tbuckley/cabot-search huggingface dataset:
Mutation Analysis of Melanoma Patients with Leptomeningeal Disease (Lmd) Receiving Intrathecal Interleukin-2 (It-Il-2) at Md Anderson Cancer Center (Mdacc)
Authors: M.L. Rohlfs, J. Richard, T. Dett, N. Gonzalez, C. Lacey, D. Gerber, P. Fox, N. Papadopoulos, S. Patel
Journal: Annals of Oncology (2014)
Rituximab Given after High Dose Therapy and Autologous Stem Cell Transplantation Induces Durable Clearance of Minimal Residual Disease in about Half of the Patients with Follicular Non Hodgkin’s Lymphoma : 36 Months Results of a Multicenter Open Label Phase II Trial (M39012 Trial).
Authors: Franck Morschhauser, Christian Recher, Noel Milpied, Remi Gressin, Gilles Salles, Pauline Brice, Norbert Vey, Corinne Haioun, Philippe Colombat, Jean-Henri Bourhis, Jean-Francois Rossi, Nathalie Berriot-Varoqueaux, Loic Bergougnoux, Andre Bosly, Georges Delsol, Michel Attal
Journal: Blood (2004)
Matched Cohort Study on Patients with Cervical Cancer Diagnosed During Pregnancy
Authors: F. Amant, C. Uzan, S.N. Han, R. Fruscio, K. Dahl Steffensen, J. Škultéty, D. Giuliani, A. Mephon, R. Rouzier, P. Witteveen, A. Locatelli, L. Rob, M.J. Halaska
Journal: Annals of Oncology (2014)
Predictive and prognostic potential of angiogenic serum factors and circulating endothelial cells in metastatic melanoma patients receiving temozolamide plus bevacizumab (SAKK 50/07).
Authors: G. Fuerstenberger, E. Boneberg, M. Simcock, R. Dummer, S. M. Goldinger, O. Michielin, B. Seifert, A. F. Ochsenbein, M. R. Schlaeppi, R. von Moos
Journal: Journal of Clinical Oncology (2010)

8585 Background: First line chemotherapy/bevacizumab has shown a positive effect in melanoma in two phase II trials. However, there is a need for biomarkers to allow selection of patients who are more likely to benefit from this therapy. Methods: We investigated the predictive and prognostic potential of vascular endothelial growth factor- A (VEGF-A), stromal cell-derived factor-1alpha (SDF-1alpha), hematopoietic stem cells (CD34+), a subpopulation containing endothelial progenitor cells (CD34+, CD133+ [EPC]) and mature circulating endothelial cells (CECs) in 60 patients with metastatic melanoma treated with first-line temozolomide (days 1 to 7 of each cycle) and bevacizumab (day 1 of each cycle), each cycle lasting 2 weeks,from the trial SAKK 50/07, collected on day 1 (baseline) and 14 (follow-up). Results: There was a significant decrease of VEGF levels and EPC numbers from baseline to follow-up with a boarder-line significant association between VEGF levels and EPCs numbers at baseline (p = 0.068) and between change of VEGF levels and change of EPC numbers from baseline to follow-up (p = 0.092). Neither EPC nor CEC numbers at baseline or at follow-up (nor absolute changes) had a prognostic or a predictive potential, whereas VEGF-A levels below median baseline value (1,140 pg/mL) were associated with better overall survival (13.4 vs. 8.3 months; p = 0.018). This was also true for median follow-up VEGF levels (500 pg/mL) (13.7 vs. 8.4 months, p = 0.038). SDF1alpha levels above median baseline value (5,906 pg/mL) were associated with better median progression free survival (5.3 vs. 4.0; p = 0.029). Conclusions: Optimal inhibition of VEGF was associated with a better prognosis in this clinical setting. Interestingly, SDF1alpha was upregulated through the treatment. Their baseline levels were unexpectedly associated with a better prognosis. Changes of EPCs or CECs through treatment were not of prognostic value. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Essex Pharma, Novartis, Roche Essex Pharma, Roche AstraZeneca, Novartis
The long term follow-up of a prospective randomised controlled trial of nutritional therapy in head and neck cancer patients submitted to radiotherapy
Authors: P. Ravasco RD, I. Monteiro Grillo, M. Camilo
Journal: Journal of Clinical Oncology (2008)

17000 Background: A randomized controled trial conducted in 75 head-neck cancer (HNC) patients, proved individualized nutritional counseling to be the most effective regimen in reducing RT toxicity, improving nutritional intake & status, & Quality of Life, persisting at 3 months after intervention. The present aim was to assess survival & late RT toxicity after a long term follow-up. Methods: Original study groups comprised: G1=25 received individualized nutritional counseling & education (regular foods), G2=25 ad lib+2 polymeric protein supplements & G3=25 ad lib intake. Some data was collected from patients’ records at follow-up appointments every 3–6 months; in addition, validated questionnaires to assess symptoms were used at programmed interviews after a median follow-up of 3.8 (range 2.0–6.3) yrs (PR). Analyses, per group & in-between group comparisons were adjusted for cancer stage, age, follow- up time, & survival. Results: Kaplan Meier method was used to calculate survival curves: in G1, 4 (16%) patients died, in G2 there were 8 (32%) deaths & 12 (48%) patients died in G3, p<0.05. Late RT toxicity (permanent xerostomia and/or taste alterations) was higher in G3 & G2 by comparison to G1, p<0.04; those symptoms were experienced and/or reported by 10 (80%) of G3 patients, by 12 (72%) of G2 patients and by 10 (52%) patients in G1: G3≈G2>G1, p=0.05. Conclusions: This study is the first to convey information on long term follow-up designed to assess the possible effectiveness of nutrition as adjuvant therapy throughout RT treatment in HNC patients; altogether early individualized nutritional counseling & education seems to improve well-being and possibly prognosis. No significant financial relationships to disclose.
A first-in-human, first-in-class, phase (ph) I study of systemic Hedgehog (Hh) pathway antagonist, GDC-0449, in patients (pts) with advanced solid tumors
Authors: P. M. LoRusso, C. M. Rudin, M. J. Borad, L. Vernillet, W. C. Darbonne, H. Mackey, J. F. DiMartino, F. de Sauvage, J. A. Low, D. D. Von Hoff
Journal: Journal of Clinical Oncology (2008)

3516 Background: Aberrant Hh signaling pathway activation has been implicated in a variety of cancers via both Hh ligand-independent and ligand-dependent overexpression. GDC-0449 is a first-in-human, first-in-class, potent systemic inhibitor of Hh signal transduction. Methods: Refractory solid tumor pts were enrolled in a 3+3 ph I study to evaluate safety, tolerability and pharmacokinetics/pharmacodynamics (PK/PD). GDC-0449 was administered orally as a single dose on Day 1 with a 1-week PK break, and then once daily continuously (cycle 1=35 days). Surrogate tissues were assessed for the expression of Hh downstream target gene, Gli1. Results: 19 pts were treated: 150 mg/day (n=7), 270 mg/day (n=9), and 540 mg/day (n=3); median pt age 63 yrs (range 39–84) with ECOG performance status 0–2. There have been no dose-limiting toxicities. Reversible drug-related Gr 3 hyponatremia and fatigue (1 each) were reported. One partial response (150 mg) in basal cell carcinoma (BCC) and 2 stable disease (270 mg) in BCC and adenocystic carcinoma were seen. Unexpectedly high plasma drug concentrations at the 150 and 270 mg dose levels led to the expansion of those cohorts. GDC-0449 PK properties showed a prolonged terminal half-life and drug accumulation, which resulted in surprisingly similar mean steady state plasma concentrations (30–35 μM) across dose levels. Gli1 was down modulated >2-fold in skin biopsies from 11 of 14 pts analyzed. Conclusions: The Hh antagonist GDC-0449 was evaluated at 3 dose levels and demonstrated a unique PK profile. Continuous oral dosing at 150 mg/day demonstrated safety, effective PK concentrations, PD activity, an objective response and clinical benefit, and was selected for ph II studies. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology Genentech™ BioOncology Genentech™ BioOncology Genentech™ BioOncology Genentech™ BioOncology
Towards rapid and cost-effective point-of-care detection of TMPRSS2:ERG fusion transcripts in urine via a novel methodology.
Authors: Eugene J.H. Wee, Kevin M Koo, Paul N. Mainwaring, Mattias Trau
Journal: Journal of Clinical Oncology (2015)

11063 Background: The TMPRSS2:ERG gene fusion is a highly-specific prostate cancer biomarker which is present in about 50% of all prostate cancer cases. The present use of serum PSA for prostate cancer screening is controversial due to its lack of specificity as a screening biomarker. In contrast, the presence of TMPRSS:ERG fusions could offer better screening potential. However, current detection methodologies of TMPRSS2:ERG, such as RT-PCR or FISH, are time consuming, expensive and require specialized equipment. Therefore, a new rapid and cost-effective point-of-care detection methodology is needed to enhance and enable the clinical utility of TMPRSS2:ERG and other cancer-related fusion transcripts. Methods: We developed a methodology by combining robust isothermal amplification with a novel readout based on amplified DNA-mediated bridging flocculation. This instrument-free visual evaluation of successful amplification complements the binary biomarker characteristic of TMPRSS2:ERG to give a simple positive/negative outcome. Results: The method is sensitive to as few as 105 copies (single cell level) of TMPRSS2:ERG fusion transcripts. We were also able to detect fusion transcripts in both whole urine and urinary sediments. Finally, to demonstrate clinical utility, the method was applied to 10 metastatic, castration-resistant prostate cancer urine specimens and results were validated with standard PCR-based methods. Conclusions: A simple, rapid ( ≤ 90 min) and inexpensive ( ≤ $5 USD) assay was developed to detect TMPRSS2:ERG fusion transcripts in urine. The approach may have broader applications in detecting other gene fusion events in prostate cancer or other cancers to enable quick and convenient clinical decisions.
Stromal reaction of adenomyosis protects from uterine endometrial cancer invasion to myometrium
Authors: H. Fujiwara, T. Nishisaka, T. Urabe, H. Miyoshi, Y. Kudo
Journal: Journal of Clinical Oncology (2007)

16064 Background: It is unclear that stromal reaction plays role in endometrial cancer (Em Ca) invasion to uterine muscle with adenomyosis. Methods: One hundred and five patients with Em Ca (stage 0=38, 1a=18, 1b=26, 1c=10, 2b=3, 3a=4, 3c=5, 4a=1) received operative therapy with hysterectomy. Evaluation of stromal reaction using immunohistochemical method with alpha-smooth muscle actin and h-caldesmon antibody. In case of alpha-smooth muscle actin had immunoreactivity and h-caldesmon had not immunoreactivity, there was stromal reaction with myofibroblast. Evaluation of cell proliferation, using immunohistochemical method with epidermal growth factor receptor (EGFR) by global score with six degrees and MIB-1 by labeling Index (LI). Results: All cases had stromal reaction with myofibloblast in myometrial invasion area in forty nine cases with myometrial invasion equal or more than stage 1b. Em Ca invaded near to and in adenomyosis lesion in eleven cases. In stroma of adenomyosis without cancer invasion, EGFR was positive in one case (9%) and global score was two (average 0.18). In contrast, EGFR was positive in eight cases (73%) with Em Ca invasion to adenomyosis stroma and global score was from two to three (average 1.6). LI of MIB-1 was from 0 to 0.2 (average 0.05) in adenomyosis stroma without Em Ca invasion and 0.2 to 0.75 (average 0.41) with Em Ca invasion. Conclusions: When Em Ca invades to adenomyosis, myofibloblast cell proliferation in stromal reaction increases more than in adenomyosis without Em Ca invasion. Stromal reaction of adenomyosis plays role in protecting from Em Ca invasion to uterine muscle and it may contribute to being good prognosis compared with Em Ca without adenomyosis. No significant financial relationships to disclose.
Quantitative analysis of 0<sup>6</sup>-methylguanine-DNA methyltransferase (MGMT) promoter methylation in patients with low-grade gliomas
Authors: A. F. Ochsenbein, A. D. Schubert, E. Vassella, L. Mariani
Journal: Journal of Clinical Oncology (2009)

2069 Background: Loss of heterozygosity (LOH) on the chromosomes 1p and 19q is associated with sensitivity to alkylating agents like temozolomide (TMZ) in patients with low-grade gliomas; whether methylation of the MGMT-promoter, a predictive factor in glioblastoma patients, also correlates with tumor response to TMZ in low-grade gliomas is unclear. Methods: We performed a retrospective analysis of patients with histologically verified low-grade gliomas (WHO Grade II) who were treated with TMZ for tumor progression at our hospital between November 1999 and November 2007. Objective tumor response was assessed by MRI at 6-month intervals. LOH of microsatellite markers on chromosomes 1p and 19q was determined by polymerase chain reaction (PCR) amplification of the matched pairs of blood and tumor DNA. A methylation-specific, primer extension based PCR method was developed to quanitatively assess the MGMT methylation status in the tumour tissue. Results: Twenty-two patients with a median age of 53 years (range 27–72) were included in the study; 59% were male. Seven patients had prior surgical resection of the tumor. Histological classification revealed 10 oligodendrogliomas, 7 oligoastrocytomas, and 5 astrocytomas. All patients were treated with TMZ 200mg/m2 day1–5 in a 4 wk cycle. Grade 3–4 hematological toxicity occurred in 32% of the patients (9% leucopenia, 23% thrombocytopenia). The progression free survival was 32 months. Combined LOH 1p and 19q was found in 14 pts; 1 patient had LOH 1p alone and 1 patient LOH 19q alone. The LOH status could not be determined in two patients and was normal in the remaining four. MGMT promoter methylation was detectable in 20 pts by conventional PCR and quantitative analysis revealed a methylation status between 12%-100%. The volumetric response to chemotherapy analyzed after 6 months by MRI correlated with the level of MGMT promoter methylation (p = 0.012). Conclusions: Quantitative methylation-specific PCR of the MGMT promoter correlates with radiological response to chemotherapy with temozolomide in WHO grade II gliomas. No significant financial relationships to disclose.
Ibandronate in the treatment of patients (pts) with breast cancer (BC) with metastatic bone disease (MBD): Final results of a large-scale noninterventional study (NIS).
Authors: I. J. Diel, T. Hesse, C. A. Lerchenmuller, M. Schmidt
Journal: Journal of Clinical Oncology (2010)

1026 Background: Bisphosphonates (BP) are standard care for BC pts with MBD. In randomized clinical trials (RCT) ibandronate (IBA), a BP available in IV and oral formulations, demonstrated sustained effects on skeletal related events (SRE) and bone pain with a low incidence of renal adverse events. To verify those results under real life conditions, a large-scale NIS was conducted in Germany. Methods: BC pts with MBD received 6 mg IBA IV every 3-4 weeks or 50 mg of oral IBA once daily (at the physician's discretion) for up to 24 weeks. Pain severity (VAS), analgesic use, SRE, and renal function (estimated creatinine clearance, eCrCl; Cockcroft-Gault formula) were recorded in 4-week intervals. Results: 3,515 pts, mean age 63.6 +11.7 years, were evaluated. 2,320 (66%) were BP-naïve; 418 (12%) had received prior treatment with IBA, 777 (22%) with other BPs, including zoledronic acid (ZOL) (503; 14%) and pamidronate (256; 7%). At baseline, mean pain severity (VAS) was lower for pts pretreated with IBA (2.5 ± 2.1) compared to BP-naïve pts (3.2 ± 2.4; p < 0.0001) or pts pretreated with other BPs (3.1 ± 2.4; p < 0.0001) and analgesic use was less frequent (38% vs. 47% and 44%, respectively). For pts evaluable for renal function throughout the observation period, mean baseline eCrCl was significantly lower in pts pretreated with ZOL (72.4 ± 31.7 ml/min) than in BP-naïve (79.5 ± 30.7 ml/min; p < 0.0001) or IBA-pretreated pts (77.8 ± 28.8 ml/min; p > 0.0087). In pts reporting pain at baseline, mean pain severity decreased on IBA treatment throughout the observation period (3.1 ± 2.4 to 2.3 ± 2; p < 0.0001). In parallel, there was an overall reduction of analgesic use with 57% of pts not requiring analgesics at the last observation. SRE were rare (7%), irrespective of prior treatment. Changes in renal function during IBA treatment were small and balanced across all subgroups. Overall tolerability of IBA treatment was rated as good or very good by 98% of physicians. Conclusions: In this NIS in BC pts with MBD, the largest-to-date study with IBA, IV, and oral IBA showed marked and sustained pain relief with an overall reduction of analgesic use and a renal safety profile comparable to results of RCT. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Roche Roche Amgen, Novartis, Roche Roche Roche
Use of global expression profile from non-small cell lung carcinoma (NSCLC) surgical samples to predict response to pemetrexed (P)
Authors: J. De Castro, C. Belda-Iniesta, R. Machado-Pinilla, P. Cejas, V. Rodriguez-Fanjul, E. Casado Sáenz, J. Feliú, L. G. Paz-Ares, M. González-Barón, R. Perona
Journal: Journal of Clinical Oncology (2008)

2542 Background: We have evaluated the global profile of expressed genes associated to P response in resected NSCLC. Methods: 120 surgical samples were obtained from stages I to III in NSCLC patients. Each sample was divided in two parts: one was frozen to preserve RNA integrity and other one was kept in culture media (RPMI/HAMF-12 plus 10% FCS) and subsequently subjected to enzymatic digestion to disperse tumor cells. Then, cells were cultured in 96-well dishes (previously coated with 1% agarose in order to avoid cell growth), by quadruplicates in 5 increasing doses of P. Parallel studies were carried with NSCLC cells lines in order to establish the range of sensitivity to the drug and therefore classify the tumor samples as resistant or sensitive to P. Viability of cells was estimated after 8 days of treatment by cell staining with alamar-blue. Tumor samples were classified as resistant when the IC50 was not reached at the maximum dose of P used. Total RNA was extracted from the corresponding frozen samples, cDNA was synthesized, followed by an in vitro transcription (IVD) and the labeled cRNA was hybridized into a Codelink whole genome platform array. Results: In a preliminary study of 58 out of 120 patients, we have found 189 genes predicting in vitro response to P treatment. The Bioarray analysis was carried out with the Codelink expression analysis software. BRB array tools software was used to normalize the CT data and select those genes whose expression levels were changed at least two fold over the average values. A class comparison analysis statistically significant (p <0.001), was performed to identify 189 genes differentially expressed between groups. From the total surgical samples, 22 were sensitive and 36 resistant to P by the drug sensitivity assay. In a non-supervised hierarchical clustering, 16 samples were classified as sensitive and 31 as resistant to P. Conclusions: The specificity of our microarray screen is 76% (sensitive) and 84% (resistant), respectively, indicating that is a valid model to correctly classify the response to P in NSCLC surgical samples based upon gene profile analysis. This strategy would be adequate for predicting outcome of treatment of NSCLC patients with P. Complete analysis from 120 patients will be reported at the meeting. No significant financial relationships to disclose.
Adjuvant gemcitabine alone versus gemcitabine-based chemoradiation after curative resection for pancreatic cancer: Updated results of a randomized EORTC/FFCD/GERCOR phase II study (40013–22012/9203)
Authors: J. L. Van Laethem, F. Mornex, D. Azria, G. van Tienhoven, M. Mauer, M. Praet, V. Budach, P. Hammel, E. Van Cutsem, K. Haustermans
Journal: Journal of Clinical Oncology (2009)

4527 Background: The role of adjuvant chemoradiotherapy (CRT) in resectable pancreatic cancer is debated. This randomized phase II intergroup study demonstrated the feasibility and tolerability of a gemcitabine-based CRT regimen after R0 resection of pancreatic head cancer (Proc ASCO 2008, 4514). Long term and survival data are now reported. Methods: Patients were randomized within 8 weeks after surgery to receive either 4 cycles of gemcitabine 1000 mg/m 2 given over 30 minutes every 3 weeks (control arm) or gemcitabine 1000 mg/m 2 for 2 cycles followed by weekly gemcitabine 300 mg/m 2 with concurrent radiation of 50.4 Gy given in 28 fractions of 1.8 Gy (experimental arm). The co-primary endpoints were completion of treatment and tolerability. Secondary endpoints were late toxicity, DFS and OS. Results: Between 9/04 and 1/07, 90 patients were randomized by 29 centers (45:45). Treatment arms were balanced in terms of patient/tumour characteristics. Follow-up was equal for both arms with an overall median follow-up of 27.1 months. In the control arm, 5 patients were ineligible, including 2 not treated. In the experimental arm, CRT was delivered to 36 of 45 patients (80%). Treatment was completed per protocol by 86.7% and 73.3% (80% CI 63.1–81.9%) of randomized patients in the control and experimental arms, respectively. Grade 4 toxicity was 0% and 4.4%, respectively. In the CRT arm, 2 patients experienced grade 3 late toxicity (anorexia 1 and epigastric pain 1). In the CRT experimental arm, 33 DFS events were noted and 23 deaths versus 34 and 24, respectively, in the control arm. Median DFS was 12 months in the experimental arm vs. 11 months in the control arm (p=0.6). Median overall survival was 24 months both in the experimental arm and the control arm. Distant progression was similar in both arms while the rate of first local recurrence was lower in the chemoradiation arm (11 vs 24 %, p=0.16). Conclusions: Post-op modern gemcitabine-based CRT is feasible and well- tolerated after long-term follow-up, and a larger trial should assess its true benefit to that of standard gemcitabine alone. [Table: see text]
Predictors and outcomes in hemodialysis (HD) patients with peripheral vascular disease: Results from the dialysis outcomes and practice patterns study (DOPPS).
Authors: R Saran, Michel Jadoul, S Satayathum, N. Lameire, A Saito, Takashi Akiba, N Ginsberg, Bw. Gillespie, M Keen, EW Young, S Rajagopalan
Journal: Journal of the American Society of Nephrology (2003)