tbuckley/cabot-search huggingface dataset:
AB0514 PARATHORMONE BUT NOT VITAMIN D SERUM LEVELS ARE ASSOCIATED WITH SUBCLINICAL ATHEROSCLEROSIS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Mayra Giannelou, Aikaterini Stamouli, Eleni Antypa, Haralampos M. Moutsopoulos, Clio Mavragani
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Growing evidence supports a link between alterations in bone metabolism and cardiovascular (CV) disease in both general and autoimmune populations. <h3>Objectives:</h3> In the current study we aimed to explore whether vitamin D deficiency and/or increased parathormone (PTH) levels, as well as impairment of bone mass density, influence CV risk in patients with systemic lupus erythematosus (SLE). <h3>Methods:</h3> 138 consecutive SLE patients were enrolled in the study. Clinical features, hematological, serological and immunological profile, as well as therapeutic regimens was recorded in all patients. Classical CV and osteoporosis risk factors were assessed in all participants. Intima-medial thickness scores (IMT) and carotid and/or femoral (C/F) plaque formation were evaluated by ultrasound. Assessment of bone mineral density (BMD) and asymptomatic osteoporotic fractures was also performed by dual X-ray absorptiometry and lateral thoracic and/or lumbar spine X-rays, respectively. Univariate and multivariate models were implemented for statistical analysis. <h3>Results:</h3> PTH -but not 25(OH)vitamin D3- serum levels were found to be increased in lupus patients with subclinical atherosclerosis (plaque formation and/or arterial wall thickening) compared to those without (51.1±27.7 vs 37.4±18.4 pg/ml, p= 0.003 and 54±32.7 vs 40±18.3 pg/ml, p= 0.02, respectively). Abnormal PTH serum concentrations (&gt;65 pg/ml) in SLE patients was identified as a risk factor for both plaque formation and high IMT scores (&gt;0.9mm) [OR 95% (CI): 8.2 (1.8-37.4) and OR 95% (CI): 3.9 (1.3-11.8), respectively]. High PTH levels were found to be associated with low 25(OH)vitaminD3 levels, advanced age and increased triglycerides in the lupus cohort. Moreover, SLE patients with plaque formation exhibited increased rates of osteoporosis (based on WHO classification) compared to those without [19.5% vs 5.3%, p= 0.017, OR 95% (CI): 4.4 (1.2-15.9)]. Finally, an inverse correlation between femoral neck BMD values and total IMT scores was observed (r:-0.42, p=0.008). <h3>Conclusion:</h3> Subclinical atherosclerosis in patients with lupus is associated with increased serum PTH levels and reduced bone mass density. These findings further support the presence of shared etiopathogenetic mechanisms between atherogenesis and altered bone metabolism. <h3>Disclosure of Interests:</h3> None declared
A nomogram to predict outcomes of lung cancer patients after pneumonectomy based on 47 indicators.
Authors: Bo Cheng, Cong Wang, Xue Meng
Journal: Journal of Clinical Oncology (2019)

e20014 Background: Nomograms are commonly used tools to estimate prognosis in oncology and medicine.We aimed to establish a nomogram with patients’ characteristics and all available hematological biomarkers for lung cancer patients. Methods: All indexes were cataloged according to clinical significance. Principle component analysis (PCA) was used to reduce the dimensions. Each component was transformed into categorical variables based on recognized cut-off values from receiver operating characteristic (ROC) curve. Kaplan-Meier analysis with log-rank test was used to evaluate the prognostic value of each component. Multivariate analysis was used to determine the promising prognostic biomarkers. Five components were entered into a predictive nomogram. The model was subjected to bootstrap internal validation and to external validation with a separate cohort from Shandong Cancer Hospital. The predictive accuracy and discriminative ability were measured by concordance index (C index) and risk group stratification. Results: Two hundred thirty-six patients were retrospectively analyzed in this study, with 134 in the Discovery Group and 102 in the Validation Group. Forty-seven indexes were sorted into 8 subgroups, and 20 principle components were extracted for further survival analysis. Via cox regression analysis, five components were significant and entered into predictive nomograms. The calibration curves for probability of 3-, and 5-year overall survival (OS) showed optimal agreement between nomogram prediction and actual observation. The new scoring system according to nomogram allowed significant distinction between survival curves within respective tumor-node-metastasis (TNM) subgroups. Conclusions: A nomogram based on the clinical indexes was established for survival prediction of lung cancer patients, which can be used for treatment therapy selection and clinical care option. PCA makes big data analysis feasible.
Safety and activity of venetoclax in combination with high-dose cytarabine in children with relapsed or refractory acute myeloid leukemia.
Authors: Seth E Karol, Thomas Alexander, Soumyasri Das Gupta, Stanley B. Pounds, Kristin Canavera, Jeffery M Klco, Norman James Lacayo, Ching-Hon Pui, Joseph T Opferman, Jeffrey E Rubnitz
Journal: Journal of Clinical Oncology (2019)

10004 Background: Venetoclax is an orally available BCL-2 antagonist with demonstrated activity in adults with newly diagnosed or relapsed acute myeloid leukemia (AML). Here, we describe the first use of venetoclax 1) in combination with high-dose cytarabine and idarubicin 2) in patients 2-22 years old with relapsed AML. Methods: Patients with relapsed AML or AML refractory to at least two courses of induction therapy were enrolled in this Phase 1 study with a rolling-six design. All patients received venetoclax (240 or 360 mg/m 2 ) on days 1-28 and low-dose (LD: 100 mg/m 2 every 12 hours x 20 doses) or high-dose (HD: 1000 mg/m 2 every 12 hours x 8 doses) cytarabine beginning on day 8 (Table). Patients who had previously received &lt; 270 mg/m 2 of doxorubicin equivalents also received idarubicin 12 mg/m 2 on day 8 in dose level 4; other patients were enrolled on the expansion cohort at dose level 3. Non-hematologic CTCAE grade 3 or higher toxicities were intensity limiting (ILT), excluding those anticipated with HD cytarabine. Results: Among 18 evaluable patients, a single ILT (prolonged hematological suppression beyond day 50) was observed (Table). Toxicities were consistent with the underlying cytotoxic chemotherapy, with 14 patients experiencing a total of 40 grade 3 toxicities including 6 documented infections and 23 episodes of febrile neutropenia. There was 1 grade 4 fungal sepsis. The recommended phase 2 dose of venetoclax was 360 mg/m 2 (max 600 mg) when combined with HD cytarabine or HD cytarabine/idarubicin. Of the 12 patients with &gt; 50% reduction in blasts following the 7-day venetoclax window therapy, end-of-cycle marrow responses included 7 CR/CRi and 3 PR. Minimal residual disease negative remissions occurred in 4 patients. BH3 profiling of samples and a phase 2 expansion of both dose levels 3 and 4 to further characterize the promising activity of these combinations are underway. Conclusions: Venetoclax combined with cytarabine or cytarabine/idarubicin is active and well tolerated in pediatric patients with relapsed/ refractory AML. Clinical trial information: NCT03194932. [Table: see text]
Whole transcriptome sequencing in metastatic cancer: A review of expression outliers in 113 metastatic breast cancer patients.
Authors: Nathalie LeVasseur, Veronika Csizmok, Melika Bonakdar, Yaoqing Shen, Lindsay Zibrik, Eric Yang Zhao, Sophie Sun, Karen A. Gelmon, Janessa J. Laskin, Marco A. Marra, Stephen K. L. Chia
Journal: Journal of Clinical Oncology (2019)

3080 Background: The genomic profiling of breast cancers has led to a greater understanding of the mutational landscape of metastatic breast cancer (MBC) with potential therapeutic implications. Despite these advances, there is a paucity of data regarding the additive value and relevance of gene expression across histological and molecular subtypes, which represents the majority of informative and actionable findings identified in the BC Cancer personalized oncogenomics program (POG). Methods: Informative findings with potential clinical application from whole genome sequencing (WGS) and whole transcriptome sequencing (WTS) in MBC patients between 2012-2018 were reviewed. Variants observed in pathway genes of potential clinical relevance, as defined by a curated list of genes, were examined across histological subtypes. High and low expression outliers relative to TCGA breast cases, defined as expression greater than 98th percentile and FC &gt; 2 compared to Illumina breast dataset and lower than 25th percentile and FC &lt; -2 compared to Illumina breast dataset, respectively, were then analyzed to establish how many outliers were observed in pathways of potential clinical relevance. Results: A total of 113 cases were included. WGS revealed that TP53 was the most frequent single nucleotide variant (SNV) in triple negative breast cancer (23/30, 77%), whereas PIK3CA (37/78, 47%), PTEN (11/78, 14%) and ESR1 (19/78, 24%) were most frequent in ER positive cases and CDKN2A (2/18, 11%) in HER2 positive cases. Across all subtypes, the mTOR and cell cycle pathways were found to have the highest frequency of SNVs, with the identification of 86 and 71 variants, respectively. Expression data for 113 RNA-sequenced patients revealed a high frequency of expression outliers in the mTOR pathway (26 high expression and 424 low expression outlier genes) and cell cycle pathways (35 high expression and 331 low expression outlier genes), but also in the WNT pathway (96 high expression and 490 lower expression outlier genes) and NOTCH pathway (84 high expression and 564 low expression outlier genes). Conclusions: Frequently identified SNVs across histological subtypes were correlated with expression outliers in pathways of clinical relevance in breast cancer. Additional informative findings, in pathways of potential clinical relevance not historically targeted in breast cancer, were identified with WTS. The clinical utility of these findings warrants further study.
Outcomes of immunotherapy administration for hospitalized cancer patients.
Authors: Houry Leblebjian, Megan Duperrault, Brett Glotzbecker, Mark M. Awad, Sylvia Bartel, Anne McDonnell, Craig A. Bunnell, Andrew J. Wagner, Lauren M. Hamel, David W. Dougherty
Journal: Journal of Clinical Oncology (2019)

e18225 Background: With approvals across multiple cancer types and favorable toxicity profiles, oncologists may consider using immunotherapy (IMT) while their patients are hospitalized. Inpatient IMT may be cost-prohibitive to administer for most institutions due to high cost and inpatient payment structure, but little data are available to evaluate outcomes for IMT in hospitalized patients. We investigated the survival benefit of administering IMT to hospitalized patients with cancer at an NCI-designated cancer center. Methods: We conducted a retrospective chart review of all patients receiving ipilimumab, nivolumab, or pembrolizumab during inpatient admission at Dana-Farber Cancer Institute/Brigham &amp; Women’s Hospital in 2017. For each patient, we assessed: total dose, indication for dosing, cancer type, time between dose and discharge, time between discharge and death, and total cost (average wholesale price). Study follow up was January 1, 2017 to July 1, 2018. Results: Fifty doses of IMT were administered to 44 patients. Most patients (40) received 1 dose, 2 patients received 3 doses, 1 patient received 2 doses, and 1 patient received a combination of ipilimumab/nivolumab. The most common cancer types were lung (41%), gastrointestinal (18%), and head and neck (16%). Indications for IMT administration were: patient due for next dose (48%), disease progression (42%), and new diagnosis (11%). The majority of doses (70%) were received within 7 days prior to discharge, with 32% of doses within 1 day of discharge. The majority of patients (86%) died in the study period; 14% of patients died during admission. Average survival between discharge and death was 54 days (range: 0-444 days). Total cost of inpatient IMT administration was $413,370, an average of $9,395 per patient. Conclusions: To our knowledge, this is the largest analysis of outcomes for patients receiving IMT during a hospitalization. Inpatient use of IMT in cancer patients is associated with high cost and poor clinical outcomes. Dosing within one week prior to hospital discharge was common. Clinical factors such as PD-L1 status, disease status, and reason for admission, which may be important to understand which patients may benefit most from inpatient IMT, should be examined.
The 6th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2015), Evidence and Consensus on HCC Management. Osaka, Japan, July 3-5, 2015: Abstracts
Journal: Liver Cancer (2015)

Many studies report high response rates in patients with advanced HCC receiving HAIC, and clinical responses translate to survival benefits. Therefore, prediction of an antitumor response is important in selecting appropriate treatments. There are no proven post-sorafenib therapeutic procedures or procedures for HCC patients with poor liver function, and HAIC is one of the few options for patients in these situations. Despite studies showing its effectiveness, the use of HAIC for treatment of advanced HCC is unclear because convincing data from large-scale randomized clinical trials are lacking. For HAIC to become a standard treatment for HCC, such trials must establish its efficacy compared with other HCC therapies; prediction of antitumor response in HAIC may aid trial design, and a multi-center, open-label, randomized clinical trial of HAIC in advanced HCC is in progress. Optimization of HCC treatment protocols and regimens is also required.
Innovative dual system for selective eradication of cancer cells using exosomes carrying natural bacterial toxin-antitoxin (TA).
Authors: Shiran Shapira, Ilana Boustanai, Dina Kazanov, Ahmad Fokra, Ezra Bernstein, Ido Wolf, Nadir Arber
Journal: Journal of Clinical Oncology (2019)

e14635 Background: Inactivation of P53 and activation of ras are frequent genetic alterations in cancer. We have shown in vitro and in vivo, that the TA system can selectively and effectively eradicate RAS-mutated cancer cells. Aim: Selective killing of cancer cells while sparing the normal cells based on tumor genetic signature. Methods: A “first generation” ΔE1/ΔE3 human type-5 adenoviral-vectors for gene delivery were designed and constructed to specifically target cancer cells. They are designated as "PY4-mazF-mCherry" (PY4, ras responsive element), "ΔPY4-mazF-mCherry" (control viruses) and "RGC-mazE-IRES-GFP" (RGC, P53 responsive element). Their potency was tested in vitro, by the enzymatic MTT assay, microscopic observation, colony formation assay and FACS analysis, and in a xenograft model of CRC. Next, we generated, small natural vesicles, exosomes, that directly targeted cancer through specific small antibody fragments against CD24 that is expressed in most cancer cells and rarely on normal cells. Results: The TA system ("PY4-mazF-mCherry"+"RGC-mazE-IRES-GFP") induced a massive cell death, in a dose-dependent manner in vitro, 69% as compared to 19% in control co-infected ("ΔPY4-mazF-mCherry"+"RGC-mazE-IRES-GFP") HCT116 CRC cells (mutated RAS and p53). In vivo, growth of HCT116 -/- ( KRAS mut and P53 mut ) and HCT116 +/+ ( KRAS mut and P53 wt ) tumors were significantly inhibited (70% and 65%, respectively). Conclusions: 1. Abusing the P53 genetic status and the activated Ras pathway holds promising effective and safe strategy to target tumor cells while sparing normal tissues. 2. It is a proof of concept for personalized cancer therapy based on the tumor genetic profile.
Olaparib maintenance therapy in patients (pts) with a BRCA1 and/or BRCA2 mutation (BRCAm) and newly diagnosed advanced ovarian cancer (OC): SOLO1 China cohort.
Authors: Lingying Wu, Jianqing Zhu, Rutie Yin, Xiaohua Wu, Ge Lou, Jing Wang, Yunong Gao, Beihua Kong, Xin Lu, Qi Zhou, Yueling Wang, Youguo Chen, Weiguo Lu, Wei Li, Ying Cheng, Jihong Liu, Xin Ma, Jing Zhang
Journal: Journal of Clinical Oncology (2019)

5554 Background: SOLO1 (NCT01844986) is a randomized, double-blind, Phase III trial evaluating the efficacy and safety of the PARP inhibitor, olaparib, as maintenance monotherapy in newly diagnosed advanced OC pts with a BRCAm. A separate pt cohort evaluated the efficacy and safety of olaparib in Chinese pts in this setting. Methods: The China cohort of SOLO1 planned to enroll ~53 newly diagnosed OC pts who had completed first-line platinum-based chemotherapy and were in clinical complete or partial response. This sample size provided around a 90% chance to observe an HR &lt; 1, assuming a true HR = 0.62. Pts were randomized 2:1 to olaparib (300 mg bid; tablet) vs placebo. The primary endpoint was investigator-assessed progression-free survival (PFS; modified RECIST v1.1). Sensitivity analysis of PFS was performed by blinded independent central review (BICR). Results: All 64 randomized pts received study treatment (olaparib, n = 44; placebo n = 20). Median follow-up was ~30 months in both arms. Median PFS was not reached in the olaparib arm and was 9.3 months in the placebo arm (Table). The most common AEs in the olaparib group were nausea (n = 28, 63.6%), anemia (n = 25, 56.8%) and vomiting (n = 18, 40.9%). Grade ≥3 AEs occurred in 56.8% of olaparib pts vs 30.0% of placebo pts; the most common grade ≥3 AE was anemia (n = 16, 36.4%). Olaparib dose interruptions, reductions and discontinuations occurred in 56.8%, 27.3% and 6.8% of pts, respectively (vs in 30.0%, 10% and 0% of pts in the placebo arm). Conclusions: In the China cohort of SOLO1, a clinically relevant improvement in investigator-assessed PFS was observed in newly diagnosed OC pts receiving olaparib maintenance therapy. Olaparib treatment led to a 54% reduction in risk of progression or death vs placebo. The safety results were consistent with the known profile of olaparib in Chinese pts. Clinical trial information: NCT01844986. [Table: see text]
Case 16-1987
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely
Journal: New England Journal of Medicine (1987)

Presentation of Case A 14-year-old boy was admitted to the hospital because of recurrent epistaxes and a nasopharyngeal mass. He was well until one year earlier, when intermittent backaches developed, increased in frequency, and required ibuprofen for relief. Six weeks before admission he began to have repeated brief epistaxes. One month before entry fatigue, diffuse aches in the back and legs, and anorexia developed. One week before admission a productive cough occurred, and his temperature rose to 39.4°C; erythromycin was prescribed. On the evening before entry he had a more profuse epistaxis, which was controlled by packing of the right . . .
Activity of osimetrinib/AZD9291 in pretreated patients (pts) with epidermal growth factor receptor mutant (EGFRmt) non-small cell lung cancer (NSCLC), according to EGFR mutations detected in circulating plasma DNA (ctDNA).
Authors: Emmanouil Kontopodis, Jordana Nuria, Aliki Ntzifa, Panayiotis Katsaounis, Charalambos Haris Charalambous, Ioannis Boukovinas, Emily Tsaroucha, Amanda Psyrri, Anna Koumarianou, Michail Nikolaou, Nikolaos K. Kentepozidis, Rafael Rosell, Vassilis Georgoulias, Niki Karachaliou, Athanasios Kotsakis
Journal: Journal of Clinical Oncology (2019)

e20608 Background: Osimertinib is an irreversible EGFR tyrosine kinase inhibitor (TKI), selective for EGFR TKI-sensitizing mutations and the T790M resistance mutation. We sought to determine the activity of osimertinib after progression on EGFR TKIs in pts with T790-negative ctDNA. Methods: A multicenter phase II study ( clinicaltrials.gov NCT02771314) of osimertinib (80 mg daily) was conducted in pts with metastatic EGFRmt NSCLC, who had progressed after previous treatment with EGFR TKIs. Serial serum and/or plasma samples were drawn for ctDNA analysis at enrollment, 1 month and every 3 months of treatment, until disease progression. Efficacy outcomes in pts without the T790M mutation in ctDNA at baseline are reported. Results: Thirty-seven NSCLC patients with undetectable baseline T790M in the plasma have been enrolled. Median age was 67 years, 21.6% were male, and histology was adenocarcinoma in 100%. More frequent adverse events (grade 1/2) included diarrhea (12.5%), fatigue (12.5%), anorexia (12.5%) and acneiform rash (10.4%). The overall response rate (ORR) was 40.5% (95% CI, 24.7-56.4%) and the disease stabilization rate 37.8%; the median progression-free survival (PFS) was 8.9 months (range, 1.6-30), and the estimated median overall survival (OS) 26 months (range, 2.2-30). At enrollment, EGFR mutations del19 and L858R were detected in ctDNA in 9 and 3 pts, respectively. After one month of treatment with osimertinib, EGFR mutations in ctDNA were not detectable in 4/9 and 2/3 of pts with del19 and L858R at baseline, respectively. Pts without detectable EGFRm ctDNA at baseline remained negative throughout the study. Efficacy according to baseline ctDNA status was as follows: Clinical trial information: NCT02771314. Conclusions: Osimertinib was effective in EGFR TKI pretreated pts without EGFR T790M mutation in plasma. Pts with detectable del19 or L858R mutations in ctDNA before treatment had worse clinical outcomes, despite the elimination of EGFRmt ctDNA.[Table: see text]