tbuckley/cabot-search huggingface dataset:
Preliminary outcome of the survival rate and possible prognostic factors for locally advanced nasopharyngeal carcinoma patients treated with neoadjuvant chemotherapy followed by concurrent chemoradiotherapy.
Authors: Jin Yi Lang, Mei Feng, Mengzhen Yuan, Yecai Huang, Yangkun Luo, Zhixuan Fan
Journal: Journal of Clinical Oncology (2015)

e17044 Background: Neoadjuvant was a promising chemotherapy modality for head and neck cancer. However there was still controversy for it. We did an retrospectively analysis to evaluate the early survival results of locally advanced NPC patients treated with neoadjuvant chemotherapy, and aim to explore the substantial prognostic factors further. Methods: 147 squamous NPC patients of stage Ⅲ-Ⅳa+b (UICC2002 statging system) treated with IMRT in our center from Oct. 2007 to Oct. 2013 were analyzed retrospectively. They were divided into two groups. Group NACT (76 patients) was treated with neoadjuvant chemotherapy followed with concurrent chemoradiotherapy, and group CCRT (71 patients) treated with concurrent chemoradiotherapy. NACT received 2 cycles of neoadjuvant chemotherapy with the TP (docetaxel 75 mg/m2 d1 + cisplatin 80 mg/m2 d1) or TPF (docetaxel 75 mg/m2 d1 + cisplatin 80 mg/m2 d1 + 5-Fu 750 mg/m2 d1-5) regimens, and then received 2-3 cycles of the platinum-based concurrent chemoradiotherapy. CCRT only received 2-3 cycles of concurrent chemoradiotherapy. Cumulative survival rate was analyzed by Kaplan Meier method. The log-rank test and Cox proportional hazard model was used for prognostic analyses. Results: the median follow-up time was 26 and 30 months in NACT and CCRT respectively. The 3-year LRRFS, DMFS and OS for group NACT and CCRT were 94.5%, 96.8%; 85.8%, 81.6% and 83.3%, 85.0% respectively (p< 0.05). Age, sex, HGB, clinical stage, T, N stage and radiation dose was included in prognostic analysis. For univariate analysis, only N stage was the adverse prognostic factor for 3-year DMFS (p< 0.05). However, for multivariate analyses, there was no statistical significance for these possible prognostic factors. Conclusions: There was no statistical significance for early survival results in NACT and CCRT groups, however the neoadjuvant chemotherapy followed with concurrent chemoradiotherapy could increase the DMFS for locally advanced NPC patients in some degree. N stage was also a possible prognostic factor for the survival results of the local advanced NPC patients.
A phase Ib dose escalation study of JX-594 (TK-vaccinia virus expressing GM-CSF) administered by biweekly intravenous infusion in patients with metastatic, refractory colorectal carcinoma.
Authors: Young Suk Park, Jeeyun Lee, Ho Yeong Lim, Jihye Lee, Adina Pelusio, James M. Burke, Caroline Breitbach, David H. Kirn
Journal: Journal of Clinical Oncology (2012)

e13044 Background: JX-594 is a recombinant vaccinia virus engineered to selectively replicate in and destroy cancer cells while stimulating a systemic anti-tumor immune response and inducing a reduction in tumor blood perfusion. Preclinical data has demonstrated JX-594 activity is enhanced in cells with up regulation of the EGFR pathway. JX-594 anti-tumor activity in multiple advanced solid tumors has been observed in early stage clinical studies. This study was designed to assess the safety, MTD/MFD, and initial anti-tumor activity of JX-594 administered IV every other week x 4 total treatments in patients with metastatic CRC after failure of standard chemotherapy. Methods: A standard 3+3 dose escalation design was used to enroll patients into three dose levels (10 6 , 10 7 or 3x10 7 pfu/kg) of JX-594 administered IV every 2 weeks x4. Safety was assessed using CTCAEv3.0. Anti-tumor activity was determined based on serial CT scans and CEA measurements. Patient samples were collected for pharmacokinetics and pharmacodynamics. Results: Enrollment is ongoing with 8 patients treated at total doses ranging from 5x10 7 to 2x10 9 pfu. Adverse events have generally been limited to grade 1/2, transient flu-like symptoms (fever, chills, headache). No DLT was reported. Three patients in the top two dose levels demonstrated SD on week 4 CT scan with one maintained at week 8. In these same 3 patients, CEA declined by 50% in a single patient while the other 2 had no significant change in CEA. Conclusions: Preliminary data for this dose escalation trial demonstrates JX-594 is well tolerated after 4 IV treatments administered every other week. CEA and CT scan assessment suggest possible efficacy. Enrollment continues and an expansion cohort at the MTD is planned. Updated data is expected at the time of presentation.
Characteristics of sarcoma patients with long-term response to gemcitabine and paclitaxel.
Authors: Daniela Katz, Firas Elyan, Amir Sonnenblick, Ofer Merimsky, Inna Ospovat, Orit Cohen, Asher Salmon, Hovav Nechushtan, David Edelmann, Tamar Peretz, Nili Peylan-Ramu
Journal: Journal of Clinical Oncology (2012)

10034 Background: The combination of fixed-dose-rate gemcitabine and docetaxel has demonstrated efficacy in advanced uterine leiomyosarcoma and nonleiomyosarcoma sarcomas. We evaluated the tolerability and efficacy of modified taxol-gemcitabine (GemTax) protocol for patient with advanced sarcoma. The protocol was designed on a weekly basis to reduce toxicity. The purpose of this retrospective study was to evaluate the characteristics of long term-responders (≥12 treatments) to weekly GemTax, among pre-treated advanced high-grade sarcoma patients. Methods: From May 2004 to October 2011, 48 advanced sarcoma patients were treated with combination paclitaxel (60-90 mg/m2) and gemcitabine (600-900 mg/m2 over 100 min), on days 1,8 of every 3-week cycle or on days 1, 8 and 15 of every 4-week cycle at a wide-range treatment lines. Two patients are still on the protocol. Results: Fifteen patients (6 males and 9 females) completed 12 weekly treatments or more (mean 22.3 range 12-37) of which 4 completed &gt;30 treatments. These include 5 leiomyosarcomas (one retroperitoneal), 2 uterine leiomyosarcomas, 3 MFH, 2 spindle sarcoma, 1 osteosarcoma, 1 adamantimoma and 1 pleomorphic rhabdomyosarcoma. GemTax was administered as 1st or 2nd line treatment in 2 and 8 patients, respectively, and as 3rd -6th line in 5. Of these patients, none achieved complete response (CR), 7/15 (47%) achieved a partial response (PR) and 8/15 (53%) had stable disease (SD). Median treatment duration was 10.3 months (range 4-22) Median progression-free survival was 28.85 months (range 5-84 months), and median overall survival was 51.2 months (range 16-95 months). A lower starting dose of paclitaxel (60-70 mg/m2) and gemcitabine (600-700 mg/m2) characterized the 4 patients with responses &gt;30 cycles. Only five patients required dose reduction ranging between 10-40% due to grade 3 hematological toxicity. None of these patients, however, had febrile neutropenia, or bleeding events, and all non-hematologic toxicities including neurotoxicity were manageable. Conclusions: GemTax is a reasonable treatment option for patients with advanced pre-treated high-grade sarcomas. The regimen is well tolerated and dose adjustments do not seem to impact response.
Efficacy and safety of first-line (1L) pertuzumab (P), trastuzumab (T), and docetaxel (D) in HER2-positive MBC (CLEOPATRA) in patients previously exposed to trastuzumab.
Authors: Eva Maria Ciruelos Gil, Adam Brufsky, Young-Hyuck Im, Sung-Bae Kim, Emma Clark, Adam Knott, Graham Ross, David Miles
Journal: Journal of Clinical Oncology (2013)

600 Background: CLEOPATRA is a global phase III trial of P + T + D vs placebo + T + D in HER2-positive 1L MBC. Results showed a significant improvement in PFS (Baselga NEJM 2012) and OS (Swain SABCS 2012) favoring P + T + D. CLEOPATRA started recruitment in 2008 soon after the approval of T in the adjuvant setting in 2006 and mandated a disease-free interval (DFI) of ≥12 mos from the end of adjuvant therapy to MBC diagnosis. Due to this, a low proportion of pts with prior T exposure was included. Here we present the efficacy and safety of 1L P + T + D in the subset of pts in CLEOPATRA with prior T exposure. Methods: Pts received P + T + D or placebo + T + D, had a DFI ≥12 mos, baseline left ventricular ejection fraction (LVEF) ≥50% and no LVEF decline to &lt;50% during/after prior T therapy. Exploratory analyses of PFS and OS in pts with (neo)adjuvant therapy with or without T were conducted. Results: Of the study population, 47% had received (neo)adjuvant therapy and 11% had received (neo)adjuvant T; 82% of the prior T group came from Europe or North America. A univariate Cox regression analysis did not identify prior T therapy as a statistically significant risk factor for developing left ventricular systolic dysfunction (LVSD). However, due to the low number of LVSD events overall, this analysis has limited sensitivity. Conclusions: Data from CLEOPATRA show that pts with HER2-positive 1L MBC who have received prior T (DFI ≥12 mos) derive the same magnitude of benefit from the combination of P + T + D when compared with the whole study population or those who are T-naïve. This is in agreement with prior evidence of the activity of P + T in pts pretreated with T (Baselga JCO 2010). Efficacy and safety of P-T-based therapy is being explored in the PERUSE and PHEREXA trials, in a pt population with wider exposure to prior T and a shorter DFI, which may better represent current clinical practice. Clinical trial information: NCT00567190. [Table: see text]
MANAGEMENT OF TAKOTSUBO CARDIOMYOPATHY COMPLICATED BY LEFT VENTRICULAR OUTFLOW TRACT OBSTRUCTION
Authors: Sohaib Tariq, Anoshia Raza, Roshni Narurkar, Srikanth Yandrapalli, Abdallah Sanaani, Mina'a Shahid, Ali Ahmed, Wilbert Aronow, Julio Panza, Howard Cooper
Journal: Journal of the American College of Cardiology (2017)
A NEW SCORE FOR PREDICTION OF SLOW/NO-REFLOW PHENOMENON DURING PRIMARY PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Authors: Mohamed Abo Bakr, Hisham Samir Roshdy, Mohamed Ibrahim Mostafa Elawadi, Mohamed Hossam Eldein Elshaer
Journal: Journal of the American College of Cardiology (2017)
Are generic multisource (generic) chemotherapy (CT) drugs as effective as proprietary single-source (proprietary) drugs: Evidence from in vitro CT-induced apoptosis (APOP) in non-small cell lung cancer (NSCLC), colorectal cancer (Colon CA) compared to recurrent/metastatic breast carcinoma (Breast CA).
Authors: Misagh Karimi, Swapnil Padmakar Rajurkar, Linda D. Bosserman, Karl Rogers, Dirk C. Davidson, Carl Rogaston Willis, James Rutledge, Allan Hallquist, Cary A. Presant
Journal: Journal of Clinical Oncology (2012)

e13003 Background: We have demonstrated that cancer cells from patients (Pts) with recurrent or metastatic Breast CA frequently show as much or better APOP with Generics compared to Proprietaries (separately submitted to ASCO, 2012). We have compared these observations to in vitro APOP in Pts with NSCLC and Colon CA. Methods: Purified tumor cells from Pt biopsies were placed into short term culture using the microculture kinetic (MiCK) assay. APOP was analyzed every five minutes over 48 hours. APOP was defined in kinetic units (KU) of apoptosis. Significant APOP was &gt; 1.0 KU, significant differences between individual assays were defined as &gt; 0.57 KU based on replicate analyses. Results from Breast CA, Colon CA and NSCLC were compared. Results: 41 Pts with NSCLC, 8 Pts with Colon CA and 67 Pts with Breast CA had successful cultures. Generics produced APOP greater than Proprietaries in 25/32 Pts with NSCLC (78%), 4/7 Pts with Colon CA (57%) and 36/43 Pts (84%) with Breast CA. Generics produced APOP = Proprietaries in 5 Pts with NSCLC (16%), 1 Pt with Colon CA (14%) and 6 Pts (14%) with Breast CA. Proprietaries produced APOP greater than Generics in 2 Pts with NSCLC (6%), 2 Pts with Colon CA (29%) and 1 Pt (2%) with Breast CA. There were 0 Pts with NSCLC, Colon CA or Breast CA in whom no drug produced significant APOP (KU less than 1.0). Proprietaries produced more APOP in Colon CA than in Breast CA (p&lt;0.05). Detailed comparisons of drugs by disease will be presented. Conclusions: Generic drugs can produce APOP in vitro equal to or better than Proprietary drugs in most Pts with NSCLC, Colon CA, and Breast CA. The frequency of Generic drugs being at least as active as Proprietary drugs varies by disease, and was higher in Breast CA compared to Colon CA. However, the MiCK APOP assay can identify which individual Pts might require use of Proprietary drugs. These conclusions justify prospective clinical trials to confirm these in vitro results. Increased use of Generic drugs based on the APOP assay may help to control healthcare costs.
Initial findings from the Memorial Sloan-Kettering Early Onset and Familial Gastric Cancer Registry (EOFGCR)
Authors: M. Harlan, E. Sheehy, J. Randazzo, D. Schrag, M. M. Kemeny, D. P. Kelsen, M. A. Shah
Journal: Journal of Clinical Oncology (2007)

4619 Background: Hereditary Diffuse Gastric Cancer(HDGC) is an autosomal dominant cancer susceptibility syndrome defined as having 2 or more diffuse GC(one of which diagnosed before the age of 50) or 3 or more diffuse GC in 1 st or 2 nd degree relatives. A germline mutation in E-Cadherin(CDH1) is found in 20–30% of HDGC families. HDGC is responsible for 30% of all hereditable GC. The genetic cause for the remaining 70% of hereditable GC is unknown. We created a registry for early onset and familial gastric cancer to capture epidemiologic and family history data matched with DNA and tissue to characterize various phenotypic and risk factor profiles and their associations with HDGC and other non-HDGC hereditable GC. Methods: Patients with a family history(patients with one first degree relative or 2 second degree relatives with GC) or who developed GC at an early age(age &lt; 50) were eligible for registry participation. Participants complete a GC risk factor questionnaire, family history, provide blood and tissue for repository, and meet with a genetics counselor to consider germline CDH1 mutation testing. Results: 57 patients have enrolled since January 2006: 36 patients with early onset, 21 with familial GC. Eleven patients have a family history meeting HDGC criteria, two with known CDH1 mutations. Three of the 11 HDGC families are from Ecuador. GC risk factor questionnaires are available from 46 patients(81%), see table . Although no novel CDH1 mutations were found in 13 fully sequenced patients, 4 patients(31%) were found to have uncommon genotypes, including two with early onset of disease diagnosis (ages 22 and 34) with multiple variants in CDH1. Conclusions: HDGC patients tend to have more high risk features including smoking history, use of salt, and H. pylori infection. We have identified a cluster of patients with HDGC of Ecuadorian descent. Genetic variation in CDH1 suggests that novel haplotypes may be associated early onset GC risk.(Supported by the DeGregorio Family Foundation) [Table: see text] No significant financial relationships to disclose.
New approach shows no association between maternal milk fatty acid composition and childhood wheeze or asthma
Authors: C. A. Logan, S. Brandt, M. Wabitsch, H. Brenner, F. Wiens, B. Stahl, T. Marosvölgyi, T. Decsi, D. Rothenbacher, J. Genuneit
Journal: Allergy (2017)

Abstract Background Previous observational studies have implied breastmilk fatty acid composition may play a role in the development of atopic eczema or atopic sensitization in breastfed infants and toddlers. However, studies investigating associations with wheeze and asthma in later childhood are scarce and did not account for inherent correlation of compositional data. Our aim was to explore the association of maternal milk fatty acid composition with childhood wheezing phenotypes and asthma up to age 13 years using a new statistical approach. Methods Breastmilk was collected 6 weeks and 6 months postdelivery in the Ulm Birth Cohort Study (n=720 and n=454, respectively). Concentrations of 28 fatty acids were measured by high‐resolution capillary gas‐liquid chromatography. To control for constant‐sum constraint, concentration data were transformed using the centered log ratio method. Compositional biplots and correlation matrices were used to group centered log ratio transformed fatty acids. Adjusted risk ratios with parent‐reported wheezing phenotypes and doctor‐diagnosed asthma were computed using a modified Poisson regression. Results We observed no straightforward evidence of associations between overall breastmilk fatty acid composition and specific wheeze phenotypes or doctor‐diagnosed asthma. Conclusion Using appropriate statistical methodology, we report null associations. These findings may partly be attributable to several cohort‐specific factors associated with breastfeeding and breastmilk collection. Further studies could improve on ours by analyzing samples of breastmilk and formula and by including all children for whom these are exclusively or together the major source of fatty acids in the first months of life.
Effect of long noncoding RNA <i>RUNXOR</i> on the epigenetic regulation of <i>RUNX1</i> in acute myelocytic leukemia.
Authors: Hong Wang, Rui Guo, Andrew R Hoffman, Jifan Hu, Wei Li
Journal: Journal of Clinical Oncology (2015)

7018 Background: RUNX1, a master regulator of hematopoiesis, is the most commonly perturbed target of chromosomal abnormalities in hematopoietic malignancies. About 30%–40% of acute myeloid leukemia (AML) patients carry the t(8;21) translocation. However, little is known regarding the molecular mechanisms underlying RUNX1-associated translocation. Long non-coding RNAs (lncRNAs) have been implicated in a variety of important biological processes by epigenetic mechanisms. Methods: Using a novel R3C (RNA-guided Chromatin Conformation Capture) method developed in our lab, we identified lncRNAs that participate in the regulation of RUNX1 in AML. Full length of lncRNAs was characterized by Marathon cDNA Amplification Kit. Expression of lncRNAs in AML was quantitated by qPCR. Reverse transcription-associated trap (RAT) and chromatin conformation capture (3C) assays were used to map DNA/RNA interaction. The protocol of AML patients bone marrow and peripheral blood cell samples was approved by the Human Medical Ethical Review Committee from Jilin University First Hospital and informed consent was obtained from each AML patient and normal donor. Results: 1)We discovered a novel intragenic 216 kb long noncoding RNA within the RUNX1 locus, named RUNXOR (RUNX1 overlapping promoter-derived noncoding RNA). RUNXOR was transcribed from an upstream promoter that overlaps all of the RUNX1 gene's exons and introns. 2) RUNXORlncRNA was overexpressed both in AML cell lines and AML patients' bone marrow, and was upregulated by Chemotherapeutic drug Ara-C. 3) RUNXOR lncRNA interacted with the promoter and enhancer of RUNX1. By recruiting histone methyltransferase EZH2, it induced H3K27 modification and epigenetically regulated RUNX1. 4) Using the 3C assay, we showed that RUNXOR interacted with the most frequent translocation break regions in translocation related genes, including EVI1, ETO, TEL, and CBFA2T3. Conclusions: This study identifies RUNXOR as a novel lncRNA involved in long range DNA interaction of RUNX1 in AML. The lncRNA may function as a putative tumor suppressor by epigenetically regulates RUNX1 and scaffolds the translocation associated DNA in AML.
Single nucleotide polymorphisms of TSER, ATM, RecQ1 genes association with survival in pancrease cancer
Authors: C. Weekes, S. Nallapareddy, A. Jimeno, M. Hidalgo, D. Laheru, M. A. Rudek, S. Baker, C. Redlinger, K. Murphy, W. Messersmith
Journal: Journal of Clinical Oncology (2009)

e14590 Background: Pancreatic cancer (PaCa) is the 4 th leading cause of cancer-related mortality in the U.S . We tried to determine whether ATM, RecQ1 gene polymorphisms correlate with gemcitabine (G) and TSER gene polymorphism with capecitabine (C) response and over all survival(OS). We also tested the hypothesis that PaCa pts homozygous for the S/S variant of the TSER will have a higher 6-month survival with C compared to historical controls. TS expression is regulated by a polymorphism in the TSER and has been shown that pts with S/S variant have high response rate and increased toxicity in colon cancer pts. ATM and recQ1 genes are involved with DNA damage response and repair and correlate with G response. Methods: DNA isolated from peripheral blood samples in 82 pts with Stage IV pancreatic cancer was tested for the TSER, ATM and RecQ1 gene polymorphisms. All patients were treated with G 1,000mg/m2 wkly for 3/4 wks. Pts homozygous for the S/S variant were treated with C, 2,000 mg/m2/day for 14 /21days. Pts were evaluated for response to therapy according to the RECIST. Results: 16 pts (19.5%) were positive for S/S variant of TSER, but only 4 (4.8%) were treated. The reasons for declining treatment were geographic, logistic or progression issues. Only 1 pt was evaluable, receiving at least 3 cycles of C . All pts needed dose reductions due to toxicities. Grade 3 hand foot syndrome, diarrhea and vomiting were dose limiting toxicities. No complete or partial responses were seen. The pt who received 3 cycles came off study due to progressive disease and the other 3 pts came of the study due to toxicities. TSER polymorphism was correlated to OS and only S/S variant was significant with a trend towards improved OS by log rank test and Kaplan Meier plot. ATM and RecQ1 gene polymorphisms subtypes did not correlate with G response and OS ( not statistically significant). Conclusions: Our study represents an initial effort to apply pharmacogenetics to PaCa therapy. 19.5% of pts had the S/S variant of the TSER polymorphism, but only 4.8% enrolled. C administration was associated with excess toxicity. The toxicities observed in this study appear to outweigh the benefit of using C in this pt population. There is no correlation between ATM and RecQ1 genotypes with OS. However the sample size is too small to draw conclusions. [Table: see text]
TRANSRADIAL VERSUS TRANSPEDAL ACCESS APPROACH FOR ENDOVASCULAR INTERVENTION OF SUPERFICIAL FEMORAL ARTERY CHRONIC TOTAL OCCLUSION
Authors: Apurva Patel, Roosha Parikh, Robert Bellavics, John Coppola, Joseph Puma, Olivier Bertrand, Zoltán Ruzsa, Tak Kwan
Journal: Journal of the American College of Cardiology (2017)