bluuebunny/crossref_metadata_2025_split huggingface dataset:
Albumin levels and Prognostic Nutritional Index in glioblastoma.
Authors: Saeed Bamashmos Anas , Barnett Addison , Ali Assad , Li Hong , Angelov Lilyana , Barnett Gene H. , Mohammadi Alireza Mohammad , Chao Samuel T. , Yu Jennifer S. , Murphy Erin Sennett , Suh John H. , Stevens Glen , Peereboom David M. , Ahluwalia Manmeet Singh , Wei Wei (Auston) 
Published: May 2019

e13567 Background: Albumin levels are widely used to estimate patients’ nutritional status. Low perioperative albumin levels are associated with worse outcomes. Moreover, Prognostic Nutritional Index (PNI), which is calculated from serum albumin levels and peripheral blood lymphocyte count as follows: PNI = (Albumin x 10) + (0.005 x ALC), has been used to predict both short and long term outcomes in patients with wide variety of tumors. The primary objective of this study was to characterize perioperative albumin levels and PNI in newly diagnosed GBM patients. Secondary objectives included associations between albumin levels and PNI on progression free survival (PFS) and overall survival (OS). Methods: We retrospectively reviewed 568 newly diagnosed GBM patients who underwent surgery followed by standard of care chemoradiation. We analyzed the association between albumin and PNI on age, sex, MGMT methylation status, and extent of surgical resection on PFS and OS using a multivariate Cox proportional hazard model. Results: Of the 568 patients collected, 355 (62.5%) were males, 158 (27.8%) had gross total resection of the tumor, and 197(42.5%) were MGMT methylated. Both albumin and PNI were associated with OS but not PFS. The hazard ratio (HR) for OS among the top 2 quartiles of both albumin level and PNI were significantly higher than the bottom two quartiles. The median albumin level was 4.0 and the median PNI was 40. The point for significant high hazard ratio (HR) was around median value for both Albumin and PNI based on restricted cubic spine Cox regression models. The Kaplan-Meir (KM) estimated median OS was 15.2 months for albumin > 4, and 7.6 for albumin ≤4. The KM estimated median OS was 14.6 months for PNI > 40, and 5.7 for PNI≤40 (P logrank < 0.001 for both). While controlling for other factors that may also be associated with early death including age, gender, surgery type and MGMT status, HR = 1.9 (95% CI = 1.4- = 2.6) for Albumin < 4, and HR = 2.1 (95% CI = 1.5- 3.0) for PNI < 40 compared to their counterpart. Conclusions: Glioblastoma patients with perioperative albumin > 4 had a median OS of 15.2 months and 7.6 months for albumin ≤4, and a median OS of 14.6 months for PNI > 40 and 5.7 months for PNI≤40 (P logrank < 0.001 for both).
Impact of EGFR amplification status in newly diagnosed glioblastoma treated with Stupp protocol.
Authors: Barnett Addison , Saeed Bamashmos Anas , Ali Assad , Jia Xuefei , Wei Wei (Auston) , Sagar Soumya , Barnett Gene H. , Angelov Lilyana , Mohammadi Alireza Mohammad , Peereboom David M. , Stevens Glen , Suh John H. , Murphy Erin Sennett , Yu Jennifer S. , Ahluwalia Manmeet Singh 
Published: May 2019

e13569 Background: Standard post-surgical glioblastoma (GBM) treatment, per Stupp protocol, includes six-weeks of concurrent Temozolomide chemoradiation followed by at least six cycles of adjuvant-Temozolomide. Previous investigations into epidermal growth factor receptor (EGFR) amplification as a prognostic factor in GBM have yielded contradicting results, requiring further investigation. The primary aim of this study was to determine the degree to which EGFR amplification, in newly diagnosed GBM, impacted progression free survival (PFS) and overall survival (OS). Methods: Data from 582 patients who underwent surgical intervention for GBM at a tertiary care institution between 2012 and 2018 were analyzed. Only adult patients who underwent treatment per Stupp protocol and had pathological analysis on EGFR and CEP7 were included. Amplification and non-amplification status was calculated by a ratio of EGFR/CEP7 > 2 and < 2, respectively. PFS and OS outcomes were compared using Cox proportional hazard models stratified by surgery type and sex. Results: Of the original 582 patients, 122 were treated per Stupp protocol and had documented EGFR analysis. Of patients who were EGFR amplified, 41 (58.5%) were male and 25 (48.1%) were female (p = 0.38) and median amplification was 1.07 and 1.16 (p < 0.001), respectively. EGFR non-amplified patients had a PFS hazard ratio, HR = 0.70 (95% CI = 0.44 – 1.12, p = 0.14); and an OS HR = 0.60 (95% CI = 0.35 – 1.03, p = 0.065). When the EGFR/CEP7 ratio was stratified by quartile, it was found that Q4 compared to Q1 (Q4 > 6.50 vs 0 < Q1 ≤ 1.06) had a PFS HR = 2.1 (95% CI = 1.11 – 4.07, p = 0.024); and an OS HR = 2.48 (95% CI = 1.10 – 5.60, p = 0.028). Conclusions: There was no statistical difference in prevalence of EGFR amplification by sex. However, despite statistical significance, there was minimal difference in median degree of amplification by sex (0.09). Trends begin to show that patients who were EGFR non-amplified had better PFS and OS outcomes than patients who were EGFR amplified, although this was not statistically significant. Patients with very high EGFR amplification (Q4) had significantly poorer PFS and OS outcomes than patients with very low EGFR amplification (Q1).
Avelumab in newly diagnosed glioblastoma multiforme: The SEJ study.
Authors: Jacques Francois Henri , Nicholas Garth , Lorimer Ian , Sikatifoko Victorine , Prévost Jasmine 
Published: May 2019

e13571 Background: Glioblastoma Multiforme (GBM) has well documented systemic and local immunosuppressive mechanisms to escape immune surveillance and grow. GBM tumor cells as well as the microglia within it have a high PD-L1 surface expression which may make it susceptible to anti-PD-L1 antagonism and ADCC with avelumab therapy. Standard combination temozolomide/radiotherapy is associated with a median survival of 14.6 months and a median progression free survival of 6.9 months. Methods: This is a single center, phase 2, open label study of avelumab 10 mg/kg Q2W for 156 weeks duration in patients receiving standard therapy for newly diagnosed GBM. Thirty patients will be entered into the study within 3 weeks of completing combined radiotherapy/temozolomide. Here, we report the results of the first interim analysis completed when the first eight patients completed 52 weeks or an end of study visit. Results: To date 24 patients have started therapy. The median follow-up is 4.9 months (1-22 months). There has been overall no unexpected treatment emergent adverse event (TEAE). The most common TEAE was elevated liver or pancreatic enzymes. Two patients transiently withheld therapy because of immune related TEAE’s (both hepatitis) and none permanently. The objective response rate by iRANO criteria, at week 52 for the first eight patients was 4 (50%) with 2 (25%) having a complete response, 1 (12.5%) a partial response and 1 (12.5%) stable disease. The median progression free survival was 11.9 months. Conclusions: These preliminary results suggest that the addition of avelumab to standard combination therapy early on, in patients with GBM is safe. Efficacy trends look promising. Clinical trial information: NCT03047473.
Hyperprogressive disease in patients with recurrent high grade gliomas treated with immune checkpoint inhibitors or other therapies.
Authors: Donovan Laura , Gedailovich Samuel , Joanta-Gomez Adela , Schulte Jessica , Kreisl Teri Nguyen , Lassman Andrew B. , Welch Mary Roberta , Haggiagi Aya , Iwamoto Fabio Massaiti 
Published: May 2019

e13575 Background: Hyperprogressive disease (HPD) has been described in solid tumor patients treated with immune checkpoint inhibitors (ICI). HPD is defined as a ≥2-fold increase in tumor growth rate (TGR) following initiation of ICI. HPD has not been explored in patients with high grade gliomas (HGG) on ICI or standard cytotoxic regimens. In advanced cancer patients receiving ICI, MDM2/4 amplification or EGFR alterations, both found in HGG, correlated with HPD. We compared the rate of HPD in recurrent HGG patients receiving ICIs to those treated with non-immunotherapy agents. Methods: Patients with HGG on ICIs for 1st or 2nd recurrence were compared to a control group receiving other therapies at 1st recurrence. Patients with prior or concurrent bevacizumab or anti-VEGFR were excluded due to pseudoresponse and decreased enhancement with these drugs. HPD was calculated by comparing TGR immediately before and after treatment. Results: 49 patients met inclusion criteria (27 ICI, 25 control). 25/27 patients treated with ICIs and 20/22 patients in the control group had complete imaging and were eligible for analysis. In the ICI group, 60% were men (15/25) and 88% (22/25) had a diagnosis of GBM. 68% were treated at first progression (17/25). Controls were 80% male (16/20) and all had a diagnosis of GBM. 30% (6/20) were 65 years or older at diagnosis in the control group compared to 28% (7/25) in the ICI group. In total, 7/25 patients met criteria for HPD in the ICI group (28%) compared to 4/20 patients in the control group (20%). 10/25 patients (5/7 with HPD) in the ICI group and 8/20 patients (2/4 with HPD) in the control group had next generation sequencing of their tumors. EGFR alterations and MDM2/4 amplifications were not associated with HPD whereas PTEN mutations were more common in the HPD group (71% HPD vs. 33.3% no HPD). Conclusions: HPD is observed in patients with HGG treated with ICI at comparable rates to those with other cancers, but was also observed in 20% of patients receiving other therapies. While the numbers are small, PTEN mutations may be associated with HPD in patients with HGG. In contrast to other solid tumors, EGFR alterations and MDM2/4 amplifications were not associated with HPD in HGG.
First-line stereotactic radiosurgery combined with systemic targeted and immune checkpoint inhibitor therapy in melanoma patients with newly diagnosed brain metastases.
Authors: Heumann Thatcher Ross , Wu Peter , Ye Rebecca , Sansosti Alexandra , Habibi Akram , Kryger Marc , Beaudreault Cameron , Bernstein Kenneth , Silverman Joshua Seth , Weber Jeffrey S. , Pavlick Anna C. , Kondziolka Douglas 
Published: May 2019

e13577 Background: Of solid tumors, melanoma has the highest propensity for central nervous system spread with historic median survivals of 5-8 months following brain metastasis diagnosis. We evaluated the impact of systemic BRAF targeted and immune checkpoint inhibitor (ICI) therapies on survival outcomes in patients receiving stereotactic radiosurgery (SRS) for melanoma brain metastases (MBM) and assessed patient treatment burden associated with prolonged survival. Methods: We retrospectively reviewed the demographics, disease characteristics, therapeutic regimens, overall survival, and first-year cumulative incidence of comorbid disease for patients with de novo MBM treated between 2013 and 2017 at a major melanoma referral center. Results: Among 123 newly diagnosed MBM patients:65% were male, 24%were 50 years old or less, 50% were BRAF mutated, 63% had multiple intracranial lesions at diagnosis . Locally, 73% received SRS as first-line treatment.Systemically, 73% received ICI, 46% received BRAF targeted therapy, and 12% received neither. With median follow up of 11 months (mo), totalcohort median OS was 13.2 mo, 20.5 mo for BRAF mutated patients, 10.8 mo for BRAF wild-type patients. Median OS for first-line SRS was 31.0 mo (47% 3-year OS) when combined with both ICI and BRAF targeted therapy, 17.5 mo (31% 3-year OS) when combined with ICI monotherapy, and 6.1 mo (22% 3-yr OS) with neither systemic therapy. SRS and BRAF targeted therapy were associated with improved OS. BRAF status, ICI therapy, intratumoral hemorrhage were not significant prognosticators for OS.At one-year follow-up, comorbid conditions with the greatest cumulative incidence were fatigue, nausea, intracranial hemorrhage, deep vein thrombosis, major depressive disorder, and pneumonia. Patients averaged one inpatient visit every 4.5 mo (1 week average length of stay), and 2 advanced imaging studies (MR/CT/PET-CT) per month following MBM diagnosis. Conclusions: In one of the largest reported MBM series, survival has improved markedly for patients receiving first-line brain radiosurgery combined with BRAF targeted therapies and immunotherapies. Simultaneously, longer life expectancy comes with increasing incidences of comorbid conditions reflecting an evolving complexity of and need for coordination of care for patients with MBM.
Integrating salvage hypofractionated radiosurgery plus low-dose adjuvant bevacizumab for locally recurrent brain metastasis with high dose irradiation previously.
Authors: Guan Yun , Zhu Huaguang , Wang Chaozhaung , Li Jing , Xu Wenqian , Sun Lei , Pan Li , Dai Jiazhong , Wang Yang , Wang Enmin , Wang Xin 
Published: May 2019

e13579 Background: Treatment for recurrent brain metastasis remains uncertain. The purpose of this research was to evaluate the efficacy and toxicity of FSRS with adjuvant bevacizumab as a new salvage treatment for locally recurrent brain metastases with high dose irradiation previously. Methods: Patients with locally recurrent intracranial metastasis with irradiation previously were enrolled in this prospective study. Salvage FSRS dose ranged from 9.5 to 29 Gy in two to five sessions with 62–75% isodose line. Adjuvant bevacizumab was prescribed four cycles (5 mg/kg, q3w). Magnetic resonance imaging (MRI), Karnofsky Performance Scale (KPS), adverse events and clinical outcomes were recorded. The primary objective of this study was to identify the overall survival after salvage treatment. Secondary objectives included clinical response (KPS), imaging response (MRI) and adverse events. Results: From December 2009 to October 2016, 24 patients were enrolled. Of these patients, 9 received WBRT followed by SRS, and 15 underwent SRS. The median 1-year overall survival (OS) after salvage SRS was 87.5%. No treatment-related grade 4 adverse events were recorded. Grade 1/2 fatigue was observed in 8 (33%) patients followed by headache, hypertension and nausea. Grade 3 fatigue and headache occurred in 1 patient. No grade 4 toxicity was observed. Conclusions: Salvage FSRS with early use of low dose adjuvant bevacizumab treatment showed favourable clinical and radiologic control with manageable toxicity for locally recurrent brain metastasis patients who underwent high dose irradiation previously. The diagnosis of RN and LR after salvage FSRS merit further study. [Table: see text][Table: see text][Table: see text]
Effect of oligometastatic disease management with stereotactic body radiation therapy on survival in patients with metastatic lung cancer.
Authors: Raez Luis E. , Botero Ana , Castillo Miguel , Castellon Ignacio , Hunis Brian , Falchook Aaron 
Published: May 2019

e13582 Background: Overall survival (OS) of metastatic non-small cell lung cancer (NSCLC) patients (pts) is improving with the development of targeted therapies (TARGET) and immunotherapy (IMMUNO), however is limited by disease progression (PD) which necessitates a change in systemic therapy. Stereotactic body radiation therapy (SBRT) can allow NSCLC pts to stay longer with the same therapy by eliminating oligometastatic progression (OMP) improving progression free survival (PFS) and OS. Methods: 100 pts with metastatic NSCLC undergoing chemotherapy (CHEMO), IMMUNO or TARGET that had OMP defined as less than 4 sites of metastasis and underwent SBRT were evaluated for PFS and OS. PFS1: Time between initiation of systemic therapy and development of OMP. PFS2: Time between OMP treated with SBRT and development of further PD requiring a change in systemic therapy. Pts received IMMUNO for second line and beyond. Robotic SBRT was delivered in 1-5 fractions on consecutive days or every other day. SBRT doses were determined based on the disease site and dose tolerance of the adjacent organs. Results: Brain metastasis (BM) were seen in 45 pts and 55 pts had extracranial metastasis (EM). 34 pts were receiving CHEMO, 34 Target and 32 IMMUNO at the time of OMP. Main endpoints (m) are shown (Table) Pts with BM that received SBRT were able to continue the same therapy for a period of 6.5-9 extra months due to the control of BM. Pts with EM that have developed PD were able to continue the same therapy 17-21 extra months due to the ablation of OMP by SBRT. Overall PFS was: 16.5m for BM and 34m for EM and the OS were: 31m and 53m respectively. Conclusions: Substantial prolongation was observed in PFS/OS compared with historical controls thanks to the use of SBRT in pts that develop OMP while on systemic therapy. SBRT allowed patients to continue with the same systemic treatment. Our CHEMO cohort is composed of long term survivors under therapy and may not represent the average PFS/OS of pts on CHEMO. Survival data from prospective trials will be essential in determining the value of this resource-intensive treatment.[Table: see text]
A new option in brain-metastases: Hippocampal-sparing whole-brain radiotherapy with simultaneous integrated boost VMAT-IGRT.
Authors: Marin Alicia , Martin Margarita , Gonzalez Emma , Torres Lisselott , Hernandez David , Casado Margarita , Montijano Miguel , Lopez Mario , Castro Pablo , Cerezo Laura , Perez Leopoldo , Murillo Maria Teresa 
Published: May 2019

e13589 Background: We report our experience with volumetric modulated arc therapy (VMAT-IGRT) use to plan and deliver whole brain radiotherapy whit a simultaneous integrated boost in patients with brain metastases, using hippocampal sparing. Methods: In this retrospective study 57 patients with brain metastases were treated with radiotherapy VMAT-IGRT were administered in 12 daily fractions of 2.7Gy for a total of 32.4Gy (EBD 40Gy) to whole-brain and simultaneous integrated boost to brain metastases, multiple targets, in 12 fractions to 3.4Gy for a total dose of 40.8Gy (EBD 60Gy). The primary endpoint was intracranial progression-free survival (PFS) and secondary endpoints were preserves neurocognitive function and overall survival (OS). Survival rates were determined by Kaplan-Meier method. Differences between survival curves were analyzed by the log-rank test. Results: From January 2015 to December 2018, 57 patients were enrolled. The median follow-up time was 7 months. PFS6, PFS12 and PFS18 were 91.3%, 70.8% and 70.8% respectively. mOS, OS6, OS12 and OS18 were 10 months (95% IC 4.2-15.7 months), 67.2%, 48.6% and 35.3% respectively. Response rates were as follows: 29RC (50.9%), 21RP (36.8%), 7SD (12.3%) and 0PD (0%). Long progression-free survival patients: PFS > 12, 15 and 18 months for initial diagnosis 70%, 70% and 70% respectively. Conclusions: Whole-brain radiotherapy with simultaneous integrated boost to brain-metastases: VMAT-IGRT is safe and promising and possibly produces survival and tolerance benefits. Sparing the hippocampus during cranial irradiation poses important technical challenges with respect to contouring and treatment planning.
Active postmarketing surveillance: Results from a manufacturer's patient support program for patients under treatment with the first biosimilar trastuzumab (MYL-1401O) approved in Brazil.
Authors: Silva Allisson Monteiro da , Dib Gislaine Villarta Capeleti , Saraiva Emanuela Lopez Fernandes , Watanabe Thais Tiemi , Paulo Jaqueline Amália de 
Published: May 2019

e14000 Background: The development of biosimilars is increasing around the world, and facilitates patient’s access to these high-tech therapies. Active pharmacovigilance is considered one of the main tools for monitoring the safety of biologics and biosimilars, especially in post marketing. In 2017, trastuzumab (MYL-1401O) became the first trastuzumab biosimilar approved in Brazil. A program to support patients under trastuzumab (MYL-14010) treatment was sponsored by the manufacturer in order to closely monitor adverse events (AE). Methods: This is a prospective observational study based in data from a manufacturer’s patient support program. Patient diagnosed with initial or advanced HER2+ breast cancer (BC) and HER2+ gastric cancer (GC) who received prescription for trastuzumab (MYL-1401O) were invited to participate. They are followed by periodical phone calls after each infusion and up to 3 months after the last infusion of trastuzumab. Treatment related data and AEs were collected. Results: A total of 21 female patients with HER2+ BC receiving trastuzumab (MYL-14010) were enrolled in the program between May 2018 and January 2019. 16 (76,2%) out of these patients with median age 52 years (range 33 to 76) reported 101 AEs (all-causality): 94 (93,1%) non-serious (73 expected / 21 unexpected) and 7 (6,9%) serious (5 expected / 2 unexpected). Considering all unexpected AEs causality assessment was unlikely in 47,8% AEs. The most frequently reported AEs according SOC (system organ classification) were general disorders and administration site conditions (18,8%), nervous system disorders (14,9%) and gastrointestinal disorders (14,9%). The most reported symptoms were nausea, asthenia, infusion reactions, paresthesias and pain in the body. Conclusions: Safety data for biosimilar trastuzumab (MYL-1401O) is consistent with original trastuzumab in female patients with HER2+ BC. Most of the reported AEs were non-serious (93,1%) and expected (77,2%). No new safety signals were detected.
Potent targeting of B cell lymphoma and plasma cell tumors by a tetravalent, Fc-engineered antibody directed against the glycoantigen CD75s.
Authors: Klausz Katja , Karimzadeh-Tabrizi Amir , Buck Malena , Otte Anna , Krohn Steffen , Kellner Christian , Klapper Wolfram , Peipp Matthias , Gramatzki Martin 
Published: May 2019

e14004 Background: Monoclonal antibodies are established treatment options for B cell-derived malignancies, but relapse is still the major challenge. Novel target structures may open alternative avenues to develop effective antibody therapies. Here, we characterized the novel tetravalent antibody ‘EBU-141 Tetra’ and identified the glycoantigen CD75s (α-2,6-sialylated lactosamines) as suitable target structure for antibody-based therapy. CD75s was detected on most B cell lymphomas, including Burkitt’s lymphoma, FL, DLBCL, MCL, CLL, and plasma cell tumors. Classical Hodgkin lymphomas were consistently negative while reactivity on individual cases of peripheral T cell lymphoma was seen. To evaluate CD75s as a target for antibody therapy, we generated a tetravalent, Fc-engineered chEBU-141 IgG1 antibody with enhanced avidity for CD75s and potent effector functions. Methods: ‘EBU-141 Tetra’ was produced by transient transfection and purified by affinity chromatography. Direct anti-tumor effects and Fc-mediated effector functions were investigated in cell proliferation assays, by fluorescence microscopy and in 51Cr release experiments using lymphoma and myeloma cell lines and patient-derived tumor cells. Peripheral blood mononuclear cells and monocyte-derived macrophages of healthy donors were used as human effector cells in the experiments. Results: ‘EBU-141 Tetra’ showed improved binding to CD75s on cell surface of mature B cell lymphoma as well as myeloma plasma cells compared to the conventional chimeric antibody chEBU-141 IgG1. The higher avidity for CD75s resulted in markedly improved ADCC activity of ‘EBU-141 Tetra’ against Daudi Burkitt’s lymphoma, U266 plasma cells and CLL patient-derived tumor cells with EC50 values in the low nanomolar range. In addition, ‘EBU-141 Tetra’ demonstrated efficient phagocytosis of Burkitt’s lymphoma and myeloma cell lines. Thus, the novel tetravalent, chimeric, Fc-engineered antibody ‘EBU-141 Tetra’ efficiently recruits immune effector cells for tumor cell lysis. Conclusions: Our findings further demonstrate that highly potent IgG-like antibodies against glycan-structures can be generated from mouse IgM antibodies and may open a new therapeutic window for therapy of patients with mature B cell lymphomas and multiple myeloma.