bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resource and reimbursement barriers to comprehensive cancer care (CCC) delivery: An Association of Community Cancer Centers (ACCC) survey research analysis.
Authors: Benson Al Bowen , Boehmer Leigh , Shivakumar Latha , Trosman Julia Rachel , Weldon Christine B. , Hahn Elizabeth A. , Kircher Sheetal Mehta 
Published: May 2020

2075 Background: CCC delivery is recommended in guidelines, required by accreditation bodies, and essential for high-quality cancer management. Barriers, such as insufficient reimbursement and lack of specialist staff, prevent consistent access to and delivery of CCC, particularly supportive oncology services. Challenges especially persist in community programs, where access to philanthropy and similar funding is limited. ACCC conducted a representative survey of its member programs to elucidate capacity and barriers to CCC delivery in the community/academic setting in order to inform policy and value-based payment reform. Methods: Survey development methodology included item generation with expert review, iterative piloting and cognitive interviews to achieve content and internal validity. An online survey was piloted at the ACCC 2018 Annual Meeting and sent to member programs via email link. The final survey included 22 questions on availability and funding for supportive services. Twenty-seven supportive oncology services were assessed for availability, reasons not offered, reimbursement/funding and patient payment. Analyses were conducted with SAS. Results: 172 of 704 ACCC member programs responded and completed the majority of survey as of 10/7/19. Despite a high proportion of programs offering supportive oncology services, gaps between cost and reimbursement were present for all (Table). Deficits in reimbursement are compensated by patient out-of-pocket payments, grants and donations. Most centers report needing more staffing in psychology (61%), social work (60%), navigation (59%), nutrition (57%), palliative care (56%), genetic counseling (52%), and financial counseling (53%). Gaps were observed regardless of region or practice type. Conclusions: There is a lack of sufficient reimbursement, staffing, and budget to provide CCC across the U.S., regardless of region or practice type. Oncology care models and reimbursement policies must include CCC services to optimize delivery of care. [Table: see text]
Documentation patterns and impact on observed side effects of the CANKADO ehealth application: An exploratory analysis of the PreCycle trial.
Authors: Degenhardt Tom , Harbeck Nadia , Fasching Peter A. , Wuerstlein Rachel , Lüftner Diana , Kates Ronald E. , Schumacher Johannes , Wenzel Claudia , Schinkoethe Timo , Schmidt Marcus 
Published: May 2020

2083 Background: PreCycle (NCT03220178), a multicenter, randomized phase IV Intergroup trial evaluates the impact of ePRO assessment on quality of life (QoL) in HR+/HER2- locally advanced or metastatic breast cancer patients (pts) treated by palbociclib (P) and an aromatase inhibitor or P+fulvestrant. Pts willing to use the web/APP-eHealth solution CANKADO are eligible. Patients are randomized (2:1, stratified by therapy line) to the active (CANKADO PRO-React) or inactive inform arm. Primary endpoint is time to deterioration (TTD) of QoL. Methods: The trial started in 2017 and is ongoing (81 centers); regular safety reports are routinely provided to the study sponsor. Analysis of distribution of serious adverse events (SAE) was initiated by the trial leadership and performed using the Oct 15, 2019 safety report. Data that could bias primary or secondary endpoints were not analyzed. Bayesian inference (non-informative prior) was used to estimate probabilities; no corrections for potential multiplicities were made. Results: At data cut-off, 261/281 randomized patients had received study medication and provided CANKADO documentation. At time of evaluation, a total of 40298 days were documented. CANKADO was used on 59% (+/-10%) of all days over a 2-year period. SAEs were observed in 26/175 (14.9%) of all active-arm patients vs. 18/86 (20.9%) of inform-arm patients (90% probability of reduction in inform patients). Total SAEs were 36 (active) vs. 27 (inform); corresponding SAE incidence per hundred patients was 20.6 vs. 31.4, a relative reduction of about one-third. Conclusions: CANKADO is well accepted and used regularly by pts in PreCycle, so far over a 2-year period. The present (unplanned) analysis suggests a potentially substantial, clinically relevant reduction in relative SAE incidence among 1stL pts using PRO-React, with a more modest decrease overall. This analysis is preliminary, representing a snapshot, and cannot provide a definitive explanation for the observed SAE reduction. PreCycle will continue to enroll patients in order to further evaluate the potential benefits of interactive eHealth support. Collaborators: WSG WOMEN´S HEALTHCARE STUDY GROUP, CANKADO, Pfizer, AGO-TraFo, AGO-B, Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie e.V. Sponsor: Palleos Healthcare GmbH Keywords: eHealth, Adverse Events, Palbociclib Clinical trial information: NCT03220178.
The role of tumor markers for relapse detection in central nervous system non-germinomatous germ cell tumors (CNS-NGGCT): A pool analysis of cooperative group clinical trials.
Authors: Fonseca Adriana , Faure-Conter Cecile , Murray Matthew , Fangusaro Jason R. , Goldman Stewart , Bailey Shivani , Calaminus Gabriele , Khatua Soumen , Frappaz Didier , Dhall Girish , Nicholson James , Bouffet Eric , Bartels Ute Katharina 
Published: May 2020

2503 Background: CNS-NGGCT are rare tumors that have been successfully treated with multimodal therapies. With a 5-yr EFS and OS of 72-84% and 82-93% respectively, surveillance and relapse detection is essential. Tumor marker (TM) elevation has proven to be a highly sensitive method of relapse detection in extra-cranial-NGGCT. We aim to determine the role of TM for relapse surveillance in children and adolescents with CNS-NGGCTs. Methods: European and North American data from germ cell tumor trials (SIOP GCT96, SFOP-TGM TC 90/92, COG-ACNS0122 and COG-ACNS1123) were pooled for analysis. Additionally, patients treated in the UK, Germany and France under strict protocol-guidelines were included. Details regarding imaging, pathology and TM elevation at diagnosis and relapse were collected. We report the proportion of relapses detectable by TM elevation. Results: Four-hundred and eighty-four patients enrolled in prospective cooperative group CNS-NGGCT trials from 1989 to 2016 were pooled for analysis. One-hundred and thirteen (23%) patients experienced a relapse/progression (SIOP GCT96: n = 57; SFOP TGM TC 90-92 n = 23, COG-ACNS0122 n = 16 & COG-ACNS1123 n = 17) and constitute the population of this report. Median age at diagnosis was 13 (range:1-30) years. The most common primary location was pineal in n = 60 (53%) patients. The site of relapse was available for 100 patients, 48 patients relapsed locally, 36 relapsed with distant disease, combined relapses were seen in 22 patients and 4 patients relapsed with TM elevation alone. TM in serum and/or CSF at diagnosis was available in 93(82%) patients, and in 90(80%) patients at the time of relapse. Eighty-four patients had TM available at both timepoints. At diagnosis 81 (96%) patients had TM elevation and 3 (4%) had negative TM. At relapse, 74(94%) patients with positive TM at diagnosis had TM elevation, while 7(6%) had TM negative. Conversely, 2/3 patients with negative TM at diagnosis, relapsed with elevated TM. Conclusions: Herein, we have assembled the largest prospective cohort to date of relapsed intracranial germ cell tumors. TM are highly sensitive detecting relapse/progression in CNS-NGGCT patients with elevated TM at diagnosis. The routine use of TM for relapse surveillance in patients with CNS-NGGCT can decrease the frequency of cross-sectional imaging, therefore, reducing lengthy hospital visits, sedation procedures and decreasing health-care costs.
Utilizing phenotypic characteristics of metastatic brain tumors to predict the probability of circulating tumor DNA detection from cerebrospinal fluid.
Authors: Li Meichen , Li Delan , Hou Xue , Zhang Xiangheng , Wang Na , Liang Jianzhong , Chen Jing , Wang Kaicheng , Wang Fufeng , Chen Yedan , Zhang Xian , Bao Hua , Wu Xue , Wang Xiaonan , Shao Yang , Chen Likun 
Published: May 2020

2507 Background: Brain metastases occur in approximately 20% of tumor patients and is often associated with terminal events and poor prognosis. Cerebrospinal fluid (CSF) can be a promising source for detecting circulating tumor DNA (ctDNA) specific to the central nervous system (CNS) instead of peripheral blood due to the blood-brain barrier. However, CSF’s suboptimal ctDNA detection rate might limit its clinical application. Precise screening of suitable patients is needed to maximize clinical benefit. Methods: We sequenced 425 cancer-relevant genes in CSF and matched extracranial tissue or blood samples obtained from 67 lung cancer patients with brain metastases. The impact of clinical factors, including age, gender, tumor size, number of lesions, and distance of lesions to the ventricle on CSF ctDNA detection was then evaluated by univariate logistic regression. To predict the probability of successful CSF ctDNA detection, best subsets regression was employed for feature selection and cross validation was used for performance assessment to determine the final model. Results: We detected somatic alterations in 39/67 (58%) CSF ctDNA, 57/66 (86%) plasma ctDNA and 45/49 (92%) tissue samples. Mutation detection rate of CSF ctDNA was significantly lower than that from extracranial tissue and plasma (P < 0.001). Univariate analysis revealed significant association (P < 0.05) of high CSF ctDNA detection rate with the following features: (1) intracranial lesion size ( T), (2) shortest distance between the largest lesion and the ventricle ( Dtop), and (3) shortest distance between all intracranial lesion and the ventricle ( Dall). We also revealed a trend of higher detection rate in patients with CNS symptoms ( SCNS). Subsequent best subsets analysis and cross validation suggested best prediction power with lesion size and largest lesion-ventriclar distance (area under curve [AUC], 0.76 [95% CI, 0.71 to 0.85]; accuracy, 0.75 [95% CI, 0.70 to 0.81]). Final probability can then be derived from Logit P = 0.11×T−0.16×Dall (AUC, 0.82; sensitivity, 0.91; specificity, 0.74). The detection of CSF ctDNA was significantly improved from 58% to 83% (P = 0.03) based on the model. Conclusions: This study established a regression model to predict the probability of CSF ctDNA that can be useful to facilitate clinical decisions and avoid excessive practice when monitoring tumor evolution in the brain.
A prospective validation cohort study of baseline plasma cell-free DNA (cfDNA) as a prognostic biomarker in newly diagnosed glioblastoma (GBM).
Authors: Bagley Stephen Joseph , Nabavizadeh Seyed Ali , Till Jacob , Abdalla Aseel , Sanga Hareena , Mays Jazmine , Prior Timothy , Jurgielewicz Andrew , Guiry Samantha , Davtyan Karapet , Yee Stephanie S. , Binder Zev A , O'Rourke Donald M. , Brem Steven , Desai Arati Suvas , Carpenter Erica L. 
Published: May 2020

2508 Background: Due to significant interpatient heterogeneity, survival outcomes vary widely in patients with GBM. Novel prognostic biomarkers are needed. We aimed to determine the prognostic impact of baseline plasma cfDNA concentration in patients with GBM. Methods: We analyzed 84 patients with newly diagnosed GBM and at least 7 months of follow-up time. The first 41 patients comprised a previously published derivation cohort (Bagley, Clin Cancer Res 2020). The subsequent 43 patients served as an independent validation cohort. cfDNA was extracted from plasma collected prior to initial surgical resection and quantified by qPCR for a 115 bp amplicon of the human ALU repeat element. Receiver operating characteristic (ROC) curve analysis was used in the derivation cohort to (1) assess the accuracy of plasma cfDNA concentration for predicting progression-free survival status at 7 months (PFS-7), a landmark based on the median PFS for newly diagnosed GBM (Stupp, N Engl J Med 2005), and (2) derive the optimal cutoff for dichotomizing patients into high- and low-cfDNA groups. In the validation cohort, logistic regression was used to measure the association of plasma cfDNA concentration (high vs. low) with PFS-7, adjusted for age, isocitrate dehydrogenase ( IDH) 1/2 mutational status, 0-6-methylguanine-methyltransferase ( MGMT) methylation, extent of resection, and performance status. Multivariate Cox regression was used for overall survival (OS) analysis. Results: In the derivation cohort, the optimal cutoff for plasma cfDNA was 25.0 ng/mL (area under the curve [AUC] = 0.663), with inferior PFS and OS in patients with cfDNA above this cutoff (PFS, median 4.9 vs. 9.5 months, log-rank p = 0.001; OS, median 8.5 vs. 15.5 months, log-rank p = 0.03). In the validation cohort, baseline plasma cfDNA concentration over the cutoff was independently associated with a lower likelihood of being alive and progression-free at 7 months (adjusted OR 0.13, 95% CI 0.02 – 0.75, p = 0.02). OS was also worse in in the validation cohort in patients with high plasma cfDNA (adjusted HR 3.0, 95% CI 1.1 – 8.0, p = 0.03). Conclusions: In patients with newly diagnosed GBM, high baseline plasma cfDNA concentration is associated with worse survival outcomes independent of other prognostic factors. Further validation in a larger, multicenter study is warranted.
Phase I/II study to evaluate the safety and clinical efficacy of atezolizumab (atezo; aPDL1) in combination with temozolomide (TMZ) and radiation in patients with newly diagnosed glioblastoma (GBM).
Authors: Weathers Shiao-Pei S. , Kamiya-Matsuoka Carlos , Harrison Rebecca A. , Liu Diane D. , Dervin Shannon , Yun Cindy , Loghin Monica Elena , Penas-Prado Marta , Majd Nazanin , Yung W. K. Alfred , O'Brien Barbara Jane , De Groot John Frederick 
Published: May 2020

2511 Background: Immunotherapy strategies such as PD-1/PD-L1 inhibition may work synergistically with radiation, which is known to increase antigen presentation and promote a pro-inflammatory tumor microenvironment. This trial evaluated the safety and clinical efficacy of concurrent atezo with radiation therapy and TMZ followed by adjuvant atezo and TMZ in patients with newly diagnosed GBM, unselected for MGMT status. Methods: Eligibility criteria included patients with newly diagnosed GBM age > 18 yrs who had undergone only surgery. The primary endpoint was safety in Phase I (n = 10) and OS in Phase II (n = 50). Secondary endpoints included progression free survival (PFS), overall response rate (ORR), and duration of response. All 60 patients were evaluated for efficacy. Correlative endpoints include profiling of tumor immune cell populations and peripheral blood for evaluation of circulating chemokines/cytokines. Results: 60 patients were enrolled. With median follow-up time of 16.7 months (data cutoff = 30 Dec 2019), 24 patients had died and 32 had progressed. Median OS was 17.1 months (95% CI: 13.9, not reached). Median PFS was 9.7 months (95% CI: 7.6-15). Median PFS in MGMT methylated patients (n = 18) was 16.7 months (95% CI: 7.85, not reached) and 7.9 months (95% CI: 6.70-12.4) in MGMT unmethylated patients (n = 33). Treatment-related adverse events with maximum CTCAE grade > 3 occurred in 33 patients; the most common were LFT elevation (n = 5) and lymphopenia (n = 23). To date, 17 of the enrolled 60 patients underwent re-resection post treatment with atezo. The matched paired tumor analysis of pre and post treatment tissue will provide valuable insights into mechanisms of anti-PD-L1 therapy resistance. Tumor immunocorrelative studies are pending. Conclusions: Concurrent use of atezo with radiation and TMZ was tolerable and demonstrated modest efficacy. Clinical trial information: NCT03174197 .
INO-5401 and INO-9012 delivered intramuscularly (IM) with electroporation (EP) in combination with cemiplimab (REGN2810) in newly diagnosed glioblastoma (GBM): Interim results.
Authors: Reardon David A. , Brem Steven , Desai Arati Suvas , Bagley Stephen Joseph , Kurz Sylvia Christine , De La Fuente Macarena Ines , Nagpal Seema , Welch Mary Roberta , Hormigo Adilia , Carroll Nicholas , Bartra Sarah K , Campbell Patricia , Bhatt Kamalnayan , Lowy Israel , Boyer Jean , Kraynyak Kimberly , Morrow Matthew P , McMullan Trevor , Weiner David B. , Skolnik Jeffrey 
Published: May 2020

2514 Background: Novel T cell-enabling therapies, in combination with checkpoint inhibition, may improve OS in GBM. INO-5401 (synthetic DNA plasmids encoding for hTERT, WT-1 and PSMA), plus INO-9012 (synthetic DNA plasmid encoding IL-12), with the PD-1 checkpoint inhibitor cemiplimab, is given to patients with newly-diagnosed GBM to evaluate tolerability, efficacy and immunogenicity of the combination. Methods: Phase I/II, single arm, 2 cohort study (A: MGMT unmethylated, B: MGMT methylated). The primary endpoint is safety; efficacy and immunogenicity are secondary. Nine mg INO-5401 plus 1 mg INO-9012 (every 3 weeks for 4 doses, then Q9W) is given with EP by CELLECTRA 2000 with cemiplimab (350 mg IV Q3W). RT is given as 40 Gy over 3 weeks. TMZ is given with radiation (all patients), followed by maintenance (Cohort B only). Results: Fifty two subjects were enrolled: 32 in Cohort A; 20 in Cohort B. 35% women and 90% white. Median age 60 years (range 19-78 years). Common Grade ≥3 AEs reported were: platelet count decreased (11.5%), tumor inflammation (7.7%), seizure (7.7%), ALT increased (7.7%), lymphocyte count decreased (7.7.%). One Grade 5 unrelated event of urosepsis was reported. Of 69 SAEs reported there was only 1 related to the combination therapy, Grade 1 pyrexia. 48% of subjects reported irAEs, most frequently ALT increased (9.6%), AST increased (7.7%), diarrhea (7.7%), pyrexia (7.7%) and tumor inflammation (7.7%). 71% of the reported SAEs and irAEs occurred within the first 12 weeks of treatment. OS at 12 months was 84.4% (95% CI 67.2, 94.7) in Cohort A; Cohort B will be presented at ASCO. ELISpot assessments demonstrated T cell responses to INO-5401. Flow cytometry demonstrated evidence of activated INO-5401-specific CD8+T cells with lytic potential (CD38+Prf+GrzA+) when compared with baseline, post-treatment in the majority of patients assayed. Conclusions: INO-5401 + INO-9012 in combination with cemiplimab and RT/TMZ has an acceptable safety profile, is immunogenic and may show a survival advantage in patients with newly-diagnosed GBM. OS18 data will be presented later this year. Clinical trial information: NCT03491683 .
Superior therapy response predictions for patients with glioblastoma (GBM) using Cellworks Singula: MyCare-009-03.
Authors: Wen Patrick Y. , Watson Drew , Kapoor Shweta , Alam Aftab , Alam Aktar , Lala Deepak Anil , Sahu Diwyanshu , Agrawal Ashish , Basu Kabya , Ganesh Naga , Pampana Anusha , Grover Himanshu , Mundkur Nirjhar , Kumar Chandan , Mohapatra Subrat , Raman Rahul K , Elangovan Preethi , Patil Mamatha , Birajdar Shivgonda , Ahluwalia Manmeet Singh 
Published: May 2020

2519 Background: Despite using cytogenetic and molecular-risk stratification and precision medicine, the current overall outcome of GBM 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 treatment selection. 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 109 GBM patients aged 17 to 83 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 PPT for each patient and calculated the quantitative drug effect on a composite GBM 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 = 4.130, p < 0.000) and OS (HR = 2.418, p < 0.0001). In multivariate PH regression analyses, Singula (HR = 4.033, p < 0.0001) remained an independent predictor of PFS after adjustment for PPT (p = 0.1453) and patient age (p = 0.4273). Singula (HR = 1.852, p = 0.0070) was also a significant independent predictor of OS after adjustment for PPT (p = 0.4127) and patient age (p = 0.0003). Results indicate that Singula is a superior predictor of both PFS and OS compared to PPT. Singula provided alternative therapy selections for 29 of 52 disease progressors detected by Cellworks. Conclusions: Singula is a superior predictor of PFS and OS in GBM patients compared to PPT. Singula can identify non-responders to PPT and provide alternative therapy selections.