tbuckley/cabot-search huggingface dataset:
Mastocheck: Notable plasma protein biomarker for diagnosis of breast cancer in the real clinical practice by using multiple reaction monitoring-based mass spectrometry.
Authors: Yumi Kim, Un-Beom Kang, Sungsoo Kim, Han-Byoel Lee, Jigwang Jung, Hong Kyu Kim, Hyeong-Gon Moon, Wonshik Han, Dong-Young Noh
Journal: Journal of Clinical Oncology (2019)

3044 Background: Breast cancer is the most frequently diagnosed cancer and the most leading cause of cancer-related deaths among women worldwide. Although screening mammography is available, there is an ongoing interest in improved early detection and prognosis. And also, serum tumor marker levels, such as CA 15-3 and others, may reflect disease progression and recurrence, they have not proven to be sensitive for early disease detection. Research investigating biomarkers for early detection, prognosis and the prediction of treatment responses in breast cancer is rapidly expanding. However, no validated biomarker currently exists for use in routine clinical practice, and breast cancer detection and management remains dependent on invasive procedures We aimed to develop biomarker for diagnosis of breast cancer in the real clinical practice by using proteomics technology. Methods: Based on our previous studies, we performed verification and validation of 124 candidate proteins by using proteomics approach. Among these 124 candidate proteins, the three proteins (neural cell adhesion molecule L1-like protein, apolipoprotein C-1, carbonic anhydrase-1) with highest statistical significance were selected. We created the performance algorithm of the 3-protein diagnostic model to predict of the breast cancer. We performed several experiments for establishment and validation of cut-off value. Furthermore we conducted test for acquisition of sample stability and more experiments to achieve the reproducibility and level of evidence, compared with other cancers (colon, thyroid, ovary, pancreas and lung cancer) and established effect of anesthesia. Results: Total 1226 samples (532 patients of breast cancer, 562 healthy women and 100 sample of other cancers) was analyzed. The sensitivity, specificity and accuracy from confirmation experiment was 71.58%, 85.25% and AUC 0.8323, respectively. The result of comparison with other cancers, there are no statistical significant difference and no relevance with effects of anesthesia. With these results, we recently got permission it to use for in vitro diagnostic use from Korea Food and Drug Administration. Conclusions: In this study, we developed a plasma protein biomarker that may help to diagnosis of breast cancer in the real clinical practice. By using MRM approach, the 3-protein biomarker was validated in an independent cohort with acceptable accuracy for early diagnosis of breast cancer.
Health-related quality-of-life in patients with cholangiocarcinoma: Results of a systematic literature review.
Authors: Yohan Cho, Claire Chadwick, Scott Barrett, Kristen Bibeau, Wissam El-Hadi, Devan Hopkinson
Journal: Journal of Clinical Oncology (2019)

e15623 Background: Cholangiocarcinoma (CCA) is a rare biliary tract cancer (BTC) with a historically poor prognosis and limited treatment options. Both quality and quantity of life can be important factors when deciding treatment, thus assessment of health-related quality-of-life (HRQoL) is needed to justify the use of novel therapies. HRQoL questionnaires are a standardized way to understand the patients’ perspective and treatment experience. The objective of this review was to examine the published literature specific to HRQoL in CCA. Methods: A systematic literature search was conducted using EMBASE and MEDLINE from Jan 2008 to June 2018 to identify abstracts with published HRQoL data in CCA patients. This review also included global conference proceedings (2015-2018) and HTA websites. Articles were considered relevant if they reported HRQoL data in patients with CCA, bile duct carcinoma, and/or hepatobiliary system cancer. Results: Of the 2,933 studies initially identified, 7 ongoing or completed studies met the scoping criteria to be included in the review. No articles in this literature review reported data from clinical trials. Multiple HRQoL measures were utilized; however within the studies, EORTC QLQ-BIL21 was the only HRQoL measure developed and validated specifically for BTC (CCA, gallbladder, or ampulla vater) identified in this review. 3/7 studies included information on CCA subtypes (intrahepatic, extrahepatic) with 2/3 studies reporting HRQoL by subtype. Patient symptoms were reported in 4/7 studies, including gastrointestinal distress, abdominal pain, fatigue, fever, itching, difficulty sleeping, anxiety, jaundice and weight loss. Conclusions: Within this literature review, few studies have been published with HRQoL data in CCA patients. Data from the existing published literature is generally from a heterogeneous patient population, and not consistently specified for CCA stage or subtype. To better understand HRQoL in CCA patients, more data needs to be generated that include clinical trials for novel therapies.
Psychosocial and clinical factors of probands impacting intrafamilial disclosure and uptake of genetic testing in families with BRCA1/2 or MMR gene mutations.
Authors: Pascal Pujol, Nathalie Alegre, Pierre vande Perre, Yves-Jean Bignon, Jean Chiesa, Marie Christine Picot, Virginie Galibert, Helena Bertet, Carole Corsini
Journal: Journal of Clinical Oncology (2019)

e13151 Background: Intrafamilial disclosure of hereditary cancer predisposition in BRCA1/2 and mismatch repair gene (MMR) syndromes allows appropriate prevention strategies in at-risk relatives. We previously showed in a nationwide study that the uptake of genetic targeted testing (GTT) in these families by relatives was only 30%. We aimed to identify the medical and psychosocial factors affecting the proband’s intrafamilial disclosure and relatives’ uptake of GTT in BRCA1/2 or MMR syndromes. Methods: We assessed clinical variables, family history and several psychological variables of probands (depression, anxiety, alexithymia, optimism, coping, family relationship, perception of cancer risks and of hereditary transmission risks), together with disclosure and verified uptake of GTT in BRCA1/2 or MMR families. Results: Among relatives eligible for GTT, 68% were informed of the predisposition and 37% underwent GTT, according to proband reports. Intrafamilial disclosure was inversely associated with the degree of kinship (P &lt; 0.01). In multivariable analysis, disclosure increased with time since proband’s genetic diagnosis (P &lt; 0.01) and proband’s feeling of family cohesion (P = 0.01). GTT uptake increased with proband’s depression score (P = 0.02) and decreased with proband’s perception of cancer risks (P = 0.03). BRCA1/2 and MMR groups did not differ in findings concerning family information and GTT uptake. Conclusions: This study identified factors affecting disclosure to relatives and GTT uptake in BRCA1/2 and MMR syndromes and gives new insights to improve probands’ follow-up and intrafamilial sharing of genetic information.
Fibrinolytic Therapy to Reduce Microvascular Obstruction After Myocardial Infarction
Authors: Murat Sezer, Sabahattin Umman
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
State Variation in Early-Onset Colorectal Cancer in the United States, 1995–2015
Authors: Rebecca L Siegel, Genet A Medhanie, Stacey A Fedewa, Ahmedin Jemal
Journal: JNCI Journal of the National Cancer Institute (2019)

The extent to which the increase in early-onset colorectal cancer (CRC) in the United States varies geographically is unknown. We analyzed changes in CRC incidence and risk factors among people aged 20-49 years by state using high-quality population-based cancer registry data provided by the North American Association of Central Cancer Registries and national survey data, respectively. Early-onset CRC incidence was mostly stable among blacks and Hispanics but increased in 40 of 47 states among non-Hispanic whites, most prominently in western states. For example, rates increased in Washington from 6.7 (per 100 000) during 1995-1996 to 11.5 during 2014-2015 (rate ratio = 1.73, 95% confidence interval = 1.48 to 2.01) and in Colorado from 6.0 to 9.5 (rate ratio = 1.57, 95% confidence interval = 1.30 to 1.91). Nevertheless, current CRC incidence was highest in southern states. From 1995 to 2005, increases occurred in obesity prevalence in all states and heavy alcohol consumption in one-third of states, but neither were correlated with CRC incidence trends. Early-onset CRC is increasing most rapidly among whites in western states. Etiologic studies are needed to explore early life colorectal carcinogenesis.
Infigratinib in upper tract urothelial carcinoma vs urothelial carcinoma of the bladder and association with comprehensive genomic profiling/cell-free DNA results.
Authors: Nazli Dizman, Jonathan E. Rosenberg, Jean H. Hoffman-Censits, David I. Quinn, Daniel Peter Petrylak, Matt D. Galsky, Ulka N. Vaishampayan, Ugo De Giorgi, Sumati Gupta, Howard A. Burris, Harris S. Soifer, Gary Li, Carl L. Dambkowski, Susan Moran, Yining Ye, Siamak Daneshmand, Dean F. Bajorin, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2019)

4510 Background: Infigratinib (BGJ398) is a potent and selective FGFR1–3 inhibitor with significant activity in patients (pts) with advanced or metastatic urothelial carcinoma (mUC) bearing FGFR3 alterations [Pal et al 2018]. Given the distinct biologic characteristics of upper tract UC (UTUC) and urothelial carcinoma of the bladder (UCB), we sought to determine if infigratinib had varying activity in these settings. Methods: Eligible pts had mUC with activating FGFR3 mutations/fusions and prior platinum-based chemotherapy, unless contraindicated. Pts received infigratinib 125 mg orally daily (3 wks on/1 wk off). Overall response rate (ORR: CR+PR) and disease control rate (DCR; CR+PR+SD) were characterized in UCB and UTUC pts. Comprehensive genomic profiling was performed on FFPE tissues in a CLIA-certified lab (Foundation Medicine; Cambridge, MA). Blood was collected for cell-free (cf)DNA analysis using a 600-gene panel on an Illumina HiSeq 2500 sequencer. Results: 67 pts were enrolled; the majority (70.1%) had received ≥2 prior antineoplastic therapies. ORR was 25.4% and DCR was 64.2%. In the 8 pts with UTUC, 1 CR and 3 PRs were observed (ORR 50%); the remainder had a best response of SD (DCR 100%). UTUC pts were predominantly 2 nd line (62.5%), with only 2 (25%) showing response to previous treatment. In pts with UCB, 13 PRs were observed (ORR 22%), and 22 pts had a best response of SD (DCR 59.3%). Notable differences in genomic alterations between cohorts included a higher frequency of FGFR3-TACC3 fusions (12.5% vs 5.8%) and FGFR3 R248C mutations (50% vs 11.5%), and a lower frequency of FGFR3 S249C mutations (25% vs 59.6%) in UTUC vs UCB. Consistent with previous reports [Sfakianos et al 2016], UTUC pts had a differential frequency of alterations in HRAS, CDKN2B and ARID1A. Sufficient cfDNA yield was obtained in UTUC and UCB pts and a comprehensive comparison of these data will be presented. Conclusions: Differences in cumulative genomic profile were observed between UCB and UTUC in this FGFR3-restricted experience, underscoring the distinct biology of these diseases. Results with infigratinib in UTUC support a planned phase III adjuvant study predominantly in this population. Clinical trial information: NCT01004224.
Proof-of-concept study evaluating a new tool for standardizing radiological assessment of tumor response to treatment in routine clinical practice.
Authors: Charles Mastier, Christelle De La Fouchardiere, Pierre-Etienne Heudel, Jerome Fayette, Matthieu Sarabi, Nathan Banaste, Marion Barma, Elodie mercier-Bischoff, Medhi Brahmi, Philippe Alexandre Cassier, Gwenaelle Garin, David Pérol, Frank Pilleul, Jean-Yves Blay
Journal: Journal of Clinical Oncology (2019)

e18079 Background: Internationally recognised criteria to evaluate tumour response, such as Response Evaluation Criteria In Solid Tumors (RECIST) and iRECIST (for immunotherapeutics) are not widely used in clinical practice. The main reason is that communications amongst health professionals are insufficiently standardised. To this purpose, ON’COHUB (MIRIO in France), a newly developed tool, automatically streamlines interactions between oncologists and radiologists to optimise and facilitate response evaluation according to the standard criteria. This study aims to identify the benefits in terms of user satisfaction and to provide preliminary data for the standardisation of the tool. Methods: Five oncologists, 3 radiologists, 1 clinical research associate and 1 clinical project officer used ON’COHUB to assess patients’ tumour responses according to RECIST, in an anti-cancer center, over five months. An oncologist compared patients’ regular radiology reports (n = 110) and ON’COHUB’s reports (n = 106), using the following report quality indicators: information on the patient’s context, target and non-target lesions , baseline, NADIR, and overall evaluation. Then a questionnaire on the user’s satisfaction was administered. Two-tailed chi-square tests were performed to compare patients’ regular radiology reports and ON’COHUB’s reports. Results: ON’COHUB was reported to significantly improve the following quality indicators compared to regular reports: presence of the treatment (99% vs 42%; p &lt; 0,001), follow-up criteria (98% vs 5%; p &lt; 0,001); target lesion and location (100% vs 75%; p &lt; 0,001), size of target lesions (99% vs 67%; p &lt; 0,001), value and date of the baseline (100% vs 0% and 4%, respectively; p &lt; 0,001 for both), value of the baseline lesion by lesion (99% vs 4%; p &lt; 0,001), value and date of the Nadir (97% vs 0%; p &lt; 0,001), global response according to RECIST (100% vs 17%; p &lt; 0,001), value of target lesions response (80% vs 20%; p &lt; 0,001), referential for RECIST calculation (98% vs 2% p &lt; 0,001).Finally, 9 out of the 10 users declared that they would use ON’COHUB on a daily basis. Conclusions: These preliminary data suggest that ON’COHUB may have a positive impact on the quality of the treatment response evaluation in clinical trials and in routine use. These results will be confirmed with the deployment of the interoperability with IT hospital System.
Abstract IA18: <i>MYCN</i> amplification and <i>ATRX</i> mutations are incompatible in neuroblastoma
Authors: Maged Zeineldin, Sara Federico, Xiang Chen, Beisi Xu, Elizabeth Stewart, Arlene Naranjo, Michael D. Hogarty, Michael A. Dyer
Journal: Cancer Research (2018)

Abstract Age and stage of disease at diagnosis are associated with outcome in neuroblastoma. A previous study identified ATRX point mutations and in-frame deletions in older patients with stage 4 disease. To validate the frequency of ATRX mutations and assess the relation of mutations and known prognostic variables, we collaborated with the Children’s Oncology Group and sequenced the entire ATRX genomic locus in 475 neuroblastoma tumor samples to validate the frequency of ATRX mutations and assess the relation of mutations and known prognostic variables. Older age at diagnosis, stage 4 disease, and unfavorable histology were significantly associated with mutations in the ATRX gene; MYCN amplification was mutually exclusive from ATRX mutations. To directly test if ATRX mutations and MYCN amplification are incompatible in neuroblastoma, we mutated the ATRX gene in MYCN amplified neuroblastoma cell lines and ectopically expressed MYCN in ATRX mutant neuroblastoma cell lines. Both approaches showed that ATRX and MYCN amplification are incompatible in neuroblastoma in culture and in vivo. To gain a better understanding of the underlying molecular and cellular mechanisms of this incompatibility, we performed a series of experiments including telomere analysis, epigenetic profiling, electron microscopic analysis of dying cells, and metabolic profiling. We discovered that induction of MYCN expression in ATRX mutant neuroblastoma cells leads to metabolic reprogramming, mitochondrial dysfunction, increased reactive oxygen species, and replicative stress. We propose that this leads to synthetic lethality in ATRX mutant neuroblastomas because of the underlying replicative stress in those cells as a result of dysfunction of this essential histone chaperone complex. Citation Format: Maged Zeineldin, Sara Federico, Xiang Chen, Beisi Xu, Elizabeth Stewart, Arlene Naranjo, Michael D. Hogarty, Michael A. Dyer. MYCN amplification and ATRX mutations are incompatible in neuroblastoma [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr IA18.
Identification of immune microenvironment subtypes of breast cancer in TCGA set: Implications for immunotherapy.
Authors: Chang Liu, Yi Xiao, Zhonghua Tao, Xi-Chun Hu
Journal: Journal of Clinical Oncology (2019)

e14205 Background: Checkpoint blockade immunotherapy has been reported to show promising responses in breast cancer. However, only a small quantity of patients benefited from immunotherapy. To understand the underlying molecular mechanisms of immunotherapy and distinguish appropriate patients, we profiled the immune microenvironment landscape of breast cancer. Methods: We analyzed 1092 breast cancer samples from the Cancer Genome Atlas (TCGA) profiled by RNA sequencing. Using 141 immune-related genes, the cohort was divided into 2 subtypes (Immune and non-Immune) by k-means cluster analysis. Immune-related gene signatures representing different immune statuses or immune cells were used to profile Immune Class by k-means cluster analysis, and we further classified them into Active and Exhausted Immune Classes. Results: We identified 40% of breast cancer in TCGA set (433/1092) as Immune Class and further classified them into 2 distinct subtypes, Active and Exhausted Immune Classes (17% and 23%, respectively). Compared with non-Active Immune Class, Active Immune Class was associated with black people and negative hormone receptor (all, P &lt; 0.01). We detected higher proportions of basal-like and HER2-enriched cases within Active Immune Class compared to Exhausted and non-Immune Class (basal-like, 41.0% vs. 11.3% and 12.6%; HER2-enriched, 14.1% vs. 7.1% and 6.5%). In survival analyses, Active Immune Class was significantly correlated with favorable disease-free survival ( P = 0.019) and overall survival ( P = 0.041). Multivariate analyses further identified Active Immune Class as an independent prognostic factor for overall survival ( P = 0.024). Conclusions: Our work classified breast cancer into 3 immune microenvironment subtypes. This novel classification can indicate the prognosis of patients, reveal the underlying immunological mechanisms of tumor progression and may assist immunotherapy decision-making for breast cancer patient. [Table: see text]
The effect of a structured weekly patient meeting on patient reported outcomes (PRO) and resource utilization for patients with metastatic breast cancer (MBC).
Authors: Margaret Q. Rosenzweig, Victoria Resier, Rachel Heckman, Ann Welch, Dianxu Ren
Journal: Journal of Clinical Oncology (2019)

e23116 Background: Women with MBC experience unmet unique symptom management and psychosocial needs due to chronic treatment for an eventually life ending illness. Methods: The MBC Program of Care is a 1 hour weekly, nurse led review of scheduled clinic patients by an interdisciplinary team incorporating structured needs appraisal and referral for supportive, palliative care resources. Outcomes included referral rates to supportive services, patient reported outcomes (PRO) of symptom distress, generalized anxiety and overall well-being. Health care utilization outcomes included clinic calls as well as inpatient and emergency room visits. A prospective, paired pre and post experimental design. One hundred and eighteen women with MBC who visited an urban outpatient breast cancer clinic from September 2016-November 2016 (pre) and from January 2017-March 2017 (post). Validated instruments of symptoms ( Adapted Memorial Symptom Assessment), anxiety (Generalized Anxiety Scale), and overall well-being scores (0-10 Likert) assessed PROs. Electronic chart review evaluated social work and palliative care referrals, hospital admissions, emergency room visits and phone calls to the outpatient clinic pre and post program implementation. T test and chi squared test for paired comparison of mean was performed. Results: Following program implementation, referrals to palliative care (p = .000) and social work (p = .001) increased significantly. PROs of symptoms (p = .001); anxiety (p = 0.002); and overall well-being (p = .002) improved significantly. Health care utilization including emergency department visits (p = .001) and patient calls (p = .005) decreased significantly post program implementation, although hospital admissions increased (p = .003). Cost of program was $750 weekly. Conclusions: Systematic review of patient needs and referral to existing supportive services improved MBC PROs and decreased emergency room visits and clinic calls. Post hospital admission increase may be attributed to MBC disease progression. This is a cost effective MBC model of palliative care implementation.