tbuckley/cabot-search huggingface dataset:
RTOG 0131: Phase II trial of pre-irradiation and concurrent temozolomide in patients with newly diagnosed anaplastic oligodendrogliomas and mixed anaplastic oligodendrogliomas: Relationship between 1p/19q status and progression-free survival
Authors: M. A. Vogelbaum, B. Berkey, D. Peereboom, C. Giannini, R. Jenkins, J. Suh, P. Brown, D. Blumenthal, C. Biggs, M. Mehta
Journal: Journal of Clinical Oncology (2006)

1517 Background: In a previous report, we showed in patients with newly diagnosed anaplastic oligodendrogliomas (AOs) and mixed anaplastic oligoastrocytomas (MAOs) that temozolomide (TMZ) can be given concurrently with radiation therapy (RT) with acceptable toxicity. We have now evaluated the efficacy of this regimen and correlated durability of response with tumor 1p/19q genotype. Methods: A phase II study was performed to evaluate the use of pre-RT TMZ followed by concurrent RT and TMZ in patients with newly diagnosed AO or MAO. The primary endpoint was to determine the pre-RT TMZ six-month progression rate, and secondary endpoints included progression-free survival and overall survival. Results: 40 eligible patients were entered into the trial. Thirty-two patients completed 6 months of pre-RT TMZ and concurrent RT and TMZ. Of the remaining eight patients, 4 withdrew due to toxicity and 4 other patients withdrew from study without evidence of toxicity or pre-RT progression. 1p/19q data are available in 37 cases; 23 tumors had loss of heterozygosity (LOH) of both 1p and 19q (double-deleted) while 14 tumors had LOH of either 1p or 19q (n = 3), or no LOH (n = 11). To date, 11 patients have experienced tumor progression; 1p/19q data are available for 10 of these cases (2 are double-deleted (2/23 = 9%), 8 have at least one intact chromosome (8/14 = 57%). Kaplan-Meier analysis demonstrates that progression free survival is significantly better for the double-deleted group (median time to progression not reached) than for the intact group (median time to progression = 15.2 months, p = 0.001). Overall survival is 98% (39/40) with a median follow-up of 17.5 months (2.8 - 31.1 months). Conclusions: LOH of both 1p and 19q is strongly correlated with a durable response of AO and MAO to a combined regimen of chemotherapy and radiation therapy. Tumors that are intact at 1p and/or 19q progress early despite an aggressive therapeutic regimen. These results suggest that future clinical trials should be prospectively stratified by tumor 1p/19q genotype. [Table: see text]
Pilot study of modafinil for treatment of neurobehavioral dysfunction and fatigue in adult patients with brain tumors
Authors: T. A. Kaleita, D. K. Wellisch, C. A. Graham, B. Steh, P. Nghiemphu, J. M. Ford, A. Lai, S. Peak, T. F. Cloughesy
Journal: Journal of Clinical Oncology (2006)

1503 Background: Patients with brain cancer develop neurobehavioral dysfunction and fatigue that compromise their performance of daily activities. We report results from evaluating the efficacy and safety of modafinil treatment for tumor/therapy sequelae in this medically fragile patient population. Methods: Patients: 21–65 years old with primary malignant disease or nonmalignant cerebral tumors treated with neurosurgical resection, radiotherapy, and/or chemotherapy. Clinical Global Impression of Severity ratings of mild to severe attention/memory impairment and/or fatigue. Measures: Trail Making (TM) A and B, Symbol Digit Modalities (SDM), Verbal Fluency (VF), Hamilton Depression Scale (HAM-D), Fatigue Severity Scale (FSS), Visual Analogue Fatigue Scale (VAFS), Modified Fatigue Impact Scale (MFIS). Design: Double-blind dose-controlled randomization (200 or 400 mg/day modafinil in divided doses) 3 wks; Washout 1wk; Open label extension 8 wks. Statistical analyses: Changes from baseline at scheduled visits (1, 3, 4, 8, 12 wks) using paired t-tests or Wilcoxon Signed Rank tests as appropriate. Results: Thirty patients, 63% male, mean age (SD) = 45.3 (11.7) yrs were accrued from 6/03–10/05. Illness severity: moderate 3 (10%), marked 13 (43%), severe 14 (47%). Tumor histology: glioblastoma multiforme 8 (27%), anaplastic glioma 10 (33%), low grade glioma 10 (33%), meningioma 1 (3%), CNS lymphoma 1 (3%). Treatment: neurosurgical resection 93%, radiotherapy 87%, chemotherapy 70%. The table shows relationships of nine variables at baseline and 8 and 12 weeks after initiation of modafinil. Adverse events reported by ≥4 patients: headache 13 (42%); insomnia 8 (26%); dizziness 7 (23%); dry mouth 7 (23%); depressed consciousness 5 (16%); nausea 4 (13%). Conclusions: Results show improvement across cognitive, mood, and fatigue outcome measures. Modafinil was generally well tolerated, with a low incidence of adverse events. Greatest improvements in outcomes were observed 8 wks after baseline. [Table: see text] [Table: see text]
AB0223 Evaluation of classical nsaids and cox-2 selective inhibitors on purified ovine enzymes and human whole blood
Authors: X De Leval, JM Dogne, J Delarge, JY Reginster, Y enrotin
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> In this study, we evaluated the cyclooxygenases (COX) inhibitory profile of NSAIDs in a cellular assay using human whole blood. <h3>Methods</h3> Human whole blood assay was performed using fresh blood from normal volunteers. COX-1 assay: Fresh blood was collected into tubes containing no anticoagulants, vortexed and incubated at 37°C under constant agitation for 1 h to allow the blood clot. The serum was then obtained by centrifugation and was assayed for thromboxane B<sub>2</sub> (TXB<sub>2</sub>) using a enzyme immunoassay. COX-2 assay: Fresh blood was collected in heparinized tubes and activated by treatment with lipopolysaccharide at the final concentration of 100 μg/ml. After 24 h of incubation with the drugs, plasma was collected and assayed for prostaglandin E<sub>2</sub> (PGE<sub>2</sub>). PGE<sub>2</sub> production was quantified by a specific radioimmunoassay. Drugs were tested at the concentrations ranged among 0.01 to 100 μmol/l. <h3>Results</h3> <h3>Conclusion</h3> In the whole blood test and based on the IC50 values, the majority of the NSAID tested preferentially inhibits COX-2. Aceclofenac shows the best selectivity whereas indomethacin preferentially inhibited COX-1.
Biweekly docetaxel and carboplatin as first line chemotherapy in advanced non small cell lung cancer (NSCLC)
Authors: J. L. Fírvida, G. Esquerdo, M. Amenedo, M. Salgado, C. Llorca, A. González, E. Pérez, J. M. Cervera, M. Ramos
Journal: Journal of Clinical Oncology (2006)

17016 Background: Platinum therapy has been the backbone treatment in NSCLC. The concomitant use of platinum derivatives and taxanes has shown high antitumoral activity with moderate toxicity. To improve the therapeutic index of this combination, we performed a study with biweekly carboplatin and docetaxel. Primary objective was determination of objective response rate (ORR). Secondary objectives were time to progression, tolerability and overall survival. Methods: Patients histologically confirmed of non-small cell lung cancer, aged ≥ 18, ECOG PS 0–2, measurable lesion according RECIST criteria, adequate bone marrow, renal and hepatic function were included. Prior chemotherapy was not allowed. Patients received treatment with a combination of Docetaxel 50 mg/m 2 and Carboplatin AUC-4 each 15 days for a maximum of 8 cycles. Results: Fifty patients were included between March 2004 and July 2005, 84% were male, median age was 63 years old (range 48–77), 78% had ECOG PS 0–1 and 64% of patients had stage IV. Histology was squamous cell carcinoma (54%) adenocarcinoma (36%) and large cell carcinoma (10%). A total 316 cycles were administrated (median 7, Range 1–12). Over 46 evaluable patients for response, one achieved CR, 13 PR, 21 SD and 11 PD, with an overall response rate of 30.5% (95% CI: 17.2–43.8). Median follow up of patients is 8.3 months, with a median TTP of 6.3 months and median overall survival of 11.1 months. Grade 3–4 toxicity per patient was: neutropenia (22.0%), asthenia (16.0%), anaemia (10.0%), thrombocytopenia (2%), mucositis (2%) and nauseas (2%). Conclusions: These results suggest that biweekly schedule of carboplatin / docetaxel is a safe and active regimen in first line advanced NSCLC patients. No significant financial relationships to disclose.
Abstract 20936: Determinants of PFA-100 Closure Time: A Genome-Wide Association Study
Authors: Rehan Qayyum, Diane M Becker, Nauder Faraday, Lisa R Yanek, Bhoom Suktitipat, Lewis Becker
Journal: Circulation (2010)

The Platelet Function Analyzer-100 (PFA-100, Dade-Behring) is an in vitro blood test of platelet function in the presence of shear stress and agonist stimulation. The aim of the current study was to identify genetic variants that determine collagen-epinephrine closure time (CEPI-CT) of the PFA-100in African Americans (AA) with replication in European Americans. Fasting blood samples were drawn from 836 healthy AA subjects and PFA-100 test was performed with prefabricated cartridges containing a combination of collagen and epinephrine as platelet agonists. Closure time was recorded in seconds. Genotyping was conducted with the Illumina 1M BeadChip array. Linear mixed effects models in SAS were used to test for association between each SNP and PFA-100 for all SNPs that met standard quality control criteria, after adjusting for age and sex. A replication sample consisted of 1244 healthy European Americans. Three SNPs were significantly associated with CEPI-CT at the GWAS Bonferroni threshold (p<10−8) in AA. ...
Cost of illness of renal cell carcinoma in Canada
Authors: A. Abugaber, K. Lang, N. Danchenko, D. Thompson, T. Bhardwaj, G. Bjarnason, A. Finelli, A. Kapoor, B. Jaszewski
Journal: Journal of Clinical Oncology (2007)

15560 Background: Renal cell carcinoma (RCC) is the most common form of kidney cancer. RCC patients have limited treatment options and low survival rates, particularly for advanced-staged patients. Despite its importance, data on the economic burden of RCC are limited. Methods: A prevalence-based approach was used to estimate the aggregate annual societal cost burden of RCC in Canada. Key relationships represented in the model include the annual number of patients treated for RCC by age group and cancer stage; utilization of cancer treatments; unit costs; work-days missed, and wage rates. Results: The annual prevalence of RCC in Canada in 2005 was estimated to be 17,845 cases. The associated annual burden of RCC (Canadian $2005) was approximately $357 million ($19,981 per patient). Health-care costs and lost productivity accounted for 65.6% ($234 million) and 34.4% ($123 million) of the total, respectively. Reflecting its higher prevalence, the total cost associated with Stage II RCC accounted for the greatest share (67%) followed by Stage I, Stage III, and Stage IV RCC, at 19.8%, 11.6% and 1.6%, respectively. Conclusions: The economic burden of RCC in Canada is substantial at a cost of $357M which represents 2% of the total cost of illness of cancer in Canada ($16.64B, inflated to $2005). Interventions to reduce the prevalence of RCC have the potential to yield considerable economic benefits. [Table: see text]
Colectomy after rescue therapy for intravenous-steroid resistant acute ulcerative colitis : a 3-year follow-up study of the Swedish-Danish infliximab/placebo trial
Authors: A. Gustavsson, G. Järnerot, E. Hertervig, I. Friis-Liby, L. Blomquist, P. Karlen, C. Grännö, M. Vilien, M. Ström, H. Verbaan, P. M. Hellström, Jonas Halfvarson, A. Magnuson, Curt Tysk
Journal: Gut (2008)

Colectomy after rescue therapy for intravenous-steroid resistant acute ulcerative colitis : a 3-year follow-up study of the Swedish-Danish infliximab/placebo trial
Is there an anti-androgen withdrawal effect with enzalutamide?
Authors: Alejo Rodriguez-Vida, Diletta Bianchini, Simon Hughes, David Lorente, Danielle Crawley, Mieke Van Hemelrijck, Mark Voskoboynik, Noan Minh Chau, Sarah Maria Rudman, Thomas Powles, Heather Payne, Johann Sebastian De Bono, Simon Chowdhury
Journal: Journal of Clinical Oncology (2014)

200 Background: The second generation anti-androgen enzalutamide has demonstrated improved survival in patients with metastatic castration-resistant prostate cancer (CRPC) progressing after docetaxel. While an anti-androgen withdrawal effect has been reported for bicalutamide, flutamide, and other non-steroidal and steroidal anti-androgens, there is no published evidence of any withdrawal effect with enzalutamide. Methods: We retrospectively identified 30 consecutive patients with advanced prostate cancer who were treated with enzalutamide post-docetaxel at three London hospitals. All patients were withdrawn from enzalutamide due to clinical (73%), PSA (87%) and/or radiological progression (47%). Post-discontinuation prostate-specific antigen (PSA) results were available for all patients and were determined two-weekly for at least six weeks until starting further anti-cancer treatment. PSA withdrawal response was defined as a 50% decline in PSA from baseline, with a confirmed decrease after 3 weeks or more. Clinical tumor and patient characteristics were evaluated in relation to the withdrawal effects using multivariate logistic regression analyses. Results: Median age was 71 (range 54 to 87). The median follow-up was 5.4 months (range: 0.5 to 16.0 months). At enzalutamide initiation, ECOG performance status was 0 and 1 in 10% and 69% of patients, respectively. The most common metastatic sites were bone (87%), lymph nodes (68%), liver (17%), and lung (6%). Most patients (70%) had been on abiraterone previously and 11 patients (37%) had also received prior cabazitaxel. The median treatment duration with enzalutamide was 3.7 months. Only one patient (3%) had a confirmed PSA response of 50% or more after enzalutamide discontinuation and two patients (7%) had a confirmed PSA response between 30% and 50%. None of the clinical variables assessed in relation to withdrawal effects were found to be statistically significantly associated. Conclusions: This preliminary case series represents the first clinical evidence that enzalutamide may have an anti-androgen withdrawal effect in a minority of patients. These results warrant further prospective and controlled validation of a potential enzalutamide withdrawal effect and its clinical relevance in prostate cancer management.
Acute toxicities associated with radiation in the second National Wilms' Tumor Study.
Authors: P R Thomas, M Tefft, G J D'Angio, P Norkool
Journal: Journal of Clinical Oncology (1988)

Twenty-three of 303 patients (7.6%) entered into National Wilms' Tumor Study Number 2 (NWTS-2) with groups II, III, and IV disease experienced 26 toxic events thought to be related to radiotherapy (RT). The randomization between vincristine (VCR) plus dactinomycin (AMD) and the same two drugs plus doxorubicin (ADR) had a minimal effect on RT toxicity. Five (1.6%) fatalities were recorded and the surviving 18 patients recovered without discernible residua. Sixteen patients had hepatic, four had pulmonary, and three had cardiac toxicity. Hepatic toxicity was significantly more common when the right side of the abdomen or the whole abdomen was irradiated than when the left side was treated (P = .01). We conclude that acute RT-related toxicity in NWTS-2 was very similar to that in NWTS-1, in which 26 (7.2%) of 359 randomized patients developed RT-related toxicity and three died. This acceptable rate was maintained despite more intensive chemotherapy (CT) in NWTS-2.
Quality of life outcomes of breast cancer in an integrative treatment setting: The Cancer Treatment Centers of America experience
Authors: J. Granick, C. G. Lis, R. Levin, R. Neelam, D. Brikshavana, D. Gupta
Journal: Journal of Clinical Oncology (2004)

6136 Background: There is evidence to suggest that patients undergoing aggressive treatment for breast cancer can experience an initial deterioration of quality of life (QoL). The goal of this investigation was to evaluate the QoL outcomes in patients with breast cancer treated at our integrative cancer treatment setting. Methods: A case series of 34 patients with stages I-IV breast cancer treated at Cancer Treatment Centers of America at Midwestern Regional Medical Center between March 2001 and September 2003 was included in this study. All patients underwent a comprehensive program of nutritional, spiritual, physical, naturopathic, and emotional support while receiving aggressive conventional cancer treatment. QoL was evaluated using the EORTC QLQ-C30 (EORTC) and the Ferrans and Powers Quality of Life Index (QLI). The mean QoL scores were compared using Analysis of Variance across three different time periods; baseline, 1 and 3 months. Results: Patients received a variety of treatments: all 34 received chemotherapy, 12 (35.3%) radiation, 7 (20.6%) hormone replacement therapy, 4 (11.8%) immunotherapy, and 3 (8.8%) surgery. Mean QoL scores showed statistically significant improvement during the three month period for the emotional function (mean scores 60, 72.5 and 71.5 at baseline, 1 and 3 month; p=0.04) and insomnia symptom subscale (mean scores 41.2 p=0.08) in EORTC. In all other domains, mean QoL scores in both EORTC and QLI showed no significant difference across the three time periods. Conclusion: This study suggests that QoL outcomes in breast cancer are either well-maintained or improved while undergoing treatment in our integrative cancer treatment setting. In future studies, we will be examining the impact of specific treatment protocols on the Qol outcomes of these patients. No significant financial relationships to disclose.
Ten-year analysis of vaccinia melanoma oncolysate (VMO) phase III trial.
Authors: M. K. Wallack, M. Berenji, K. Alam, A. A. Bartolucci
Journal: Journal of Clinical Oncology (2010)

e19031 Background: We present a 10-year analysis of the first randomized, prospective, double-blind, multi- institutional melanoma vaccine trial with patients treated with either vaccinia melanoma oncolysate (VMO) or attenuated vaccinia virus (VV) between June 1988 and June 1991. Methods: Patient data was collected from eleven institutions over the course of trial, as well as from the Social Security Death Index. This data was analyzed in April 2008 for disease-free interval (DFI) and overall survival (OS) using log-rank analysis. Results: At time of analysis, 109 patients were evaluable with 78 patients living (35 VMO, 43 VV). The patients were divided as such: VMO_Alive, VV_Alive, VMO_Deceased, VV_Deceased. Gender-wise, 79% of females treated with VMO have survived, compared to 52% of males (p = 0.0473). There was no statistical significance among VMO- and VV-treated groups with reference to age (p = 0.3286), number of nodes (p = 0.6855), time (p = 0.5525), or size of lesion (p = 0.4008). Conclusions: This phase III trial was the first of its kind to employ a live attenuated vaccinia virus- augmented tumor cell vaccine (vaccinia oncolysate) as a specific active immune stimulator against advance stages of melanoma. The ensuing 10-year follow-up analysis shows no difference in patients who had received VMO compared to those who had received VV. But per FDA guidelines at the time, VV was originally designed as a negative control. The fact that VV had underlying activity made it difficult to interpret the efficacy of the vaccine. Moreover, our long-term results are in clear opposition to other melanoma vaccine trials, namely Morton (2005) and Hersey (2002). It should be noted that the first-generation melanoma vaccine demonstrated statistically-significant activity in males 44-57 years of age at time of initial analysis. Additionally, a significant number of patients from the original trial are alive at time of the 10-year analysis, demonstrating that there is an immune response generated by this vaccine. From this trial experience, we have developed a second-generation melanoma vaccine, which includes components from the first-generation melanoma vaccine, but is further enhanced to elicit a more potent immune response. No significant financial relationships to disclose.
Prevalence and outcomes of patients (pts) with EGFR S492R ectodomain mutations in ASPECCT: Panitumumab (pmab) vs. cetuximab (cmab) in pts with chemorefractory wild-type <i>KRAS</i> exon 2 metastatic colorectal cancer (mCRC).
Authors: Timothy Jay Price, Kathryn Newhall, Marc Peeters, Tae Won Kim, Jin Li, Stefano Cascinu, Paul Ruff, Attili Venkatasatya Suresh, Anne Thomas, Sergei Tjulandin, Michael Boedigheimer, Kathy Zhang, Roger Sidhu, Swaminathan Murugappan
Journal: Journal of Clinical Oncology (2015)

740 Background: Mutations resistant to anti-EGFR treatment (tx), beyond those in RAS, have been reported and include EGFR S492R. We report results for pts with EGFR S492R mutations in the phase 3 ASPECCT trial. Methods: Pts were randomized 1:1 to receive pmab or cmab. Crossover was not allowed. The primary endpoint was non-inferiority of overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. EGFR S492R was evaluated by digital droplet PCR in plasma samples collected pre-tx and post-tx (safety follow-up 4 wks after the last dose). Outcomes were analyzed by EGFR S492 status. Results: Of 999 pts randomized and treated, post-tx samples were available for EGFR S492 assessment from 53% of pts (261/496) in the pmab arm and 57% of pts (285/503) in the cmab arm. EGFR S492R was detected in 1% of pts in the pmab arm and 16% of pts in the cmab arm in post-tx samples. EGFR S492R was not detected in pre-tx samples. Results are shown (table). Conclusions: In a retrospective analysis of pts with available samples from ASPECCT, 16% of pts in the cmab arm and 1% of pts in the pmab developed EGFR S492R mutations. Pts with EGFR S492R in the cmab arm had longer tx duration before progressive disease (PD) and appeared to have worse OS vs pts with wild-type S492 in the cmab arm. Clinical trial information: NCT01001377. [Table: see text]