tbuckley/cabot-search huggingface dataset:
HER2 positivity in advanced gastric cancer is comparable to breast cancer
Authors: J. León-Chong, F. Lordick, Y. K. Kang, S. R. Park, Y. J. Bang, A. Sawaki, E. Van Cutsem, O. Stoss, B. W. Jordan, A. Feyereislova
Journal: Journal of Clinical Oncology (2007)

15057 Background: Accurate HER2 testing is required to identify patients eligible for treatment with trastuzumab (Herceptin®). HER2 positivity is reported as 6–35% in gastric cancer (GC). This range is due to small sample sets and differing methods of evaluation or scoring. A specific HER2-testing process was established for the Phase III ToGA trial, which is evaluating trastuzumab added to chemotherapy in HER2-positive advanced GC. Methods: A validation study was completed to standardise IHC (HercepTest™) and FISH (PharmDx™) protocols, and to establish a scoring system specific for GC (M Hofmann et al. ASCO Gastrointestinal Cancers Symposium 2006. Abstract no. 24). Tumour samples for ToGA were then centrally tested by both IHC and FISH to identify patients eligible for enrolment. Results: To date, 1024 tumour samples have been assessed (243 HER2 positive and 781 HER2 negative) giving an overall HER2-positivity rate of 23.7%. Both IHC and FISH results are available for 960 patients, with 87% concordance. Differences were largely due to FISH-positive cases that were IHC 0/1+. HER2 positivity differed significantly by histological subtype: 36% in intestinal, 7% in diffuse and 23% in mixed. HER2 positivity also varied according to the site of the tumour: 36% (8/22) for gastro-oesophageal junction tumours and 21% (60/291) for gastric tumours. Sample numbers were very small so these results must be treated with caution. The HER2- positivity rate was similar in specimens obtained by biopsy (168/689; 24%) and surgery (71/322; 22%). Conclusions: Using validated methodology and based on the large sample set from the ongoing ToGA trial, the HER2-positivity rate observed in advanced GC is as high as in breast cancer: ∼24%. The first efficacy data from ToGA are expected in 2009. No significant financial relationships to disclose.
HER2 Amplification and HER2 Mutation Are Distinct Molecular Targets in Lung Cancers
Authors: Bob T. Li, Dara S. Ross, Dara L. Aisner, Jamie E. Chaft, Meier Hsu, Severine L. Kako, Mark G. Kris, Marileila Varella-Garcia, Maria E. Arcila
Journal: Journal of Thoracic Oncology (2015)
Impact and timing of palliative care referral.
Authors: Leslie J Blackhall, Paul W Read, George Stukenborg, Margaret Barclay, Patrick M Dillon, Harrison James, Joshua Barclay
Journal: Journal of Clinical Oncology (2014)

50 Background: Recent studies suggest that early integration of palliative care services into the care of patients with advanced cancer can improve end of life care. Unfortunately, there are insufficient resources for all advanced cancer to see palliative care from time of diagnosis. This 2012 CMS innovation award is attempting to improve identification of cancer patients in need of palliative care. Methods: In Year 1 of this award, increased staffing was added to existing palliative care resources to improve access. Patients were referred at discretion of their oncologist. A control group consisting of patients with similar diagnoses not referred to palliative care was identified including those without any contact with palliative care, and those who only saw palliative care in the hospitalization prior to death. Data regarding hospitalization in the last month of life, and hospice utilization was obtained. Results: Median time between referral to palliative care clinic and death was 72.5 days (mean 112). See table below. Conclusions: These data suggest patients referred to palliative care clinic within 3 months of death had benefits similar referral at time of diagnosis. However, many patients were never referred or referred only at the very end of life. The next phases of this award will utilize patient-reported outcome data to better identify those who need palliative care. Although most palliative care services are hospital-based, in this study, in-patient consultation only was too late to provide much benefit for these patients. Re-focusing scarce palliative care resources to the out-patient setting may have greater impact on patient care. [Table: see text]
Alterations in insulin receptor and substrate phosphorylation in hypertensive rats.
Authors: C R Kahn, M J Saad
Journal: Journal of the American Society of Nephrology (1992)

Insulin stimulates tyrosine phosphorylation of the insulin receptor and of an endogenous substrate of approximately 185 kd (insulin receptor substrate 1 or IRS-1) in most cell types. Tyrosine phosphorylation of insulin receptor and of IRS-1 have been implicated in insulin signal transmission based on studies with insulin receptor mutants. In the study presented here, the levels and phosphorylation state of the insulin receptor and IRS-1 in liver and muscle after insulin stimulation in vivo have been examined in spontaneously hypertensive rats (SHR) by immunoblotting with antipeptide antibodies to insulin receptor and IRS-1 and antiphosphotyrosine antibodies. It was found that the levels of insulin receptor and IRS-1 protein in liver and muscle are similar in controls (Wistar-Kyoto rats) and SHR. By contrast, there is a decrease in autophosphorylation in the liver and muscle of SHR and a parallel decrease in phosphorylation of IRS-1. These data indicate that reduced insulin receptor kinase activity and reduced substrate phosphorylation may play an important role in the impaired insulin action in the hypertensive rat.
Genetic analysis of proteasome-related pathways in patients with advanced gastric adenocarcinomas (AGA) treated on a phase II study with PS-341 (bortezomib) with or without irinotecan
Authors: A. J. Ocean, M. E. Lane, Z. Xiang, X. Huang, F. Schnoll-Sussman, S. B. Holloway, B. Yu, J. Wright, S. Wadler
Journal: Journal of Clinical Oncology (2004)

9717 Background: We are conducting a phase II trial of the proteasome inhibitor, PS-341, with or without irinotecan in patients (pts) with AGA. Effects of PS-341 downstream of the 26S proteasome are poorly understood. The overall aims are to assess the effects of PS-341 on gene expression in AGA using microarray analysis of paired tissue samples obtained pre- and post-treatment and to correlate the expression profiles with clinical outcome. Methods: Gastric or gastroesophageal (GE) tumor samples obtained by fine needle aspiration or endoscopic biopsies prior to treatment and 24h post PS-341 administration were assessed. Tissue was collected in RNAlater (Qiagen), homogenized in lysis buffer, processed for total RNA isolation using the RNeasy mini kit (Qiagen), and analyzed using an Agilent 2100 Bioanalyzer. RNA amplification, in vitro transcription, labeling, and fragmentation were performed according to Affymetrix protocol. Samples were hybridized to test 3 chip (Affymetrix) to assess the quality, followed by hybridization to the human U133 A chip (Affymetrix) containing 14,593 genes. Chips were scanned using the Affymetrix scanner. Results: Nine pts have been enrolled; 7 are evaluable. Five pts were treated with the combination of irinotecan and PS-341, and 2 with PS-341 alone. All pts were eligible and the 7 treated pts were fully evaluable. Paired samples from 3 pts have been fully analyzed. 196 genes changed significantly (p<0.05) between pre- and post- treatment. Expression levels of 73/196 genes changed by ≥ 2-fold. Of note, RUNX1, a member of the three-gene family encoding the runt domain transcription factor, was downregulated. RUNX3 was recently identified as a tumor suppressor in gastric cancer.Conclusions: Patterns of gene expression in AGA changed significantly following treatment with PS-341 alone or in combination with irinotecan. Evidence for induction or repression of specific pathways will identify targets for study. We plan to identify patterns of gene expression that are predictive of response to PS-341 in gastric tumors. No significant financial relationships to disclose.
Validation of toxicity burden score for use in phase I clinical trials
Authors: S. M. Lee, D. Hershman, P. Martin, J. Leonard, K. Cheung
Journal: Journal of Clinical Oncology (2009)

2514 Background: In phase I clinical trials, dose limiting toxicity (DLT) is defined as a binary outcome (DLT Yes/No). Concerns have been raised since this does not account for multiple non-DLTs that have a cumulative effect on drug tolerability and do not differentiate the severity of DLTs. Having a continuous toxicity burden score (TBS) as an outcome may provide more information regarding toxicity. We propose a new method for obtaining TBS. Methods: We illustrate the method using a phase I trial in lymphoma. The two main toxicities related to the experimental drug were low platelets and neuropathy with DLT defined as platelet count &lt; 10,000/mm3 or grade 3 neuropathy. Three oncologists were asked to assign severity scores for the two main toxicities by assigning scores based on their impression of the impact of the toxicity on the patient and keeping in mind that DLT should be assigned a score of 1 and no toxicity should be assigned a score of 0. They were then given data from 25 patients along with their observed toxicities and the respective NCI toxicity grades and were asked to assign TBS to each patient. A mixed effects regression model was fit to the data. To validate the model, two of the oncologists assigned TBS to an additional list of 17 patients. Assuming the estimated TBS to be a rating, the three ratings (two oncologists and the estimated TBS) were compared using a mixed effects regression model. Results: The significant predictors of TBS are listed in the Table . Since no patient in the training data experienced grade 3 low- platelet and grade 4 neuropathy, model coefficients for these were not obtained. In the validation data, the TBS among the oncologists and the estimated TBS obtained using the fitted model were not different (P=0.18). Conclusions: A fitted model can be used to obtain TBS from maximal NCI toxicity grades suggesting the feasibility of using a continuous outcome such as TBS in dose finding studies. [Table: see text] No significant financial relationships to disclose.
Randomized trial of epirubicin and cisplatin chemotherapy followed by pelvic radiation in locally advanced cervical cancer. Cervical Cancer Study Group of the Asian Oceanian Clinical Oncology Association.
Authors: M H Tattersall, V Lorvidhaya, V Vootiprux, A Cheirsilpa, F Wong, T Azhar, H P Lee, S B Kang, A Manalo, M S Yen
Journal: Journal of Clinical Oncology (1995)

PURPOSE Pelvic radiation is standard treatment for women with stage IIb to IVa cervical cancer, but treatment results are disappointing, particularly for women with bulky tumors. We investigated the role of primary chemotherapy followed by pelvic radiotherapy in a randomized trial. PATIENTS AND METHODS Two hundred sixty patients with stage IIb and IVa cervical cancer received either standard pelvic radiotherapy or primary chemotherapy with cisplatin 60 mg/m2 and epirubicin 110 mg/m2 administered at 3-week intervals for three cycles, followed by pelvic radiotherapy. RESULTS Ninety-nine patients have relapsed with a median follow-up duration of 1.3 years; in 62 patients, the first site of progressive disease was the pelvis. Patients who received primary chemotherapy had a significantly higher pelvic failure rate than those who received radiotherapy alone (P &lt; .003). Seventy-six patients have died, and those who received primary chemotherapy had significantly inferior survival compared with those who received radiotherapy alone (P = .02). Tumor response following chemotherapy was observed in 63%. After radiotherapy, tumor response occurred in 72% of those who received combined modality treatment, compared with 92% of those who received radiotherapy alone. CONCLUSION Primary chemotherapy with epirubicin and cisplatin, although resulting in tumor response in a significant proportion of patients, is accompanied by an inferior local control rate and survival compared with standard pelvic radiotherapy alone.
Pilot trial of cisplatin, radiation, and WR2721 in carcinoma of the uterine cervix: a New York Gynecologic Oncology Group study.
Authors: S Wadler, J J Beitler, J S Rubin, H Haynes, F McGill, A Rozenblit, G Goldberg, C Cohen, J Speyer, C Runowicz
Journal: Journal of Clinical Oncology (1993)

PURPOSE A phase I trial of WR2721 was initiated to determine the maximal safe dose for incorporation into a consecutive 5-day schedule of cisplatin administered concurrently with radiation therapy in patients with cervical cancer. PATIENTS AND METHODS WR2721 was administered at 340 to 910 mg/m2/d immediately before cisplatin. Cisplatin was administered at 20 mg/m2/d for 5 days every 3 weeks in combination with external-beam radiation therapy and at 100 mg/m2 after each brachytherapy treatment. Pelvic radiation consisted of external-beam therapy to a dose of 39.6 Gy, followed by brachytherapy with cesium 137 tandem and ovoid insertions to deliver 80 Gy to point A and 55 Gy to point B. RESULTS Twenty patients were enrolled; 19 were assessable. The dose-limiting toxicity of WR2721 was hypotension. No patients developed serious sequelae, but hypotension required a reduction in the dose of WR2721 at the highest dose level tested. The major grade 3 or 4 toxicities included transient azotemia (five of 19), leukopenia (nine of 19), vomiting (four of 19), and neurotoxicity (two of 19). One patient experienced an anaphylactic reaction to cisplatin. CONCLUSION The recommended dose of WR2721 administered in conjunction with cisplatin on a daily x 5 schedule plus radiation therapy is 825 mg/m2/d for 5 days.
Survey of medical students' overdrafts
Authors: E. Wilkinson, J Ford
Journal: BMJ (1998)

Breast cancer screening: false positive rate is lower in older womenEditor-Werneke and McPherson 1 question the detection rates of cancer observed in the breast screening programme in East Sussex, Brighton, and Hove that we reported in our recent paper. 2 They suggest that these are the result of a high proportion of false positive screens.It is unfortunate that they did not consult us beforehand.The paper gives results of an ongoing study, but the cancers reported are those confirmed by histological examination after surgery, not preliminary suspected cancers at "positive" screens.The statistical programme was not run until some months after the end of the screening period, when all the screening episodes had been completed and the women concerned had been assessed, diagnosed, and operated on as appropriate.The East Sussex area has always tended to have a high detection rate for cancer, possibly because of the local sociodemographic composition of the population, and the rate over this period was higher than in the following year, without being exceptional.The 1995-6 result for the whole South West Thames region was 7.6 women with cancer for every 1000 women screened overall. 3he small study of older women in north London found 14.2 women with cancer per 1000 women screened aged 65-9. 4uring the period reported in our study the recall for assessment rate in women aged 65-7 was 4.6% (95% confidence interval 3.9% to 5.2%) and 6.2% (5.2% to 7.2%) in those aged 68-9, compared with 6.1% (5.8% to 6.4%) in those aged 50-64.Given the higher number of cancers detected this indicates a lower false positive rate in older women.This is to be expected because of the relative ease of interpreting mammograms and decreasing incidence of benign breast lesions in older women. 5 We now have the first year's results from the other two pilot sites, which will be published in due course.They confirm higher detection rates of cancer in older women but similar recall rates.Attendance is also encouragingly high.
Predictive value of MRP2, p53, bcl2 and topoisomerase II immunostainings for the efficacy of anthracyclines-based adjuvant chemotherapy in breast cancer: Results from two randomized trials
Authors: R. Conforti, T. Boulet, G. Tomasic, M. Spielmann, S. Delaloge, R. Arriagada, A. S. Veillard, L. Zitvogel, S. Michiels, F. André
Journal: Journal of Clinical Oncology (2008)

616 Background: The identification of predictive biomarkers for the efficacy of adjuvant treatments could allow to better tailor adjuvant treatments. We evaluated the predictive value of MRP2, bcl2, topoisomerase IIα (Topo IIα) expression and p53 status for the efficacy of adjuvant anthracyclines (A)-based chemotherapy. Methods: Tumor samples from 823 patients included at Institut Gustave Roussy (IGR) in two randomized trials comparing an A-based chemotherapy with no treatment were used to perform a tissue-array. Chemotherapy consisted of 5FU (500mg/m2), farmorubicine (90% of patients) or doxorubicin (50 mg/m2) and cyclophosphamide (500 mg/m2) (D1=D28) for 6 cycles. Immunostainings (cut-off: >10% stained cells) were performed for MRP2 (M2III-6; 1:300; Alexis), p53 ( DO-7; 1:50; Dako), bcl2 (124; 1:50; Dako), and Topo IIα (KI-S1; 1:5000; Chemicon). We previously reported predictive values of ER, HER2 expression and molecular subclassification using the same tissue-array (Conforti, Annals of Oncology, 2007). Results: After a median follow-up of 10 years, 174 patients (22%) have presented a relapse and 186 patients (24%) died. Chemotherapy improved DFS (HR = 0.77, 95% CI: 0.63- 0.9), but not OS (HR = 0.88, 95% CI: 0.66–1.1). A positive staining for MRP2, p53, Topo IIα and bcl2 was observed in 122 (16%), 157 (20%), 267 (35%) and 251 (34%) assessable samples respectively. P53 and Topo IIα were more frequently expressed in patients with basal-like (51% and 53%) or HER2-overexpressing tumors (44% and 57%), as compared to other groups (HER2- and nonbasal BC) (11% and 28%). Bcl2 was more frequently positive in patients with luminal-like breast cancer (47% versus 16%, p<0.01). No significant interaction was observed between the four biomarkers expression and treatment efficacy for both DFS and OS (adjusted p values for interaction ranged between 0.30 and 0.85). Conclusions: In this study, we did not detect significant interaction between MRP2, p53, bcl2 and Topo Iia expressions and treatment efficacy. Nevertheless, such study cannot exclude a possible interaction with a higher number of events or different methods (DNA sequencing for p53 mutations and lower dilution [1:200] for S1 Ab). No significant financial relationships to disclose.
Riluzole blocks perioperative ischemia-reperfusion injury and enhances postdecompression outcomes in cervical spondylotic myelopathy
Authors: Spyridon K. Karadimas, Alex M. Laliberte, Lindsay Tetreault, Young Sun Chung, Paul Arnold, Warren D. Foltz, Michael G. Fehlings
Journal: Science Translational Medicine (2015)

Riluzole complements surgical decompression in an animal model of cervical spondylotic myelopathy, improving long-term outcomes.
Statistical methods of DNA sequence analysis: detection of intragenic recombination or gene conversion.
Authors: J C Stephens
Journal: Molecular Biology and Evolution (1985)

Simple but exact statistical tests for detecting a cluster of associated nucleotide changes in DNA are presented. The tests are based on the linear distribution of a set of s sites among a total of n sites, where the s sites may be the variable sites, sites of insertion/deletion, or categorized in some other way. These tests are especially useful for detecting gene conversion and intragenic recombination in a sample of DNA sequences. In this case, the sites of interest are those that correspond to particular ways of splitting the sequences into two groups (e.g., sequences A and D vs. sequences B, C, and E-J). Each such split is termed a phylogenetic partition. Application of these methods to a well-documented case of gene conversion in human gamma-globin genes shows that sites corresponding to two of the three observed partitions are significantly clustered, whereas application to hominoid mitochondrial DNA sequences--among which no recombination is expected to occur--shows no evidence of such clustering. This indicates that clustering of partition-specific sites is largely due to intragenic recombination or gene conversion. Alternative hypotheses explaining the observed clustering of sites, such as biased selection or mutation, are discussed.
Reproducibility of scoring systems used for breast density and breast parenchymal pattern assessment on X-ray mammography
Authors: S. M. van de Ven, M. A. van den Bosch, A. Kwong, J. Rosenberg, A. Kamaya, G. Lo, D. M. Ikeda
Journal: Journal of Clinical Oncology (2008)

1547 Background: Breast density assessment is clinically important, since extensive mammographic density is associated with an increased risk of breast cancer (4–6 times higher). In addition, increased breast density makes cancer detection by mammography more difficult. This study was designed to assess and compare intra- and interobserver reproducibility of four scoring systems used in clinical practice for mammographic breast density and parenchymal pattern assessment. Methods: We reviewed 92 mammograms of 49 women with normal breast imaging findings. The mammograms were independently scored by two breast radiologists. The observers assessed each mammogram on two separate occasions. On each mammogram breast density was scored according to BI-RADS (fatty, scattered fibroglandular, heterogeneously dense, dense) and six category classification (SCC, 0%, 1–10%, 11–24%, 24–49%, 50–74%, >75%). Parenchymal patterns were scored according to Wolfe (N1, P1, P2, DY) and Tabar grade (I, II, III, IV, V). Weighted Kappa coefficients and 95% confidence intervals were calculated for each system as indicators of intra- and inter-observer agreement. Results: The inter-observer agreement was the highest for the BI-RADS scoring system and the lowest for the Wolfe grading system, i.e. BI-RADS k=0.64 (0.55–0.73), SCC k= 0.62 (0.52–0.71), Wolfe k= 0.50 (0.37–0.62), Tabar k=0.62 (0.46–0.75). The intra-observer agreement was comparable for all four scoring systems. The intra-observer agreement of observer 1 ranged from 0.63 to 0.72, i.e. BI-RADS k=0.63, SCC k=0.68, Wolfe k=0.72, and Tabar k=0.71. For observer 2 the intra-observer agreement ranged from 0.50 to 0.92, i.e. BI- RADS k=0.80, SCC k=0.86, Wolfe k=0.92, Tabar k=0.50. Conclusions: Although the BI-RADS system showed the highest level of inter-observer agreement, the same high level of intra-observer agreement was achieved for all four scoring systems, which proved they are all reproducible and reliable in clinical practice. No significant financial relationships to disclose.
Incidence of Conjunctival Colonization by Bacteria Capable of Causing Postoperative Endophthalmitis
Authors: C B Walker, C M P Claoué
Journal: Journal of the Royal Society of Medicine (1986)

Increased awareness of the range of pathogens capable of causing postoperative endophthalmitis prompted a study of the conjunctival flora in 100 patients admitted for intraocular surgery. Bacteria capable of causing endophthalmitis were present in 74% of these patients, a much higher proportion than previously documented. No correlation was found with blockage of the nasolacrimal duct.
Carboplatin dosimetry in renal failure.
Authors: A P Kudelka, Z M Siddik, O Balat, J J Kavanagh
Journal: Journal of Clinical Oncology (1995)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1995.13.8.2147 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7636563 Carboplatin dosimetry in renal failure. A P KudelkaxA P KudelkaSearch for articles by this author , Z M SiddikxZ M SiddikSearch for articles by this author , O BalatxO BalatSearch for articles by this author , J J KavanaghxJ J KavanaghSearch for articles by this author https://doi.org/10.1200/JCO.1995.13.8.2147 PDF "Carboplatin dosimetry in renal failure.." Journal of Clinical Oncology, 13(8), pp. 2147–2148© 1995 by American Society of Clinical Oncology