Cholangiocarcinoma With FGFR Genetic Aberrations: A Unique Clinical Phenotype

2018 ◽  
pp. 1-12 ◽  
Author(s):  
Apurva Jain ◽  
Mitesh J. Borad ◽  
Robin Kate Kelley ◽  
Ying Wang ◽  
Reham Abdel-Wahab ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Positive Impact ◽  
Prognostic Impact ◽  
Younger Patients ◽  
Genetic Aberrations ◽  
Exact Test ◽  
Kaplan Meier ◽  
History Of ◽  
Indolent Disease

Purpose FGFR genetic aberrations (GAs) occur in an estimated 10% to 16% of intrahepatic cholangiocarcinomas (CCAs). The natural history of CCA with FGFR GAs, the prognostic role of coexisting GAs, and the outcome with FGFR-targeted inhibitors are unknown. Patients and Methods Patients with CCA with FGFR GAs were identified using next-generation sequencing or fluorescence in situ hybridization from four tertiary cancer centers and compared with FGFR wild-type counterparts. Data reviewed included demographic, treatment, overall survival (OS), and GA data. Fisher’s exact test, Kaplan-Meier plots, and log-rank tests were used for statistical analysis. Results Three hundred seventy-seven patients with CCA were identified, and 95 had FGFR GAs. FGFR2 GA was most common (n = 74, with 63 fusions) and seen in intrahepatic CCA. In patients with CCA, FGFR GAs occurred more frequently in younger patients (≤ 40 years; 20%) compared with older patients (> 40 years; 6.7%; P < .001), presented at an earlier stage (TNM stage I/II v III/IV: 35.8% v 22%, respectively; P = .001), and were associated with a longer OS compared with patients without FGFR GAs (37 v 20 months, respectively; P < .001). This difference remained significant after excluding 36 patients treated with FGFR inhibitors. There was no OS difference ( P = .60) between CCA with FGFR2 fusions (n = 63) versus other FGFR GAs (n = 29). Patients with FGFR GAs had a better OS with FGFR-targeted therapy compared with standard treatment ( P = .01). BAP1 mutation was the most common coexisting mutation without prognostic impact, whereas TP53 ( P = .04) and CDKN2A/B ( P = .04) were correlated with a shorter OS. Conclusion CCA with FGFR GAs represents a unique subtype occurring in younger patients with an indolent disease course. FGFR-targeted therapy may have a positive impact on OS in this subgroup.

scholarly journals Restating the case: How revisiting the development of the case method can help us think differently about the future of the business school

2020 ◽  
Author(s):  
Todd Bridgman ◽  
Stephen Cummings ◽  
C McLaughlin
Keyword(s):  
Business School ◽  
Business Schools ◽  
Positive Impact ◽  
Case Method ◽  
Harvard Business School ◽  
Linear Evolution ◽  
Management Learning ◽  
Innovative Thinking ◽  
History Of

© Academy of Management Learning & Education. Although supportive of calls for business schools to learn the lessons of history to address contemporary challenges about their legitimacy and impact, we argue that our ability to learn is limited by the histories we have created. Through contrasting the contested development of the case method of teaching at Harvard Business School and the conventional history of its rise, we argue that this history, which promotes a smooth linear evolution, works against reconceptualizing the role of the business school. To illustrate this, we develop a "counterhistory" of the case method-one that reveals a contested and circuitous path of development-and discuss how recognizing this would encourage us to think differently. This counterhistory provides ameans of stimulating debate and innovative thinking about how business schools can address their legitimacy challenges, and, in doing so, have a more positive impact on society.

scholarly journals CMET-28. DECREASED FREQUENCY OF BRAIN METASTASES DUE TO THE USE OF PDL1-INHIBITORS IN RCC

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi57-vi57
Author(s):  
Mark Damante ◽  
Kristin Huntoon ◽  
Dante Pezzutti ◽  
Thomas Olencki ◽  
J Bradley Elder
Keyword(s):  
Clinical Trials ◽  
Brain Metastases ◽  
Cytotoxic T Lymphocyte ◽  
Exact Test ◽  
Treatment Groups ◽  
Kaplan Meier ◽  
Systemic Treatments ◽  
History Of ◽  
Cell Death Protein ◽  
Metastatic Rcc

Abstract INTRO Programmed cell death protein 1 (PD1)-inhibitor, nivolumab, and cytotoxic T-lymphocyte-associated protein 4 (CTLA4)-inhibitor, ipilimumab, have been shown to be efficacious in treatment of metastatic renal cell carcinoma (RCC). Clinical trials utilizing PD1- and CTLA4-inhibitors to treat RCC have demonstrated an increase in survival, however history of brain metastases (BM) has typically excluded patients from these trials. This study evaluated the benefit of these agents in terms of overall survival from RCC diagnosis (OSRCC), from BM diagnosis (OSBM) and frequency of BM occurrence in patients with metastatic RCC. METHODS A retrospective single-center review between 2011–2018 identified 1149 patients treated for RCC. The study group included patients who received immunotherapy and/or non-immunotherapeutic agents during the course of their disease. Data analyzed included demographic information, systemic treatments, OS and status of BM. Two-sided Fisher’s exact test was used to evaluate frequency of BM occurrence. OSRCC and OSBM were assessed using Kaplan-Meier curves and log-rank tests. RESULTS Of 1149 patients, 425 (35.6%) were treated with systemic therapies during their clinical course and divided into two treatment groups: those receiving immunotherapy (n=125) and those receiving non-immunotherapeutic agents (n=300). OSRCC was improved in the immunotherapy group (80.3months 95%CI 58.7–101.9 vs 45.0 95%CI 36.4–53.6, p=0.003), with 1-, 3- and 5-year survival of 93.6%, 74.2% and 62.6%. BM were diagnosed in 113 of 425 patients. Use of immunotherapy was associated with increased OSBM (21.7months vs 8.5, p=0.001). In patients receiving systemic treatment prior to a potential BM diagnosis, BM occurred at a frequency of 8.0% in the immunotherapy group compared to 17.7% for the control (n=100 and n=266 respectively, p=0.021). CONCLUSION Immunotherapy not only improves OSRCC and OSBM, but also decreases the incidence of BM in patients with metastatic RCC. Prospective clinical trials are needed to further evaluate the activity of immunotherapy in treatment of RCC BM.

P2659Difference of prognostic impact of Killip classification in ACS patients with or without hemodialysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Takasaki ◽  
T Kurita ◽  
J Masuda ◽  
K Dohi ◽  
K Hoshino ◽  
...  
Keyword(s):  
Cox Regression ◽  
Chronic Phase ◽  
Prognostic Impact ◽  
Chi Square ◽  
Coronary Syndrome ◽  
Kaplan Meier ◽  
All Cause Mortality ◽  
History Of ◽  
Artery Disease

Abstract Background Cardiovascular deaths are more frequently in hemodialysis (HD) patients compared to general population. However, difference of prognosis of acute coronary syndrome (ACS) patients with or without HD were not well evaluated. Purpose The purpose of this study was to evaluate the clinical and prognostic characteristics of ACS patients with HD compared to that of ACS patients without HD. Methods We investigated 3427 ACS patients including 63 HD and 3364 non-HD patients between 2013 and 2017 using date from Mie ACS registry, a retrospective and multicenter registry. The primary outcome was defined as all-cause mortality. Results HD patients showed significantly higher prevalence of diabetes mellitus, past treatment of coronary artery disease, history of myocardial infarction and Killip ≥2 compared to non-HD patients (p<0.05, respectively). During the follow-up periods (median 719 days), 425 (12.4%) patients experienced all-cause death. HD patients demonstrated the higher all-cause mortality rate compared to that of non-HD patients during the follow-up (11.9% versus 38.1%, p<0.001, chi square). Kaplan Meier survival curves demonstrated that HD and non-HD patients with Killip 1 showed similar 30-day mortality, and Killip ≥2 patients also showed similar prognosis (Left side of figure). On the other hand, all cause mortality at 2 years were higher in Killip 1 HD patients compared to Killip 1 non-HD patients and similar between Killip 1 HD patients and Killip ≥2 non-HD patients in the 30 days landmark analysis (Right side of figure). In addition, cox regression analyses for all cause mortality demonstrated that HD was a strongest independent prognostic factor not of 30-day mortality but of after 30-day mortality with hazard ratio of 4.09 (95% confidential interval: 2.32–7.21, p<0.001). Figure 1 Conclusion Careful management are required in chronic phase for ACS patients with HD even in Killip 1 classification.

scholarly journals The Role of Hyponatraemia Before Surgery in Patients With Radical Resected Pancreatic Cancer

2020 ◽  
Vol 14 ◽  
pp. 117955492093660
Author(s):  
Rossana Berardi ◽  
Silvia Rinaldi ◽  
Giulio Belfiori ◽  
Stefano Partelli ◽  
Stefano Crippa ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Cox Regression ◽  
Radical Surgery ◽  
Ductal Adenocarcinoma ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Kaplan Meier ◽  
Negative Prognostic Factor ◽  
Significant Difference

Objectives: Hyponatraemia represents a negative prognostic factor in patients with cancer. The aim of this study was to assess, for the first time, the role of hyponatraemia in patients undergoing radical surgery for pancreatic ductal adenocarcinoma. Methods: A total of 89 patients with stage I-III pancreatic ductal adenocarcinoma underwent radical surgery between November 2012 and October 2014. Relapse-free survival (RFS) and disease-specific survival (DSS) were estimated using Kaplan-Meier method. A Cox regression model was carried out for univariate and multivariate analyses. Fisher exact test was used to estimate correlation between variables. Results: In total, 12 patients (14%) presented with hyponatraemia at diagnosis. The median DSS was 20 months in patients with hyponatraemia and not reached in patients with eunatraemia ( P < .1073), while a statistical significant difference was observed in terms of median RFS (10 months vs 17 months, respectively; P = .0233). Considering clinical features (hyponatraemia, smoke and alcoholic habit, diabetes, pain, and jaundice), patients with 4 or more of these factors had a worse prognosis (mDSS: 30 months vs not reached; hazard ratio [HR]: 0.40, 95% confidence interval [CI] = 0.16-0.80; P = .0120). Conclusions: The presence of hyponatraemia and its prompt correction at the diagnosis time should be considered for the correct management of patients with pancreatic carcinoma.

scholarly journals FASHION IS A COMMUNICATION AXIS TO REPRESENT CIVILIZATIONS IN CONTEMPORARY MEDIA

2021 ◽  
Vol 03 (06) ◽  
pp. 521-530
Author(s):  
Zainab Abd Ali MUHSEN
Keyword(s):  
Positive Impact ◽  
Cultural Development ◽  
Human Beings ◽  
Human Communication ◽  
Media Communication ◽  
The World ◽  
History Of ◽  
Contemporary Media

The fashion is the interface of the world for human communication and the overlap of cultures, and globalization in contemporary fashion can have a positive impact as it is important in the development of design and executive awareness to achieve the job through economic and cultural development, stressing that the role of the contemporary designer artist is the continuous communication between the global heritage and the new visions used in the present and the aesthetics of design. Fashion and clothing are considered as the language full of symbols, which reflects the (identities) of human societies, because of the different environments in which they are present, as the costume is the title of world cultures as each environment of the world has special costumes that distinguish it, although it shares the fact that it is inspired by the traditional heritage of that region, and expresses the environment in which women live, and this is reflected in many forms of executive model technology carried by different costumes. Although they vary from region to region due to the demographics of the environment, tastes are multiplied by media communication with different peoples and civilizations. They are any costumes that tell the history of human beings from the beginning to the present. In recent times, a phenomenon has emerged characterized by a return to heritage and typical.

The impact of weight change during treatment with targeted therapy in patients with metastatic renal cell carcinoma (mRCC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 557-557
Author(s):  
Laurence Albiges ◽  
Rana R. McKay ◽  
Xun Lin ◽  
Guillermo de Velasco ◽  
Ronit Simantov ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Weight Change ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Baseline Body Mass Index ◽  
Free Survival ◽  
Management Measures ◽  
Kaplan Meier ◽  
The Impact

557 Background: A growing body of evidence suggests a relationship between baseline body mass index and outcomes in patients (pts) with mRCC. However, the role of weight loss (WL) during treatment in pts with mRCC is poorly characterized. The aim of this study was to investigate the impact of weight change in mRCC pts treated with targeted agents. Methods: We conducted an analysis of mRCC pts treated on phase II-III clinical trials sponsored by Pfizer from 2003-2013. Weight change was defined as WL (≥ 5% weight reduction from baseline), stable weight (SW) or weight gain (WG, ≥2 % weight increase). We assessed the impact of weight change on overall survival (OS) (primary endpoint), progression-free survival (PFS) and overall response rate (ORR) at week (wk) 12. Statistical analyses were performed using Cox regression and Kaplan-Meier method. Multivariate analysis was adjusted for known prognostic factors for mRCC, including IMDC criteria. Results: Among 3,311 pts, 1,916 (58 %) had SW, 936 (28 %) had WL and 459 (14%) had WG at wk 12. Overall, pts with WL demonstrated both reduced OS and PFS compared to SW (median OS: 18.68 vs. 26.94 vs. 23.03 months in WL, SW and WG respectively; median PFS: 7.17 vs. 10.12 vs. 9.93 months in WL, SW and WG), and were consistent when considering 2 other time points (table). WL at wk 12 was associated with worse ORR (23.4 vs. 32.1 vs. 35.9% in WL, SW, WG; adjusted odd ratio 0.715, 95% CI 0.590-0.867, p=0.03). Discontinuation rate due to adverse events was similar between groups. Conclusions: We demonstrated that WL during therapy for mRCC is strongly associated with worse clinical outcomes. This observation remains valid for WL at 6, 12 and 24 weeks. Weight change may be an early prognostic factor and guide physician in clinical management. Measures to avoid WL during therapy may lead to better outcomes from targeted therapy. [Table: see text]

Is PAX3-FOXO1 associated with worse outcome in adults with rhabdomyosarcoma (RMS)?

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e22525-e22525
Author(s):  
Sheena Guram ◽  
Julia Dirks ◽  
Shivali Barot ◽  
Anthony Griffin ◽  
Ilan Weinreb ◽  
...  
Keyword(s):  
Fusion Gene ◽  
Distant Metastases ◽  
Rank Test ◽  
Transactivation Domain ◽  
Nodal Disease ◽  
Exact Test ◽  
Negative Results ◽  
Kaplan Meier ◽  
Test Event

e22525 Background: Rhabdomyosarcoma (RMS) is a rare soft tissue sarcoma in adults. The PAX3-FOXO1 fusion gene is associated with alveolar rhabdomyosarcoma. PAX3-FOXO1 results from a stable reciprocal translocation of chromosomes 2 and 13, which fuses in-frame the DNA binding domain of PAX3 with the transactivation domain of FOXO1. Occasionally, PAX7-FOXO1 is expressed. In children, the PAX3-FOXO1 fusion gene is associated with worse outcome. We evaluated the prognostic role of FOXO1 fusion status in adults with RMS treated in a single, large volume sarcoma centre. Methods: A retrospective review of adult RMS patients (pts) diagnosed from 1984 to 2018 was done. Information on demographics, treatment, fusion status and survival was collected. Primary favourable site was defined as tumour arising in orbit, non-bladder/prostate genitourinary system and non-parameningeal head and neck. Factors were compared using Fisher’s Exact test. Event-free survival (EFS) was estimated by the Kaplan-Meier method and compared with log rank test. FOXO1 fusion status was coded as FP (fusion positive) or FN (fusion negative). Results: Of 134 pts identified in our database, fusion testing was performed in 55 (41%). Of these, PAX3 fusion was detected in 22 (40%). PAX7 was not detected. The median age of FP and FN pts was 25 yrs (range 18, 90) and 27 yrs (range 18, 65), respectively. Gender distribution was similar between FP and FN. Favourable site was seen in 13 (60%) FP and 21 (64%) FN. Nodal disease was present in 21 (95%) FP and 21 (64%) FN (p = 0.02). Distant metastases were present in 10 (45%) FP and 9 (27%) FN (n.s.). Treatment received was as follows for FP and FN, respectively: chemotherapy (21(95%), 33(100%)), radiation (14(64%), 22(67%)) and surgery (4(18%), 17(52%)). 5-yr EFS for pts without distant metastases was 27% (CI 22.6-76.6) and 46% (CI 21.5 – 70.5) for FP and FN respectively (n.s.). Conclusions: FP and FN RMS occurs in adults of all ages. Similar to children, adults with FP are more likely to present with nodal disease. Our study did not show that fusion status was associated with poorer EFS in adult RMS, however, larger series are needed to confirm this preliminary data.

Primary metastatic breast cancer in the era of targeted therapy – Prognostic impact and the role of breast tumour surgery

2017 ◽  
Vol 83 ◽  
pp. 116-124 ◽  
Author(s):  
Jana Barinoff ◽  
Marcus Schmidt ◽  
Andreas Schneeweiss ◽  
Winfried Schoenegg ◽  
Marc Thill ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Targeted Therapy ◽  
Metastatic Breast ◽  
Breast Tumour ◽  
Prognostic Impact

scholarly journals Restating the case: How revisiting the development of the case method can help us think differently about the future of the business school

2020 ◽  
Author(s):  
Todd Bridgman ◽  
Stephen Cummings ◽  
C McLaughlin
Keyword(s):  
Business School ◽  
Business Schools ◽  
Positive Impact ◽  
Case Method ◽  
Harvard Business School ◽  
Linear Evolution ◽  
Management Learning ◽  
Innovative Thinking ◽  
History Of

© Academy of Management Learning & Education. Although supportive of calls for business schools to learn the lessons of history to address contemporary challenges about their legitimacy and impact, we argue that our ability to learn is limited by the histories we have created. Through contrasting the contested development of the case method of teaching at Harvard Business School and the conventional history of its rise, we argue that this history, which promotes a smooth linear evolution, works against reconceptualizing the role of the business school. To illustrate this, we develop a "counterhistory" of the case method-one that reveals a contested and circuitous path of development-and discuss how recognizing this would encourage us to think differently. This counterhistory provides ameans of stimulating debate and innovative thinking about how business schools can address their legitimacy challenges, and, in doing so, have a more positive impact on society.

NOVEL Recurrent Genetic Aberrations in Pediatric AML: An AIEOP AML-2002 Study Group.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2494-2494
Author(s):  
Martina Pigazzi ◽  
Elena Manara ◽  
Valeria Bisio ◽  
Sabrina Gelain ◽  
Sanja Aveic ◽  
...  
Keyword(s):  
De Novo ◽  
Conflicts Of Interest ◽  
Fusion Gene ◽  
Prognostic Impact ◽  
Genetic Aberrations ◽  
Molecular Approaches ◽  
Kaplan Meier ◽  
Genetic Abnormalities ◽  
Recurrent Translocation ◽  
Pediatric Aml

Abstract Abstract 2494 Introduction. Acute myeloid leukemia (AML) is an heterogeneous disease with known specific recurrent genetic aberrations. The continuous and increasing identification of new genetic mutations has permitted to identify new subgroups with different prognosis. In the present work we evaluated the incidence of rare genetic abnormalities in pediatric AML such as del(4)(q12)FIP1L1-PDGFRA, t(16;21)(p11;q22)FUS-ERG, t(8;16)(p11;p13)MOZ-CBP, t(11;17)(q23;q12–21)MLL-AF17, t(4;11)(q35;q23)MLL-ArgB2, t(5;11)(q35;p15.5)NUP98-NSD1, t(3;5)(q25;q34)NPM1-MLF1, and MLLPTD. Methods. We selected 306 patients with AML other than acute promyelocytic leukemia, negative for known recurrent genetic abnormalities involving MLL, CBF-beta and FLT3 genes. RNA was extracted from fresh bone marrow at diagnosis, and multiplex RT-PCR was employed. Sequencing by Sanger method was applied to all positive cases to characterize breakpoints of fusion. The Kaplan-Meier method was used for estimating the probability of event-free survival (EFS). Results. We identified one patient each positive for t(16;21)(p11;q22)FUS-ERG, t(11;17)(q23;q12–21)MLL-AF17, and t(4;11)(q35;q23)MLL-ArgB2, respectively, this suggesting that these rearrangements are rare in pediatric AML. 2/306 patients had del(4)(q12)FIP1L1/PDGFRA, and 4/306 the t(8;16)(p11;p13)MOZ-CBP; both these anomalies should be investigated in larger cohorts for definining their prognostic value. Interestingly 6/306 (2%) patients had the t(3;5)(q25;q34)NPM1-MLF1, 6/306 (2%) the MLLPTD, and 8/306 (2.6%) were found to carry the t(5;11)(q35;p15.5)NUP98-NSD1. Since the t(5;11) fusion was recently associated to FLT3ITD, we enlarged the screening to 42 de novo AML harbouring FLT3ITD mutation enrolled in the AIEOP-LAM 2002 protocol finding that 6 of them (14%) had the NUP98-NSD1 fusion gene. We documented a poor EFS for patients with t(5;11)NUP98-NDS1 (n=12) as compared to patients negative for molecular lesions and enrolled in the LAM 2002-AIEOP protocol (25% vs 53.1% at 3 years, p<0.01, n=154). We did not find differences in clinical or biological features of the isolated t(5;11) and t(5;11)+FLT3ITD positive patients (Table 1). We then evaluated the prognostic impact of the t(5,11) in the FLT3ITD+ cohort of AML, finding that the NUP98/NSD1 identifies a previously unrecognized subgroup of FLt3ITD patients with worse prognosis (EFS 33.3% vs 42.7 at 8y, p= 0.2). Furthermore, to analyze whether MLLPTD might also have a role in the progression to relapse, we screened 40 AML at relapse; however, we did not find the abnormality in this cohort. By contrast, 4 patients harbored at relapse the same MLLPTD found at diagnosis, suggesting the stability of this mutation. Conclusions. We provide evidence that NUP98-NSD1 may be considered a recurrent translocation in pediatric AML with poor prognosis. Being cryptic to conventional karyotyping, we confirmed the need of using molecular approaches for a proper identification of this anomaly. We also suggest that the NUP98-NSD1 fusion gene be considered for a better evaluation of the FLT3ITD+ patients. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document