bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between Medicaid expansion under the Affordable Care Act and survival among newly diagnosed cancer patients.
Authors: Han Xuesong , Zhao Jingxuan , Yabroff Robin Robin , Johnson Christopher J. , Jemal Ahmedin 
Published: June 2021

1502 Background: Medicaid expansion under the Affordable Care Act (ACA) is associated with increased insurance coverage and early stage at diagnosis among patients with cancer. Whether these gains translate to improved survival is largely unknown, however. This study examines changes in one-year survival rates among persons newly diagnosed with cancer following the ACA Medicaid expansion. Methods: Patients aged 18-62 years from 41 population-based state cancer registries diagnosed pre-(2010-2012) and post-(2014-2016) ACA Medicaid expansion were followed through October 1, 2013 and December 31, 2016, respectively. Difference-in-differences (DD) analysis was conducted to estimate changes in one-year overall and cause-specific survival rates associated with Medicaid expansion, adjusting for age group, sex, race/ethnicity, area-level poverty, urban/rural status and region. Stratified analysis was conducted by cancer type, sex and area-level poverty. Results: A total of 2,537,818 patients diagnosed with cancer were included from Medicaid expansion (N = 1,492,729) and non-expansion (N = 1,045,089) states. During follow-up, 291,854 patients died including 246,660 deaths from cancer. The one-year overall survival rate (%) increased from 88.1 pre-ACA to 89.1 post-ACA in Medicaid expansion states and from 85.6 to 86.4 in non-expansion states for both sexes combined, resulting in a net increase of 0.4 (95%CI = 0.3-0.6) in expansion states after adjusting for sociodemographic factors. By cancer site and for both sexes combined, the increase in adjusted one-year overall survival in expansion states versus non-expansion states was greater for cancers of lung (DD = 1.6; 95%CI = 0.8-2.5), pancreas (DD = 2.2; 95%CI = 0.5-3.9) and liver (DD = 3.4; 95%CI = 1.7-5.1); as were the increases for cervix (DD = 1.3; 95%CI = 0.1-2.5), melanoma (DD = 0.4;95%CI = 0.04-0.9), non-Hodgkin lymphoma (DD = 1.2; 95%CI = 0.1-2.2) and esophagus (DD = 7.1; 95%CI = 0.5-13.7) among women. The improvement in one-year overall survival was larger among patients residing in the poorest areas (DD = 0.7; 95%CI = 0.3-1.1) compared to those in the richest areas (DD = 0.2; 95%CI = -0.2 to 0.5), leading to a narrowing survival disparity by area-level poverty. Patterns in one-year cause-specific survival were similar. Conclusions: Medicaid expansion was associated with greater increase in one-year overall survival rates, largely driven by the improvements in survival for cancer types with poor prognosis, suggesting improved access to timely and effective treatments. Furthermore, the increase was largest in poorest areas, highlighting the promising role of Medicaid expansion in reducing health disparities. Future studies should monitor changes in longer-term health outcomes following the ACA.
Extracting non-small cell lung cancer (NSCLC) diagnosis and diagnosis dates from electronic health record (EHR) text using a deep learning algorithm.
Authors: Rich Alexander S. , Leybovich Barry , Estevez Melissa , Irvine Jamie , Singh Nisha , Cohen Aaron B. , Birnbaum Ben 
Published: June 2021

1556 Background: Identifying patients with a particular cancer and determining the date of that diagnosis from EHR data is important for selecting real world research cohorts and conducting downstream analyses. However, cancer diagnoses and their dates are often not accurately recorded in the EHR in a structured form. We developed a unified deep learning model for identifying patients with NSCLC and their initial and advanced diagnosis date(s). Methods: The study used a cohort of 52,834 patients with lung cancer ICD codes from the nationwide deidentified Flatiron Health EHR-derived database. For all patients in the cohort, abstractors used an in-house technology-enabled platform to identify an NSCLC diagnosis, advanced disease, and relevant diagnosis date(s) via chart review. Advanced NSCLC was defined as stage IIIB or IV disease at diagnosis or early stage disease that recurred or progressed. The deep learning model was trained on 38,517 patients, with a separate 14,317 patient test cohort. The model input was a set of sentences containing keywords related to (a)NSCLC, extracted from a patient’s EHR documents. Each sentence was associated with a date, using the document timestamp or, if present, a date mentioned explicitly in the sentence. The sentences were processed by a GRU network, followed by an attentional network that integrated across sentences, outputting a prediction of whether the patient had been diagnosed with (a)NSCLC and the diagnosis date(s) if so. We measured sensitivity and positive predictive value (PPV) of extracting the presence of initial and advanced diagnoses in the test cohort. Among patients with both model-extracted and abstracted diagnosis dates, we also measured 30-day accuracy, defined as the proportion of patients where the dates match to within 30 days. Real world overall survival (rwOS) for patients abstracted vs. model-extracted as advanced was calculated using Kaplan-Meier methods (index date: abstracted vs. model-extracted advanced diagnosis date). Results: Results in the Table show the sensitivity, PPV, and accuracy of the model extracted diagnoses and dates. RwOS was similar using model extracted aNSCLC diagnosis dates (median = 13.7) versus abstracted diagnosis dates (median = 13.3), with a difference of 0.4 months (95% CI = [0.0, 0.8]). Conclusions: Initial and advanced diagnosis of NSCLC and dates of diagnosis can be accurately extracted from unstructured clinical text using a deep learning algorithm. This can further enable the use of EHR data for research on real-world treatment patterns and outcomes analysis, and other applications such as clinical trials matching. Future work should aim to understand the impact of model errors on downstream analyses.[Table: see text]
EORTC 1709/CCTG CE.8: A phase III trial of marizomib in combination with temozolomide-based radiochemotherapy versus temozolomide-based radiochemotherapy alone in patients with newly diagnosed glioblastoma.
Authors: Roth Patrick , Gorlia Thierry , Reijneveld Jaap C. , De Vos Filip Yves Francine Leon , Idbaih Ahmed , Frenel Jean-Sebastien , Le Rhun Emilie , Sepulveda Sánchez José Manuel , Perry James R. , Masucci Laura , Freres Pierre , Hirte Hal W. , Seidel Clemens , Walenkamp Anna Maria Elisabeth , Dhermain Frederic , Van Den Bent Martin J. , O'Callaghan Christopher J. , Vanlancker Maureen , Mason Warren P. , Weller Michael 
Published: June 2021

2004 Background: Patients with newly diagnosed glioblastoma receive postoperative standard therapy with radiotherapy (RT), and concomitant and up to six cycles of maintenance temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). Marizomib is a novel, irreversible and brain-penetrant pan-proteasome inhibitor with encouraging findings in preclinical models and early-stage clinical trials for patients with newly diagnosed and recurrent glioblastoma. Therefore, a phase 3 trial was designed to explore the activity of marizomib in addition to TMZ/RT→TMZ. ClinicalTrials.gov Identifier: NCT03345095 Methods: EORTC 1709/CCTG CE.8 is a multicenter, randomized, controlled, open label phase 3 superiority trial. Eligibility criteria included histologically confirmed newly diagnosed glioblastoma and a Karnofsky performance status (KPS) > 70. Eligible patients were stratified for institution, age, KPS as well as extent of surgery, and centrally randomized in a 1:1 ratio. The primary objective of this study is to compare overall survival (OS) in patients receiving marizomib in addition to standard treatment with patients receiving standard treatment only. Secondary endpoints include progression-free survival (PFS), safety, neurocognitive function, and quality of life. Results: The study was opened at 49 EORTC sites in Europe, 23 CCTG sites in Canada, and 8 sites in the US. Patient enrolment started in June 2018 and was close to completion at the time of a planned interim analysis in September 2020. A total of 749 patients (of the planned 750) were randomized when the IDMC recommended to discontinue enrollment. Age, KPS and extent of resection were well balanced between the 2 study arms. No difference in median OS was observed between the standard arm (15.9 months) and the marizomib arm (15.7 months; HR = 0.99). Median PFS was 6.1 vs. 6.2 months (HR = 1.02). Patients in the marizomib group had more often grade 3/4 treatment-emergent adverse events (TEAE) compared to the standard therapy group (42.6% vs. 20.5%), including ataxia, hallucinations and headache. Conclusions: The addition of marizomib to standard radiochemotherapy did not improve OS or PFS in patients with newly diagnosed glioblastoma. Final survival analyses including determination of MGMT promoter methylation status and analyses of other secondary endpoints are ongoing. Clinical trial information: NCT03345095.
Long-term results of the GEINO 1401 TRIAL: Randomizing patients to stop or to continue temozolomide until 12 cycles.
Authors: Domenech Marta , Fabregat-Franco Carles , Mesia Carlos , Esteve Anna , Berron Sonia Del Barco , Pineda Estela , Gironés Sarrió Regina , De las peñas Ramon , Fuster Jose , Navarro L Miguel , Alonso Miriam , Olier Clara , Perez Pedro , Berrocal Alfonso , Covela Rúa Marta , Hernandez Gonzalez Ainhoa , Carrato Cristina , Sanz Carolina , Sepulveda Sánchez José Manuel , Balana Carmen 
Published: June 2021

2013 Background: We previously presented our results of the GEINO 1401 trial that randomized patients diagnosed with glioblastoma and treated with chemoradiotherapy and adjuvant temozolomide (TMZ) followed by six cycles of TMZ, to receive an extended use of TMZ up to 12 cycles or to control. We found no differences in 6-months neither progression free survival (PFS) nor overall survival (OS). In this report we actualize our results and analyse long-term survivor patients (LTSP). Methods: The trial NCT02209948 randomized (ratio 1:1) 159 patients diagnosed with glioblastoma who had been treated with standard therapy to stop treatment or to continue up to 12 cycles of TMZ. Patients were stratified based on their O6-methylguanine-DNA-methyltransferasa (MGMT) methylation status and presence or absence of measurable disease at inclusion. We update here OS outcomes and analyse the data of LTSP defined as an OS over 30 months from diagnosis. Results: At a median follow-up of 20 months, 82.4% of the patients had died and 89.9% had progressed. The median OS from randomization was 22.0 months for the control arm and 18.2 for the experimental arm: HR 0.957 (95%CI 0.806-1.136, p = 0.615). At 2 years from randomization there were a 61% of survivors in the TMZ group and 62% in the control group. There were a 49.7% of LTSP showing no differences between TMZ and control group. We found a higher prevalence of methylated MGMT in LTSP, but no differences were shown in patients with or without measurable disease at inclusion, status of IDH and the use of bevacizumab after progression. Conclusions: Adding 6 cycles of TMZ after the first 6 adjuvant cycles confers no additional benefit in OS. Nearly 50% of the patients included in GEINO 1401 who had been previously treated with TMZ 6 cycles without progressing were LTSP. Clinical trial information: NCT02209948.
Randomized phase 2 study of nivolumab (nivo) plus either standard or reduced dose bevacizumab (bev) in recurrent glioblastoma (rGBM).
Authors: Ahluwalia Manmeet Singh , Rauf Yasmeen , Li Hong , Wen Patrick Y. , Peereboom David M. , Reardon David A. 
Published: June 2021

2015 Background: Trials with anti-PD1 in rGBM have shown limited efficacy. VEGF is highly up regulated proangiogenic growth factor in GBM contributing to tumor-associated immunosuppression. Preclinical data suggests a potential dose effect of anti-VEGF therapy on immunomodulation. Hence, a combination of anti-PD1 and anti-VEGF may be a promising approach in rGBM. Methods: 90 patients with first-recurrent GBM were randomized (1:1) to nivolumab (240 mg IV Q2 weeks) with bevacizumab at standard (10 mg/kg; Arm A) or at low dose (3 mg/kg; Arm B) IV Q2 weeks. Stratification included extent of resection, age, performance status and MGMT methylation status. Single cell RNA sequencing with CITE-seq was used to analyze blood samples from pre- and 8 weeks post-treatment among 8 responders and 8 non-responders. Progression-free survival (PFS) and overall survival (OS) were compared between two arms. Results: 90 patients (Median age 60.6 years ranged 27.4-86.4, 67.8% male, median KPS 80) were enrolled between May 2018 and Jan 2020. Patients were followed in median 7.7 months (Range 0.7, 28.2). 35 of 88 patients were MGMT methylated (2 indeterminate). Overall OS was not significantly different between arm A and arm B (1 year: 41.1 vs 37.7%, p = 0.14), while OS was better for arm A in age > 60 (At 1-year: 46.2% vs 23.8%; Median: 10.6 vs 5.9 months; P = 0.046). OS was no different in the two arms for age ≤ 60 years (At 1-year: 35.6% vs 56.4; Median 8.0 vs 12.4 months; P = 0.90). Single cell RNA sequencing with CITE-seq was used to analyze blood samples from 16 patients, baseline and 8 weeks post treatment. Standard dose bevacizumab treated patients had decreased myeloid derived suppressor cells and an inflammatory response gene signature at 8 weeks. Most frequent toxicities ( > 20%) included fatigue (45.6%), proteinuria (34.4 %), diarrhea (28.9%), hypertension (23.3%) and lipase increase (21.1%). Toxicities in grade 3-4 were hypertension (7.8%), fatigue (5.6) and other non-neurological toxicities including DVT, PE, infection, and abnormal liver function. Conclusions: Overall PFS and OS rates appear similar for nivolumab with either standard or low-dose bevacizumab compared to historical benchmarks of bevacizumab monotherapy. Nivolumab with standard bevacizumab may benefit older but not younger patients. Ongoing response evaluation and immunocorrelative data will be presented. Clinical trial information: NCT03452579.
Presentation and management of patients with brain metastases of primary melanoma, non-small cell lung cancer, and breast cancer origin.
Authors: Kawahara Yuki , Mills Matthew , Potluri Thrisha , Fahey Matthew , Figura Nicholas B , Soyano Aixa , Washington Iman , Diaz Roberto , Oliver Daniel Eli , Yu Hsiang-Hsuan Michael , Etame Arnold B. , Vogelbaum Michael A. , Czerniecki Brian J. , Arrington John , Sahebjam Solmaz , Soliman Hatem Hussein , Forsyth Peter A. J. , Han Hyo S. , Ahmed Kamran A. 
Published: June 2021

2033 Background: As systemic therapy improves; the prevalence of brain metastases is increasing. Screening brain MRIs are currently recommended for all stage ≥ II non-small cell lung cancer (NSCLC) and stage IIIB–IV melanoma patients, but only when neurologic symptoms arise in stage IV or recurrent breast cancer (BC) patients. This study assessed the presentation and institutional outcomes treating brain metastases (BM) of BC, NSCLC, and melanoma origin. Methods: Patients with BM treated between 2014 and 2019 with primary melanoma, NSCLC, and BC were identified. Characteristics of initial BM diagnoses were retrieved from clinical chart review. Kruskal-Wallis and Pearson’s chi-square tests were used to test differences between groups. Overall survival (OS) was calculated from dates of initial BM diagnosis using the Kaplan–Meier method. Results: A total of 959 patients were identified (BC 18%, NSCLC 51%, melanoma 31%). BC patients were younger at initial presentation (BC median age: 57, NSCLC 65, melanoma 62, p< 0.0001). At BM diagnosis, BC patients were more likely to have concurrent systemic metastasis (BC 77%, NSCLC 42%, melanoma 69%, p< 0.0001), at least 5 BM (BC 27%, NSCLC 14%, melanoma 13%, p= 0.0004), and leptomeningeal disease (BC 23%, NSCLC 6%, melanoma 6%, p< 0.0001). Patients with BC were significantly more likely to receive whole brain radiation therapy (WBRT) (BC 58%, NSCLC 37%, melanoma 22%, p< 0.0001) and less likely to receive stereotactic radiation (BC 26%, NSCLC 48%, melanoma 58%, p< 0.0001) following initial BM diagnosis. There were no significant differences in surgical resection between cancer types (BC 24%, NSCLC 24%, melanoma 29%, p =0.166). Median OS was shorter for BC (BC 9.9 months, NSCLC 10.3 months, melanoma 13.7 months, p= 0.0006) following BM diagnosis. Conclusions: Our institutional analysis found BC patients were more likely to be younger, present with more advanced brain disease, require WBRT, and have poorer OS than NSCLC and melanoma patients following initial brain metastasis diagnosis. This may be due in part to a lack of brain MRI screening recommendations in BC. Further investigation is needed to determine which BC patients are at sufficient risk to warrant brain MRI screening.
Phase 1 dose-escalation study of ACT001 in patients with recurrent glioblastoma and other advanced solid tumors.
Authors: Lickliter Jason D. , Jennens Ross , Lemech Charlotte Rose , Kichenadasse Ganessan , Cai Dongpo , Su Steven Yung-Chang 
Published: June 2021

2037 Background: ACT001, an orally-available parthenolide derivative targeting NF-κB and STAT3 signaling pathways, has immunomodulatory effects and showed promising activity in preclinical models of glioblastoma (GBM). The updated data in this report summarizes clinical findings from this first-in-human clinical trial of ACT001 in patients with advanced solid tumors, including GBM. Methods: Eligible patients were adults with ECOG PS 0-1 and satisfactory hematologic, renal and hepatic function. Additionally, GBM patients had progressive disease despite initial radiation and temozolomide, measurable tumor and no radiation treatment within 3 months prior to enrollment. ACT001 was given orally BID until intolerance or disease progression. Dose escalation followed a standard 3+3 design. Gliomas were imaged with MRI every 8 weeks and responses assessed using RANO criteria. Results: A total of 24 patients were enrolled as of this report: 14 with primary GBM, 2 with secondary GBM, 2 with anaplastic astrocytoma, 2 with colorectal cancer and 1 with each of anaplastic oligioastrocytoma, diffuse intrinsic pontine glioma, non-small cell lung cancer and pleural epithelioid mesothelioma. Median age was 49 years old (range 32-72). ACT001 dose levels were 100 mg BID, 200 mg BID, 400 mg BID, 600 mg BID, 900 mg BID and 1200 mg BID. Study drug treatment was well tolerated with no dose-limiting toxicity or ACT001-related SAE observed. The originally-planned maximum dose of 600 mg BID and the 1200 mg BID dose were expanded to 7 and 5 patients, respectively. The plasma half life of ACT001 was approximately 3-4 hours and no accumulation was observed after multiple dosing. Cmax and AUC0-last were approximately dose linear across the evaluated dose range. Of the 19 patients with recurrent malignant gliomas, a complete remission was observed in 1 patient with GBM (ongoing 27 months from starting ACT001) and stable disease lasting ≥ 6 months was seen in 3 patients. Preliminary biomarker analysis of PBMC samples revealed a post-treatment reduction in CD4+ Treg cells at some dose levels. Conclusions: In this first-in-human phase 1 study, ACT001 was well tolerated and showed satisfactory bioavailability and preliminary evidence of anti-tumor activity in malignant glioma patients dosed at 400 mg BID or lower. A phase 1b trial in recurrent GBM patients of ACT001 at 200-400 mg BID in combination with anti-PD-1 therapy is planned. Clinical trial information: ACTRN12616000228482.
Gene fusions in glioblastoma: Results of Gliocat project.
Authors: Hernandez Gonzalez Ainhoa , Esteve-Codina Anna , Carrato Cristina , Munoz Ana , Pineda Estela , Gallego Rubio Oscar , Arpi Oriol , Gut Marta , Martinez Garcia Maria , Lopez Raquel , Mesia Carlos , Barco Berron Sonia DEL , Sanz Carolina , Chen Sun , Domenech Marta , Alameda Francesc , Balana Carmen 
Published: June 2021

2042 Background: Malignant gliomas are heterogeneous diseases in genetic basis. The development of sequencing techniques, such as RNA-Sequencing, has identified many gene rearrangements encoding novel oncogenic fusions. Gene fusion discovery can potentially lead to the development of novel treatments, however studies of gene fusions in glioma remain limited. Methods: The GLIOCAT project studied 139 patient samples of newly diagnosed glioblastoma who had received the standard first-line treatment from 2004 to 2015, to identify gene fusion events from glioblastoma transcriptome data (RNA-Seq). The molecular subtype could be studied in 124 cases. RNA-Seq reads were mapped against the reference human genome with STAR-fusion version 0.7.0, specifically, with FusionInspector validate ( http://star-fusion.github.io ). Two other platforms, FusionHub ( https://fusionhub.persistent.co.in ) and Oncofuse ( www.unav.es/genetica/oncofuse.html ), were applied to eliminate false positives or previously described in healthy tissue and to predict of the oncogenic potential each fusion. Results: A total of61 patients showed 103 different fusions, a median of two fusions by sample. The majority of gene fusions were intrachromosomal and most frequently implied chromosome was 12 followed by 7. In addition, fusions were more common in patients with MGMT promoter methylation, TCGA classical subtype and 18 IGS subtype. There were no differences in age, sex, type of surgery or long survivors ( > 30 months). Ten fusions were already described in cancer, including three in gliomas (FRS2-KIF5A, EGFR-SEPT14 and FGFR3-TACC3). From the detected fusions, 22 of them included an oncogene or protooncogene. Conclusions: In our study, we report the landscape of gene fusions from a large data set of glioblastomas analyzed by RNA-seq. The majority of the fusions were private fusions. A minority of these recur in a low frequency but as many as a quarter of them included an oncogene or protooncogene. RNA-seq of GBM patient samples it is an important tool for the identification of patient-specific fusions that could drive personalized therapy. Furtherless, we will plan to validate this gene fusions.