tbuckley/cabot-search huggingface dataset:
Combined use of MammaPrint and molecular subtyping profile (BluePrint) to identify subgroups with marked differences in response to neoadjuvant treatment.
Authors: L. Stork-Sloots, F. De Snoo, P. Roepman, O. Krijgsman, R. Bernards, A. Glas
Journal: Journal of Clinical Oncology (2011)

42 Background: Concordance between the IHC receptor status and the molecular subtype suggests that molecular profiles represent oncogenic processes that are driven by pathways in which ER, PR and HER2 play pivotal roles. It is, therefore, likely that the use of gene expression arrays will enable the identification of previously unappreciated subtypes of breast cancer that differ in clinical outcomes. Methods: The cohort consists of 133 (T1-4, N0-3) breast cancer patients treated with T/FAC neoadjuvant chemotherapy. Genome wide expression data was publicly available and downloaded from bioinformatics.mdanderson.org/pubdata.html. The data was used to determine the response to T/FAC neoadjuvant chemotherapy for patients stratified by MammaPrint and molecular subtype (BluePrint). The MammaPrint and BluePrint result were used to subtype the patients into 4 groups: MammaPrint Low-risk/Luminal-type, MammaPrint High-risk/Luminal-type, Basal-type and ERBB2-type. Results: Within this patient cohort, 20% (n=27) were classified as Basal-type, 62% (n=82) as Luminal-type, and 18% (n=24) as ERBB2-type. The overall pCR of this patient cohort was 26% and differed substantially among the subgroups. pCR was observed in 9% of all Luminal-type samples (i.e. 3% of MammaPrint Low Risk/Luminal-type and 11% of MammaPrint High Risk/Luminal-type), in 50% of the ERBB2-type samples and in 56% of the Basal-type samples. The pCR rates observed for the ERBB2-type and Basal-type patient groups were higher compared to classification based on IHC/CISH assessed ER and HER2 receptor status: 50% for ERBB2-type versus 39% for HER2+ and 56% for Basal-type versus 47% for ER-/HER2- samples. Conclusions: We observed marked differences in response to neo-adjuvant treatment in groups stratified by MammaPrint and BluePrint. These findings confirm differences in chemotherapy response among molecular subgroups and indicate that the BluePrint profile described here will help to further establish a clinical correlation between molecular subtyping and treatment response.
Hasford Score Is Correlated with 18 Month Molecular Response for Chronic Myeloid Leukemia Patients Treated with Second Generation Tyrosine Kinase Inhibitors and It May be Useful to Differentiate Low and Intermediate Risk Patients: A Single Institution Experience
Authors: Jaroslaw Dybko, Olga Haus, Bozena Jazwiec, Tomasz Lonc, Mateusz Sawicki, Kazimierz Kuliczkowski
Journal: Blood (2015)
Differences in prostate cancer survival between Denmark, Iceland, and Sweden: A high-resolution study.
Authors: Inga Jona Ingimarsdottir
Journal: Journal of Clinical Oncology (2012)

159 Background: Register-based studies have demonstrated large differences in relative survival and excess mortality following the diagnosis of PC in the Nordic countries. These differences may reflect differences in patient characteristics, diagnostics (PSA-use) and treatment strategies. This high-resolution study explores the background for the differences in PC survival between Denmark, Iceland and Sweden. Methods: Patients with newly diagnosed PC in 1997 were identified through population-based national cancer registers in Denmark and Iceland. Information on clinical findings was retrieved by reviewing hospital files. In Sweden information was gathered from two regional population-based prostate cancer registers providing both time of diagnosis and clinical information. Country specific excess mortality rates were compared adjusting for available information on known prognostic factors. Results: The overall relative survival in the cohorts was comparable to population-based results previously published. Across countries significant differences in excess mortality rates were seen. These differences were largely explained by differences in patient characteristics at diagnosis, and when adjusting for differences in patient characteristics i.e. metastatic / non-metastatic disease, clinical T-stage, and PSA level at diagnosis, the differences in excess mortality diminished or disappeared. The difference in percentage of patients with metastatic disease at diagnosis was the one factor responsible for the major differences in mortality-rates across countries. Conclusions: Register-based studies on relative survival and excess mortality following a PC diagnosis may be influenced by national differences in clinical presentation at diagnosis. Differences between countries in the proportion of patients with metastatic spread at diagnosis apparently explains most of the difference in relative survival previously reported. Further studies and cross country comparisons of survival and excess mortality for PC should adjust for differences in patient characteristics, mainly TNM.
The relationship between prostate volume and histopathologic criteria of known prognostic importance in 2,207 men with prostate cancer.
Authors: P. Sooriakumaran, A. Srivastava, M. John, D. Bhagat, S. Grover, S. Rajan, Y. El-Douaihy, R. Leung, A. Tewari
Journal: Journal of Clinical Oncology (2011)

197 Background: There is a paucity of data investigating the relationship between histopathologic variables of oncologic importance and prostate volume, and we aimed to investigate this. Methods: 2,207 consecutive patients who underwent robotic-assisted radical prostatectomy (RARP) were studied. Preoperative demographic and both pre- and post-operative histopathologic parameters were compared among the small prostate (&lt; 40cc), intermediate size (40-70cc), and large prostate (&gt; 70cc) groups. Results: Patients with smaller prostates were younger, had slightly lower BMIs, and lower PSAs than those with smaller prostates (p &lt; 0.001). They also had worse histopathologic criteria (Gleason, core positivity, and maximum percent cancer) on preoperative biopsy and had worse radical specimen Gleason sums (p &lt; 0.001), percent cancer (p &lt; 0.001), and pathologic stage (p = 0.016). 11.5% of men in the small prostate group suffered a positive surgical margin (PSM) compared to 8.3% and 5.6% in the intermediate and large prostate groups, respectively (p = 0.008; Table). Basilar, posterolateral, and multifocal PSMs were commoner in the small prostate group. Conclusions: Younger men have smaller prostates and worse preoperative histopathologic parameters despite lower PSAs. Men with small prostates undergoing RARP have worse final Gleason sums, tumor volume, extraprostatic extension (EPE), and PSM rates than those with larger prostates. We would thus caution against conservative management of men with clinically localized prostate cancer who have small prostates. [Table: see text] No significant financial relationships to disclose.
Caveolin-1 as a biomarker of Src family kinase/Abl inhibition in castrate-resistant prostate cancer.
Authors: B. C. Carthon, S. Tahir, J. C. Araujo, S. Wen, G. E. Gallick, C. Logothetis, T. C. Thompson
Journal: Journal of Clinical Oncology (2011)

45 Background: Bone metastases cause significant morbidity in men with castrate-resistant prostate cancer (CRPC). Caveolin-1 (Cav-1), a Src kinase substrate, is overexpressed in primary prostate cancer (PCa) and in PCa bone metastases. In addition, PCa-derived and secreted Cav-1 contributes to malignant progression. We reasoned that Cav-1 may serve as a biomarker of dasatinib (a Src family kinase [SFK]/Abl inhibitor) activity in CRPC patients enrolled in a phase II clinical trial of docetaxel plus dasatinib. Methods: Levels of prostate-specific antigen (PSA), Cav-1, and markers of bone turnover were measured from baseline and cycle-2, day-1 samples from patients (n = 32) enrolled in this trial. Changes in these markers were stratified by response (responders [R] vs. nonresponders [NR]) and by predominant disease site (lymph node vs. bone). We evaluated Cav-1 expression in human PCa bone metastases samples from trial patients by immunohistochemistry. In parallel, Cav-1 secretion in response to dasatinib treatment was analyzed in PCa cells and osteoblasts. Results: Serum Cav-1 levels correlated directly with PSA levels in responding patients with node-positive disease (R vs. NR, p = 0.08) but correlated inversely in responding patients with bone-predominant disease (R vs. NR, p = 0.001). Serum from a separate cohort of patients treated with docetaxel only showed no effect on serum Cav-1 levels (R vs. NR, p = 0.85). Levels of Cav-1 were high in the active OBLs in bone specimens with PCa metastases, but not in bone specimens without metastases. Dasatinib treatment led to reduced secretion of Cav-1 in PC-3 and DU145 PCa cells but to increased secretion of Cav-1 in primary mouse osteoblasts or pre-osteoblast MC3T3-E1 cells. Conclusions: Our results suggest that serum Cav-1 serves as a novel discriminating biomarker for SFK/Abl inhibition in both node-positive and bone-metastatic CRPC. The expression of Cav-1 in OBLs of patients with PCa bone metastases suggests that tumor-associated OBLs are an important source of Cav-1 production in bone marrow. Our data provide evidence that the increase in serum Cav-1 in these patients with bone disease likely occurs through a direct effect of dasatinib on osteoblasts. No significant financial relationships to disclose.
Therapy-Associated Immunosuppression and Opportunistic Infections in Multiple Myeloma Patients.
Authors: Philipp Schutt, Dieter Brandhorst, Werner Stellberg, Miriam Poser, Peter Ebeling, Siemke Muller, Ulrike Buttkereit, Bertram Opalka, Monika Lindemann, Hans Grosse-Wilde, Siegfried Seeber, Thomas Moritz, Mohammad R. Nowrousian
Journal: Blood (2005)
Utilization of pegfilgrastim in adjuvant chemotherapy regimens for breast cancer in the community.
Authors: D. A. Patt, J. L. Espirito, B. Turnwald, J. R. Hoverman, M. A. Neubauer, L. T. Busby, B. D. Brooks, M. A. Kolodziej, R. W. Anderson, R. A. Beveridge
Journal: Journal of Clinical Oncology (2011)

213 Background: Selection of adjuvant breast cancer (BC) therapy varies based on patient risk factors. Choice of chemotherapy (CT), schedule, duration, and supportive care affects costs and toxicity. Because pegfilgrastim (PEG) is a large driver of cost in adjuvant therapy it is important to understand the utilization characteristics. We aimed to characterize PEG utilization during neoadjuvant/adjuvant (N/Ad) CT by age and regimen type. Methods: Using the US Oncology iKnowMed EHR database, we retrospectively identified female BC patients (pts) diagnosed with stage I-III BC, between 7/2006 and 11/2010. Secondary diagnoses were excluded. Pts were characterized by age, ER and HER2 status, tumor size, grade, and nodes. CT utilization was determined by the number of pts assigned an N/Ad line of therapy (LOT) during the study period. Regimens were categorized by CT title and drugs. Clinical trial pts were included. PEG utilization was characterized if administered within 6 months of being assigned to an N/Ad CT regimen. Results: During the time period, 40,881 newly diagnosed localized BC pts were identified. Of these, 15,328 pts (37%) were assigned an N/Ad CT regimen and 72% (11, 022 pts) received PEG at any time within 6 months of their N/Ad CT. When analyzed by regimen type, TC, TAC, TCH, and dose-dense AC-paclitaxel were the most highly utilized regimens accounting for 64% of all PEG use. PEG use with the TC regimen was 70% and represented 25% of all N/Ad PEG utilization. PEG utilization by age was characterized as 81% of pts &lt;40 yrs, 74% of pts 40-49 yrs, 70% of pts 50-59 yrs, 71% of pts 60-69 yrs, 68% of pts 70-79 yrs, and 40% of pts ≥80 yrs. Conclusions: While 37% of women treated in the N/Ad setting received CT, PEG was given to 72% of that subset. Utilization was high among all age groups. Dose-dense and docetaxel-containing regimens accounted for the majority of PEG use. With availability of generic docetaxel, commonly used drugs in adjuvant BC except trastuzumab will have generic equivalents and PEG will be the largest cost driver in women receiving adjuvant CT in the community. Since febrile neutropenia occurred in 5% of pts on the original TC trial, determination of appropriate level of use of PEG in the adjuvant setting needs further study.
The effect of aerobic exercise on the metabolic risk profile of breast cancer survivors 2-6 months post chemotherapy.
Authors: E. M. Guinan, J. M. Hussey, J. M. Walsh, M. J. Kennedy, E. M. Connolly
Journal: Journal of Clinical Oncology (2011)

244 Background: Current literature suggests that weight gain during treatment for breast cancer is associated with a poorer prognosis and an increased risk of developing secondary health problems such as the metabolic syndrome (MetSyn). Physical activity (PA) can alter features of the MetSyn and improve body composition by reducing abdominal adiposity. We report metabolic results of a prospective randomized controlled trial (PEACH trial; Walsh JM, et al. [2010] BMC Cancer. 10[42]) which examines the effect of an exercise intervention on the metabolic risk profile of breast cancer survivors 2-6 months post chemotherapy. Methods: All subjects gave written informed consent and were randomized to an 8-week, twice weekly aerobic exercise intervention programme or a usual care control group consisting of routine medical advice about PA. The five clinical features of the MetSyn were measured: waist circumference (WC), resting blood pressure (BP), triglycerides, high-density lipoprotein cholesterol (HDL-C) and fasting glucose. Insulin resistance was estimated by the homeostatic model assessment (HOMA). Statistical analysis was carried out using independent sample t-tests with significance set at p &lt; 0.05. Results: Twenty-six breast cancer survivors participated (mean (± SD) age 48.13 (8.75) years). At baseline, 50% (n = 13) of subjects were overweight and 23.1% (n = 6) were obese, with 73.1% (n = 19) centrally obese. 34.6% (n = 9) of subjects were classified with the MetSyn. There were no significant differences between groups at baseline. Intention-to-treat analysis showed no significant changes, however, analysis of those who adhered to &gt; 70% of the supervised exercise intervention showed a significant improvement in WC when compared to the control group (p &lt; 0.05). Conclusions: Results show that an 8-week aerobic exercise intervention significantly reduced WC but did not modify other features of the MetSyn. The decrease in WC demonstrated by this short intervention may have important implications in terms of improving survival and the metabolic risk profile of breast cancer survivors. Final follow-up assessments are ongoing and will enable change in WC over time to be evaluated further.
Chemotherapy near end-of life: aiming for appropriateness at the Cancer Institute of Romagna (IRST IRCCS)
Authors: I. Massa, M. Maltoni, F. Foca, E. Sansoni, S. Derni, N. Gentili, M. Valgiusti, A. Casadei Gardini, S. Pini, D. Amadori, M. Altini, O. Nanni
Journal: Annals of Oncology (2015)
Abstract 1135: Loss of HSulf-1 promotes defective autophagy and increased lipid droplet biogenesis in ovarian cancer
Authors: Debarshi Roy, Susmita Mondal, Ashwani Khurana, Xiaoping He, Edward Hammond, Keith Dredge, Viji Shridhar
Journal: Cancer Research (2015)

Abstract Dysregulation of autophagy and altered metabolic pathways are frequently observed in cancer. Due to these alterations, pharmacological targeting of these two pathways simultaneously could provide a viable therapeutic option. Although the association between these two pathways is well characterized in metabolic disorders, it is not well defined in ovarian cancer (OVCA). In this regard, we found that loss of endosulfatase HSulf-1, a known putative tumor suppressor, suppresses LC3-GFP foci formation and promotes increased lipid droplet (LD) biogenesis suggesting that absence of HSulf-1 in OVCA affects both autophagy and lipid metabolism. While isogenic cells with genetic ablation of HSulf-1 (OV202Sh1/2 and TOV2223Sh1 cells) displayed LDs, the nontargeted control transduced (NTC) OV202 and TOV2223 cells had significantly less LDs. In contrast, Transmission Electron Micrographs (TEMs) showed that OV202 and TOV2223 NTC cells had significantly more autophagic vacuoles (AVs) compared to their isogenic ShRNA targeted cells. Conversely, ectopic expression of HSulf-1 in SKOV3 cells decreased the number of LDs and increased the number of AVs compared to vector transfected controls. Here we report that OV202Sh1 cells and HSulf-1 deficient OV2008 cells have increased p-cPLA2α(ser505) levels that are associated with biogenesis of large number of LDs with reduced AVs. Interestingly, pharmacological inhibition of cPLA2α with AACOCF3 in OV202Sh1 cells resulted in reduced LD biogenesis, inhibited colony formation and reduced tumorigenesis in vivo. More importantly, treatment of HSulf-1 deficient cells with HS mimetic PG545 which can compensate for loss of HSulf-1, reduced LD biogenesis, promoted autophagy and inhibited tumor growth in vivo. Collectively, these results show a critical role of HSulf-1 in regulating both autophagy and LD biogenesis in ovarian cancer. Citation Format: Debarshi Roy, Susmita Mondal, Ashwani Khurana, Xiaoping He, Edward Hammond, Keith Dredge, Viji Shridhar. Loss of HSulf-1 promotes defective autophagy and increased lipid droplet biogenesis in ovarian cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1135. doi:10.1158/1538-7445.AM2015-1135
P0378 : Time to progression of AFP is an independent prognostic factor of survival in hepatocellular carcinoma treated with sorafenib. Internal validation
Authors: M. Varela, L. Blanco-García, O. Castaño-Fernández, M.L. González-Diéguez, V. Cadahía-Rodrigo, C. Álvarez-Navascués, R. Pérez-Álvarez, A. Mesa, L. Hernández-Luyando, M. Rodríguez
Journal: Journal of Hepatology (2015)
The role of 3D-CT mammary lymphography with the arm lymph flow enhancement on sentinel node biopsy and selective axillary dissection.
Authors: K. Yamashita
Journal: Journal of Clinical Oncology (2011)

e11504 Background: In early breast cancer, the presence of metastasis in axillary lymph nodes (AN) is an important factor in prognosis and further treatment. However, AN dissection causes many complications such as contracture of shoulder joint, lymph edema, and paralysis of upper extremities. Sentinel node (SN) biopsy provides us a valuable information about no need to dissect AN for node-negative patients. However, on node-positive patients, the conventional AN dissection has been performed. 3D-CT lymphography (LG) can show the precise individual lymphatic flow not only from the breast tumor to SN but also from SN to venous angle, which means breast lymphatic channel. We applied 3D-CT LG to distinguish them from the arm channel to avoid any arm complications. Methods: 3D-CT LG was performed before surgery to mark SN on the skin. Above the tumor and near the areola and the arm pit, 2 ml of Iopamidol 300 was injected subcutaneously. Images of CT scan were taken at 1, 3 and 10 min after injection. They were reconstructed to produce a 3D image of lymph ducts and lymph nodes by the volume rendering software. The axillary node groups were classified to 5 groups as described before. The arm lymph channel was classified to 4 regions. SN biopsy and AN sampling were performed by dye-staining method using endoscopy. Results: We have performed 3D-CT LG on 200 patients and evaluated the arm lymph flow on 50 patients. The average age was 55.1 years old. The average tumor size was 2.4 cm. The average sampled number of SN was 2.3. The arm lymph channels were observed at 10 minutes after injection. They were divided into 4 directions: around and above the axillary vein (64%), the axilla (12%), the supraclavicule (8%), and the lateral chest (16%). The connection between the breast and the arm channel was observed in each five groups of axillary nodes shown by 3D-CT LG. We could detect their position on the axillary lymphatic mapping by 3D-CT LG during surgery. The selective axillary dissection can be performed by avoiding the arm lymph channel. Conclusions: The arm lymph channel can be observed by 3D-CT LG with the arm enhancement, which will help the selective axillary dissection to prevent the arm lymph edema.
Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline
Authors: Saro H. Armenian, Christina Lacchetti, Ana Barac, Joseph Carver, Louis S. Constine, Neelima Denduluri, Susan Dent, Pamela S. Douglas, Jean-Bernard Durand, Michael Ewer, Carol Fabian, Melissa Hudson, Mariell Jessup, Lee W. Jones, Bonnie Ky, Erica L. Mayer, Javid Moslehi, Kevin Oeffinger, Katharine Ray, Kathryn Ruddy, Daniel Lenihan
Journal: Journal of Clinical Oncology (2017)

Purpose Cardiac dysfunction is a serious adverse effect of certain cancer-directed therapies that can interfere with the efficacy of treatment, decrease quality of life, or impact the actual survival of the patient with cancer. The purpose of this effort was to develop recommendations for prevention and monitoring of cardiac dysfunction in survivors of adult-onset cancers. Methods Recommendations were developed by an expert panel with multidisciplinary representation using a systematic review (1996 to 2016) of meta-analyses, randomized clinical trials, observational studies, and clinical experience. Study quality was assessed using established methods, per study design. The guideline recommendations were crafted in part using the Guidelines Into Decision Support methodology. Results A total of 104 studies met eligibility criteria and compose the evidentiary basis for the recommendations. The strength of the recommendations in these guidelines is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms. Recommendations It is important for health care providers to initiate the discussion regarding the potential for cardiac dysfunction in individuals in whom the risk is sufficiently high before beginning therapy. Certain higher risk populations of survivors of cancer may benefit from prevention and screening strategies implemented during cancer-directed therapies. Clinical suspicion for cardiac disease should be high and threshold for cardiac evaluation should be low in any survivor who has received potentially cardiotoxic therapy. For certain higher risk survivors of cancer, routine surveillance with cardiac imaging may be warranted after completion of cancer-directed therapy, so that appropriate interventions can be initiated to halt or even reverse the progression of cardiac dysfunction.
sarcoma Full-dose neoadjuvant anthracycline + ifosfamide chemotherapy is associated with a relapse free survival (RFS) and overall survival (OS) benefit in localized high-risk adult soft tissue sarcomas (STS) of the extremities and trunk wall: Interim analysis of a prospective randomized trial
Authors: A. Gronchi, S. Ferrari, V. Quagliuolo, J. Martin Broto, A. Lopez-Pousa, G. Grignani, V. Ferraresi, J.-Y. Blay, P. Rutkowski, F.D. Merlo, E. Marchesi, P. Ledesma, A.P.i. De Tos, S. Bague Rosell, J.-M. Coindre, C. Morosi, S. Stacchiotti, P. Picci, P. Bruzzi, P.G. Casali
Journal: Annals of Oncology (2016)
Survivin Is Highly Expressed in AML Stem Cells and Predicts Poor Clinical Outcome
Authors: Bing Z Carter, Yihua Qiu, Xielin Huang, Lixia Diao, Nianxiang Zhang, Kevin R Coombes, Duncan H Mak, Marina Konopleva, Jorge E. Cortes, Hagop M. Kantarjian, Michael Andreeff, Steven M. Kornblau
Journal: Blood (2011)
Classification of Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) According to the Han's Criteria Defines Two Groups of Patients with Different Clinical Outcomes Following Systemic Rituximab-Multi Agent Anthracycline-Based Therapy.
Authors: Julio Chavez, Mark Walsh, Francisco J Hernandez-Ilizaliturri, Anjana Elefante, Myron S. Czuczman
Journal: Blood (2009)