tbuckley/cabot-search huggingface dataset:
BRCA1 and RAP80 mRNA levels and median survival (MS) of advanced gastric cancer patients (p) treated with oxaliplatin plus 5-fluorouracil (FOLFOX).
Authors: J. Wei, L. Yu, C. Costa, Z. Zou, H. Chen, S. Benlloch, J. Sanchez, M. Taron, R. Rosell, B. Liu
Journal: Journal of Clinical Oncology (2010)

e14602 Background: In a previous study (Wei et al. BJC 2008), advanced gastric cancer p with high ERCC1 mRNA expr ession had significantly shorter MS when treated with FOLFOX. To further identify predictive biomarkers in gastric cancer, we examined the expression of genes involved in the repair of chromatin damage through the homologous recombination pathway. Low levels of BRCA1 mRNA confer hypersensitivity to radiotherapy and cisplatin. RAP80 is a linker of BRCA1 and can cause DNA repair regardless of BRCA1 status. Methods: We have examined the expr ession of BRCA1 and RAP80 by RT-QPCR in a new series of 200 advanced gastric cancer p treated with FOLFOX. Expression levels by terciles were correlated with MS. In ancillary analyses, we examined the expression of PIAS1 and PIAS4 as a surrogate of BRCA1 SUMOylation and the expression of SIAH2 and ERCC1. Results: Interim data is available on 135 p: median age, 61 years (range, 34- 92); 106 males; prevalent histology, adenocarcinoma (118 p); 49 stage IIIA, 45 stage IIIB, 41 stage IV. Median expression levels: BRCA1, 6.72 (range, 0.58-39.4); RAP80, 2.85 (range, 0.34-12.13). MS was 13.5 months (m) overall, compared to 7.5 m for p with high RAP80 levels and intermediate or high BRCA1 levels. The influence of second-line docetaxel is being examined. Conclusions: While the role of BRCA1 and RAP80 expression levels is not conclusive in the interim analysis, the effect could have been influenced by second-line treatment. The role of BRCA1 SUMOylation could further clarify the potential relevance of BRCA1 as a predictive biomarker. No significant financial relationships to disclose.
Barber test as a screening tool in multidimensional geriatric evaluation in elderly women with early breast cancer
Authors: M. Molina-Garrido, C. Guillen-Ponce, J. Santiago, M. Muñoz, A. Olaverri, L. Haro, A. Carrato
Journal: Journal of Clinical Oncology (2009)

e20645 Background: The Comprehensive Geriatric Assessment (CGA) is a key component of the treatment approach for older cancer patients, but it is time consuming. In this study, we have evaluated the validity of a brief frailty screening tool, the Barber test (BT), for identifying disability in older patients with early breast cancer (BC) in the University General Hospital in Elche. Methods: Between January 2007 and December 2007, a total of 41 patients older than 65 years who were actively receiving chemotherapy for early BC, were enrolled in our study. Eligible patients were screened with the Barber test and completed a standardized CGA (Activities of Daily Living measured by Barthel Scale, Instrumental Activities of Daily Living measured by Lawton-Brody Scale, cognitive evaluation measured by Pfeiffer Test, comorbidity (Charlson´s index), risk of malnutrition (Nutritive Initiative Screening), and ECOG). The validity of the BT in this population was assessed by comparing the BT results with results from a simultaneous CGA. A receiver operating characteristic (ROC) analysis was employed. The ROC evaluated the BT as a screening measure for impairment compared with the CGA (using the definition of impairment on the CGA as deficits on ≥2 individual tests within the battery, and on the BT as a score &gt;0). The area under the ROC curve (AUC) was calculated to reflect the predictive value of the BT for identifying impairment. Results: Forty-one women were recruited. Median age was 72.88 years (range 65.03 to 85.46). 30 patients (73.2%) were older than 70 years. 36.6% were dependent in Barthel Scale, and 46,3% were dependent in Lawton-Brody Scale. 19,5% had cognitive impairment. The Barber test was moderate predictive for identifying impairment compared with the CGA, with an AUC of 0.730 (standard error, 0.081; 95% confidence interval for detecting asymptomatic normals, 0.571–0.889); p=0.012). Conclusions: Functional impairments are prevalent among older patients with early BC who receive adjuvant chemotherapy treatment. The current results indicate that the brief Barber test performed nearly as well as a conventional CGA in detecting geriatric impairment in this population. No significant financial relationships to disclose.
A phase I study of imatinib mesylate and paclitaxel in patients with advanced (stage IIIC/IV) or recurrent uterine papillary serous carcinoma (UPSC)
Authors: B. M. Slomovitz, L. M. Ramondetta, T. Johnston, K. H. Lu, R. R. Broaddus, P. Muller, R. B. Iyer, T. W. Burke, D. M. Gershenson, J. Wolf
Journal: Journal of Clinical Oncology (2007)

16025 Background: Uterine serous carcinoma (USC) is a rare, aggressive uterine tumor biologically distinct from typical endometrial cancers. Imatinib mesylate (IM)-associated kinases (kit, abl, PDGFR-B) are overexpressed and activated in most tumors from patients (pts) with USC. Single agent paclitaxel (TAX) has a good response rate but short duration of response in pts with USC. The purpose of this study was to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of escalated doses of IM with a fixed dose of TAX. Methods: Pts with newly diagnosed (stage IIIC/IV) or recurrent USC were eligible (pts were required to have tumors that expressed at least one of the IM-targeted kinases by immunohistochemistry). Measurable disease was not required. TAX was administered at 175 mg/m 2 every three weeks. One dose reduction to 135 mg/m 2 was allowed. IM was given daily (400 mg, 500 mg or 600 mg). A 3+3 design was implemented. Pts with measurable disease were treated until progression or treatment associated toxicity. Pts with no measurable disease were treated for six cycles. Results: 11 pts were enrolled. The median age was 62 years (47–79). A total of 50 cycles were administered. Three pts were treated at the first dose level (400 mg), 6 pts treated at the second dose level (500 mg), and 2 pts were treated at the highest dose level (600 mg). Three DLTs were observed (1 at 500 mg level and 2 at 600 mg level) including: rash, neutropenia, and fatigue. IM 500 mg daily and TAX 175 mg/m 2 every three weeks was the MTD. There were 3 serious adverse events not related to treatment (infection, dyspnea, pain). Neutropenia was the most common grade 3 or 4 toxicity but only one patient required TAX dose reduction. 8 pts were evaluated for efficacy (2 with measurable disease, 6 with no measurable disease). 1 (of 2) pts with measurable disease had a partial response and was treated for 13 cycles. Of the 6 pts with no measurable disease, 2 recurred (5 and 10 months). The median disease free interval for the pts without recurrent disease was 22 months (6–30). Conclusion: Combination therapy of IM and TAX is well tolerated with minimal side effects in pts with advanced or recurrent USC. Initiation of the phase II component of this study is warranted to better evaluate efficacy. No significant financial relationships to disclose.
The Effect of Postoperative Face-Down Positioning and of Long- versus Short-Acting Gas in Macular Hole Surgery
Authors: Rohan W. Essex, Zabrina S. Kingston, Margarita Moreno-Betancur, Bruce Shadbolt, Alex P. Hunyor, William G. Campbell, Paul P. Connell, Ian L. McAllister
Journal: Ophthalmology (2016)
Prescribing Habits for Theophylline Preparations
Authors: J K Wiffen, S H D Jackson
Journal: Journal of the Royal Society of Medicine (1983)

Information concerning the prescriptions for theophylline preparations for a group of 80 inpatients and 55 outpatients were examined. Slow-release preparations were overwhelmingly preferred. The majority of patients were receiving low daily doses of theophylline or equivalent, and serum drug level monitoring was almost non-existent.
Tai Chi for Patients with Parkinson's Disease
Authors: Tao Liu, Lixing Lao
Journal: New England Journal of Medicine (2012)

To the Editor: The article by Li et al. (Feb. 9 issue)1 reported that tai chi was successful in improving various functional outcomes in patients with mild-to-moderate Parkinson’s disease, as compared with conventional physical exercises (resistance training and stretching). However, that success might be due to placebo effects rather than to the specific efficacy of tai chi itself. Since this study did not use a double-blind study protocol, participants were aware of their intervention assignments, possibly allowing their beliefs and expectations to bias treatment outcomes. Indeed, Parkinson’s disease is one of a number of conditions that are particularly subject to the influence of placebo effects.2 Tai chi is definitely more than a mere set of body movements. At the core of tai chi is a unique theory based on ancient Chinese culture about the value of moving vital energy, or qi, throughout the body. Tai chi can hardly be practiced in the absence of its cultural underpinnings. In fact, performing tai chi can be considered to be just a “healing ritual [that] creates a receptive person susceptible to the influences of authoritative culturally sanctioned powers,”3 thus producing robust placebo responses.
Preoperative prediction of histopathological outcome in basal cell carcinoma: flat surface and multiple small erosions predict superficial basal cell carcinoma in lighter skin types
Authors: I. Ahnlide, I. Zalaudek, F. Nilsson, M. Bjellerup, K. Nielsen
Journal: British Journal of Dermatology (2016)

Prediction of the histopathological subtype of basal cell carcinoma (BCC) is important for tailoring optimal treatment, especially in patients with suspected superficial BCC (sBCC).To assess the accuracy of the preoperative prediction of subtypes of BCC in clinical practice, to evaluate whether dermoscopic examination enhances accuracy and to find dermoscopic criteria for discriminating sBCC from other subtypes.The main presurgical diagnosis was compared with the histopathological, postoperative diagnosis of routinely excised skin tumours in a predominantly fair-skinned patient cohort of northern Europe during a study period of 3 years (2011-13). The study period was split in two: during period 1, dermoscopy was optional (850 cases with a pre- or postoperative diagnosis of BCC), while during period 2 (after an educational dermoscopic update) dermoscopy was mandatory (651 cases). A classification tree based on clinical and dermoscopic features for prediction of sBCC was applied.For a total of 3544 excised skin tumours, the sensitivity for the diagnosis of BCC (any subtype) was 93·3%, specificity 91·8%, and the positive predictive value (PPV) 89·0%. The diagnostic accuracy as well as the PPV and the positive likelihood ratio for sBCC were significantly higher when dermoscopy was mandatory. A flat surface and multiple small erosions predicted sBCC.The study shows a high accuracy for an overall diagnosis of BCC and increased accuracy in prediction of sBCC for the period when dermoscopy was applied in all cases. The most discriminating findings for sBCC, based on clinical and dermoscopic features in this fair-skinned population, were a flat surface and multiple small erosions.
Prognostic significance of nuclear excision (NER) and base excision (BER) DNA repair gene polymorphisms in esophageal cancer
Authors: P. A. Bradbury, A. L. Marshall, M. H. Kulke, W. Zhou, R. S. Heist, L. Su, T. J. Lynch, F. A. Shepherd, D. C. Christiani, G. Liu
Journal: Journal of Clinical Oncology (2007)

2511 Background: DNA repair pathways are involved in cisplatin-induced damage (NER pathway) &amp; radiation damage (BER pathway). Some single nucleotide polymorphisms (SNPs) of DNA repair genes are associated with DNA repair capacity, cancer risk &amp; outcomes. We investigated the prognostic significance of 7 NER/BER SNPs on disease free (DFS) &amp; overall survival (OS) in esophageal cancer. Methods: 150 patients with esophageal cancer treated with cisplatin-based chemoradiation &amp; surgery were genotyped for BER (XRCC1 Arg399Gln; APE1 Asp148Glu; hOGG1 Ser326Cys) &amp; NER (ERCC1 8092C/A; ERCC1 codon 118 C/T; XPD Asp312Asn; XPD Lys751Gln) SNPs. Analysis involved Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models. Results: Median age: 63 years (range 28–80); 91% male; 100% ECOG performance status (PS) 0–1; adenocarcinoma 79%; stages IIA 22%, IIB 30%, III 33%, and IVA 15%. No SNPs were associated with stage or PS. Multiple NER SNP was independently prognostic for OS and DFS (see Table ). When compared to individuals who were wildtype in all four studied NER SNPs, individuals with variants in all four NER SNPs were associated with substantial improvement in OS (Adjusted Hazard Ratio (AHR) = 0.40, 95% confidence interval (CI) = 0.2–0.7) and DFS (AHR = 0.44, 95%CI = 0.2–0.8). Furthermore, increasing numbers of variant genotypes were associated with a progressive increase in OS &amp; DFS when all seven NER/BER pathway SNPs were analysed together ( Table ). There was a 3.8- fold increase in OS (75 vs. 20 months) and five-fold increase in DFS (51 vs. 10 months) when comparing individuals with 6–7 SNPs with variant alleles to individuals with 0–1 SNPs with variant alleles. Conclusions: The ERCC1 8092 C/A, XPD Asp312Asn &amp; XPD Lys751Gln SNPs in the NER pathway are associated individually with prognosis in esophageal cancer patients treated with cisplatin-based trimodality regimens. In addition, as the number of NER and BER SNPs carrying variant alleles increased, OS and DFS improved dramatically. [Table: see text] No significant financial relationships to disclose.
Phase I/II study of idarubicin (Ida), high-dose ara-C, and sorafenib (S) in patients (pts) younger than 65 years with acute myeloid leukemia (AML)
Authors: F. Ravandi Kashani, J. Cortes, S. Faderl, D. Jones, A. Byrd, M. Brandt, G. Garcia-Manero, M. Levis, M. Andreeff, H. Kantarjian
Journal: Journal of Clinical Oncology (2009)

7018 Background: S is an oral multi-kinase inhibitor with activity against the Raf/ERK/MEK pathway and FLT3. It selectively induces apoptosis in FLT3-mutant human AML cell lines at nM concentrations. Methods: Objectives of this study are to determine the tolerability and efficacy of combination of S with chemotherapy. Ara-C 1.5 g/m 2 over 24 hrs daily x 4 (x 3 for pts over 60) and Ida 12 mg/m 2 daily x 3 are administered with S. In the phase I part, pts with relapsed AML were treated with escalating doses of S (400 mg qod, 400 mg daily, 400 mg bid) for 7 days during induction, and 400 mg bid was established as safe. Pts achieving CR receive up to 5 courses of consolidation with Ida 8 mg/m 2 daily x 2 and Ara-C 0.75 g/m 2 daily x 3 in addition to S 400 mg bid for up to 28 days per cycle repeated every 4 to 6 weeks. Maintenance is with S 400 mg bid for up to a year. Results: 10 pts (median age 34, range 21–58) with relapsed AML (median prior therapy 2, range 1–6) were treated in the phase I . 7 were FLT3-ITD positive. 4 achieved CR; 6 failed. In the phase II part, 45 pts (12 with FLT3-ITD and 2 with FLT3-TKD) were treated. Median age is 53 (range 18 - 65). Cytogenetics were diploid in 19, +8 in 5, -5/-7 in 5, 11q23 in 2, other in 14. Median presentation WBC was 4.9 x 10 9 /L (range 0.6 - 122.7 x 10 9 /L). 8 pts were FLT3-ITD+/NPM1-. 40 pts are evaluable for response and 85% achieved CR (n = 30) or CRp (n = 4) (13 of 14 FLT3 mutated pts); 5 pts are too early (1 FLT3 mutated). Most frequent grade 3 and higher related adverse events: hyperbilirubinemia (5), rash and hand-foot syndrome (3), raised transaminases (2), diarrhea (2), hypertension (2). With a median f/u of 5.4 mo (range, 0.5 - 11.3), the probability of survival at 6 mo is 81.6%. 5 pts have relapsed; median CR duration has not been reached, (range; 0.2+ - 10.6+ mo). Among pts with FLT3 mutation, 4 have relapsed and 9 remain in CR. Plasma inhibitory assay was performed using day 7 samples from 10 pts; mutant FLT3 was suppressed by all with 5-fold more potent suppression against mutant versus wild-type FLT3. Conclusions: S can be safely combined with IA; it has a high CR rate in frontline therapy of younger pts with AML, in particular those with FLT3 mutations. Correlative studies confirm potent activity of S against FLT3 signaling. [Table: see text]
Cardiac safety of the lapatinib/letrozole combination as first-line therapy in patients (pts) with metastatic breast cancer (MBC)
Authors: D. Zembryki, H. Gomez, M. Koehler, M. Koehler, S. Johnston, J. Pippen, A. Florance, L. O'Rourke, J. Maltzman, X. Pivot
Journal: Journal of Clinical Oncology (2009)

1095 Background: Cardiotoxicity of traztuzumab therapy increases in pts pretreated with anthracyclines (A), radiotherapy to left breast, hypertension, or low baseline ejection fraction (EF). We report the cardiac safety profile of lapatinib, an oral, dual EGFR/HER-2 tyrosine kinase inhibitor, in a chemotherapy naïve or A-exposed pts with MBC. Methods: Women (n = 1286) with endocrine sensitive, previously untreated MBC received lapatinib and letrozole (L+L) or letrozole and placebo (L+P): 33% received previous A; 48% previous tamoxifen; &lt;1% previous trastuzumab (T); &lt;2% previous aromatase inhibitor. EF was evaluated by MUGA or echocardiogram at baseline, every 8 wk and at study withdrawal. Rate of cardiac events (NCI CTCAE grading), median time to onset, and duration of EF depression were assessed. Results: Cardiac events (CE; MEDRA terms: ejection fraction decreased, left ventricular dysfunction, ventricular dysfunction and cardiac failure) were infrequent in both arms. Grade 3/4 and 1/2 CE were reported in 0.9% and 4.0% of pts, respectively, in the L+L arm, and in 0.3% and 2.1%, respectively, in the L+P arm. The only symptomatic CE was a grade 4 event in the L+L arm. There was no apparent relationship between previous A exposure and CE frequency and severity. Median L exposure was 40 wk on L+L, 38 wk on L+P. Median time to onset and duration of EF decrease were 21.8 and 8.1 wk, respectively, on L+L, and 34.6 and 5.4 wk, respectively on L+ P. On the L+L arm, the dose was adjusted/interupted for 8 CE cases, discontinued for 6, and unchanged for 22. On the L+P arm, interuption of L was reported for 2 CE cases, discontinuation for 5, and in 7 CE events there was no change in therapy. Eight CE on L+L and 1 CE on L+P had not resolved as of the last report. Conclusions: This is the first long-term evaluation of lapatinib cardiac signals in a controlled trial in a trastuzumab-naïve MBC pt population. The frequency of cardiac events and degree of absolute EF decrease was low and occurred at similar rates in pts with or without anthracycline exposure. These encouraging cardiac safety data in first line metastatic BC study are promising for the ongoing study of lapatinib in patients with early HER-2+ BC treated on ALTTO trial. [Table: see text]
Heterozygous Mutation Of Dynamin 2 Expands The Pool Of IL-7 Responsive Leukemic Stem Cells In T-Cell Acute Lymphoblastic Leukemia
Authors: David J. Curtis, Fiona C. Brown, Michael Collett, Sarah E. Lucas, Jesslyn Saw, Phillip J. Robinson, Cedric Stevens Tremblay
Journal: Blood (2013)
Prognostic factors in Sézary syndrome: A multivariate analysis of clinical, haematological and immunological features
Authors: M.G. Bernengo, P. Quaglino, M. Novelli, N. Cappello, G.C. Doveil, F. Lisa, A. De Matteis, M.T. Fierro, A. Appino
Journal: Annals of Oncology (1998)
Exatecan (DX-8951f), a new topoisomerase I - inhibitor, is inactive in heavily pretreated patients (pts.) with advanced soft tissue sarcoma (STS): A phase II - study of the EORTC Soft Tissue and Bone Sarcoma Group
Authors: D. Pink, P. Reichardt, O. S. Nielsen, S. Bauer, J. T. Hartmann, P. Schöffski, A. T. van Oosterom, S. Daugaard, K. Stoichkov, C. Hermans, I. R. Judson
Journal: Journal of Clinical Oncology (2005)

9058 No standard treatment is established for patients with advanced soft tissue sarcoma after previous chemotherapy with anthracyclines and ifosfamide, given either in combination or sequentially. DX-8951f is a totally synthetic analogue of the topoisomerase I - inhibitor camptothecin, which was synthesized to impart increased aqueous solubility, greater tumor efficacy, and less toxicity than camptothecin itself, topotecan or irinotecan. Since some activity against soft tissue sarcomas, especially leiomyosarcomas has been reported for topoisomerase I - inhibitors, a study with a new and more potent agent seemed justified. Thirty-nine patients were included and received a total of 141 cycles (median 2). Using a two step statistical design, the trial was stopped after the first step due to lack of activity. Median age was 61 years, range 25 to 76. Stratification was used for leiomyosarcoma (16 pts.) and non-leiomyosarcoma (23 pts.) histologies. Exatecan was given as i. v. infusion over 30 minutes at a dose of 0.5 mg/m2 every day for 5 consecutive days, every 21 days. 74% of cycles could be given without dose or schedule modification. The main toxicity was hematotoxicity with grade 3/4 neutropenia in 49% of pts., grade 3/4 thrombocytopenia in 23%, and grade 3/4 anemia in 15% of pts., respectively. Non hematological toxicity consisted mainly of grade 2/3 dyspnea in 36% of pts. and grade 2/3 fatigue in 28%. One treatment related toxic death due to septic shock was reported. Best overall response was no change in 46% of pts. with 56% in the leiomyosarcoma group and 39% in the non-leiomysarcoma group, respectively. No objective response was reported. Conclusions: In pretreated soft tissue sarcoma pts., Exatecan was well tolerated but did not result in any objective response. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Daiichi
New Societal Approaches to Empowering Antibiotic Stewardship
Authors: Brad Spellberg, Arjun Srinivasan, Henry F. Chambers
Journal: JAMA (2016)

Substantial concern regarding the ever-worsening crisis of antibiotic resistance has been raised by the World Health Organization, US Centers for Disease Control and Prevention (CDC), European Centre for Disease Prevention and Control, European Medicines Agency, Institute of Medicine, World Economic Forum, and the US Presidential Advisory Council on Science and Technology. The question is no longer whether to act, but how.

Antibiotic stewardship is the term used to describe efforts to optimize selection of antibiotic therapy. Formal antibiotic stewardship programs are essential to help society address antimicrobial resistance by reducing the estimated more than 50% of antibiotic use that is unnecessary or inappropriate.1 The US government has recently emphasized the need for implementation of antibiotic stewardship programs at all hospitals.2 To be effective, antibiotic stewardship programs must incorporate best practices, which include dedicating sufficient resources to the program, appointing a single leader to be accountable for performance, having appropriate antibiotic expertise, implementing action plans, monitoring bacterial resistance, reporting antibiotic usage to staff, and providing education