tbuckley/cabot-search huggingface dataset:
Prospective multicenter study of the impact of the Prosigna assay on adjuvant clinical decision-making in women with early stage breast cancer: which patients are the best candidates?
Authors: Roman Rouzier, David Gentien, Jean Marc Guinebretiere, Marie-Ange Mouret-Reynier, Coraline Dubot, Paul H. Cottu, Cyrille Huchon, Sonia Zilberman, Helene Berseneff, Cyril Foa, Remy Salmon, Myriam Delomenie, Diane De Croze, Aurelie Roulot, Amandine Bonhomme, Anne Vincent- Salomon, Anne Cayre, Celine Callens, Frederique Madeleine Penault-Llorca, Delphine Hequet
Journal: Journal of Clinical Oncology (2016)

543 Background: Prosigna is a standardized test measuring expression levels of 50 classifier genes (PAM50) in formalin-fixed, paraffin-embedded (FFPE) breast tumor tissue using nCounter Technology (NanoString Technologies, Inc., Seattle, WA). It provides intrinsic subtype and risk of recurrence (ROR) score predicting 10y recurrence probability. This Decision Impact study examines whether the Prosigna test influences adjuvant treatment decision beyond immunohistochemistry (IHC) testing. Methods: The analytic sample was comprised of postmenopausal early-stage breast cancer (EBC) women with estrogen-receptor positive, HER2 negative, pT1-T2 pN0/pN1mi tumors. FFPE surgical specimens were centrally analyzed using Prosigna to classify patients according to the intrinsic tumor subtype and ROR score. The primary endpoint was the effect of the Prosigna test on oncologists’ adjuvant treatment recommendations, and the actual treatment received by patients. Secondary endpoints included evaluation of tumor and patient characteristics that are associated with treatment modification. Results: A total of 205 patients met eligibility criteria and were enrolled in 8 centers between March 2015 and January 2016: 59% of tumors were classified by PAM50 as Luminal A, 39% as Luminal B, 1% Basal, .5% HER2. Clinicians, using local IHC, classified 15% of PAM50 Luminal A as Luminal B, and 40% PAM50 Luminal B as luminal A (overall 27% discordance). Prosigna results led to a reported change in chemotherapy indication in 17% overall (23% according to the French guidelines). Grade 1-2 tumors with progesterone receptor expression less than 20% or Ki67 between 10 and 20% were significantly associated with modification of adjuvant treatment (p < .001). Conclusions: In this prospective Decision Impact study, Prosigna results led to a 17% change in chemotherapy indication. The 27% discordance in intrinsic subtyping between PAM50 and IHC underlines the importance of molecular testing for optimal systemic therapy indications in EBC, particularly fot grade 1-2 tumors with progesterone receptor expression less than 20% or Ki67 between 10 and 20%. Clinical trial information: NCT02395575.
Genome-Wide Mutational Landscape of Infant Acute Lymphoblastic Leukemia
Authors: Tomoya Isobe, Kenichi Yoshida, Chika Kobayashi, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Shiro Fukuda, Shogo Yamamoto, Kenji Tatsuno, Yuki Aoki, Takako Miyamura, Shuichi Tsutsumi, Nobutaka Kiyokawa, Takashi Ishihara, Daisuke Tomizawa, Eiichi Ishii, Satoru Miyano, Seishi Ogawa, Hiroyuki Aburatani, Shuki Mizutani, Junko Takita, Masatoshi Takagi
Journal: Blood (2016)
Prediction of exemestane benefit in patients with advanced breast cancer based on diagnostic biopsy mRNA analysis.
Authors: Troels Dreier Christensen, Anna Sofie Kappel Buhl, Ib Jarle Christensen, Knud Mejer Nelausen, Eva Balslev, Ann Søegaard Knoop, Eva Harder Brix, Peter Michael Vestlev, Bent Ejlertsen, Iben Kumler, Adam Luczak, Sven Tyge Langkjer, Soeren Linnet, Erik Jakobsen, Jurij Antonovic Bogovic, Vesna Glavicic, Ulla Hald Buhl, Peter Buhl Jensen, Steen Knudsen, Dorte Nielsen
Journal: Journal of Clinical Oncology (2017)

e12532 Background: Exemestaneis a steroidal aromatase inhibitor used in the treatment of postmenopausal patients with estrogen receptor(ER)-positive adjuvant and advanced breast cancer. We aimed to determine the predictive value of a multigene mRNA-based mathematical algorithm (Drug Response Predictor (DRP)) for benefit of exemestane. The DRP is founded on measuring the full cancer transcriptome in sensitive and drug resistant cell lines compared with expression patterns in tumors and broadly validated in several studies (Wang et al. JNCI (2013) 105 (17): 1284-1291.) (Knudsen, S. et al. PLoS One (2014) 9(2): e87415.) (Christensen, TD et al. J Clin Oncol (2016) 34: suppl; abstr e12056.) (Kappel, IB et al. J Clin Oncol (2016) 34: suppl; abstr e20007.). Methods: Among 838 consecutive patients from a DBCG cohort with advanced breast cancer treated at 10 participating sites we identified 163 patients who between November 2008 and November 2015 initiated exemestane. All but one patient were ER-positive. Patients were evaluated every 3 to 4 months using CT scans and clinical examination. After patient informed consent mRNA was extracted and assayed on Affymetrix Gene Chip U133p2 arrays from formalin fixed paraffin embedded diagnostic biopsies. The primary endpoint was progression free survival (PFS). Analysis of the DRP’s ability to predict PFS was performed using a Cox regression model adjusted for treatment line. Results: Median PFS was 8.5 months. Of the 163 patients, 101 received prior adjuvant antihormone therapy and 60 did not. Data regarding adjuvant therapy was inaccessible for two patients. Hazard ratios for patients with predicted good vs. poor effect of exemestane are shown in the table. Conclusions: In a clinical setting, a mathematical algorithm using mRNA from a diagnostic biopsy can in patients unexposed to previous adjuvant endocrine therapy with statistical significance predict who will benefit from exemestane. [Table: see text]
New Editorial Board Members—July 2017
Authors: Melina R. Kibbe
Journal: JAMA Surgery (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
A phase I/II trial of olaparib in combination with eribulin in patients with advanced or metastatic triple negative breast cancer (TNBC) previously treated with anthracyclines and taxanes: The analyses of efficacy and safety from phase II.
Authors: Masato Takahashi, Kan Yonemori, Harukaze Yamamoto, Ken-ichi Watanabe, Chikako Shimizu, Hiroyuki Yasojima, Norikazu Masuda, Seiki Takashima, Kenjiro Aogi, Nobuaki Matsubara, Yoichi Naito, Satoru Shimizu, Naohito Yamamoto, Rikiya Nakamura, Hirofumi Michimae, Akinobu Hamada, Kenji Tamura, Yasuhiro Fujiwara
Journal: Journal of Clinical Oncology (2016)

1080 Background: Metastatic TNBC has a poorer prognosis compared with other subtypes because of the lack of a confirmed effective target. Eribulin is a standard treatment for metastatic TNBC and olaparib (Lynparza), a PARP inhibitor, has shown efficacy in breast cancer with germline (g)BRCA1/2 mutations. We designed this Phase I/II trial with an expectation of a synergistic effect for metastatic TNBC patients (pts) enrolled, irrespective of gBRCA1/2 mutation status. In Phase I, we reported at ASCO 2015 the recommended dose of olaparib tablets was 300 mg BID. We will present the efficacy and safety of this combination treatment from phase II. Methods: Pts with advanced or metastatic TNBC previously treated with anthracyclines and taxanes were eligible. Confirmation of a BRCA1/2 mutation was not mandatory before enrollment. This trial was conducted at 8 institutions in Japan. According to the results from Phase I, 1.4 mg/m2 of eribulin was administered intravenously on Days 1 and 8. Olaparib tablets were orally administered at a dose of 300 mg BID. The primary efficacy endpoint was tumor response rate. Results: From June 2014 to December 2014, 24 pts were enrolled. The median age was 46 years old (range: 27 to 73). The median number of prior chemotherapy regimens was 3 (range: 2 to 6). Sixteen pts (66.7%) had visceral metastasis and 8 non visceral metastasis. The relative dose intensity of eribulin was 74.9% and olaparib 75.4%. The response rate was 37.5% (95% CI: 18.8–59.4), including CR in 1 pt. Median progression free survival was 4.2 months (95% CI: 2.7–7.6). The median overall survival was not reached and 11 pts died. Severe adverse events (G3 and G4) were leukocytopenia (83.3%), neutropenia (83.3%), febrile neutropenia (33.3%), anemia (37.5%) and thrombosis (8.3%). Conclusions: The combination of olaparib and eribulin indicates a promising clinical interaction in pts with metastatic TNBC, without intolerable adverse events. The next step is exploratory research into the relationship between gBRCA1/2 mutation status and/or HRD, and the clinical efficacy of this combination treatment. Clinical trial information: 12.
Pretreatment neutrophil to lymphocyte ratio (NLR) in patients with triple negative breast cancer (TNBC) treated with neoadjuvant chemotherapy.
Authors: Paul R. Walker, Jessica R. Hildebrand
Journal: Journal of Clinical Oncology (2016)

e12570 Background: Neutrophils are known to promote tumor cell proliferation, angiogenesis, and distant metastasis while lymphocytes play an important role in immune activity against tumor cells. Neutrophil to lymphocyte ratio (NLR) has been shown to have prognostic value in various types of malignancies including TNBC. (Pristelli et al BMC Cancer 2015) Prognostic biomarkers of response and outcome are needed to optimally teat TNBC in the curative setting. We assessed NLR as a prognostic indicator in patients with TNBC treated with neoadjuvant metronomic chemotherapy. Methods: Retrospective chart analysis was performed on patients with TNBC who were treated as part of a phase II protocol neoadjuvant metronomic chemotherapy in TNBC (NCT00542191) with weekly doxorubicin 24 mg/m2 + daily oral cyclophosphamide 60 mg/m2 x 12 weeks followed by weekly paclitaxel 80 mg/m2 + weekly carboplatin AUC 2 x 12 weeks. NLR was measured pretreatment, after completion of Doxorubicin and Cytoxan, and after completing Paclitaxel and Carboplatin. Results: The NLR at these points was assessed in 21 patients. NLR ranged from 1.3 to 12. NLR < 3 before treatment was associated with a significantly better OS (p = 0.046) and PFS (p = 0.039). There was no correlation between NLR and pathologic complete response in our patients. Conclusions: Low NLR < 3 predicts a favorable prognosis in patients with TNBC treated with neoadjuvant metronomic chemotherapy. Clinical trial information: 00542191.
MCAM Mediates Chemoresistance in Small-Cell Lung Cancer via the PI3K/AKT/SOX2 Signaling Pathway
Authors: Satyendra C. Tripathi, Johannes F. Fahrmann, Muge Celiktas, Mitzi Aguilar, Kieren D. Marini, Mohit K. Jolly, Hiroyuki Katayama, Hong Wang, Eunice N. Murage, Jennifer B. Dennison, D. Neil Watkins, Herbert Levine, Edwin J. Ostrin, Ayumu Taguchi, Samir M. Hanash
Journal: Cancer Research (2017)

Abstract Despite favorable responses to initial therapy, small-cell lung cancer (SCLC) relapse occurs within a year and exhibits resistance to multiple drugs. Because of limited accessibility of patient tissues for research purposes, SCLC patient-derived xenografts (PDX) have provided the best opportunity to address this limitation. Here, we sought to identify novel mechanisms involved in SCLC chemoresistance. Through in-depth proteomic profiling, we identified MCAM as a markedly upregulated surface receptor in chemoresistant SCLC cell lines and in chemoresistant PDX compared with matched treatment-naïve tumors. MCAM depletion in chemoresistant cells reduced cell proliferation and reduced the IC50 inhibitory concentration of chemotherapeutic drugs in vitro. This MCAM-mediated sensitization to chemotherapy occurred via SOX2-dependent upregulation of mitochondrial 37S ribosomal protein 1/ATP-binding cassette subfamily C member 1 (MRP1/ABCC1) and the PI3/AKT pathway. Metabolomic profiling revealed that MCAM modulated lactate production in chemoresistant cells that exhibit a distinct metabolic phenotype characterized by low oxidative phosphorylation. Our results suggest that MCAM may serve as a novel therapeutic target to overcome chemoresistance in SCLC. Cancer Res; 77(16); 4414–25. ©2017 AACR.
L'infection évolutive est un facteur prédictif de mortalité précoce après gastrostomie percutanée endoscopique
Authors: C Joubert, LE Tiengou, R Gloro, H Castel, E Vander Eecken, S Dargère, J Parienti, M Vergnaud, JM Reimund, MA Piquet
Journal: Endoscopy (2006)

Les travaux disponibles sur les facteurs pronostiques de morbidité et de mortalité après GPE sont discordants, et présentent des faiblesses comme leur caractère rétrospectif ou de faibles effectifs. Le but de notre étude était d'évaluer prospectivement les facteurs prédictifs d'infection péristomiale et de mortalité précoce (<1 mois) après GPE.
Optimal patient selection for electron intraoperative radiotherapy (IORT) as sole treatment for breast cancer.
Authors: Kathleen C. Horst, Sergio Maluta, Frank Vicini, Samir Abdallah Hanna, Catherine Philippson
Journal: Journal of Clinical Oncology (2016)

1059 Background: Several phase III trials of breast IORT have recently been published with findings that have generated significant controversy and discussion. As different techniques were used in these trials in a broad range of patients, it is unclear if the results obtained were due to differences in technique, type of radiation or patient selection. The goal of the current study was to review findings from studies using only electron IORT in appropriately selected patients considered suitable for APBI. Methods: We performed a literature search addressing the use of electron IORT as the sole radiation treatment for early stage breast cancer. Publications that delivered IORT prior to tumor excision, and those that did not deliver the prescription dose as deeply as the chest wall, were excluded. The ASTRO and ESTRO Consensus guidelines were used to select patients from these studies based upon society derived criteria for the application of APBI. ESTRO Good category differs from ASTRO Suitable in that it allows patients ≥ 50, tumors up to 3 cm, and any ER/PgR status. Results: A total of 2,449 patients (pts) met the search criteria in 7 trials (1 phase III, 6 retrospective). Median follow up ranged from 2-6 yrs. In the 715 pts who met the ASTRO Suitable criteria, the actuarial rate of LR varied from 0 -1.5%. Of the 1017 pts that met the ESTRO Good criteria, the rate of LR varied from 0 -1.9%. Conclusions: Excellent results were observed using electron IORT as the sole radiation treatment in appropriately selected patients using ASTRO and ESTRO guidelines for APBI. Longer follow-up and additional studies are necessary to validate these findings and explore if additional patients may be suitable for this form of APBI if the total dose and QA techniques are optimized. Reference Median FU (yrs) Total # pts # LR LR (%) # ASTRO Suitable #LR LR (%) # ESTRO Good #LR LR (%) ELIOT (1) 5.8 585 34 5.8 135 2 1.5 - - - 1822-ELIOT Out Trial (2,3) 3.5 * 1822 75 4.1 294 3 1.0 573 7 1.2 U. of Verona (4,5) 5 226 4 1.8 128 1 0.8 160 3 1.9 Brussels (6) 2 204 1 0.5 87 1 1.1 151 1 0.7 Japan (7) 6 32 0 0 16 0 0 28 0 0 Brazil (8) 4.3 152 5 3.2 48 0 0 92 2 1.9 Naples (9) 4 13 0 0 7 0 0 13 0 0 Total 2449 119 715 7 1017 13 *Projected 5-yr rates reported as 1.5% for ASTRO Suitable and 1.9% for ESTRO Good.
Apport de l'échographie dans le diagnostic de la tuberculose péritonéale: étude prospective à propos de 335 cas
Authors: N Benzzoubeir
Journal: Endoscopy (2005)

La tuberculose péritonéale demeurre une affection fréquente dans les pays en voie de developpement. Son diagnostic positif repose essentiellement sur l'étude histologique des prélèvements effectués au cours de la coelioscopie. L'échographie de plus en plus utilisée de première intention s'avère d'un grand apport pour le diagnostic et la surveillance de cette affection.
Radiomics method to predict loss of heterozygosity on chromosome 1p/19q of oligodendroglial tumor.
Authors: Jingwei Wei, Jie Tian
Journal: Journal of Clinical Oncology (2017)

2043 Background: Oligodendroglial tumor (OT) is one of the main types of gliomas, which is incurable in current situation. As a tumor-specific genetic alteration of OTs, loss of heterozygosity (LOH) on chromosome 1p/19q indicates a preferable response to chemo/radiotherapy and a better survial, which could be used as a key molecular signature for personalized treatment decision making. However, 1p/19q LOH status is now commonly obtained by fluorescence in situ hybridization after the tumor resection, which is highly likely to lead functin deficit with tumor locating on eloquent area. Thus, a noninvasive predicition on 1p/19q LOH is required. Here, we used a "Radiomics" method to achieve the prediction based on magnetic resonance imaging in this study. Methods: A cohort of 113 OT patients was collected from Beijing Tiantan Hospital. 593 three-dimensional imaging features were extracted on T2-weighted images including textural and non-textural features. We used "minimum redundancy maximum relevance" and "iterative backward elemination and forward inclusion" algorithms to pick up the most effective features with a p-value &lt; 0.05. With the selected features as the input, support vector machine algorithm was adopted to predict the 1p/19q LOH status with 10-fold cross validation. Comparisons were made between the traditional clinical predictors and the established model. Results: The prediction accuracy for 1p/19q LOH turned out to be 86.6%. The top three features contributing most to the prediction were respectively: GlobalUniformity, GaborBankD4GLRLMLGRE and GaborBankD4GLRLMSRLGE. The predictive performance of the radiomics model was proved to be far more valid than the clinical predictors (indistict tumor border and heterogeneous signal intensity) with the higher area under curve (AUC). Compared with the best single feature (GlobalUniformity, AUC: 0.749), this combined-feature model has the best diagnostic performance with an AUC of 0.898. Conclusions: This study reveals the intrinsic association between the imaging features and 1p/19q LOH status, meanwhile, realizes the high precision prediction, providing reliable basis for the pre-operative treatment regime.
Bevacizumab plus hypofractionated radiotherapy versus radiotherapy alone in elderly patients with glioblastoma: Efficacy and imaging analyses of the ARTE trial.
Authors: Hans-Georg Wirsching, Ghazaleh Tabatabai, Ulrich Roelcke, Andreas Felix Hottinger, Andrea Schmid, Ludwig Plasswilm, Katrin Lisa Conen, Thomas Hundsberger, Francesca Caparrotti, Roger Von Moos, Christian Alexander Riklin, Luca Remonda, Patrick Roth, Leonhard Held, Elisabeth Jane Rushing, Adrian Ochsenbein, Michael Weller
Journal: Journal of Clinical Oncology (2017)

2014 Background: The addition of bevacizumab (BEV) to first-line temozolomide chemoradiotherapy prolonged progression-free survival (PFS), but not overall survival (OS) in newly diagnosed glioblastoma in two phase III trials. Elderly and frail patients are underrepresented in most clinical trials, but early uncontrolled reports of BEV treatment of glioblastoma suggested preferential benefit in this patient population. Methods: ARTE was a 2:1 randomized, multi-center, open-label trial of hypofractionated radiotherapy (RT) in combination with intravenous BEV every 2 weeks (Arm A, N = 50) versus RT alone (Arm B, N = 25) in patients with newly diagnosed glioblastoma aged 65 years or older. Quality of life (QoL) was monitored by the EORTC QLQ-C30/BN20 modules. Response was assessed using Response Assessment in Neuro-Oncology (RANO) criteria. Exploratory imaging studies included apparent diffusion coefficient (ADC) mapping and 18F-fluoro-ethyl-tyrosine (FET) positron emission tomography (PET). Results: Established prognostic factors including age, Karnofsky performance score (KPS), O6-methylguanine DNA methyltransferase (MGMT) gene promoter methylation and steroid intake at study entry were balanced between arms. Median PFS was longer in Arm A vs. Arm B (7.6 vs. 4.8 months, p = 0.003), but OS was similar (12.1 vs 12.2 months, p = 0.8). Prior to progression, no differences in QoL were noted, but clinical deterioration was deferred in Arm A vs. Arm B. In a Cox model that controlled for established prognostic factors, an association with prolonged PFS was detected for Arm A versus Arm B (hazard ratio [HR] 0.36, p = 0.001) and for KPS 90-100% versus 60-80% (HR 0.50, p = 0.02). Applying a similar Cox model to OS detected an association with age 65-69 vs 70+ (HR 0.52, p = 0.02) and KPS 90-100% versus 60-80% (HR 0.53, p = 0.03). Exploration of imaging predictors of OS for Arm A identified response by RANO (HR 0.52, p = 0.02), but detected no prognostic role for T2, ADC or FET signal intensity. Conclusions: Efficacy outcomes and exploratory imaging analyses of the ARTE trial do not support the notion that benefit from BEV is more pronounced in elderly glioblastoma patients. Clinical trial information: NCT01443676.
Guideline: USPSTF makes no recommendation for pelvic exams to screen for gynecologic conditions in asymptomatic women
Authors: Brian Budenholzer
Journal: Annals of Internal Medicine (2017)

Source Citation US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al. Screening for gynecologic conditions with pelvic examination: US Preventive Services Task Force recommendation statement. JAMA. 2017;317:947-53. 28267862
Day 14 bone marrow examination in the management of acute myeloid leukemia
Authors: Christopher M. Terry, Rory M. Shallis, Elihu Estey, Seah H. Lim
Journal: American Journal of Hematology (2017)

The National Comprehensive Cancer Network (NCCN) recommends that a repeat bone marrow evaluation is carried out seven to ten days following completion of induction therapy so that if a patient's day 14 bone marrow shows residual blast cell counts of >10%, the patient would proceed early to a second cycle of induction therapy. Although blast cell counts of <5% on day 14 bone marrow is sensitive in predicting remission on day 28, various studies have found that day 14 bone marrow is highly nonspecific because a large proportion of patients with blast cell counts of >5% on day 14 bone marrow would still attain a complete remission of the disease without any further chemotherapy. Clinical decision based on day 14 bone marrow will result in some of these patients being given a second induction therapy unnecessarily. A second cycle of chemotherapy is associated with not only higher risk for treatment-related mortality but also increased use of hospital resources such as increased intravenous antimicrobials use, longer hospital stay, and higher demand for blood products. In this article, we examined the utility, discussed the shortfalls, and re-appraised the values of day 14 bone marrow in the management of patients with AML. On the basis of our review, we suggest that the practice of day 14 bone marrow examination should be re-evaluated and should probably only be carried out in the setting of clinical trials with clear questions to address its role in predicting outcome of the therapeutic intervention.