tbuckley/cabot-search huggingface dataset:
Prognostic model to predict outcomes in non-small cell lung cancer patients with erlotinib as salvage treatment.
Authors: S. Kim, J. Lee, J. Sun, K. Park, M. Ahn, Y. Park, J. Ahn
Journal: Journal of Clinical Oncology (2010)

e18125 Background: To devise a prognostic model based on clinical parameters for non-small cell lung cancer (NSCLC) patients treated with erlotinib as a salvage therapy. Methods: Between July, 2006 and September, 2008, 257 metastatic or relapsed NSCLC patients who had been treated with erlotinib as a salvage therapy were analyzed retrospectively. Results: For the 257 patients, the median overall survival (OS) and the progression-free survival (PFS) from the start date of erlotinib treatment were 12.4 months and 2.8 months, respectively. Multivariate analysis showed that ECOG performance status of 2 or more (p = 0.001), elevated serum LDH level (p = 0.007), and absence of skin rash (p = 0.002) were independent adverse prognostic factors for OS and the presence of intra-abdominal metastasis (p = 0.047), prior chemotherapy ≥ 2 (p = 0.015), and absence of skin rash (p = 0.001) for PFS, respectively. OS and PFS were significantly reduced with a greater number of adverse predictive factors. Patients were categorized into four prognosis groups estimated on the basis of each adverse prognostic factor; good prognostic group (0 risk factors), intermediate group (1 risk factor), poor prognostic group (2 risk factors), and very poor prognostic group (3 risk factors). The median OS for the good, intermediate, poor, and very poor prognostic group were 22.0, 9.3, 5.4, and 2.7 months, respectively (p < 0.001) and and the median PFS were 6.5, 3.0, 1.2, and 0.9 months, respectively (p < 0.001). Conclusions: This prognostic model based on clinical parameters would be useful to identify patients who might be most likely to benefit from erlotinib therapy in clinical practice. No significant financial relationships to disclose.
Paired Samples Analyses Of GATA2 mutations During Clinical Follow-Ups In 138 Patients With Acute Myeloid Leukemia-The Mutation Is Unstable During Disease Evolution
Authors: Yun-Chu Lin, Hsin-An Hou, Wen-Chien Chou, Chien-Yuan Chen, Jih-Luh Tang, Ming Yao, Shang-Yi Huang, Bor-Sheng Ko, Szu-Chun Hsu, Shang-Ju Wu, Woei Tsay, Yao-Chang Chen, Hwei-Fang Tien
Journal: Blood (2013)
Paclitaxel and carboplatin (TP) for treatment of advanced or recurrent endometrial cancer: A retrospective study
Authors: M. A. Sovak, S. Chuai, S. Anderson, R. Barakat, J. Dupont, M. L. Hensley, P. Sabbatini, D. R. Spriggs, C. Aghajanian
Journal: Journal of Clinical Oncology (2005)

5020 Background: For patients with advanced or recurrent endometrial cancer, a community standard treatment is TP, though there have been no large supportive studies. GOG trial #209 is comparing the control arm of paclitaxel, doxorubicin and cisplatin (TAP) to TP in the treatment of advanced or recurrent endometrial cancer but results of this trial are years away. Methods: A retrospective analysis was performed on patients with advanced or recurrent endometrial cancer who were treated with TP at our institution between 1/1/90 and 5/30/04. A total of 142 patients were identified, of which the first 68 consecutively treated patients are presented here. Forty patients who had received at least 1 cycle of therapy were eligible for analysis if they met the following conditions that correspond to GOG #209 entry criteria: advanced disease (defined as primary stage III or IV disease or stage III or IV patients with persistent, measurable disease after surgery), recurrent measurable disease, chemotherapy naïve. Twenty-eight patients were excluded (synchronous ovarian carcinoma, prior chemotherapy, carcinosarcoma pathology, incomplete records, no measurable disease at time of treatment). Data were extracted from electronic medical records. This study was approved by the IRB. Results: The median age at diagnosis was 59.9 years (range 47–80 years). Twenty-five percent of patients received treatment in the primary advanced setting, 75% at the time of disease recurrence. Prior radiation therapy had been delivered to 60% of patients. The median number of cycles of TP delivered was 4, with 35% of patients receiving 6 or more cycles of therapy. The overall response rate was 47%, with a complete response rate of 2% and a partial response rate of 45%. Median progression-free survival was 4.2 months (range 0.7–14.5 months). Median overall survival was 11 months (range 1.4–31.6 months). Conclusion: TP achieves high objective response rates in patients with advanced or recurrent endometrial cancer. All 142 patients will be analyzed to further characterize the activity of TP in patients with advanced or recurrent endometrial cancer. No significant financial relationships to disclose.
A high throughput assay for mammalian target of rapamycin (mtor) kinase activity
Authors: Matt Hickman, Brian Cathers, Mahan Abbasian, Steve Pierce, Christian Lombardo, Gary Chiang, Sabita Sankar, Sarah Cox, David Giegel
Journal: Cancer Research (2008)

1537  Background: The goal of this study was to develop an automation-friendly, homogenous, time-resolved fluorescence resonance energy transfer (HTR-FRET) assay to screen for mTOR kinase inhibitors. The assay was adapted from an ELISA assay, which utilized a partially purified rat brain extract as the source of mTOR kinase activity and an 81-amino acid GST-p70S6 kinase fragment as the substrate.  Methods: Protocols for enrichment of mTOR kinase activity from rat brain extract as well as an ELISA-based assay to measure mTOR kinase activity were transferred from the Burnham Institute. The extract was shown to contain activity which phosphorylated both mTOR-raptor subtrates and mTOR-rictor substrates. Using the GST-p70S6K fragment as the substrate, the assay was shown to be specific for mTOR by immunodepletion studies. The mTOR kinase activity was profiled against thirty-five known kinase inhibitors with only Wortmannin (>90% Inhibition) and LY294002 (27% Inhibition) identified as inhibitors. Rapamycin, a well-characterized inhibitor of mTOR-raptor was active as an inhibitor when pre-incubated with recombinant FKBP12. FKBP12 alone was not inhibitory. The FKBP12-Rapamycin complex at 1 μM resulted in 50% inhibition of mTOR activity suggesting the existence of a Rapamycin-resistant component of mTOR kinase activity. Using the HTR-FRET assay the mTOR activity was shown to be dependent on Mn2+ similar to other lipid kinases, and unlike protein kinases that typically prefer Mg2+.  Results: The HTR-FRET assay was needed to screen a collection of 170,000 compounds. The screen resulted in finding compounds that were both ATP competitive and reversible. Recently recombinant mTOR has become available from Invitrogen. A number of compounds were tested with both enzyme sources and comparable IC50 values were obtained.  Conclusion:We have successfully developed a homogenous HTR-FRET assay for mTOR kinase using purified rat brain extract as a source for mTOR enzyme and identified ATP competitive inhibitors of mTOR kinase.
Ion Mobility Analysis of Lipoprotein Subfractions Identifies 3 Independent Axes of Cardiovascular Risk
Authors: Kiran Musunuru, Marju Orho-Melander, Michael P. Caulfield, Shuguang Li, Wael A. Salameh, Richard E. Reitz, Sekar Kathiresan, Olle Melander, Ronald M. Krauss
Journal: Circulation (2009)
Circulating endothelial cells and acute toxicity in rectal cancer patients receiving postoperative radiotherapy with concurrent UFT administration
Authors: Y. Chen, T. Hsu, M. Hsu, C. Hsieh
Journal: Journal of Clinical Oncology (2008)

15102 Background: Concurrent chemoradiation (CCRT) is now a standard postoperative adjuvant treatment for high-risk rectal cancer patients. However, no surrogate marker for optimization of adjuvant CCRT is available. Circulating endothelial cells (CEC) and endothelial progenitor cells (EPC) were observed to correlate the tumor response after metronomic therapy. This study aimed to examine the feasibility of CEC and/or EPC as a marker for adjuvant CCRT toxicity in rectal cancer. Methods: Between November 2006 and Sep 2007, 9 rectal cancer patients treated with radical proctectomy were enrolled (ClinicalTrials.gov Identifier NCT00325871). Postoperative RT with concurrent UFT followed by metronomic UFT administration was applied as adjuvant treatment. Peripheral blood was sampled weekly before and during CCRT as well as monthly thereafter. The kinetics of CEC, apoptotic CEC and EPC was estimated by flow cytometry with parameters including CD45, CD31, CD34, CD133, KDR and 7AAD. CCRT toxicity was graded according to version 3.0 of the NCI-CTCAE. Results: At various time points, 5 patients developed grade 3 diarrhea, 1 had grade 2 cystitis, 1 suffered from acute urinary tract infection and 1 experienced peritonitis. In all patients with acute CCRT toxicity, a burst of increase in the amounts of CEC, was consistently noted at the time that severest toxicity developed. These changes recovered while symptoms/signs subsided. Neither the EPC nor the white blood cells (WBC) kinetics shows such evident correlation. The amounts of CEC and EPC had no significant correlation with WBC counts. The follow-up CEC kinetics during metronomic UFT administration as an adjuvant is undergoing. Conclusions: The kinetics of CEC correlates with that of CCRT toxicity. To suggest CEC as a surrogate marker for optimization of CCRT, further validation by clinical investigations is warranted. No significant financial relationships to disclose.
Chronic musculoskeletal pain and sleep disturbances as predictors for lower vitality measured by the short form 36 (SF-36) - A eight-year follow up study
Authors: Susann Arvidsson, Barbro Arvidsson, Bengt Fridlund, Stefan Bergman
Journal: Annals of the Rheumatic Diseases (2006)

Background: Subjects with  musculoskeletal pain or sleep disturbances have been shown to have a poor healthstatus as measured by the SF-36 health survey. Fatigue is commonly reported by subjects with  musculoskeletal pain and sleep disturbances. There is little known about the temporal relationship between  pain, sleep disturbances and changes of vitality.Objectives: The aim of this study was to evaluate the predictive value of  musculoskeletal pain and sleep disturbances with regard to changes in vitality as measured by SF-36 over an eight year period.Method: An eight year follow up of 2 425 subjects aged 20-74 from the general population that in 1995 answered the same postal questionnaire. The questionnaire assessed  musculoskeletal pain, sleep disturbances, and included the SF-36 health survey. Pain was considered chronic if persistent for three months or more. Sleep disturbances assessed were difficulty in falling asleep, frequent awakenings, early awakenings and not feeling rested. Main outcome measure was change of vitality as measured by SF-36 in those that at baseline reported vitality over the median value. Statistical analyses were done with use of logistic regression. Besides the studied variables, the logistic regression analyses also controlled for gender, age, socio-economic group, and the use of analgesics and sleeping pills.Results: At baseline 1212 subjects reported a vitality score on SF-36 above the median score of 75. There were 943 subjects (78%) responding at the eight-year follow up. Chronic pain at baseline predicted (OR=1,64, 95% CI 1,14-2,36%, p=0,01) worsening of vitality over time. Loss of vitality was also predicted by moderate problems with falling asleep (OR=2,17, 95% CI 1,31-3,60%, p<0,01), and problems with not feeling rested (moderate problems OR=2,08, 95% CI 1,23-3,50%, p=0,01, and major problems OR=4,76, 95% CI 1,53-14,78%, p=0,01).Conclusion: Loss of vitality in SF-36 over an eight-year period was predicted by  musculoskeletal pain, problems with falling asleep and problems with not feeling rested. Problems with frequent awakenings and early awakenings did not predict lower value of vitality over an eight-year period. It could thus be important to attend to sleeping problems and especially the feeling of not being rested in subjects with  musculoskeletal pain.
Impact of mulitfocal/multicentric versus unifocal breast cancer on local recurrence.
Authors: R. Woods, K. A. Gelmon, S. Tyldesley, H. F. Kennecke, C. Speers, R. Yerushalmi
Journal: Journal of Clinical Oncology (2010)

514 Background: We compared local recurrence rates (LRR) after mastectomy (Mx) or breast-conserving surgery (BCS) in multifocal/multicentric (M/M) versus unifocal (U) breast cancer. Methods: Women diagnosed with stage I-II breast cancer between 1989 and 2005 and referred to the BC Cancer Agency were classified as having U or M/M disease. Tumor and patient characteristics were prospectively collected and obtained from the Breast Cancer Outcomes Unit database. Univariate and multivariate analyses for LRR were performed using cumulative incidence curves and Fine and Gray regression models respectively. Results: Of 19,754 eligible women, 11,983 had BCS (U:11,683, M/M: 300) and 7,771 had mastectomy (U: 6,884, M/M: 887). Median follow-up was 7.9 years (IQR: 4.8 – 12.0); LRRs among U and M/M disease were comparable in univariate analyses both after BCS (p=0.672) or after Mx (p=0.773) (Table). When multivariate analysis (MVA) was performed for the Mx group (adjusted for tumor size, node positivity, grade, ER, LVI, hormone use, XRT use, and M/M disease), there was an increased risk of local relapse in the M/M group (HR = 1.42, 95% CI: 1.04-1.96, p=0.029). When adjusting for the same variables in the BCS group, this difference was not observed (HR=1.21, 95% CI: 0.64-2.27, p=0.56). Conclusions: M/M disease is a risk factor for local recurrence in early stage breast cancer, even with Mx. Although we found no significant difference between M/M and U disease in the BCS cases, this might be related to case selection despite adjusting for known risk factors or to the smaller sample size (n=300 for BCS, M/M patients). However, given the relatively low rate of local recurrence, BCS may be considered as a reasonable option in certain M/M cases. 5- and 10-year LRR (95% CI) BCS Mx Year U M/M U M/M 5 2.65 (2.36, 2.97) 1.82 (0.68, 4.02) 4.03 (3.57, 4.52) 3.85 (2.70, 5.32) 10 4.56 (4.12, 5.03) 5.47 (2.61, 9.86) 5.83 (5.23, 6.47) 6.53 (4.73, 8.71) No significant financial relationships to disclose.
Bevacizumab continuation versus no continuation after first-line chemo-bevacizumab therapy in patients with metastatic colorectal cancer: A randomized phase III noninferiority trial (SAKK 41/06).
Authors: Dieter Koeberle, Daniel C. Betticher, Roger Von Moos, Daniel Dietrich, Peter Brauchli, Daniela Baertschi, Klazien Matter-Walstra, Ralph C. Winterhalder, Markus M. Borner, Sandro Anchisi, Peter Moosmann, Attila Kollar, Piercarlo Saletti, Arnaud Roth, Martin Frueh, Marc Kueng, Razvan A. Popescu, Sabina Schacher, Viviane Hess, Richard Herrmann
Journal: Journal of Clinical Oncology (2013)

3503 Background: Chemotherapy plus bevacizumab is a standard option for first-line treatment in metastatic colorectal cancer patients. We assessed whether no continuation is non-inferior to continuation of bevacizumab after stop of first-line chemotherapy. Methods: In an open-label, phase 3 multicenter study conducted in Switzerland, patients with unresectable metastatic colorectal cancer having non-progressive disease after 4-6 months of standard first-line chemotherapy plus bevacizumab were randomly assigned in a 1:1 ratio to continuing bevacizumab (7.5 mg/kg every 3 weeks) or no treatment. CT scans were done every 6 weeks between randomization and disease progression. The primary endpoint was time to progression (TTP). A non-inferiority limit for hazard ratio (HR) of 0.727 was chosen to detect a difference in TTP of 6 weeks or less, with a one-sided significant level of 10% and a statistical power of 85%. Results: The per-protocol population comprised 262 patients. Median follow-up is 28.6 months (range, 0.6-54.9 months). Median TTP was 17.9 weeks (95% CI 13.3-23.4) for bevacizumab continuation and 12.6 weeks (95% CI 12.0-16.4) for no continuation; HR 0.72 (95% CI 0.56-0.92). Median progression free-survival and overall survival, both measured from start of first-line treatment, was 9.5 months and 24.9 months for bevacizumab continuation and 8.5 months (HR 0.73 (95% CI 0.57 - 0.94)) and 22.8 months (HR 0.87 (95% CI 0.64 – 1.18)) for no continuation. Median time from randomization to second-line treatment was 5.9 months for bevacizumab and 4.8 for no continuation. Grade 3-4 adverse events in the bevacizumab continuation arm were uncommon. Conclusions: Non-inferiority could not be demonstrated. The 95% confidence intervals for the TTP HR indicate superiority of bevacizumab continuation after stop of first-line chemotherapy. The median differences in TTP and in time between randomization and start of second-line treatment were of moderate magnitude being less than 6 weeks. The results of an accompanying cost analysis will be presented at the meeting. Clinical trial information: NCT00544700.
A fixed-sequence, open-label study to determine the activity of SCH 717454 (robatumumab) as assessed by positron emission tomography in patients with relapsed or recurrent colorectal cancer.
Authors: E. H. Lin, H. Lenz, M. N. Saleh, S. Badarinath, J. A. Knost, M. J. MacKenzie, B. N. Polite, P. Kavan, E. X. Chen, L. P. Leichman, K. Pathiraja, B. D. Lu
Journal: Journal of Clinical Oncology (2011)

3584 Background: This study was to evaluate the antitumor activity of SCH717454 (robatumumab) by positron emission tomography in patients with metastatic colorectal cancer. Methods: Eligible patients (n = 67) were those with metastatic colorectal cancer refractory to first-line chemotherapy and whose tumors were 3 cm or more in diameter with a tumor to background ratio of 3:1 on PET-CT scan. All patients were randomized 1:3 to receive either chemotherapy or robatumumab at 0.3 mg/kg biweekly in period 1 and all patients received robatumumab at 10 mg/kg biweekly in period 2. The primary endpoint of the study was to determine the proportion of subjects who had a SUVmax response (defined by >20% decrease) after the first cycle of SCH 717454 in period 2. It was hypothesized that higher doses of SCH 717454 would result in a greater SUVmax response. The chemotherapy arm served to validate change in SUVmax in this disease and timing setting as a potentially useful anti-tumor activity marker. Results: Seven out of 41 evaluable subjects 17% (95% CI 7-32) had a >20% decrease in SUVmax. Five of the 7 had minimal decrease in SUVmax between period 1 and period 2. One subject (2%) had a partial response, 17 (27%) stable disease, and 39 (61%) progressive disease per investigator assessment. The utilization of FDG-PET as a treatment response was also validated using the chemotherapy arm in period 1. In general, SCH 71745 treatment was associated with marked decreases in IGFBP2 and IGF1R and with a marked increase in IGFBP3. The treatment was well tolerated with the most frequently reported SAE being fatigue (35 [55%], nausea (33 [52%], anorexia (23 [36%] subjects), and vomiting (23 [36%] subjects). Conclusions: Biweekly IV infusions of 10 mg/kg SCH 717454 resulted in some anti-tumor activity detected by PET in patients with metastatic colorectal cancer, with one subject experiencing a potential partial response. SUVmax changes were consistent with being a sensitive marker for SCH 717454 activity. Further studies with SCH717454 or other IGFR antagonist in colorectal are warranted, potentially in a selected subset of patients.
Factors influencing long-term altered quality of life, sexual functioning, and menopausal symptoms after prophylactic bilateral salpingo-oophorectomy (PBSO) among high-risk women (wm).
Authors: C. Touboul, C. Uzan, J. Ichante, O. Caron, A. Dunant, S. Dauchy, S. Gouy, P. Morice, M. Spielmann, S. Delaloge
Journal: Journal of Clinical Oncology (2010)

1564 Background: To determine risk factors of long-term decreased quality of life (QOL), altered sexual functioning, and increased anxiety and menopausal symptoms (MS) after PBSO. Methods: All wm with high-risk for hereditary breast and/or ovarian cancer who underwent PBSO during the past 15 years (yrs) were sent 5 questionnaires: i) general social and demographical questions ii) EORTC QLQ-C30; iii) sexual functioning (SAQ); iv) MS (FACT-ES) and v) anxiety (STAI-A). Logistic analyses were used to identify factors associated with altered results. Due to multiple testing, only p values ≤ 0.01 were considered significant. Results: Among 175 wm sent questionnaires in March 2009, 112 had completed and returned the questionnaires by 1/09/09 (64%). Mean delay since PBSO: 6 yrs. Mean age at PBSO: 48 yrs (35-74). Personal history of breast cancer (BC): 86 (77%), BRCA1/2 carrier: 92 (82%). High educational level (p=0.01), executive occupation (p=0.01) at PBSO positively influenced QOL. Younger age at PBSO was associated with decreased social functioning (p=0.007) and increased anxiety (p=0.01). None of the other 10 baseline factors tested were significant. Practice of sport at time of study was highly related to better QOL (p= 0.004) and emotional functioning (p=0.001), higher sexual pleasure (p=0.007), and decreased anxiety (p=0.006). Weight gain was associated with decreased QOL (p= 0.004) increased anxiety (p=0.01) and MS (p=0.0002). In the multivariate analysis, sport and weight gain were both highly predictive of better QOL and lower anxiety. Conclusions: Wm < 50 yrs at PBSO (as currently recommended) are at higher risk of anxiety and decreased social functioning. Practice of sport and absence of weight gain might potentially allow better overall health status after PBSO. At surgery At time of study Married or in couple 85% 80% Menopausal 48% - Sexually active 80% 65% Practice of sport - 60% Practice of hobbies - 72% No significant financial relationships to disclose.