bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between IDH1 mutation status and magnetic resonance imaging features in WHO grade II and III oligodendroglial tumors.
Authors: Toulgoat Frederique , Arrigoni Pierre Paul , Loussouarn Delphine , Leux Christophe , Frenel Jean-Sebastien , Denis Marc G. , Le loupp Anne-Gaelle , Aumont Maud , Campone Mario , Martin Stephane , Desal Hubert 
Published: March 2020

2082 Background: In gliomas, relationship between radiological characteristics and several biomarkers was the subject of numerous publications. Mutations in the isocitrate dehydrogenase 1 (IDH1) gene have been identified recently to play a key role in these tumors occuring in up to 75% of low-grade diffuse (WHO grade II) and anaplastic (WHO grade III) astrocytic, oligodendroglial and mixed oligodendroglial neoplasms. However, the correlation with magnetic resonance imaging (MRI) features has been little studied. Methods: Patients treated for WHO grade II and III oligodendroglial tumors between 2005 and 2011 were retrospectively identified. Each case has been reviewed by the same neuropathologist. IDH1 and IDH2 mutations were available. Preoperative MRI, including T1 weighted, T2 weighted, T1 contrast enhanced, FLAIR, T2* weighted, diffusion weighted (ADC ratio), perfusion weighted (CBV ratio) and MR spectroscopy, were analyzed by two radiologists blinded from molecular data. Logistic regression analysis and Fisher’s test were used to develop predictive models of genetic profile from imaging. Results: Sixty eight patients, WHO grade II (n= 37) and grade III (n=31) patients were identified. Mean age at diagnosis was 46 years; ratio male/female was 40/28. IDH1 mutations were identified in 42 patients (62 %), IDH2 in 4 patients (6 %). Analysis of tumor location, size, borders, morphological aspect, and signal did not shown any significant difference between IDH1 mutated group and IDH1 non mutated group neither in grade II nor in grade III oligodendroglial tumors. In the same way, MR spectroscopy (Choline/NAA ratio and detection of lipid and lactate) was not relevant to discern the two groups. As well, ADC ratio (1,5 versus 1,4; p=0,35) and CBV ratio (3,4 versus 4,2; p= 0,46) did not reveal any difference between mutated group and non mutated group. Conclusions: In our study, IDH1 mutations were not correlated with MRI features available during routine MRI. Nevertheless, recent studies suggest the ability of MR spectroscopy to detect 2-hydroxyglutarate as an MRI marker of IDH1 mutated tumors, which encourage carrying on research in molecular imaging.
The final report of a phase I trial of surgical resection with biodegradable carmustine (BCNU) wafer placement followed by vaccination with dendritic cells pulsed with tumor lysate for patients with glioblastoma.
Authors: Rudnick Jeremy , Hu Jethro Lisien , Luptrawan Anne , Mazer Mia , Wheeler Chris , Nuno Miriam , Chu Ray M , Phuphanich Surasak , Black Keith L. , Yu John 
Published: March 2020

2084 Background: Our prior immunotherapy trials demonstrated efficacy in generating a tumor specific immune response in malignant glioma and the potential for high tumor-specific toxicity and sustained tumoricidal activity. Immunotherapy may synergize with chemotherapy and biodegradable carmustine (BCNU) wafers and have a modest impact to extend overall survival. We exploited this synergistic effect to maintain a cytotoxic environment around the tumor milieu, and this is a presentation of the final results of our clinical trial. Methods: Patients with glioblastoma were eligible after maximal resection with biodegradable carmustine (BCNU) wafer placement. Screening leukapheresis was used to isolate mononuclear cells which were differentiated into dendritic cells, pulsed with tumor lysate, and then 3 intradermal vaccines administered at 2-week intervals. Patients continued systemic chemotherapy after vaccine or at progression. Results: Twenty three patient with glioblastoma received therapy including 8 with newly diagnosed disease (35%) and 15 with recurrent disease (65%) were evaluable. Immune response data is available for 20/23 patients although survival data is present for all. One grade 3 SAE of fever and chills was noted otherwise therapy was well tolerated. Within the newly diagnosed GBM cohort the median overall survival (OS) was 25.5 months (15,31+), and within the recurrent GBM cohort, the median OS was 16 months (8,23+). Among the recurrent GBM an increase of >1.5 X baseline interferon gamma production post vaccination was associated with a prolonged median OS 22 months (8,40) in 4/12 patients versus 17 months (9,27) in 8/12 patients. Conclusions: We were able to generate an immune response in 25% of patients which is lower than what we have seen in previous trials and suggests a limited synergy with local control. However, within the recurrent GBM cohort we did find prolonged survival in both groups with an increased survival noted in immune responders demonstrating the potential for this therapy.
Phase II study of bevacizumab plus irinotecan and carboplatin for recurrent WHO grade 3 malignant gliomas with no prior bevacizumab failure.
Authors: Desjardins Annick , Vredenburgh James J , Peters Katherine B. , Threatt Stevie , Herndon James Emmett , Sampson John Howard , Friedman Allan H. , Friedman Henry S. , Reardon David A. 
Published: March 2020

2095^ Background: No standard treatment exists for recurrent WHO grade 3 malignant glioma patients. Bevacizumab (BV) with irinotecan has significant anti-tumor activity for recurrent glioblastoma. Carboplatin has anti-glioma activity and can potentiate the cytotoxicity of irinotecan. We evaluated the progression-free survival (PFS) of BV in combination to irinotecan and carboplatin in recurrent WHO grade 3 malignant gliomas, as well as its safety. Methods: Adult patients with measurable recurrent WHO grade 3 malignant glioma, ≥12 weeks after radiation therapy, ≥4 weeks after chemotherapy, with adequate organ function, KPS ≥70%, no prior failure or grade ≥3 toxicity to the agents, and no contraindications to BV were eligible for study. Patients received BV at 10 mg/kg with irinotecan on days 1 and 15 of a 28-day cycle. The dose of irinotecan was 125 mg/m2 for patients not on enzyme inducing anti-epileptics (EIAEDs) and 340 mg/m2 for patients on EIAEDs. All patients received carboplatin at an AUC of 4 on day 1 of each cycle. MRIs were obtained every 8 weeks. Results: As planned, 39 WHO grade III malignant glioma patients were enrolled on study. Median age was 47 (range, 26-71). At a median follow up of 14 months, the 6-month PFS is 69% and the median PFS is 11 months. A median of 8 cycles were given. Seven patients completed the planned course of treatment (12 cycles) with hypometabolic PET scan and nine patients remain on study. Fifteen patients came off study due to disease progression and eight due to toxicity. As of 1/25/2012, 22 patients are still alive and 17 have died. Grade 3-4 toxicities included: neutropenia (grade 3, n=12; grade 4, n= 1), thrombocytopenia (grade 3, n=6; grade 4, n=4), nausea (grade 3, n=7), diarrhea (grade 3, n=2), deep venous thrombosis (grade 3, n=2), febrile neutropenia (grade 3, n=1; grade 4, n=1), fatigue (grade 3, n=8; grade 4, n=1), cerebral infarction (grade 4, n=3), intracranial hemorrhage (grade 4, n=1), posterior reversible encephalopathy syndrome (grade 3, n=1). Conclusions: The combination of bevacizumab, irinotecan and carboplatin for WHO grade 3 malignant glioma patients is effective and with no more than expected toxicity.
Prognostic nomogram in elderly patients with glioblastoma.
Authors: Patel Mital , Hashemi-Sadraei Neda , Elson Paul , Ahluwalia Manmeet Singh 
Published: March 2020

2096 Background: Glioblastoma (GBM) is the most common malignant primary brain tumor. More than half the cases occur in patients aged ≥65 years; however, there is limited data on specific prognostic factors in these patients and there is a lack of easy to use nomograms in elderly GBM patients to provide them prognostic information. Methods: The Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database was used to identify elderly patients with GBM ( ≥65 years at the time of diagnosis). Multivariable analysis was conducted to identify independent predictors of survival using a Cox proportional hazards model and a stepwise selection algorithm with p=.10 as criteria for entry and retention. "Points" were assigned to each of these poor prognostic features and prognostic groups were formed based on the total number of calculated points. Results: 512 GBM patients with a median age of 73 years (range 65-96, 54% male) were included in the final analysis. On multivariable analysis six factors were identified as having an independent impact on overall survival after controlling for non-surgical treatment related factors like chemotherapy and radiation: age at diagnosis (p<.0001), surgery (p< .0001), multifocal disease (p=.0008), seizure at presentation (p=.02), hypertension (p=.05) and Karnofsky Performance Status (p<.0001). Prognostic groups were developed as summarized in the table. 28% of the patients had the most favorable profile which was associated with 56% one year survival and a 13.2 months median survival. In contrast, almost all patients in the least favorable group (27%) died within one year. Conclusions: This is an easy to use nomogram in elderly GBM patients to provide them prognostic information. [Table: see text]
Primary CNS lymphoma: A review of clinicopathologic characteristics, therapy, and outcomes of 54 patients with primary CNS DLBCL.
Authors: Hasija Nalini , Jaglal Michael , Duong Vu , Bello Celeste M. , Tomblyn Michael B. , Forsyth Peter A. J. , Sotomayor Eduardo M. , Pan Edward , Sokol Lubomir 
Published: March 2020

2099 Background: Primary central nervous system lymphoma (PCNSL) is a rare aggressive variant of diffuse large B cell lymphoma (DLBCL) with a poor prognosis. Optimal therapeutic strategies have not yet been defined. High dose methotrexate (HD MTX) is an effective chemotherapeutic agent with superior outcomes compared to historical studies using whole brain radiation therapy (WBRT). Purpose: To review clinicopathologic characteristics, therapy and outcomes of 54 patients (pts) with primary CNS DLBCL. Methods: This was a single center retrospective review of pts with confirmed diagnosis of primary CNS DLBCL from 1999 to 2009. Data was extracted from the Moffitt Cancer Center (MCC) electronic records. Baseline demographics, clinical, pathological and treatment data were collected and analyzed. Pts were stratified according to their treatment regimens including HD MTX (8g/m2) alone or in combinations and WBRT alone or in combination with CT. Descriptive statistical analyses were utilized. Chi square analysis and t- test were performed to compare categorical and continuous variables. Kaplan-Meier method was used to estimate OS and log rank test was used to compare the groups. All data was analyzed using SPSS version 20.0 statistical software. Results: 54 pts who underwent CT and/or WBRT for PCNSL between 1999 and 2009 were identified. The age range at diagnosis was 19-85 years with median age of 63. 31 of 54 pts (57%) were ≥ 60 years old. Male to female ratio was 1.25 :1 (30:24). The median ECOG PS was 1. Only 2 pts had HIV. A majority of pts presented with motor deficits. The most common location of lymphoma was in the cerebral hemispheres. The median survival of the entire cohort was 42 months. 15 of 54 pts (23%) survived ≥ 60 months. In the cohort of pts that survived ≥ 60 months, a majority 11 of 15 (73%) received HD MTX. Pts treated with initial WBRT revealed inferior overall survival (OS) compared to pts treated with induction CT (OS 37 months vs. 50 months) (p=0.056). Conclusions: HD MTX was the most frequently utilized CT regimen in the cohort of pts surviving > 60 months. Administering WBRT as an initial modality was associated with worse outcomes in this retrospective analysis.
Phase IB study on combined intradermal (ID) and intravenous (IV) administration of autologous mRNA electroporated dendritic cells (DC) as a single-agent cellular immunotherapy or combined with ipilimumab.
Authors: Neyns Bart , Wilgenhof Sofie , Van Nuffel An M. T. , Benteyn Daphné , Corthals Jurgen , Heirman Carlo , Aerts Cindy , Van Riet Ivan , Bonehill Aude , Thielemans Kris 
Published: March 2020

2507 Background: Autologous monocyte-derived DC electroporated with synthetic mRNA encoding CD40 ligand, a constitutively active TLR4, and CD70 (TriMix-DC) have superior T-cell stimulatory capacity. In a pilot clinical trial, ID administration of TriMixDC-MEL (a mixture of TriMix-DC co-electroporated with mRNA encoding a fusion of DC.LAMP and 1 of 4 melanoma associated antigens) was immunogenic but resulted in limited anti-tumor activity in patients (pts) with advanced melanoma. Ipilimumab (IPI) is a CTLA-4 blocking mAb with established activity in pts with advanced melanoma. Methods: TriMixDC-MEL by the IV and ID-route was investigated as a single-agent or in combination with IPI (10 mg/kg q3wks x4, allowing for maintenance with IPI-alone q12wks in pts PFS at >24 wks). Ratio of ID/IV administered DC: Cohort-1: 20.106/4.106 DC [2pts], -2: 12.106/12.106 DC [3pts], -3: 4.106/20.106 [6pts], and -4: 0/24.106 DC [4pts]; DC were administered 4x q2w, and a 5th administration on w16. in cohort-5, DC (4.106-ID/20.106-IV) were first administered alone and 2w thereafter in combination with IPI for a total of 4 administrations [6pts]. Results: Local skin reactions (gr1-2) were observed in all pts receiving DC ID, flu-like symptoms (< gr2) were observed in 12/21 pts, post IV-infusion chills (gr2) in 7/21 pts. Cytokines release (including a >2-fold rise in the serum levels of IL-1RA, IL-6, IL-8, IL-17, G-CSF, IFN-g, MIP-1a, MIP-1b, TNF-a) was documented during chills. Best objective tumor response: 2x PR + 2x CR (by RECIST) out of 15 pts (27%) treated with DC-only (ongoing after 10+, 14+, 19+, and 20+ mths) and 3 PR out of 6 pts (all stage IV-M1c) treated with DC+IPI (ongoing after 5+, 5+, 6+ mths). Conclusions: ID/IV-administration of TriMixDC-MEL as a single-agent cellular immunotherapy or combined with IPI is associated with distinct but manageable side-effects and has clinical activity against pretreated advanced melanoma. Activity compares favorably with TriMixDC-MEL by ID-administration-only. Combined ID/IV administration of TriMixDC-MEL with IPI is currently under further evaluation in a phase II trial.
Interim analysis of a phase II randomized clinical trial of samrium-153 (Sm-153) with or without PSA-TRICOM vaccine in metastatic castration-resistant prostate cancer after docetaxel.
Authors: Heery Christopher Ryan , Madan Ravi A. , Bilusic Marijo , Kim Joseph W. , Singh Nishith K. , Rauckhorst Myrna , Chen Clara , Dahut William L. , Stadler Walter Michael , DiPaola Robert S. , Stein Mark N. , Hodge James W. , Schlom Jeffrey , Gulley James L. 
Published: March 2020

2526 Background: A prior randomized, placebo-controlled, multi-center phase 2 trial of PSA-TRICOM (PROSTVAC) demonstrated an overall survival benefit. Sm-153 is a radiopharmaceutical that targets osteoblastic bone lesions. Preclinical data indicated that Sm-153 could alter tumor phenotype, causing upregulation of Fas, MHC Class I, and tumor-associated antigens, making tumor cells more amenable to immune-mediated killing. Methods: This is a phase 2 multi-center trial design intended to randomize 68 patients (pts) to Sm-153 with or without PROSTVAC. Eligibility included castrate resistant prostate cancer bone metastases, no visceral disease, prior docetaxel, ECOG ≤2, and normal organ function. Sm-153 was given at 1mCi/kg IV on day 8 and then every 12 weeks. PROSTVAC was given on days 1, 15, 29, then every 4 weeks. The 1° endpoint is a comparison of progression-free survival at 4 months (mo) utilizing PCCWG, but not PSA criteria. 68 patients will provide 80% power to detect a difference of 15% vs. 40% without progression at 4 mo with a one-tailed alpha = 0.10 assuming Fisher’s exact test comparing these fractions as the primary method of analysis. 2° endpoints are OS, ORR, PSA changes, immunologic, toxicity, and palliation. Reported here is the result of a pre-specified interim analysis, which required ≥20% conditional power to detect 15% vs. 40% without progression at 4 months for the trial to continue. Results: Of 37 enrolled pts, 3 were not evaluable for PFS. PFS and PSA findings are found below. Hematologic toxicities (anemia, thrombocytopenia, neutropenia, or lymphocytopenia) are most common, with grade 3 or 4 thrombocytopenia occurring in 22% and 26% of treatment cycles on Arms A and B, respectively. The conditional power for the comparison of fractions without progression at 4 mo is 77%. Conclusions: This interim analysis suggests the combination of PROSTVAC and Sm-153 is well tolerated with similar toxicity profile to Sm-153 alone. The early indication of improved TTP warrants continued study accrual. [Table: see text]
Response to epidermal growth factor vaccine in patients with metastatic non-small cell lung cancer (NSCLC) after progressing to first-line therapy.
Authors: Venegas Diego , Neninger Elia , Iberico Carlos , Oliva Claudia , Alarcon-Rozas Ashley E. , Lozada Claudia Patricia , Galvez Jose , Gonzalez Gisela 
Published: March 2020

2531 Background: A direct correlation between anti–epidermal growth factor (EGF)antibody titers and survival was demonstrated in vaccinated patients with novel NSCLC advanced in Phase II studies. We show the results of treatment with anti-EGF vaccine in a cohort of patients with metastatic NSCLC after progressing to first line therapy. We evaluated immunogenicity, safety, treatment response and effect on survival. Methods: 12 patients with metastatic NSCLC after progressing to first-line therapy received anti EGF-vaccine alone or in combination with chemotherapy. Results: From October 2009 until August 2011, 12 patients started treatment with anti EGF vaccine; mean age 56.5 (42-79 y); 66.7% male; ECOG 0 and 1: 41.7% and 58,3% respectively. Adenocarcinoma (50%), bronchioloalveolar (33.3%), adenosquamous (16.7%). Metastatic sites: lung (41.7%), pleura (25%), CNS (16.7%), Kidney (8.3%). In addition to chemotherapy previous used: radiotherapy (50%), surgery (41.7%), erlotinib (41.7%), bevacizumab (25%). The 50% patients received vaccine alone. The 83.3% of patients had titers 1/4000 sera dilutions or more (good responders). According to RECIST 1.1: CR: 8.3%, PR: 16.7%, SD: 41.7%, PD 25%. Median overall survival was 18.8 months (95% CI: 13.3- 24.4 m). Median progression-free survival was 7.3 months (95% CI: 6.4 -8.2 m). We found no statistically significant differences in OS and PFS when comparing vaccine alone or combined (p = 0.181 and p = 0.801). 75% of patients had adverse effect: more frequently were: 42.4% application site pain, 15.1% fever and 10.38% chills, none of them serious. Conclusions: Vaccination anti EGF in patients with metastatic NSCLC after progressing to first line, alone or in combination, was safe and provoked an increase in anti-EGF antibody titers, produced clinical benefit, improved overall survival and progression free survival.
Effect of age on the pharmacokinetics of busulfan (Bu): An alliance study.
Authors: Beumer Jan Hendrik , Lewis Lionel D. , Owzar Kouros , Jiang Chen , Holleran Julianne L. , Christner Susan M. , Blum William G. , Devine Steven M , Kolitz Jonathan E. , Linker Charles A. , Larson Richard A. , Ratain Mark J. , Egorin Merrill J. 
Published: March 2020

2533 Background: Older acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients (pts) have been excluded from myeloablative regimens including agents such as busulfan because of the potential for non-disease related morbidity and mortality. Busulfan, often used as part of myeloablative regimens, is cleared in part by glutathione–S-transferase and CYP3A4. We hypothesized that busulfan clearance (BuCL) in the elderly (> 60 years) would be reduced compared to that in young patients (< 60 years), thus potentially explaining differences in tolerability. Methods: AML and MDS pts in three CALGB bone marrow transplant studies across a wide age range (17-74) were treated with a conditioning regimen using IV busulfan, dosed at 12.8 mg/m2 in CALGB studies 10503 and 19808 and 6.4 mg/m2 in CALGB 100103. Blood samples were collected for determination of busulfan plasma pharmacokinetics (PK). Plasma busulfan was quantitated by LC-MS. BuCL was determined using non-compartmental modeling, and normalized to actual (ABW), ideal (IBW) and corrected (CBW) body weight (kg). Differences between age groups were examined using the Wilcoxon rank sum test. Results: A total of 185 pts were accrued and signed consent, of which 174 provided useable PK data. Twenty-nine pts ≥60 years old (median age 66.3) had a significantly higher mean BuCL vs those < 60 years old (median age 49.8); BuCL 263 vs 186 mL/min, p=0.0002; BuCL/ABW 3.22 vs 2.34 mL/min/kg, p=0.0001; BuCL/IBW 3.63 vs 2.91 mL/min/kg, p=0.0035; BuCL/CBW 3.50 vs 2.70 mL/min/kg, p=0.0005. Inter-patient variability in clearance (CV%) was up to 47% in the elderly and up to 48% in young patients. Phenytoin use, a potential confounder, did not affect BuCL, regardless of weight normalization (p=0.74). Conclusions: Contrary to our hypothesis, BuCL is significantly higher in pts ≥60 years old compared to younger patients and does not explain the previously reported increase in Bu toxicity observed in the elderly.
Patient-specific immunotherapy utilizing putative tumor stem cells in patients with metastatic melanoma: A pooled analysis comparing tumor cell and dendritic cell vaccines in two phase II trials and a randomized phase II trial.
Authors: Dillman Robert Owen , DePriest Carol , de Leon Cristina , Barth Neil M. , McClay Edward Francis , Amatruda Thomas , Schwartzberg Lee Steven , Sheehy Patrick Frank , Mahdavi Khosrow , Mayorga Cheryl Ann , Ellis Robin Anne 
Published: March 2020

2569 Background: Metastatic melanoma is seldom cured, even in patients who achieve a complete remission, because new sites of disease emerge. Autologous, proliferating, self-renewing tumor cells (putative tumor stem cells and/or early progenitor cells), are critical to establishment of new depots of metastatic cancer, and may be excellent sources of antigen for vaccines. These trials addressed the impact on survival from immunizing with antigens from such cells. Methods: Data was pooled from 3 successive phase II trials, all of which included patients with documented metastatic melanoma, who were treated in protocols that utilized antigens from cell cultures of autologous tumor cells. S.C. injections were given weekly for 3 weeks, then monthly for 5 months. 1992-2000: 74 patients were injected with irradiated tumor cells (TC). 2000-2006: 54 patients were injected with autologous dendritic cells (DC) that had been co-cultured with irradiated autologous tumor cells (NCI-V01-1646). 2007-2011: in a randomized phase II trial, 24 patients were injected with TC, and 18 with DC (NCT00436930). Results: The table summarizes overall survival (OS) in each trial. In the pooled analysis there were 98 TC and 72 DC patients. Characteristics were similar in terms of age (51, 52), male gender (62%, 62%), no evidence of disease at the time of treatment (46%, 47%), and presence of M1c visceral disease at the time of treatment (13%, 14%). OS was longer in patients treated with DC (median 63.1 vs 20.2 months, 5-year OS 51% vs 26%, p=0.0002 Mantle-Cox log-rank test). The difference in OS in the randomized trial is also significant (p=0.007). Conclusions: Patient-specific DC vaccines primed with antigens from autologous proliferating, self-renewing tumor cells are associated with encouraging long-term survival rates, and are superior to patient-specific TC vaccines in populations of patients who have been diagnosed with metastatic melanoma. [Table: see text]