tbuckley/cabot-search huggingface dataset:
Comparison of survival and nodal staging in rectal cancer patients undergoing sentinel lymph node mapping versus conventional surgery.
Authors: Sukamal Saha, Lindsay Berbiglia, Ujwala Koduru, Gregory Johnston, Vikrom K. Dhar, Jacob Burke, Jack Nettleton, Kiran Devisetty, Hersham Gayar, Trevor Singh, Madan L. Arora
Journal: Journal of Clinical Oncology (2014)

3641 Background: Nodal metastasis (mets) is one of the most important prognostic factors in rectal cancer (RCa). Sentinel lymph node (SLN) mapping (M) identifies more nodal mets compared to conventional surgery (ConvSx). This identification may lead to upstaging and change in adjuvant treatment, thereby impacting survival. A retrospective study was undertaken comparing RCa patients (pts) undergoing total mesorectal excision (TME) with SLNM (Group A) vs. ConvSx without SLNM (Group B) for survival and nodal staging. Methods: SLNM was performed by using a blue dye injected subserosally for tumors above the peritoneal reflection, and trans-anally for tumors below the reflection, prior to TME. Data was collected for pts demographics, neoadjuvant and adjuvant therapy, TNM staging, SLN status, and 5 year overall survival. Results: Group A had 99 pts with an average (avg) age of 66 yrs (M:F = 57:42). Group B had 183 pts with an avg age of 63 yrs (M:F = 125:60). Avg number of LNs for Group A vs. Group B was 12 vs. 12.5. SLNM was successful in 87% of pts with an avg number of SLN per patient being 2.1. Overall nodal positivity was 24% vs. 33% for Group A vs. Group B, probably due to much higher use of neoadjuvant chemo-radiation in Group A (79%) vs. Group B (28%). For Group A pts the SLN was the only positive node in 33%. Overall 5 year survival for Group A vs. Group B was 57% vs. 40%. For both node -ve and node + pts, 5 year survival for all pts receiving neoadjuvant therapy for Group A was 50% vs. 22% for Group B, and not receiving neoadjuvant therapy was 71% vs. 48%, respectively. (See Table.) Conclusions: SLNM in RCa pts is highly feasible with better overall survival for both node positive and node negative patients when compared to pts who underwent ConvSx, irrespective of whether or not neoadjuvant therapy was received. SLNM may be performed during surgery for RCa pts. Comparison of five year survival: Group A vs. Group B. Node positive Node negative Group A Group B Group A Group B T1 N/A 75.0% 68.0% 56.0% T2 20% 36% 71.0% 48.0% T3 47% 27% 50.0% 45.0% T4 67% 40% 50% 13.0% Group A Group B Neoadjuvant therapy 50% 22% No neoadjuvant therapy 71% 48%
ERCC-1 high-stage IIb/III esophageal cancer treated with nonplatinum-based neoadjuvant or definitive chemoradiotherapy.
Authors: Sulochana Devi Cherukuri, Paul R. Walker, Teresa Parent, Sharon Ben-Or, Jon Moran, Richard Fred Williams, Hyder Husain Arastu, Clinton Leinweber
Journal: Journal of Clinical Oncology (2014)

e15047 Background: Optimal curative outcomes in esophageal cancer are achieved with tri-modality therapy of neoadjuvant chemoradiotherapy (CRT) followed by surgery; if not a surgical candidate, definitive CRT. A platinum agent is the standard of care in esophageal cancer CRT. ERCC-1 is a DNA repair enzyme that will repair the DNA adduct damage by platinums decreasing therapeutic efficacy. SWOG S0356 noted a markedly lower 3-year survival in oxaliplatin based CRT in ERCC-1 high (mRNA) esophageal adenocarcinomas, yet no correlation with pathologic response. With this data, our Thoracic Oncology Program changed our programmatic approach of utilizing irinotecan-paclitaxel and not platinum-based CRT in ERCC-1 high (H-score) esophageal cancers. Methods: Patients with ERCC-1 high by H-score esophageal cancers were treated with one full cycle D1 and D8 irinotecan 65mg/m2 and nab-paclitaxel 100mg/m2 bringing in concurrent radiation therapy to 50.4 Gy commensurate with cycle 2, receiving 4 total cycles. Results: 8 patients were identified in our database. 4 males/4 females. 4 adenocarcinoma/4 squamous. Ages 32 to 73. 5 treated with CRT followed by surgery; 2 CRT alone; 1 progressed at end of CRT. 4 of the surgical 5 had pathologic complete responses/ypT0N0 (2 squamous/2 adenocarcinoma). One (squamous) had ypN0 with confirmed pre-op EUS and PET stage III disease with only scattered islands of residual T tumor. (Of potential note, this patient received only 2.5 of the 4 cycles with the taxane given a delayed return of his ERCC-1 H-score.) 80%pCR and 100% ypN0. 2/2 treated with CRT alone with complete PET metabolic responses. Only 1 patient required enteral feeding support. A notable clinical observation was immediate dysphagia improvement. Conclusions: Our programmatic experience has identified a high complete pathologic response with irinotecan-paclitaxel based CRT in ERCC-1 high esophageal cancer.
MINT: Multi-institutional, neoadjuvant therapy MammaPrint project.
Authors: Charles E. Cox, Peter William Blumencranz, Ruben A. Saez, Robert Wesolowski, William C. Dooley, Lisette Stork, Femke De Snoo, Jessica Gibson, Eli Avisar
Journal: Journal of Clinical Oncology (2014)

TPS1137 Background: Women with locally advanced breast cancer (LABC) are often treated with neo-adjuvant chemotherapy to reduce the size of the tumor prior to surgery, to enable breast conserving surgery and to observe the clinical effect of therapy in real time. Studies have shown that the 25–27% of individuals who have a pathologic complete response (pCR) to neoadjuvant therapy have a survival advantage of 80% in 5 years, which is double the expected survival of the remaining patients without pCR. If patients who are likely to show a pCR could be identified prior to initiation of therapy, it would enable more informed treatment decisions [von Minckwitz et al. JCO 2006]. Genomic assays, which are widely used to provide prognostic and predictive information in early breast cancer, have the potential to provide information on the likelihood of a patient with LABC responding to neo-adjuvant therapy [Glück et al. BRCRT 2013]. Methods: MINT is a prospective study designed to test the ability of molecular profiling, as well as traditional pathologic and clinical prognostic factors, to predict response to neo-adjuvant chemotherapy in patients with LABC. MammaPrint risk profile, BluePrint molecular subtyping profile, TargetPrint ER, PR and HER2 single gene readout, and TheraPrint Research Gene Panel will be analyzed on a fresh or formalin fixed paraffin embedded tumor specimen using the whole genome array. Patients will receive neo-adjuvant chemotherapy pre-specified in the protocol. Response will be measured by pCR and by centrally assessed RCB. The study will include women with histologically-proven invasive breast cancer T2 (≥3.5cm)-T4, N0M0 or T2-T4N1M0, adequate bone marrow reserves and normal renal and hepatic function who signed informed consent. Standard statistical tests such as the Pearson Chi-square test will be used to characterize and evaluate the relationship between chemoresponsiveness and gene expression patterns. A total of 226 eligible patients will be enrolled from 10 US institutions. 85 patients have been enrolled. Clinical trial information: NCT01501487.
Intensity of end-of-life care among adolescents and young adults with cancer.
Authors: Jennifer W. Mack, Lie H. Chen, Robert Michael Cooper, Chun Chao
Journal: Journal of Clinical Oncology (2014)

9541 Background: Cancer is the leading disease-related cause of death among adolescents and young adults (AYAs), but little is known about the care that AYA patients with cancer receive at the end of life (EOL). Previous work suggests that younger adults may be at risk for receiving aggressive EOL care. However, prior work has focused on the over-65 population in Medicare, with younger adults defined as those closer to 65. Thus much remains unknown about the care that AYA patients receive at the EOL. Methods: We evaluated existing measures of EOL care intensity among 381 AYA patients with stage IV/disseminated cancer who received care in Kaiser Permanente Southern California (KSPC), an integrated health care delivery system, and died in the years 2001 to 2010. Patients were eligible for study if they were aged 15-39 at death. Patient characteristics and measures of EOL care intensity were evaluated using KPSC’s SEER-affiliated cancer registry and electronic medical records. Intense EOL care measures included chemotherapy use in the last 14 days of life, intensive care unit (ICU) care in the last 30 days of life, more than one emergency room (ER) visit in the last 30 days of life, and hospitalization in the last 30 days of life. We also evaluated a composite measure of medically intensive EOL care comprising any of the aforementioned measures. Results: Patients were aged 15-24 (23%), 25-34 (34%), and 35-39 (43%) at death; 50% were male and 48% were white (12% black, 12% Hispanic, 29% Asian, 1% other). Primary cancers included leukemia (25%), lymphoma (12%), colorectal (9%), lung/bronchus (8%), breast (7%), and bone/soft tissue (6%). 11% of patients received chemotherapy within 14 days of death. In the last 30 days of life, 17% of patients were admitted to the ICU; 48% had >1 ER visit; and 66% were hospitalized. Overall, 76% of subjects received at least one aspect of medically intensive EOL care. Conclusions: AYA patients frequently receive medically intensive EOL care, with more than three-quarters of patients receiving at least one aspect of aggressive EOL care. These findings suggest the need to better understand EOL needs and access to palliative care in this young population.
Trastuzumab administration in HER2-postive gastric or GEJ cancer: Analysis of clinical practice.
Authors: Anuj Kishor Patel, Michael K. Gibson, James Ohr, David Friedland, James D. Luketich, Ryan M. Levy, Jon M. Davison, Aatur D. Singhi, Reetesh K. Pai, Weijing Sun
Journal: Journal of Clinical Oncology (2014)

e17681 Background: The landmark ToGA study demonstrated a significant overall survival benefit in HER2-positive gastric cancer patients with the addition of trastuzumab to chemotherapy with cisplatin and either 5-flourouracil or capecitabine. Methods: We conducted a retrospective data analysis in patients diagnosed with HER2-positive gastroesophageal junction or gastric cancer in the University of Pittsburgh Cancer Center network between September 2005 and September 2013. Their clinical characteristics and treatment plans were reviewed. Results: Of the 78 HER2-positive patients diagnosed at our institution, 44 were considered appropriate for combination chemotherapy and trastuzumab by the criteria identified in the ToGA study. From these, the treatment courses for 34 patients were available. 30 patients (88.2%) received trastuzumab in combination with chemotherapy. Among these, only 7 patients (23.2%) received cisplatin with either 5-flourouracil or capecitabine. 11 patients (36.7%) received carboplatin and 8 patients (26.7%) received oxaliplatin in place of cisplatin. 13 patients (43.3%) received taxane-based regimens. Irinotecan was administered to 4 patients (13.3%). 2 patients (6.1%) proceeded on to maintenance therapy that included chemotherapy in addition to trastuzumab. Also, a number of patients received trastuzumab in either the neoadjuvant or adjuvant settings. Conclusions: The high rate of trastuzumab administration within our network highlights the importance of education and coordination in maintaining optimal treatment through a health system. However, a wide variety of chemotherapy regimens were utilized with trastuzumab in clinical practice, largely based on physicians’ own preference or judgment, without published data for these combinations. To ensure that such practice represents good quality of care, the role of trastuzumab in these different regimens and settings requires further study through prospective clinical trials.
NT-proBNP Goal Achievement Is Associated With Significant Reverse Remodeling and Improved Clinical Outcomes in HFrEF
Authors: Melissa A. Daubert, Kirkwood Adams, Eric Yow, Huiman X. Barnhart, Pamela S. Douglas, Susan Rimmer, Casey Norris, Lawton Cooper, Eric Leifer, Patrice Desvigne-Nickens, Kevin Anstrom, Mona Fiuzat, Justin Ezekowitz, Daniel B. Mark, Christopher M. O’Connor, James Januzzi, G. Michael Felker
Journal: JACC Heart Failure (2019)
Endothelium structure and function in kidney health and disease
Authors: Noemie Jourde-Chiche, Fadi Fakhouri, Laetitia Dou, Jeremy Bellien, Stéphane Burtey, Marie Frimat, Pierre-André Jarrot, Gilles Kaplanski, Moglie Le Quintrec, Vincent Pernin, Claire Rigothier, Marion Sallée, Veronique Fremeaux-Bacchi, Dominique Guerrot, Lubka T. Roumenina
Journal: Nature Reviews Nephrology (2019)
Referal for bone and soft tissue tumors: New pathway for resource constrained health care systems.
Authors: Samuel UWALE Eyesan, Oluwaseyi KAYODE Idowu, Obinna Mbah
Journal: Journal of Clinical Oncology (2014)

e21500 Background: Delay in diagnosis of bone and soft tissue tumours is associated with adverse outcome especially in malignant musculoskeletal tumours particularly in resource constrained environment. The study aims to identify referral pathway and factors associated with delay in diagnosis. Methods: We prospectively evaluated 67 patients presenting with bone and soft tissue tumour (of the extremities) to our service; to identify the referral pathways, and factors associated with delay in diagnosis. The study was conducted over a 12 months period in patients presenting with bone and soft tissue tumour in a specialist unit. Patients were interviewed and data collected included demographic details, duration of symptoms, source of referal, tumour size, histological diagnosis, treatment center attended before presentation and reasons for delay in diagnosis. Results: The patients reviewed (mean age 26.7) had duration of symptoms from 2 - 240 weeks. Patients with malignant tumours had mean duration of symptoms of 18.3 weeks and mean time interval to dignosis of 7.8 weeks. Patients with benign tumours had mean duration of symptoms of 39.7 weeks and mean time to dignosis of 8.5 weeks. There were five patterns of presentation identified based on the healthcare facility patients initially attended. While the duration of symptom was not significantly different within the groups, there was reduced mean time interval to dignosis in patients presenting directly into the unit. The referral pattern identified enabled us to develop a referral pathway/algorithm for the management of suspected bone and soft tissue tumours which may however require modification and re-evaluation. Conclusions: Delay in diagnosis for musculoskeletal tumour is still a problem. The need for early referral to a specialist in bone and soft tissue tumour unit is further enhanced by this study. We emphasize that approprate referral is a form of treatment. This referral pathway hopefully should be a guide for proper management in a resource-poor setting. It is however still subject to further modification and re-evaluation.
Chronic Myeloid Leukemia Italian Multicenter Observational Study (CML-IT-MOS): Clinical Characteristics of Chronic Myeloid Leukemia (CML) Patients Treated in Real-Life between 2012 and 2016 in 66 Italian Hematology Centers of the Gimema Study Group
Authors: Giorgina Specchia, Patrizia Pregno, Maura Nicolosi, Fausto Castagnetti, Bruno Martino, Massimo Breccia, Massimiliano Bonifacio, Fabio Stagno, Antonella Gozzini, Mario Tiribelli, Micaela Bergamaschi, Michele Pizzuti, Giovanni Caocci, Luigia Luciano, Pietro Leoni, Anna Guella, Franca Falzetti, Roberto Di Lorenzo, Fabio Saccona, Chiara Monagheddu, Francesco Albano, Fabrizio Pane, Giovannino Ciccone, Michele Baccarani, Giuseppe Saglio
Journal: Blood (2018)
Perioperative Glucose Control in Patients With Diabetes Undergoing Elective Surgery
Authors: Vinaya Simha, Pankaj Shah
Journal: JAMA (2019)

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Tumor expression levels of CSC markers in resectable non-small cell lung cancer.
Authors: Silvia Calabuig, Eloisa Jantus-Lewintre, Rut Lucas, Rosa Farras, Marta Usó, Eleonora Chakarova, Sandra Gallach, Miguel Martorell, Ana Blasco, Santiago Figueroa, Carlos Camps
Journal: Journal of Clinical Oncology (2014)

7562 Background: Cancer stem cells (CSCs) have been proposed as the driving force of tumorigenesis and the seeds of metastases. However, their existence and role remain a topic of intense debate. The purpose of this study is to analyze differentially expressed CSC genes from a large cohort of resectable NSCLC patients and its prognostic implications. Methods: mRNA was isolated from 188 frozen samples from resectable NSCLC patients (tumor and normal lung). The mRNA expression of OCT4, NANOG, SOX2, CD44, CD133, was analyzed by RTqPCR using hydrolysis probes. Relative expression levels were obtained using GUSB as endogenous gene and Pfaffl formulae. Statistical significance was considered at p<0.05. Results: Patient’s median age was 64 years [26-85], 87.8 % were males and 66 % presented PS= 0. Squamous histology represented a 45.9%. There were positive correlations (Spearman test) between the expression levels of the CD44 and OCT4 (p=0.002), OCT4 and NANOG (p<0.001) whereas no correlation were found between CD133 and the other CSC markers studied. Correlation analysis of gene expression values and clinico-pathologic characteristics of the cohort showed that the higher levels of CD44, OCT4 and NANOG were associated with poor differentiation grade (p=0.003, p=0.05, p=0.007). Clinico-pathological variables such as histology, PS, stage or smoking status show no association with the levels of expression of the analyzed genes. Kaplan-Meier curves show no statistical differences between groups (median as cut-off) for CD133, NANOG and OCT-4. Interestingly, higher levels of CD44 correlates with increased overall survival in our cohort of resected NSCLC patients (median 42.90 months vs NR, p=0.013). Conclusions: CD44 may play a role as prognostic biomarker in NSCLC. Our results are in concordance with recent findings regarding the relationship between increased levels of expression of CD44 and better overall survival for patients with resectable NSCLC. Therefore, further investigations of the role of CD44 in CSC maintenance and regulation are still needed. Supported in part by ISCIII grants PI12/02838, RD12/0036/0025, SEOM grant 2012.
Monoamine oxidase‐B inhibitors as potential neurotherapeutic agents: An overview and update
Authors: Rati Kailash Prasad Tripathi, Senthil Raja Ayyannan
Journal: Medicinal Research Reviews (2019)

Abstract Monoamine oxidase (MAO) inhibitors have made significant contributions and remain an indispensable approach of molecular and mechanistic diversity for the discovery of antineurodegenerative drugs. However, their usage has been hampered by nonselective and/or irreversible action which resulted in drawbacks like liver toxicity, cheese effect, and so forth. Hence, the search for selective MAO inhibitors (MAOIs) has become a substantial focus in current drug discovery. This review summarizes our current understanding on MAO‐A/MAO‐B including their structure, catalytic mechanism, and biological functions with emphases on the role of MAO‐B as a potential therapeutic target for the development of medications treating neurodegenerative disorders. It also highlights the recent developments in the discovery of potential MAO‐B inhibitors (MAO‐BIs) belonging to diverse chemical scaffolds, arising from intensive chemical‐mechanistic and computational studies documented during past 3 years (2015‐2018), with emphases on their potency and selectivity. Importantly, readers will gain knowledge of various newly established MAO‐BI scaffolds and their development potentials. The comprehensive information provided herein will hopefully accelerate ideas for designing novel selective MAO‐BIs with superior activity profiles and critical discussions will inflict more caution in the decision‐making process in the MAOIs discovery.
What is the economic value created by adding rituximab to chemotherapy in the United States from 1998 to 2013?
Authors: Mark D. Danese, Carolina M. Reyes, Michelle L. Gleeson, Marc Halperin, Sandra L. Skettino, Joseph Mikhael
Journal: Journal of Clinical Oncology (2014)

e17553 Background: Rituximab has become the standard in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). The incremental cost of adding rituximab to existing chemotherapy and the value of the life years saved have not been estimated at the population level. Methods: We constructed a population effectiveness model from 1998-2013. Age group, gender, and year-specific incidence rates for each cancer were estimated from the Surveillance, Epidemiology, and End Results (SEER) program. Incidence rates were multiplied by Census estimates to calculate total diagnosed patient counts. Utilization, survival and cost inputs were estimated using SEER Medicare merged data for patients diagnosed 1999-2009 and followed through 2010, extrapolated through 2013. First-line utilization of rituximab plus chemotherapy (R+Chemo) and Chemo Alone were calculated as a proportion of all diagnosed patients to estimate treated patient counts. Differences in mean survival between R+Chemo and Chemo Alone for each cancer were estimated using flexible parametric survival models. The incremental cost of R+Chemo versus Chemo Alone for each cancer was based on Medicare paid amounts for all Part A and B services using regression, accounting for censoring. Costs were computed over 72-months to capture short and long-term effects, and inflated to 2013 US dollars. The value of a life year saved ($90,941 in 2013 dollars) was based on published literature (Lee, et al. 2009). Monte Carlo sampling was used to estimate the 95% uncertainty intervals (UI). Results: Across all three cancers from 1998 to 2013, there were 280,819 cumulative life years saved (95% UI, 269,136-293,345). The additional total costs of care for R+Chemo were $33,525, $23,511, and $31,435 in DLBCL, FL, and CLL, respectively. Across all 3 tumors, the incremental direct medical cost of R+Chemo compared to Chemo Alone was $7.0 billion (95% UI $5.8-$8.2 billion), and the resulting economic value of the life years saved was $25.5 billion (95% UI $11.7-$69.1 billion). Conclusions: For DLBCL, FL and CLL patients treated with R+Chemo in the US from 1998-2013, 281,000 life years were saved that created a net economic value of $18.5 billion.
Safety and Efficacy of Tisagenlecleucel Treatment in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (r/r DLBCL) and No Evidence of Active Disease Following Bridging Chemotherapy in the JULIET Trial
Authors: Michael R. Bishop, Richard Thomas T. Maziarz, Edmund K. Waller, Christopher del Corral, Ranjan Tiwari, Özlem Anak, Rakesh Awasthi, Vadim V. Romanov, Stephen J. Schuster
Journal: Blood (2018)