tbuckley/cabot-search huggingface dataset:
Standardisation and consensus guidelines for minimal residual disease assessment in Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) by real-time quantitative reverse transcriptase PCR of e1a2 BCR-ABL1
Authors: H. Pfeifer, G. Cazzaniga, V. H. J. van der Velden, J. M. Cayuela, B. Schäfer, O. Spinelli, S. Akiki, S. Avigad, I. Bendit, K. Borg, H. Cavé, L. Elia, S. C. Reshmi, G. Gerrard, S. Hayette, M. Hermanson, A. Juh, T. Jurcek, M. C. Chillón, C. Homburg, G. Martinelli, V. Kairisto, T. Lange, T. Lion, M. C. Mueller, F. Pane, L. Rai, C. Damm-Welk, T. Sacha, S. Schnittger, T. Touloumenidou, H. Valerhaugen, P. Vandenberghe, J. Zuna, H. Serve, E. Herrmann, S. Markovic, J. J. M. van Dongen, O. G. Ottmann
Journal: Leukemia (2019)
Abstract 21055: Baseline Cardiovascular Magnetic Resonance Imaging Measurements Are Associated With Clinical Outcomes at Three Years of Follow-Up: Results From a Prospective, International, Multi-Site Study of Patients With Significant Pulmonary Regurgitation Late After Tetralogy of Fallot Repair
Authors: Rachel M Wald, Michael Farkouh, Christopher Caldarone, Nagib Dahdah, Frédéric Dallaire, Christian Drolet, Jasmine Grewal, Camilla Kayedpour, Paul Khairy, Adrienne Kovacs, Benedetta Leonardi, Brian McCrindle, Syed Najaf Nadeem, Ming Yen Ng, Erwin Oechslin, Andrew Redington, Candice Silversides, Edythe Tham, Judith Therrien, Isabelle Vonder Muhll, Andrew Warren, Bernd Wintersperger, Edward Hickey
Journal: Circulation (2017)

Introduction: Late complications after tetralogy of Fallot repair (rTOF) often arise from chronic pulmonary regurgitation (PR). Prospective studies of outcomes in those with rTOF and significant PR are lacking. Hypothesis: We hypothesized that cardiovascular magnetic resonance imaging (CMR) imaging measurements would be associated with poor outcomes in an “at risk” population with rTOF and ≥moderate PR. Methods: This was a prospective, international study (North America, Europe and Asia) of children and adults. Inclusion criteria were rTOF in childhood, age ≥12 years, ≥moderate PR, and CMR within 18 months of enrollment. All CMR analysis occurred in a central core laboratory. Patient reported outcomes were collected using standardized tools. The primary clinical outcome was death or sustained (&gt;30 seconds) ventricular tachycardia (VT) recorded at 3 year follow-up. Results: We enrolled 629 patients (55% male) at 29±14 years (2013-2017). Primary rTOF was done at 1.6 years (IQR 0.6,4.2) with a transannular patch in 55%. By standardized symptom assessment, 78% were asymptomatic (NYHA 1). Baseline CMR findings included PR fraction 38±14%, right ventricular (RV) end-diastolic volume indexed (EDVi) 155±41mL/m2, RV ejection fraction (EF) 44±7%, RV mass indexed 59±16 g/m2, left ventricular (LV) EDVi 85±18mL/m2, LVEF 55±7% and LV mass indexed 88±27 g/m2. Outcomes at 3 years were recorded (available in n=101). During follow-up, surgical pulmonary valve replacement (PVR) occurred in 38 patients (38%). In the PVR group compared with the non-PVR group, baseline RVEDVi was larger (189 vs. 152 mL/m2, p&lt;0.0001) and RV mass was higher (65 vs. 58 g/m2, p=0.04); RVEF, LVEF and LV mass did not differ between groups. At 3 year follow-up, 4 patients (4%) had an outcome (n=2 deaths, n=2 VT) and half of these patients (n=2) had PVR. Those with outcomes had higher baseline RV mass and LV mass as compared to those without outcomes (73±12 vs. 59±13g/m2, p=0.04 and 132±32 vs. 89±28g/m2, p=0.01); volumes and function did not differ between groups. Conclusions: Despite significant PR, most patients with rTOF were asymptomatic. At 3 year follow-up, PVR occurred in more than one third of patients. Death or VT was observed in a small number of patients who had higher RV and LV mass on baseline CMR.
High cutoff versus high-flux haemodialysis for myeloma cast nephropathy in patients receiving bortezomib-based chemotherapy (EuLITE): a phase 2 randomised controlled trial
Authors: Colin A Hutchison, Paul Cockwell, Veronica Moroz, Arthur R Bradwell, Lesley Fifer, Julian D Gillmore, Mark D Jesky, Markus Storr, Julie Wessels, Christopher G Winearls, Katja Weisel, Nils Heyne, Mark Cook
Journal: The Lancet Haematology (2019)
Resection of lung metastases from colorectal cancer: Analysis of outcome and prognostic factors.
Authors: Alessandra Cassano, MariaTeresa Congedo, Ettore D'Argento, Carmelo Pozzo, Ernesto Rossi, Stefano Margaritora, Dania Nachira, Armando Orlandi, Giovanni Schinzari, Michela Quirino, Cinzia Bagalà, Pierluigi Granone, Carlo Barone
Journal: Journal of Clinical Oncology (2015)

e14556 Background: Surgical removal of liver metastases can provide a chance of cure for selected patients (pts) with metastatic colorectal cancer (CRC). Less data are currently available on CRC lung metastases resection. The aim of our study was to analyse the effectiveness of CRC lung or lung and hepatic metastases resection. Methods: We retrospectively analysed outcome and clinicopathologic features of 79 pts who underwent only lung or both liver and lung resection for metastatic CRC from 2000 to 2014 at our institution. Results: Among pts, 45 were men and 34 women. Mean age was 62.6 years. All pts underwent resection of primary tumour and 81% received an adjuvant chemotherapy treatment. Pts with unilateral metastases were 90% and 64.6% had a single metastasis. Most of pts (64.6%) had small lung nodules with larger diameter less than 2 cm. Most of them (70.9%) received also a peri-operative chemotherapy treatment. Fifthy-two pts (65.8%) had lung and liver resection, 42 pts (80.8%) liver first, 9 (17.3%) lung first and 1 a simultaneous resection of liver and lung. At a median follow-up of 35.1 months, 77.1% are alive and 64.1 are disease-free. Median survival was 26.3 months (87.3% at 1 year, 34.7% at 3 years and 23.6% at 5 years). Pts with unilateral disease had a significantly higher survival (87 vs 31 months; p = 0.02; confidence interval 0.04-0.8). Survival from lung resection for pts who underwent both liver and lung resection was 29.2 months. Prognostic factors for this subset of pts were the presence of solitary or multiple lung metastases (87 vs. 31 months, respectively, p = 0.03; confidence interval 0,11-0,91) and unilateral vs bilateral disease (87 vs 23 months; p = < 0,0001; confidence interval 0,11-0,91). A trend of benefit on survival was observed in pts with K-RAS wild-type tumours and disease-free interval ≥ 36 months. Conclusions: Our data suggest that the resection of lung metastases for patients with CRC is feasible and could have an impact on overall survival, also for those who underwent hepatic resection. More data on clinical and biological prognostic factors from larger and prospective studies are necessary for a better selection of patients who could benefit from a repeated surgical approach in the continuum of care.
MC1R variants in childhood and adolescent melanoma: a retrospective pooled analysis of a multicentre cohort
Authors: Cristina Pellegrini, Francesca Botta, Daniela Massi, Claudia Martorelli, Fabio Facchetti, Sara Gandini, Patrick Maisonneuve, Marie-Françoise Avril, Florence Demenais, Brigitte Bressac-de Paillerets, Veronica Hoiom, Anne E Cust, Hoda Anton-Culver, Stephen B Gruber, Richard P Gallagher, Loraine Marrett, Roberto Zanetti, Terence Dwyer, Nancy E Thomas, Colin B Begg, Marianne Berwick, Susana Puig, Miriam Potrony, Eduardo Nagore, Paola Ghiorzo, Chiara Menin, Ausilia Maria Manganoni, Monica Rodolfo, Sonia Brugnara, Emanuela Passoni, Lidija Kandolf Sekulovic, Federica Baldini, Gabriella Guida, Alexandros Stratigos, Fezal Ozdemir, Fabrizio Ayala, Ricardo Fernandez-de-Misa, Pietro Quaglino, Gloria Ribas, Antonella Romanini, Emilia Migliano, Ignazio Stanganelli, Peter A Kanetsky, Maria Antonietta Pizzichetta, Jose Carlos García-Borrón, Hongmei Nan, Maria Teresa Landi, Julian Little, Julia Newton-Bishop, Francesco Sera, Maria Concetta Fargnoli, Sara Raimondi, Mauro Alaibac, Andrea Ferrari, Barbara Valeri, Mariacristina Sicher, Daniela Mangiola, Gianluca Nazzaro, Giulio Tosti, Giovanni Mazzarol, Giuseppe Giudice, Simone Ribero, Chiara Astrua, Antonella Romanini, Laura Mazzoni, Irene Orlow, Urvi Mujumdar, Amanda Hummer, Klaus Busam, Pampa Roy, Rebecca Canchola, Brian Clas, Javiar Cotignola, Yvette Monroe, Bruce Armstrong, Anne Kricker, Melisa Litchfield, Paul Tucker, Nicola Stephens, Teresa Switzer, Beth Theis, Lynn From, Noori Chowdhury, Louise Vanasse, Mark Purdue, David Northrup, Stefano Rosso, Carlotta Sacerdote, Nancy Leighton, Maureen Gildea, Joe Bonner, Joanne Jeter, Judith Klotz, Homer Wilcox, Helen Weiss, Robert Millikan, Dianne Mattingly, Jon Player, Chiu-Kit Tse, Timothy Rebbeck, Amy Walker, Saarene Panossian, Richard Setlow, Harvey Mohrenweiser, Philippe Autier, Jiali Han, Saverio Caini, Albert Hofman, Manfred Kayser, Fan Liu, Tamar Nijsten, Andre G. Uitterlinden, Rajiv Kumar, Tim Bishop, Faye Elliott, DeAnn Lazovich, David Polsky, Johan Hansson, Lorenza Pastorino, Nelleke A. Gruis, Jan Nico Bouwes Bavinck, Paula Aguilera, Celia Badenas, Cristina Carrera, Pol Gimenez-Xavier, Josep Malvehy, Joan Anton Puig-Butille, Gemma Tell-Marti, Leigh Blizzard, Jennifer Cochrane, Wojciech Branicki, Tadeusz Debniak, Niels Morling, Peter Johansen, Susan Mayne, Allen Bale, Brenda Cartmel, Leah Ferrucci, Ruth Pfeiffer, Giuseppe Palmieri, Katerina Kypreou, Anne Bowcock, Lynn Cornelius, M. Laurin Council, Tomonori Motokawa, Sumiko Anno, Per Helsing, Per Arne Andresen, Stefania Guida, Terence H. Wong
Journal: The Lancet Child & Adolescent Health (2019)
Racial differences in long-term prostate cancer specific mortality following conservative management for low-risk prostate cancer: A population-based study.
Authors: Grace L. Lu-Yao, Nikita Nikita, Scott W Keith, Joshua Banks, Nathan Handley, Timothy Rebbeck, Jennifer Cullen, Josep Domingo-Domenech, William Kevin Kelly
Journal: Journal of Clinical Oncology (2019)

121 Background: It is uncertain whether the same criteria for active surveillance can be applied universally across races. This population-based study was undertaken to quantify racial differences in long-term risk of prostate cancer-specific mortality (PCSM) among patients with low-risk prostate cancer (PCa) receiving conservative management. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify patients who had low-risk PCa (T1-T2a &amp; Gleason 6 &amp; PSA ≤ 10 ng/mL &amp; N0 &amp; M0) diagnosed in 2004 – 2015 and did not receive radical prostatectomy or radiation therapy within one year of diagnosis. Kaplan-Meier analysis was used to calculate PCSM. The Clopper-Pearson method was used to calculate associated 95% confidence intervals. Hazard ratio of PCSM among those with a high PSA (PSA 4-10) compared to those with a low PSA (PSA &lt; 4) was calculated using Cox proportional hazards models adjusted for covariates (including age, race, marital status, insurance status, U.S. region, year of diagnosis, and AJCC clinical tumor stage). Results: Among 33,740 patients with low-risk PCa, long-term PCSM varied with race and PSA levels at diagnosis. For instance, 10-year PCSM was 2.62% (95% CI: 1.15%-5.05%) among African Americans with PSA 4-10 and 0.98% (95% CI:0.16%-3.12%) among Caucasian patients with PSA &lt; 4. There was no significant statistical interaction between race and PSA level on PCSM (p = 0.81). After adjusting for potential confounders, men with PSA 4-10 experienced 2-fold higher PCSM relative to those with PSA &lt; 4 (HR = 1.96, p = 0.011) and African Americans men experienced a 43% higher PCSM compared to Caucasians (HR = 1.43, p = 0.03). Conclusions: Among men diagnosed with low-risk PCa, long-term PCSM varies by race and PSA at diagnosis. More refined risk stratification may improve PCa management among low-risk PCa patients. [Table: see text]
3D-Tissue Engineered Bone Marrow (3DTEBM) Culture Retrospectively Predicts Treatment Clinical Outcomes of Multiple Myeloma Patients
Authors: Amanda Jeske, Feda Azab, Pilar De La Puente, Barbara Muz, Justin King, Daniel R. Kohnen, Ravi Vij, Abdel Kareem Azab
Journal: Blood (2018)
The effect of loss of SETD2 on mitochondrial dysfunction in clear cell renal cell carcinoma.
Authors: Robert Hapke, Katy Beckermann, Kimryn Rathmell, Scott Mattox Haake
Journal: Journal of Clinical Oncology (2019)

567 Background: SET domain-containing protein 2 ( SETD2) is among the most commonly mutated genes in clear cell renal cell carcinoma (ccRCC). Classically, SETD2 modulates chromatin structure via the methylation of lysine 36 on histone H3. However, histone-independent functions of SETD2 are emerging. We sought to discover novel SETD2-dependent changes to the cellular lysine methylation landscape during kidney cancer tumorigenesis. Methods: In this study, we used HKC human proximal tubule kidney cell lines, the likely nephrogenic region of origin for ccRCC. The proteomes of wild type (WT) and SETD2-knock out (KO) cells were labeled using stable isotope labeling by amino acids in cell culture (SILAC). Proteins were trypsinized and lysine-methylated peptides were immunoprecipitated. Relative abundance of lysine-methylated peptides and total peptides were calculated in the WT and SETD2-KO using nano-liquid chromatography/tandem mass spectrometry (LC/MS-MS). Results: &gt; 30,000 peptides were quantified, including &gt; 50 lysine methylated peptides. We observed decreased lysine methylation of eukaryotic elongation factor 1A1 (eEF1A1), including K165 trimethylation (K165me3) and K318 monomethylation (K318me1). eEF1A1 is classically known for delivery of aminoacyl-tRNA to the ribosome, and its function is modulated via the lysine methyltranferases eEF1AKMT1-4. eEF1AKMT3 is responsible for trimethylation of K165, and expression of this enzyme was decreased in SETD2-KO cells. In addition, we observed significant decrease in expression in proteins of the electron transport chain (ETC) complex 1 in SETD2-KO cells yet normal gene expression, suggesting a translational defect. Functionally, SETD2-KO cells are characterized by decreased cellular oxygen consumption rate and increased mitochondrial mass, suggestive of ETC dysfunction. Conclusions: We observe decreased expression of eEF1AKMT3 in SETD2-KO cells, resulting in decreased K165me3 of eEFA1A, decreased translation of ETC proteins, and mitochondrial dysfunction. As mitochondrial dysfunction is commonly observed in RCC, we expect this represents a novel mechanism of SETD2-mediated tumorigenesis.
Quality-of-life (QoL) assessment and reporting in prostate cancer: A systematic review of phase III trials published between 2012 and 2016.
Authors: Laura Marandino, Anna La Salvia, Cristina Sonetto, Emmanuele De Luca, Daniele Pignataro, Clizia Zichi, Rosario F Di Stefano, Eleonora Ghisoni, Pasquale Lombardi, Annapaola Mariniello, Maria Lucia Reale, Elena Trevisi, Gianmarco Leone, Leonardo Muratori, Consuelo ButtIgliero, Marcello Tucci, Massimo Aglietta, Giorgio V. Scagliotti, Francesco Perrone, Massimo Di Maio
Journal: Journal of Clinical Oncology (2019)

219 Background: We previously reported that QoL is not included among endpoints and QoL results are significantly underreported in a high proportion of recently published phase III trials in oncology. In this study our aim was to describe QoL prevalence and heterogeneity in QoL reporting in prostate cancer (PC) phase III trials. Methods: Whole database included all primary publications (P) of phase III trials evaluating anticancer drugs published between 2012 and 2016 by 11 major journals. For this analysis, we extracted the subset of PC trials. We analyzed QoL inclusion among endpoints, presence of QoL results and methodology of QoL analysis. Results: 35 P were identified (21 in castration-resistant [CRPC], 9 in advanced hormone sensitive [aHSPC], incl. both metastatic and biochemical relapsed, and 5 in earlier stages). In 13 (37.1%) QoL was not listed among study endpoints: 7/21 (33.3%) in CRPC, 3/9 (33.3%) in aHSPC, and 3/5 (60%) in earlier stages. Out of 22 primary P of trials including QoL among endpoints, QoL results were not reported in 9 (40.9%). Overall, no QoL data were available in 22/35 (62.9%) primary P (61.9% in CRPC, 44.4% in aHSPC and 100% in earlier disease). QoL data were not available in 15/25 (60%) trials with overall survival (OS) as primary endpoint, and in 7/10 (70%) trials with other primary endpoints. QoL data were not available in 7/16 (43.8%) trials with a positive result (25% in CRPC, 40% in aHSPC, 100% in earlier stages). In 18 trials with available QoL results (incl. secondary publications), most common QoL tools were FACT-P (11, 61.1%) and EORTC QLQ-C30 (6, 33.3%). Common methods of analysis were mean changes (6, 33.3%), mean scores over time (6, 33.3%), time to deterioration (6, 33.3%) and proportion of responders (3, 16.7%). QoL analysis was focused on the impact of toxicity in 10 cases (mostly in earlier stages), and on disease symptoms in 10 cases (mostly in CRPC). Conclusions: QoL is absent in a high proportion of recently published phase III trials in PC, although presence of QoL results is better in positive trials, especially in CRPC. Methodology of QoL analysis is heterogeneous in terms of type of instruments, analysis and presentation of results.
Combined Inhibition of STAT3 and DNA Repair in Palbociclib-Resistant ER-Positive Breast Cancer
Authors: Nicole M. Kettner, Smruthi Vijayaraghavan, Merih Guray Durak, Tuyen Bui, Mehrnoosh Kohansal, Min Jin Ha, Bin Liu, Xiayu Rao, Jing Wang, Min Yi, Jason P.W. Carey, Xian Chen, T. Kris Eckols, Akshara S. Raghavendra, Nuhad K. Ibrahim, Meghan Sri Karuturi, Stephanie S. Watowich, Aysegul Sahin, David J. Tweardy, Kelly K. Hunt, Debu Tripathy, Khandan Keyomarsi
Journal: Clinical Cancer Research (2019)

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are currently used in combination with endocrine therapy to treat advanced hormone receptor-positive, HER2-negative breast cancer. Although this treatment doubles time to progression compared with endocrine therapy alone, about 25%-35% of patients do not respond, and almost all patients eventually acquire resistance. Discerning the mechanisms of resistance to CDK4/6 inhibition is crucial in devising alternative treatment strategies.Palbociclib-resistant cells (MCF-7 and T47D) were generated in a step-wise dose-escalading fashion. Whole-exome sequencing, genome-wide expression analysis, and proteomic analysis were performed in both resistant and parental (sensitive) cells. Pathway alteration was assessed mechanistically and pharmacologically. Biomarkers of altered pathways were examined in tumor samples from patients with palbociclib-treated breast cancer whose disease progressed while on treatment.Palbociclib-resistant cells are cross-resistant to other CDK4/6 inhibitors and are also resistant to endocrine therapy (estrogen receptor downregulation). IL6/STAT3 pathway is induced, whereas DNA repair and estrogen receptor pathways are downregulated in the resistant cells. Combined inhibition of STAT3 and PARP significantly increased cell death in the resistant cells. Matched tumor samples from patients with breast cancer who progressed on palbociclib were examined for deregulation of estrogen receptor, DNA repair, and IL6/STAT3 signaling, and results revealed that these pathways are all altered as compared with the pretreatment tumor samples.Palbociclib resistance induces endocrine resistance, estrogen receptor downregulation, and alteration of IL6/STAT3 and DNA damage response pathways in cell lines and patient samples. Targeting IL6/STAT3 activity and DNA repair deficiency using a specific STAT3 inhibitor combined with a PARP inhibitor could effectively treat acquired resistance to palbociclib.
Impact of Aurora kinase A and B expression on response to neoadjuvant chemotherapy and patient outcome in muscle-invasive bladder cancer (MIBC).
Authors: Earle Frederick Burgess, Chad Livasy, Sally J Trufan, Aaron Hartman, Renato Guerrieri, Caroline Naso, Peter E Clark, Claud Grigg, James Thomas Symanowski, Derek Raghavan
Journal: Journal of Clinical Oncology (2019)

393 Background: Identification of robust biomarkers that predict likelihood of benefit from neoadjuvant chemotherapy (NAC) in patients with MIBC remains an unmet need. Previous studies have implicated tumor overexpression of aurora kinases A (AURKA) and B (AURKB) as a mechanism of chemo-resistance. Because overexpression of AURKA has also emerged as a potential biomarker for detection of high-risk urothelial carcinoma, we sought to characterize the expression of AURKA, AURKB with clinical outcomes in MIBC patients who received NAC and to test the hypothesis that tumor overexpression of AURKA and AURKB would predict for residual MIBC. Methods: 47 patients with MIBC who received NAC prior to cystectomy were retrospectively identified. Immunohistochemistry for AURKA and AURKB was performed on pre-treatment diagnostic transurethral resection of bladder tumors and matched cystectomy specimens. Logistic regression models were estimated to determine the impact of pre-NAC expression on pathologic staging at cystectomy. Receiver Operator Characteristic curves (ROC) were calculated to assess diagnostic predictive ability of AURKA and AURKB. AURKA and AURKB were assessed for association with relapse-free survival (RFS) and overall survival (OS) using Kaplan-Meier techniques and Cox proportional hazards models. Results: 22 of 47 [46.8%] patients had residual muscle-invasive (ypT2-4) urothelial carcinoma after NAC. Neither baseline tumor expression of AURKA (ROC = 0.54, p = 0.71) nor AURKB (ROC = 0.46, p = 0.98) predicted for ypT2-4 status. However, baseline expression of AURKA above the 75th percentile for this cohort, determined by the percentage of tumor cells positive, was associated with an inferior RFS, [HR = 3.79, [1.40, 10.26] p = 0.005] and OS, [HR = 5.84, [2.14, 15.98], p &lt; 0.001]. Similar trends for worse survival outcomes were also observed for high AURKB levels. Conclusions: Although baseline tumor AURKA and AURKB expression did not predict for pathologic residual MIBC after NAC, high expression of AURKA and AURKB predicted for inferior RFS and OS. Further evaluation of AURKA and AURKB as potential biomarkers and therapeutic targets in MIBC is warranted.