tbuckley/cabot-search huggingface dataset:
Results of the Turkish prospective multi-center study utilizing the 21-gene Onco<i>type</i> DX assay: Decision impact analysis.
Authors: Vahit Ozmen, Ajlan Atasoy, Erhan Gokmen, Mustafa Ozdogan, Emine Nilufer Guler, Cihan Uras, Engin Ok, Orhan Demircan, Abdurrahman Isikdogan, Kezban Nur Pilanci, Cetin Ordu, Oben Duman, Ozturk Ates, Fatma Sen, Halil Kara, Bahadir Oz, Pinar Saip
Journal: Journal of Clinical Oncology (2015)

e11515 Background: The 21-gene Oncotype DX assay is accepted as an important predictive factor in the adjuvant treatment of node negative, estrogen receptor (ER) positive and HER2 (-) breast cancer. The test is not widely available for Turkish physicians as itÕs currently not reimbursed.We performed a prospective analysis to find the impact of the Recurrence Score result (RS) on treatment decisions. Methods: Ten centers across Turkey participated in this prospective trial. Consecutive breast cancer patients with pT1-3, pN0-N1mic, ER(+) , and HER2 (-) tumors were identified and adjuvant treatment decisions were made at breast tumor boards. The pre assay treatment decision was recorded on a questionnaire form. Cases were discussed at tumor boards again when the RS was available and investigators filled the post-assay questionnaire forms with the final decision. Results: 165 patients were enrolled. Mean age was 49.8 (SD±10.3) years. 108(65.5%) patients had pT1 tumors. Mean RS was 18.8±14.0. RS was low in 56.8%, intermediate in in 35.2% and high in 8.5%. There was an overall treatment decision change in 33% of patients with a reduction of chemotherapy (CT) from 56% to 35% overall and a 48% reduction in patients originally recommended CT. Among the patients with low and intermediate results, the decision changed from CT to Òhormonal therapy (HT) aloneÓ in 36 (85.7%) and 7 (36.8%) patients, respectively. Conclusions: The 21-gene assay has a significant impact on treatment decisions at specialty tumor boards in Turkish hospitals. Our initial findings warrant further consideration for the use of this genomic assay in patients with early stage breast cancer in Turkey. Health economic analysis will be reported separately in the near future. Chemotherapy decision in patients before and after RS by risk groups. Post-RS Decision HT CT+HT N n % n % p value* Pre-RS Decision All patients HT 73 63 86.3 10 13.7 <0.001 CT+HT 92 44 47.8 48 52.2 Total 165 107 64.8 58 35.2 Low RS HT 51 51 100.0 0 0.0 CT+HT 42 36 85.7 6 14.3 Total 93 87 93.5 6 6.5 Intermediate RS HT 19 12 63.2 7 36.8 CT+HT 39 8 20.5 31 79.5 Total 58 20 34.5 38 65.5 High RS HT 3 0 0.0 3 100.0 CT+HT 11 0 0.0 11 100.0 Total 14 0 0.0 14 100.0 *McNemar test
Serum IGFBP3, IGF-I, and MMP7 changes in advanced colorectal cancer (ACRC) patients (pts) treated with anti-EGFR therapy: A GEMCAD study
Authors: E. Pineda, C. Pericay, X. García-Albéniz, J. Augé, V. Alonso, P. Escudero, C. Fernández-Martos, R. Gallego, J. Maurel
Journal: Journal of Clinical Oncology (2009)

e15109 Background: Insulin-like growth factor-I (IGF-I) is a potent mitotic and anti-apoptotic peptide, whereas IGF binding protein-3 (IGFBP3) seems to have pro-apoptotic effects. Matrix metalloproteinase-7 (MMP7), an enzyme with in vitro ability to degrade IGFBP3, has been shown to be a prognostic factor in ACRC. Methods: This is a prospective single cohort traslational study. Pts undergoing second/third line with irinotecan plus anti-EGFR therapy were eligible as cases. Patients with ACRC not undergoing therapy were eligible as controls. IGFBP3 and MMP7 were measured in serum with immunoassays at baseline and at 48h after treatment start. KRAS mutation status in codons 12/13 was determined by sequencing in 53 pts. The primary endpoint is to define the IGFBP3 and MMP7 variation under anti-EGFR therapy. IGFBP3 was used as a continuous variable and MMP7 was used to create two groups by its third quartile. Results: Eighty-five cases and 25 controls were recruited. No significant changes at 48h in IGF-I and IGFBP3 were found, but a significant decrease in MMP7 from 10.8 (95%IC 8.3–13.3) to 8.4 ng/ml (95%IC 6–10.9) was observed in cases (p&lt;0.001) in contrast with controls, where no changes were found. Splitting the sample by the third quartile of MMP7 interesting changes in IGFBP3 variations were found. In the group with low levels of MMP7, IGFBP3 increases from 1,859 to 1,959 ng/ml (p=0.043) 48h after treatment initiation; on the contrary, in the group with high levels of MMP7, IGFBP3 decreases from 1,811 to 1,757 ng/ml (p=0.741). We found no association with IGFBP3 and neither response rate, time to progression nor overall survival. This latter analysis was also done only in pts with wild-type KRAS, without any change in the results. Conclusions: In pts with ACRC treated with anti-EGFR therapy, serum levels of IGFBP3 variations depend on basal MMP7 levels. IGFBP3 failed to be a predictive/prognostic factor in our sample although the limited number of KRAS pts analyzed can influence our results. [Table: see text] No significant financial relationships to disclose.
ISCHEMIC TIME AND RISK FACTORS ASSOCIATED WITH THE INCIDENCE OF CARDIOGENIC SHOCK IN PATIENTS PRESENTING WITH ST ELEVATION MYOCARDIAL INFARCTION
Authors: Daniel Amponsah, Tigran Khachatryan, David Hamilton, Jonathan Evans, Andrew Stewart, Eric Suh, Kenneth Jutzy, Islam Abudayyeh, Anthony Hilliard
Journal: Journal of the American College of Cardiology (2017)
The role of prophylactic antimicrobials during autologous stem cell transplantation: A single center experience
Authors: D. Yoon, B. Sohn, J. Kim, C. Yoo, S. Kim, D. Lee, S. Kim, J. Huh, J. Lee, C. Suh
Journal: Journal of Clinical Oncology (2009)

7105 Background: The aim of this retrospective study was to investigate the efficacy of antibiotic prophylaxis during autologous peripheral stem cell transplantation (ASCT) in patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). Methods: We searched Asan Medical Center Registry for NHL and MM: Total 114 cases received antimicrobial prophylaxis; while 118 cases did not receive antimicrobial prophylaxis during ASCT. Results: In prophylaxis group, 80 of 114 (70.2%) patients had experienced febrile episodes at median day +6 after transplantation with a statistically significant difference (P&lt;0.001). In no-prophylaxis group, 111 of 118 (94.1%) patients had experienced at median day +5. Documented infection occurred in 14 of 114 (12.3%) patients in prophylaxis group, and 16 of 118 (13.6%) patients in no-prophylaxis group (P=0.846). In these patients, the positive blood culture was seen in 12 (10.5%) of 114 patients in prophylaxis group, and 12 (10.7%) of 118 patients in no-prophylaxis group (P=1.000). Documented viral infection or reactivation was not observed in prophylaxis group, but observed in 4 patients of no-prophylaxis group. Both groups showed no invasive fungal infection or serious adverse event during ASCT. The day of infection resolved was a median day +15 (range, 3–29) in prophylaxis group and day +14 (range, 2–70) in no-prophylaxis group (P=0.945). The duration of antimicrobial treatment was median 10 days both in prophylaxis group and in no-prophylaxis group (P=0.565). Conclusions: In our experience, the antimicrobial prophylaxis seems to decrease the incidence of febrile episodes during ASCT, but seems to have no beneficial effect on reducing infectious complications. The antimicrobial prophylaxis of our study did not show the difference in the detection of causative organism as an infective agent, duration of antimicrobial therapy and hospitalization between two groups. No significant financial relationships to disclose.
Efficacy of pemetrexed for EGFR mutated lung carcinoma between L858R and Exon 19 deletion.
Authors: Yoshihito Kogure, Hideo Saka, Masahide Oki, Chiyoe Kitagawa, Masashi Nakahata, Rie Tsuboi, Saori Oka, Kazumi Hori, Yasushi Murakami, Yuko Ise
Journal: Journal of Clinical Oncology (2015)

e19073 Background: A subgroup analysis of the Japanese patients in a LUX-LUNG 3 trial showed different progression-free survival (PFS) of cisplatin (CDDP) + pemetrexed (PEM) between an Exon 21 L858R (L858R) group (8.3 months) and Exon 19 deletion (19 del) group (3.1 months). PEM might have a different efficacy between L858R and 19 del. Methods: Consecutive patients with advanced/recurrent non-small cell lung cancer (NSCLC) harboring activating EGFR mutation were treated with platinum combined with PEM from our institute. The primary endpoint was to compare PFS of patients with L858R and that with 19 del in patients with EGFR mutated NSCLC. Results: A total of 32 patients treated between 2009 and 2013 were included. Median age was 67 years (range: 40 - 78). 13 patients (41%) had L858R and 19 patients (59%) had 19 del. Patients were treated with CDDP (n = 5) or carboplatin (n = 27) combined with PEM. Compared with 19 del, L858R included more female patients (64% versus 47%, p = 0.002); fewer patients treated with CDDP (8% versus 21%, p = 0.018) and more patients with maintenance therapy of PEM (50% versus 29%, p = 0.003). Median cycles of platinum combined with PEM were 4 (range: 1 - 6) and 13 patients received maintenance therapy. The response rate (RR) of L858R was 33.3% and 19 del was 22.2% (p = 0.651). The median PFS for L858R was 5.13 months and 5.40 (p = 0.824, HR = 1.098, 95% CI: 0.48-2.50) for 19 del. The median OS for L858R was 29.17 months and 32.60 (p = 0.232, HR = 1.75, 95% CI: 0.69-4.45) for 19 del. Conclusions: This study did not show that PFS of platinum combined with PEM of L858R was superior to that of 19 del. RR and OS were consistent with PFS. To confirm the result of this study, a prospective trial is warranted.
Open lung biopsy (OLB) to diagnose pulmonary complications (PC) after high dose chemotherapy (HDC) and allogeneic stem cell transplant (ASCT)
Authors: B. Engelhardt, J. Greer, J. Johnson, A. Kassim, A. Milstone, S. Mineishi, M. Ninan, F. Schuening, M. Jagasia
Journal: Journal of Clinical Oncology (2004)

6646 Background: HDC and ASCT often lead to infectious and non-infectious PC. Non-infectious PC includes interstitial pneumonitis, bronchiolitis obliterans (BO), BO with organizing pneumonia (BOOP), and diffuse alveolar hemorrhage. Patients (pts.) often undergo bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) to establish a diagnosis. It is unclear if BAL and TBB establish a firm diagnosis or alter therapy. The purpose of this study was to examine the safety, diagnostic yield, and the ability of OLB to influence therapy in pts. with PC after HDC and ASCT. Methods: Out of 180 patients who underwent HDC and ASCT from April 1998 to February 2003, 10 underwent an OLB. Results: In these 10 pts.,14 bronchoscopies were done prior to OLB. All pts. except 2 had at least 1 bronchoscopy, 2 pts. had 2 bronchoscopies, and 2 pts. had 3 bronchoscopies. From these 14 BAL's an infectious etiology was found in 3 (21%). In addition, 8 TBB were done in 6 pts., with 1 patient undergoing 3 TBB. 4 pts. did not undergo TBB for concern of bleeding. All TBB were nondiagnostic except 1 (13%) which revealed BOOP. In all 10 pts. undergoing OLB, a pathologic diagnosis was made: 4 (40%) had BO, 4 (40%) had BOOP, 1 (10%) with hypersensitivity pneumonitis and 1 (10%) with invasive aspergillosis. OLB led to a change in therapy in 8 (80%) of the 10 pts. (caspofungin started in 1 patient, and change in immunosuppression-7 patients). Thus, in these 10 pts., bronchoscopy/BAL and TBB established the same diagnosis as OLB in only 1 patient (10%). There were no immediate surgical complications and no deaths related to the procedure. In this cohort of pts.,OLB had a high diagnostic yield, and rarely identified infection as a cause of PC after HDC and ASCT. This differs from previous reports where OLB have commonly identified infectious PC. Conclusions: We conclude that OLB is safe, with high diagnostic yield and affects therapeutic decisions in pts. with PC after HDC and ASCT. In our cohort, the most common diagnoses were BO and BOOP. We recommend that pts. undergo OLB, if an initial bronchoscopy/BAL and TBB are negative or if a non-infectious PC is being considered. No significant financial relationships to disclose.
Prevalence of non-recommended screening for prostate cancer and breast cancer in the United States.
Authors: Quoc-Dien Trinh, Firas Abdollah, Jesse D. Sammon, Paul Linh Nguyen, Toni K. Choueiri, Mark A Preston, Mani Menon, Joel S. Weissman, Adam Stuart Kibel
Journal: Journal of Clinical Oncology (2015)

e17528 Background: In individuals with limited life expectancy, screening for prostate (PCa) and breast (BCa) cancer is not recommended, due to the increasing risk of over diagnosis/treatment. However, the size of such non-recommended practice nationwide is unclear. We sought to estimate the nationwide, and state-by-state prevalence of non-recommended PCa and BCa screening in individuals with a life expectancy < 10 years. Methods: We relied on 150,452 individuals aged ≥ 65 years (weighted population size of 43.857 million) who responded to the 2012 Behavioral Risk Factor Surveillance System survey.Self-reported prostate specific antigen (PSA) test (without history of prostate cancer/problems) or mammogram within the past year.Life tables relying on age, sex, race, and comorbidity were used to calculate life expectancy. Results: Overall, 16.3% of individuals aged ≥ 65 years underwent non-recommended screening. This represents 32.1% of the individuals aged ≥ 65 years who were screened. At adjusted analysis, the prevalence of non-recommended screening was higher in older (OR: 1.11; 95%CI: 1.10-1.11), and in Black (OR: 1.27, 95%CI: 1.11-1.46) individuals. Conversely, it was lower in females (OR: 0.63; 95%CI: 0.59-0.67). Likewise, individuals without access to a health care provider (0.43; 95%CI: 0.36-0.51) or who lacked health insurance (OR: 0.47; 95%CI: 0.36-0.61) were less likely to receive non-recommended screening. Significant state-by-state variation in non-recommended screening was observed, especially for PCa. Conclusions: Non-recommended screening is reported in nearly one out of three screened individuals aged ≥ 65 years, and varies significantly by state. The prevalence of non-recommended screening is higher for PCa than for BCa screening. Policy should be directed to incentivize appropriate use of screening tests, which could lead to more cost-efficient utilization of health care resources.
Novel Chromatin Modifying Gene Alterations and Significant Survival Association of ATM and P53 in Mantle Cell Lymphoma
Authors: Kai Wang, Michelle K. Nahas, Roman Yelensky, Geoff A. Otto, Doron Lipson, Jie He, Jeff Ross, Phil J Stephens, Kar Fai Chow, Tania Zielonka, Pritish K Bhattacharyya, Ewelina A Protomastro, Tatyana Feldman, Anthony R. Mato, Alan P Skarbnik, Coleen Bejot, Gabriella Gadaleta, Andrew L Pecora, Vincent A. Miller, Andre Goy
Journal: Blood (2014)
CD123-Specific Chimeric Antigen Receptor Redirected T Cells Exhibit Potent Cytolytic Activity and Multiple Effector Functions Against Acute Myeloid Leukemia without Altering Normal Hematopoietic Colony Formation in Vitro
Authors: Armen Mardiros, Cedric Dos Santos, Tinisha McDonald, Christine Brown, Xiuli Wang, Wen-Chung Chang, Julie R Ostberg, Ravi Bhatia, Michael C. Jensen, Stephen J. Forman
Journal: Blood (2012)
RISK STRATIFICATION OF PATIENTS SUSPECTED OF CORONARY ARTERY DISEASE USING AN ACOUSTIC DETECTION ALGORITHM
Authors: Simon Winther, Louise Nissen, Samuel Schmidt, Jelmer Westra, Laust Dupont, Jane Kirk, Bjarke S. Larsen, Lars Frost, Niels Holm, Hans Botker, Morten Boettcher
Journal: Journal of the American College of Cardiology (2017)
Fibroblastic niches prime T cell alloimmunity through Delta-like Notch ligands
Authors: Jooho Chung, Christen L. Ebens, Eric Perkey, Vedran Radojcic, Ute Koch, Leonardo Scarpellino, Alexander Tong, Frederick Allen, Sherri Wood, Jiane Feng, Ann Friedman, David Granadier, Ivy T. Tran, Qian Chai, Lucas Onder, Minhong Yan, Pavan Reddy, Bruce R. Blazar, Alex Y. Huang, Todd V. Brennan, D. Keith Bishop, Burkhard Ludewig, Christian W. Siebel, Freddy Radtke, Sanjiv A. Luther, Ivan Maillard
Journal: Journal of Clinical Investigation (2017)

Alloimmune T cell responses induce graft-versus-host disease (GVHD), a serious complication of allogeneic bone marrow transplantation (allo-BMT). Although Notch signaling mediated by Delta-like 1/4 (DLL1/4) Notch ligands has emerged as a major regulator of GVHD pathogenesis, little is known about the timing of essential Notch signals and the cellular source of Notch ligands after allo-BMT. Here, we have shown that critical DLL1/4-mediated Notch signals are delivered to donor T cells during a short 48-hour window after transplantation in a mouse allo-BMT model. Stromal, but not hematopoietic, cells were the essential source of Notch ligands during in vivo priming of alloreactive T cells. GVHD could be prevented by selective inactivation of Dll1 and Dll4 in subsets of fibroblastic stromal cells that were derived from chemokine Ccl19-expressing host cells, including fibroblastic reticular cells and follicular dendritic cells. However, neither T cell recruitment into secondary lymphoid organs nor initial T cell activation was affected by Dll1/4 loss. Thus, we have uncovered a pathogenic function for fibroblastic stromal cells in alloimmune reactivity that can be dissociated from their homeostatic functions. Our results reveal what we believe to be a previously unrecognized Notch-mediated immunopathogenic role for stromal cell niches in secondary lymphoid organs after allo-BMT and define a framework of early cellular and molecular interactions that regulate T cell alloimmunity.
Beta-Catenin Depended and Independent Effects Induced by Myeloma Cells in Human and Murine Osteoblasts and Osteoblast Progenitors.
Authors: Francesca Morandi, Sara Tagliaferri, Sabrina Bonomini, Mirca Lazzaretti, Luca Ferrari, Vittorio Rizzoli, Nicola Giuliani
Journal: Blood (2006)
Subclinical Atherosclerosis, Statin Eligibility, and Outcomes in African American Individuals
Authors: Ravi V. Shah, Aferdita Spahillari, Stanford Mwasongwe, J. Jeffrey Carr, James G. Terry, Robert J. Mentz, Daniel Addison, Udo Hoffmann, Jared Reis, Jane E. Freedman, Joao A. C. Lima, Adolfo Correa, Venkatesh L. Murthy
Journal: JAMA Cardiology (2017)

Modern prevention guidelines substantially increase the number of individuals who are eligible for treatment with statins. Efforts to refine statin eligibility via coronary calcification have been studied in white populations but not, to our knowledge, in large African American populations.To compare the relative accuracy of US Preventive Services Task Force (USPSTF) and American College of Cardiology/American Heart Association (ACC/AHA) recommendations in identifying African American individuals with subclinical and clinical atherosclerotic cardiovascular disease (ASCVD).In this prospective, community-based study, 2812 African American individuals aged 40 to 75 years without prevalent ASCVD underwent assessment of ASCVD risk. Of these, 1743 participants completed computed tomography.Nonzero coronary artery calcium (CAC) score, abdominal aortic calcium score, and incident ASCVD (ie, myocardial infarction, ischemic stroke, or fatal coronary heart disease).Of the 2812 included participants, the mean (SD) age at baseline was 55.4 (9.4) years, and 1837 (65.3%) were female. The USPSTF guidelines captured 404 of 732 African American individuals (55.2%) with a CAC score greater than 0; the ACC/AHA guidelines identified 507 individuals (69.3%) (risk difference, 14.1%; 95% CI, 11.2-17.0; P < .001). Statin recommendation under both guidelines was associated with a CAC score greater than 0 (odds ratio, 5.1; 95% CI, 4.1-6.3; P < .001). While individuals indicated for statins under both guidelines experienced 9.6 cardiovascular events per 1000 patient-years, those indicated under only ACC/AHA guidelines were at low to intermediate risk (4.1 events per 1000 patient-years). Among individuals who were statin eligible by ACC/AHA guidelines, the 10-year ASCVD incidence per 1000 person-years was 8.1 (95% CI, 5.9-11.1) in the presence of CAC and 3.1 (95% CI, 1.6-5.9) without CAC (P = .02). While statin-eligible individuals by USPSTF guidelines did not have a significantly higher 10-year ASCVD event rate in the presence of CAC, African American individuals not eligible for statins by USPSTF guidelines had a higher ASCVD event rate in the presence of CAC (2.8 per 1000 person-years; 95% CI, 1.5-5.4) relative to without CAC (0.8 per 1000 person-years; 95%, CI 0.3-1.7) (P = .03).The USPSTF guidelines focus treatment recommendations on 38% of high-risk African American individuals at the expense of not recommending treatment in nearly 25% of African American individuals eligible for statins by ACC/AHA guidelines with vascular calcification and at low to intermediate ASCVD risk.
tnAcity: A phase II/III trial of weekly nab-paclitaxel (nab-P) plus gemcitabine (gem) or carboplatin (carbo) versus gem/carbo as first-line treatment for metastatic triple-negative breast cancer (mTNBC).
Authors: Denise A. Yardley, Adam Brufsky, Robert E. Coleman, Pier Franco Conte, Javier Cortes, Stefan Glück, Jean-Marc A. Nabholtz, Joyce O'Shaughnessy, Li Li, Debora Barton, Robert M. Beck, Nadia Harbeck
Journal: Journal of Clinical Oncology (2014)

TPS1146 Background: TNBC, which is characterized by a lack of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) overexpression, is associated with a poor prognosis. In combination with gem or carbo/bevacizumab, nab-P has demonstrated high response rates as first-line treatment for mTNBC. tnAcity (triple-negative Albumin-bound paclitaxel combination international treatment study) is a phase 2/3 trial evaluating the efficacy and safety profiles of 2 nab-P combination regimens (with gem or carbo) as first-line treatment for mTNBC, using gem/carbo as a control. Methods: The phase 2 portion of the study will evaluate 240 patients (pts), randomized 1:1:1 (stratified by disease-free interval [DFI]: ≤ 1 y vs > 1 y) to nab-P 125 mg/m2 plus gem 1000 mg/m2, nab-P 125 mg/m2 plus carbo area under the curve (AUC) 2, or the control regimen of gem 1000 mg/m2 plus carbo AUC 2, all given days 1 and 8 of a 21-day cycle. Eligibility criteria include measurable mTNBC (defined as ER and PgR in < 1% of tumor cell nuclei and HER2 IHC 0 or 1+ or 2+ and FISH-negative); no prior chemotherapy for metastatic disease; prior adjuvant/neoadjuvant anthracycline use required if indicated; adjuvant/neoadjuvant treatment with a taxane, platinum, or gem is permitted if completed ≥ 12 months prior to randomization; ECOG performance status ≤ 1; peripheral neuropathy grade < 2; and absence of brain metastases. The primary objective of the phase 2 portion is to identify the nab-P combination arm to be evaluated in the phase 3 study by a ranking algorithm of 5 efficacy and safety parameters. In the phase 3 portion, 550 pts will be randomized 1:1 (stratified by DFI [≤ 1 y vs > 1 y] and prior taxane use) to the nab-P combination arm selected from the phase 2 portion or to the control arm. The primary endpoint of the phase 3 portion is PFS by independent radiological assessment; secondary endpoints include ORR, OS, disease control rate, duration of response, and safety. Biomarker and circulating tumor cell analyses will also be performed. As of the submission deadline, 21 patients have been randomized. Clinical trial information: NCT01881230.