tbuckley/cabot-search huggingface dataset:
Characterizing the end-of-life period in young patients with sarcomas.
Authors: Sujana Movva, Margaret von Mehren, Elizabeth Handorf, Eric Daniel Tetzlaff, Anjali Albanese, Kathleen Murphy, Marcin Chwistek
Journal: Journal of Clinical Oncology (2017)

11027 Background: There is a paucity of data surrounding the end-of life transition (EOLT) in young adult (YA) patients with sarcoma. Discussions surrounding prognosis, goals of care (GOC), hospice and death can be challenging in these patients as they may be at a particularly hopeful stage of their life. The purpose of this study is to better understand the EOLT in YA patients with sarcoma by determining the survival and number of lines of treatment at different periods in the disease course. In addition, the study aims to determine what impacts the decision to discontinue anti-cancer therapy. Methods: Fox Chase Cancer Center (FCCC) patients, 18-39 years old who died from sarcoma between January 2013 and December 2016 were included in this study. Patient demographics, tumor specific data, treatment and treatment decisions were collected from electronic medical records and retrospectively analyzed. Results: 38 FCCC patients who were diagnosed between the ages of 18-39 died between January 2013 and December 2016. Of these 21 patients were between the ages of 18-39 at the time of their death. Median age at death was 30 (range: 22-40). The most common histologies were Ewing Sarcoma, GIST (n = 3) and osteosarcoma, synovial sarcoma (n = 2). Median time from diagnosis of metastatic disease to death was 21.4 months. Median time from metastatic disease to discussion of GOC and hospice by any provider was 9.6 and 16.7 months respectively. The hospice discussion was held by the treating oncologist 87.5% (n = 16) of the time (outpatient 35.7% and inpatient 64.3%). 60% (n = 15) of patients/family selected hospice when it was originally presented to them (multi-organ failure, unarousable, paralysis). The hospice discussion was held at a median of 21 days prior to death and median time on hospice was 13 days (range: 1-63). Patients were treated a median of 54 days prior to their death (range: 6-1823). Median times on first, 2 nd to last and last treatments were 273, 67 and 22.5 days respectively (P = 0.002). Conclusions: Focusing on this particular group of patients will generate benchmark data that can help counsel them about their specific expected survival and changes in clinical status as their disease progresses. We plan to compare this data with that of older patients.
Unexpected pharmacokinetics of evofosfamide observed in phase III MAESTRO study.
Authors: Jack P. Higgins, Nenad Sarapa, Jason Kim, Eric Poma
Journal: Journal of Clinical Oncology (2018)

2568 Background: Evofosfamide (Evo) is a prodrug of Br-IPM that is preferentially activated under hypoxic conditions. Hypoxia in locally advanced unresectable pancreatic ductal adenocarcinoma (PDAC) is associated with disease progression and poor prognosis. Methods: Gemcitabine (Gem) was evaluated with or without Evo in a randomized phase II (Ph 2) trial (N = 214) in US patients with advanced PDAC (NCT01144455). Two doses of Evo (240 mg/m2 or 340 mg/m2) were tested with 340 mg/m2 showing a significant improvement in ORR and PFS.MAESTRO was an international, randomized, double-blind, placebo-controlled phase III (Ph 3) trial (N = 693) of Evo + Gem versus Placebo (Pbo) + Gem in patients with locally advanced unresectable or metastatic PDAC (NCT01746979) using the same Ph2 schedule and 340 mg/m2 Evo dose. Results: Median OS in the Ph 3 study was 8.7 mo with Evo + Gem vs 7.6 mo with Pbo + Gem; HR = 0.84 (p = 0.059). Median PFS was 5.5 mo with Evo + Gem vs 3.7 mo with Pbo + Gem; HR = 0.77 (p = 0.004). The outcomes observed in the Ph 3 study (340 mg/m2 dose) were similar to the 240 mg/m2 dose Ph 2 outcomes (median OS = 8.7 mo; median PFS = 5.6 mo). Notably, a new ethanol-based formulation to improve drug product solubility was introduced after the Ph 2 study and before the start of the Ph 3 study. Conclusions: : Comparison of the Evo PK profile from the Ph 3 and Ph 2 studies suggest the formulation change may have substantially reduced Evo serum exposure (Table 1). This reduction in Evo exposure could explain why the efficacy seen in the Ph 2 study at the 340 mg/m2 dose were not replicated in the Ph 3 study. Evo is currently being tested at higher doses with the new formulation (ethanol-based) in an attempt to replicate the PK seen with the previous formulation at 340 mg/m2. Clinical trial information: NCT01746979.Evo PK Comparison: Ph 2 (old formulation) and Ph 3 (new formulation). PK Parameters Ph 2 Evo + Gem Ph 3 Evo + Gem Evo 240 mg/m2 + Gem Evo 340 mg/m2 + Gem Evo 340 mg/m2 + Gem N Geometric Mean Mean (SD) N Geometric Mean Mean N Geometric Mean Mean (SD) Cmax (µg/mL) 47 5.32 6.09 (3.11) 51 9.27 10.17 (4.92) 317 6.34 7.54 (5.49) AUC (µg-h/mL) 44 5.33 5.90 (2.81) 47 8.94 9.76 (4.54) 302 6.02 6.61 (3.03) AUC (AUCINF) = Area under the concentration-time curve from 0 to infinity; Cmax = maximum peak observed concentration;SD = standard deviation
Variant angina and reperfusion ventricular tachyarrhythmias.
Authors: P Carbonin, M Di Gennaro, F Furlanello
Journal: Circulation (1980)

EDITORwith autopsy series, stating, "Previous autopsy studies have reported vegetative valvular lesions in 53% of patients who died of active infective endocarditis.'`However,they misinterpreted the data from these studies.2 3 In fact, all patients in the necropsy studies cited by Stewart et al. had valvular vegetations.The fact that these vegetations were superimposed on previously normal valves in 53% of the cases may be the source of confusion.
ZUMA-7: A phase 3 randomized trial of axicabtagene ciloleucel (Axi-Cel) versus standard-of-care (SOC) therapy in patients with relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL).
Authors: Olalekan O. Oluwole, Michael Russell Bishop, Christian Gisselbrecht, Leo I. Gordon, Marie Jose Kersten, David G. Maloney, Norbert Schmitz, María Dolores Caballero Barrigon, John Kuruvilla, Kevin W. Song, Caron A. Jacobson, Loretta J. Nastoupil, Peter Riedell, Yizhou Jiang, John M. Rossi, Lillian Lee, Paul C. Cheng, Frederick Lundry Locke
Journal: Journal of Clinical Oncology (2018)

TPS7585 Background: For pts with DLBCL who fail 1st-line therapy, the only potentially curative treatment is salvage chemotherapy followed by autologous stem cell transplant (ASCT). Only »50% of pts receiving salvage chemotherapy proceed to ASCT and 3-y progression-free survival (PFS) is 53% after ASCT (Gisselbrecht et al. JCO. 2010). In ZUMA-1, the pivotal, single-arm study of axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, the objective response rate (ORR) was 82% (58% complete response [CR] rate) in pts with refractory large B cell lymphoma; 40% remained in CR with 15.4-mo median follow-up (Neelapu & Locke et al. NEJM. 2017). This trial was primarily in pts with ≥ 2 prior lines of therapy and supported US FDA approval of axi-cel for the treatment of adult pts with R/R DLBCL after ≥ 2 prior lines of systemic therapy. ZUMA-7 investigates axi-cel as 2nd-line therapy for pts with R/R DLBCL. Methods: ZUMA-7 (NCT03391466) is a randomized (1:1) Phase 3, open-label, multicenter study of axi-cel vs SOC 2nd-line treatment in pts with R/R DLBCL. Planned enrollment is 350 pts. Eligible pts must have R/R DLBCL after 1st-line therapy (including an anti-CD20 antibody and an anthracycline) and intend to proceed to ASCT if they respond to 2nd-line therapy. Exclusion criteria include prior SCT, prior CD19-targeted therapy, or active infection. Pts randomized to axi-cel will undergo leukapheresis, then lymphodepleting chemotherapy (fludarabine 30 mg/m2/d and cyclophosphamide 500 mg/m2/d for 3 d), followed by a single infusion of axi-cel at 2 × 106 CAR T cells/kg. Corticosteroid bridging therapy is allowed for pts with high disease burden at screening. Pts in the SOC arm will receive investigator's choice of 2nd-line salvage therapy (R-ICE, R-DHAP, R-ESHAP, or R-GDP); pts who respond after 2–3 cycles will receive high-dose therapy and ASCT. The primary endpoint is event-free survival defined as time from randomization to disease progression, start of new lymphoma therapy, or death. Secondary endpoints include ORR, overall survival, PFS, duration of response, safety, and pt-reported outcomes. Accrual is ongoing. Clinical trial information: NCT03391466.
Abstract 20752: In-Hospital Telemetry Monitoring in Patients With Acute Coronary Syndrome - Arrhythmias and Long Term Survival
Authors: Nina Fålun, Jørund Langørgen, Per Ivar Hoff, Roy M Nilsen, Jan Erik Nordrehaug, Trond R Pettersen, Tone M Norekval
Journal: Circulation (2017)

Introduction: In-hospital telemetry monitoring is recommended in all patients with ACS to reveal severe arrhythmias and sudden cardiac death. According to the Practice Standards for Electrographic ...
Inflammatory biomarkers for prediction of tumor responses and adverse events in non-small cell lung cancer patients treated with anti-PD-1 inhibitor.
Authors: Norikazu Matsuo, Koichi Azuma, Satoshi Hattori, Akihiko Kawahara, Hidenobu Ishii, Takaaki Tokito, Kazuhiko Yamada, Yuji Shibata, Tadasuke Shimokawaji, Tetsuro Kondo, Terufumi Kato, Haruhiro Saito, Kouzo Yamada, Tetsuro Sasada, Tomoaki Hoshino
Journal: Journal of Clinical Oncology (2018)

e21050 Background: Although programmed death (PD)-1 immune checkpoint inhibitors have been shown to elicit durable responses and prolong survival in patients with non-small cell lung cancer (NSCLC), no clinically reliable and useful biomarkers of response to anti-PD-1 therapy are available. Here we attempted to identify biomarkers in peripheral blood from 27 patients with advanced/recurrent NSCLC receiving anti-PD-1 therapy. Methods: Peripheral blood samples were taken from NSCLC patients before nivolumab treatment and every 6-12 weeks from the patients who continued nivolumab treatment. The levels of 88 different soluble factors in peripheral blood were examined before and after PD-1 blocker treatment. Univariate logistic regression and cox regression analysis were used to select and built soluble factors correlating with whether those soluble factors were associated with patient survival and treatment-related adverse events (AEs), respectively. Results: The plasma levels of GM-CSF and Chitinase 3-like-1 before treatment were significant correlated with PFS (P= 0.005 and P= 0.007, respectively). In addition, the changes in the plasma levels of CXCL2, VEGF, IFNa2, and MMP2 after treatment were significantly correlated with PFS (P < 0.001, P= 0.019, P= 0.014, and P= 0.010, respectively), and changes in the plasma CXCL2 level were also significantly associated with treatment-related AEs (P= 0.017). Notably, in 24 (77%) of the 31 patients with disease progression, relapse closely coincided with elevation of the plasma CXCL2 level above the baseline. Conclusions: These six soluble factors identified in plasma can be easily measured by minimally invasive blood sampling, they could be clinically applicable as biomarkers for predicting the clinical benefit of PD-1 blocker therapy for NSCLC patients, thus avoiding unnecessary treatments and minimizing the associated AEs and costs.
Comparative genomic analysis for pediatric cancer patients evaluated in a California Initiative to Advance Precision Medicine Demonstration Project.
Authors: Olena Morozova, Sofie R. Salama, Isabel Bjork, Theodore C. Goldstein, Sabine Mueller, Leonard S. Sender, Alejandro Sweet-Cordero, David Haussler
Journal: Journal of Clinical Oncology (2017)

TPS10578 Background: California Kids Cancer Comparison (CKCC), a demonstration project for the California Initiative to Advance Precision Medicine, evaluates the utility of incorporating gene expression information into the genomic analysis of difficult-to-treat pediatric cancers. CKCC is a partnership between UC Santa Cruz and clinical genomic trials conducted by Children’s Hospital of Orange County, UC San Francisco (Pacific Pediatric Neuro Oncology Consortium), and Stanford University. Methods: CKCC compares each prospective tumor’s RNA sequencing profile to over 11,000 uniformly analyzed tumor profiles from pediatric and adult cancer patients. These comparisons are used to identify genes and pathways that are significantly over expressed in each patient’s tumor. The pathways are reviewed by data analysis for the potential for clinical impact and presented to the treating oncologist in a molecular tumor board setting.
P03.03 Case management in the Functional Unit of Neuro-Oncology in adult patients
Authors: A Hernández Marfil, V Granados Casas, L Garrote Moliner, S Cabrera Jaime
Journal: Neuro-Oncology (2018)

Currently in Spain there are between 6 and 7 cases of primary tumors of the Central Nervous System (CNS) per 100,000 inhabitants per year. Despite being a rare pathology, it requires a comprehensive and multidisciplinary approach given its complexity. The Functional Unit of Neuro-oncology (UNO) is a multidisciplinary oncological care unit specialized in CNS tumors and its approach. The UNO integrates all those professionals involved in making decisions about the diagnosis and treatment of CNS tumors. We work as a single team, with the main objective of offering and carrying out the best therapeutic strategy decided in the care committee of the functional unit; to achieve the best clinical results and the holistic approach of the person and family. Describe the autonomous and interdisciplinary role of the case management nurse during the neuro-oncological process in adults and their families, from diagnosis to outcome of the pathology. Autonomous role: First nursing visit: completion of the reception to the center and assessment and comprehensive screening of the patient and family environment, coordinating the care process globally and safely, according to the healthcare needs. Internal assessment visit: evaluation of the complications derived from the treatment (toxicity, guidelines to follow, dosage, etc). In successive nursing visit monitoring of the toxicities produced by the treatment. Treatment visits made alternately with the medical practitioner according to the treatment scheme. Telematics follow-up of the patient: a week after the start of treatment for evaluation of adherence and tolerance to treatment and detection of complications, assessment of the needs of the caregiver, and resolution of spontaneous consultations of the health process. Interdisciplinary role: Prescription and planning of chemotherapy and its effects; the indication of corticosteroid use; the prescription / indication of anticompetitive treatment; the alternate visits with medical practitioner according to the treatment scheme; the joint visit with a doctor in cases of high complexity and / or information approach. Given the deterioration of the basic functions of patients added in most cases with a cognitive, sensitive, motor, physical and emotional deterioration presented by patients; the need for the presence of the case manager is essential for a multidimensional approach and thus reach excellence in care.
Predicting tumor-immune response to checkpoint inhibitors using a novel patient-derived live tumor explant model.
Authors: Padhma Radhakrishnan, Aaron Goldman, Baraneedharan Ulaganathan, Allen Thaya Kumar, Laura Maciejko, Hans Gertje, Basavaraja U Shanthappa, Debapriya G G Mehrotra, Manjusha Biswas, Saravanan Thiyagarajan, Biswanath Majumder
Journal: Journal of Clinical Oncology (2017)

e20035 Background: Immunotherapy has emerged as a powerful treatment paradigm wherein therapies primarily target immune components. For example, blockade of PD-1 and PD-L1 offers effective treatment options for patients with aggressive tumors such as head and neck squamous cell carcinoma (HNSCC) and in non-small cell lung carcinoma (NSCLC). However, clinical responses to immotherapy vary widely among patients. There is an unmet need to understand these disparities at the individual patient level. Rationally combining checkpoint inhibitors may address many of these underlying challenges. Methods: Here, we describe a patient-derived ex-vivo platform technology CANscript™, which captures the 3D profiles of native tumor microenvironment by incorporating tumor tissue, autologous immune cells, and immune-targeted agents. Utilizing late stage HNSCC and NSCLC patient tumors we interrogated the phenotypic changes in the tumor-immune contexture in response to standard-of-care agents, PD-1 and PD-L1 inhibitors. Flow cytometry and immunohistochemistry profiling of CD8, CD45, FOXP3, CXCR4, CD68, PDL1, PD1), cytokine profile (IL6, IL8, IFN-g, IL12 and others), and tumor proliferation/apoptosis were measured. Results: The data suggest that PD-1 and PD-L1 blockade induced patient-specific response, which was characterized by differential distribution and infiltration of CD8+ and CD4+ lymphocytes, distinct patterning of cytokines linked to functional dysregulation, and changes in tumor proliferation and apoptosis. Interestingly, the data demonstrated unique immune signatures associated with single agent vs. combination therapy that imply functionally distinct mechanisms of orchestration of response. Conclusions: Our data highlights the translational underpinnings of of CANScript™ as an ex vivo platform for predicting patient driven therapeutic response of immune checkpoint inhibitors where distinct tumor-immune networks influence clinical response to therapy. Information obtained from this study can re-shape our understanding of patient selection and rational combinations for novel immune checkpoint inhibitors.
Next generation sequencing (NGS) in lung adenocarcinoma (LA) as a guide to treatment selection.
Authors: Emmet Jordan, David Barron, Nikolaus Schultz, Debyani Chakravarty, Mark G. Kris, Charles M. Rudin, Bob T. Li, Helena Alexandra Yu, Alexander E. Drilon, Valerie W. Rusch, Jose Baselga, Barry S. Taylor, David Michael Hyman, David B. Solit, Marc Ladanyi, Michael F. Berger, Maria E. Arcila, Gregory J. Riely
Journal: Journal of Clinical Oncology (2016)

9084 Background: Tumor genomic profiling is standard for LA patients (pts). The identification of actionable drug targets has prompted efforts to develop multiplexed assays that identify both clinically validated biomarkers and driver alterations for rational clinical trials. We analysed molecular profiling data to assess if identification of a driver mutation prompted administration of matched standard/ investigational therapy (MT). Methods: Prospective genomic analysis of LA was performed using MSK-IMPACT, a multiplexed NGS assay that detects base substitutions, short indels, copy number alterations and select rearrangements involving 341 (v1) or 410 (v2) cancer related genes from Jan 2014 - Dec 2015. Samples were reviewed for the presence of validated or putative drivers that would be predicted to confer sensitivity to MT. Potential targetable mutations (MUT) were assigned to one of four levels based upon published evidence that a mutation predicts for drug sensitivity. Cases with > 1 targetable MUT were grouped with the mutation with the highest level of evidence. Results: 847 LA pts were profiled, 783 pts had recurrent/metastatic (R/M) LA. 664 (84.8%) had an actionable somatic MUT (see table for select MUT). 276 pts had clinically validated biomarkers of drug response [Levels 1 (EGFR mut, Alk fusion (fus)], Level 2A [RET/ROS fus, BRAF (V600E), MET splice/amp] of which 88% received MT with 86% having clinical benefit (CB). Pts with level 3, 4 MUT were less likely to receive MT (5%), a notable outlier being ERBB2 MUT (53% received MT, 40% CB). Pts with level 3, 4 MUT were more likely to receive immunotherapy (IT) than pts with Level 1, 2A MUT. Conclusions: Potentially actionable genetic MUT are identified in most LA pts. Most but not all pts with clinically validated (CV) actionable genetic events received MT. A significant minority of pts with putative but not CV actionable MUT enrolled onto investigational clinical trials; most accruals were for trials of IT and not MT. Level Gene No. R/M No. Receive MT MT% IT% 1 EGFR 182 170 93 11 ALK fus 24 22 92 8 2A RET fus 12 7 58 8 ROS1 fus 19 13 68 6 BRAF V600E 14 10 71 21 MET Splice/AMP 25 20 80 16 2B ERBB2 AMP 5 0 0 0 3 KRAS 227 2 1 19 ERBB2 MUT 19 10 53 26 MAP2K1 3 0 0 0 4 BRAF NonV600E 10 2 20 40 Exon 20 EGFR 14 1 7 36 RAF1 2 0 0 50
Abstract 17841: Heart or Heart and Lung Transplantation for Patients With Congenital Heart Disease in England: Outcomes and Future Predictions
Authors: Konstantinos Dimopoulos, Kavitha Muthiah, Rafael Alonso-Gonzalez, Stephen J Wort, Gerhard P Diller, Michael A Gatzoulis, Aleksander Kempny
Journal: Circulation (2016)

Introduction: Increased longevity in patients with congenital heart disease (CHD) is associated with an increase in long-term complications, mainly heart failure, which may not be amenable to surgi...
Conventionally fractionated radiation and anti-PD-L1 treatment to relieve radiation resistance via regulation proliferation pathway and immunity system.
Authors: Xiao Mei Gong, Cai Cun Zhou, Xuefei Li, Chao Zhao, Shi xiong Liang
Journal: Journal of Clinical Oncology (2016)

e14563 Background: Patients with local advanced non-small-cell lung cancer frequently receive prolonged treatment with chemotherapy and/or fractionated radiotherapy (RT). Unfortunately, local relapses often occur following RT treatment. The PD1/PD-L1 axis is involved in the maintenance of peripheral tolerance through inhibition of T cell function. We characterized PD-L1 in NSCLC cell lines, and explore the relationship between immunology escaping and tumor cell proliferlation and apoptosis with receiving radiotherapy. Methods: To detect the PD-L1 in NSCLC cell after RT by western blot and flow cytometry. To analysis PI3K/AKT and STAT3 pathway and Bcl2 family pathway in A549 radiationresistance cell (A549/X) by western blot. SiRNA of PD-L1 was used to A549/X, and then to observe the difference in proliferation pathway. As for in mice study, immunohistochemistry was used to detect the PD-L1, TGFβ, and NF-KB in control, anti-PD-L1, radiation and radiation plus anti-PD-L1 group. We further detected the CD8+ T cell and iTregs in immunity system. We also evaluate the relationship between the PD-L1, CD8+ T cell and the radiation resistance with immunohistochemistry in tumor tissue from NSCLC patients. Results: Patients whose tumor expressed the higher PD-L1, who had the more radiation resistance and had less CD8+ T cell around tumor microenvironment. We observed the activation of the anti-apoptosis protein bcl2 and the inhibition of the pro-apoptosis protein Bim in A549/X. After siRNA interfering to A549/X, it’s PD-L1 decreased. A549/X came to be apoptotic. While the p-AKT, p-STAT3 and NF-KB didn’t change. The higher expression of PD-L1 could exhaust CD8+ T cells and attract the iTregs infiltrate around tumor cells. Conclusions: Conventionally RT can activate the TGFβ. The TGFβ could evoke the PI3K/AKT and the STAT3 pathway. Finally, the two proliferation pathway activated the NF-KB protein. The NF-KB is the key to up-regulation PD-L1. When PD-L1 over-expression, lung cancer would be apoptosis less and immunity escaping. SiRNA interfering PD-L1 can eliminate the radiation resistance of the A549/X.