tbuckley/cabot-search huggingface dataset:
NY-ESO-1 as a predictive marker for neoadjuvant chemotherapy in stage IIIa non-small cell lung cancer (NSCLC).
Authors: T. John, Y. Chen, M. H. Starmans, M. Walkiewicz, P. Russell, A. Azad, S. Deb, N. K. Altorki, P. C. Boutros, P. Mitchell, J. S. Cebon
Journal: Journal of Clinical Oncology (2011)

10576 Background: The use of neoadjuvant chemotherapy in stage IIIa NSCLC is controversial with trials consistently failing to demonstrate a significant benefit. The ability to identify chemoresponsive tumors should aid clinical trial design and outcome. Cancer-Testis antigens (CTAg), such as MAGE A3, are currently being investigated as immunotherapeutic targets in the adjuvant setting. CTAgs are expressed in over 50% of both squamous cell and adenocarcinomas but restricted to testis in normal tissues. Since CTAgs have been proposed as markers of drug-resistant stem-like cells, we investigated their expression and association with chemosensitivity. Methods: Stage IIIa patients treated with neoadjuvant chemotherapy at the Austin Hospital (AH) Melbourne and Weill Cornell Medical College (WCMC) New York were investigated. Preoperative mediastinal lymphadenectomy tissues were stained for a panel of CTAgs including NY-ESO-1, MAGE-A, MAGE-C1/CT7, GAGE and CT45 by immunohistochemistry. DNA was isolated from paraffin sections from the WCMC dataset and mutationally profiled using Sequenom’s MassArray platform. Molecular results were correlated to clinical characteristics, chemoresponsiveness (defined as pathological down-staging of TNM status), progression free and overall survival (OS). Results: 95 patients (WCMC: 70, AH: 25) were studied. Staining for one or more CTAgs was positive in 50% of samples regardless of histology. NY-ESO-1 was expressed in 33% of samples. DNA was isolated from 63/70 WCMC samples. Mutations were seen predominantly in the EGFR (5/63) and KRAS (8/63) genes. CTAg expression occurred independent to KRAS mutant tumors. NY-ESO-1 expression occurred independent to EGFR and KRAS mutations and was significantly associated with chemosensitivity in both datasets (Chi square p=0.010). Improved OS was only seen in the AH dataset (HR 0.36; 95% CI 0.14-0.96, p=0.04). Conclusions: Expression of NY-ESO-1 predicts response to neoadjuvant chemotherapy in stage IIIa NSCLC. Expression occurred independent of common mutations but in both adenocarcinoma and squamous cell carcinoma. Given their immunogenicity, immunological mechanisms for these responses are being investigated.
A phase Ia/Ib trial of trametinib in combination with sorafenib in patients with advanced hepatocellular cancer.
Authors: Heloisa P. Soares, Richard D. Kim, Nishi Kothari, Jennifer Cooksey, Gregory M. Springett, Amit Mahipal
Journal: Journal of Clinical Oncology (2016)

TPS469 Background: MEK inhibitors have demonstrated preclinical activity in hepatocellular carcinoma (HCC). More importantly, in xenograft models, this class of inhibitors acts synergistically with sorafenib to inhibit tumor growth, prevent metastatic spread and increase survival. In preclinical models, sorafenib leads to overactivation of the MAPK pathway, which can be counterbalanced by the use of MEK inhibitors. Trametinib is a reversible, highly selective, allosteric MEK inhibitor. Methods: This is an open label, single group, phase I study with cohort expansion that utilizes the standard 3+3 design for dose escalation. The primary objective of this study is to determine maximally tolerated dose (MTD) of trametinib in combination with sorafenib as first-line systemic treatment for patients with locally advanced or metastatic HCC. Secondary objectives are to explore and characterize the safety and tolerability of this combination at the established MTD and to explore its efficacy profile. Up to 24 patients will be enrolled in 4 dose levels. Once the MTD is reached and/or the recommended dose for expansion is determined, an additional cohort of 10 patients with advanced HCC will be accrued. Only patients with Child-Pugh score A will be included. Trametinib will be administered orally daily beginning day 8 of cycle 1. Sorafenib will be administered twice daily beginning day 1 of 28 days cycle. Patients will get restaging scans every 2 cycles. Correlative studies between various biomarkers and clinical outcomes will also be performed. Biomarkers will be assessed in archival tumor tissue. The pre- and post-dose expression level of biomarkers including pan and phospho-Mek and Erk will be measured on peripheral blood mononuclear cells during treatment. Pre and post treatment biopsies will be performed for patients participating in the dose expansion cohort for correlative studies including gene expression. As per September 2015, 3 patients have been enrolled in this trial. ClinicalTrials.gov identifier: NCT02292173 Clinical trial information: NCT02292173.
Association between KRAS mutation and lung metastasis in advanced colorectal cancer.
Authors: Allan Andresson Lima Pereira, Juliana Florinda De Mendonga Rego, Van Karlyle Morris, Michael J. Overman, Cathy Eng, Chris R. Garrett, Renata Ferrarotto, Michael Sangmin Lee, Zhiqin Jiang, Paulo Marcelo Hoff, Jean-Nicolas Vauthey, Eduardo Vilar Sanchez, Dipen M. Maru, Scott Kopetz
Journal: Journal of Clinical Oncology (2014)

494 Background: The role of KRAS status in the time-dependent pattern of metastasis in colorectal cancer (CRC) patients has been reported but not validated in independent series of unresectable metastatic CRC. We aimed to determine its potential value as a predictive factor for development of lung metastasis. Methods: We retrospectively evaluated data from MD Anderson Cancer Center from 494 patients diagnosed with metastatic CRC with KRAS mutation testing (codons 12, 13, 61) by Sanger sequencing or mass spectroscopy genotyping in 2008 through 2010. Medical records and image reports were assessed to determine date of lung metastasis diagnosis, pattern of lung involvement and presence of thoracic lymph nodal metastasis. Time-to-lung metastasis (TTLM), lung-metastasis-free survival (LMFS) and overall survival (OS) were calculated from the time of diagnosis of first metastasis in any site according to the Kaplan-Meier method and were compared by log-rank test. Results: We included 494 patients (41% female) with a median age of 55 years. 292 tumors were KRAS wild type (WT, 59%) and 202 (41%) were KRAS mutants. OS was not different between the groups (45.5 months for KRAS mutants vs. 50.6 months for KRAS wild type; p=0.6). At the time of diagnosis of metastatic disease, 36% of patient had lung metastases, with 1.6-fold higher odds of lung metastases with a KRAS mutation (p=0.013, 95% CI 1.1 – 2.4). Compared to KRAS WT, KRAS mutations were associated with a shorter TTLM (15.2 vs. 22.4 months; p=0.002) and LMFS (12.9 vs. 16.7 months; p= 0.019). There was no difference in thoracic lymph node involvement (p= 0.18), number of lung metastasis (p=0.71), lung lobes involved (p=0.19) or disease in bilateral lung (p=0.27) according to KRAS status. There were no differences in lung metastasis frequency or pattern between codons 12, 13, and 61 mutations. Conclusions: In this retrospective analysis, lung metastases were more common at diagnosis of mCRC in KRAS mutant patients and more likely to develop during the disease course. This data suggests a potential role for KRAS mutations in determining a metastatic tropism of CRC to the lung and can be used to risk stratify patients.
Pre-diagnostic circulating sex hormone levels and risk of prostate cancer by <i>TMPRSS2:ERG</i> status.
Authors: Rebecca E Graff, Allison Meisner, Thomas Ahearn, Michelangelo Fiorentino, Howard D. Sesso, Edward L. Giovannucci, Lorelei A. Mucci, Andreas Pettersson
Journal: Journal of Clinical Oncology (2016)

93 Background: Experimental studies have shown that androgen receptor stimulation can facilitate formation of the TMPRSS2:ERG gene fusion in prostate cell lines. No study has tested whether higher pre-diagnostic circulating sex hormone levels in men increase the risk of developing TMPRSS2:ERG positive prostate cancer specifically. Methods: We conducted a nested case-control study of 200 prostate cancer cases and 1,057 controls from the Physicians’ Health Study and Health Professionals Follow-up Study. We examined associations between pre-diagnostic circulating levels of total testosterone, free testosterone, DHT, androstanediol glucuronide, estradiol, and SHBG and risk of prostate cancer by TMPRSS2:ERG status. TMPRSS2:ERG was assessed by ERG immunohistochemistry. We used multivariable unconditional polytomous logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of fusion-positive (n = 94) and, separately, fusion-negative (n = 106) disease. Results: Free testosterone was significantly associated with the risk of ERG-positive prostate cancer (OR: 1.37, 95% CI: 1.05-1.77), but not ERG-negative prostate cancer (OR: 1.09, 95% CI: 0.86-1.38) (p-diff: 0.17). None of the remaining hormones evaluated showed clear differential associations with ERG-positive versus ERG-negative disease. Conclusions: These findings provide some suggestive evidence that higher pre-diagnostic free testosterone levels are associated with an increased risk of developing TMPRSS2:ERG positive prostate cancer but are not associated with prostate cancer that lacks TMPRSS2:ERG.
Effect of gemcitabine-ALK-014 combination on MMP9 expression in primary pancreatic adenocarcinoma CELL cultures (PCCs).
Authors: Niccola Funel, Giuseppe Genova, Vittorio Perrone, Fabio Caniglia, Ugo Boggi
Journal: Journal of Clinical Oncology (2015)

332 Background: Pancreatic ductal adenocarcinoma (PDAC) is the fourth highest cause of death in the western world. The adjuvant chemotherapy can increase the overall survivor (OS) of PDAC patients. The Gemcitabine (GEM) and alkaloids mixture (ALK-014) combination shows the increase two time the OS non resectable in PDAC patients with respect to gemcitabine treatment alone. Indeed the Alkaoids compound modulated the Matrix MetalloProteinase 9 (MMP9) in PDAC cell clines. AIM: Our goal was to investigate the MMP 9 protein modulation in primary cell cultures (PCCs) of PDAC by Gem and ALK-014 combination treatment. Methods: Two PCCs (LPc006 and LPc028) were seeded in 4 multi-well chamber slids (8,000 each/well) for cytotoxicity study by Gem [10 Nm], ALk-014 [1µm]and their combination. After 48 h of treatment the cells were stained Immunocytochemistry (IHC) using polyclonal antibody for MMP9. We used no-treated cells to evaluate basic level of MMP9 protein. No–stained cells were used as negative control. All experiments were done in triplicates. We evaluated protein expression and cellular morphology by computer for imaging analysis (D-Sight, Menarini, Italy). The expression differences was evaluated by ANOVA and t-test analyses. Results: We found a significant reduction of MMP9 expression in both cell lines treated with Gem/ALK-014 combination with respect to their controls ( p&lt;0.01). The same drug combination reduced significantly the number of proliferating cells and showed the modification of the structure of nuclei with respect to untreated cells (p&lt;0.001). Conclusions: New therapeutic approaches are warranted to reduce the metastatic behavior of PDAC. The present drug combination seems to be a promising tool for PDAC treatment in vitro. The new computerized approach for MMP9 evaluation could be a first quantitative attempt for protein quantification in preclinical model.
Natural Killer Cells Recovery After Consolidation Chemotherapy in Elderly Patients with Acute Myeloid Leukemia (AML)
Authors: Jerome Rey, Nicolas Anfossi, Pascale Andre, Jean-Marie Boher, Florence Orlanducci, Violette Breso, Valentine Perri, Thomas Prebet, Aude Charbonnier, Eloïse Perrot, Francois Romagne, Norbert Vey, Daniel Olive
Journal: Blood (2011)
Effects of admission (adm) source, time, and provider on inpatient (inpt) oncology (onc) outcomes at the Cleveland Clinic Foundation (CCF).
Authors: Wee Christopher, Lindsey Martin Goodman, Lisa A. Rybicki, Alberto J. Montero, Bassam N. Estfan, Carolyn Best, James Stevenson
Journal: Journal of Clinical Oncology (2016)

140 Background: The quality of care transfers is known to influence clinical outcomes. In an inpt onc setting at a major tertiary care referral center, patient (pt) adm originate from many different areas and times. A detailed evaluation of onc adm by source of transfer, admission time, and provider type, may identify opportunities to improve inpt clinical outcomes. Methods: We retrospectively reviewed all adm to the inpt solid tumor onc service from July - December 2014 from CCF regional hospital emergency departments (ED), outside hospital (OSH) ED, OSH inpt services, and CCF outpt clinics. Pts were excluded if the adm was planned or if admitted from the CCF Main Campus ED. Data collected included pt and encounter characteristics and provider type (house-staff or nocturnal hospitalist). Clinical outcomes, including activation of the adult medical emergency team (AMET), ICU transfers, length of stay (LOS), and in-hospital mortality were compared using chi-squared test; ECOG PS and LOS with the Kruskal-Wallis tests and Wilcoxon rank sum test. Results: A total of 413 unique pt admissions were reviewed. 213 were included after exclusion criteria were applied. The probability of AMET activation, mortality, and LOS differed by origin of transfer. Pts admitted from CCF regional EDs had the lowest median LOS and no deaths. OSH int transfers demonstrated significantly higher mortality vs other origins of transfer. Pts whose first orders were placed after 5pm had no significant differences in AMET activation, ICU transfers, LOS, or mortality vs daytime adm. There were no differences in adverse outcomes by the type of admitting provider. Conclusions: Onc inpts transferred from an outside healthcare setting were at highest risk for adverse outcomes (AMETs, increased LOS, and mortality) include those originating from OSH inpt services. Process and communication interventions focused on transfers from outside inpt facilities may improve safety and outcomes in this population. [Table: see text]
Utilization and effectiveness of extended-duration thromboprophylaxis after high-risk abdominopelvic cancer surgery.
Authors: Jason Dennis Wright, Ling Chen, Soledad Jorge, William M. Burke, Ana Tergas, June Hou, Jim Hu, Alfred I. Neugut, Cande Ananth, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2016)

62 Background: Extended-duration thromboprophylaxis for 4 weeks after discharge has been demonstrated to reduce venous thromboembolic events (VTE) in cancer patients undergoing abdominopelvic surgery and is recommended in national guidelines. We examined the utilization and effectiveness of extended-duration low molecular weight heparin prophylaxis in high-risk cancer patients after surgery. Methods: We analyzed patients with colon, ovarian, and uterine cancer who underwent surgery from 2009-2013 and who were recorded in the MarketScan database. Multivariable models and propensity score analysis with inverse probability of treatment weights were developed to examine uptake and predictors of use of post-discharge low molecular weight heparin (LMWH) use, VTE incidence, and associated adverse events (transfusion, and hemorrhage). Results: A total of 63,280 patients were identified. Use of extended-duration prophylaxis increased from 2009 to 2013 from 1.4% to 1.7% (P = 0.67) for colectomy, 5.9% to 18.3% for ovarian cancer surgery (P &lt; 0.001), and 6.3% to 12.2% (P &lt; 0.001) for hysterectomy for endometrial cancer. There was no association between use of extended-duration prophylaxis and reductions in VTE for any of the procedures: colectomy (2.4% with extended-duration prophylaxis vs. 2.9% without prophylaxis, OR = 0.84; 95% CI, 0.54-1.31), ovarian cancer-directed surgery (3.7% vs. 3.6%, OR = 1.01; 95% CI, 0.76-1.33), hysterectomy (2.1% vs. 2.1%; OR = 0.96; 95% CI, 0.67-1.38). Extended-duration prophylaxis was associated with an increased risk of adverse postoperative events: 2.20 (95% CI, 1.51-3.19) after colectomy, 1.24 (95% CI, 0.92-1.68) following ovarian cancer-directed surgery and 0.99 (95% CI, 0.66-1.48) for hysterectomy for endometrial cancer. Conclusions: Use of extended-duration thromboprophylaxis is low among high-risk cancer patients undergoing surgery. The effectiveness of prophylaxis in real world populations requires further evaluation.
Superior Lethal Activity of Novel BET Protein Proteolysis Targeting Chimera (BETP-PROTACs) Versus Betp Bromodomain Inhibitor (BETi) Against Post-Myeloproliferative Neoplasm (MPN) Secondary (s) AML Cells
Authors: Dyana T Saenz, Warren Fiskus, Kanak Raina, Taghi Manshouri, Kevin Coleman, Jim Winkler, Yimin Qian, Andrew Crew, Angela Shen, Christopher P Mill, Baohua Sun, Srdan Verstovsek, Craig Crews, Kapil N. Bhalla
Journal: Blood (2016)
Angiocardiographic evaluation of ventricular septal defect. Pre- and post-operative cardiac volume characteristics.
Authors: Akio Sunakawa, Yoshihide Nakamura, Toru Shinohara, Tatsuo Yokoyama, Hidetaka Oku, Jun Kawai, Hitoshi Shirotani
Journal: Circulation (1983)

The characteristics of the left and the right heart volume in isolated ventricular septal defect were investigated in 62 patients before surgery and in 17 after corrective surgery, which was undergone at ages ranging from 0.5 to 13. Postoperative cardiac catheterization was performed one to two months after surgery. Preoperatively, the right atrial maximal volume increased in accordance with the pulmonary to systemic pressure ratio, and the left ventricular end-diastolic volume, the left atrial maximal volume and the right ventricular end-diastolic volume increased in accordance with the degree of the left-to-right shunt. These volumes decreased considerably after surgery, although they still remained above normal. The left ventricular mass also increased in accordance with the degree of the left-to-right shunt preoperatively and did not decrease postoperatively. The left and the right ventricular ejection fractions were close to or within normal limits preoperatively and remained so after surgery. On the basis of our results and the findings previously published in the literature, factors which may influence the postoperative cardiac function in ventricular septal defects were discussed.
Roar: A Phase Ib Trial of Oral Azacitidine in Combination with Lenalidomide and Dexamethasone for Relapsed Multiple Myeloma (MM) Patients Refractory to Prior Lenalidomide
Authors: Anna Kalff, Kate Reed, Tiffany T. Khong, Sridurga Mithraprabhu, Malarmathy Ramachandran, Richard Hall, Krystal Bergin, Andrew Spencer
Journal: Blood (2015)
Which is the better prognostic factor in rectal cancer patients who received neoadjuvant chemoradiotherapy: cTNM stage vs. ypTNM stage?
Authors: HyungJin Kim, Gun Kim, Ri Na Yoo, Bong-Hyeon Kye, Hyeon-Min Cho
Journal: Journal of Clinical Oncology (2016)

693 Background: Neoadjuvant chemoradiotherapy (nCRT) in rectal cancer is widely applied in patients with cTNM II and III stage. However, it is still obscure which staging system, either clinical (c) or pathologic (yp), influences in prognosis. This study aims to evaluate the current staging system predicting prognosis in the locally advanced rectal cancer patients. Methods: Among 221 patients who were diagnosed with rectal cancer and underwent curative resection from January 2009 to February 2013, 141 patients who received nCRT were included. The ypTNM stage was categorized: complete remission and stage I to ypI. Results: Mean follow-up period was 36.3 ± 15.1 months. Disease-free survival (DFS) was not associated with age, sex, Anesthesiologists classification, types of operative procedure, tumor cell differentiation, tumor location, tumor infiltration, preoperative CEA level, adjuvant chemotherapy. cTNM stage did not demonstrate any correlation with DFS (cII % vs cIII %, P = 0.266). However, DFS did exhibit statistically significant association with postoperative CEA level (P &lt; 0.001) and ypTNM stage. 3-year DFS rate for each categorized stage is as followed – ypI, 87.9%; ypII, 67.8%; ypIII, 53.3% (ypI vs. ypII P = 0.009, ypI vs. ypIII P &lt; 0.001, ypII vs. ypIII P= 0.185). Conclusions: Oncologic outcome of the patients with locally advanced rectal cancer is associated with pathologic TNM stage. Based on our results, we think that adjuvant chemotherapy given to patients with complete remission or pathologic stage I may be reconsidered.
The effect of surgery in determining pseudoprogression and predicting outcome in adults with glioblastoma.
Authors: I. Melguizo, K. R. Hess, D. Blas-Boria, J. Bruner, N. Guha-Thakurta, V. K. Puduvalli
Journal: Journal of Clinical Oncology (2011)

2067 Background: Pseudoprogression (PsPD) refers to an increase in size or appearance of new areas of contrast enhancement on MRI scans, seen in about 30% of the patients with newly diagnosed glioblastoma soon after completing chemoradiation (chemoRT). It is distinguished from true progression by its improvement independent of treatment; however, timely diagnosis of PsPD to guide clinical decisions has been a challenge. Given that tissue sampling of the MRI changes, when initially seen, could potentially distinguish PsPD from true progression, we examined the utility of surgery in the diagnosis of PsPD and its impact on patient outcome. Methods: A retrospective review of data from adults with GBM between October 2006 and March 2009 identified 140 patients with MRI changes suggestive of progression within 3 months of chemoRT; of these, 34 underwent surgical resection for diagnostic purposes. Three subsets - progression, PsPD or mixed -were identified based on imaging characteristics in the nonsurgical group and by histology in the surgical group. TTP and OS were calculated using the Kaplan Meier method and log rank analysis for significance of differences. Results: The median TTP was 4.8, 5.8 and 7.5 months (p=0.69) for PsPD, progression and mixed in the surgical group respectively compared to 3.9, 4.1 and 6.2 months (p=0.67) in the nonsurgical group. The median OS was 14.4, 18.5 and 17.1 months (p=0.82) for PsPD, progression and mixed in the surgical group compared to 13.4, 11.6 and 14.5 months (p=0.12) in the nonsurgical group respectively. No significant differences in TTP or OS were seen. Conclusions: These findings suggest that routine surgical sampling and histologic review of MRI changes after chemoRT does not help identify differences in outcome compared to the nonsurgical group. Additionally, no significant differences in outcome were seen among the three categories in the surgical or nonsurgical groups. Refinement of the histological criteria, careful intraoperative selection of areas of interest and advances in imaging studies are critically needed to permit early differentiation of PsPD versus progression to allow appropriate clinical management and formulate prospective studies.