tbuckley/cabot-search huggingface dataset:
A comprehensive safety trial of chimeric antibody 14.18 (ch14.18) with GM-CSF, IL-2, and isotretinoin in high-risk neuroblastoma patients following myeloablative therapy: A Children's Oncology Group study.
Authors: Mehmet Fevzi Ozkaynak, Andrew Lee Gilman, Alice L. Yu, Wendy B. London, Paul M Sondel, Malcolm A. Smith, Robert Seeger, C. Patrick Reynolds, John M. Maris, Julie R. Park
Journal: Journal of Clinical Oncology (2014)

10044 Background: In a Phase 3 randomized study (COG ANBL0032), we demonstrated that the addition of ImmRx to standard therapy isotretinoin for high-risk neuroblastoma (NB) patients in CR or VGPR after intensive induction and consolidation significantly improved outcome (Yu, NEJM, 2010). ANBL0931 study was designed to collect FDA-required comprehensive safety/toxicity data for ImmRx to support a new Biological License Application. Efficacy data were collected as a secondary endpoint. Methods: Newly diagnosed high-risk NB patients who achieved ≥PR to induction therapy and received myeloablative consolidation with stem cell rescue then received isotretinoin x 6 with 5 concomitant cycles of ch14.18 combined with GM-CSF (cycles 1,3,5) or IL2 (cycles 2,4). Ch14.18 infusion time was 10 hrs. which was prolonged compared to 5.75 hrs for the initial 245 patients on ANBL0032. Toxicity data were collected. Results: Of105 patients enrolled (none ineligible), five patients developed protocol-defined unacceptable toxicities and came off study (four grade 4 allergic reactions, one sudden death - sudden onset of abdominal pain and arrest). The most common grade 3 or higher non-hematologic toxicities of ImmRx were neuropathic pain (cycles 1, 2, 3, 4, 5 were 30.9%, 22%, 13.3%, 20%, 17%, respectively), hypotension (9.6%, 17%, 3.1%, 12.2%, 5.7%), allergic reactions (2.9%, 9%, 3%, 6.6%, 2.2%), capillary leak syndrome (1%, 4%, 0, 2.2%, 0), fever (21%, 58%, 6.1%, 31.1%, 4.5%). Toxicities occurred more frequently during IL-2 cycles compared to GM-CSF cycles. Dose modifications were reported in 73 patients (69%) most of which are thought to be prolongation of the ch14.18 infusion time beyond 10 hrs. The 2-year EFS and OS were 74±6% and 84±5%, respectively (n=105). Conclusions: This study has confirmed the significant, but manageable treatment-related toxicities of the ImmRx including pain, allergic reactions, hypotension and capillary leak syndrome. Decreased toxicity compared to ANBL0032 may be due to the 10 hr minimum ch14.18 infusion time for all patients in this study. EFS and OS appear similar to that observed on ANBL0032.
First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial
Authors: Pascal Joly, Maud Maho-Vaillant, Catherine Prost-Squarcioni, Vivien Hebert, Estelle Houivet, Sébastien Calbo, Frédérique Caillot, Marie Laure Golinski, Bruno Labeille, Catherine Picard-Dahan, Carle Paul, Marie-Aleth Richard, Jean David Bouaziz, Sophie Duvert-Lehembre, Philippe Bernard, Frederic Caux, Marina Alexandre, Saskia Ingen-Housz-Oro, Pierre Vabres, Emmanuel Delaporte, Gaelle Quereux, Alain Dupuy, Sebastien Debarbieux, Martine Avenel-Audran, Michel D'Incan, Christophe Bedane, Nathalie Bénéton, Denis Jullien, Nicolas Dupin, Laurent Misery, Laurent Machet, Marie Beylot-Barry, Olivier Dereure, Bruno Sassolas, Thomas Vermeulin, Jacques Benichou, Philippe Musette
Journal: The Lancet (2017)
How should we tackle financial and prosocial biases against unattractive people?
Authors: Francesca Minerva
Journal: Behavioral and Brain Sciences (2017)

Abstract The fact that attractive people benefit from their good looks is not bad per se. Rather, what is worrisome is the fact that unattractive people are discriminated against, and that such discrimination negatively affects many aspects of their lives. I focus on the moral implications of this discrimination and on the possible measures that could be taken to alleviate it.
Efficacy of ocaratuzumab (AME-133v) in relapsed follicular lymphoma patients refractory to prior rituximab.
Authors: Jennifer L. Wayne, Kristen N. Ganjoo, Brad L. Pohlman, Sven De Vos, Ian W. Flinn, Nam H. Dang, Markus Y. Mapara, Mitchell R. Smith, Adrienne M. O'Reilly, Shashidhara Y. Marulappa, Vinay Kumar Jain
Journal: Journal of Clinical Oncology (2012)

8081 Background: Ocaratzumab, previously known as AME-133v, is a humanized next-generation anti-CD20 monoclonal antibody. It has been optimized with a 13 to 20-fold increase in binding affinity to CD20 and improved binding to the low-affinity (F/F and F/V) polymorphisms of FcγRIIIa (CD16), which are thought to predict lower response rates and shorter duration of responses to rituximab. Methods: In a phase I dose escalation study in relapsed follicular lymphoma (FL) patients, ocaratuzumab was well-tolerated at doses up to 375 mg/m 2 (Forero-Torres et al. CCR 2012). In a follow-on phase II trial, 44 patients with relapsed FL following prior rituximab and the low-affinity FcγRIIIa polymorphism (F-carriers) received 375 mg/m 2 of ocaratuzumab weekly for 4 doses. In this study, overall response rate (ORR) was 36% and median progression free survival (PFS) was 91 weeks (Ganjoo et al. Haematologica 2011). Results: Amongst the 56 patients receiving 100 and 375 mg/m 2 of ocaratuzumab, 8 patients had a previous time to progression of ≤ 180 days following their last rituximab treatment. These patients had a median of 2 prior rituximab treatments, (range 1-6 treatments), and median PFS following last treatment of 159 days. Five of the 8 patients showed a longer PFS after ocaratuzumab administration, compared with last rituximab treatment. All 5 patients expressed the homozygous low-affinity genotype of FcγRIIIa (F/F). At the time of study closure, 3 of the patients were still in remission (indicated by * in the table). Conclusions: This retrospective analysis suggests that ocaratuzumab may be non-cross-resistant to rituximab in patients with the low-affinity FcγRIIIa polymorphism. Prolonged PFS in selected patients following ocaratuzumab suggests that the increased binding affinity to CD16 and improved antibody-dependent cell-mediated cytotoxicity (ADCC) of this antibody is clinically relevant. As a single agent, ocaratuzumab may provide prolonged clinical benefit in relapsed FL patients and a clinical trial comparing ocaratuzumab to rituximab is in preparation. [Table: see text]
The negative prognostic impact of downstaging after neoadjuvant chemotherapy in patients with hormone-receptor positive breast cancer.
Authors: Yuko Takahashi, Naoki Hayashi, Naoko Matsuda, Yuka Kajiura, Atsushi Yoshida, Hiroshi Yagata, Seigo Nakamura, Koyu Suzuki, Hiroko Tsunoda, Hideko Yamauchi
Journal: Journal of Clinical Oncology (2013)

e11524 Background: While pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) improves patients’ survival, it is not well known whether or not chemosensitivity contributes to improve survival of patients who had non-pCR. The aim of this study was to evaluate the impact of chemosensitivity presented by downstaging after NAC on prognosis in patients with primary breast cancer. Methods: We assessed retrospectively 773 patients with primary breast cancer who underwent surgical resection after NAC between 2001 and 2008 (a median age 49 years, range 26-79 years). 572 patients (74.0%) had hormone-receptor positive tumor and 131 patients (16.9%) had HER2 positive tumor. One hundred forty six patients (18.9%) underwent sentinel node biopsy before NAC. We divided patients into two groups based on chemosensitivity: the downstaging (DS) group and the non-downstaging (non-DS) group. We compared the groups with respect to both disease-free survival (DFS) and overall survival (OS).According to hormone-receptor status and HER2 positivity, pCR was defined as no residual invasive and ypN0. Results: Before NAC, 37 patients had clinical Stage I (4.8%), 613 had cStage II (79.3%), and 123 had cStage III (15.9%). After NAC, 181 had ypStage I (23.4%), 306 had ypStage II (39.6%), and 175 had ypStage III (22.6%). One hundred eleven patients (14.4%) had pCR. Two hundred ninety seven patients (38.4%) had DS and 476 patients (61.6%) had non-DS. Of all patients, patients with DS had significantly longer DFS and OS than non-DS patients (p=0.01, 0.04, respectively). However, among 252 hormone-receptor positive patients with ypStage II, patients with DS (cStage III, n=21) had significantly shorter DFS than patients with non-DS (c Stage±/II, n = 231) (p&lt;0.001). In terms of overall survival, patients with DS had a similar trend compared to patients with non-DS in this population. Conclusions: Our results indicated that hormone-receptor positive breast cancer patients with cStage III before NAC, even after having ypStage II, have worse prognosis than patients with cStage II, therefore, these patients may need additional treatment in the adjuvant setting.
Cholinergic Stimulation Improves Hemostasis in a Hemophilia Mouse Model
Authors: Shilpa Shukla, Jason R. Fritz, Crystal A. Kyaw, Sara P. Valentino, Catherine W. Imossi, Susmita N. Sarangi, Kevin J. Tracey, Christopher J. Czura, Jared M. Huston
Journal: Blood (2015)
Detection of <i>EGFR</i> alterations in circulating cell-free DNA of lung tumor patients: Higher sensitivity obtained with plasma compared to serum.
Authors: Marc G. Denis, Marie Marcq, Paul Hofman, Acya Bizieux-Thaminy, Jaafar Bennouna, Claude El Kouri, Jean-Yves Douillard, Herve Lacroix, Audrey Vallee
Journal: Journal of Clinical Oncology (2013)

e19046 Background: Detection of EGFR alterations is critical for predicting the response to tyrosine kinase inhibitors (TKI) in patients with non-small-cell lung cancer (NSCLC). In clinical practice, molecular testing is performed on tumor tissues when available. We investigated the use of circulating cell-free DNA for the detection of EGFR alterations in patients with NSCLC. Methods: Serum and plasma were obtained by centrifugation (10 min, 2,000 g, 20°C) performed within 3 hours following blood collection. Cell-free DNA was extracted using the QIAamp Circulating Nucleic Acid kit (Qiagen). Detection of EGFR alterations was performed using the approved Therascreen EGFR RGQ kit (Qiagen). Samples were tested positive for EGFR mutation when the ΔCt value (Ct of the mutation specific PCR – Ct of the control PCR) was lower than 12 for exon 19 deletions, and below 14 for L858R mutation. Results: No EGFR alteration was detected in samples collected from healthy donors (n=6), NSCLC patients with a wild type EGFR (n=60), and early stages NSCLC patients presenting an EGFR mutation in their tumor (n=11). Thirteen metastatic patients presenting an EGFR mutation in their tumor were tested before initiation of TKI treatment. When available, both serum and plasma were analyzed. Nine of these patients (9/13; 69.2%) were tested positive in their serum. The ΔCt values obtained were lower for plasma than for serum in most cases, and more patients (10/11; 90.9%) were EGFR mutation positive when plasma was tested. Finally we tested 3 patients during TKI treatment on a monthly basis. For 2 patients we were unable to detect the mutation initially found in pretreatment samples. Clinically, both patients were partial responders. The third patient did not respond to TKI, and we detected the EGFR mutation with stable ΔCt values at all points tested. Conclusions: EGFR alterations can be found in patients presenting an EGFR mutation in a metastatic NSCLC. Plasma samples allowed a better detection rate. Our results suggest that DNA circulating in plasma is a useful alternative source of tumor DNA that could be used for determining EGFR mutation status, and for follow-up of treatment. Supported by a grant from Astra-Zeneca.
Perfomance of identification criteria for Lynch syndrome (LS) in a prospective population-based registry of Endometrial Cancer (EC): Prognostic value.
Authors: Ignacio Romero, Zaida Garcia-Casado, Pedro Martinez, Carmen Illueca, Berta Gonzalez-Lopez, Cristina Zorrero, Jose Manuel Bosch, Antonio Fernandez-Serra, Salvador Blanch, Pedro Mallol, Lucas Minig, Jose Antonio Lopez-Guerrero, Andres Poveda
Journal: Journal of Clinical Oncology (2015)

e16516 Background: Endometrial cancer associated to Lynch Syndrome (EC-LS) is rare and several criteria are currently used to identify them; our aim is to compare several diagnostic methods and explore their prognostic value. Methods: Prospective registry of consecutive, unselected EC patients in our institution were included. Clinical data, family history of cancer and criteria for LS were evaluated. MSI and MMR protein expression were performed in the complete series; in addition MMRgene complete sequencing and large genomic rearrangements of germline MLH1, MSH2, MSH6 were analyzed in 30 cases. Results: From June 2009 to December 2014 127 EC patients were included with a median age of 62 years (31-86). Histology was classified as type I (78%) and type II (22%: 14 serous). At diagnosis FIGO stages were I (76%) vs II-IVA (15%) vs IVB (9%). MSI-H was described in 29% (33/115) and loss of MMRpro in 23% (12/28 with MLH1 hypermethylation). Tumor tissue was unavailable in 5 cases for molecular analysis. No B-RAF mutation and 15/114 K-RAS mutation were identified. Revised Bethesda Criteria (rBC), Amsterdam II (AII), criteria defined by the Society Gynecologic Oncology ( > 20%-to-25% risk of LS) (SGO-H) and above 5-10% (SGO-L) and loss of MMR protein without MLH1methylation were able to distinguish mutation carriers (4) from noncarriers (26) (AUC of 0.80, 0.73, 0.82, 0.78 and 0.73 respectively), among our population-based cases. With a median follow-up of 28 months (0-78), 18 (16%) relapses and 18 deaths (16%) occurred. Considering I-IVA stages that underwent surgical resection (102), age ( > 62), EC-LS, histology (serous vs others), positive hormone receptor status and FIGO stage had a negative prognostic impact according to RFS in univariate analysis. After multivariate analysis histologic type, hormone receptor status and stage remained independent prognostic factors. Conclusions: In our seriesclinical criteria have limited utility for identification of EC-LS, they perform slightly better than molecular screening. Interestingly hormone receptor status remains of prognostic importance.
Phase II, open-label study of erlotinib (ERL) in patients with NSCLC with activating mutations of the EGFR identified on tissue samples, plasma DNA, and CTC-trigger.
Authors: Lucio Crino, Armando Santoro, Antonio Chella, Fausto Barbieri, Paola Venturino, Antonio Marchetti, Michele Milella, Ariela Brandes, Tommaso De Pas
Journal: Journal of Clinical Oncology (2013)

e19020 Background: Patients (pts) with advanced NSCLC and activating mutations of EGFR represent a biologically distinct disease that shows exquisite sensitivity to the reversible EGFR-TK inhibitors (TKIs) as ERL, demonstrated in phase III randomized studies. Unfortunately, tumor tissue needed for mutation analysis is in some cases insufficient for an accurate molecular characterization of the tumor before treatment and re-biopsies after treatment are challenging. Therefore it is crucial to develop new diagnostics techniques. Methods: Pts with histologically or cytologically confirmed stage IIIB/IV NSCLC, previously untreated with chemotherapy who present activating mutations of EGFR received ERL 150 mg/d until PD. The primary endpoint was 12-month PFS. Secondary endpoints included: ORR; OS; correlation between EGFR testing results obtained from basal tumor biopsies, from circulating tumor cells (CTC), from plasma DNA and by immunoistochemical detection; primary and secondary resistances and correlation to response and safety and tolerability. Results: Between 03-2011 and 11-2012, a total of 50 pts were enrolled from 7 centers. Median age was 63 years; 98% had adenocarcinoma, 54% had never smoked and 68% were female. Exon 19 deletions were more common (70%) than exon 21 (30%). EGFR screening methods applied at a site level were different: pyrosequencing (41%), Sanger (29%), SSCP (8%), Pyrosequencing and DNA melting (4%) and others (18%). Central evaluation confirmed the presence of an EGFR mutation in all cases. EGFR testing from CTC and from plasma DNA resulted feasible. EGFR mutations were identified by next generation sequencing in CTC preparations from 31 (84%) of 37 pts so far examined, corresponding to those present in matching tumor tissue. Treatment discontinuation was observed in 25 pts, mainly due to PD (30%) and death (10%). Results of plasma DNA and of immunoistochemical detection at baseline are ongoing as well as analysis on CTC and plasma DNA at progression. Conclusions: This trial confirms the feasibility of new diagnostics techniques and will help in improving understanding in the resistance mechanisms to EGFR TKIs. Clinical trial information: EudraCT Number: 2010-023892-24.
The Detection of Minimal Residual Disease By Multiparameter Flow Cytometry Predicts a Higher Risk of Relapse in Patients with ELN Intermediate Risk Acute Myeloid Leukemia Where Molecular Markers Are Not Available
Authors: Erika Borlenghi, Mirko Farina, Marco Chiarini, Viviana Giustini, Cinzia Lamorgese, Angela Passi, Enrico Morello, Luisa Imberti, Giuseppe Rossi
Journal: Blood (2016)
Racial and gender disparities in therapy and outcomes of squamous cell cancer of the anus.
Authors: Arjun Gupta, Nivedita Arora, Hong Zhu, Alana Christie, Jeffrey John Meyer, Saad A. Khan, Muhammad S. Beg
Journal: Journal of Clinical Oncology (2017)

691 Background: Squamous cell carcinoma of the anus (SCCA) is one of the few cancers with a rising incidence in the United States. We aimed to characterize race and gender-based disparities in receipt of therapy, and overall survival (OS) of SCCA using the Surveillance, Epidemiology and End Results (SEER) database. Methods: Cases of locoregional SCCA diagnosed between 2000-2012 in the SEER database were included. Demographics, tumor characteristics, therapy and outcomes were extracted. Primary end point was OS. Univariable and multivariable Cox proportional hazard models were constructed to test factors associated with OS. Data were reported as hazard ratios (HR) and 95% confidence intervals (CI). SAS version 9.4 was used for analysis. Results: We identified 7882 cases of locoregional SCCA, median age 58 years, 61.2% women, 86.3% white. A majority of patients (82.3%) received radiation therapy; with the lowest rate in black males (76.7%) and highest in white females (86.1%). The median OS was 135 months, and it was lower in the elderly, &gt; 65 years (68 months), men (108 months), blacks (109 months) and those who did not receive radiation therapy (121 months). In multivariate analysis, increasing age (HR 1.19, 95 % CI 1.16-1.20 per 5 years increase), gender (HR 1.59, 95% CI 1.47- 1.73, men vs women), race (HR 1.51, 95% CI 1.34- 1.71, blacks vs whites), and receipt of radiation therapy (HR 0.90, 95% CI 0.82-0.99), were associated with OS (all p &lt; 0.05). Race was a significant predictor of receiving radiation therapy on univariate analysis. Table 1 outlines the rates of receipt of radiation and the median OS of the four racial/gender groups. Conclusions: Significant race and gender-based disparities exist in the survival of patients with locoregional SCCA. Even after adjusting for baseline and treatment characteristics, blacks had poorer OS, suggesting difference in tumor biology. Further investigation into the causes, and methods to eliminate these disparities are warranted. [Table: see text]
Practice type &amp; race influence enrollment onto clinical oncology trials: A Patterns of Care Study analysis
Authors: B. Movsas, J. Moughan, J. Owen, L. R. Coia, M. J. Zelefsky, G. E. Hanks, J. F. Wilson
Journal: Journal of Clinical Oncology (2004)

6106 Background: The purpose of this study was to identify key factors influencing accrual to clinical oncology trials.Methods: Patterns of Care Study (PCS) surveys from sites studied between 1992–94 and 1996–99 (prostate cancer [1149 patients], breast cancer [1080 patients], esophageal cancer [818 patients]) were analyzed. PCS is an NCI-funded national survey of randomly selected radiation (RT) institutions in the U.S. Patients with non-metastatic disease, who received RT as definitive or adjuvant therapy, were randomly selected. To determine national estimates, the sample size was weighted by the relative contribution of each institution and patients within each institution. Accordingly, 3,047 patient records were reviewed by trained research associates; the weighted sample size was 132,890. The following factors (age, gender, race, type of insurance and practice type of treating institution [academic or not]) were studied by univariate and multivariate (MVA) analyses.Results: Only 2.7% of all patients were accrued to clinical oncology protocols, consistent with national estimates. On MVA, practice type (p=0.009) and race (p=0.012) were significant predictors of accrual. On univariate analysis, 9.4% of patients treated with RT at an academic practice were accrued vs. 1.7% at non-academic sites (p=0.011). Yet, the vast majority (87%) of all patients were seen at non-academic sites. White patients enrolled onto studies more than African Americans (2.8% vs. 0.8%, p=0.024). Younger age demonstrated a trend towards increased enrollment (3.5% for <70 yrs vs. 1.5% for ≥70 yrs, p=0.058). However, gender and type of insurance were not predictive. A trend towards increased accrual over time was observed (1.5% from '92-'94 vs. 4.2% from '96-'99, p=0.058).Conclusions: Practice type and race significantly influence accrual onto clinical oncology trials. To enhance enrollment, increased communication & education regarding protocols is essential, particularly focused on physicians in non-academic settings and minority patients. Supported by NCI grant CA 65435. No significant financial relationships to disclose.