tbuckley/cabot-search huggingface dataset:
Dynamic perspective of neutrophil-lymphocyte ratio in metastatic gastric cancer.
Authors: Antia Cousillas, Elena Gallardo Martin, Lidia Maria Vazquez Tunas, Iria Carou, Nazaret Quiroga, Cristina Azpitarte, Cristina Lopez Jato, Francisco Ramon Garcia Arroyo, Manuel Constenla
Journal: Journal of Clinical Oncology (2018)

e16095 Background: This study explores the prognostic value of a baseline and dynamic measure of neutrophil-lymphocyte ratio (NLR and dNLR) in metastatic gastric cancer (mGC), as well as chemotherapy (QT) response. NLR reflects the balance between host pro-tumor inflammatory response and immune status. Recent meta-analysis confirms prognostic value of baseline NLR, the only study which investigates the dynamic change after treatment is in resectable GC. It is necessary to explore the prognostic impact of dNLR for overall survival (OS) and QT response. Methods: 100 patients with mGC were retrospective reviewed from 2009 to 2017. Clinical and lab data were recorded. The optimal cut-off levels were defined as NLR = 3.67, ROC curve was performed. NLR was calculated as the absolute neutrophil count divided by the absolute number of lymphocyte count. NLR was measured baseline and after 2 cycles of QT. The dNLR was calculated as a subtraction between NLR after 2 cycles of CT and baseline (dNLR > 0: increase). QT regimen was decided according to physician choice. Radiological (Rx) response of tumor was based on RECIST criteria. Levels of these data were related with OS by Kaplan-Meier and compared by long-rank test, univariate and multivariate analysis were carried out. Results: Among 100 patients, mean age was 65.9 years old, 31.7% female and 79% had no comorbidity. Univariate analysis indicated NLR > 3.67 (8.06 vs 16.8 months, p = 0.005), dNLR > 0 (9.3 vs 16.7months, p = 0.02) were correlated with OS. Increase dNLR was related with Rx progression after two cycles, p = 0.044. Multivariate analysis indicated NLR > 3.67 (HR = 3.3, 95% CI: 1.85 – 5.99, p = 0.001) and dNLR > 0 (HR = 2.08, 95%CI: 1.20- 3.5, p = 0.008) were a poor factor for OS. Conclusions: High NLR ( > 3.67) and increase NLR after QT (dNLR > 0) were associated with worse outcomes in mGC. An increase of NLR was related with Rx progression disease. Dynamic measure of NLR provides further information to stratify patients in risk groups and guide us to treat them.
Minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) in newly diagnosed transplant eligible multiple myeloma (MM) patients: Results from the EMN02/HO95 phase 3 trial.
Authors: Stefania Oliva, Davine Hofste op Bruinink, Lucie ŘÍhová, Stefano Spada, Bronno van der Holt, Rossella Troia, Manuela Gambella, Lucia Pantani, Sara Grammatico, Milena Gilestro, Massimo Offidani, Rossella Ribolla, Monica Galli, Roman Hajek, Antonio Palumbo, Michele Cavo, Paola Omedè, Vincent van der Velden, Mario Boccadoro, Pieter Sonneveld
Journal: Journal of Clinical Oncology (2017)

8011 Background: MRD detection is a sensitive tool to measure response in MM. We assessed MRD by MFC in newly diagnosed MM patients (pts) enrolled in the EMN02/HO95 phase 3 trial. Methods: Pts were ≤65 years old and received Bortezomib-Cyclophosphamide-Dexamethasone (VCD) induction, intensification with Bortezomib-Melphalan-Prednisone (VMP) vs High-Dose-Melphalan (HDM) followed by stem cell transplant, consolidation with Bortezomib-Lenalidomide-Dexamethasone (VRD) vs no consolidation, and Lenalidomide maintenance. MRD analysis was performed in pts achieving at least a very good partial response (VGPR) before starting maintenance (after HDM, VMP or VRD) and during maintenance every 6-12 months; samples were centralized to 3 European labs. MFC was performed on bone marrow according to Euroflow-based methods (8 colors, 2 tubes) with a sensitivity of 10 -5 . Quality checks were performed to compare sensitivity and to show correlation between protocols (Hofste op Bruinink D ASH 2016 abstract 2072). Results: 316 pts were evaluable before maintenance: median age was 57 years, 18% (57/316) pts had ISS III and 22% (70/316) had high risk cytogenetic (HR-C) defined as having at least one among del17, t(4;14) or t(14;16); 63% (199/316) had received HDM and 37% (117/316) VMP; thereafter 51% (160/316) had received VRD. 76% (239/316) were MRD negative (MRD-) of whom 64% (153/239) received HDM vs 36% (86/239) VMP, with a median follow-up time of 30 months from MRD enrolment. 3-year PFS was 50% in MRD positive (MRD+) vs 77% in MRD- pts (HR: 2.87, p &lt; 0.001). Subgroup analyses were performed to evaluate the risk factors for MRD+ according to baseline characteristics and therapies: HR-C was the most important risk factor (HR 9.87, interaction-p = 0.001). Finally, 48% of MRD+ pts at pre-maintenance who had a second MRD evaluation after at least 1 year of lenalidomide became MRD-. Conclusions: MRD by MFC is a strong prognostic factor in MM pts receiving intensification with novel agents or transplant; lenalidomide maintenance further improved depth of response; HR-C is the most important prognostic factor in MRD+ pts. Clinical trial information: NCT01208766.
Laparoscopy-assisted versus open D2 distal gastrectomy for advanced gastric cancer: Five year overall survival and morbidity results from a randomized phase II multicenter clinical trial (COACT 1001).
Authors: Young Woo Kim, Byung-Ho Nam, Young-Joon Lee, Youngkyu Park, Sang Eog Lee, Oh Jeong, Jun Ho Lee, Ki Young Yoon, Sang-Ho Jeong, Oh Kyoung Kwon, Taebong Kim, Wansik Yu, Young sook Kim, Mira Han, Susie Kim, Keun Won Ryu
Journal: Journal of Clinical Oncology (2018)

4041 Background: For advanced gastric cancer (AGC), D2 gastrectomy is the standard treatment. However, a laparoscopic D2 gastrectomy(LG) is technically challenging surgery. Our previous report of COACT 1001 study, which is randomized phase II study to evaluate the feasibility of LG compared with open surgery(OG) for AGC, showing primary endpoint of non-compliance of lymph node dissection and three-year disease-free survival supported role of LG for AGC. Herein we report five-year overall and disease-free survival outcome of the study. Methods: Patients with cT2-T4a and cN0-2 (AJCC 7th staging system) distal gastric cancer were randomly but not blindingly assigned to LG or OG groups. Patients were followed up for recurrence and survival for 5 years. Results: Between Jun 2010 and Oct 2011, 204 patients were enrolled and underwent either LADG (n = 105) or ODG (n = 99). Of those, 196 patients (100 in LADG and 96 in ODG) were included in the intention-to-treat analysis. There were no significant differences in the five- year overall survival between LG and OG groups (85.1% vs 84.1%, respectively; p = 0.749). In the subgroup analysis, five-year overall survival was not different in between the groups according to the clinical stage (stage I: 95.7 % vs 95.5 %; p = 0.988, stage II: 96.1 % vs 84.6 %; p = 0.057, stage III: 48.3 % vs 74.1 %; p = 0.156) and pathological stage (stage I: 97.5 % vs 94.4 %; p = 0.512, stage II: 100 % vs 90.8 %; p = 0.099, stage III: 48.7 % vs 72.7 %; p = 0.151, stage IV: 100 % vs 0 %; p = 0.18). Five-year disease-free survival also was not significantly different between two groups (74.5 % vs 78.7 %, respectively; p = 0.604). The trend of overall and disease-free survival was favorable for LG in stage II but OG in stage III. Conclusions: LG was feasible for AGC based on the five-year overall and disease-free survival rate. Further research should be done in large scale for stage III gastric cancer. Clinical trial information: NCT01088204.
TCT-317 Impact of Coronary Artery Disease on Transcatheter Aortic Valve Replacement Outcome
Authors: Paolo Olivares, Franco Fabbiocchi, Stefano Galli, Giuseppe Calligaris, Luca Grancini, Giovanni Teruzzi, Stefano De Martini, Paolo Mario Ravagnani, Daniela Trabattoni, Antonio Bartorelli
Journal: Journal of the American College of Cardiology (2018)
A meta-analysis of randomized controlled trials for efficacy and safety of vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) adjuvant therapy in high-risk renal cell cancer (RCC).
Authors: Irbaz Bin Riaz, Saad Malik, Muhammad Husnain, Qurat Ul Ain Riaz Sipra, Warda Faridi, Farva R. Gondal, Hao Xie, Siddhartha Yadav, Manish Kohli
Journal: Journal of Clinical Oncology (2018)

4567 Background: Three large randomized placebo controlled trials (RCTs) (ASSURE, S-TARC, PROTECT) with adjuvant VEGF-TKIs in high risk RCCs have provided variable results for improving disease free survival (DFS) with concerns for increased toxicity. We performed a meta-analysis of these trial results to asses a risk-benefit for adjuvant post-op treatments in high risk RCC patients by assessing reported disease free survival (DFS) and toxicity endpoints. Methods: A generic variance weighted random effects model was used to derive estimates for DFS and common side effects in the three trials. A separate analysis was performed for Sunitinib alone because of its FDA approval. Heterogeneity was assessed with Cochrane Q -statistic and was quantified with I2test. I2> 75% was consistent with a high degree of heterogeneity. Results: The three RCTs involved 4096 patients. Adjuvant therapy with TKIs yielded no significant improvement in DFS or OS as compared to placebo (DFS HR = 0.92, 95% CI 0.82-1.04 and OS HR = 1.00, 95% CI 0.86-1.17). Separate analysis of DFS in sunitinib vs placebo did not show any benefit (2 studies, N = 1909; HR = 0.90, 95% CI 0.67-1.19). Use of TKIs was associated with significantly increased risk of drug toxicity. Increased risk of grade 3 or 4 adverse events (RR = 2.73, 95% CI 2.51-2.97), diarrhea (RR = 14.57, 95% CI 7.93-26.79), fatigue (RR = 3.63, 95% CI 2.13-6.18), hypertension (RR = 3.95, 95% CI 3.18-4.91) and palmar/plantar dysesthesia (RR = 21.4, 95% CI 12.91-35.47) was observed. Conclusions: No OS or DFS benefit for VEGF TKIs including for Sunitinib was observed in this meta-analysis, while there was a significantly increased risk of toxicity in greater than half of the patient population. Subgroup analyses based on age, sex, pharamacokinetics, pharmacogenomics may help to identify potential candidates. Analysis from ongoing adjuvant TKI trial results (SORCE,ATLAS,2810) and immunotherapy (IMMotion,Keynote-564,checkmate 914) are awaited and may provide more refinement in selecting high risk RCC candidates with favorable benefit-risk ratios for post op drug therapies.
Big data for supporting precision medicine in lung cancer patients.
Authors: Maria Torrente, Ernestina Mensalvas, Fernando Franco, Alejandro Rodriguez-Gonzalez, Virginia Calvo, Maria Auxiliadora Brenes, George Paliouras, Mariano Provencio-Pulla
Journal: Journal of Clinical Oncology (2018)

e20546 Background: Lung cancer is a heterogeneous disease, with characteristics that differ between patients and even among regions of the same tumor. One of the main challenges of precision medicine is the integration and analysis of clinical data. Electronic Health Records (EHR) are comprised of clinical notes and medical reports written in free text containing information from each patient that remains stored in the EHR system unused. Our aim is to exploit and integrate this information to improve lung cancer management using Big Data technologies. Methods: Clinical data from 706 patients diagnosed with lung cancer from 2012 to 2017 and treated at the Medical Oncology Department at Puerta de Hierro University Hospital was obtained. A total of 7,146 clinical reports and 171,878 clinical notes were analyzed, post-anonymization. Our method is based on the execution of a framework built on top of Apache UIMA, a framework that analyses large volumes of unstructured information and ingests the text provided by the hospital and performs Natural Language Processing tasks to structure the information and allows performing complex queries and retrieve new knowledge. A descriptive analysis of the population and Kaplan Meier tests were performed. Results: An initial subset of variables was analyzed and survival curves were obtained. Long survivors were considered those patients still alive after two years since diagnosis. More than half of our patients are long survivors. Correlation was observed between presence of risk factors, such as dyslipidemia, high blood pressure, smoking habit and COPD, and significant decrease in survival. Survival in females was significantly higher than in males, despite the smoking habit, stage and comorbidities; the age of diagnosis in all stages was predominantly 55-65 years old. Conclusions: This process is capable of processing large amounts of data (thousands of reports from hundred of patients) and provide a unified knowledge base with all the information from the patients. We believe with this information, physicians will be able not only to retrieve complex information about their patients but also create predictive models that will lead to a personalize medicine approach.
Relationship between oncogenic mutations (<i>RAS</i>, <i>BRAF</i> and <i>PIK3CA</i>) and tumor location and prognosis in colorectal cancer.
Authors: Daisuke Inagaki, Manabu Shiozawa, Tetta Satoyoshi, Yosuke Atsumi, Masaaki Murakawa, Keisuke Kazama, Akio Higuchi, Naoto Yamamoto, Soichiro Morinaga, Yasushi Rino, Munetaka Masuda, Yohei Miyagi
Journal: Journal of Clinical Oncology (2017)

e15109 Background: Several studies have reported that right-sided colon cancers (RCC) and left-sided colorectal cancers (LCRC) differ in several factors including genetic features. We investigated the difference in clinicopathological characteristics and oncogenic mutation status between patients with RCC and LCRC in all stages and assessed outcome. Methods: This study was a prospective, observational study. Patients were recruited from November 2014 to February 2016. Formalin-fixed paraffin-embedded tissue blocks were collected and DNA wes extracted from tissue sections from 227 cases. There was no double cancer. Mutations in KRAS, NRAS, HRAS, BRAF and PIK3CA were detected by next-generation DNA sequencer. Tumors from cecum to transverse colon were defined as RCC, and tumors from descending colon to rectum were defined as LCRC. The median follow-up period was 521 days. Results: KRAS, NRAS, BRAF and PIK3CA mutations were present in 95 patient (41.9%), 7 patients (3.1%), 10 patients (4.4%) and 23 patients (10.1%) respectively, and there was no HRAS mutation in all patients. RCC was 68 patients and LCRC was 159 patients. Poorly differentiated adenocarcinoma and mutinous adenocarcinoma were significantly more frequent in RCC compared to LCRC (P = 0.031). KRAS mutations were detected in 37 patients with RCC (54.4%) and in 58 patients with LCRC (36.5%). BRAF mutations were detected in 7 patient with RCC (10.3%) and in 3 patients with LCRC (1.9%). KRAS and BRAF mutation in RCC were significantly more frequent than in LCRC (P = 0.012 and P = 0.005, respectively). The incidence of NRAS and PIK3CA mutation was no difference between two groups. In all patients, overall survival was evaluated. On univariate Cox regression analysis, BRAF mutation was associated with significantly poorer overall survival than BRAF wild type (HR = 4.831, P = 0.013). Other oncogenic mutation status and tumor location weren’t associated with overall survival. Conclusions: KRAS and BRAF mutation were more frequent in the patients with RCC compared to those with LCRC in all stages. This study suggested BRAF mutation correlated with poor outcomes in patients with colorectal cancer.
HMGB1 Accelerates Regeneration of Multiple Tissues By Transitioning Stem Cells to GAlert
Authors: Geoffrey Lee, Ana Espirito Santo, Stefan Zwingenberger, Emilie Venereau, Lawrence Cai, Thomas Vogl, Marc Feldmann, Nicole Horwood, Marco Bianchi, James Chan, Jagdeep Nanchahal
Journal: Blood (2017)
Rising proportion of young individuals with rectal and colon cancer.
Authors: Pashtoon Murtaza Kasi, Faisal Shahjehan, Jordan Cochuyt, Zhuo Li, Dorin Colibaseanu, Amit Merchea
Journal: Journal of Clinical Oncology (2018)

e13575 Background: Recent trends have identified increasing number of young individuals with rectal and colon cancers. These individuals, who are less than the age of 50 years, in most instances would not meet the current screening guidelines. We aimed at reporting the characteristics and the trend of rising proportion of young individuals being diagnosed with rectal and colon cancers. Methods: This study included 3,381 colorectal cancer patients from Mayo Clinic Cancer registry between the years 1972 to 2017 who were diagnosed with colorectal cancer under age 50. Patient and cancer characteristics were described. Percentage of each age group was calculated against the total population diagnosed of colorectal cancer of each year. Cochran-Armitage trend test was used to see if the change in percentage diagnosed less than 50 years old had a significant trend over the years. Linear regression model was fit to estimate the percentage change per year when the trend was approximately linear. All tests were two-sided with alpha level set at 0.05 for statistical significance. Results: The percentage of patients diagnosed of rectal cancer or colon cancer at different age category over the years showed a rising trend for individuals less than the age of 50 years. The percentage of patients diagnosed with rectal cancer under age of 50 increased at a rate of 0.26/year (P < 0.001), however, the percentage of patients diagnosed with colon cancer under age of 50 rose but did not change following a linear pattern (p = 0.296). Conclusions: Our study affirms the rising proportion of colorectal cancers seen in young individuals at academic centers; with a linear ongoing rise of rectal cancers in particular. This would have implications on current screening recommendations for colon and rectal cancers.
Recent progress and challenges in screening and characterization of UGT1A1 inhibitors
Authors: Xia Lv, Yangliu Xia, Moshe Finel, Jingjing Wu, Guangbo Ge, Ling Yang
Journal: Acta Pharmaceutica Sinica B (2018)

Uridine-diphosphate glucuronosyltransferase 1A1 (UGT1A1) is an important conjugative enzyme in mammals that is responsible for the conjugation and detoxification of both endogenous and xenobiotic compounds. Strong inhibition of UGT1A1 may trigger adverse drug/herb–drug interactions, or result in metabolic disorders of endobiotic metabolism. Therefore, both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have recommended assaying the inhibitory potential of drugs under development on the human UGT1A1 prior to approval. This review focuses on the significance, progress and challenges in discovery and characterization of UGT1A1 inhibitors. Recent advances in the development of UGT1A1 probes and their application for screening UGT1A1 inhibitors are summarized and discussed in this review for the first time. Furthermore, a long list of UGT1A1 inhibitors, including information on their inhibition potency, inhibition mode, and affinity, has been prepared and analyzed. Challenges and future directions in this field are highlighted in the final section. The information and knowledge that are presented in this review provide guidance for rational use of drugs/herbs in order to avoid the occurrence of adverse effects via UGT1A1 inhibition, as well as presenting methods for rapid screening and characterization of UGT1A1 inhibitors and for facilitating investigations on UGT1A1ligand interactions.
Achievement of a negative minimal residual disease state after hypomethylating agent therapy in older patients with AML to reduce risk of relapse.
Authors: Prajwal Boddu, Jeffrey L. Jorgensen, Hagop M. Kantarjian, Gautam Borthakur, Tapan M. Kadia, Naval Guastad Daver, Yesid Alvarado, Naveen Pemmaraju, Prithviraj Bose, Kiran Naqvi, Musa Yilmaz, Sherry Pierce, Mark Brandt, Courtney Denton Dinardo, Elias Jabbour, Guillermo Garcia-Manero, Jorge E. Cortes, Farhad Ravandi
Journal: Journal of Clinical Oncology (2017)

7018 Background: Persistence of minimal residual disease (MRD) post therapy is a powerful predictor of outcome in patients with AML treated with traditional cytarabine and anthracycline based regimens. The clinical relevance of MRD in the context of hypomethylating agents has not been evaluated extensively. Methods: Among 194 patients with AML treated with single agent azacytidine, decitabine, or gaudecitabine, 116 (median age 76, range 60 - 92) had MRD analysis performed on bone marrow specimens obtained at time of assessment of response or thereafter; among them 69 (59%) achieved either morphologic complete remission (CR) or CR with incomplete recovery of platelets (CRp) or counts (CRi), and 61 (53%) had evaluable MRD data; MRD was assessed using an 8-color flow panel, with a detection sensitivity of 0.01%. Results: Median cycles to achieving response was 2 (range, 1-6). Sixty one patients had evaluable MRD data at the time of response, of whom 19 (28%) became MRD negative (-). This was associated with a reduced cumulative risk of relapse (p = 0.012) but did not translate to an improved relapse-free survival (RFS; p = 0.17) or overall survival (OS; p = 0.79) due to high frequency of non-relapse deaths (attributable to comorbidities and infections) in the MRD- group. Patients who achieved a MRD- state at the time of achieving response had a higher mortality [5/8 (62%)] when compared with those who achieved a MRD- state in subsequent cycles [1/13 (7.6%); p = 0.01], resulting in an inferior OS (6.2 months (mo) vs 20 mo, p = 0.012). Similarly, achieving negative MRD at CR and at any time up to 3 months post response was not associated with improved RFS or OS despite a lower cumulative risk of relapse (p = 0.045). There was no impact of MRD, on OS, whether the MRD- state was achieved after 1 st , 3 rd or 6 th cycle of therapy. Association between depth of MRD response at time of remission and RFS was borderline significant (p = 0.08). On multivariate analysis, response (CR vs CRi/CRp), but not a negative MRD, was predictive for RFS or OS. Conclusions: In this cohort of older AML patients treated with hypomethylating agents, achieving a MRD- state was associated with a reduced risk of relapse but not improved RFS or OS.