tbuckley/cabot-search huggingface dataset:
Risk of neutropenia-related hospitalization (NRH) related to duration of short-acting granulocyte colony stimulating factor (sG-CSF) for primary prophylaxis.
Authors: Shuling Li, Jiannong Liu, Tingting Gong, Haifeng Guo, Prasad L. Gawade, Michael Anthony Kelsh, Brian D. Bradbury, Rajesh Belani, Gary H. Lyman
Journal: Journal of Clinical Oncology (2019)

e18181 Background: In clinical trials, efficacy of 1011 days of primary prophylactic (PP) sG-CSF is similar to a single dose of pegfilgrastim for preventing febrile neutropenia (FN). However, most patients receive &lt; 10 days of PP sG-CSF in clinical practice. This study assessed the effect of PP sG-CSF duration on the risk of NRH. Methods: Using Medicare 20% sample data, we conducted a nested case-control study within a cohort of patients aged ≥66 y with breast, colorectal, lung, ovarian, or prostate cancer or NHL who initiated first cycle of chemotherapy 1/1/20089/30/2016, had ≥1 y continuous coverage in Medicare parts A and B before cycle day 1 (baseline), and received PP sG-CSF. We identified NRH cases (ICD-9, 288.0X; ICD-10, D70.X) from cycle day 5 to end of cycle 1. We matched each case to up to 4 controls based on age (± 1 y), tumor type, regimen risk for FN (intermediate/high [ &gt; 10%], other), and year using incidence density sampling. Duration of sG-CSF (days of use from cycle day 1 to the day before case date) was categorized as &lt; 5 and ≥5 days. We used conditional logistic regression adjusted for race, sex, and Charlson comorbidity index (CCI) at baseline to estimate relative risk of NRH related to duration of sG-CSF. Results: Of 1431 patients receiving PP sG-CSF, 68 cases matched 231 controls. Cases were similar to controls in age (76 vs 75 y), tumor type (NHL, 62% vs 62%; lung cancer, 25% vs 25%), intermediate-/high-risk regimen (65% vs 67%), and male sex (50% vs 48%) but had slightly higher CCI (3.9 vs 3.3). The percentage of patients with ≥5 days of PP sG-CSF use was 26% in cases and 41% in controls. The adjusted OR (95% CI) for NRH was 0.48 (0.250.93) for ≥5 vs &lt; 5 days of PP sG-CSF; results were consistent across sensitivity analyses (Table). Conclusions: Among elderly cancer patients receiving PP sG-CSF, ≥5 days of sG-CSF use was associated with substantial reduction in the risk of NRH.[Table: see text]
Case 31-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Richard Platt, Robert H. Rubin
Journal: New England Journal of Medicine (1985)

CASE 31–1985Presentation of CaseA 43-year-old man was referred to the hospital because of fever of unknown origin.There was a history of coarctation of the aorta, with surgical repair at the age of 12 years; an appendectomy was performed two years later. Thereafter he was well until 10 years before admission, when he had a urinary tract infection, from which he recovered. Approximately one year later he began to experience repeated bouts of fever that occurred at infrequent intervals, sometimes associated with a sore throat and upper respiratory tract symptoms. During the episodes of fever the patient experienced . . .
A population-based model for predicting sentinel lymph node (SLN) status for cutaneous melanoma patients and a clinical decision rule (CDR) for sparing a SLN biopsy (SLNB).
Authors: Phyllis A. Gimotty, Giorgos Karakousis, Meghan A. Buckley, DuPont Guerry
Journal: Journal of Clinical Oncology (2019)

9589 Background: Generally, a SLNB is offered to the patient whose likelihood of positivity is ≥ 5%. Using population-based cohorts, we sought to [1] develop and validate a predictive model to estimate the individualized risk (IR) of SLNB positivity (SLNBp) and its confidence interval (CI), [2] evaluate an IR-based CDR to identify patients with sufficiently low IRs to avoid SLNB, and [3] compare the performance of the CDR with that of the 2019 NCCN guideline. Methods: The learning cohort (n = 18,214; SLNBp rate = 10.7%; 2010-2014) and validation cohort (n = 3,924; SLNBp rate = 11%; 2015) included SEER patients 18-99 years old who had a SLNB as part of definitive surgery. A multivariable logistic regression model for SLNBp, including 4 AJCC related-factors (thickness, ulceration, level and mitotic rate) and age, was used to estimate the IR of SLNBp and its one-sided 95% CI. The CDR was defined using the IR and CI and then used to classify patients into 3 categories: SLNB not indicated (IR and upper limit of the one-sided CI &lt; 5%), SLNB indicated (IR and lower limit of the one-sided CI ≥ 5%), and borderline. Results: In the learning cohort all 5 factors were significant in the multivariate model, which had a c-statistic of 0.742 (95%CI, 0.731-0.753). In the validation cohort the model c-statistic was 0.728. Based on the CDR, 21.6%, 56.9%, and 21.5% of patients would not be offered SLNB, would be offered SLNB, or would need further shared decision making. Compared to the guideline, the CDR classified more patients as “SLNB not indicated” (21.6% vs. 7.1%) and fewer as “SLNB indicated” (56.9% vs. 68.5%). Of the 16,137 SLNB negative patients, 3815 (23.6%) would not be offered SLNB based on the CDR compared to 1258 (7.8%) who would not be offered SLNB based on the guideline. The false negative rates associated with “not indicated” by the CDR and guideline were 4.6% and 1.2%, respectively. Conclusions: Use of this CDR rather than the NCCN guideline will spare more low-risk patients the expense and harms of SLNB and increase only marginally their likelihood of a false negative test (still &lt; 5%).
Technologies for circulating tumor cell separation from whole blood
Authors: Petra Bankó, Sun Young Lee, Viola Nagygyörgy, Miklós Zrínyi, Chang Hoon Chae, Dong Hyu Cho, András Telekes
Journal: Journal of Hematology & Oncology (2019)

The importance of early cancer diagnosis and improved cancer therapy has been clear for years and has initiated worldwide research towards new possibilities in the care strategy of patients with cancer using technological innovations. One of the key research fields involves the separation and detection of circulating tumor cells (CTC) because of their suggested important role in early cancer diagnosis and prognosis, namely, providing easy access by a liquid biopsy from blood to identify metastatic cells before clinically detectable metastasis occurs and to study the molecular and genetic profile of these metastatic cells. Provided the opportunity to further progress the development of technology for treating cancer, several CTC technologies have been proposed in recent years by various research groups and companies. Despite their potential role in cancer healthcare, CTC methods are currently mainly used for research purposes, and only a few methods have been accepted for clinical application because of the difficulties caused by CTC heterogeneity, CTC separation from the blood, and a lack of thorough clinical validation. Therefore, the standardization and clinical application of various developed CTC technologies remain important subsequent necessary steps. Because of their suggested future clinical benefits, we focus on describing technologies using whole blood samples without any pretreatment and discuss their advantages, use, and significance. Technologies using whole blood samples utilize size-based, immunoaffinity-based, and density-based methods or combinations of these methods as well as positive and negative enrichment during separation. Although current CTC technologies have not been truly implemented yet, they possess high potential as future clinical diagnostic techniques for the individualized therapy of patients with cancer. Thus, a detailed discussion of the clinical suitability of these new advanced technologies could help prepare clinicians for the future and can be a foundation for technologies that would be used to eliminate CTCs in vivo.
Recombinant humanized anti-PD-1 monoclonal antibody toripalimab in patients with metastatic urothelial carcinoma: Preliminary results of an open-label phase II clinical study (POLARIS-03).
Authors: Xinan Sheng, Haige Chen, Bin Hu, Xudong Yao, Ziling Liu, Xin Yao, Hongqian Guo, Yi Hu, Zhigang Ji, Hong Luo, Benkang Shi, Jiyan Liu, Jin WU, Fang-Jian Zhou, Zhisong He, Yiran Huang, Jun Guo
Journal: Journal of Clinical Oncology (2020)

504 Background: Patients with advanced metastatic urothelial carcinoma (UC) who experience disease progression after standard therapy have limited treatment options. Phase I studies of toripalimab in subjects with heavily pretreated metastatic UC have demonstrated an acceptable safety profile and promising clinical activity. Here we report the preliminary safety and efficacy result of toripalimab in a Phase II clinical study in Chinese patients with refractory/metastatic UC (Clinical trial ID: NCT03113266). Methods: Metastatic UC patients received toripalimab, also known as JS001, 3 mg/kg Q2W until disease progression or unacceptable toxicity. All patients with measurable disease were assessed for clinical response every 8 weeks according to RECISTv1.1. Tumor PD-L1 expression and tumor mutational burden was measured for correlation with clinical response. Results: From May 2017 to Sep 2019, 151 patients were enrolled from 15 participating centers. Patient enrollment was completed for this study. The median age was 62.0 years with 66.9% of the population being male. By the cut-off date of 21 Oct 2019, common treatment related AEs were mostly Grade 1 or 2, including anemia, blood triglycerides increased, fever, protein urine present and blood glucose increased. Among 128 efficacy evaluable patients, 4 complete responses, 25 partial responses, and 35 stable diseases were observed, for an objective response rate (ORR) of 22.7% and a disease control rate of 50.0%. 62.1% (18/29) of responses were ongoing at the cut-off date. PD-L1 expression results were obtained from 121 efficacy evaluable subjects. PD-L1+ patients (n = 39, 32.2%) had significant better ORR than PD-L1- patients (n = 82), 38.5% versus 13.4%. Conclusions: Toripalimab has demonstrated encouraging clinical activity in chemo-refractory UC patients and a manageable safety profile. Toripalimab elicited a favorable 38.5% ORR in PD-L1+ patients. Nevertheless PD-L1- patients also achieved a 13.4% ORR, including one complete response. Patients will be continuously monitored for additional safety and efficacy readouts (DOR, PFS and OS). Clinical trial information: NCT03113266.
Transcriptional characterization of microenvironment and their prediction role for the prognosis of hepatocellular carcinoma after surgery.
Authors: Kehe Chen, Haiming Wei, Tianqi Liu, Zhenxiang Chen, Deng Pan, Jingning Huang, Ting Gao, Min Huang, Xiaoshuang Ren, Jiao Zhang, Beibei Mao, Ying Yang, Wenbo Han, Hongbo Zheng, Henghui Zhang
Journal: Journal of Clinical Oncology (2019)

e15650 Background: Hepatocellular carcinoma (HCC) is one of the most common prevalent fatal cancers worldwide with poor prognosis due to high incidence of recurrence. For patients with HCC, surgical treatment is a potentially cutative therapy. However, the puzzle in the therapy was the rapid recurrence after surgery. The purpose of this study was to integrate the impact of different immune context present in HCC microenvironment on patients’ prognosis, provide the molecular prediction clue of HCC recurrence. Methods: RNA targeted sequencing was performed on 12 primary tumor specimens from HCC patients. Transcripts of 395 immune related genes expressed in FFPE tumor samples were analyzed. The lima package was used to analyze the different expressed genes (DEGs) between patients with different prognosis. The gene set variance analysis (GSVA) analysis was performed to explore gene sets enrichment related to the recurrence post-resection. Results: 15 DEGs were detected in tissue samples between the two groups (group A: patients who relapsed within one year after surgery; group B: patients who hadn't relapsed beyond two years after surgery). The Antigen processing pathway enrichment may associate with the favorable prognosis (p &lt; 0.05). HLA-A gene expression in group A was lower than that in group B; The gene expression of IL23A, TP63, ALOX15B, BUB1, CXCR2, CCL20, CLEC4C, PTK7, MPO, IL1B, MMP9, GAGE2C, GAGE2A, GAGE2E, DMBT1, FOXM1 in group A was higher than that in group B. Additionally, the combination of 3 genes (TP63, IL23A and BUB1) can distinguish the patients recurrent within 1 year or beyond 2 years post-resection. The joint diagnostic equation is logit (Y = 1) = 0.073 +0.740 *(TP63) + 0.589 * (IL23A)+0.959(BUB1), (Optimal threshold: 0.667, specificity: 1, sensitivity: 0.833). Conclusions: Our results suggest that RNA-seq of immune related genes from FFPE sample can effectively profile the specific landscape of tumor immune microenvironment and predict the survival of HCC. 3 genes’ expression (TP63, IL23A and BUB1) might correlate with recurrence in HCC patients after surgery.
Abstract 13307: Inorganic Pyrophosphate (PPi) Protects Against Early Asystole in Ex-Vivo Model of Cardiac Arrest and Prevents Mitochondrial Depolarization in Hypoxic Cardiomyocytes
Authors: Junko Shibayama, Tyson G Taylor, Paul W Venable, Alicja E Booth, Nathaniel L Rhodes, Ryan B Gil, Mark Warren, James Cox, Kenneth W Spitzer, Alexey V Zaitsev
Journal: Circulation (2012)

Asystole following ventricular fibrillation (VF) and global ischemia (VF/ischemia) is a typical and adverse outcome of cardiac arrest. We hypothesized that the incidence of asystole may depend on p...
Response to: ‘Association of proton pump inhibitors with fracture risk in patients with rheumatoid arthritis’ by Sugiyama
Authors: Gulsen Ozen, Kaleb Michaud
Journal: Annals of the Rheumatic Diseases (2019)

We appreciate the interest shown by Dr Sugiyama1 concerning our recent study on medications associated with fracture risk in patients with rheumatoid arthritis (RA).2 He emphasises the lack of association between proton pump inhibitor (PPI) use and fracture risk in patients with RA, which has been a conflicting issue for the general population. We agree that the previous studies showing an increased fracture risk with PPIs in the general population may be confounded by the indication as it is known that PPI …
Analysis of a profile of lipid metabolism genes in advanced non-small cell lung cancer.
Authors: Maria Merino, Lara Fernández, Ana Ramirez de Molina, Juan Moreno, Gonzalo Colmenarejo, Sandra Falagan, César Gómez, Miriam Lopez-Gomez, Francisco Zambrana, Ana M. Jimenez Gordo, Cristina Aguayo, Enrique Casado, Maria Sereno Moyano
Journal: Journal of Clinical Oncology (2019)

e20619 Background: Non- small cell lung cancer (NSCLC) is one of the tumors with the highest mortality rate. The underlying metabolic alterations involved in its carcinogenesis are becoming more interesting. According to this, the analysis of the dysregulation of genes involved in lipid metabolism (LM) is subject to a growing research. To evaluate a profile of genes involved in lipid metabolism in NSCLC, we analyzed the correlation of this gene expression profile with different clinical-pathological variables. Methods: We performed a retrospective analysis of 22 genes related to LM in samples of NSCLC as well as clinical-pathological features. Advanced NSCLC patients enrolled from 2008 through 2015 were included. Clinical and pathological data were collected from medical reports. This study was approved in our ethical committee and all patients signed the consent inform. Samples were deparaffinated and RNA was extracted using RNeasy FFPE Kit (Qiagen Gmbh, Germany). A Taq-Man Low Density Array (Applied Biosystems) was specifically designed and gene-expression assays were performed in a HT-7900 Fast Real time PCR. RT-StatMiner software (Integromics Inc., Madison, USA) was used to detect and determine the quality control and differential expression analyses of data. Quantification of gene expression was calculated with the 2–ΔCt method. The Kaplan–Meier method was used for survival probabilities, and the log-rank test was to test differences between subgroups. Results: Ninety patients with advanced NSCLC were included. Median age was 64, 68/90 (75%) were male; 46/90 (51%) were ECOG 1; 68/90 (75%) adenocarcinoma vs 22/90 (24%) squamous; 47/90 (52%) smokers and 34% former smokers; metformine intake was presented in 9/90 (10%) and statins 24/90 (27%). In retrospective RT-PCR analysis including a lipid metabolism gene profile of 22 genes, we obtained an overexpression of 2 genes (an Acyl-CoA sintetase and a adipocine encoding gene). They were significantly correlated with overall poor survival in the multivariate analysis (table). These results were confirmed in an in silico validation using 994 NSCLC patients from TCGA study. Conclusions: This is the first study demonstrating a significant relation with a poor survival between a metabolic lipid gene profile expression and survival in advanced non- small cell lung cancer [Table: see text]
Demographic factors associated with financial toxicity: Results from the multisite cost study.
Authors: Divya Ahuja Parikh, Meera Vimala Ragavan, Ritika Dutta, Jeffrey Edwards, Debeshi Maitra, Manali I. Patel
Journal: Journal of Clinical Oncology (2019)

e18362 Background: Financial toxicity (FT) is a major cause of distress for cancer patients. We have previously reported that FT was high among patients at a county hospital and a tertiary academic center. In this study, we sought to compare factors associated with FT at these institutions. Methods: Patients with clinic visits were asked to fill out an 11-item validated FT survey, the COST tool, and demographic questions from 10/2017 - 2/2018 at the county hospital and 7/2015 - 10/2018 at the academic center. We used a logistic regression model to analyze demographic factors associated with FT. Results: Mean COST score was significantly higher at the county hospital (28.7) compared to the academic center (20.4) (p &lt; 0.001). Distribution of cancer stage was similar between the institutions. Patients at the county hospital were more likely to have an annual household income (AHI) &lt; $25K (p &lt; 0.001), and be insured by Medi-cal (p &lt; 0.001). Patients at the academic center were more likely to be White (p &lt; 0.001). Monthly OOP spending was more likely to be &gt; $500 at the academic center (p &lt; 0.001). Conclusions: Overall, FT was higher at the county hospital as compared to the academic center. FT at both institutions was associated with higher OOP spending and lower AHI. However, variations in FT among other demographic factors may reflect differences in care delivery systems and patient populations. Our study demonstrates that demographic groups at risk for FT differs between institutions suggesting the factors that contribute financial toxicity are complex and variable. Thus local assessments of FT may be necessary for individual health systems to develop targeted interventions to improve FT among their patients.[Table: see text]
SHERLOC: A phase 2 study of MM-121 plus with docetaxel versus docetaxel alone in patients with heregulin (HRG) positive advanced non-small cell lung cancer (NSCLC).
Authors: Lecia V. Sequist, Pasi A. Janne, Rudolf M. Huber, Jhanelle Elaine Gray, Enriqueta Felip, Maurice Perol, Fred R. Hirsch, Daniel Shao-Weng Tan, Geoffrey Kuesters, Alena Zalutskaya, Sergio Santillana, J. Marc Pipas, Frances A. Shepherd
Journal: Journal of Clinical Oncology (2019)

9036 Background: Seribantumab (MM-121) is a human monoclonal IgG2 antibody that blocks the HRG domain of HER3. Preclinical data suggest that seribantumab reverses HRG mediated drug resistance across multiple cancer models. In prior retrospective analyses, addition of seribantumab to standard of care (SOC) appeared to improve outcomes in pts with HRG+ tumors. Here we tested if seribantumab plus SOC improved progression-free survival (PFS) in pts with HRG+ lung adenocarcinoma who had received prior platinum-based therapy. Methods: SHERLOC was a randomized, open-label, multicenter, Phase 2 study in pts with advanced HRG+ adenocarcinoma of the lung. Archival or pre-treatment tumor samples were assessed for HRG+ by RNA in situ hybridization. Eligibility criteria included prior platinum-based therapy for advanced disease with ≤ 2 total prior lines of therapy (prior IO was allowed) and no EGFR or ALK mutations. Pts were randomized 2:1 to receive seribantumab 3000 mg/docetaxel 75 mg IV q3w (experimental; exp) or docetaxel 75 mg IV q3w alone (control). Primary endpoint was PFS. Key secondary endpoints were overall survival (OS), objective response rate (ORR), and adverse event (AEs) profile. Results: At a pre-specified interim analysis of 75% of total PFS events, 108 pts were enrolled (exp n = 71, control n = 37). Median age was 62y (range 34-83y); female 34%; one prior treatment only 39%. Median PFS was 3.0m for exp and 4.0m for control, HR = 1.66m (p = 0.084). Median OS was 7.9m for exp and 8.4m for control, HR = 1.50 (p = 0.235). ORR was 19.7% for exp and 5.6% for control (p = 0.052). Serious AEs were more frequent in the exp arm (40.8%) vs control (24.3%). Most common treatment emergent AEs (TEAEs) in the exp arm were diarrhea (47%), fatigue (37%), and neutropenia (27%). Based on a determination of futility at interim analysis, the study was terminated early. Conclusions: Seribantumab failed to improve PFS when added to docetaxel among previously treated advanced HRG+ NSCLC pts. A higher response rate and a higher incidence of TEAEs were observed in the exp arm. No further study of seribantumab is planned in NSCLC. Clinical trial information: NCT02387216.