tbuckley/cabot-search huggingface dataset:
Maintenance Treatment with 5-Azacitidine for Patients with High Risk Myelodysplastic Syndr–ome (MDS) or Acute Myeloid Leukemia Following MDS (MDS-AML) in Complete Remission (CR) after Induction Chemotherapy
Authors: Michael Grövdal, Rasheed Khan, Anni Aggerholm, Petar Antunovic, Jan Astermark, Per Bernell, Lena-Maria Engström, Lars Kjeldsen, Olle Linder, Lars Nilsson, Anna Olsson, Jonas Wallvik, Jon Magnus Tangen, Gunnar Öberg, Sten Eirik Jacobsen, Anna Porwit, Peter Hokland, Eva Hellström-Lindberg
Journal: Blood (2008)
Antitumor Activity of Bevacizumab Combined with Erlotinib in T790M Resistance Mutation Positive Non-Small Cell Lung Cancer Xenograft Models
Authors: K. Furugaki, K. Yamamoto, Y. Moriya, K. Suda, H. Mizuuchi, T. Mitsudomi, N. Harada
Journal: Annals of Oncology (2014)
Induction of apoptosis in human melanoma by the BRAF inhibitor PLX4720: The key to therapeutic success?
Authors: P. Hersey, X. Zhang, C. Jiang
Journal: Journal of Clinical Oncology (2010)

8559 Background: A high proportion of Patients with metastatic melanoma have shown clinical responses when treated with the PLX4032/NP22657 inhibitor against the mutated V600E form of BRAF. The present study examined an analogue of this inhibitor for its ability to inhibit viability and induce apoptosis in a large panel of established and short term cultured melanoma. Methods: The oncocarta mutation panel was used to assess muations in 31 melanoma lines and short-term cultures. Each line was tested for viability in MTS assays and apoptosis by subG1 PI fractions over 72 hours. Western blots were used to measure Bcl-2 family protein expression. Results: There were 7 lines with no detectable mutations, 10 with mutations in NRAS or KRAS,13 with BRAF mutations and one with mutated cKit.Apoptosis induction was highest in the lines with mutated BRAF and correlated inversely with cell viability except for 2 lines with mutated CDK4 (R24c) which had low viability and low apoptosis.Inhibition of caspases indicated that apoptosis was the main mechanism for reduced cell viabilty. Induction of apoptosis correlated with upregulation of the proapoptotic BH3 protein Bim as reported in previous studies on the MEK inhibitor UO126. In particular there was selective upregulation of the short form of Bim and this correlated with induction of apoptosis. There were no significant changes in the the other BH3 only proteins PUMA or NOXA Combination of a MEK inhibitor with the BRAF inhibitor had strong potentiating effects on cell lines that were relatively resistant to the BRAF inhibitor. Conclusions: These studies confirm that the BRAF inhibitor PLX4720 induces apoptosis in human melanoma with mutated BRAF at concentrations achievable in vivo. Melanoma lines with mutated CDK4 or EGRF receptors had lower cell viability. Apoptosis was correlated with the induction of the proapoptotic Bim, particularly Bim short and may be a useful biomarker to assess apoptotic responses and guide drug doses and combinations in the clinic. No significant financial relationships to disclose.
Cognitive functioning pre- and postradiotherapy (RT), chemoradiotherapy (CRT), or bioradiotherapy (BRT) in patients with locally advanced squamous cell cancer of the head and neck (LA-SCCHN).
Authors: L. J. Bernstein, H. K. Gan, A. R. Abdul Razak, K. M. Tirona, J. Ringash, B. O'Sullivan, J. N. Waldron, A. J. Hope, D. P. Goldstein, L. L. Siu
Journal: Journal of Clinical Oncology (2010)

e19629 Background: There is increasing evidence that cancer and/or its treatment can impair thinking abilities. We recently reported on cognitive functioning (CF) in LA-SCCHN pts 1-2 yrs post RT or CRT and found that pts performed significantly below expectation (Gan et al. ASCO 2009). Without baseline testing, however, impact of treatment remains ambiguous. Here we report CF data from an ongoing prospective study evaluating LA-SCCHN pts pre and post treatment. Methods: Eighteen LA-SCCHN pts completed a 2-hr battery of tests/questionnaires assessing objective CF, subjective CF, quality of life (QoL) and affect prior to treatment and 6 months later. Treatment regimens included RT, or CRT (RT with cisplatin or 5-FU/carboplatin) or bioradiotherapy (RT with anti-EGFR antibody). Cognitive domains of intelligence, attention, memory, processing speed, and executive functioning were assessed using standardized tests. Results: Ptdemographics are: M:F = 15:3; mean age = 59 yrs (range 48-73); mean cigarette pack yrs = 13.4; mean alcohol units/week prior to diagnosis = 20.4, after diagnosis = 2.6, mean school yrs = 13.7. Of the 18 pts, RT = 3, CRT = 10, BRT = 5. At both baseline and 6 month follow up, pts showed reduced memory ability compared to other cognitive domains (p<0.05). However, there was no significant difference in any cognitive domain, affect, or general QoL between the two assessments, regardless of treatment regimen. In contrast to objective CF, subjective report of cognitive difficulties increased from pre to post treatment (p<0.05). Conclusions: Results indicate that LA-SCCHN pts exhibit memory disturbance prior to treatment and 6 months later, but no cognitive decline is captured with objective testing. This suggests that cognitive difficulties may have less to do with treatment than with the cancer itself, the impact of having a cancer diagnosis, and/or pre-existing conditions. Recruitment is ongoing and follow up will continue for 5 years to assess whether there are any changes over time. In addition, control participants will be assessed longitudinally at similar time points to provide comparison data. No significant financial relationships to disclose.
Psychodynamics and psychiatric diagnoses of pseudoseizure subjects
Authors: E S Bowman, O N Markand
Journal: American Journal of Psychiatry (1996)

The goal of this study was to determine current and lifetime rates of DSM-III-R disorders in patients with pseudoseizures and to ascertain whether trauma is associated with the occurrence of pseudoseizures.Adult pseudoseizure patients (N = 45) were interviewed regarding seizure course and life events, and they were given the Structured Clinical Interview for DSM-III-R--Patient Version, the Structured Clinical Interview for DSM-III-R Dissociative Disorders, the Dissociative Experiences Scale, and the Personality Diagnostic Questionnaire--Revised. The pseudoseizures were diagnosed in a tertiary-care video-EEG facility. Most of the subjects (78%) were female, and the mean age of the overall patient group was 37.5 years (SD = 9.7).The mean duration of the subjects' seizure history was 8.3 years (SD = 8.0). Common current psychiatric diagnoses included somatoform disorders (89%), dissociative disorders (91%), affective disorders (64%), personality disorders (62%), posttraumatic stress disorder (PTSD) (49%), and other anxiety disorders (47%). The lifetime occurrence of nonseizure conversion disorders was 82%. The mean Dissociative Experiences Scale score was 20.2 (SD = 18.2). Trauma was reported by 84% of the subjects: sexual abuse by 67%, physical abuse by 67%, and other traumas by 73%.Pseudoseizure subjects have high rates of the psychiatric disorders found in traumatized groups; they closely resemble patients with dissociative disorders. Reclassification of conversion seizures with the dissociative disorders should be considered. Pseudoseizures often appear to express distress related to abuse reports. Clinicians should screen pseudoseizure patients for adult and childhood trauma, dissociative disorders, depression, and PTSD.
Integrating primary care and the cancer system: Program evaluation of the UPCON Network in Manitoba, Canada
Authors: J. J. Sisler, P. McCormack-Speak, D. Chateau
Journal: Journal of Clinical Oncology (2008)

6605 Background: Cancer care facilities have generally been poorly integrated with primary care. CancerCare Manitoba (CCMB) created the UPCON (Uniting Primary Care and ONcology) Network to address this problem through partnerships with 13 primary care clinics in Winnipeg MB. A “Lead Family Physician (FP)” from each clinic was provided with focused CME and identified as a cancer resource to their colleagues. Each clinic was given access to the provincial electronic medical record for cancer patients and educational outreach undertaken with all clinic staff. Surveys were performed to assess the impact of UPCON on the perceptions of FPs of their working relationship with CCMB. Methods: The survey was adapted from other instruments, piloted and administered at baseline in 2004, and in 2005 and 2007 to 83 FPs in UPCON clinics and 228 other randomly selected FPs not involved in UPCON. A modified Dillman method was used and REB approval obtained. Results: Response rates were 44% in 2004, 32% in 2005 and 37% in 2007. UPCON FP respondents were less likely to be in fee-for-service practice and had fewer years in practice than the comparison group. Factor analysis revealed three scales with highly correlated items: 1) Information Flow (4 items, Cronbach alpha 0.79); 2) Avoiding Miscues (3 items, alpha 0.64); and 3) FP Role Satisfaction (5 items, alpha 0.64). There was a significant interaction between time and UPCON status for scales 2 and 3 (p= 0.027 and 0.0039) and a trend towards significance for scale 1 (p=0.060). These analyses were controlled for sex, FT/PT, method of payment, solo/group, and years in practice. When Lead FPs were excluded from the analysis, the interaction for scale 3 remained significant (p= 0.022). UPCON FPs were less satisfied at baseline for all three scales (p= 0.029, 0.072, 0.010) and equivalent to controls at follow-up. Conclusions: The Network had a positive impact over 3 years on UPCON FPs' perceptions but succeeded only in making their views similar to that of controls. UPCON FPs were more critical at baseline, perhaps due to “priming” during recruitment about collaboration problems or self-selection for involvement in this project. The results do not clarify which UPCON interventions in particular were effective. No significant financial relationships to disclose.
Can We Predict Which Patients Will Benefit Most From a Transcatheter Aortic Valve Implantation
Authors: Christophe de Meester de Ravenstein, Sophie F. Piérard, Stéphanie Seldrum, Parla Astarci, Bernhard Gerber, Joëlle Kefer, Agnes Pasquet, Jean Renkin, David Vancraeynest, Jean-Louis Vanoverschelde
Journal: Circulation (2010)

Background: Transcatheter Aortic Valve Implantation (TAVI) has recently emerged as an attractive alternative for treating patients with severe aortic stenosis (AS) who are not candidate for conventional aortic valve replacement. Because TAVI prosthesis are quite expensive and not every patient in whom they are implanted benefit from the procedure, we aimed at investigating if any preimplantation patient's characteristics would help predicting an unfavorable outcome after TAVI. Methods: Between January 2008 and May 2010, 70 consecutive patients with severe AS (31 women; mean age: 84 ± 5years) underwent TAVI using the Edwards-Sapien valve. The clinical outcome was assessed at 1 and 6 months after implantation. Overall and cardiovascular survivals were computed. Logistic and Cox regression analyses were used to identify independent predictors of clinical improvement and/or outcome. Results: 18 patients died during a mean follow-up of 8 months. At 20 months, mean overall survival was 60%. Among the 58 patients who survived up to the 6 months follow-up, 45 were in NYHA class II or less and reported significant clinical improvement, whereas 13 were still in NYHA class III–IV and reported no significant clinical improvement. Cox survival analysis identified age (p<0.026) and renal dysfunction (p<0.029) as independant predictors for mortality. Logistic regression analysis identified LV ejection fraction (p<0.001) and chronic obstructive pulmonary disease (COPD, p=0.078) as being associated with functional improvement at 6 months (see Table). Conclusion: In high risk patients undergoing TAVI, advanced age and renal dysfunction are associated with an increased risk of death, whereas pre-TAVI LV dysfunction and COPD identify patients who are more likely to remain symptomatic after the procedure.
Role of staging PET/CT scanning in detecting brain metastases in small cell lung cancer.
Authors: M. Almubarak, S. Virani, G. Marano, K. Veselicky, J. S. Rogers
Journal: Journal of Clinical Oncology (2010)

e18116 Background: Up to one-third of small cell lung cancer (SCLC) patients are diagnosed with brain metastases. Our study aims to evaluate the role of staging PET/CT in detecting asymptomatic brain metastases in this patient population. Methods: We performed a retrospective chart review of 77 consecutive small cell lung cancer patients seen at Mary Babb Randolph Cancer Center at West Virginia University between February 2005 to November 2009. 26 patients with brain metastases, 12 at diagnosis, were identified. Information regarding cancer staging and neurological symptoms at the time of discovery of brain metastases was collected. In addition, data was acquired from PET/CT and brain MRI reports including study date, findings and any changes in staging secondary to the study. Results: The median age at diagnosis was 59 years (range 35-84). 50 out of 77 patients had PET/CT scans for initial staging. 12/77 patients had brain metastasis at the time of diagnosis. PET/CT scan detected brain metastasis in 8 out of 9 patients studied (6 of the 9 patients had asymptomatic brain mets). Restaging PET/CT scans detected brain metastasis in 7 additional patients during the course of their treatment (6 with CNS symptoms). Overall, PET/CT scan had a sensitivity of 91% (10/11 patients) in detecting brain metastasis confirmed by brain MRI. Conclusions: PET/CT scan with IV contrast has a high sensitivity in detecting brain metastasis in patients with small cell lung cancer when compared to MRI brain. It is effective in detecting asymptomatic metastasis in this population and can be utilized as tool for surveillance of asymptomatic CNS metastasis. MRI should be considered in symptomatic patients with negative PET/CT scan. No significant financial relationships to disclose.
End of life treatments and events in ovarian cancer: A comparison of short versus long-term outcomes
Authors: V. E. Von Gruenigen, B. Daly, H. Frasure, J. Hutchins, A. Green
Journal: Journal of Clinical Oncology (2006)

5096 Background: To identify the aggressiveness of treatment and events in ovarian cancer patients during the last year of life based on survival time. Methods: Patient charts of deceased epithelial ovarian cancer patients were retrospectively reviewed from 2000–2005. All patients included had debulking surgery and received adjuvant chemotherapy. Patients were separated into groups based on survival quartiles. Aggressiveness of care was measured by chemotherapy regimens, ER visits and hospitalizations. Significant clinical events (SCE) were defined as ascites, bowel obstruction, and pleural effusion. Comparison of quartiles was done using chi-square and t-test statistic. Multiple regression analysis was done using survival duration as a dependent variable. Results: 97 patients with epithelial ovarian cancer were reviewed. There was no difference in patterns of hospitalizations and SCE between the top and bottom survival quartiles. Patients with a shorter survival time received more chemotherapy during their last 3 months of life and had increased overall aggressiveness of care measures (Table). In patients who had a remission, regression analysis revealed length of initial remission time was significant in predicting survival (p &lt; 0.01). Time to 2 nd relapse was also significant in predicting survival time (p &lt; 0.01). Number of SCE during the last year of life events trended for predicting survival (p = 0.10). Conclusions: Duration of ovarian cancer remission is predictive of survival. Those patients with a short trajectory of disease receive more aggressive care, chemotherapy at the end of life, less hospice care; however, they die similarly to those with longer survival duration. Those patients with short remissions and / or SCE during recurrence should receive less aggressive care at the end-of-life. [Table: see text] No significant financial relationships to disclose.
ACOSOG Z1031:臨床病期II/IIIエストロゲン受容体陽性乳癌を有する閉経後女性におけるエキセメスタン,レトロゾール,およびアナストロゾールを比較する無作為化第2相試験
Authors: H R Bonnefoi, J Bogaerts, M Piccart, L Maunac, P Fumoleau, J Jassem, V Becette, D A Cameron, J Bergh, R Iggo
Journal: Journal of Clinical Oncology (2010)
Contribution of tumor-associated lymphocytes to a niche for “stem cell-like” breast cancer cells
Authors: A. Rody, U. Holtrich, R. Gaetje, K. Engels, G. Von Minckwitz, S. Loibl, E. Ruckhäberle, A. Ahr, T. Karn, M. Kaufmann
Journal: Journal of Clinical Oncology (2008)

11102 Background: Lymphocyte infiltration is often seen in breast cancer and has been suggested as a marker of host antitumor immune response but its importance remains controversial. Moreover, only few of tumor associated lymphocytes display activation markers and there is no definitive proof of cytotoxic activity of these cells against the tumor in vivo. Methods: We have previously identified two subtypes of “stem cell-like” (SCL+) breast cancers which are characterized by the coordinative expression of several “stem cell markers” while differing in their ER status. Here we used a combined Affymetrix microarray dataset of 2165 breast cancer samples to analyze the relationship of these different subgroups and tumor associated lymphocytes. Immunohistochemistry was performed to verify the results obtained from bulk biopsies. Results: Two tumor groups were associated with high expression of lymphocyte specific markers suggesting the presence of considerable amounts of lymphocytes in those bulk tumors: First, the ER negative subtype of the “stem cell like” (SCL+) cancers, and second a subset of HER2+ tumors. Immunohistochemical analyses verified this conclusion deduced from microarray data. Interestingly, those HER2+ samples positive for lymphocyte infiltration were also characterized by markers of the SCL+ tumor type like SOX10 and Prominin1. This might suggest that interactions between lymphocytes and SCL+ tumors could contribute in maintaining these tumor cells in an undifferentiated state. Clinically the subsetof HER2+ tumors with expression of SCL+ markers and associated lymphocytes was characterized by a favourable prognosis. Conclusions: Tumors with the “stem cell-like” (SCL+) marker profile might either generate an environment which attracts lymphocytes or as an alternative hypothesis the interaction of lymphocytes and tumor cells may generate the functional homologue of a stem cell niche for undifferentiated cancer cells. No significant financial relationships to disclose.
Quality of life (QoL) in osteosarcoma: First results of the presurgery treatment period of EURAMOS-1 (NCT00134030).
Authors: A. Wiener, R. Nagarajan, L. Hjorth, M. Jenney, P. De Vos, M. L. Bernstein, M. D. Krailo, M. R. Sydes, G. Calaminus
Journal: Journal of Clinical Oncology (2010)

10062 Background: The impact of treatment intensity on QoL of osteosarcoma patients is becoming increasingly important to assess. At present, no studies reflect QoL of osteosarcoma patients at diagnosis prior to surgery. EURAMOS-1 is an international randomized controlled trial to improve outcomes in osteosarcoma therapy. Concurrent with treatment, QoL is assessed as a secondary outcome measure across all participating countries through four oncology groups (COG, COSS, EOI, and SSG). Methods: For serial QoL assessment comparable QoL tools are used depending on group practice and patients' age. Questionnaires are the EORTC QLQ-C30 (self-rating) for all patients aged >=16y and the PedsQL or PEDQOL for patients aged <16y (self- and proxy). QoL is assessed 5 ±1 week after start of chemotherapy (T1), 10 weeks post surgery, 72 weeks and 142 weeks after diagnosis, respectively. T1 data was used to reflect QoL at diagnosis and analyzed in respect to age / gender and the instruments used. Results: As of October 2009, 1520 patients joined the trial, 1268 patients consented to QoL assessments and 888 (70%) submitted a T1 QoL assessment. Respondents/non-respondents did not differ by age and sex. As indicated by the overall QoL scales all questionnaires reveal a markedly reduced subjective well-being. Independent of age physical functioning is affected in all patients regardless of the instrument used. The <16y age group and female patients demonstrate the poorest baseline QoL. In older patients role functioning and social functioning are the most prominently restricted. Patients <16y and their parents appraise the different domains broadly similarly with a tendency for better patients' ratings. Conclusions: QoL data can be collected for these patients. Restrictions in physical functioning seems to explain much of the variance in general QoL over all ages at T1. In addition, in patients >=16y role functioning and social functioning are of importance for QoL appraisal. Patients' self-ratings and parents' ratings demonstrate broad concordance with only minor differences. Supported by the European Science Foundation (ESF/EUROCORES) No. ERASCT-2003-980409 of the European Commission, DG Research, FP6. No significant financial relationships to disclose.
Patient’s Anastrozole Compliance to Therapy Programme (PACT): Influence of the addition of a standardized information and reminder service on compliance in comparison to standard clinical care alone in women with early-stage breast cancer
Authors: P. Hadjii, M. Blettner, R. Haidiner, N. Harbeck, C. Jackisch, H. Lück, R. R. Martin, A. Rexrodt v. Fircks, J. Torode, R. Kreienberg
Journal: Journal of Clinical Oncology (2008)

11582 Background: An important requirement for the effectiveness of any therapeutic intervention is optimal compliance. In the adjuvant treatment of hormone responsive breast cancer, existing data document that 23% and 50% of patients were non-compliant after the first and fourth year of tamoxifen (TAM) therapy. To date, no data on compliance to aromatase inhibitors (AI) outside of randomized clinical trials (RCTs) has been reported. Methods: PACT programme has a two arm, randomized, parallel group design with a primary duration of 12 months and observation extended to 60 months. From July 2006 to September 2008, we intend to enroll 4,674 postmenopausal, receptor positive breast cancer patients assigned to adjuvant AI therapy in accordance with standard local practice and independent of participation in the programme. After written informed consent, patients will be randomized to a standardized information and reminder service or to routine clinical care alone. Compliance will be evaluated by self report using standardized, detailed questionnaires at baseline and after each year of treatment. In addition, we will collect the prescription data for each patient from hospital records and physician recall. Finally, we will assess quality of life and patient’s satisfaction using standardized questionnaires. Secondary endpoints include persistence on therapy, reasons for non- compliance, influence of baseline characteristics on compliance as well as the influence of compliance on clinical outcome parameters. Conclusions: An important goal of any therapeutic intervention is to achieve comparable efficacy in routine clinical practice to that demonstrated in RCTs. The aim of the PACT programme is to evaluate whether a simple intervention such as a standardized information and reminder service can lead to a significant increase in compliance in women with primary breast cancer. If successful, such simple measures could greatly improve the efficacy of adjuvant endocrine treatment and would thus have significant impact on individual patient outcomes as well as the health care system. No significant financial relationships to disclose.