tbuckley/cabot-search huggingface dataset:
The prognostic significance of white adipose tissue inflammation in advanced-stage, high-grade, and serous endometrial cancers.
Authors: Vance Broach, Neil M. Iyengar, Xi K. Zhou, Hanhan Wang, Dilip D. Giri, Samantha Williams, Nadeem Abu-Rustum, Maria M Rubinstein, Andrew J. Dannenberg, Vicky Makker
Journal: Journal of Clinical Oncology (2019)

5589 Background: Obesity is associated with worse outcomes in endometrial cancer, but the underlying mechanisms are poorly understood. In other obesity-related cancers, white adipose tissue inflammation (WATi) is an independent predictor of shortened cancer-specific survival. We hypothesized that WATi occurs in patients with endometrial cancers and is a prognostic marker of shortened survival. Methods: We conducted a retrospective cohort study in which patients with stage III or IV grade 3 endometrioid (G3) or serous endometrial cancer were included. Eligible subjects had archived omental and/or peri-nodal adipose tissue available. WATi was detected by the presence of dead/dying adipocytes surrounded by CD68+ macrophages forming a crown-like structure (CLS). Clinicopathologic data were abstracted from medical records. For association with WATi, Wilcoxon rank sum test was used for continuous variables, Fisher’s exact test for categorical variables. Log rank test was used to assess the association of WATi and survival. Results: A total of 95 patients who underwent debulking surgery from 2001–2017 were included (median age, 67 years; range, 33-86 years). Of these, 51 (54%) had WATi. The presence of WATi was unaffected by race, tumor histology or stage. Patients with WATi had a higher median body mass index (BMI) than those without WATi (32.17 and 27.33 kg/m 2 , respectively; P &lt; 0.001) and were more likely to be obese (P = 0.01). Patients with the most severe WATi (n = 20) had shorter progression-free survival (PFS) and a trend suggesting shorter overall survival (OS) than those patients with less severe or no WATi (n = 75) (median PFS 15.8 vs 59.2 months, respectively, P = 0.001; median OS 33.9 vs 59.4 months, respectively, P = 0.059). Conclusions: Visceral adipose inflammation is prevalent in obese patients with advanced G3 and serous endometrial cancer. Severe inflammation was associated with significantly worse PFS.
10-year patient journey of stage III non-small cell lung cancer patients: A single-center, observational, retrospective study in Korea real-time automatically updated data warehouse in health care (UNIVERSE - ROOT study).
Authors: Keunchil Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Joohwan Lee
Journal: Journal of Clinical Oncology (2019)

8536 Background: The current standard of care (SoC) for locally advanced stage III NSCLC is concurrent chemoradiotherapy (CCRT) but the outcomes are poor and unsatisfactory. The purpose of this study is to analyze the clinical features of patients with locally advanced lung cancer for 10 years in order to help develop future treatment strategy. Methods: This study through big data analysis retrospectively collected de-identified patient data from clinical data warehouse (CDW) using an unique algorithm with Standard Query Language (SQL). This new algorithm was developed by the close interactive collaboration between senior data scientists and medical oncologists. These algorithms include clinical natural language processing (NLP) systems that generate structured information from unstructured free text and structured data capture (SDC). We performed pre-processing work and data quality management (DQM) operation using over 700 clinical variables from 23,735 patients with NSCLC. Through data extraction, transformation, cleansing, and organization, we have developed a systematic and optimized program for lung cancer cohorts, including clinical features and molecular study and outcomes. It is also automatically updated every 24 hours in real time. Results: In the past 10 years, 23,735 patients were diagnosed with NSCLC and complete clinical data were available in 22,718 patients (95.7%). Out of total 22,718 patients 4,138 (18.2%) were diagnosed with stage III NSCLC. Among them, 2,676 patients (64.7%) received any type(s) of anti-cancer treatments or regular follow up at our institute. Of these 2,676 patients, 1,275 (47.6%) received curative surgery (+/- neo- and/or adjuvant CCRT); 685 (25.6%) patients definitive CCRT ; 220 (8.2%) patients palliative thoracic RT; 76 (2.8%) patients best supportive care. Median OS was 48.0 months for neoadjuvant CCRT followed by curative surgery, 51.8 months for curative surgery +/- adjuvant treatment, 29.4 months for unresected definitive CCRT (PFS 10.0 months (range: 9.1-10.9). Molecular profiles as well as updated clinical data will be presented. Conclusions: This unique in-house algorithm enables us to do a rapid and comprehensive analysis of the big data through CDW, which can be also automatically updated daily. This should provide clinically relevant information about real-world treatment outcomes and help implement or develop new treatment strategy in a timely manner.
Demographic stratification of inflammatory signature in lung cancer patients in North Carolina: A prospective cohort study.
Authors: Nitika Sharma, Paul R. Walker, Chipman Robert Geoffrey Stroud, Cynthia R. Cherry
Journal: Journal of Clinical Oncology (2019)

e14200 Background: Lung Cancer remains the major cause of cancer related mortality in the state of North Carolina. There is a growing body of evidence that implicates inflammation as a mechanism of disease progression and reduced survival in patients with advanced cancer (Laird et al, Oncologist 2013). Smoldering inflammation in the tumor microenvironment regulates and escalates cancer invasion, angiogenesis and immune surveillance escape (Balkwill and Mantovani, Lancet 2001). We investigated the predictive value of inflammatory signature according to social stratification of cancer patients using Modified Glasgow Prognostic Score (mGPS). mGPS is a composite inflammatory score based on CRP and serum albumin with proven prognostic and predictive value in various tumor types. Methods: A prospective observational single institutional study was conducted whereby serum albumin and CRP were drawn at baseline for 333 patients with diagnosis of cancer regardless of stage from 30 counties in Eastern North Carolina. The mGPS score was compared according to rural urban divide and occupational regional exposure of various counties stratified per US Census Data. Results: Lung cancer was the predominant cancer type in 93% of patients. The mGPS of zero in Urban vs Rural counties was noted in 36% and 24% patients respectively. The mGPS score of two in Urban vs Rural counties was noted in 26% and 41% respectively. The mGPS of two in areas of hog farming, cattle farming and wet waste lands was seen in 41%, 38% and 43% respectively (p = 0.0019). The mGPS of zero was seen in 24%, 20% and 27% respectively (p = 0.0008). Conclusions: This study suggests a strikingly unfavorable inflammatory signature in rural population as well as areas of hog farm, cattle farm and wet waste lands. The hog and poultry operations heighten the harmful effect on waterways and can adversely affect the inflammatory signature, hence the tumor biology. This underscores additional interventions in these high risk populations that can have significant implications for quality of life and survival, especially in the era of immunotherapy.
Cost-minimization analysis of using tumor cell-free DNA as monitoring tool in cancer immunotherapy.
Authors: Alexander Kuhlmann, Glen J. Weiss, Julia Beck, Michael Oellerich, Ronja Westphal, Ekkehard Schütz, J.-Matthias Graf von der Schulenburg
Journal: Journal of Clinical Oncology (2019)

6642 Background: Albeit showing great benefit in individual cancer patients, only the minority of patients benefit from checkpoint inhibitor immunotherapies (IMTs). Mutation load and PD-L1 staining are used for response prediction, but are imperfect predictors. A universal method to quantify tumor cell-free DNA (TcfDNA) enables the early and effective evaluation of individual IMT efficacy[1], by comparing TcfDNA to pre-therapeutic values. Here we present a health economic evaluation of test usage. Methods: This cost-minimization study determines the economic efficiency of TcfDNA-test from the perspective of the statutory health insurance in Germany. The assumption is that the effectivity of the intervention (TcfDNA monitoring) and of the comparator (no test), is comparable with regards to the patient-relevant-endpoints (morbidity, mortality, quality of life). The model simulates the course of treatment for each patient with and without TcfDNA testing, calculating the respective cost. Treatment details, outcome (RECIST) and TcfDNA results are derived from an earlier clinical trial.[1] Costs are obtained from publicly accessible data bases. Two testing strategies are explored. Strategy 1: Testing all patients only before the second cycle. Strategy 2: Same as strategy 1 plus a confirmation test before the third cycle, in patients with initial result in a defined grey zone. Results: Both testing strategies correctly classified 68% of progressive disease patients. Testing strategy-1 misclassifies about 8% of disease control patients, which would lead to discontinuation of successful therapies in those. In contrast strategy-2 correctly classifies all patients with disease control, whilst requiring only 24% more tests, since ~50% of patients are undoubtedly classified after one cycle. Assuming six cycles at average costs of 4,781 EUR in the no-test-setting, average costs savings per patient with strategy-1 are 5,735 EUR (20% of treatment costs), with strategy-2 are 2,010 EUR (7%) compared to no testing. Conclusions: TcfDNA monitoring is a cost-saving strategy. However, a confirmatory strategy is desirable to avoid early discontinuation of successful IMT. [1] Weiss GJ et al.: Clin Cancer Res: 2017;5074-81.
Case 16-1988
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Robert S. Brown, Alain Marion
Journal: New England Journal of Medicine (1988)

Presentation of CaseAn 83-year-old woman was admitted to the hospital because of anemia and azotemia.She was in vigorous health until 30 months earlier, when she noticed a lump near the left axilla. A physician found a mass near the axillary tail of the left breast, and microscopical examination of a biopsy specimen of the mass showed large-cell lymphoma. A radionuclide scan of the liver and spleen and bilateral mammographic examinations, performed elsewhere, were reported to be negative, and the patient was referred to this hospital. A computed tomographic (CT) scan of the abdomen revealed a questionable small retrocrural . . .
Association of immune-related adverse events (irAEs) with clinical benefit in patients with metastatic urothelial carcinoma (mUC) treated with immune-checkpoint inhibitors (ICIs).
Authors: Nuzzo Pier Vitale, Gregory Russell Pond, Sarah Abou Alaiwi, Amin Nassar, Ronan Flippot, Toni K. Choueiri, Lauren Christine Harshman, Guru Sonpavde
Journal: Journal of Clinical Oncology (2019)

e16038 Background: In other cancers such as metastatic lung and melanoma, pts who experience irAEs may have a greater degree of clinical benefit. We sought to evaluate whether the development of irAEs correlates with clinical benefits in mUC pts. Methods: We identified mUC pts who received PD-1/L1 inhibitors at the Dana-Farber Cancer Institute (DFCI). The severity of irAEs was graded using CTCAE v.5.0. Clinical benefit was defined as any objective reduction (complete- or partial- response) in tumor burden. Fisher’s exact test was used to evaluate for differences in the proportion of pts experiencing clinical benefit between pts experiencing an irAEs within 90 days after starting therapy and those who did not experience an irAEs. The log-rank test assessed differences in progression-free survival (PFS) and overall survival (OS) between cohorts. Results: A total of 199 mUC pts were enrolled between July 2013 and October 2018 [median (range) age, 69.6 (26.6-89.0) years; 141 men (70.9%), 58 women (29.1%)]. 114 (57.3%) pts were treated with anti-PD-1 and 85 (42.7%) with anti-PD-L1. irAEs were observed in 67 pts (33.7%), of which 34 (17.1%) &lt; 90 days from start of therapy. Common irAEs included 20 (29.9%) hypothyroidism, 17 (25.4%) colitis, 12 (17.9%) rash/pruritus, and 10 (14.9%) transaminitis. Grade ≥3 irAEs were observed in 14 pts (20.9%).13 (40.6%) pts with irAE &lt; 90 days experienced clinical benefit compared with 21 (17.8%) of pts with no irAE (p-value = 0.008). No difference (p = 0.26 and 0.18) was observed for either PFS (6-month PFS = 19.2% vs 35.3% for no irAE and irAE &lt; 90 days) or OS (1-year OS = 41.8% vs 57.7% for no irAE vs irAE &lt; 90 days). Conclusions: The development of irAEs within 90 days from starting therapy in mUC pts may herald clinical benefit in pts with mUC. Further evaluation of this potential relationship in a large prospective study is warranted.
THU0160 FEATURES OF LIPID PROFILE INDICATORS IN PATIENTS WITH RHEUMATOID ARTHRITIS IN CONNECTION WITH ARTERIAL HYPERTENSION
Authors: Roman Yatsyshyn, Oleksandr Shtefiuk, Bohdana Doskaliuk, Oleksandra Hotsaniuk, Irina Mykhaloiko
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Patients with rheumatoid arthritis (RA) have an early development of endothelial dysfunction, an increase of the atherogenicity index (AI), and a high risk of fatal cardiovascular events. The presence of arterial hypertension (AH) in patients with RA accelerates the process of early atherogenesis and increases the risk of fatal cardiovascular events. <h3>Objectives:</h3> To evaluate the dynamics of lipid profile changes in patients with RA in combination with AH. <h3>Methods:</h3> It was examined 47 patients with RA in combination with AH (by all patients was discovered IIstage/2degree of AH). The age of the patients ranged from 18 to 72 years. Among the surveyed group dominated men (41 patients). All patients were assessed for the levels of total cholesterol (TC), low density lipoprotein (LDL), very low density lipoprotein (VLDL), triglycerides (TG), high density lipoprotein (HDL), AI (AI = TC – HDL/LDL), antibodies to modified citrulline vimentin (anti-MCV), rheumatoid factor (RF), C-reactive protein (CRP) before treatment. All patients were also assessed for the risk of death for 10 years by the SCORE scale (&gt; 15% - very high risk, 10-14% high, 5-3% - moderate, &lt;1% - low) and RA activity by DAS28 score. <h3>Results:</h3> Due to the obtained data, it can be asserted, that in patients with seronegative RA the moderate risk by SCORE was prevalent, and among seropositive RA patients– high risk. The high level of anti-MCV titres was directly corelated with the risk of the death by SCORE (p &gt; 0,05, r = 0,64). We found that patients with RA and AH had relatively low levels of TC (5,82 ± 2,21 mmol/L) and LDL (2,82 ± 0,81 mmol/L), but the AI in these patients was 4,42 ± 0,68. It was measured the correlation between the levels of LDL and the activity of the inflammatory process DAS28, the level of CRP and the duration of RA (r = 0,56, p &lt;0,05, r = 0,49, p &lt;0,05, r = 0,53; p &lt;0,05, respectively). There was also a reverse correlation between the duration of RA and the level of HDL (r = -0,47; p &lt;0,05). <h3>Conclusion:</h3> 1. Seropositivity, high activity and anamnesis of RA for more than 10 years are the factors, that are associated with high risk of fatal cardiovascular events. 2. In patients with RA in combination with AH, serum lipid levels have paradoxical ratio, resulting in lower levels of TC and LDL associated with an increased risk of cardiovascular events ("lipid paradox"). 3. The presence of high anti-MCV titres serves as a prognostically unfavorable feature of the course of RA and AH, since its association with a high risk of fatal cardiovascular events. <h3><b>Disclosure of Interests</b>:</h3> None declared
Nintedanib plus docetaxel in lung adenocarcinoma patients (pts) following treatment with immune checkpoint inhibitors (ICIs): Preliminary efficacy and safety results of the non-interventional study VARGADO.
Authors: Christian Grohé, Wolfgang Blau, Wolfgang Gleiber, Siegfried Haas, Harald Mueller-Huesmann, Mathias Schulze, Judith Atz, Rolf Kaiser
Journal: Journal of Clinical Oncology (2019)

9074 Background: The treatment landscape of non-targetable advanced NSCLC pts has changed considerably following the introduction of ICIs. Data are scarce regarding optimal treatment choice and treatment sequence for pts who progressed on ICI. Methods: VARGADO (NCT02392455) is a prospective non-interventional study investigating the efficacy and tolerability of the oral triple angiokinase inhibitor nintedanibplus docetaxel in pts with advanced lung adenocarcinoma after first-line chemotherapy. The present analysis focused on its clinical activity in pts who received nintedanib plus docetaxel in 3 rd line following progression on ICIs in 2 nd line. Results: 25 pts whose disease has progressed on previous ICI therapy received subsequently nintedanib plus docetaxel. Median age was 59 years (range: 45 – 76); 17/25 pts (68.0%) were men, 17/25 pts (68.0%) were ECOG PS0/1, and 24/25 pts (96.0%) were current or former smokers. 1 st line chemotherapy included pemetrexed (18/25 pts, 72.0%), cisplatin (15/25 pts, 60.0%), carboplatin (12/25 pts, 48.0%), bevacizumab (8/25 pts, 32.0%), vinorelbine (4/25 pts, 16.0%), paclitaxel (2/25 pts, 8.0%), and docetaxel (1/25 pts, 4.0%). 2 nd line treatment included nivolumab (18/25 pts, 72.0%) and pembrolizumab (6/25 pts, 24.0%). Under nintedanib and docetaxel, 9/20 pts (45.0%) showed a partial response, and 7/20 pts (35.0%) showed stable disease, resulting in a DCR of 80.0% (16/20 pts). Median PFS was 5.5 months (95%CI 2.5 – 8.2). Treatment emergent adverse events (TEAEs) grade ≥3, serious TEAEs, and TEAEs leading to discontinuation occurred in 15/25 pts (60.0%), 13/25 pts (52.0%), and 9/25 pts (36.0%), respectively. Conclusions: Nintedanib, in combination with docetaxel, showed clinically meaningful efficacy and an acceptable safety profile in advanced lung adenocarcinoma pts following chemotherapy and ICIs. These findings support the use of nintedanib plus docetaxel as a therapeutic option in lung adenocarcinoma pts progressing under ICI therapy. Clinical trial information: NCT02392455.
Combination efficacy with MetMAb and erlotinib in a NSCLC tumor model highlight therapeutic opportunities for c-Met inhibitors in combination with EGFR inhibitors
Authors: Merchant Mark, Yu-Wen Zhang, Yanli Su, Maria Romero, Sharianne Louie, Christophe Severin, Nerissa Mendoza, Zhong Zheng, Thomas Dekoning, Dafna Kaufman, George Vande Woude, Jiping Zha, Robert Yauch, Ellen Filvaroff
Journal: Cancer Research (2008)

1336  Crosstalk between EGFR and c-Met has been implicated in a number of biological systems. In tumors, interactions between these two pathways may affect tumor cell growth, survival, and response to treatment. Accordingly, MET gene amplification has been shown to be a mechanism of resistance to EGFR inhibitors in non-small cell lung cancer (NSCLC). Our data indicate that combining c-Met and EGFR antagonists may be an effective treatment for NSCLC beyond instances of acquired resistance. First, EGFR and c-Met show a significant overlap of expression in primary NSCLC specimens and cell lines. Second, EGFR and c-Met can co-associate and their activation in several tumor cell lines appears to be linked. In NSCLC lines lacking EGFR mutation or constitutive activity, HGF stimulation can induce activation of EGFR. Inhibition of c-Met in cell lines with elevated levels of c-Met protein decreases basal phosphorylation of EGFR. Conversely, in lines overexpressing or harboring mutations in EGFR, high EGFR activity can drive c-Met phosphorylation and pathway activation. Inhibition of EGFR in these lines results in rapid de-phosphorylation of c-Met and other downstream mediators, including trans-activation of ErbB3 resulting in PI-3K and Akt activity. Third, modulation of c-Met activity can inversely affect response to erlotinib in HGF-responsive cells. More specifically, c-Met activation protects cells from erlotinib-induced apoptosis, and c-Met inhibition can restore erlotinib responsiveness. Fourth, combinations of c-Met and EGFR inhibitors in xenograft tumor models show enhanced tumor growth inhibition beyond that observed with either agent alone. An example of this is the NCI-H596 NSCLC xenograft tumor model that shows robust enhancement of growth in human HGF-Tg-SCID mice, indicating that this tumor model is strongly HGF-driven. Despite robust inhibition of other HGF-driven tumor models in HGF-Tg-SCID mice by the monovalent anti-c-Met antibody, MetMAb, treatment of HGF-Tg-SCID mice harboring established NCI-H596 tumors with MetMAb resulted in ~65% tumor inhibition, indicating that blockade of HGF by MetMAb is not sufficient for full tumor inhibition in established tumors. Treatment of NCI-H596 xenograft tumors with erlotinib alone had minimal effects. However, combination of MetMAb plus erlotinib very potently inhibited tumor growth ~90%, indicating that EGFR plays a major role in tumor survival and growth in the face of potent c-Met inhibition in this model. Taken together these data indicate that simultaneous targeting c-Met and EGFR may have a great impact on NSCLC tumors, where co-activation of these receptor pathways is frequently observed.
Perioperative chemotherapy alone versus preoperative chemoradiotherapy for locally advanced distal esophageal and gastroesophageal junction cancer: A 10-year review of the British Columbia (BC) Cancer Registry.
Authors: Shiru Lucy Liu, Irene S. Yu, Sally CM Lau, Yizhou Zhao, Devin Schellenberg, Sharlene Gill, Howard John Lim
Journal: Journal of Clinical Oncology (2019)

4028 Background: The optimal treatment strategy for resectable cancer of the distal esophagus (ESOPH) and gastroesophageal junction (GEJ) remains controversial. This study evaluates patterns of practice in BC, rates of complete surgical resection, and survival outcomes of patients treated with perioperative chemotherapy alone (CA), per MAGIC or FLOT4 protocol, versus preoperative chemoradiotherapy (CRT), per CROSS protocol. Methods: We undertook a provincial analysis of initially resectable, locally advanced, cancer of the ESOPH and/or GEJ who underwent surgery in BC, from 2008 to 2018. Baseline patient, tumor, treatment, and clinical outcome data were collected from the BC Cancer Registry. Kaplan-Meier survival and multivariate regression analyses were conducted. Results: Among 575 patients, 468 underwent surgery and were included (Table). More surgeries were aborted intraoperatively in the CA cohort compared to CRT (12% vs 2%, p&lt;0.001). There was no difference in age, sex, or ECOG performance status among the cohorts, and 83% were adenocarcinoma. While 82% of ESOPH involving GEJ (N = 251, 54%) is treated with CRT, only 53% of GEJ alone (N=217, 46%) is treated with CRT (p&lt;0.001). CRT is associated with a higher rate of complete or partial pathologic response compared to CA (59% vs 39%, p=0.002). R0 resection rate was 90% and 94% in the CA and CRT cohort, respectively (p=0.383). There is no statistically significant difference in overall survival, with medians of 29.6 and 26.0 months for patients treated with CA and CRT, respectively (p=0.723). Cancer-specific survival is also not significantly different (p=0.565). In the CA cohort, 37% of patients complete all 8 cycles of FLOT and 52% of patients complete all 6 cycles of MAGIC (p=0.396). Conclusions: Patients treated with CRT have higher rates of complete resection and pathologic response, but their survival is not significantly different compared to those treated with CA. [Table: see text]