tbuckley/cabot-search huggingface dataset:
Biomarkers for immunotherapy: Results from the analysis of an HLA-status double-blind, biologically randomized phase II study of five therapeutic epitope-peptides with oxaliplatin-based chemotherapy as first-line therapy for advanced colorectal cancer (FXV study).
Authors: Shoichi Hazama, Yusuke Nakamura, Hiroaki Tanaka, Ko Tahara, Ryoichi Shimizu, Fumiaki Sugiura, Kiyotaka Okuno, Koichiro Sakata, Kazuhiko Yoshimatsu, Hiroko Takenouchi, Ryouichi Tsunedomi, Yuka Inoue, Shinsuke Kanekiyo, Yoshitaro Shindo, Shigefumi Yoshino, Hirokazu Shinozaki, Hiroyuki Furukawa, Tomonobu Fujita, Yutaka Kawakami, Masaaki Oka
Journal: Journal of Clinical Oncology (2014)

3038 Background: Biomarkers to predict the efficacy of immunotherapy have been awaited. A phase II study of five therapeutic epitope-peptides with oxaliplatin-based chemotherapy as first-line therapy for advanced colorectal cancer (CRC) using five novel HLA-A*2402-binding peptides derived from not only three oncoantigens, RNF43, TOMM34, and KOC1 but also antiangiogenic cancer vaccine targeting VEGFR1 and VEGFR2 was presented at 2013 ASCO Oral Abstract Session (No. 3006). We further explored the predictive biomarker for the response to immunotherapy. Methods: Between February 2009 and November 2012, 96 chemotherapy naïve CRC pts were enrolled in this study. Each of the five peptides (3 mg each) was mixed with 1.5 ml of IFA and subcutaneously administered weekly for 12 weeks and after then biweekly. Chemotherapy was performed simultaneously as mFOLFOX6 (n=93) or XELOX (n=3) with bevacizumab (n=5). All enrolled pts had received the therapy without knowing HLA-A status double-blindly, and the HLA-A genotypes were key-opened at analysis point. Pretreatment serum IL-6 and CRP, lymphocyte%, neutrophil/lymphocyte (N/L) ratio and comprehensive expression profiles microRNA of the tumor were evaluated between HLA-A*2402 positive (treatment) group and HLA-A*2402 negative (placebo) group. Results: IL-6 <1.0 (pg/ml) and Lymphocyte% >15% were the significant predictive markers (p=0.007, 0.034) for the long survival, which was observed only in HLA-A*2402 positive group. In the patients with IL-6 <1.0 or lymphocyte% >15, obvious trend to long survival in HLA-A*2402 positive group was observed. MiR-a and miR-b (will be opened in the meeting) were selected for the predictive biomarkers. Patients with low miR-a (<550) or low miR-b (<350) were significantly survived longer than high miR groups (p=0.002, 0.012), which significances were observer only in HLA-A*2402 group. Conclusions: Serum IL-6, Lymphocyte%, and miRs expression were the predictive biomarkers for the response to peptides vaccine and the selection of patients. Clinical trial information: UMIN000001791.
Treatment of distal rectal cancer with preoperative intensity modulated radiation therapy (IMRT) combined with chemotherapy and transanal endoscopic microsurgery: 6-year results of 16 patients.
Authors: Albert S. DeNittis, John Marks, Joe Frenkel, Erik Zeger, Gerald J. Marks
Journal: Journal of Clinical Oncology (2014)

e14554 Background: Preoperative chemoradiotherapy is currently the standard of care for patients with distal rectal cancer. With intensity modulated radiation therapy (IMRT), more conformal doses of radiation can be delivered to tumor while sparing normal tissue. It is our intent to present updated data showing five-year follow up on patients treated concurrently with chemotherapy and IMRT reporting on local control, overall survival, and toxicity Methods: From April 2007 to February of 2014 a study of 16 patients at Lankenau Medical Center were treated for distal rectal cancer using IMRT. Patients staged from T1- T3 N0M0 received 5580 cGy to the pelvis using a nine field plan to tumor, involved and uninvolved lymph nodes. The median age was 64. All patients received 5FU based chemotherapy. All patients then went on to surgery 8-12 weeks following neoadjuvant therapy. All sixteen patients had undergone full thickness local excision via transanal endoscopic microsurgery (TEM). Chemotherapy (FOLFOX) was given to three patients adjuvently and one patient received xeloda. Patients were analyzed for local control (LC), median survival (MS), overall survival (OS), and toxicity. Results: The median follow-up was 47 months (range 3-72 months). Complete pathological response was achieved in five patients, and partial response was achieved in 11 pateints. Two patients had local recurrence (12.5%) and no patients progressed with distant metastatic disease. Both patients were re-irradiated and had undergone surgical salvage. All patients are currently no evidence of disease with an OS at six years of 100% with a MS of 42 months. Toxicity was acceptable with only one grade 2 toxicity (diarrhea), and two patients with grade 1 neutropenia. All patients were free of diversion and stoma. Conclusions: With six years of follow-up data, our experience has shown that neoadjuvant chemoradiotherapy with IMRT followed by TEM to treat rectal cancers in the distal third is well tolerated and effective. Local excision may provide excellent tumor control in properly chosen patients.
Candida Endocarditis after TAVR
Authors: Thierry Carrel, Balthasar Eberle
Journal: New England Journal of Medicine (2019)

A 76-year-old man with a history of heart failure presented with shortness of breath and fever 9 months after transcatheter aortic-valve replacement. Blood cultures grew Candida parapsilosis. A video shows findings of prosthetic-valve endocarditis on echocardiography.
Сapecitabine with cisplatin or with oxaliplatin in first-line chemotherapy in patients with metastatic gastric carcinoma (mGC): Single-center experience.
Authors: Mekhri Narimanov, Mikhail Fedyanin, Varlam Zarkua, Alexey Tryakin, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2014)

e15033 Background: Cisplatin, capecitabine, and oxaliplatin are active agents for treatment of mGC. We underwent analysis of efficacy and toxicity of douplets (CX and XELOX) which were used in our department as a first line chemotherapy in patients with mGC. Methods: Pts with metastatic gastric carcinoma were nonrandomly allocated to XELOX regimen (oxaliplatin 75 mg/m2 i.v. day 1, capecitabine 2000 mg/m2 days 1-14) or CX regimen (cisplatin 75 mg/m2 i.v. day 1, capecitabine 2000 mg/m2days 1-14 ). Up to 6 cycles were provided every 3 weeks. Results: From 2008 to 2013, 71 pts were treated (XELOX–27 pts, CX–44 pts). Pts characteristics were similar in both groups (see in table). Median number of cycles in both groups was 5 (range, 1-6). Grade 3-4 toxicity (per cycle) in XELOX and CX groups were neutropenia 14,9% and 16,1%, deep venous thrombosis – 1% and 0%, diarrhea – 4.1% and 7,4%, stomatitis – 2.4% and 2,2%, infection – 0%, anemia 5,1% and 13,5% pts, peripheral neurotoxicity 3(11,1%) and 0%, respectively. No toxic deaths were observed. Objective response rate in XELOX and CX groups were 37% and 17,5%, median PFS - 7,4 months and 5,4 months (HR 1,76 95% CI 1,18-3,39; p=0.01), median OS - 11,8 months and 9,3 months (HR 2,0 95% CI 1,02-3,02, p=0.04), respectively. Conclusions: Combination of capecitabine and oxaliplatin are more effective than combination of capecitabine and cisplatin. Safety profile of both regimens are similar. Regimens chemotherapy XELOX CX N. of pts 27 44 Median age 52 (39-66) 51 (24-74) ECOG 2/1/0 6/20/1 11/31/2 Male/female 19/8 18/26 Metastatic sites: Liver 14 (51.8%) 25 (56.8%) Subclavian lymph nodes 2 (7,4%) 5 (11,3%) Peritoneum 6 (22,2%) 7 (15,9%) Retroperitoneal lymph nodes 12 (44,4%) 19 (43,1%) Ovarii 3 (11.1%) 4 (9%)
<i>KRAS</i> mutations: Does ethnicity play a role?
Authors: Itrat Mehdi, Essam Abdulmonem, Bassim J. Al Bahrani
Journal: Journal of Clinical Oncology (2014)

e14628 Background: v-Ki-ras2 Kirsten rat sarcoma (KRAS) mutations are frequently detected in colorectal cancer (CRC) and non-small cell lung cancer (NSCLC), having significant and pertinent therapeutic and prognostic implications. A relatively higher rate of mutations observed in NSCLC among Asians, a reflection of ethnic influence. The ethnic variation for KRAS mutations in CRC, is much less evaluated. The aim of this study was to assess the KRAS status among CRC patients in Oman and to compare it with reported regional and international data. Methods: This is a retrospective observation study. Patients with confirmed histopathological diagnosis of CRC and known KRAS status were identified from the patient's electronic medical records. Patients with mutations considered as mutant type (MT), and others with no detected mutations regarded as wild type (WT). Results: A total 100 Omani patients with CRC had been tested for KRAS status, the mean age was 47.5 years (range 22-79years) with 53% male and 47% female. KRAS mutation was detected in 31 patients (MT) (31%), while 69 patients (69%) had no mutation (WT). Conclusions: Determination of KRAS mutation status has been suggested to be included in the management algorithm of CRC. Data from USA showed KRAS mutation rate slightly higher among African Americans compared to Caucasians (47% vx.43%). The European data showed mutation rate in Netherland (37%), Germany (39%) and Slovenia (46%). Reports from Asia revealed lower rates; Thailand (23%), Taiwan (27%), and South Korea (27%). Few data have been reported from Middle East and Arab ethnicity. A report from Saudi Arabia showed 32% mutation rate. Our study showed less mutation rates than Western data, but similar results from our neighboring Saudi Arabia. Further large scale studies are needed within our region to evaluate the rate of KRAS mutation, and to validate the ethnic variation and its subsequent implications.
Abstract 18667: Impact of Direct Contact Force Measurement on Electrical Reconnections after Circumferential Pulmonary Vein Isolation for Atrial Fibrillation Using a Contact Force-Sensing Catheter
Authors: Kohki Nakamura, Shigeto Naito, Takehito Sasaki, Kentaro Minami, Masahiro Nakano, Koji Kumagai, Nobusada Funabashi, Yoshio Kobayashi, Shigeru Oshima
Journal: Circulation (2014)

Purpose: To prospectively evaluate the incidence of pulmonary vein (PV) reconnections (PVRs) and identify predictors of PVRs after circumferential PV isolation (CPVI) using a contact force (CF)-sensing ablation catheter. Methods: Sixty-five patients (51-males; 61±10 years) undergoing an initial CPVI were studied. Both the right and left CPVI lines were divided into 12 segments and multiple regression models were used to predict PVRs in the four regions (each including 6 segments), the anterior and posterior RPVs and LPVs (A-RPVs, P-RPVs, A-LPVs, and P-LPVs). Each radiofrequency application was delivered with 15-30W for &lt;30s along the P-LPVs and 30-40W for 40-60s along the others. Results: In 63 reconnected gaps, the right-PVs had more gaps in the anterior and posterior carina, while the left-PVs had more in the posterior carina than elsewhere, respectively (P&lt;0.05). The P-RPVs and P-LPVs had significantly more gaps than the A-LPVs (17 A-RPVs, 21 P-RPVs, 6 A-LPVs, and 19 P-LPVs; P&lt;0.05). The mean CF in the A-RPVs and P-RPVs (odds ratios (ORs), 0.916 and 0.854; P=0.014 and &lt;0.001, respectively) and Force-Power-Time Index (FPTI) in the A-LPVs (OR, 0.99; P=0.012) were significant negative predictors of PVRs. According to the receiver operating characteristics analysis, at optimal cutoffs of mean CFs of 18g (A-RPVs) and 12g (P-RPVs), and FPTI of 36,737g.W.s (A-LPVs), the sensitivity and specificity for predicting PVRs were 81.3% and 61.9%, 71.3% and 52.9%, and 58.6% and 100%, respectively. Conclusions: The carina regions can be common sites for PVRs despite a higher CF and FPTI. An optimal CF and FPTI may be needed to prevent PVRs during an initial CPVI, especially in the RPVs and A-LPVs.
Determining efficacy and side effects from concurrent use of chemotherapy and radiation therapy for the management of adult solid tumors.
Authors: Cynthia Sinha Anderson, Reecca Quinones, Michael Ray Olson
Journal: Journal of Clinical Oncology (2014)

e17640 Background: For adults diagnosed with solid tumors, treatment can combine the use of chemotherapy and radiation therapy (RT). Absence of prospectively gathered data on drug-radiation efficacy or side effects can alter the treatment course and options for patients. We sought to determine both the availability and the ease of locating data on drug-radiation therapy interactions for clinical efficacy and toxicity. Methods: We identified 42 drugs approved for the management of solid tumors in adults as of July 2013. Excluded were drugs used for the management of leukemia, anti-hormonal agents, and bone strengthening agents. Sources included a PubMed search for published literature between 1970-2013, chemotherapeutic agent package inserts, drug informational websites, and personal communication with drug company pharmacists including relevant studies from their own searches. Results: A PubMed literature search on drug-radiation efficacy and toxicity yielded 49 reports on 36 (86%) agents. 41 (86%) were from clinical trials and 7 (14%) from case reports. 41 agents had available package inserts, 16 (38%) with clear guidelines on its interactions with RT, 11 (26%) with unclear guidelines, and 14 (34%) with no information. 21 (50%) of drug websites had relevant information. 37 (88%) of drug pharmacists responded to inquiry requests. Only 4 (9%) recommended usage of their drug during RT, 17 (41%) did not recommend concurrent therapy, and 21 (50%) of respondents had no relevant data. Of all studied agents, 6 (14%) had no data available from any source. Conclusions: This study addresses a common and practical problem facing medical and radiation oncologists in the management of adult solid malignancies. For the majority of agents, data are either not clear or easily available or for administration with radiation therapy. Clinical implications include breaks in systemic therapy, avoidance of radiation therapy, or exposure to unquantifiable side effects. As oncologic treatment options continue to develop and as patients may face multiple lines of therapy throughout their disease course, this issue requires greater attention during prospective drug testing and clinical trial design.
Evaluation of All Cause of Death after High Dose Chemotherapy and Autologous Stem Cell Transplant in Hodgkin Lymphoma and Non-Hodgkin Lymphoma
Authors: Danielle Roberts, Subir Goyal, Zhao Chang, Christopher R Flowers, Mary Jo Lechowicz, Amelia Langston, Edmund K. Waller, Sagar Lonial, Pamela Allen, Kristie A. Blum, Jean L. Koff, Jonathan L Kaufman, Ajay K Nooka, Michael Graiser, Cecilia Rosand, Alexandra Palmer, Nassoma Bumpers, Catherine Fenner, Joel O Andrews, Caleb J. Raine, Jonathon B. Cohen
Journal: Blood (2018)
Assessment of Use of Combined Dextromethorphan and Quinidine in Patients With Dementia or Parkinson Disease After US Food and Drug Administration Approval for Pseudobulbar Affect
Authors: Michael Fralick, Chana A. Sacks, Aaron S. Kesselheim
Journal: JAMA Internal Medicine (2019)

In 2010, the US Food and Drug Administration (FDA) approved a combination of dextromethorphan hydrobromide and quinidine sulfate for the treatment of pseudobulbar affect after studies in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This medication, however, may be commonly prescribed in patients with dementia and/or Parkinson disease (PD).To investigate the prescribing patterns of dextromethorphan-quinidine, including trends in associated costs.This population-based cohort study of patients prescribed dextromethorphan-quinidine used data from 2 commercial insurance databases, Optum Clinformatics Data Mart and Truven Health MarketScan. The Medicare Part D Prescription Drug Program data set was used to evaluate numbers of prescriptions and total reported spending by the Centers for Medicare & Medicaid Services. Patients were included if they were prescribed dextromethorphan-quinidine from October 29, 2010, when the drug was approved, through March 1, 2017, for Optum and December 31, 2015, for Truven. Data were analyzed from December 1, 2017, through August 1, 2018.The proportion of patients prescribed dextromethorphan-quinidine with a diagnosis of MS, ALS, or dementia and/or PD, as well as the number of patients with a history of heart failure (a contraindication for the drug).In the commercial health care databases, 12 858 patients filled a prescription for dextromethorphan-quinidine during the study period. Mean (SD) age was 66.0 (18.5) years, 66.7% were women, and 13.3% had a history of heart failure. Combining results from both databases, few patients had a diagnosis of MS (8.4%) or ALS (6.8%); most (57.0%) had a diagnosis of dementia and/or PD. In the Medicare Part D database, the number of patients prescribed dextromethorphan-quinidine increased 15.3-fold, from 3296 in 2011 to 50 402 in 2016. Reported spending by Centers for Medicare & Medicaid Services on this medication increased from $3.9 million in 2011 to $200.4 million in 2016.Despite approval by the FDA for pseudobulbar affect based on studies of patients with ALS or MS, dextromethorphan-quinidine appears to be primarily prescribed for patients with dementia and/or PD.
<i>In vitro</i> and <i>in vivo</i> characterization of <i>Clostridium scindens</i> bile acid transformations
Authors: Solenne Marion, Nicolas Studer, Lyne Desharnais, Laure Menin, Stéphane Escrig, Anders Meibom, Siegfried Hapfelmeier, Rizlan Bernier-Latmani
Journal: Gut Microbes (2018)

The human gut hosts trillions of microorganisms that exert a profound influence on human biology. Gut bacteria communicate with their host by secreting small molecules that can signal to distant organs in the body. Bile acids are one class of these signaling molecules, synthesized by the host and chemically transformed by the gut microbiota. Among bile acid metabolizers, bile acid 7-dehydroxylating bacteria are commensals of particular importance as they carry out the 7-dehydroxylation of liver-derived primary bile acids to 7-dehydroxylated bile acids. The latter represents a major fraction of the secondary bile acid pool. The microbiology of this group of gut microorganisms is understudied and warrants more attention. Here, we detail the bile acid transformations carried out by the 7-dehydroxylating bacterium Clostridium scindens in vitro and in vivo. In vitro, C. scindens exhibits not only 7α-dehydroxylating capabilities but also, the ability to oxidize other hydroxyl groups and reduce ketone groups in primary and secondary bile acids. This study revealed 12-oxolithocholic acid as a major transient product in the 7α-dehydroxylation of cholic acid. Furthermore, the in vivo study included complementing a gnotobiotic mouse line (devoid of the ability to 7-dehydroxylate bile acids) with C. scindens and investigating its colonization dynamics and bile acid transformations. Using NanoSIMS (Nanoscale Secondary Ion Mass Spectrometry), we demonstrate that the large intestine constitutes a niche for C. scindens, where it efficiently 7-dehydroxylates cholic acid to deoxycholic acid. Overall, this work reveals a novel transient species during 7-dehydroxylation as well as provides direct evidence for the colonization and growth of 7-dehydroxylating bacteria in the large intestine.
A randomized phase II trial of concurrent chemoradiation of oral vinorelbine and two doses of radiotherapy, 60 and 66 Gy, in local-regionally advanced non-small cell lung cancer (LA-NSCLC).
Authors: Olfred Hansen, Marianne Knap, Azza Khalil, Christa Haugaard Nyhus, Tine McCulloch, Bente Holm, Carsten Brink, Lone Hoffmann, Tine Schytte
Journal: Journal of Clinical Oncology (2014)

7557 Background: A high rate of isolated loco-regional failure is a problem in RT of LA-NSCLC. This study tested two doses of radiotherapy (RT), 60 Gy/ 30 F (A) and 66Gy/ 33 F (B), 5 F W, concurrent with oral Vinorelbine (Nav) 50 mg q 3 wk. Methods: The primary endpoint was local progression failure free survival (LPFS) 9 months (m) after start of RT. Secondary endpoints included overall survival (OS) and safety. The results were compared with a historical cohort (CTRL) of pts, stage 2B-3B and PS 0-1 treated with same induction chemotherapy as in the study and 1 cycle of Ca-Nav during RT 66 Gy/33 F. Main inclusion criteria were histological/cytological proven stage 2B-3B NSCLC, PS 0-1. Prior to randomization the pts received induction chemotherapy, and the pts had to be proven able to receive 66 Gy/33F. No elective nodes were treated. Follow up with CT was every 3 m from RT start. At 9 m. a FDG-PET-CT scan was applied. The LPFS was calculated as the time of randomization to the date of the scan demonstrating local or distant failure. From Jul 2009-Aug 2013, 121 pts were randomized from 5 centers. All together, 117 pts were eligible. By Jan 2014, 102 pts had +10 m. follow-up forming the basis of this preliminary analysis. The final analysis is expected in May 2014. Results: The LPFS at 9 m. was arm A: 46% (95% CI: 40%; 53%), and in B: 56% (95% CI: 40%; 63%), and 76% (95% CI 67%; 82%) in CTRL. The overall survival in A, B, and CTRL were similar. No hematological G4 side effects were observed. Dysphagia and dyspnoe tended to be higher in B. One G4 pneumonitis was observed in Arm and 1 G5 in Arm B, and 1 G5 in CTRL. Conclusions: Both regimens were well tolerated, but neither of the arms met the phase II criteria. OS was comparable to CTRL. This suggests that the inferior local control observed at 9 m was due to the use of FGD-PET-CT, but omission of platin-chemotherapy during RT may have influenced the results. Clinical trial information: NCT 00887783.
Proteomic Landscape of De Novo Pediatric Acute Myeloid Leukemia
Authors: Fieke W Hoff, Yihua Qiu, Wendy Hu, Amina A Qutub, Alan S Gamis, Richard Aplenc, E. Anders Kolb, Todd A Alonzo, Eveline S. de Bont, Terzah M. Horton, Steven M. Kornblau
Journal: Blood (2018)