in C3, and in 3 pts in C4; pts received a median of 4 (0-10) and 3 (0-7) postoperative IC/IV administrations in C3 and C4, respectively. Two pts in C2 and 1 pt in C3 had an increased perilesional cerebral edema (G3) with neurological deterioration after surgery/IT-injection, that was reversible with steroids. Most frequent AE were fatigue (32 pts, 64%), fever (20 pts, 44%), and headache (25 pts, 50%). In 4 pts from C3, the Ommaya was removed because of bacterial colonization (asymptomatic). There were no G5 AE. There was no dose/AE correlation with increasing IC NIVO doses in C3/C4. Repetitive CSV analysis during therapy (C3/C4) revealed increased lymphocyte counts in 4 pts; scRNA- and TCR-sequencing is ongoing. Gene expression profiling for C1/C2, and pharmacokinetic analysis of NIVO and IPI in CSV for C3/C4 are ongoing. After a median FU of 62w (16-165) for pts in C1/C2, 16 pts have died; median OS is 71w (95% CI 8-134), 1- and 2y-OS% are respectively 51% (95% CI 31-71), and 34% (95% CI 10-59). OS compares favorably to a historical cohort of Belgian rGB pts (n = 469; Log-Rank p .001). After a median FU of 10w (1-37) for pts in C3/C4, 2 pts have died; median OS has not been reached. One pt in C3 achieved a PR that is ongoing at 12m. Conclusions: IT/IC administration of NIVO and IPI is feasible and sufficiently safe to warrant further investigation in pts with rGB. Clinical trial information: NCT03233152 .
Defining the prognostic role of MGMT methylation value by pyrosequencing assay in glioblastoma patients: A large Italian multicenter study.
Authors: Lombardi Giuseppe , Simonelli Matteo , Bellu Luisa , Villani Veronica , Rizzato Simona , Ius Tamara , Pasqualetti Francesco , Russo Marco , Franchino Federica , Rosina Amoroso , Bertorelle Roberta , Cavallin Francesco , Dipasquale Angelo , Carosi Mariantonia , Pizzolitto Stefano , Cesselli Daniela , Gardiman Marina Paola , Caccese Mario , Padovan Marta , Zagonel Vittorina 
Published: May 2020

2539 Background: MGMT methylation (MGMTmet) status represents an important prognostic factor for glioblastoma (GBM) patients (PTS). Quantitative pyrosequencing approach has proven to be feasible for MGMTmet testing but its value is still unclear. We performed a large, multicentre, retrospective study to identify the association between MGMTmet values and clinical outcome. Methods: from 9 Italian neuro-oncology centres, we collected consecutive GBM PTS with assessment of MGMTmet by pyrosequencing approach evaluating CpG islands from 75 to 84. Other inclusion criteria were: histological diagnosis of GBM, ECOG PS ≤2, therapy with RT+TMZ. Kaplan-Meier method was used to estimate the survival curves, time-dependent ROC curve for defining the optimal cut-off value of mean percentage of MGMTmet in terms of 2y-OS, Cox regression for multivariable analysis, and restricted cubic spline to investigate the non-linear association between methylation values and OS. Results: 681 PTS were enrolled; median age was 60 ys; ECOG PS was 0 in 292 PTS, 1 in 306 PTS, 2 in 83 PTS; 391 PTS (58%) had a complete resection. 8% of PTS received a second surgery. IDH was mutated in 6%. 2y-OS was 31.6%, median OS was 17.4 ms. Median MGMTmet was 3.5% (IQR 0-22%). ROC curve identified a cutoff of 15% of MGMTmet in terms of 2y-OS (sens 78%, spec 57%, AUC = 0.67). 2y-OS was 19.7% and 53.7% for PTS with MGMTmet < and ≥15%, respectively (p < 0.0001). At multivariable analysis, MGMTmet < 15% was associated with impaired survival (HR 2.7, 95% CI 2.1-3.4; p < 0.00001), adjusting for age, KPS, type of surgery and second surgery. A non-linear association between MGMT methylation and survival was identified (non-linear term: p < 0.0001), with lower values of MGMT methylation associated with lower survival; indeed, estimated median OS was lowest (14 months, 2ys-OS: 17.4%) with MGMTmet of 4%, 21ms (2yr-OS: 40.9%) with MGMTmet of 20%, 27ms (2yr-OS: 40.9%) when MGMTmet was 40%, then leveled around 30ms (2yr-OS: 54.5-59.8%) when MGMTmet was > 40%. Conclusions: this study represents one of the largest trials analyzing MGMTmet by pyrosequencing approach. Lower values of MGMTmet were associated with impaired survival and the relationship was non-linear. Noteworthy, we identified a strong prognostic value of MGMTmet which could be used as stratification factor in prospective clinical trials
Superior therapy response predictions for patients with low-grade glioma (LGG) using Cellworks Singula: MyCare-009-04.
Authors: Ahluwalia Manmeet Singh , Watson Drew , Kapoor Shweta , Parashar Rajan , Ghosh Roy Kunal Ghosh , Alam Aftab , Rajagopalan Swaminathan , Tyagi Anuj , Sahu Diwyanshu , Suseela Rakhi Purushothaman , Ganesh Naga , Nair Prashant , Birajdar Shivgonda , Raju Karthik Sundara , Gopi Reshma , G Poornachandra , Gupta Neha , Lunkad Neelesh , Patil Vivek , Wen Patrick Y. 
Published: May 2020

2569 Background: Despite using cytogenetic and molecular-risk stratification and precision medicine, the current overall outcome of LGG patients remains relatively poor. Therapy selection is often based on information considering only a single aberration and ignoring other patient-specific omics data which could potentially enable more effective treatments. The Cellworks Singula report predicts response for physician prescribed therapies (PPT) using the novel Cellworks Omics Biology Model (CBM) to simulate downstream molecular effects of cell signaling, drugs, and radiation on patient-specific in silico diseased cells. We test the hypothesis that Singula is a superior predictor of progression-free survival (PFS) and overall survival (OS) compared to PPT. Methods: Singula’s ability to predict response was evaluated in an independent, randomly selected, retrospective cohort of 137 LGG patients aged 14 to 73 years treated with PPT. Patient omics data was available from TCGA. Singula uses PubMed to generate protein interaction network activated and inactivated disease pathways. We simulated the PPT for each patient and calculated the quantitative drug effect on a composite LGG disease inhibition score based on specific phenotypes while blinded to clinical response. Univariate and multivariate proportional hazards (PH) regression analyses were performed to determine if Singula provides predictive information for PFS and OS, respectively, above and beyond age and PPT. Results: In univariate analyses, Singula was a significant predictor of both PFS (HR = 3.587, p < 0.0001) and OS (HR = 3.044, p = 0.0007). In multivariate PH regression analyses, Singula (HR = 3.707, p < 0.0001) remained an independent predictor of PFS after adjustment for PPT (p = 0.3821) and patient age (p = 0.0020). Singula (HR = 2.970, p = 0.0013) was also a significant independent predictor of OS after adjustment for PPT (p = 0.0540) and patient age (p < 0.0001). Results indicate that Singula is a superior predictor of both PFS and OS compared to PPT. Singula provided alternative standard of care therapy selections for all 34 disease progressors. Conclusions: Singula is a superior predictor of PFS and OS in LGG patients compared to PPT. Singula can correctly identify non-responders to PPT and provide alternative therapy selections.
Safety and efficacy results of GC027: The first-in-human, universal CAR-T cell therapy for adult relapsed/refractory T-cell acute lymphoblastic leukemia (r/r T-ALL).
Authors: Wang Xinxin , Li Shiqi , Gao Lei , Yuan Zhongtao , Wu Kun , Liu Lin , Luo Le , Liu Yao , Zhang Cheng , Liu Jia , Yang Chunhui , Li Yu , He Jiaping , Ye Xun , Li Zhimin , Tan Xu , Ge Jianning , Cao Wei , Wang Sanbin , Zhang Xi 
Published: May 2020

3013 Background: Patients with r/r T-ALL usually have high relapse and mortality rates. Due to shared common surface antigen and potential contamination by malignant cells, development of autologous CAR-T therapies for r/r T-ALL has been lagged, regardless of the costly and lengthy process of autologous CAR-T production. Through targeting CD7, a common T cell antigen highly expressed in >95% T-ALL samples, universal CAR-T product GC027 has been developed using lentivirus and CRISPR/Cas9 system with demonstrated anti-leukemia ability in a murine xenograft model. Methods: Preliminary safety, anti-leukemic activity and expansion kinetics of GC027 are being evaluated in a single-arm, open-label, multi-center, prospective study for treating adult patients with r/r T-ALL. To date, a total of 5 patients (age 19-38 yrs, median 24 yrs) were enrolled with marrow tumor load 4-80.2% (median prior lines 5). All 5 pts have received a 6-day enhanced preconditioning chemotherapy followed by a single infusion of GC027. No patient was bridged to HSCT. Adverse events, disease response, and expansion kinetics were evaluated in this study. Results: As of Feb. 6, 2020, 5 pts had received a single dose of GC027, including 1 at 0.6x107/kg, 3 at 1x107/kg, 1 at 1.5x107/kg. 3 pts achieved MRD negative complete responses (MRD- CR) at D28 evaluation and remained MRD- at follow-up re-evaluations (161, D118, 61, respectively) without bridging to HSCT. 1 pt just achieved D28 MRD- CR at time of submission. 1 pt achieved MRD+ CR at D14, but his disease progressed at D29 and deceased due to relapse. In all 4 pts with MRD- CR, peak expansions of GC027 in peripheral blood were observed between week 1-2, analyzed by flow cytometry and Q-PCR. Grade 3 cytokine release syndrome (CRS) occurred in 4 pts and Grade 4 CRS occurred in 1 pt (ASBMT Consensus Grading). CRS symptoms were manageable and resolved after treatment and supportive care. None developed neurotoxicity or GvHD. One had prolonged cytopenia due to fungal infection and required anti-fungal therapy. Conclusions: With a single infusion of GC027, 80% of the patients had robust CAR-T cell expansion and achieved persistent MRD- CR without using any biologics as part of the preconditioning therapy or bridging to HSCT. The first-in-human, universal CAR-T therapy for r/r T-ALL, GC027 has demonstrated superior clinical efficacy and induced deep response in patients with acceptable safety profile. The trial enrollment is ongoing and updated data will be presented at the meeting. Clinical trial information: ChiCTR1900025311 .
Impact of radiotherapy on risk of adverse events in patients receiving immunotherapy: A U.S. Food and Drug Administration pooled analysis.
Authors: Anscher Mitchell Steven , Arora Shaily , Weinstock Chana , Lubitz Rachael , Amatya Anup , Fiero Mallorie , Tang Shenghui , Bandaru Pradeep , Sanchez Jacquelyn , Girvin Andrew , Tang Chad , Amiri-Kordestani Laleh , Theoret Marc Robert , Pazdur Richard , Beaver Julia A. 
Published: May 2020

3018 Background: Immune checkpoint inhibitors (ICIs) are widely used in the treatment of multiple advanced malignancies. Radiotherapy (RT) has been used in combination with ICIs to activate tumor-specific T cell responses, and RT also promotes non-specific acute and chronic inflammatory responses both locally and systemically. More than 50% of patients receive RT at some point during their course of cancer therapy, and relatively little information is available pertaining to the impact of RT, if any, on the risk of adverse events (AEs) in patients receiving ICIs. Methods: Pooled data from prospective trials of ICIs submitted to the FDA in initial or supplemental BLAs or NDAs through 12/2019 were included (N=66). Trials from applications that were withdrawn or not approved were not included. Patients were subdivided by whether or not radiotherapy was administered at any time during the course of their cancer treatment. AEs common to both ICI treatment and RT were identified to focus on the following reactions: neutropenia, thrombocytopenia, colitis, hepatitis, pneumonitis, and myocarditis. Descriptive statistics were used to examine AEs associated with the use of radiation and ICIs. Results: A total of 25,836 patients were identified, of which 9087 (35%) received RT and 16,749 (65%) did not. Radiation was associated with similar rates of AEs overall with numerically higher hematologic toxicities and pneumonitis and numerically lower colitis, hepatitis and myocarditis (Table). Patients receiving RT were more likely to experience Grade 3-5 hematologic toxicities compared to those not receiving RT. Conclusions: To our knowledge, this is the largest report of AE risk associated with the use of radiation and ICIs. Our results show that the incidence of hematologic toxicity and pneumonitis in patients receiving RT may be slightly higher. Analysis to determine comparability of baseline demographic characteristics, comprehensive AE profile, and timing of RT is underway. [Table: see text]