tbuckley/cabot-search huggingface dataset:
Pneumonitis in advanced non-small-cell lung cancer (NSCLC) patients (pts) treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI): Meta-analysis of 153 trial cohorts with 15,713 pts.
Authors: Chong Hyun Suh, Hyesun Park, Kyung Won Kim, Junhee Pyo, Hiroto Hatabu, Mizuki Nishino
Journal: Journal of Clinical Oncology (2018)

e21223 Background: Pneumonitis is a significant toxicity of EGFR-TKI in NSCLC pts. We studied the incidence of EGFR-TKI pneumonitis in clinical trials published in 2003-2017, and performed subgroups analyses to identity predisposing factors. Methods: Ovid-MEDLINE and EMBASE search up to 4/17/17 using the keywords, “erlotinib”, “gefitinib”, “afatinib”, “osimertinib”, and “lung cancer”, resulted in a total of 153 eligible trial cohorts with 15,713 pts treated with EGFR-TKI for advanced NSCLC. The pooled incidence of all-grade, high-grade, and grade 5 pneumonitis was obtained with the binormial-normal model. Subgroup analyses were performed with multivariate meta-regression using study-level covariates. Cohorts with EGFR-TKI retreatment were analyzed separately. Results: Among the pts without prior exposure to EGFR-TKI, the overall incidence was 1.12% (95%CI: 0.79-1.58%) for all-grade, 0.61% (95%CI: 0.40-0.93%) for high-grade, and 0.20% (95%CI: 0.11-0.38%) for grade 5 pneumonitis. The incidence was significantly higher in studies from Japan compared to studies of non-Japan origin, for all grade (4.77% vs 0.55%, p < 0.001), high grade (2.49% vs 0.37%, p < 0.001), and grade 5 pneumonitis (1.00% vs 0.18%, p < 0.001). Multivariate analyses demonstrated higher odds of pneumonitis in studies from Japan for all-grade (odds ratio [OR]: 5.04; 95%CI: 3.15-8.06, p < 0.001), high-grade (OR: 4.45; 95%CI: 2.51-7.87, p < 0.001), and grade 5 pneumonitis (OR: 4.55; 95%CI: 2.21-9.37, p < 0.001) compared to those of non-Japan origin, after adjusting for types of EGFR-TKI and lines of therapy. In pts with EGFR retreatment analyzed separately, the pooled incidence was 1.13% (95%CI: 0.40-3.15%) for all-grade, 0.49% (95%CI: 0.21-1.11%) for high-grade, and 0.16% (95%CI: 0.04-0.65%) for grade 5 pneumonitis. Conclusions: The overall incidence of EGFR-TKI pneumonitis was 1.12% in pts without prior exposure to EGFR-TKI, and 1.13% in EGFR-TKI retreatment group. The cohorts from Japan had significantly higher incidence of pneumonitis, providing insights for further studies of risk factors and biomarkers for pneumonitis.
A retrospective analysis of the efficacy of immune checkpoint inhibitors (ICIs) to advanced non-small cell cancer (NSCLC) patients (pts) with central nerve system (CNS) metastasis.
Authors: Takashi Sone, Kazuo Kasahara, Hiroki Shirasaki, Yoshiaki Amino, Koichi Nishi, Koji Kurokawa, Toshiyuki Kita, Tomoyuki Araya, Taro Yoneda, Kota Tanimura, Tamami Sakai, Nanao Terada, Hiroki Matsuoka, Hayato Koba, Yuichi Tambo, Hideharu Kimura
Journal: Journal of Clinical Oncology (2018)

e21042 Background: In clinical practice of advanced NSCLC pts, a control of CNS metastasis is important issue. Several clinical trials of ICIs have demonstrated the survival benefit in advanced NSCLC. However, the efficacy to pts with CNS lesion is unclear, because most trials exclude pts with active CNS metastasis. In order to clarify the efficacy of ICIs to NSCLC pts with CNS metastasis in real-world clinical practice, we planned the observational research. Methods: We retrospectively collected clinical information of all pts treated with ICIs at Kanazawa university hospital and 5 cancer institutions from Dec 2015 to Sep 2017. Results: Of 191 pts treated with ICIs, 65 pts, including 46 men, 11 pts with squamous cell carcinoma histology, 56 smokers, 54 pts with good PS (0-1) had CNS metastasis (65 brain, 4 both brain and leptomeningeal). PD-L1 expression was assessed in 27 pts (0%:2 pts, 1-49%:10 pts, 50%< 15 pts). Fifty-one pts received nivolumab and 14 pts received pembrolizumab. 51 pts were received local radiotherapy to CNS metastasis prior to ICIs. Tumor shrinkage by ICIs was able to assessed in 61 pts and response rate was 16.9% (CR:2, PR:9, SD:17, PD:33). At the time of analysis, 56 pts showed progression, 4 pts progressed by only CNS lesion, 32 pts progressed by only extracranial lesion and 20 pts showed systemic progression including CNS lesion. Median progression free survival was 2.0 months (95%CI, 1.4-3.9 m) and median overall survival (OS) was 10.3 months (95%CI 3.6-13.9 m). These survival time were not different from those of pts without CNS metastasis. PFS was not correlated with any patients' characteristic factor (sex, age, histology, PS, history of local radiotherapy). OS was prolonged in pts with good PS (11.7m vs 1.7 m, p=0.0004) and in pts those received prior local radiotherapy to CNS lesion (11.7m vs 5.2 m, p=0.004), these were significant prognostic factors in multivariate analysis too. Conclusions: In this analysis, the efficacy of ICIs to pts with CNS metastasis was not different to pts without CNS metastasis. Good PS and prior local radiotherapy were good prognostic factors in pts with CNS metastasis those were treated with ICIs.
Hereditary cancer syndromes and prostate cancer development among African American men: The importance of complete family cancer history.
Authors: Elias Obeid, Sarah Hegarty, Lisa Bealin, Susan Montgomery, Laura Gross, David Y. T. Chen, Veda N. Giri
Journal: Journal of Clinical Oncology (2016)

e16625 Background: African American (AA) men are at increased risk for developing and dying from prostate cancer (PC). While family history PC has been recognized to raise the risk for PC in AA men, there is a knowledge gap regarding how the full spectrum of family cancer history may inform PC risk and enable AA men to make screening decisions. We characterized pedigrees of AA men enrolled in a high-risk PC screening program to determine prevalence of hereditary cancer syndromes (HCS) and PC development, to gain insight into the role of comprehensive family cancer history in PC risk assessment for African American men. Methods: Prostate Risk Assessment Program (PRAP) is a screening and research program at Fox Chase Cancer Center for men at high risk for developing PC. Eligibility criteria include men ages 35-69 years with 1 first-degree relative with PC, 2 second-degree relatives with PC on same side of the family, or any AA male regardless of family history. Self-reported family cancer history was characterized into three HCS in which PC has been implicated: hereditary breast-ovarian cancer (HBOC) syndrome, Lynch syndrome (LS), and hereditary prostate cancer (HPC) by established criteria. PC screening by PSA was performed, with biopsies to establish diagnosis based on PSA level. Multivariate analyses were performed to determine if HCS predicted PC diagnosis among AA participant. Results: This analysis included 196 AA PRAP participants in active follow-up or having been diagnosed with PC as a result of the screening protocol. Overall, 15.3% of the 196 AA participants reported a family cancer history consistent with at least one HCS. After controlling for PSA, HCS remained strongly associated with PC diagnosis (OR = 3.32, 95% CI 1.41-7.83, p = 0.006). Conclusions: This is the first report to our knowledge of the prevalence of HCS in AA men undergoing PC screening. Our data showed a 3-fold increased risk for prostate cancer development among AA men with family cancer history meeting criteria for HCS. This highlights the importance of performing a thorough family cancer history intake among AA men.
Colorectal liver metastases with concomitant extrahepatic disease: Is there a hope of cure?
Authors: Katsunori Imai, Carlos Castro Benitez, Marc Antoine Allard, Eric Vibert, Antonio Sa Cunha, Daniel Cherqui, Denis Castaing, Henri Bismuth, Hideo Baba, Rene Adam
Journal: Journal of Clinical Oncology (2016)

e15056 Background: Although the advent of effective chemotherapy has enable surgery in patients with colorectal liver metastases (CRLM) and concomitant extrahepatic disease (EHD), the potential of cure in these patients is still unclear. The aims of this study were to define the rate of cure based on 5-year disease-free survival (DFS) after surgery in patients with CRLM and concomitant EHD, and to identify the predictive factors of cure. Methods: All patients who underwent hepatectomy for CRLM and who had diagnosed concomitant EHD were identified. Among them, the patients who had a minimum follow-up of 5 years from surgery were enrolled in this study. Cure was defined as a DFS > 5 years after last curative surgery. Results: Concomitant EHD was located in the lung in 89 (41.2%), lymph nodes in 37 (17.1%), peritoneum in 35 (16.2%), others in 18 (8.3%), and multiple sites in 37 patients (17.1%). The 5-year overall survival (OS) rate was 29.4%, and 5-year DFS rate was 6.9%, respectively. Among the 175 patients with a follow-up from last curative surgery > 5 years (intention-to-treat (ITT) cohort), cure was achieved in 24 (13%) patients. Among the patients who underwent curative resection for both hepatic and extrahepatic metastases (resection cohort, n = 109), cure was achieved in 22 (19%) patients. Multivariate logistic analysis identified primary T stage 1-2 (relative risk (RR) 47.4, P= 0.0001), metachronous metastases (RR 4.9, P= 0.026), carbohydrate antigen 19-9 (CA19-9) ≤ 37 U/mL (RR 8.37, P= 0.015), cumulative number of liver and EHD tumors (RR 11.2, P= 0.0058), and non-incidentally EHD diagnosis (RR 8.41, P= 0.018) in the ITT cohort, and primary T stage 1-2 (RR 22.2, P= 0.013), primary N stage (RR 4.42, P= 0.031), metachronous metastases (RR 6.48, P= 0.013), and CA19-9 ≤ 37 U/mL (RR 27.4, P= 0.012) in the resection cohort as independent predictive factors of cure. Conclusions: An agressive oncological approach could achieve cure in 13% of patients with CRLM and concomitant EHD on an ITT basis. When complete resection of both hepatic and extrahepatic diseases is performed, cure rate could raise 19% of the patients. Therefore, even in the presence of EHD, an aggressive oncosurgical approach should be intended in patients with CRLM with a hope of cure.
Neoangiogenesis factors determine incidence rates of colorectal cancer in men and women.
Authors: Elena Alekseevna Dzhenkova, Oleg I. Kit, Elena M. Frantsiyants, Alexander Vasilievich Shaposhnikov, Valeria A. Bandovkina, Larisa S. Kozlova, Evgeniy N. Kolesnikov, Aleksandr V. Snezhko, Vladimir Trifanov, Mikhail A. Averkin, Sergey V. Sanamyants, Roman E. Myagkov, Leonid V. Kharin, Roman E. Tolmakh
Journal: Journal of Clinical Oncology (2018)

e15623 Background: Growth factors and neoangiogenesis maintain the endothelial barrier homeostasis, form new vasculature for a tumor and interact with sex hormones. Rectal and sigmoid tumors are more frequent in men than in women. The purpose of the study was to analyze levels of some growth factors in primary adenocarcinomas (PAs) of the rectum (R) and sigmoid colon (SC) in men (M) and women (W). Methods: Levels of VEGF-A, IFR-1 IFR-2 and TGF-β1 were studied in cytosols of tissue obtained from 78 patients (РА, st. III, G2, 49 men and 29 women aged 38-73 years, T1-3N0M0) by the ELISA method using standard test kits. The data were compared with the values in intact tissues of the resection line. Results: VEGF-A levels in RL were similar to the levels in SC and R in both M and W. VEGF-A in PA tissues of SC and R was 2.3 times higher in W. IFR-1 levels were similar in M and W in all tissues. IFR-2 in PA SC and R of M was 1.4 and 1.8 times higher than in W. TGF-β1 in PA R in W was 3.3 times higher than in M. Levels of VEGF-A, IFR-1 and IFR-2 in M and W and TGF-β1 in W was higher in PA compared to RL in both SC and R. TGF-β1 in PA R in M was lower than in RL by 1.3 times. Surprisingly, levels of all the studied growth factors in perifocal tissues of PA of the colon, regardless its segment, were similar to the levels in intact tissues of RL in both M and W. Conclusions: The VEGF-А activation regulated by IGF-1 and IGF-2 in malignant tumors of SC and R in M and W apparently was a common mechanism. However, the regulatory role of TGF-β1 towards VEGF-А was observed only in PA R tissues of W (r = 0.99, p < 0.05). Activation of VEGF-A in W in PA SC and R significantly weaker depended on IFR-2 as its level was lower than in M (p < 0.01). Production of such neoangiogenesis factors as VEGF-A, IFR-II and TGF-β1 by colorectal tumors is gender-dependent which probably explains the incidence rates in men and women.
Abstract 18132: Prenatal Evaluation of the Fetal Cardiovascular Profile Score in a Multicenter Study of Ebstein Anomaly/Tricuspid Valve Dysplasia
Authors: Grace Freire, Lindsay Freud, Wayne Tworetzky, Maria Escobar, Rukmini Kumarlu, James Huhta, Marilyn Wilhm, Ernest Amankawh, Denise Martinez, Margaret Vernon, Erik Michelfelder, john Kovalchin, Catherine Ikemba, Cyrus Samai
Journal: Circulation (2015)

Introduction: The cardiovascular profile (CVP) score is an echo based multivariable approach for assessment of fetal hemodynamics. The CVP score has been shown to be useful in predicting the outcome of fetuses with heart failure, growth restriction, and select congenital heart defects. The score ranges from 0 to 10, with points deducted for abnormal hemodynamics. In a previous pilot study of 21 fetuses with EA/TVD, a CVP score &lt;7 was associated with poor outcomes. The aim of this study was to investigate the prognostic significance of the CVP score in a larger cohort of fetuses with EA/TVD. Methods: This 23-center study was a retrospective review of fetal echo data and outcomes in a cohort of 243 fetuses diagnosed with EA/TVD from 2005-2011. Both the first and last fetal echo in gestation were evaluated. Hydrops, heart size, cardiac function, and umbilical arterial and venous Dopplers were scored. The primary outcome was perinatal death, defined as fetal demise or death prior to neonatal discharge. Categorical variables were compared using Chi-squared tests; p-values &lt;0.05 were considered statistically significant. Results: Complete data on the first and last fetal echocardiograms to calculate a CVP score were available in 144 fetuses at the time of the first fetal echo (median GA 26.07 wks, range 14-40) and 73 fetuses at the time of the last fetal echo (median GA: 25 wks, range 18 -34). The median CVP scores for the first and last fetal echo were 8 (range 4-9) and 7 (range 7-9) among survivors vs. 7 (range 0-10) and 6 (range 1-8) among non-survivors. Fetuses with EA/TVD that died were more likely to have a CVP score &lt;7 compared to those that survived: 33.3% vs. 11.6 %, (p=0.004) on the first fetal echo and 60.0% vs. 28.6 % (p=0.015) on the last fetal echo. However, no statistically significant difference in survival was observed for fetuses whose CVP score decreased from the first to the last echo. (p=0.95). Conclusions: In this study, fetuses with EA/TVD with CVP scores &lt;7 on the first or last fetal echo were less likely to survive. The CVP score may be a valuable tool to identify fetuses with EA/TVD at risk of poor outcome for whom novel therapeutic approaches might be warranted.
Clinical and demographic characteristics of CLL patients receiving first-line bendamustine plus rituximab using the Flatiron Health database.
Authors: Boxiong Tang, Susan Gabriel, Ashutosh K. Pathak, Danielle M. Brander, Jifang Zhou
Journal: Journal of Clinical Oncology (2017)

e19010 Background: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the Western world, with 20,110 new cases estimated for 2017 in the US alone. Combination therapy with bendamustine plus rituximab (BR) is among the approved first-line therapies for CLL patients without the 17p deletion. The purpose of this analysis was to characterize CLL patients receiving first-line BR therapy using real-world data. Methods: CLL patients (ICD-9: 204.1x or ICD-10: C91.1x, C83.0x) receiving first-line BR therapy between 11/01/2008 and 11/01/2016 were identified in the Flatiron Health electronic health records database. This database is a large, longitudinal, demographically and geographically diverse database consisting of 250 cancer clinics representing more than 1.5 million active US cancer patients. Results: Of the 2736 CLL patients in the database, 738 patients (male = 70%; mean age = 68.71 years, SD = 9.070) received first-line BR therapy. The majority of patients received treatment in a community setting (93%; 7% in academic hospitals). Prior to first-line BR therapy, immunoglobulin heavy chain variable region ( IGHV) mutation analysis was conducted in 21% of patients, of which 46% were IGHV mutated. Fluorescence in situhybridization (FISH) testing was conducted in 60% of patients: 17p deletion was detected in 8% and 11q deletion in 19%. Trisomy 12 and 13q deletion as a single abnormality was identified in 17% and 27% of tested patients, respectively. Conclusions: CLL patients from the Flatiron database initiating first-line BR therapy have an older median age, male predominance, and community-based treatment setting, which offers a more real-world patient population in comparison with patients reported from clinical trials. Less than a quarter of these CLL patients were tested for IGHV mutations, and only 60% were tested for FISH. The low frequency of testing prior to first-line therapy is similar to other published registry data. This representative patient population offers an insight into the real-world use of BR in CLL patients.
Illness understanding of oncology patients in a community-based cancer institute.
Authors: Shanthi Sivendran, Sarah Jenkins, Sarah Svetec, Michael Horst, Kristina Braine Newport, Kathleen J. Yost, Manshu Yang
Journal: Journal of Clinical Oncology (2017)

e21605 Background: Several studies have demonstrated patients have a poor understanding of prognosis, survival and effectiveness of chemotherapy, particularly in the setting of advanced cancer. This study examines oncology patients’ understanding of their illness based on accurate reporting of stage at diagnosis as well as knowledge of remission status. Methods: 208 cancer patients previously treated at our large community based cancer institute participated in The Consumer-Based Cancer Care Value Index (CCCVI) Field Survey. Electronic medical record (EMR) documentation of stage at diagnosis and remission status were compared to patients’ self-reported responses. Concordance of responses and variables influencing discordance were evaluated. Results: 51.0% of patients’ self-reported cancer stage matched the abstracted stage with the highest concordance in the advanced cancer patients (72%) versus stage I-III patients (36.4%-61.5%). Unexpectedly, discordance was lower among advanced cancer patients as compared to stage I-III patients (p = 0.0528) Those who were concordant for cancer stage at diagnosis were significantly more likely to be female (p = 0.001), under the age of 65 (p = 0.01), have an income greater than $60,000 (p = 0.03), and have more education (p = 0.02). 64.4% of patients’ self-reported remission status matched the abstracted status. Nearly 30% of patients were not sure about their status even when they were in remission. Conclusions: Our findings confirm that more than one quarter of patients with advanced cancer have poor illness understanding, as well as highlights that an even greater number of patients with early stage I-III cancers have poor illness understanding. These observations highlight the need to improve illness understanding for patients across the entire cancer continuum.
Molecular profiles of endometrial cancers in a Caribbean black population.
Authors: Yi-Chun Lee, Erica Testani, Michael Chen, Regina Lee, Albert Palileo, Margaux Jenna Kanis
Journal: Journal of Clinical Oncology (2018)

e24152 Background: We examined the molecular profiles of Type 1 and 2 endometrial cancer (EC) in a unique patient population of immigrant Caribbean Black women, and identified the most frequently mutated genes and carcinogenic molecular pathways. We also compared the frequency of somatic mutations in this population with previously reported nationwide data. Methods: 55 samples of EC collected from 2015-2017 at our institution (24 Type 1 & 31 Type 2) were submitted to Caris Life Sciences (Irving, TX) and analyzed using immunohistochemistry (IHC) and next generation sequencing (NGS) of 165 genes. Statistical analysis was performed using the χ2 test. Results: In Type 1 EC, PTEN was the most frequently mutated gene (56.5%), followed by BRCA2 (45.5%), PIK3CA (43.5%) and CTNNB1 (38.4%). The most frequently mutated pathway was PI3K/PTEN/AKT. In Type 2, TP53 was the most frequently mutated gene (66.7%), followed by FBXW7 (17.2%), PIK3CA (16.7%) and APC (13.3%). The most frequently mutated pathway was Wnt/TP53. When compared to Caris data of 3,133 ECs collected across the US from 2011-2014, our population had different molecular profiles in both EC types. Most notable were the significant differences of BRCA2 and APC mutations in both Type 1 & 2 tumors between the nationwide and our data. Conclusions: Molecular profiling is critical for developing individualized targeted therapy. In this study we highlight the unique genetic variations of EC in a specific ethnic group, demonstrating that women of different racial and geographical backgrounds may have different molecular profiles, which may contribute to different treatment response and survival. Pathway Gene Type 1 Type 2 Our study USA p Our study USA p DNA repair BRCA1 13.6% 8.3% 0.365 0% 10.8% 0.053 BRCA2 45.5% 38.9% 0.033* 0% 17.2% 0.011* ATM 8.7% 3.6% 0.198 6.7% 2.2% 0.12 PI3K/PTEN/AKT PTEN 56.5% 41.1% 0.135 3.4% 12.4% 0.123 PIK3CA 43.5% 35.6% 0.431 16.7% 26.5% 0.195 AKT1 4.3% 5.2% 0.855 0% 0.9% 0.596 EGFR/MAPK/HER2 KRAS 9.1% 24.0% 0.103 3.3% 12.3% 0.125 Wnt/TP53 APC 17.4% 21.1% 0.028* 13.3% 2.9% 0.001* CTNNB1 34.8% 19.6% 0.069 6.7% 2.8% 0.225 TP53 4.3% 23.7% 0.03* 67% 66.7% 0.797 HGF/cMET cMET 0.0% 2.1% 0.485 6.9% 2% 0.083
TCT-821 Patent Foramen Ovale Closure in Patients with Cryptogenic Stroke: Meta-analysis of Randomized Controlled Trials
Authors: Fahed Darmoch, Yasser Al-khadra, Homam Moussa Pacha, Mohamad Soud, Zaher Fanari, Amr Idris, Ziad SayedAhmad, Amir Kaki, M Chadi Alraies
Journal: Journal of the American College of Cardiology (2018)