tbuckley/cabot-search huggingface dataset:
Screening tools for interferon-related cognitive decline in melanoma patients.
Authors: D. Combs, A. Baker, S. Jordan, S. S. Morgan, L. Pestana, A. Herring, J. M. Jeter, E. Hersh, L. D. Cranmer
Journal: Journal of Clinical Oncology (2010)

8539 Background: Interferon α-2b (IFN) is the only approved adjuvant therapy for high-risk melanoma. IFN-related cognitive deficiencies and mood alterations have been reported. Antidepressants are able to remedy mood, but therapies targeting the cognitive effects of IFN are lacking. Development of therapies requires validation of quantitative measures of cognitive dysfunction in this population. Methods: Melanoma patients who received 1 month high-dose IFN (n = 9), were compared to IFN eligible patients (> stage IIA) who declined therapy (n = 10). Five cognitive function tests were administered: mini-mental status exam, Hopkins Verbal Learning Test-Revised (HVLT), controlled oral word association test (COWAT), Ruff 2 and 7 and Trail Making Tests A and B. The Profile of Mood States-Short Form (POMS) was used to assess mood changes. Test scores were compared as the change from baseline to after IFN or 1-3 months of observation. Welch's t test was used to determine significance. Results: Significant differences were seen in the COWAT, HVLT and POMS. COWAT results showed a significant decrease in word generation (p = 0.013) in IFN patients. HVLT results showed a significant decrease in immediate recall (p = 0.017), but no change in delayed recall or recognition. Significant self-reported mood changes included increased fatigue (p = 0.034), decreased vigor (p = 0.046) and increased confusion (p = 0.034). 8 of 9 IFN patients scored 1 standard deviation (SD) below the observation patient mean on at least one cognitive function test. 5 patients scored 1 SD below on either the HVLT or COWAT. 3 patients scored 1 SD below on the HVLT while 4 scored 1 SD below on the COWAT. Conclusions: In this pilot study, COWAT and HVLT results demonstrate neurocognitive differences between IFN-treated and untreated melanoma patients. It may be possible to use these tests to screen for cognitive dysfunction in IFN patients. Based on these preliminary results, the combination of COWAT and the HVLT immediate recall item is most sensitive. COWAT alone may be more practical than the combination, as it is freely available, easy to administer, and has a sensitivity of 80% vs. the combination. These results must be validated in a larger population and correlated with functional impairment. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Schering-Plough Merck, Schering-Plough
Identification of genes involved in endometrial cancer etiopathogenesis by the mean of MacroArray technique
Authors: T. Kubiatowski, K. Rózynska, K. Futyma, A. Smolen, R. Tarkowski, E. Staroslawska, J. Kotarski, J. Wojcierowski
Journal: Journal of Clinical Oncology (2006)

20102 Endometrial cancer is one of the most common neoplasms of reproductive system. According to data accumulated in last decades it has been concluded that microsatellite instability and PTEN, K-ras, β-catenin gene mutations are crucial for endometrial cancer etiopathogenesis. Moreover, it is well known that all genes encoded proteins involved in cell cycle regulation, cell differentiation or surrounding tissues infiltration contribute to tumor and metastases development. It has been stressed that different factors such as VEGF, which play a key role in neoplastic angiogenesis are also very important for tumor growth. Complexity of molecular mechanisms leading to endometrial cancer development implies that only experiments utilizing array technique can collect enough data to understand all relationships between different molecular pathways during tumor development and to identify new clinically usable markers of neoplasm. Using MacroArray technique we analyzed expression profile of neoplastic tissue derived from 40 patients diagnosed with endometrial cancer. After data collection all genes present on chip were assigned to different groups according to their role in oncogenesis and artificial neuronal network analysis were performed in order to individuate genes those expression was significantly different in neoplastic tissue regarding to controls. Such procedure allowed us to give shape to preliminary gene expression profile typical for neoplastic tissue and to estimate protein expression of the most significant predictors of neoplastic transformation. Comparison of obtained data with tumor grade can reveal new markers of endometrial cancer useful in routine diagnostic procedures. No significant financial relationships to disclose.
After HERA trial: Safety and activity of trastuzumab plus chemotherapy as first-line therapy for patients with breast cancer previously treated with trastuzumab in adjuvant setting—A single-institution experience.
Authors: G. Scandurra, E. Taibi, R. A. Aiello, M. Chiarenza, A. Mazzola, M. Vita Sano, E. Miano, G. Fallica, M. Caruso
Journal: Journal of Clinical Oncology (2010)

1136 Background: Trastuzumab received in 2006 the European Medicines Agency approval for the adjuvant treatment of patients affected by HER2-overexpressing early breast cancer after the results of HERA Trial. Our purpose was to evaluate cardiologic toxicity and efficacy of first-line trastuzumab plus chemotherapy in patients previously treated according to HERA trial. Methods: Since August 2006 to December 2009 in our institution were treated 135 patients with adjuvant anthracyclines ± taxanes, followed by 1 year of trastuzumab. Follow up lasted at least 1 year in 104 evaluable patients. Median age was 53 years (range 28-83). 19 patients underwent quadrantectomy and radiotherapy, 14 patients radical mastectomy. All the patients received adjuvant anthracyclines, 46 also taxanes. Twenty-four percent of patients had TNM stage I, 48% IIA, 18% IIB, 10% IIIA, 2% IIIB. Results: Severe cardiotoxicity leading to stop therapy was recorded in 6 patients (5.7%). Two patients on the total sample relapsed during the adjuvant treatment with trastuzumab. Nine patients (8,6 %) relapsed in: liver (1/9), lung (2/9), lymph nodes (2/9), brain plus bones (1/9), skin (2/9), and bones plus lymph nodes (1/9) within a median time of 6 months (range 3-12 months). All these patients were then treated with trastuzumab and vinorelbine, without any droop of left-ventricular ejection fraction or other relevant toxicities. The responses to the first-line therapy were 1 CR, 5 PR, 1 SD, and 2 PD. Conclusions: Toxicity and efficacy of adjuvant trastuzumab at our institution were comparable to the literature data. Trastuzumab appeared to be safe and effective also in the above small group of quickly relapsed patients previously treated according to HERA trial. No significant financial relationships to disclose.
Pooled analyses of two international, multicenter clinical studies of romidepsin in 167 patients with cutaneous T-cell lymphoma (CTCL)
Authors: M. Demierre, S. Whittaker, Y. Kim, E. Kim, R. Piekarz, M. Prince, J. Nichols, J. Balser, A. Prentice, S. Bates
Journal: Journal of Clinical Oncology (2009)

8546 Background: Romidepsin is a novel pan-HDAC inhibitor with demonstrated single-agent activity in 2 open-label clinical studies of 167 patients (pts) with CTCL [mycosis fungoides or Sézary Syndrome (SS)]. Data for these 2 studies were pooled for more accurate estimates of endpoints and investigation of subpopulations. Methods: GPI-04–0001 (pivotal study) enrolled 96 pts with confirmed CTCL who had recieved ≥1 prior systemic therapy. NCI 1312 (supportive study) enrolled 71 pts with CTCL. Pts recieved romidepsin, 14mg/m 2 as a 4-hr infusion on days 1, 8, and 15 every 28 days until disease progression (≥25% increase). The primary efficacy endpoint for both studies was overall response rate (ORR) using a composite endpoint that included skin assessment, lymph node and visceral involvement and abnormal circulating T-cells/Sézary cells. Results: 167 pts received romidepsin (as-treated); 135 pts (81%) were in the efficacy evaluable population. Mean age was 57±12 yrs, 67% men, 87% white. 103 pts (76%) had stage ≥IIB disease. Median number of prior systemic therapies was 2 (range 1–8). ORR in the table. Responses were noted in: 42% of pts with stage ≥IIB; 11 (58%) of 19 pts with SS (erythroderma + Sézary cells, &gt;1000/ml or &gt;20% ); and 20 (38%) of 52 pts who received prior bexarotene and 8 (40%) of 20 pts who had received denileukin diftitox. Most common drug-related adverse events (AE), all grades, included: nausea (67%), fatigue (49%), anorexia (37%), ECG T-wave changes (29%), anemia (26%), dysgeusia (23%), neutropenia (22%), leucopenia (20%). Related serious AEs in 2% of pts: supraventicular arrhythmia, ventricular arrhythmia, infection, neutropenia, WBC decreased, hyperuricemia, hypotension; all other serious AEs in ≤1 pt. 3 deaths reported as possibly related. Conclusions: Romidepsin is a valuable new therapy for pts with CTCL based on the ORR, CR, durability of response, improvement in all disease compartments and responses at all stages and in all subpopulations analyzed. [Table: see text] [Table: see text]
Analysis of survival of older patients with frontline AML treated with clofarabine with or without low-dose cytarabine or intermediate-dose cytarabine: A matched cohort comparison.
Authors: S. Faderl, F. Ravandi Kashani, G. Borthakur, T. M. Kadia, E. Jabbour, G. Garcia-Manero, M. Brandt, S. Pierce, H. Kantarjian
Journal: Journal of Clinical Oncology (2010)

6551 Background: Outcome following standard or higher-dose cytarabine plus an anthracycline (e.g., “3+7”) in older patients (pts) is historically poor with low survival rates and substantial toxicities. Recent data showing a survival benefit of low-dose cytarabine over supportive care led to the design of lower-intensity induction programs with clofarabine, a second generation deoxyadenosine analog, ± low-dose cytarabine. As the comparative efficacy of these 2 treatments in elderly AML induction is unknown, we compared their efficacy profiles in this analysis. Methods: From 2001 to 2009, we identified 120 pts with untreated AML ≥ 60 yrs who received clofarabine (30 mg/m2/dose) or clofarabine plus low-dose cytarabine (CA). The pts were matched based on age, karyotype, and WBC at diagnosis with 120 pts who were treated with intermediate-dose cytarabine plus idarubicin (IA) based combinations during the same time. Response, early mortality, remission duration, and survival were compared between the two groups. Results: Median age was 70 yrs in both groups (range 60 to 85 years). Median WBC was 3.4 x 109/L (0.8 to 433) for CA and 4.1 (0.3 to 263) for IA. There were also no significant differences in the distribution of cytogenetic abnormalities. The complete remission rate was 58% with CA and 53% for IA. CR with low platelets (CRp) was 3% for CA and 5% for IA for an overall response rate of 61% for CA and 58% for IA (p = 0.51). Mortality at 4 wks was 13% with CA versus 18% with IA (p = 0.21) and, at 8 wks, 16% with CA versus 26% with IA (p = 0.056). Remission duration was 10.8 mos (CA) and 10.6 mos (IA), respectively (p = 0.31). With a median follow up of 21 mos (CA) and 18 mos (IA), median survival was 11.3 mos for CA versus 8.7 mos for IA (p = 0.41). Conclusions: Lower-intensity therapy has better 8-week mortality and is at least as effective as higher-dosed therapy for older patients with untreated AML. Future studies should focus on modifications of lower- intensity therapy to further improve survival. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genzyme Genzyme Genzyme
Efficacy of adjuvant chemotherapy with oral fluorinated pyrimidines for patients with curatively resected gastric cancer. A meta-analysis of centrally randomized controlled clinical trials
Authors: J. Sakamoto, S. Morita, A. Tsuburaya, Y. Kodera, T. Matsui, O. Kobayashi
Journal: Journal of Clinical Oncology (2005)

4022 Background: Standard adjuvant therapy for curatively resected has not been established in Japan. To evaluate the efficacy of oral fluorinated pyrimidine over surgery alone control, a meta-analysis was performed after investigating 14 clinical trials for gastric cancer. Methods: Fourteen randomized trials comparing oral fluorinated pyrimidine and surgery alone after curative resection for gastric cancer was evaluated. Trials with improper randomization using envelop method or trials with low quality control were meticulously examined and excluded from the analysis. A total of 1047 patients, enrolled in three relevant trials (JCOG 8401, JCOG 8801, and JCOG 9206–1)mostly using UFT for the treatment arm using central randomization were defined eligible for the meta-analysis. The endpoint was overall survival and analysis on intent to treat basis was implemented. Results: The 5 year overall survival odds ratio was 0.66(95% CI; 0.48–0.91) The treatment effect of oral fluorinated pytimidine was shown to be statistically significant (p=0.011). The results of this meta-analysis suggest that chemotherapy after surgery with oral fluorinated pyrimidines (mainly UFT) can improve the survival of patients with curatively reected gastric cancer and could be one of the standard adjuvant chemotherapies for locally advanced gastric cancer in Japan. No significant financial relationships to disclose.
Abstract 17718: Association of Ideal Cardiovascular Health in Midlife with Healthcare Costs in Later Life: the Cooper Center Longitudinal Study
Authors: Benjamin L Willis, Ang Gao, David Leonard, Laura DeFina, Amit Khera, Justin Bachmann, James de Lemos, Jarett D Berry
Journal: Circulation (2012)

Background: The American Heart Association 2020 Strategic Impact Goals established the concept of ideal cardiovascular health (CH) which is strongly associated with lower cardiovascular (CV) event ...
<i>VHL</i> gene mutation and hypermethylation in patients with renal cell carcinoma: Preliminary results and clinical correlation
Authors: P. E. Shaheen, S. A. Vaziri, R. Ganapathi, P. Elson, M. Zhou, L. Wood, R. M. Bukowski
Journal: Journal of Clinical Oncology (2005)

9619 Background: Von Hippel-Lindau (VHL) gene is mutated or hypermethylated in 70–80% of clear cell renal carcinoma (RCC). The objective of this study was to identify the mutations in VHL gene in tissue specimens obtained from patients with RCC, determine the methylation status of the gene and to correlate with treatment outcome. Methods: Tissue samples from 24 patients with RCC were used with the following histologic subtypes: clear cell (15), papillary (7), chromophobe (2). Mutation analysis was performed on the DNA isolated from these tissues. PCR amplification products were used for sequencing the entire coding region of VHL, which is comprised of 3 exons. Methylation-specific PCR primers were used to determine the methylation status after DNA bisulfite modification. Results: The study included 20 male patients (83%), and 4 female patients (17%). Median age was 64.5 years, (range 46–81). Low Fuhrman grade I/II was found in 14 patients (58%), high grade III/IV in 10 patients (42%). Total of 8 tissue samples (33%) showed VHL gene abnormalities. VHL mutation was found in 5 patients and hypermethylation in 3 patients. The 5 intragenic mutations identified were in specimens with clear cell histology. Two had mutations in exon 1 with the following nucleotide changes “T 302 C, 295 del C”, 1 had a mutation in exon 2 “424 del G” and 2 specimens had mutations in exon 3 with “474 del GAAAGAGCGA and 626 del AACGGATGG”. Hypermethylation of the VHL promoter region was identified in 3 specimens with clear cell histology. None of the papillary or chromophobe RCC showed mutations or hypermethylation. Four of the five patients with mutant VHL gene and 2/3 patients with hypermethylated VHL gene had high Fuhrman nuclear grade. Objective responses to cytokine based regimens were documented in 3/15 patients with clear cell RCC; 1/8 with VHL abnormalities and 2/10 with wild type VHL. Conclusions: We identified VHL gene abnormalities utilizing tissue samples from RCC patients. One third of the patients having clear cell histology demonstrated gene mutations or hypermethylation. Further correlation of VHL gene status with clinical outcome is in progress. No significant financial relationships to disclose.
Patients preferences in chemotherapy for advanced non-small-cell lung cancer in Japan
Authors: T. Hirose, N. Horichi, T. Ohmori, T. Shirai, T. Ozawa, T. Ohnishi, A. Mitsuru
Journal: Journal of Clinical Oncology (2004)

7242 Background:Although several meta-analyses have shown that chemotherapy is effective against stage IV NSCLC, increases in survival are frequently accompanied by increases in treatment toxicity. The objective of study was to determine how Japanese patients with lung cancer weigh potential survival, chemotherapy response rate, and symptom relief against the potential toxicity of different treatments in cancer chemotherapy. Methods:We used a questionnaire describing a hypothetical situation about stage IV non-small-cell lung cancer. Seventy-three patients with lung cancer who had received chemotherapy (L group) and 120 patients with other respiratory conditions (N group) as the control group were asked to rate the minimal benefit that would make two hypothetical treatments acceptable. For “chance of cure,” “response but not cure,” and “symptom relief” the subjects could give answers from 1% to 100% and for prolonging life could give answers from 1 to 60 months. Results:The median scores for “chance of cure” to accept intensive and less-intensive treatments were significantly lower in the L group (10% and 7%) than in the N group (50% and 30%; p<0.05). The L group was also significantly more likely to accept either intensive or less-intensive treatments for a potentially small benefit for “response,” “relief of symptoms,” and “prolonging life”. For an increase in survival of 3 months intensive chemotherapy was acceptable to a significantly higher percentage of patients in the L group (19%) than in the N group (9%, p=0.04), but less-intensive chemotherapy was acceptable to similar percentage of patients (L group, 21%; N group, 13%; p=0.13). Factors associated with patients' choice of chemotherapy in both groups were age and the presence of dependents. Conclusions:Oncologists must consider the substantial range of attitudes to chemotherapy among patients when making decision. No significant financial relationships to disclose.
Abstract 74: Extracorporeal Membrane Oxygenation to Support Cardiopulmonary Resuscitation in a Sheep Model of Refractory Ischemic Cardiac Arrest
Authors: Dion Stub, Melissa Byrne, Vincent Pellegrino, David M Kaye
Journal: Circulation (2012)

Background: Survival after cardiac arrest in the field remains limited. It is therefore imperative to develop new resuscitation techniques. We aimed to determine the potential role of extracorporeal membrane oxygenation assisted CPR (ECPR) in an animal model of refractory ischemic cardiac arrest. Methods: Twelve sheep were assigned to either ECPR (n = 6) or ‘conventional’ (n = 6) resuscitation. All sheep had coronary occlusion, followed by induction of ventricular fibrillation. CPR was than commenced for 10 minutes in both groups, followed by randomisation to ECPR or CPR for a further 10 minutes. At 23 minutes post induction of VF, advanced life support measures were commenced with direct cardioversion, adrenaline and amiodarone. Outcomes measures included rates of return of spontaneous circulation (ROSC), and analysis of VF wave form. Results: Baseline hemodynamics were similar between the two groups. CPR consistently produced coronary perfusion pressures (CPP) greater than 15mmHg in both groups, with significantly increased CPP post commencement of ECMO in the ECPR group (17.8 4+/-2mmHg vs 22.94+/-3mmHg, p=0.04). Number of shocks, pH, lactate and oxygenation were also comparable. Significantly greater rates of ROSC were seen in the ECPR sheep, 3/6 (50%) vs 0/6 (0%) (p=0.032), which was also associated with significantly increased VF amplitude measures (0.51+/-0.02Mv vs 0.42+/-0.04Mv, p=0.04). Conclusions: This study indicates that ECPR provides a valuable adjunct to the management of patients with refractory VF arrest. Our findings have supported the development of a pilot trial into the effectiveness and feasibility of ECPR in the clinical setting.
Efficacy of nitrosourea-based chemotherapy in recurrent malignant glioma according to time to adjuvant temozolomide failure: A pooled analysis.
Authors: A. Paccapelo, I. Lolli, S. Scoccianti, B. Detti, G. Silvano, M. G. Fabrini, F. Perrone, G. Savio, S. Cascinu
Journal: Journal of Clinical Oncology (2011)

2060 Background: Concomitant and adjuvant temozolomide (TMZ) is the standard of care of the first-line treatment in glioblastoma (GBM) patients. At recurrence patients have few therapeutic options and the use of nitrosoureas, alternative schedule of TMZ and new target therapy have been widely studied. Recently Perry and colleagues (JCO 2010;28:2051-2057) have demonstrated that time to adjuvant temozolomide failure seems to be predictable to dose-intense TMZ treatment. The aim of our pooled analysis was to assess the efficacy of nitrosourea in recurrent GBM patients according to time to adjuvant TMZ progression. Methods: Patients with GBM who failed the standard Stupp regimen have been treated with a nitrosoureas based regimen of fotemustine (FTM) 75-100mg/sqm at day 1, 8, 15 (induction phase) and after 4/5 weeks of rest 100 mg/sqm every 21 days. The primary endpoint of the study was 6-months progression free survival (PFS-6m), Overall survival at 1 year (OS1y), response rate (RR) and toxicity were secondary endpoints. Patients were stratified in 3 groups according to time to TMZ failure: GBM patients failing during the first 6 months of adjuvant TMZ (B1), those who failed after more than 6 months of therapy (B2) and GBM patients who recurred after a treatment-free interval (B3). Results: Six Italian centers participated in this study. At that time preliminary results are available: 119 patients with recurrent GBM have been evaluated. Results have been summarized in the table. Conclusions: Nitrosourea is a valuable therapeutic option for patients with recurrent GBM, not depending on time to adjuvant temozolomide failure and also patients recurred after 6 cycles of adjuvant TMZ (B2) seem to get a benefit from FTM treatment. A prospective randomized trial is warranted to define if TMZ and FTM have a different pattern of response in recurrent GBM. B1 (%) B2 (%) B3 (%) PSF-6m OS1y RR PSF-6m OS1y RR PSF-6m OS1y RR FTM 24.5 24.5 12.2 31.3 31.3 18.8 34.2 28.9 7.9 TMZ* 27.3 27.3 3 7.4 14.8 0 35.7 28.6 11.1