tbuckley/cabot-search huggingface dataset:
Comparison of MammaPrint, BluePrint, and TargetPrint with clinical parameters in patients with breast cancer: Findings from a prospective United States cohort.
Authors: B. Nguyen, K. B. Deck, R. Sinha, D. Kerlin, J. Barone, E. Rivera, A. Garcia, K. Yao, L. Stork-Sloots
Journal: Journal of Clinical Oncology (2011)

47 Background: MammaPrint (MP) is a powerful predictor of disease outcome in early stage breast cancer. In addition, TargetPrint (TP), a microarray-based test that measures the mRNA expression level of ER, PR and HER2 and an 80 gene expression Molecular Subtyping profile BluePrint (BP) were developed. In the present study, MP, BP and TP were measured in a prospective U.S. breast cancer patient cohort. Methods: MP results were evaluated in fresh tumor samples from 127 breast cancer patients (T1-4N0-2; median age 62 [39-97 yr]) collected by core needle biopsy or from a surgical specimen between July 2008 and January 2011. We compared treatment advice as recommended by NCCN guidelines and classification according to MP. In addition, we compared IHC/FISH ER, PR and HER2 assessments with TP. The MP and BP results were used to subtype the patients into molecular subgroups. Results: For the group of patients (n=59) for which NCCN recommends the use of a multi-gene signature for determining chemotherapy treatment recommendations, 42 patients were classified as High Risk and 17 as Low Risk by MP. Comparison of TP with IHC/FISH indicated a concordance of 98% for ER, 94% for PR, and 98% for HER2. For a subgroup of 53 patients combined MP and BP results were available; 18 patients were Luminal-type/MP Low Risk, 27 patients were Luminal-type/MP High risk, 1 patient was Her2-type/MP Low Risk, 1 patient was Her2-type/MP High Risk and 6 patients were Basal-type/MP High Risk. Conclusions: Adding the multi-gene signature MammaPrint, as well as BluePrint and TargetPrint provides additional information for treatment guidance. By combining MammaPrint with the BluePrint molecular subtyping profile, specific groups of patients can be recognized that are at high risk of recurrence and that would possibly benefit from specific treatment. This study shows that TargetPrint provides high quality second opinion for local IHC/FISH assessment.
Got central prostate pathology review? A cross-sectional audit of 2009 versus 2003 outcomes.
Authors: N. D'Souza, D. A. Loblaw, A. Mamedov, E. Klotz, L. Sugar, R. Nam
Journal: Journal of Clinical Oncology (2011)

196 Background: Prostate cancer is the most common non-cutaneous cancer in Canadian men; over 24,000 will be newly diagnosed and 4,300 will die from it in 2010. Estimating an individual's risk of disease spreading across the capsule and probability of recurrence with different treatment modalities is common practice in prostate cancer management and often drive the choice or extent of treatment options. A strong predictor of recurrence and organ confined disease is tumor grade. The literature recognizes differences in grading prostate cancer between genitourinary and non-specialized pathologists; we previously reported a 30% change in risk category (Low, GS 2-6; Int., GS 7; High, GS 8-10). However, this report was based on data from 2003/2004. A repeat audit was necessary given Gleason grading practice changes following the 2005 ISUP Consensus Conference. Methods: Log books from 2009/10 where our Genitourinary Pathologists (GUP) reviewed prostate needle core biopsies were used to identify cases; a retrospective chart review was completed. The following variables were extracted: 1° Gleason score; 2° Gleason score; number of sites; % Gleason 4/5 pattern (overall); perineural invasion (present/absent); extracapsular extension (present/absent). Descriptive statistics were used to summarize the results. Results: The charts of 132 patients having a GUP biopsy review were extracted. Seventeen percent (22/132) of cases changed risk category. Of the 47 low risk cases, 23% (11/47) were up-graded in risk category (21% by 1 category; 2% by 2 categories). Of the 46 intermediate risk cases, 15% (7/46) were up-graded and 2% (1/46) were down-graded. Of the 39 high risk cases, only 8% (3/39) were down-graded by 1 risk category. Comparatively, there was a 43% reduction in risk category change between 2003/04 (30%) and 2009/10 (17%). Conclusions: Despite this reduction, a clinically significant proportion of patients changed pathologic risk category upon GUP review. Thus, it is recommended that prostate cancer pathology be routinely reviewed by a GUP as a best practice to optimize management and quality of care. Strategies are still needed to address disparities in pathologic grading and represent a potential area for further investigation. No significant financial relationships to disclose.
Dose-Intensified CHOP with Rituximab (R-Double-CHOP) Followed by Consolidating High-Dose Chemotherapy Is An Effective Treatment for Younger Patients with Advanced Diffuse Large B-Cell Lymphoma
Authors: Daisuke Kurita, Katsuhiro Miura, Yoshihiro Hatta, Yukio Hirabayashi, Atsuko Hojo, Hitomi Kodaira, Mai Yagi, Satomi Kiso, Yujin Kobayashi, Toshitake Tanaka, Noriyoshi Iriyama, Sumiko Kobayashi, Kazuhiro Takei, Akira Horikoshi, Tetsuo Yamazaki, Yoshimasa Kura, Umihiko Sawada, Jin Takeuchi
Journal: Blood (2011)
An underinvestigated toxicity of sunitinib: Red cell macrocytosis.
Authors: D. J. Hands, B. Eccles, T. R. Geldart
Journal: Journal of Clinical Oncology (2011)

371 Background: Sunitinib, a multitargeted receptor tyrosine kinase inhibitor represents a standard firstline therapy for advanced renal cell carcinoma. Red blood cell (RBC) macrocytosis (with or without anaemia) is a recognized haematological toxicity but its aetiology remains uncertain. Methods: The medical records of 73 patients (55 male, 18 female) patients treated with sunitinib between 2007 and 2010 at Poole and Bournemouth NHS Trusts, UK were reviewed. Patient demographics, length of treatment, response, RBC mean cell volume (MCV) indices, and known causes of macrocytosis including B12 and folate deficiency and hypothyroidism were examined. Results: Median duration of treatment was 6 months (range 0-30). 38 (51%) have died. 24 (32%) received 2 or less cycles of treatment with the majority stopping due to early progression or death. 30 patients (41%) developed macrocytosis on treatment, but a trend to macrocytosis was identified in most patients positively correlating to time on treatment. 26 (87%) had a macrocytic anaemia. Median time to onset of macrocytosis was 4 months (range 1-11 months). Of the 30 macrocytic patients; 5 were hypothyroid, 7 had untreated borderline hypothyroidism and 13 were euthryoid throughout. Of patients tested to date 1 patient was found to be serum folate deficient at 2.5 ug/L (3-17). Supplementation corrected the macrocytosis. 1 patient was found to be serum B12 deficient; 53 ng/L (180-900) without any obvious comorbid cause. Further retrospective evaluation of other parameters such as red cell folate and reticulocyte count are currently being carried out. Conclusions: A significant proportion of patients on sunitinib (41%) develop macrocytosis. On the basis of this case series, the largest to date, underlying causes of macrocytosis (with or without anaemia) appear multifactorial. Biochemical hypothyrodism is common following sunitinib treatment and is likely to represent one of several possible contributing factors. B12 and folate deficiency should not be forgotten as a potentially reversible cause of macrocytosis secondary to sunitinib. C-kit inhibition by sunitinib is a potential mechanism, paralleling the potential C-kit mediated macrocytosis commonly recognised in imatinib therapy. No significant financial relationships to disclose.
Priming Effect with G-CSF Enhances In Vitro Apoptosis by Treatment with Ara-C and VP-16 in Leukemic Cell Line.
Authors: Jun-ichi Kitagawa, Takeshi Hara, Hisashi Tsurumi, Nobuhiro Kanemura, Masahito Shimizu, Hisataka Moriwai
Journal: Blood (2007)
New fluorescence imaging method for sentinel lymph node biopsy in patients with early breast cancer.
Authors: Y. Kawai, H. Abe, T. Mori, H. Cho, Y. Kubota, T. Umeda, Y. Kurumi, T. Tani
Journal: Journal of Clinical Oncology (2011)

e11578 Background: Indocyanine green (ICG) is a popular diagnostic reagent for the examination of hepatic function and cardiac output. In this study, based on the fluorescence characteristics of ICG, we present a new method that enables the detection of sentinel lymph nodes (SLN) with high sensitivity using ICG fluorescence imaging. Methods: Fluorescence images were obtained using the fluorescence imaging system, the Photodynamic Eye (Hamamatsu Photonics Co., Japan). A 0.5% ICG solution combined with Indigocarmine was intradermally injected for 0.3 ml in the areola closest to a tumor. Subcutaneous lymphatic channels draining from the areola to the axilla or other directions were visible by fluorescence imagings immediately. The point where the fluorescence disappeared was identified on the skin, and the skin has been pressed with the capsule. The point of fluorescence seemed was then incised, and the SLN were then dissected by fluorescence navigation. Results: This study enrolled 202 patients with clinically node-negative breast cancer. Their average age was 53.9 years (ranged from 29 to 82 years). Sixty five patients were premenopausal, and 137 patients were postmenopausal. There were five cases of Tis lesions and 117 cases with T1 lesions and 80 cases with T2 lesions. Subcutaneous lymphatic channels and SLN were successfully visualized in all patients. One lymphatic channel to the axilla was 53%, two channels were 32%, and three channels were 16%. The channels to other directions were not seen. The number of fluorescent SLN ranged from 1 to 6 (mean: 3.1), and blue dyed SLN ranged from 0 to 3 (mean: 1.2). In the latter, SLN were not identified in 76 patients (identification rate: 62.4%). Twenty three patients had lymph node metastases pathologically. All of them were recognized by fluorescence imagings, but, in 10 patients, lymph nodes with metastases were not identified by a blue dye. Conclusions: The fluorescence imaging method is therefore considered to be a new and effective method for SLN mapping, which allows easy, highly sensitive and real-time imaging-guided SLN mapping in patients with early breast cancer. The current results show that SLN mapping guided by ICG fluorescence imaging could therefore be a promising tool.
Clonal Evolutionary Analysis during HER2 Blockade in HER2-Positive Inflammatory Breast Cancer: A Phase II Open-Label Clinical Trial of Afatinib +/- Vinorelbine
Authors: Gerald Goh, Ramona Schmid, Kelly Guiver, Wichit Arpornwirat, Imjai Chitapanarux, Vinod Ganju, Seock-Ah Im, Sung-Bae Kim, Arunee Dechaphunkul, Jedzada Maneechavakajorn, Neil Spector, Thomas Yau, Mehdi Afrit, Slim Ben Ahmed, Stephen R. Johnston, Neil Gibson, Martina Uttenreuther-Fischer, Javier Herrero, Charles Swanton
Journal: PLoS Medicine (2016)

Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy.
Visual identification of pulmonary ventilation and perfusion: a new application of lung ultrasound
Authors: Guido Tavazzi, Francisca Ana Caetano, Sachin Shah, Joana Alcada, Susanna Price
Journal: Thorax (2016)

A 32-year-old lady with a history of haemochromatosis with iron infiltration of the myocardium and aplastic anaemia was admitted with H1N1-related severe adult respiratory distress syndrome with dense bilateral consolidations in all lobes at chest X-ray and CT scan (figure 1A, B). The severe hypoxaemia requiring mechanical ventilation and refractory to inhaled nitric oxide and pronation led ultimately to venovenous extracorporeal membrane oxygenation placement. Transthoracic echocardiography (TTE) demonstrated a mildly biventricular systolic impairment alike the last TTE done during the follow-up for the haemochromatosis, without any intracardiac shunt as demonstrated by agitated-saline bubble study. Lung ultrasound (LUS) showed bilateral complete consolidation of the lung (tissue-like pattern) in the mid-lower lobes, which was present from admission. …
Prevalence of BRCA1 mutations in women with triple-negative breast cancer: A systematic review.
Authors: N. M. Tun, G. M. Villani, K. Ong
Journal: Journal of Clinical Oncology (2011)

181 Background: We have reported a strong association between “triple-negative” breast cancer (TNBC) [estrogen receptor (ER) and progesterone receptor (PR) negative, HER2 negative] and the risk of having BRCA1 mutations in a meta-analysis. We hereby present a systematic review of a larger pool of specific data investigating the overall prevalence of BRCA1 mutations in women with TNBC. Methods: A Medline search combining the MeSH terms “BRCA” and “triple” and “negative” yielded 37 articles. A similar search in ASCO abstracts yielded 18 relevant articles. Prevalence in each study population as well as the overall prevalence was calculated. Results: 13 eligible studies (from year 2006 to 2011) including 1075 women with TNBC were identified. Out of 13, 1 study each was carried out on Ashkenazi Jewish and Hong Kong Chinese women respectively. Overall prevalence of BRCA1 mutations in women with TNBC is 20.93% (225 out of 1075) (range = 4.8%–43%). Ashkenazi Jewish women with TNBC have a higher-than-average prevalence of BRCA1 mutations (29.2%) although it is lower than the prevalence rates of some study populations. A remarkably low prevalence rate of BRCA1 mutations (4.8%) is found in Chinese women with TNBC. Conclusions: In view of the overall high prevalence rate of BRCA1 mutations (20.93%) in women with TNBC, genetic testing should be discussed with patients with TNBC. Further studies are suggested to evaluate the molecular basis of interestingly low BRCA1 prevalence (4.8%) in Chinese patients with TNBC.
Abstract 16683: Pretreatment With Clopidogrel In ST-segment Elevation Myocardial Infarction. Evidence From a Meta-analysis
Authors: Ramez Nairooz, Yogita Rochlani, Naga Venkata Pothineni, Partha Sardar, David Shavelle
Journal: Circulation (2015)

Background: Current ACC/AHA guidelines recommend a P2Y12 inhibitor in addition to aspirin in ST-segment elevation myocardial infarction (STEMI) patients either on presentation or in the cardiac catheterization laboratory (CCL). In contrast, European guidelines recommend P2Y12 inhibitor administration as soon as possible, but acknowledge that there is no enough evidence to support this class I recommendation. Aim: Perform a meta-analysis to examine the hypothesis that pretreatment with clopidogrel in STEMI patients is superior to no pretreatment and CCL administration. Methods: We performed a literature search for full length articles comparing clopidogrel administration on presentation (pretreatment) compared with CCL administration in STEMI patients undergoing percutaneous coronary intervention (PCI). We used odds ratio (OR) and random effects model for comparisons. We report mortality, major adverse cardiovascular events (MACE), major bleeding and reinfarction at 30 days. Results: A total of 8 studies with 32,509 STEMI patients were included in the analysis. 30 day mortality was significantly lower with pretreatment compared to CCL administration, 4% vs 5% (OR 0.62, 95% confidence interval (CI) [0.46, 0.83]; P=0.002). MACE was significantly lower with pretreatment compared to CCL administration, 6.8% vs 6.3% (OR 0.69, 95% CI [0.58, 0.83]; P&lt;0.0001). Major bleeding was also lower in the pretreatment group (OR 0.80, 95% CI [0.65, 0.97]; P=0.03) that was driven by one study which used more glycoprotein IIb/IIIa inhibitors and more 600 mg loading dose of clopidogrel in the no pretreatment arm. There was no significant difference in reinfarction rates between the groups, 2.6% vs 3.1%. Conclusion: Clopidogrel administration at presentation for STEMI patients undergoing PCI decreases 30 day major adverse cardiovascular events and improves mortality.
Prevalence of Sickle Cell Disease, Hemoglobin S, and Hemoglobin C Among Haitian Newborns: Feasibility of Newborn Screening for Hemoglobinopathies in Haiti
Authors: Genevieve Arty, Rotz Seth, Prasad Bodas, Lucia De Zen, Francesco Angelo Zanolli, Roberto Dall'Amico
Journal: Blood (2012)
Incidence of brain metastases as a first site of recurrence among women with triple receptor-negative breast cancer.
Authors: X. Lei, S. S. Dawood, J. K. Litton, T. A. Buchholz, G. N. Hortobagyi, A. M. Gonzalez-Angulo
Journal: Journal of Clinical Oncology (2011)

1039 Background: The aim of this retrospective study was to define the incidence of brain metastases as a first site of recurrence among women with triple receptor-negative breast cancer (TNBC). Methods: 2,448 patients with stage I-III TNBC diagnosed between 1990 and 2010 were identified. We computed the cumulative incidence of developing brain metastases as a first site of recurrence at 2 and 5 years. Cox proportional hazards models were fitted to determine factors that could predict for the development of brain metastases as a first site of recurrence. Kaplan-Meier product limit method was used to compute survival following a diagnosis of brain metastases. Results: At a median follow up of 39 months 115 (4.7%) patients had developed brain metastases as a first site of recurrence. The cumulative incidence at 2 and 5 years was 3.73% (95% CI 2.92%−4.55%) and 5.44% (95% CI 4.41%−6.47%), respectively. Among patients with stage I, II and III disease, the 2−year cumulative incidence of brain metastases was 0.8%, 3.1% and 8%, respectively (p<0.0001). 5- year cumulative incidence was 2.8%, 4.6% and 9.6% among patients with stage I, II and III disease, respectively (p<0.0001). In the multivariable model, patients with stage III disease had a significant increase in the risk of developing brain metastases as a first site of recurrence (HR = 3.51; 95% CI 1.85 – 6.67; p = .0001) compared to patients with stage I disease. Those with stage II disease had a non significant increased risk of developing brain metastases (HR = 1.61; 95% CI 0.92 – 2.81; p = .10) compared to patients with stage I disease. Median survival following a diagnosis of brain metastases was 7.2 months (range 5.7 to 9.4 months). Conclusions: Patients with non metastatic TNBC have a high early incidence of developing brain metastases as a first site of recurrence, which is associated with subsequent poor survival. Patients with stage III TNBC in particular would be an ideal cohort to research preventive strategies.
Chimerism Analysis of Langerhans Cells Early after T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Timo Schmitt, Kerstin Schneiker, Abdo Konur, Ali Hadian, Klaus Bender, Esther von Stebut, Karin Kolbe, Christoph Huber, Wolfgang Herr, Ralf G. Meyer
Journal: Blood (2007)
Gene Expression Profiling Identifies 4 Sub-Classes with Distinct Clinical Associations in Hyperdiploid Myeloma.
Authors: Wee-Joo Chng, Natalia Gonzalez-Paz, Shaji Kumar, Scott Van Wier, Gregory Ahmann, Tammy Price-Troska, Kim Henderson, Marta Chesi, Morie Gertz, S. Vincent Rajkumar, Robert Kyle, Martha Lacy, Angela Dispenzieri, Philip Greipp, Peter Leif Bergsagel, Rafael Fonseca
Journal: Blood (2005)
The INFORM HER2 Dual ISH assay compared with FISH to determine HER2 gene status in invasive breast carcinoma.
Authors: I. R. Loftin, A. McElhinny, R. Miller, C. Garcia, I. Bai, J. Ranger-Moore, J. Ostrem, M. Padilla, T. M. Grogan
Journal: Journal of Clinical Oncology (2011)

25 Background: The HER2 gene, located on chromosome 17 (Chr17), is amplified in 15-25% of patients with invasive breast carcinoma. Amplification and/or HER2 overexpression is associated with poor clinical outcome for these patients; however prognosis is improved if HER2 status indicates eligibility of patients for trastuzumab therapy. Thus, accurate diagnosis of HER2 status through a companion diagnostic is essential. Here we validated the INFORM HER2 Dual ISH Probe Cocktail (Dual ISH) assay as an alternative to FISH, the current gold standard for HER2 testing. The Dual ISH assay is fully automated and is scored using light microscopy. Methods: A multi-site method comparison and inter-laboratory reproducibility study were performed. 5 sites were used to compare Dual ISH results with FISH (Vysis PathVysion). 510 invasive breast carcinoma cases were stained at 3 clinical sites, FISH staining was performed at a fourth site (central laboratory). IHC status was determined at a fifth site (second central laboratory). In addition, 6 cases were evaluated for inter-site (3 sites), inter-reader (6 readers), inter-run (15 runs) and intra-run (duplicate slides) reproducibility. All assay steps were fully automated on a VENTANA BenchMark XT automated slide stainer, using a HER2 repeat-reduced, dinitrophenyl-labeled probe targeting the HER2 gene, detected with silver metallographic detection, and a digoxigenin-labeled Chr 17 probe, detected by an alkaline phosphatase-driven red chromogenic detection. HER2 and CHR17 signals were enumerated using conventional light microscopy allowing interpretation within the morphological context of the specimen. HER2 status was determined as the ratio of HER2/Chr17, where a ratio &lt;2 is non-amplified and a ratio ≥2 is amplified. Results: The positive and negative agreement rates with FISH (95% CI) were 96% (92.6-97.9) and 92.3% (88.6-94.8), respectively. The HER2 Dual ISH assay also was highly reproducible in determining HER2/Chr17 ratio across sites, days, readers and runs. Conclusions: The fully automated INFORM HER2 Dual ISH assay is reproducible and concordant with the manual FISH assay in determining HER2 status in invasive breast carcinoma.