tbuckley/cabot-search huggingface dataset:
Review: Thrombolysis for DVT reduces postthrombotic syndrome but increases bleeding complications
Authors: Susan R. Kahn
Journal: Annals of Internal Medicine (2017)

ACP Journal Club21 March 2017Review: Thrombolysis for DVT reduces postthrombotic syndrome but increases bleeding complicationsSusan R. Kahn, MD, MSc, FRCPCSusan R. Kahn, MD, MSc, FRCPCJewish General Hospital and McGill University, Montreal, Quebec, Canada (S.R.K.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2017-166-6-030 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationWatson L, Broderick C, Armon MP. Thrombolysis for acute deep vein thrombosis. Cochrane Database Syst Rev. 2016;11:CD002783. https://pubmed.ncbi.nlm.nih.gov/27830895Clinical Impact RatingsHospitalists: Hematology: References1 Enden T, Wik HS, Kvam AK, et al. Health-related quality of life after catheter-directed thrombolysis for deep vein thrombosis: secondary outcomes of the randomised, non-blinded, parallel-group CaVenT study. BMJ Open. 2013;3:e002984. [PMID: 23988361] Google Scholar2 Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149:315-52. [PMID: 26867832] Google Scholar Author, Article, and Disclosure InformationAffiliations: Jewish General Hospital and McGill University, Montreal, Quebec, Canada (S.R.K.)This article was published at Annals.org on 7 March 2017. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byInterventionelle Therapie der akuten iliofemoralen Thrombose 21 March 2017Volume 166, Issue 6Page: JC30KeywordsDeep vein thrombosisHemorrhageHemorrhagic strokeMortalityPosttraumatic stressRelative riskStrokeSurgerySystematic reviewsVenous thromboembolism ePublished: 21 March 2017 Issue Published: 21 March 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Expression of estrogen receptor beta isoforms in pancreatic adenocarcinoma.
Authors: Mamoun Younes, Charles J Ly, Kanchan Singh, Atilla Ertan, Sushovan Guha, Pamela S Younes, Jennifer M Biley
Journal: Journal of Clinical Oncology (2017)

337 Background: There have been several limited trials in which tamoxifen efficacy was tested in patients with pancreatic adenocarcinoma (PAC). Most of these studies were small series of patients with unresectable PAC and reported mixed results. In these studies, patients were not stratified by estrogen receptor status because estrogen receptor beta (ER-b) had not yet been identified, and PAC did not express the traditional ER-alpha. Recent studies showed that the effects of estrogens, phytoestrogens and tamoxifen on PAC cell lines depended on ER-b expression. The aim of this study was to investigate ER-b expression in human PAC and whether such expression correlates with any clinicopathologic parameters. Methods: Sections of tissue microarray containing 18 formalin fixed and paraffin embedded human PAC were stained by immunohistochemistry (IHC) using monoclonal antibodies to ER-b isoforms 1, 2, and 5 (ER-b1, ER-b2, and ER-b5, respectively), and for Cyclin A. The levels of ER-b isoform expression in tumor cells and the S-phase fraction (SPF) were determined using a quantitative digital image analysis solution (OTMIAS). Results: All isoforms were expressed in PAC, although at different levels. Higher mean ER-b2 levels correlated with male sex (p = 0.057), older age (p = 0.005), and lower pT stage (p = 0.008), but not with grade, pN stage, or SPF. Mean ER-b5 levels correlated negatively with SPF (p = 0.021), but not with sex, age, grade, pT or pN. Mean ER-b1 expression did not correlate with any of the above mentioned clinicopathologic factors. Conclusions: ER-b1, ER-b2, and ER-b5 are expressed in PAC. Higher ER-b2 and ER-b5 levels of expression are significantly correlated with lower tumor pT stage and with lower SPF, respectively, suggesting that they may play a tumor suppressive role in PAC. The association between ER-b2 levels and patient sex and age suggest that it could be influenced by endogenous/exogenous hormonal exposure.
Are preclinical research findings replicable: An empirical analysis based on EpoR studies in cancer.
Authors: Charles L. Bennett, Samuel J. Kessler, Richard M. Schulz, Brian Chen, Jametta Magwood, Stephen Yenzen Lai, LeAnn B. Norris, James O. Armitage, A. Oliver Sartor, William J. Hrushesky
Journal: Journal of Clinical Oncology (2014)

e17697 Background: In a Jan 2014 editorial “Reproducibility” Editor-in-Chief of Science Marcia McNutt reports that “a troubling proportion of peer-reviewed preclinical studies are not reproducible.” A former AMGEN scientist reported that before pursuing specific research avenues, AMGEN labs evaluated preclinical cancer research findings for 53 landmark preclinical cancer manuscripts studies and confirmed 11%. Three Bayer Healthcare scientists reported similarly that 20% to 25% of 67 preclinical published cancer manuscripts were confirmed in house. Neither study was replicated as corporate legal agreements prevented source manuscript dissemination. Methods: We carefully reviewed all available published and NCI workshop reports to ascertain the ability of pharmaceutical company scientists’ ability to reproduce academic scientists’ findings related to EPO-R and cancer. Results: Between 1993 and 2013, academic and AMGEN scientists evaluating EpoRs published 74 manuscripts and 4 manuscripts, respectively, based on cell lines or animal xenografts for cancers of the breast, cervix, endometrium, head and neck, lung, melanoma, brain (neuroblastoma and gliomas), ovary, and prostate. The 2007 NCI-sponsored workshop attended by 14 academic scientists and 6 industry scientists found that academic presentation findings could not be replicated by industry scientists. Between 2006- 2013, AMGEN scientists’ sought to replicate EpoR findings published and presented by academic scientists (Table). Conclusions: Published preclinical EpoR research findings from academic scientists were not replicated by industry employed scientists. We confirm low replicability rates for preclinical research- in this case with respect to EpoRs in the cancer setting. Scientists EpoRs Signaling events Harmful changes in cell function/regulation Number of studies Academic (1993-2005) 30/30 (100%) 14/15 (93.3%) 14/20 (70%) 33 Manufacturer (1993-2005) 0 0 0 0 2007 NCI Conference (academics) 7/7 (100%) 7/7 (100%) 6/8 (75%) 8 2007 NCI Conference (manufacturer) 0/2 (0%) 0/1 (0%) 0/2 (0%) 2 Academic (2006-2013) 38/40 (95%) 24/26 (92.3%) 24/30 (80%) 43 Manufacturer (2006-2013) 2/4 (50%) 0/2 (0%) 0/1 (0%) 4
Role of systemic immune-inflammatory index, tumor infiltrating neutrophils and PD-1+ T cells to predict the postoperative recurrence after S-1 adjuvant chemotherapy for gastric cancer: A retrospective study.
Authors: Hiroaki Tanaka, Tatsuro Tamura, Soichiro Hiramatsu, Kazuya Muguruma, Yuichiro Miki, Masatsune Shibutani, Sadaaki Yamazoe, Kenjiro Kimura, Hisashi Nagahara, Takahiro Toyokawa, Ryosuke Amano, Kiyoshi Maeda, Kosei Hirakawa, Masaichi Ohira
Journal: Journal of Clinical Oncology (2017)

74 Background: The adjuvant chemotherapy with S-1 is the standard treatment for Stage II/III gastric cancer in Japan. Immunological status of host is critical for treatment outcome. Several investigators showed that systemic immune-inflammaotry indexes including neutrophil lymphocyte ratio (NLR) and modified Glasgow Prognostic Score (mGPS) well reflected the tumor progression. Methods: We analyzed clinical data obtained from 170 patients with pathological stage II/III gastric cancer who underwent surgery followed by S-1 adjuvant chemotherapy at Osaka City University Hospital between 2006 and 2015. Tumor infiltrating cells were detected by immunohistochemistry. Results: We found recurrent diseases in 70 (41%) patients including 15 in stage II and 55 in stage III. In univariate analysis using Cox proportion model, 2 grade of mGPS, the increase value of post-operative CEA, CA19-9, number of lymphocytes and NLR were associated with recurrence. Post-operative elevation of CEA and NLR were identified as independent risk factors for recurrence in multivariate analysis. Increase value of pre-operative NLR and CEA was significantly associated with early recurrent within one year after surgery. Tumor infiltrating neutrophils and PD-1+ T cells had correlated with the increase of pre-operative NLR and CEA value, respectively. Patients with low PD-1+T cells and low neutrophils had better prognosis than those with high infiltration. Conclusions: Post-surgical elevation of CEA and NLR value were useful as a predictive marker for recurrence in patients treated with S-1 adjuvant chemotherapy after surgery for gastric cancer. Early recurrence had correlated with tumor infiltrating neutrophils and PD-1+T cells. Our results suggested that systemic and local immune suppression should be an important element to exacerbate prognosis after chemotherapy for resectable gastric cancer.
Prospective study of the decision-making impact of the Breast Cancer Index in the selection of patients with ER+ breast cancer for extended endocrine therapy.
Authors: Tara Beth Sanft, Bilge Aktas, Brock Schroeder, Veerle Bossuyt, Michael DiGiovanna, Maysa M. Abu-Khalaf, Gina G. Chung, Andrea Silber, Erin Wysong Hofstatter, Sarah Schellhorn Mougalian, Lianne Epstein, Christos Hatzis, Catherine A. Schnabel, Lajos Pusztai
Journal: Journal of Clinical Oncology (2015)

538 Background: The Breast Cancer Index (BCI) has been validated to quantify an individualized risk of late recurrence and to predict likelihood of benefit from extended endocrine therapy in ER+ early stage breast cancer.The purpose of this study was to prospectively assess the impact of BCI i) to change treatment recommendations regarding extended endocrine therapy, and ii) to examine its effects on patient anxiety and decision conflict. Methods: Patients with stage I-III, ER+ breast cancer treated at the Yale Cancer Center who completed at least 3.5 yrs of adjuvant endocrine therapy were prospectively enrolled over 6 months in 2014. BCI was performed on FFPE samples from the original biopsy (bioTheranostics Inc.). Patients and physicians completed pre- and post-test questionnaires. Patients completed the Traditional Decisional Conflict Scale (DCS) and State Trait Anxiety Inventory Form Y (STAI) pre- and post-test. Results: 100 patients[mean age 61y (45-88), 80% postmenopausal, 57% stage I] were included in this study. Integration of BCI resulted in a change in treatment recommendation for 27% of patients. A majority of changes were based on identification of patients with low risk of late recurrence and low likelihood to benefit from extended endocrine therapy. Extended therapy was recommended for 75% patients pre- and for 55% post-testing. No extended therapy was recommended for 25% patients pre-and for 45% post-testing. Satisfaction increased in 38% of patients. After receiving results, 52% of patients changed their treatment decision. Patients experienced less anxiety (53%) and decisional conflict (50%) after receiving results. The STAI (p = 0.03) and DCS (p < 0.001) scores decreased significantly post testing (mean difference of -2 and -9, respectively) compared to baseline scores (31 and 20, respectively). Conclusions: The Breast Cancer Index led to changes in treatment recommendations regarding extended adjuvant endocrine therapy in 27% of cases and resulted in significantly less decision conflict and anxiety for patients. Overall, knowledge of BCI resulted in fewer recommendations for extended therapy and improved patient satisfaction. Clinical trial information: NCT02057029.
Pathological determinants of oncologic outcomes in stage II renal cell carcinoma: An international multicenter analysis.
Authors: Zachary Hamilton, Daniel Han, Alp Tuna Beksac, Sean Berquist, Abd−elrahma Hassan, Charles Field, Aaron Bloch, James Proudfoot, Anthony Patterson, Haluk Ozen, Brian R. Lane, Ithaar Derweesh
Journal: Journal of Clinical Oncology (2017)

535 Background: Clinical Stage II Renal Cell Carcinoma (RCC) is a heterogeneous disease characterized by disparate oncological outcomes. The risk of progression and recurrence can vary widely. We analyzed risk factors associated with oncological outcomes in a contemporary cohort. Methods: Retrospective multicenter analysis of patients who underwent surgical excision of clinical stage 2 (T2) renal mass between 1998-2015. Patients with tumors amenable to nephron−sparing surgery, baseline chronic kidney disease, or bilateral renal masses were provided an option for partial nephrectomy (PN), otherwise radical nephrectomy (RN) was performed. Lymphadenectomy (LND) was performed at the discretion of the surgeon due to concern for lymphadenopathy on preoperative imaging or at time of surgery. Patients with pN+ disease and pathological pT upstaging/downstaging were excluded. Primary endpoint was Recurrence Free Survival (RFS). Univariable linear regression, Kaplan−Meier Analysis (KMA) log−rank test, and multivariable analysis (MVA) for factors related to RFS and overall survival (OS) were performed. Results: 695 patients were analyzed (mean age 59.3 years, median follow up 49.6 months, 61.4% male/38.6% female, 545 RN/150 PN, 193 LND/502 no LND). MVA for factors associated with worsened RFS revealed lymphovascular invasion (LVI, HR 2.27, p=0.002), positive margins (HR 2.67, p=0.008), and tumor grade 3/4 (HR 2.04, p&lt;0.008). MVA for decreased OS revealed LVI (HR 2.58, p=0.003), positive margins (HR 2.34, p=0.044), and tumor grade 3/4 (HR 2.08, p=0.023) as risk factors. KMA revealed 5 year RFS of 76.1% for LVI negative and 46% for LVI positive patients (p&lt;0.001), and 5 year RFS of 78.1% for Tumor Grade I/II and 53.7% for Tumor Grade III/IV (p&lt;0.001). KMA revealed 5 year OS of 79.2% for LVI negative and 60.6% for LVI positive patients (p&lt;0.001). Conclusions: For Stage II RCC, LVI, positive margin, and tumor grade III/IV are independently associated with worsened RFS and OS. Further investigation is requisite and may add weight to consider these specific stage II RCC patients as a higher risk subgroup with implications for staging revision and clinical trial design.
Evaluation of clinical phenotype, survival, and circulating tumor cell (CTC) enumeration in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Rhonda Lynn Bitting, Patrick Healy, Susan Halabi, Daniel J. George, Jung Hyun Ko, Andrew J. Armstrong
Journal: Journal of Clinical Oncology (2013)

5031 Background: The presence of ≥ 5 CTCs is prognostic for shorter survival in mCRPC men. However, many men have low CTCs despite widespread metastatic disease, suggesting heterogeneity in CTC phenotype or detection. We evaluated the association of baseline CTC enumeration with clinical characteristics and survival in mCRPC men at our institution. Methods: CTCs were enumerated with the standard CellSearch method in mCRPC men in a prospective correlative clinical study. The association between baseline CTC count and prostate-specific antigen (PSA), alkaline phosphatase (AP), lactate dehydrogenase (LDH) was explored using the Spearman correlation (r), and the relationship with Gleason sum, sites of metastasis (mets), and prior docetaxel exposure was explored using summary statistics. The overall survival probability (OS) was estimated by the Kaplan-Meier method. Results: In our cohort, 59/82 men had prior docetaxel exposure, and the median CTC count was 16.5. There were 25 men with visceral mets, 55 with bone-predominant mets, and 2 with lymph node only mets. We found a weak relationship between CTCs and PSA (r=0.20), but a more moderate and significant association with AP (r=0.48) and LDH (r= 0.50). We found no relationship between CTCs and Gleason sum, site of mets, or prior docetaxel. 66 men died, and the median OS was 11.2 months (95% CI: 9.2, 12.7). OS was improved in patients with &lt;5 CTCs at baseline compared to ≥ 5 (8.9 vs. 16.6 months, HR=0.47 (95% CI: 0.27, 0.80)). CTC enumeration may further stratify outcomes in men with mCRPC and either visceral or bone metastasis as shown in the table below. Conclusions: The prognostic significance of CTCs is distinct from other established biomarkers and may reflect a unique biology of metastasis, dissociated in part from androgen receptor activity (as reflected by PSA values) but related in part to bone microenvironment, hypoxia, and tumor burden (as reflected by AP and LDH values). These associations need to be validated in larger trials. [Table: see text]
Association of myeloid-derived suppressor cells (MDSCs) in peripheral blood with characteristics in breast cancer patients.
Authors: Peng Shen, Aijuan Wang, Wei Ke, Mengye He, Lanfang Yu, Sui Huang
Journal: Journal of Clinical Oncology (2013)

e22094 Background: The immune therapy of human cancer is a promising therapeutic approach. Myeloid-derived suppressor cells (MDSCs) have been confirmed as an indispensable component of immune system and associated with tumor induced immune suppression. Thus, MDSCs play an important role in immune therapy. Although a lot of research work has been done, currently there exists limited data about MDSCs status in cancer patients. The aim of this study was to determine whether MDSCs levels in peripheral blood were different in healthy volunteers, benign breast tumor patients and breast cancer patients, and to investigate the relation between MDSCs and several characteristics in breast cancer patients. Methods: Peripheral blood cells (PBC) were collected from 36 normal healthy volunteers, 52 patients with breast cancer and 62 patients with benign breast tumor. Peripheral blood samples of breast cancer patients were obtained before treatment. Circulating MDSCs (identified as Lin -/Lo HLA-DR - CD33 + ) were measured by flow cytometry. Statistical methods included two sample t tests and one way ANOVA. Results: The percentage of MDSCs was higher in breast cancer than benign breast tumor patients and healthy volunteers (2.017% vs 1.578% vs1.594%; p=0.0002), and the stage III/IV breast cancer patients had more MDSCs accumulation than those in stage I/II (2.92% vs 2.155%; P=0.0806). The levels of MDSCs in peripheral blood showed a significant correlation with HER-2/neu expression in breast cancer patients, but had no correlation with incidence age, ER status, PR status and P53 expression respectively. The percentage of MDSCs was lower in HER-2/neu over expression breast cancer patients than HER-2/neu negative patients (1.715% vs 2.882%, GP=0.0012). Conclusions: MDSCs seemed to have positive correlation with clinical stage and negative correlation with HER-2/neu expression in breast cancer patients . Further research will contribute to the better understanding of the connection between MDSCs and breast cancer, to develop better approaches to breast cancer therapy.
Outcomes of head and neck squamous cell carcinomas (HNSCC) treated with reirradiation (RRT) at Mayo Clinic.
Authors: Kelly Kevelin Curtis, Helen J. Ross, Ashley L. Garrett, Theresa Ann Jizba, Heidi Kosiorek, Samir Harishbhai Patel, William Wong, Michele Y. Halyard, Robert Leonard Foote
Journal: Journal of Clinical Oncology (2015)

6064 Background: RRT is offered as definitive (DRRT) or post-operative (PRRT) treatment for patients (pts) with loco-regionally recurrent (LRR) or new primary (NP) HNSCC in previously irradiated volumes. We report the results of a retrospective chart review of all consecutive pts with LRR and NP HNSCC treated with DRRT and PRRT at Mayo Clinic. Methods: We included LRR and NP HNSCC pts treated with DRRT/PRRT from 2003-2011 at all Mayo Clinic campuses. Patient and treatment related data were collected. Loco-regional recurrence rate (LR) and distant metastases rate (DM) at 2 years, and overall survival (OS) from end of RRT using Kaplan-Meier methods, were calculated. Results: We identified 89 pts (68 M, 21 F). 67 pts had LRR; 22 NP. Treatment included salvage surgery with PRRT (47 pts) and DRRT (42 pts). 30 pts received concurrent chemotherapy (CT) with PRRT; 33 DRRT pts received CT. Median prior RT dose was 66 Gy (26.4 – 79.2 Gy). Median PRRT dose was 60 Gy (11 – 70 Gy). Median DRRT dose was 69.6 Gy (18 – 76.8 Gy). LR occurred in 42 pts (47%) after RRT; 35 pts (39%) had LR by 2 years (95% CI, 30 – 50%). DM occurred in 20 pts (22%) after RRT; 16 pts (18%) had DM by 2 years (95% CI, 11 – 27%). Median OS was 22.2 mos (95% CI, 17.0 – 29.8 mos), with 2- and 5-year OS 47% and 16%. No difference in OS between LRR- and NP-HNSCC or PRRT and DRRT was found. CT was associated with shorter time to LR (4.3 vs. 12.1 mos, p = 0.008), but not with time to distant metastases or OS. At last follow-up (median 78.1 mos) 21 pts (24%) were alive, with 43.3 mos (95% CI, 27.6 – 52.9 mos) median OS from time of LRR/NP. Among surviving pts, 2 cases of osteoradionecrosis (10%) and 1 carotid artery pseudoaneurysm with sentinel bleed (5%) were reported, with no reported spinal cord injuries. OS was better among 70 pts treated to at least 60 Gy (n = 70) vs. pts treated with less than 60 Gy (median OS 25.2 mos, 95% CI, 19.4 – 32.0 mos; vs. median OS 9.5 mos, 95% CI, 6.8 – 28.7 mos; p = 0.06). Conclusions: RRT cures a small number of pts. 2-year OS of LRR/NP HNSCC pts treated with RRT in the time frame of this study appears superior to published outcomes. Shorter time to LR among pts receiving CT warrants further study, but may signify selection bias toward more aggressive therapy for pts with high risk LRR/NP HNSCC.
Patient-reported sources of breast cancer survivorship care four years after diagnosis.
Authors: Christopher Ryan Friese, Sarah T. Hawley, Jennifer J. Griggs, Ann S. Hamilton, John Graff, Steven J. Katz
Journal: Journal of Clinical Oncology (2013)

e20511 Background: Breast cancer survivors remain “lost in transition” after active treatment due to changing needs and fragmented care. We sought to describe the patterns of breast cancer survivorship care in a diverse sample to identify factors associated with receipt of survivorship care by medical oncologists (med onc). Methods: We conducted a mailed survey to 2,290 women who resided in the Los Angeles and Detroit SEER registry catchment areas with a confirmed invasive breast cancer case from 6/05-2/07. Women were then surveyed approximately 4 years after diagnosis (n=1,536). On the follow-up survey, women were asked to identify their main provider of breast cancer follow up care: med onc, surgeon, primary care physician (PCP)/other physician. We examined the relationship between report of med onc as main provider of survivor care and: age, race/ethnicity, insurance, tumor stage, receipt of chemotherapy, and care by med onc reported on the baseline survey. Bivariate analyses and logistic regression were used to examine med onc-led survivorship care and the factors above. Results were weighted to account for sample selection and non-response. Results: 858 women had invasive disease at time of diagnosis: 65.2% reported med oncs as the main provider of survivorship care, followed by PCP/other physicians (24.3%) and surgeons (10.5%). Of the women who did not receive chemotherapy, 56% reported med onc-led survivorship care, compared with 79% of chemotherapy recipients. In multivariable logistic regression, black women were less likely than white women to report med onc-led survivorship care (OR 0.49, 95% CI 0.34-0.71). Privately-insured patients were more likely than Medicaid recipients to report med onc-led care (OR 2.00, 95% CI 1.16-3.45). Women with higher disease stage, those who received chemotherapy, and those who saw a med onc at baseline were significantly more likely to report med onc-led survivorship care. Conclusions: The oncology workforce shortage compels the identification of optimal and efficient survivorship care models. A mismatch may exist between chemotherapy receipt and med onc-led care. Our data suggest clear guidelines are needed to direct patients to the providers most appropriate to manage their care.