tbuckley/cabot-search huggingface dataset:
Alterations in the PI3K/Akt signaling pathway and association with outcome in invasive high-grade urothelial cancer (UC).
Authors: Arjun Vasant Balar, Gopa Iyer, Hikmat Al-Ahmadie, Manickam Janakiraman, Irina Ostrovnaya, Ashley Marie Regazzi, Ilana Rebecca Garcia-Grossman, Deepa Pendse, Bernard Bochner, Dean F. Bajorin, Matthew I. Milowsky, David B. Solit
Journal: Journal of Clinical Oncology (2012)

277 Background: Activating mutations in PIK3CA have been associated with improved outcomes in patients (pts) with breast cancer (Kalinsky, Clin Cancer Res 2009). Molecular profiling of invasive high-grade UC demonstrates that PI3K/Akt pathway alterations occur in up to 15% of cases. The prognostic value of PI3K/Akt pathway alterations in invasive UC is unknown. Methods: Clinically annotated archival frozen surgical specimens from 95 pts (94 cystectomies, 1 nephroureterectomy) with high-grade invasive UC were genotyped for mutations in all coding exons of PIK3CA, PIK3R1, TSC1, PTEN and the AKT isoforms using high-throughput Sanger sequencing. Copy number alterations were examined using an Agilent 1M oligonucleotide array. Clinical variables including time to recurrence (TTR) and overall survival (OS) were correlated with the presence of mutations or copy number events in PIK3CA, PIK3R1, TSC1, PTEN and the AKT isoforms. Results: Specimens from 95 pts (71 M; 24 F) with a median age of 71 years (41-88) were evaluated. 34 (36%) received neoadjuvant chemotherapy and 75 (79%) were prior smokers. 4 pts (4%) had Stage 0, 11 (12%) had Stage I, 15 (16%) had Stage II, 33 (35%) had Stage III and 32 (34%) had Stage IV disease at surgery. The median follow-up was 31.5 months. Alterations (mutations or copy number gains/losses) in PI3K/Akt signaling pathway genes were identified in 26 (27%) specimens and were associated with a trend toward longer TTR, hazard ratio 0.53 (95%CI 0.24, 1.14) (p=0.08). Conclusions: Alterations in PI3K/Akt signaling in pts with invasive UC may be associated with an improvement in outcome similar to that observed in breast cancer. Further analysis in a large independent tumor set is ongoing.
Palonosetron (PALO), administered orally or intravenously (IV), plus dexamethasone for prevention of chemotherapy-induced nausea and vomiting (CINV)
Authors: R. V. Boccia, E. F. Gonzalez, A. G. Pluzanska, G. Clerici
Journal: Journal of Clinical Oncology (2008)

20608 Background: Palonosetron, a pharmacologically unique 5-HT3 receptor antagonist (RA), has demonstrated superior emesis prevention vs ondansetron and dolasetron when administered as a single IV dose. Three oral doses of PALO 0.25, 0.50 or 0.75 mg were shown to be clinically comparable to the approved dose of 0.25 mg IV for the prevention of CINV in a recent, multinational, multicenter, double-blind, phase 3 dose ranging study of 651 patients receiving moderately emetogenic chemotherapy (including AC-based regimens) [Grunberg et al, ECCO 2007]. In this study, 50% of enrolled patients were randomly assigned to receive DEX with single-dose oral or IV PALO; results for this subgroup of patients have not been previously reported. Methods: The primary efficacy endpoint was Complete Response (CR; no emesis, no rescue), with secondary endpoints including no emesis and nausea (severity assessed on a 4-point scale) rates throughout the 5-day study period. Confidence intervals (CI) were calculated for each treatment group. Results: In total, 319 evaluable patients received DEX 8 mg IV on Day 1 concomitant with oral PALO 0.25, 0.50, 0.75 mg or IV PALO 0.25 mg. The majority (53%) received anthracyline- and cyclophosphamide-based chemotherapy. Characteristics were similar across treatment groups: 73% female, 60% chemo-naïve, mean age 56 years. No significant differences in CR rates were observed between the oral doses and the IV dose. No emesis and nausea-free rates showed similar trends across the dose groups. No dose-response relationship was observed for adverse reactions among the oral treatment groups; headache was the most frequently related reported AE in all four groups (5% of patients). Conclusions: The combination of single-dose oral or IV PALO plus DEX was safe and effective in the prevention of acute, delayed and overall CINV. No significant financial relationships to disclose.
Long-Term Safety and Efficacy of Open-Label Dupilumab in Patients with Moderate-to-Severe Atopic Dermatitis
Authors: Mette Deleuran, Diamant Thaçi, Lisa A. Beck, Seth Forman, Weily Soong, Iftikhar Hussain, Robert Bissonnette, Jean-David Bouaziz, Joel Gelfand, Lawrence Sher, Zhen Chen, Bolanle Akinlade, Abhijit Gadkari, Laurent Eckert, Neil M.H. Graham, Gianluca Pirozzi, Marius Ardeleanu
Journal: Journal of Allergy and Clinical Immunology (2017)
PRL3 Is a Mediator of IL6/STAT3 Signaling and Defines a Population of Multiple Myeloma Patients Distinct from Those That Activate NFkB.
Authors: Michael Sebag, Keith Stewart, Chang-Xin Shi, Yuan-Xiao Zhu, Wee-Joo Chng, Jonathan Keats, Rodger E. Tiedemann, Rafael Fonseca, Marta Chesi, Peter Leif Bergsagel
Journal: Blood (2007)
National evaluation of the VA’s quality of supportive care.
Authors: Anne M. Walling, Diana M. Tisnado, Jennifer Malin, Steven M Asch, Philip Pantoja, Susan Ettner, Sydney Morss Dy, Karl A. Lorenz
Journal: Journal of Clinical Oncology (2012)

218 Background: Although known to provide more efficient end-of-life cancer care, the quality of VA’s end of life cancer care is unknown. We used Cancer Quality ASSIST to evaluate supportive care comprehensively in a national sample. Methods: We measured ASSIST QIs addressing symptoms, communication, treatment toxicities, and complications among 719 Veterans with a 2008 registry diagnosis of stage IV colorectal (37%), pancreatic (30%), or lung cancer (33%). We abstracted records from diagnosis for 3 years or until death among eligible Veterans (lived &gt;= 30 days following diagnosis with &gt;= 1 VA hospitalization or &gt;=2 VA outpatient visits). We determined patient-level overall and individual QI scores (%delivered/appropriate care) and confirmed reliability on a 5% sample, retaining 39 of 42 QIs. Results: Most Veterans were older (mean 66 years) male (97%), and white (68%) with 20% African American, and 3% Hispanic. 85% had &gt;=1 hospitalization and 93% died. Overall, subjects received 48% of recommended care. The average Veteran triggered 13 QIs, and scores ranged from 0-98% (pain 0-96%; dyspnea 11-98%, depression 36-79%, fatigue 4-80%, nausea/vomiting 41-87%, treatment toxicities 13-70%, care planning 18-86%). Notable gaps in care were identified. Inpatient pain screening was common (96%) but lacking for outpatients (58%). With opioids, bowel prophylaxis occurred for only 52% of outpatients and 70% of inpatients. Few patients had timely dyspnea evaluation (16%) or treatment (11%). Outpatient assessment of fatigue occurred for 32%. 24% of patients who received chemotherapy high risk for diarrhea were offered appropriate anti-diarrheals. Only 19% of Veterans had goals of care addressed in the month after a diagnosis of advanced cancer, and 63% of patients had timely discussion of goals following ICU admission. Most decedents (86%) were referred to palliative care or hospice before death. Single vs. multiple fraction radiotherapy should have been considered in 28 Veterans with bone metastasis, but none were offered it. Conclusions: These patient and family-centered supportive care gaps reflect important HRQOL impacts and targets for quality improvement in a system known for excellence in chronic disease care.
A phase I study of ridaforolimus (MK-8669) in pediatric patients with advanced solid tumors.
Authors: Andrew DJ Pearson, Sara Michele Federico, Isabelle Aerts, Darren R Hargrave, Steven G. DuBois, Robert Iannone, Ryan Geschwindt, Ruixue Wang, Tanya M. Trippett, Birgit Geoerger
Journal: Journal of Clinical Oncology (2013)

10027 Background: Deregulation of the PI3K/AKT/mTOR signaling pathway occurs in many poor prognosis childhood malignancies and inhibition of this pathway is a promising novel therapeutic strategy. Ridaforolimus (MK-8669) is a highly selective orally bioavailable small molecule inhibitor of mTOR. This multi-centre, phase I dose escalation study of orally administered Ridaforolimus was designed to evaluate the maximum tolerated dose (MTD), safety profile, pharmacokinetic profile (PK), antitumor activity and pharmacodynamic (PD) biomarkers (phosphorylated Akt [pAkt] in platelet-rich plasma). Methods: Patients (pts) from 6 to &lt;18 years (yrs) with advanced solid tumors were enrolled. Dose escalation was by a modified Toxicity Probability Intervals method (mTPI, Ji Y, et al. Clin Trials 2007) targeting a 30% dose limiting toxicity (DLT) ratio. Pts received 28 day cycles of Ridaforolimus (MK-8669), orally, five days out of seven. Dosing started at 22 mg/m 2 , escalated to 28 and 33 mg/m 2 , with an expansion cohort treated at the maximum administered dose. Results: 19 pts, age 8-17 (median 13.5 years), were enrolled and 18 treated from 6 international sites. Diagnoses included ependymoma (5), osteosarcoma (3), Ewings sarcoma (3) and other histologies (7). Four pts received dose level (DL) 1; 3 DL 2 and 11 DL 3. Pts received between 1-12+ courses. There was only one DLT (DL 2: grade 3 elevated alanine transaminase [ALT]) and no other grade 3-4 treatment-related toxicities. Preliminary analysis shows the most frequent drug-related adverse events were manageable grade 1-2 stomatitis (70.6%) and fatigue (52%). Dose escalation stopped at DL3 (33 mg/m2, 150% of the adult recommended phase 2 dose [RP2D]). There were no objective responses by RECIST1.1. Two pts remain on study, with continuing stable disease (pineoblastoma [12 courses], diffuse intrinsic pontine glioma [6 courses]). PK and PD analyses will be presented. Conclusions: Ridaforolimus is a safe and well tolerated, orally bioavailable mTOR inhibitor. The RP2D for Ridaforolimus in children is 33 mg/m 2 . Prolonged disease stabilization was observed in two patients. PK/PD data will provide further data to support the RP2D. Further combination studies are warranted. Clinical trial information: NCT01431547.
Platelet Adhesion, Spreading and Activation Are Mediated By Mechanosensing of Matrix Stiffness
Authors: Yongzhi Qiu, Ashley C Brown, David R Myers, Yumiko Sakurai, Robert Mannino, Reginald Tran, Byungwook Ahn, Elaissa Hardy, Matthew F Kee, Sanjay Kumar, Gang Bao, Thomas H Barker, Wilbur A Lam
Journal: Blood (2014)
Value of the primary tumor initial standardized uptake value (iSUV) of 18F-fluorodeoxyglucose positron emission tomography (PET) to predict overall survival (OS) in patients with esophageal or gastroesophageal junction carcinoma undergoing definitive chemoradiotherapy.
Authors: A. Suzuki, L. Xiao, Y. Hayashi, J. Welsh, S. H. Lin, J. H. Lee, M. S. Bhutani, W. L. Hofstetter, R. J. Mehran, J. A. Ajani
Journal: Journal of Clinical Oncology (2011)

82 Background: The value of iSUV of PET for predicting OS is unclear in patients with advanced esophageal or gastroesophageal carcinoma treated with definitive chemoradiotherapy. We tested the hypothesis that iSUV would correlate with OS and recurrence free survival (RFS). Methods: We performed retrospective analysis, selecting patients with esophageal or gastroesophageal carcinoma who had a pretreatment PET and endoscopic ultrasonography (EUS) and who received definitive chemoradiotherapy from 2002 to 2008. Correlations were performed with continuous and dichotomized iSUV, baseline EUS results, OS, and RFS. Results: Two hundred and nine patients were analyzed. The median OS time was 20.7 months (95% CI: 18.8-26.3 months) and the median RFS time was 11.2 months (95% CI: 9.44, 14.34). OS rate and RFS rate at 3 years were 35.7% (95% CI: 29.0-43.9%) and 24.8% (95 % CI: 19.1–32.1 %). The median iSUV was 12.7 (range: 0–51). In univariate analysis, iSUV was associated with OS (Cox model, P = 0.012; log-rank test, P = 0.002) and RFS (Cox model, P = 0.0003; log-rank test, P &lt; 0.0001). In multivariate analysis, dichotomized iSUV cut off by median was associated with OS (P = 0.024) but not RFS (P = 0.11). Conclusions: Data from our study suggests that higher iSUV is associated with poor survival. Baseline PET may become a useful stratification factor in randomized trials and for individualized therapy. No significant financial relationships to disclose.
Vascular toxicities of endocrine therapy in early-stage breast cancer: Encouraging observations in a nontrial setting.
Authors: Susan Faye Dent, Freya L. Crawley, Nadine A. Graham, Michelle M. Campbell
Journal: Journal of Clinical Oncology (2012)

68 Background: Endocrine therapy (ET) is the standard of care for postmenopausal (PM) women with early stage breast cancer (EBC). Studies suggest higher risk of vascular toxicities (VT) on aromatase inhibitor (AI) therapy. We report incidence/discontinuation rates of VTs in a cardiac clinic. Methods: PM women with hormone receptor positive EBC treated with ET (tamoxifen (T) ± AI) at Ottawa Hospital Cancer Center 01/99-2/06. Data included: demographics, vascular co-morbidities (VCM), ET, duration, VTs. Results: 626 pts, median age 59 years (r: 30-92), median follow-up 98 months (m), stage: I (196 pts), II (341 pts) III (89 pts) EBC. Majority (52.5%) pts had VCM at ET initiation; hypertension (HTN) (36%), hyperlipidemia (HYLP) (17%), coronary disease (12%), thrombosis (9%), angina (6%) TIA (6%). Treatment discontinued due to VT 3x more with T vs. AI. Most common VTs: edema, arrhythmias (ARR), cardiovascular (CVS) event, and HYLP. With Letrozole and T, previous VCM significantly increased risk of developing VT (chi-square: P=0.022 and 0.009). Time to develop VT shortest for T and exemestane. Previous VCM did not affect this interval. Longer exposure to T correlated with higher VT rate (t-test: p=0.046) not seen with AIs. Exposure to multiple AIs associated with higher VT rate (t-test: p=0.009). Conclusions: This cohort study reports similar VT rates with AI therapy as reported in the literature. T was associated with higher discontinuation rates (10.5%) due to VTs compared to AIs (2.8-3.3%). Longer duration of AI therapy was not associated with increased risk of VTs. These encouraging results reflect the real-life experience of women exposed to ET. [Table: see text]
146P Tolerability and pharmacokinetics (PK) of ABT-414 in Japanese patients (pts) with recurrent malignant glioma
Authors: Y. Narita, M. Nagane, N. Kagawa, K. Mishima, T. Yamamoto, T. Wakabayashi, T. Hamada, R. Odagawa, Y. Nishimura, T. Kiriyama, None Xiong, C. Ocampo, R. Nishikawa
Journal: Annals of Oncology (2016)
A study of discrepancy between laboratory-calculated and weight-based glomerular filtration rate (GFR) as a marker of renal function in a palliative care population.
Authors: Jenny Power, Miriam Colleran
Journal: Journal of Clinical Oncology (2016)

58 Background: Renal function is important in a palliative care population and can impact on frequently-used medications including chemotherapeutic agents, opioids, non-steroidal anti-inflammatory drugs and neuropathic agents. In local practice, estimated glomerular filtration rate (eGFR), calculated on a presumed weight of 70kg, is displayed in laboratory results. However, the weight of palliative patients varies considerably, for example, due to cancer cachexia or malabsorption and a considerable population weigh less than 70kg. Our aim was to assess whether there is a discrepancy between glomerular filtration rate when laboratory-estimated versus weight-based and to explore the potential clinical relevance. Methods: Data was retrospectively collated for 50 patients admitted consecutively to a specialist palliative care unit over a 6 month period. Laboratory-derived eGFR was compared to GFR using the Cockroft-Gault equation (CreatClear = Sex*(140-Age)/(SerumCreat))*(Weight/72). Results: 25 (50%) patients were admitted for end of life care, 19 (38%) for symptom control, 6 (12%) for respite. 36 patients (72%) had weight documented. 45 (90%) patients had bloods taken. 41 patients had an eGFR documented, 7 of whom had an eGFR of less than 60ml/min. 25 patients had a weight-based GFR calculated of whom 10 (40%) had a GFR less than 60ml/min A significant discrepancy was seen between estimated and calculated GFR in 7 of these (accounting for 28%). This was most notable at less than 65kg. 2 patients with a weight of 55kg had a greater than 40ml/min difference in creatinine clearance. 50% of patients with a GFR of less than 60ml/min were on at least one nephrotoxic drug, most frequently pregabalin or ibuprofen. The most frequently-used opioid was oxycodone. No patient had opioids or medications discontinued on the basis of renal function. Conclusions: Results show a significant discrepancy between estimated and calculated GFR in a palliative care population which is most pronounced at lower weights. We would recommend, where appropriate, calculating a weight-based GFR on patients, with a review of opioid and nephrotoxic medications when reduced.
Impact of race on early-stage lung cancer treatment and survival.
Authors: Christina D. Williams, Dawn T. Provenzale, Karen M. Stechuchak, Michael J. Kelley
Journal: Journal of Clinical Oncology (2012)

232 Background: Studies have documented racial differences along the lung cancer continuum and equity in care is essential to quality improvement. The purpose of this study was to investigate the influence of race on lung cancer treatment and survival among early-stage non-small cell lung cancer patients in an equal access healthcare system. We hypothesize that patients receiving similar treatment will have similar survival. Methods: Data were from the External Peer Review Program (EPRP) Lung Cancer Special Study, which was a cross-sectional study conducted to assess the quality of care among patients diagnosed with lung cancer and receiving care at a VA facility. All patients were diagnosed between October 1, 2006 and December 31, 2007. Analyses were restricted to patients with Stage I/II NSCLC (n=1,426; 1,229 whites, 197 blacks). Multivariate logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95%CI). Results: The proportion of blacks who had surgery was significantly less than that among whites (OR: 0.56, 95% CI 0.39-0.79). There was no racial difference in receipt of adjuvant therapy (chemotherapy and/or radiation therapy) among patients who had surgery (p=0.08). Among patients who did not undergo surgery, blacks were more likely to refuse surgery (OR: 2.30, 95% CI 1.29-4.13); however, the proportion of patients with contraindications to surgery and those receiving palliative treatment were similar in both race groups. The 2-year survival rate was 69% and race was not a predictor of survival when controlling for receipt of surgery along with other covariates (p=0.76). The 2-year survival rate was 82% among patients who had surgery, and 48% among patients who did not have surgery. Specifically among patients who did not have surgery due to refusal, the survival rate was 55%. Conclusions: We observed a racial disparity in surgery, partially due to the greater rate of refusal among blacks, but not adjuvant or palliative treatment. Race did not have a major impact on 2-year survival for patients with early-stage lung cancer. These findings stress the need to better understand patient preferences regarding surgery and identify ways to reduce this variation in surgery to improve quality of lung cancer care.
Prognosis of MDS Subtypes RARS, RCMD and RCMD-RS Does Not Differ by Cytomorphologic Criteria but Cytogenetics Allows to Delineate a Subgroup with Inferior Clinical Course,
Authors: Ulrike Bacher, Wolfgang Kern, Tamara Alpermann, Susanne Schnittger, Claudia Haferlach, Torsten Haferlach
Journal: Blood (2011)
NAB-PACLITAXEL (NAB-P): nanoparticle albumin-bound paclitaxel: efficacy and toxicity evaluation: our experience in advanced pancreatic and breast cancer
Authors: E. Burattini, F. Satta, A. Pellegrino, F. Todi, M.V. Zoffoli, G. Coiro, L. Marchetti, M. Di Palma
Journal: Annals of Oncology (2016)
PI3K-Independent Signaling Pathways Contribute to ICOS-Mediated T-Cell Costimulation in Acute Graft-Versus-Host Disease in Mice.
Authors: Jun Li, Julie Leconte, Kenrick Semple, Jessica Heinrichs, Claudio Anasetti, Woong-Kyung Suh, Xue-Zhong Yu
Journal: Blood (2012)
Efficacy of an Antagonistic Anti-CD40 Monoclonal Antibody, HCD122 (CHIR-12.12), in Preclinical Models of Human Non-Hodgkin’s Lymphoma and Hodgkin’s Disease.
Authors: Li Long, Montesa Patawaran, Xia Tong, Seema Kantak, Sharon L. Aukerman, Nancy Pryer, Mohammad Luqman
Journal: Blood (2006)
A regulatory network of canonical nuclear factor-κB activation predicts high-grade glioma outcome
Authors: M. Bredel, H. Phillips, G. R. Harsh, K. Aldape, B. I. Sikic
Journal: Journal of Clinical Oncology (2007)

2007 Background: The mechanism for decision between cell death and survival is under fine regulation. Nuclear factor-κB is a transcription regulator that is known to promote survival in many cellular events. Excessive and prolonged activation of NF-κB has been established as a principal mechanism of tumor chemoresistance, which is primarily mediated by its antiapoptotic activity. The pathway leading to the activation of NF-κB involves a complicated network that includes multiple modulatory signaling molecules. We have discovered alterations in several NF-κB pathway modulators in glioblastoma cells, which may act synergistically in activating NF-κB during resistance formation to O6-alkylating agents, including the TNFAIP3, NFKBIA, and TNIP1 genes. Methods: We have retrospectively evaluated the outcome relationship for these and additional endogenous inhibitors of canonical NF-κB activation in three independent high-grade glioma cohorts comprising 175 tumors. Results: We here confirmed the putative importance of NF-κB pathway activation status in predicting high-grade glioma outcome. Our data indicate an increasing complexity and linkage of several modulatory molecules (TNFAIP3, NFKBIA, TNIP1, and TNIP2) to patient outcome that interact physical and functionally in a cooperative fashion to regulate NF-κB activation. We found that for many of these molecules combined predictor models outperform the predictive power of the individual molecules. This observation is consistent with recent evidence suggesting the cooperation of these endogenous inhibitors in a negative feedback regulation of NF-κB activation and a mutual facilitation of their repressive ability. In terms of outcome prediction, we found several of these inhibitors to outperform established clinical and morphological prognostic variables such as patient age and tumor grade (III vs. IV), as well as the O6-methylguanine DNA methyltransferase (MGMT) gene, the currently most established outcome marker in glioblastomas. Conclusions: These findings raise the hope for this regulatory network as an amenable target to modulate NF-κB-mediated resistance in glioblastoma cells, with the ultimate goal of increasing the efficacy of chemotherapy in patients harboring these challenging tumors. No significant financial relationships to disclose.
Ublituximab (TGTX-1101), a Novel, Third-Generation Anti-CD20 Antibody Demonstrates Enhanced Antitumor Activity Compared to Rituximab in Primary CNS and Intraocular Lymphoma Murine Models.
Authors: Sabrina Donnou, Rym Ben Abdelwahed-Bagga, Jérémie Cosette, Hanane Ouakrim, Lucile Crozet, Alexandra Jacquet, Wolf Herman Fridman, Catherine Sautès-Fridman, Peter Sportelli, Remi Urbain, Sylvain Fisson
Journal: Blood (2012)
M3P Sequencing Panel Identifies TP53 Mutational Status As a Prognostic Factor in Chemotherapy-Naive Multiple Myeloma
Authors: Davine Hofste op Bruinink, K. Martin Kortüm, Mark van Duin, Mathijs A. Sanders, Remco Hoogenboezem, Michael Vermeulen, Laura Bruins, Jonathan Ahmann, Annemiek Broijl, Sonja Zweegman, Esteban Braggio, Bronno van der Holt, A. Keith Stewart, Pieter Sonneveld
Journal: Blood (2015)
Waiting for Godot: Thirty-Six Month Follow-Up on Accelerated FDA Approval of Drugs To Treat Hematologic Malignancies.
Authors: Veena Shankaran, June McKoy, Ben Djulbegovic, Allison Lyons, Ken Carson, Cara Tigue, Neal Dandade, Martin Tallman, Oliver Sartor, Charles Bennett
Journal: Blood (2007)