tbuckley/cabot-search huggingface dataset:
Unusual Abdominal Tumors
Authors: Vinay Raja, James T. Lin, Shu-Yuan Xiao
Journal: Journal of Clinical Oncology (2003)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.02.031 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12610201 Unusual Abdominal Tumors CASE 2. INTRA-ABDOMINAL DESMOPLASTIC SMALL ROUND CELL TUMOR Vinay RajaxVinay RajaSearch for articles by this author , James T. LinxJames T. LinSearch for articles by this author , Shu-Yuan XiaoxShu-Yuan XiaoSearch for articles by this author Show More University of Texas Medical Branch, Galveston, TX https://doi.org/10.1200/JCO.2003.02.031 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Identification of specific immune responses in monoclonal gammopathy of undetermined significance with therapeutic implications
Authors: S. Blotta, C. Mitsiades, P. Tassone, J. Negri, Y. Tai, R. Prabhala, B. Franco, S. Venuta, K. Anderson, N. Munshi
Journal: Journal of Clinical Oncology (2007)

8103 Background: Monoclonal gammopathy of undetermined significance (MGUS) is a benign condition with only 30% patients developing symptomatic multiple myeloma (MM). The events leading to the transformation from MGUS to MM remain unclear, however several evidences have supported the idea that immune surveillance play a role in preventing progression. Therefore, identification of antigenic targets with immune response in MGUS may provide insight into disease biology and immune-based therapeutic applications. Methods: Using the Serological identification of antigen by Recombinant Expression cloning (SEREX) technique, we have screened a MM cDNA library with 3 MGUS patients sera. Results: We have identified 11 gene products with an antibody response in MGUS. The response appeared to be directed against intracellular proteins involved in apoptosis (SON, Hip1), DNA and RNA binding proteins (KIAA0530, GPATC4), signal transduction regulators (AKAP11), developmental proteins (OFD1), transcriptional co-repressors (IRF2BP2), protein of the ubiquitin-proteosome pathways (PSMC1). We have further analyzed frequency of antibody response against these antigens in additional 26 MGUS sera, 10 newly diagnosed, 11 post-transplant remission and 12 relapsed MM patients and 25 normal donors. Whereas an antibody response was observed against OFD1 (20.6%), KIAA0530 (10.3%), AKAP11 (10.3%) and GPATC4 (6.8%) in MGUS patients, no responses were observed in normal donors or MM patients except against OFD1 in 3 post transplant patients. We have further focused our studies on OFD1, a developmentally expressed Hedgehog (Hh)-pathway-related protein with most frequent antibody response. We have previously showed that Hh-pathway genes are involved in development of MGUS. Our microarray analysis showed that OFD1 and other Hh pathway-related genes (Sonic, Smothened, Patched, Gli-1 and Gli-3) are selectively expressed in MM cell lines and primary cells. We have further evaluated a specific inhibitor of Hh- pathway, Cyclopamine, in MM and observed an inhibition of the proliferation in 5 MM cell lines with an IC50 between 13 - 20 μM. Conclusion: We have confirmed a specific immune response in MGUS and have identified a novel therapeutic target for treatment of MM. No significant financial relationships to disclose.
Medically Underrepresented Populations In National Cancer Institute (NCI) Sponsored Cancer Clinical Trials: Refining the Calculation of Accrual Targets.
Authors: Michael S. Katz, Allan Topham, Judith Manola, Mary Jackson Scroggins, Mary Lou Smith, Edith P. Mitchell, Robert B. Catalano, Donna M. Marinucci, Bruce J. Giantonio, Robert Leo Comis
Journal: Journal of Clinical Oncology (2015)

e17598 Background: Equitable accrual of underrepresented populations to cancer clinical trials is lacking, resulting in failure to achieve distributive justice in clinical research, and uncertainty in applying outcomes to the underrepresented.. No validated metric exists to accurately identify accrual targets for underrepresented groups. Currently, percentages are derived from the general population to set targets for NCI-sponsored trials, with performance determined from actual accruals and does'nt consider disease specific and demographic variances. We propose a metric to establish targets that more accurately measure performance. Methods: Accrual to US NCI-funded Cooperative Group clinical trials for 2007Q1-2014Q1 (~160,000 cases), SEER risk rates and US census data were used to estimate accrual targets. Each accrual is apportioned with expected values based on patient demographics, disease site and expected accrual by population. Performance estimates were determined by comparing actual accruals to the estimated target by population for age, disease site and gender. Chi square tests were used to compare observed to expected cell frequencies. Results: In the period analyzed (2007Q1-2010Q1) Whtes over-accrued (OA) by 2%, blacks under-accrued (UA) by 11.6%, and hispanics UA by 12.3% (all with P < 0.0001). Blacks OA to trials in GU cancers 18% (P < 0.0001). Significant UA for Blacks occurred in: kidney cancer (57%), CNS tumors (55%), and lymphoma (28%), each with P < 0.0001. Hispanics OA in breast cancer 5% (P = 0.01) and lung cancer 24% (P < 0.0001). Significant UA for Hispanics occurred in: CNS tumors (51%), skin cancers (48%) and lymphoma (46%) (all with P < 0.0001). Males OA by 9.7%, females UA by 3.7%, both with P < 0.0001. By age: 20-40 year olds (yo) OA by 32.7%, 40-60 yo UA by 9.8%, older than 60 yo UA by 16.9%; each with P < 0.0001. Conclusions: Compared to ideal distributions based not only on demographics but diagnosis, both OA and UA of underrepresented minority groups occur in cancer clinical trials. Objective metrics can facilitate equitable assessment and targeted interventions addressing accrual of underrepresented populations.
Clinical impact of febrile neutropenia (FN) increase among patients receiving adjuvant docetaxel/cyclophosphamide (TC) chemotherapy compared to TC plus pegfilgrastim for breast cancer.
Authors: Erika Paige Hamilton, Donna L. Topping, Jeffrey M. Peppercorn, P. Kelly Marcom, Gretchen Genevieve Kimmick, Erin Duff, Constance T. Cirrincione, Kimberly L. Blackwell
Journal: Journal of Clinical Oncology (2013)

1076 Background: The FN rate for the approved regimen of TC is 5% in pivotal studies. Other small retrospective reports have reported FN rates as high as 20-35%. We report the incidence of FN from a large retrospective series of breast cancer patients receiving TC with or without pegfilgrastim (PF) for adjuvant therapy. Methods: We reviewed records of 240 sequential patients who had received adjuvant TC (75 and 600 mg/m 2 ) between Mar ’07 and Nov ’12 for FN, upfront PF use, and adverse events by treatment cohort. FN was defined as T&gt; 100.4°F and ANC &lt;500, while upfront PF was defined as PF given at physician discretion 24-48h after 1 st cycle of TC administration. Comparisons between two proportions used exact binomial methods; effect of PF on FN after adjusting for baseline characteristics was tested using multivariate logistic regression. Results: 153 (63.7%) patients received upfront PF, while 87 (36.3%) did not (Table). Patients receiving upfront PF were older (57 vs. 52 yrs, p=0.02). Other baseline characteristics (size of primary tumor, hormone receptor status, and nodal status) were no different between groups. FN, fever, antibiotic use, hospitalization, and dose delay were significantly higher when upfront PF was not used (Table). The average length of hospital stay was 2.9 days for TC + PF, and 3.8 days for TC pts. 31/87 (35.6%) of patients without upfront PF went on to receive PF after the 1st cycle. Conclusions: FN for adjuvant TC meets clinical practice threshold and ASCO guidelines for upfront use of PF. FN-related outcomes such as fever, antibiotic use, dose delays, and number of hospitalizations, and were significantly increased without upfront PF. The cost-effectiveness of these findings will be presented and have major clinical implications for routine care. [Table: see text]
Molecular mechanisms involved in paclitaxel-resistance in advanced ovarian cancer
Authors: Cristiano Ferlini, Gabriella Ferrandina, Simona Mozzetti, Paola Concolino, Giuseppina Raspaglio, Flavia Filippetti, Enrica Martinelli, Silvia Prislei, Giovanni Scambia
Journal: Cancer Research (2004)

5431  Advanced ovarian cancer is one of the most chemosensitive of all solid tumours to chemotherapy and responses are expected in 80% patients who receive standard paclitaxel-based treatment. Nevertheless, the vast majority of women with advanced ovarian cancer will ultimately relapse and develop a drug-resistant disease with an overall 5-year survival of less than 50%. One of the main problem in fighting the clinical problem of drug-resistance, is that still now the mechanisms of drug-resistance actually operating in patients are not known, due to the absence of studies comparing several mechanisms of drug resistance in the same clinical setting. To address this issue, we have investigated in a clinical cohort of 41 patients affected by advanced ovarian cancer the three main mechanisms previously reported in clinical settings as possible mediators of paclitaxel-resistance: overexpression of mdr1 gene, point mutations at beta tubulin gene (TUBB) and selective alterations in the expression of beta-tubulin isotypes. In this clinical setting chemotherapy followed surgery and patients did not receive any treatment before paclitaxel-including chemotherapy. Mdr1 and beta tubulin isotypes expression were evaluated by semiquantitative PCR. Mdr1 expression (41/41) was below the threshold of detectability in both groups of patients (resistant and sensitive). Tubulin mutations at the level of the paclitaxel binding site was evaluated by automated DNA sequencing. Thirty-three/41 patients were evaluated and no differences were detected between resistant and sensitive cases. For that concerning expression of tubulin isoforms, a statistically significant upregulation of class III beta tubulin (TUBB4) was found in the resistant subset. As compared to the expression levels detected in ovarian tissue taken from normal biopsies (5), TUBB4 resulted four fold more expressed in the paclitaxel-sensitive subset (28) and near eight fold in the paclitaxel-resistant setting (13). By a direct comparison of the three main mechanisms of paclitaxel-resistance previously reported in clinical specimens, this study indicates that overexpression of TUBB4 is the most prominent mechanism of paclitaxel-resistance. Due to its low expression in normal ovarian tissue, TUBB4 appears as a suitable target to develop novel agents useful to overcome paclitaxel-resistance.
Circulating tumor cells (CTCs) and LDH as prognostic factors in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing during or following docetaxel treated in the orteronel phase 3 ELM-PC 5 trial.
Authors: Howard I. Scher, Karim Fizazi, Connie Lee, David Maclean, Bindu Tejura, Iain James Webb, Niels Geert Borgstein, Robert Dreicer
Journal: Journal of Clinical Oncology (2014)

5014 Background: Results from a global phase 3 study demonstrated that orteronel 400 mg BID /prednisone 5 mg (O+P), vs placebo/prednisone alone (P), improved radiographic progression (rPFS) and increased PSA50 response but resulted in no overall survival (OS) benefit (HR 0.89) (Dreicer et al., ASCO GU 2014). Methods: Whole blood samples for CTC enumeration (Veridex Cell Search, Esoterix) were obtained from 1,038 pts at baseline and 635 at end of wk 12 (primary CTC endpoint). Results were reported as number counted CD45-/EpCam+ cells/7.5 mL whole blood. Results: Baseline distribution of favorable (< 5 cells/7.5 mL) to unfavorable (≥ 5 CTCs/7.5 mL) were balanced in the two groups (40% favorable in each). In cross sectional analysis, the percent favorable remained unchanged with P at wk 12 (96/214) (45%) but increased to 62% (262/421) with O+P. Patient shift analysis showed that 99 of 231 (43%) of pts on O+P converted to favorable vs. 17 of 113 (15%) on P. A trichotomous surrogate biomarker panel (Scher et al, ESMO 2013) based on 12-wk data categorized patients as low-risk (CTC ≤ 4), intermediate-risk (CTC ≥ 5, LDH ≤ 225 U/L) or high-risk (CTC ≥ 5, LDH > 225 U/L). Distribution of risk at 12 wks by treatment was for O+P vs. P: low, 262 (36%) vs. 96 (26%); intermediate, 63 (9%) vs. 54 (15%); and high, 93 (13%) vs. 59 (16%). At 12 wks, the overall survival (OS) HRs for the three risk categories adjusted for treatment and other baseline characteristics are shown in the table. Addition of treatment effect to the K-M estimates for risk groups did not give additional predictive value at that 12-wk timepoint. Results with a dichomotous CTC-only model were similar: OS % at 1 and 2 yrs was 87 and 61 vs. 51 and 15 for ≤ 4 vs. ≥ 5 respectively (P < 0.0001). Conclusions: O+P resulted in a more favorable risk redistribution of CTCs at 12 wks and the risk categories were strongly predictive of OS. The findings support the therapeutic impact of O+P relative to P as well as the prognostic potential for CTC at 12 wks. Clinical trial information: NCT01193257. Risk at 12 wks HR CI P-value Intermediate- vs. low-risk 2.596 (1.742, 3.870) < 0.0001 High- vs. low-risk 6.218 (4.329, 8.931) < 0.0001
A phase I/II trial of the combination of romidepsin and lenalidomide in patients with relapsed/refractory lymphoma and myeloma: Activity in T-cell lymphoma.
Authors: Neha Mehta-Shah, Matthew Alexander Lunning, Adam M. Boruchov, Jia Ruan, Sumithra Nair, Peggy Lynch, Regina Byrne, Alison J. Moskowitz, Matthew J. Matasar, John F. Gerecitano, Paul A. Hamlin, John Leonard, Craig H. Moskowitz, Patricia L. Myskowski, Christiane Querfeld, Patrick Nolan, Maria Lia Palomba, David J. Straus, Andrew David Zelenetz, Steven M. Horwitz
Journal: Journal of Clinical Oncology (2015)

8521 Background: Epigenetic manipulation and immunomodulation are therapeutic strategies in hematologic malignancies. Romidepsin (romi), a histone deacetylase inhibitor, and lenalidomide (len), an immunomodulatory agent, both have efficacy and lack cumulative toxicity in relapsed/refractory (rel/ref) lymphoma and myeloma. Methods: The phase I part of the study was reported at ASCO 2014. The MTD defined in cycle 1 was romi 14 mg/m2 IV on days 1, 8, and 15 and len 25 mg oral on days 1-21 of a 28-day cycle. Patients (pts) were treated to progression or intolerance. Disease-specific cohorts in T-cell lymphoma (TCL), B-cell lymphoma and multiple myeloma were enrolled at the MTD. We report the results of the TCL subjects. Results: 21 pts with TCL (10 CTCL, 11 PTCL) were enrolled with 15 treated at the MTD. Median age was 64 with 52% male (n = 11).19 pts were evaluable for efficacy with an ORR of 53% (10/19). Two pts were not evaluable for response (one due to toxicity in cycle 1 without progression, one on steroids for idiopathic thrombocytopenic purpura with PET normalization prior to dose 1). The ORR in PTCL was 50% (5/10, 5 PR). Responses were seen in PTCL-NOS (3), AITL (1), T-PLL (1). One with relapsed ATLL remains on therapy with SD ongoing at 24 weeks (w). The ORR in CTCL was 56% (5/9, 2 CR, 3 PR). CR was seen in transformed MF (1), and Sezary syndrome (1). The median time to response was 7.3 w (range: 2.8-16.9 w). Median OS was not reached. Median event free survival was 15.5 w (CTCL 30.0 w, PTCL 13.5 w). However 48% (10/21) pts remain on therapy (2 CR, 6 PR, 2 SD) at a median of 15.3 w (range: 9.0-106.6 w). 7 pts discontinued for progression, 3 for toxicity and 1 for transplant. The median number of cycles was 4 (range: 1-27). 71% of pts had AEs ≥ Grade 3, with the most common ( ≥ 10%) being neutropenia (48%), thrombocytopenia (38%), anemia (33%), electrolyte abnormalities (K, Phos, glucose, Mg) (43%). Conclusions: The combination of romi and len appears to have significant activity in rel/ref TCL (ORR 53%) with acceptable safety profile. These results support further evaluation of romi and len in patients with TCL, including additional studies in both CTCL and PTCL. Clinical trial information: NCT01755975.
Mobile cognitive assessment battery (MCAB) for assessment of cancer-related cognitive changes.
Authors: Shelli Kesler, Douglas W Blayney
Journal: Journal of Clinical Oncology (2014)

9571 Background: A majority of patients with cancer report cognitive decline associated with cancer treatments. Traditional cognitive measures may lack adequate sensitivity to these cognitive difficulties, are weakly associated with patient self-report and have limited feasibility. We aimed to evaluate cognitive change in patients with breast cancer (BC) using our novel Mobile Cognitive Assessment Battery (MCAB) and compare MCAB with traditional neuropsychological measures. Methods: We have enrolled 39 women newly diagnosed with primary BC (mean age = 50 +/- 9 years) and 35 matched healthy women. Patients were assessed prior to any surgery requiring general anesthesia (T1) and again within one month of completing chemotherapy but prior to any radiation or hormonal therapy (T2). Controls were assessed at yoked intervals. We administered the Comprehensive Trail Making, Controlled Oral Word Association and Rey Auditory Verbal Learning tests, the Behavioral Rating Inventory of Executive Function (BRIEF) and our in-house MCAB. MCAB is administered via mobile tablet with tests including n-back, multi-tasking, and task switching. We compared cognitive function between the groups at baseline using analysis of variance, change in cognitive function over time using linear mixed modeling and correspondence between subjective and objective measures using Pearson correlations. Results: There were no differences between groups in cognitive function at T1. Compared to controls, the BC group showed no change in cognitive function from T1 to T2 as measured by traditional tests. Patients’ self-rated cognitive problems (BRIEF) increased significantly over time (p = 0.031). MCAB (requiring 15 minutes to administer), detected significantly lower cognitive function over time in the BC group compared with controls in task switching (p < 0.001) and multi-tasking (p = 0.019). Traditional tests (40 minutes) were not significantly correlated with patients’ self-ratings although MCAB tests were (p < 0.039). Conclusions: Our MCAB may be more convenient, more sensitive to changes in cognitive function and subjective patient report associated with BC treatment compared to traditional measures.
A combination of pocket, double-clip countertraction, and isolated HybridKnife as a quick and safe strategy for colonic endoscopic submucosal dissection
Authors: Jérémie Jacques, Romain Legros, Aurélie Charissoux, Jérôme Rivory, Denis Sautereau, Emmanuelle Pauliat, Mathieu Pioche
Journal: Endoscopy (2017)

The colon is considered to be one of the most technically challenging locations for endoscopic submucosal dissection (ESD) when superficial neoplastic lesions are being treated [1]. The difficulties include: the colonic loops, intestinal motility, the folded anatomy, problems caused by inconstant gravity, and constant modification of the operative field-of-view attributable to insufflation. Good exposure of the submucosal layer is key for safe and efficient ESD; this can be particularly challenging in the colon where it is difficult to maintain a tangential position close to the muscle layer. Many tips and tricks have been reported to facilitate colonic ESD, including:
Targeting the upregulation of the AKT pathway and homologous recombination repair as a therapeutic strategy for epithelial ovarian cancer.
Authors: Elena Ratner, Z-Ping Lin, Thomas J. Rutherford, Masoud Azodi, Alessandro Santin, Peter E. Schwartz, Alan Sartorelli
Journal: Journal of Clinical Oncology (2012)

e13125 Background: Epithelial ovarian cancer (EOC) is the second most common gynecologic cancer in the United States, and carries the highest mortality in this category in the West. The progression free survival and overall survival depend greatly on tumor sensitivity to a platinum chemotherapy. Once platinum resistance is encountered, response rates of only 6–30% are achieved. A relatively new modality in EOC that would allow targeted treatments is a PARP inhibitor, a drug that inhibits the enzyme poly (ADP-ribose) polymerase (PARP), which is showing promise for the treatment of EOC with mutations in the BRCA1 or BRCA2 tumor suppressors. Triapine, a novel small-molecule drug developed in our laboratory, potently inhibits the activity of ribonucleotide reductase involved in the key step of DNA synthesis and replication. Methods: 1. Cell sensitivity to varying ratios of treating drug combinations (Triapine with cisplatin; PARP inhibitor, olaparib) was carried out by clonogenic survival assays using multiple EOC cell lines (A2780, Caov-3, EFO, IGROV-1, BG-1, PEO1, SKOV3). 2. AKT level was measured in the cell lines before and after treatment. 3. BRCA1 wild-type and BRCA1-knockdown EOC cells were treated with cisplatin or PARP alone and in combination with Triapine. Drug-induced DNA damage was assessed by the levels of g-H2AX, the marker of double stranded breaks (DSBs), and of Rad51 foci, a marker of HR repair of DSBs. Results: Treatment with Triapine leads to synergistic sensitization of BRCA1 wild-type EOC cells to platinum drugs and to olaparib. Both platinum drugs and olaparib induce DNA damage that is repaired by HR. This suggests that Triapine inhibits HR and sensitizes EOC cells to these drugs. Triapine attenuates olaparib-induced Rad51 foci in BRCA1-wild type cells, which resembles the impairment of such foci formation in BRCA1-knockdown cells. Triapine causes down-regulation of AKT activity in EOC cells. Conclusions: Triapine produces synthetic lethality by inhibiting both DNA repair and pro-survival pathways. Combination of Triapine and platinum drugs/PARP inhibitors represents a rational and innovative therapy that targets EOC with a high level of AKT activity.