tbuckley/cabot-search huggingface dataset:
PET/MR Outperforms PET/CT in Suspected Occult Tumors
Authors: Tetsuro Sekine, Felipe de Galiza Barbosa, Bert-Ram Sah, Cäcilia E. Mader, Gaspar Delso, Irene A. Burger, Paul Stolzmann, Edwin E. ter Voert, Gustav K. von Schulthess, Patrick Veit-Haibach, Martin W. Huellner
Journal: Clinical Nuclear Medicine (2016)

Background To compare the diagnostic accuracy of PET/MR and PET/CT in patients with suspected occult primary tumors. Methods This prospective study was approved by the institutional review board. Sequential PET/CT-MR was performed in 43 patients (22 male subjects; median age, 58 years; range, 20-86 years) referred for suspected occult primary tumors. Patients were assessed with PET/CT and PET/MR for the presence of a primary tumor, lymph node metastases, and distant metastases. Wilcoxon signed-rank test was performed to compare the diagnostic accuracy of PET/CT and PET/MR. Result According to the standard of reference, a primary lesion was found in 14 patients. In 16 patients, the primary lesion remained occult. In the remaining 13 patients, lesions proved to be benign. PET/MR was superior to PET/CT for primary tumor detection (sensitivity/specificity, 0.85/0.97 vs 0.69/0.73; P = 0.020) and comparable to PET/CT for the detection of lymph node metastases (sensitivity/specificity, 0.93/1.00 vs 0.93/0.93; P = 0.157) and distant metastases (sensitivity/specificity, 1.00/0.97 vs 0.82/1.00; P = 0.564). PET/CT tended to misclassify physiologic FDG uptake as malignancy compared with PET/MR (8 patients vs 1 patient). Conclusions PET/MR outperforms PET/CT in the workup of suspected occult malignancies. PET/MR may replace PET/CT to improve clinical workflow.
Effect of Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram to avoid conventional axillary dissection of one node–metastasis Japanese patients with breast cancer.
Authors: S. Tominaga, Y. Kotsuma
Journal: Journal of Clinical Oncology (2011)

e11531 Background: Our aim was to define the role of MSKCC nomogram in avoiding conventional axillary dissection of one node-metastasis breast cancer patients. Methods: Between January 2009 to November 2010, clinically axillary node negative consecutive 186 patients underwent sentinel lymph node biopsy using 12 mg Indigo carmine in our institution. Results: In 14 (7.5%) of the 186 cases with metastatic axillary nodes were node positive and underwent axillary dissection. Final pathological results shows 10 of 14 patients revealed one node-metastasis and four patients revealed more than 2 node-metastasis. Assessment of MSKCC nomogram, average of probability of spread to additional lymph node were 25.4% for the former group, 54% for the latter group. Conclusions: Our study confirms MSKCC nomogram’s role in sentinel lymph node biopsy of breast cancer surgery. MSKCC nomogram may prove useful in avoiding benefit from axillary dissection of only one node-metastasis breast cancer patients.
France shows what has gone wrong in the UK and US
Authors: Danny Dorling
Journal: BMJ (2016)

The outcome of the French presidential election, in which the Republican Francois Fillon, Front National’s Marine Le Pen, and the Socialist Party will be vying for position in April 2017, could have wide reaching implications for public health in Europe. Concerns over living standards in France will influence the vote—could income inequality and poor health also influence voting, as it seems to have done in the UK referendum and the US presidential election? Marine Le Pen has already argued that Donald Trump’s victory in the US is a precursor to her own impending success.1

The strongest predictor of a rise in Republican voting for Donald Trump was a decline in the health of the residents in their local area. An age adjusted index showing falls in local life expectancy, obesity, and diabetes—as well as heavy drinking and lack of regular physical activity—best predicted those areas that swung the most to Trump.2

Donald Trump repeatedly cited the UK Brexit vote as a precedent, suggesting that he could win …
The Role of Proteinase Inhibitor 9 (PI-9) and Granzyme B in Peripheral Leukocytes for GVL and GVHD After Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Osamu Horie, Kaori Minami, Sawako Toji, Kenji Yonezawa, Hiroshi Gomyo, Akio Maeda, Ishikazu Mizuno, Tohru Murayama, Mitsuhiro Ito
Journal: Blood (2011)
Male breast cancer: An institution’s 25-year experience.
Authors: J. S. Scow, A. C. Degnim, J. W. Jakub, S. Shah, R. E. Jimenez, J. C. Boughey
Journal: Journal of Clinical Oncology (2011)

247 Background: There are no prospective and few large retrospective studies of male breast cancer (MBC). This study’s aim was to describe our institutional experience with MBC and evaluate the ability of the AJCC staging system to stratify survival. Methods: All MBC cases were identified from our institution’s cancer registry from 1984-2008. Data collected included tumor characteristics, lymph node status, treatment, age, and survival. Results: During the study period 166 MBC cases were identified. Median age at diagnosis was 62 years (range 27-87). Most common presentation was a palpable breast mass (77%). Stage at diagnosis was stage 0 (6%), stage 1 (27%), stage 2 (36%), stage 3 (17%), stage 4 (5%), and unknown (9%). Procedure performed was mastectomy in 148 patients (89%), lumpectomy in 10 patients (6%) and unknown in 8 patients (5%). Median tumor size was 2.0 cm (range 0.2-11.0 cm). Most common histology was invasive ductal carcinoma (91%). Estrogen and progesterone receptor status assessed at diagnosis was positive in 93% and 86% of cases tested respectively. HER2/neu status was positive in 6 of 47 cases tested (13%). Nodal staging was performed by axillary dissection (AD) (70%), sentinel node biopsy (SN) alone (11%), SN and AD (11%) and no axillary staging (8%); 43% were node positive, 47% node negative and 10% unknown. Adjuvant chemotherapy was given to 40 patients (24%), adjuvant hormonal therapy to 42 patients (25%) and adjuvant radiation therapy was used in 33 cases (20%). With a median follow-up of 5.5 years, 86 patients (52%) have died: 44 due to breast cancer, 23 due to causes unrelated to breast cancer, and in 19 the cause of death is unknown. Median overall survival was 9.3 years. Median cancer-specific survival was 16.0 years. For patients initially diagnosed at stage 2, 3, and 4 median cancer-specific survival was 12.9, 7.2, and 0.8 years respectively. Median cancer-specific survival was significantly different for stages 2 vs. 3 (p = 0.03) and 3 vs. 4 (p = 0.0006). Conclusions: MBC most commonly presents as a palpable mass, is hormone responsive, and is most commonly treated with mastectomy. The TNM system appropriately stratifies men with MBC by duration of survival.
Comparative analysis of myeloid-derived suppressor cell (MDSC) subsets in patients with gastrointestinal (GI) malignancies.
Authors: Austin G. Duffy, Fei Zhao, Suzanne Fioraventi, Tim Greten
Journal: Journal of Clinical Oncology (2012)

10566 Background: Immunotherapy represents a potential new treatment option for patients with cancer. Myeloid derived suppressor cells (MDSCs) constitute a heterogenous cell population, which inhibit the host anti-tumor immune response, limiting the effectiveness of both immune and non-immune treatments. MDSC are known to be increased in patients with GI cancer. Characterization of MDSC in humans has been difficult with heterogeneous phenotype classification. Differences in processing are also potentially important. The aim of this study was to perform a comparative analysis of MDSC subsets in patients with GI cancer. Methods: Fluorescence activated cell sorting (FACS) analysis was performed on PBMC and whole blood (WB) from healthy adults (N=44) and patients with GI cancer (N=41). MDSC subsets were enumerated using the following antibodies: anti-CD14; anti-CD15; anti-HLA-DR; anti-CD33; anti-CD11b; 7-AAD. Suppressor function of MDSC subsets was tested using FACS sorted MDSC subpopulations co-cultured with CD3/CD28-stimulated autologous effector cells. Proliferation and IFN-g were measured. Results: The frequencies of Monocytic (Def: CD14 + , HLA-DR -/low ) and Granulocytic (Def: CD15 + ,CD14 - CD33 + CD11b + ) MDSC are shown in the table below. Monocytic MDSC were increased in the blood of patients (vs control; P&lt;.0001) and frozen (vs fresh PBMC; P&lt;.05). While CD15+ cells were increased in cancer patients we did not find an increase in granulocytic MDSC. Functional studies will also be presented. Conclusions: Monocytic MDSC are more frequent in patients with advanced GI cancer compared to healthy volunteers. An increase in this population was also found in WB and frozen PBMC compared to fresh PBMC reflecting the need for homogenous preparation in studies evaluating this population in humans. While CD15+CD14- cells were also increased in cancer patients we did not find an increase in CD14-CD15+CD33+CD11b+ cells. [Table: see text]
High-grade prostate cancer with favorable results in the modern era.
Authors: E. Ramahi, G. P. Swanson, F. Du, J. Basler
Journal: Journal of Clinical Oncology (2011)

107 Background: Historically, patients with high-grade prostate cancer have the worst outcomes. With the advent of prostate- specific antigen (PSA) screening, diagnosing prostate cancer no longer depends on palpation of a bulky mass on digital rectal exam and prostate cancers are found at an earlier stage. Our aim is to determine the outcome of a modern cohort of high grade patients with the available treatment options. Methods: We reviewed the STVHS Tumor Registry and identified those patients diagnosed with prostate cancer between 2002 and 2008 capturing those patients with Gleason score &gt;7 on biopsy. Details including all recorded PSA values, biopsy and surgical pathology results, primary, neoadjuvant and adjuvant treatment, as well as response to treatment were recorded and analyzed using Kaplan-Meier estimates, log-rank test, and multivariate analysis using Cox proportional hazards models. Results: We identified 297 patients with Gleason 8–10 cancer with a median follow up of 35 months. Initial treatment was surgery in 136, radiation in 52, and androgen ablation in 110; one patient has both surgery and androgen ablation. Five and 10 year biochemical-free survival (BFS), metastasis-free survival, and overall survival are shown in the Table . Overall, 5 year biochemical failure-free survival was 50% and metastasis free survival was 89%, resulting in an overall survival of 77%. Conclusions: Historically, patients with a Gleason score of 8–10 have done very poorly. However, in the modern era, regardless of the initial treatment, the outcome is not as dire. Possible reasons are less bulky tumors or other facets of stage migration. While there is room for improvement, we should not have a nihilistic impression of how these patients will respond to treatment. [Table: see text] No significant financial relationships to disclose.
Sixty-eight consecutive cases of neuroendocrine tumor treated with somatostatin analogues: A 20-year single-center experience.
Authors: Theodoros Savvoukidis, Silke Cameron, Giuliano Ramadori
Journal: Journal of Clinical Oncology (2012)

e14707 Background: Neuroendocrine tumours (NET) arise from enterochromaffine and related cells found in epithelial organs throughout the body. Hormone related symptoms in neuroendocrine tumours are well treated with somatostatin analogues. Previous experience has demonstrated some antiproliferative activity of somatostatin analogues in the treatment of NET. Methods: In the last 20 years 68 patients with histologically proven NET were treated: primaries in small bowel (27), pancreas (17), rectum (9), appendix (5), lung (4), unknown (3), extra- adrenal abdominal paragangliomas (2) and stomach (1). The mean age of first diagnosis was 56 years. All of them received somatostatin analogues in long acting depot administration (or combination interferon/somatostatin analogues) for a minimum period of two months and a maximum of 139 months. Somatostatin therapy was started in patients with endocrine-active tumours immediately after the diagnosis and in patients with endocrine-inactive tumours after an observation time of 3 months without therapy if progress was observed. Tumor size was assessed every 3 months after begin of therapy. Results: Best responses were a stable disease in 46 of 68 patients (68%) and a partial remission in 2 (3%). Twenty of 68 patients (29%) showed progress. The responses achieved were in small bowel 20/27; pancreas 14/17; rectum 7/9; appendix 4/5 and lung 3/4. The median duration of response was 34 months. Conclusions: Our results document that treatment with somatostatin analogues prolongs time to progression in NET. Stabilisation of tumour mass itself is a relevant outcome for patients with NET. The benefit of somatostin analogues is indipendent to use of chemotherapy. Because of its efficacy and the good tolerability somatostatin analogues can be considered a first line treatment option.
Evaluation of combination treatment benefits of nab-paclitaxel in experimental pancreatic cancer.
Authors: Niranjan Awasthi, Katherine Ostapoff, Changhua Zhang, Margaret A. Schwarz, Roderich Schwarz
Journal: Journal of Clinical Oncology (2012)

170 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human cancers and is characterized by early tissue invasion, metastasis and high resistance to systemic therapies. Gemcitabine, a standard cytotoxic therapy for pancreatic cancer, has shown limited clinical benefits. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel), an approved treatment for breast cancer, has shown efficacy as mono- and combination therapy in multiple tumor types including pancreatic, lung and ovarian cancer. We evaluated combination treatment benefits of nab-paclitaxel with gemcitabine in experimental pancreatic cancer. Methods: In vitro cell proliferation was evaluated by WST-1 assay in human PDAC cells. Animal survival studies were performed in murine xenografts. Results: Nab-paclitaxel inhibited in vitro proliferation of PDAC cell lines with IC50 levels of 7.6 mM, 208 nM, 519 nM and 526 nM for AsPC-1, BxPC-3, MIA PaCa-2 and Panc-1 cells. Nab-paclitaxel combination with gemcitabine had significant additive effect on inhibition of PDAC cell proliferation; 72-hour incubation demonstrated that nab-paclitaxel addition caused a 2.5, 2.5, 8.9 and 2.2-fold decrease in IC50 of gemcitabine in AsPC-1, BxPC-3, MIA PaCa-2 and Panc-1 cells, respectively. In an intraperitoneal murine xenograft model, 2-week therapy demonstrated that compared to controls (median survival: 23 days), animal survival increased after gemcitabine (27 days, p=0.05) and nab-paclitaxel monotherapy (35 days, p=0.0005). In a separate 3-week therapy experiment, animal survival was significantly longer in the nab-paclitaxel treated group (41 days, p&lt;0.002 versus control and Gem) compared with gemcitabine (32 days, p=0.005 versus control), docetaxel (32 days, p=0.005) and controls (20 days). Animal survival in nab-paclitaxel / gemcitabine and docetaxel / gemcitabine sequential treatment group was 43 and 40 days, respectively. Conclusions: Nab-paclitaxel has significant antitumor activity as a single agent in experimental pancreatic cancer and can also enhance gemcitabine effects in combination. These findings provide a strong rationale for testing nab-paclitaxel in patients with pancreatic cancer.
Mesenchymal STEM CELLS Favor Tumor Growth By Generating Granulocyte-like Myeloid Derived Suppressor CELLS in CML Patients
Authors: Cesarina Giallongo, Nunziatina L Parrinello, Daniele Tibullo, Claudia Bellofiore, Piera La Cava, Alessandra Romano, Annalisa Chiarenza, Fabio Stagno, Paolo Vigneri, Giuseppe A. Palumbo, Francesco Di Raimondo
Journal: Blood (2015)
Optimized T-cell receptor-mimic chimeric antigen receptor T cells directed toward the intracellular Wilms Tumor 1 antigen
Authors: S Rafiq, T J Purdon, A F Daniyan, M Koneru, T Dao, C Liu, D A Scheinberg, R J Brentjens
Journal: Leukemia (2016)

CD19-directed chimeric antigen receptor (CAR) T cells are clinically effective in a limited set of leukemia patients. However, CAR T-cell therapy thus far has been largely restricted to targeting extracellular tumor-associated antigens (TAA). Herein, we report a T-cell receptor-mimic (TCRm) CAR, termed WT1-28z, that is reactive to a peptide portion of the intracellular onco-protein Wilms Tumor 1(WT1), as it is expressed on the surface of the tumor cell in the context of HLA-A*02:01. T cells modified to express WT1-28z specifically targeted and lysed HLA-A*02:01+ WT1+ tumors and enhanced survival of mice engrafted with HLA-A*02:01+, WT1+ leukemia or ovarian tumors. This in vivo functional validation of TCRm CAR T cells provides the proof-of-concept necessary to expand the range of TAA that can be effectively targeted for immunotherapy to include attractive intracellular targets, and may hold great potential to expand on the success of CAR T-cell therapy.
RB Loss Promotes Prostate Cancer Metastasis
Authors: Chellappagounder Thangavel, Ettickan Boopathi, Yi Liu, Alex Haber, Adam Ertel, Anshul Bhardwaj, Sankar Addya, Noelle Williams, Stephen J. Ciment, Paolo Cotzia, Jeffry L. Dean, Adam Snook, Chris McNair, Matt Price, James R. Hernandez, Shuang G. Zhao, Ruth Birbe, James B. McCarthy, Eva A. Turley, Kenneth J. Pienta, Felix Y. Feng, Adam P. Dicker, Karen E. Knudsen, Robert B. Den
Journal: Cancer Research (2016)

Abstract RB loss occurs commonly in neoplasia but its contributions to advanced cancer have not been assessed directly. Here we show that RB loss in multiple murine models of cancer produces a prometastatic phenotype. Gene expression analyses showed that regulation of the cell motility receptor RHAMM by the RB/E2F pathway was critical for epithelial–mesenchymal transition, motility, and invasion by cancer cells. Genetic modulation or pharmacologic inhibition of RHAMM activity was sufficient and necessary for metastatic phenotypes induced by RB loss in prostate cancer. Mechanistic studies in this setting established that RHAMM stabilized F-actin polymerization by controlling ROCK signaling. Collectively, our findings show how RB loss drives metastatic capacity and highlight RHAMM as a candidate therapeutic target for treating advanced prostate cancer. Cancer Res; 77(4); 982–95. ©2016 AACR.
Phase 1/2 study of pacritinib, a next generation JAK2/FLT3 inhibitor, in myelofibrosis or other myeloid malignancies
Authors: Srdan Verstovsek, Olatoyosi Odenike, Jack W. Singer, Tanya Granston, Suliman Al-Fayoumi, H. Joachim Deeg
Journal: Journal of Hematology & Oncology (2016)

Pacritinib (SB1518) is a highly selective kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CFS1R. This multicenter phase 1/2 study evaluated the maximum tolerated dose (MTD), safety, and clinical activity of pacritinib in patients with myelofibrosis (MF) and other advanced myeloid malignancies. In the phase 1 dose-escalation part of the study, 43 adults with advanced myeloid malignancies received pacritinib 100 to 600 mg once daily (QD). In the phase 2 part of the study, 31 adults with refractory or intermediate- or high-risk newly diagnosed MF and any degree of cytopenia received pacritinib 400 mg QD. The primary endpoint is a ≥35% reduction in spleen volume at week 24 as determined by magnetic resonance imaging. Five patients (11.6%) experienced a dose-limiting toxicity during cycle 1 of phase 1. The clinical benefit rate was 86.0% (13 patients achieving clinical improvement and 24 patients having stable disease). The MTD was established at 500 mg QD, and the recommended phase 2 dose was 400 mg QD. In phase 2, the primary endpoint was achieved by 23.5% of evaluable patients (4/17), with 47.4% (9/19) achieving a ≥50% spleen length reduction at week 24 as measured by physical examination. At week 24, 38.9% of evaluable patients (7/18) achieved a ≥50% decrease in MF Quality of Life and Symptom Assessment total score. Gastrointestinal toxicities were the most common adverse events and were predominantly grade 1/2 in severity. Grade 3/4 anemia was reported in 5/31 patients and grade 3/4 thrombocytopenia was reported in 3/31 patients. The most frequent AEs considered to be treatment related were diarrhea (28/31), nausea (15/31), vomiting (9/31), and fatigue (4/31). Grade 3 treatment-related AEs were reported in seven patients (22.6%), four of whom had diarrhea. No grade 4/5 treatment-related AEs were reported. No leukopenia, neutropenia, or lymphopenia were reported. Pacritinib was well tolerated and demonstrated clinical activity in MF. The study suggests that pacritinib has unique characteristics, namely a lack of substantial myelosuppression and manageable side effects, making it an attractive target for further evaluation in MF. Retrospectively registered at www.clinicaltrials.gov (# NCT00719836 ) on July 20, 2008.
Successful Result of 113 Patients for Refractory/Recurrent Leukemia By Allogeneic Hematopoietic Cell Transplantation and Prophylactic Immunotherapy
Authors: Jingbo Wang, Xiaojun Huang, Ying Hu, Song Xue, Haoyu Cheng, Yuming Yin, Weijie Zhang, Jiangying Gu, Junbao He, Fan Yang
Journal: Blood (2016)
Acquired Resistance to Tumor Necrosis Factor-Related Apoptosis- Inducing Ligand (TRAIL): Histone Deacetylase Inhibitors Resensitize TRAIL-Resistant Jurkat Acute Lymphocytic Leukemia Cells
Authors: Pavel Klener, Jan Molinsky, Tereza Simonova, Emanuel Necas, Ladislav Andera, Jan Zivny
Journal: Blood (2008)
Primary anti-VEGF-refractory metastatic renal cell carcinoma (mRCC): Clinical characteristics, risk factors, and subsequent therapy.
Authors: D. Y. Heng, M. J. MacKenzie, U. N. Vaishampayan, J. J. Knox, G. A. Bjarnason, M. Tan, L. Wood, F. Donskov, B. I. Rini, T. K. Choueiri
Journal: Journal of Clinical Oncology (2011)

305 Background: A proportion of patients treated with anti-VEGF therapy first line exhibit progressive disease (PD) as best response (per RECIST). The characteristics and outcome of this population are poorly understood. Methods: Data from patients with mRCC treated with anti-VEGF therapy were collected through the International mRCC Database Consortium from 12 centers. Results: One thousand fifty-six evaluable patients were treated with VEGF-inhibitors as their first-line antiangiogenic therapy. Of those, 272 (26%) patients had PD as best response. Their initial treatment was sunitinib (n=203), sorafenib (n=51), or bevacizumab (n=18). Six percent of patients were favorable risk, 55% intermediate risk, and 39% poor risk as per Heng et al JCO 2009 prognostic factors. On multivariable analysis, predictors of PD at first restaging were KPS &lt; 80% (OR 2.3, p &lt; 0.0001), diagnosis to treatment &lt; 1 year (OR 2.1, p &lt; 0.0001), neutrophilia (OR 1.9, p = 0.0021), thrombocytosis (OR 1.7, p = 0.0068), and anemia (OR 1.6, p = 0.0058). The median progression-free survival (PFS) and overall survival (OS) in patients with primary refractory disease vs. patients without (i.e., partial response or stable disease) was 2.4 vs. 11 months (p&lt;0.0001) and 6.8 vs. 29 months (p&lt;0.0001), respectively. Only 108 (40%) VEGF-refractory patients proceeded to receive 2 nd line VEGF inhibitors (sunitinib (n=32), sorafenib (n=44), axitinib (n=2), bevacizumab (n=4)), mTOR inhibitors (temsirolimus (n=14), everolimus (n=11)), or interferon (n=1). The response rate, PFS and OS of this second-line therapy was 9%, 2.5 months and 7.4 months, respectively. The response rate, PFS and OS of those receiving second-line VEGF vs. mTOR inhibitors was 10% vs. 6% (p=NS), 2.8 vs. 2.0 months (p=0.069) and 7.9 vs. 4.7 months (p=0.40), respectively. Conclusions: Primary anti-VEGF-refractory mRCC patients have a dismal prognosis. Second-line anti-mTOR agents may not be better than alternate anti-VEGF agents after primary anti-VEGF failure. Investigation into the mechanism of primary resistance and alternative therapeutic strategies are needed. [Table: see text]
Adoptive Infusion of Ex Vivo Expanded Autologous Natural Killer (NK) Cells in Cancer Patients Treated with Bortezomib to Sensitize to NK-TRAIL Cytotoxicity.
Authors: Andreas Lundqvist, M. Berg, A. Smith, L. Cook, R. Goodwin, C. Ramos, S. Vasu, J. Pantin, R. Lopez, H. Khuu, V. Fellowes, D. Stroncek, T. Donohue, R. Childs
Journal: Blood (2009)