tbuckley/cabot-search huggingface dataset:
Results of inverse strategy using systemic chemotherapy (CT) first, liver resection second, and primary tumor resection last for patients with advanced synchronous liver metastases (ASLM) from colorectal cancer (CRC)
Authors: A. D. Roth, L. Rubbia-Brandt, P. Majno, A. Andres, P. Gervaz, A. Allal, P. Morel, G. Mentha
Journal: Journal of Clinical Oncology (2005)

3683 Increasingly efficient CTs allow to consider patients (pts) with ASLM as potentially curable despite the number, the size and the bilobar localization of the lesions. In some pts, however, ASLM progress during treatment of the primary CRC, hindering the intent to cure. We investigated the possibility of giving ASLM-oriented CT first, resecting ASLM second, and removing the primary last. Patients and treatments: 20 pts (11 men) with non obstructive CRC, 50% rectal tumor, median age 56 years (37–68), were treated according to this protocol. The median number of ASLM was 5 (2–21), median size 4 cm (1–14) and the ASLM were bilobar in 70%. Pts were treated with 2 to 6 cycles (median 3) of CT before surgery. 12 pts received OCFL (oxaliplatin 70mg/m2 d1,15, CPT11 100mg/m2 d8,22, leucovorin (LV) 30mg and 5FU 2.3g/m2/24h d1,8,15,22 q5w), 7 OCX (like OCFL with capecitabine 800mg/m2/d d1–28 instead of 5FU/LV) and 1 XELOX (oxaliplatine 130mg/m2 d1, capecitabine 2g/m2 d1–14 q3w). 16 pts were resected. All but two rectal cancer pts received preoperative radiotherapy. Results: 4 pts (20%) could not have their ASLM resected: 1 died of septicemia during CT, 3 progressed of whom 2 died at 5 and 8 months, and 1 was alive with disease (AWD) at 41 months.16 pts (80%) had complete removal of ASLM, 6 by a two-step liver surgery and 2 after right portal embolization. All of these patients had their primary CRC resected, with downstaging observed by histology in 75%. 9 (56%) were free of disease and 4 (25%) AWD at a median follow up of 24 months. 4 pts underwent additional removal of metastases (liver, ovary and lung). Two pts died of disease progression at 44 and 53 months and 1 after repeat surgery at 14 months. Actuarial 1- and 3-year survival rates of resected pts were 100% and 89%, respectively. Conclusions: Initial ASLM-oriented CT followed by ASLM removal appears as a promising concept. It allows to downstage ASLM, to select pts with responding disease avoiding unnecessary surgery, and to deliver state-of-the-art preoperative rectal radiotherapy without the fear that liver metastases will meanwhile progress beyond the possibility of cure. No significant financial relationships to disclose.
The novel non-boronic proteasome inhibitor S-2209 induces apoptosis and growth arrest in multiple myeloma cells
Authors: P. Baumann, K. Müller, S. Mandl-Weber, R. Doblhofer, A. Ammendola, J. Leban, F. Oduncu, R. Schmidmaier
Journal: Journal of Clinical Oncology (2008)

8581 Background: Bortezomib is the first approved member of a new class of antineoplastic agents, the proteasome inhibitors. Anti- myeloma activity of Bortezomib monotherapy is only moderate and specific toxicity often limits its clinical use. Further proteasome inhibitors need to be developed. Methods: S-2209 was characterized by several assays. Inhibition of the chymotryptic activity of the human 20S proteasome was determined with the in-vivo protease inhibition assay. Additionally, proteasome inhibition was determined in isolated PBMCs from S2209-pretreated wistar rats. Inhibition of NFκB activity was determined using a NFκB reporter gene assay. Cell growth rates of MM cells were measured with the WST-1 assay. Induction of apoptosis was shown by annexin-V-FITC staining. Intracellular signal modulation was demonstrated by western blotting. Toxicity of the substance was tested in male wistar rats. Results: The proteasome inhibition assay revealed an IC50 at ∼220nM. The NFκB inhibition assay using an A549-NFκB-SEAP transfected cell line showed an EC50 of 0.9μM. Upon incubation with S-2209, cell growth as well as cell proliferation in MM cell lines was significantly inhibited (IC50 100nM - 600nM). Furthermore, the incubation with S-2209 resulted in strong induction of apoptosis in all four MM cell lines (IC50 at ∼300nm) as well as primary cells. Western blotting revealed caspase-3 cleavage and upregulation of p53 and increased phosphorylation of IκB. No induction of apoptosis was detected in PBMCs from healthy humans. Despite the administration of 5, 10 or 15mg/kg/day in wistar rats, no toxicity with respect to body weight, hepatic enzymes (ALAT ASAT, ALP), creatinin or hemoglobin was seen. Proteasome inhibition in white blood cells isolated from the treated rats was higher in the S-2209 treated animals than in control animals treated with 0.1mg/kg/d bortezomib (89% vs. 70% respectively). Conclusions: The proteasome inhibitor S-2209 inhibitis MM cell growth and induces apoptosis. This is accompanied by a strong inhibition of proteasome and of the NFκB activity. Because S-2209 shows a favourable toxicity profile in vivo, further clinical development of this promising drug is urgently needed. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration 4SC
Phase II trial of panobinostat (LBH589) in patients (pts) with refractory metastatic colorectal cancer (MCRC).
Authors: Philip Jordan Gold, David A. Smith, Desiree Iriarte, Barry Boatman, Henry G. Kaplan
Journal: Journal of Clinical Oncology (2012)

582 Background: LBH589 is a novel histone deacetylase inhibitor (HDACi) which induces apoptosis of tumor cells. LBH589 has been shown to cause regression of colon cancer in animal models and phase I trials have shown the agent to be well tolerated, providing rationale for studying this agent in pts with MCRC. Methods: This was a multicenter, open-label phase II study of single agent LBH589 in patients with MCRC who failed at least 2 prior regimens for metastatic disease. Measurable disease, adequate organ function and ECOG performance status of 0-2 were required. Pts received LBH589 30mg po on M/W/F until disease progression. Pts were evaluated for toxicity every 2 weeks and for response every 8 weeks. The primary endpoint was overall survival. Secondary endpoints included response rate, time to progression (TTP), and toxicity. Results: 29 pts were enrolled (16 male, 13 female). The median age was 59 (range 41-76). The median number of prior treatment regimes was 3 (2-11). The median survival was 5.1 months (range 1-24+). There were no objective responses. 3 pts had SD at 8 weeks. The median TTP was 7.7 weeks (range 1-38.). Six pts had grade 4 thrombocytopenia requiring platelet transfusion. Nine pts required dose reductions for toxicity. Conclusions: Single-agent LBH589 was not associated with objective tumor responses in this heavily pre-treated pt population. However, the median survival was comparable to that seen in other trials of single agent targeted therapy in the treatment of refractory MCRC. Thrombocytopenia was significant, and may complicate potential trials of combination therapy.
Social support and depression in patients with breast cancer during 1 year from diagnosis compared with the general population
Authors: M. Lee, E. Lee, J. Ro, H. Kang, K. Shin, K. Lee, K. W. Chung, S. Kim, Y. Yun
Journal: Journal of Clinical Oncology (2008)

9612 Background: The objective of our study was to observe the change of social support and depression during 1 year from diagnosis in comparison with the general population and to identify whether the change of social support predicts the change of depression in patients with breast cancer. Methods: Social support, depression and health-related quality of life (HRQOL) were assessed at the time of diagnosis, and 1 month, 3 months, and 1 year after diagnosis in 399 newly diagnosed breast cancer patients using Medical Outcome Study Social Support Survey (MOS-SSS), Zung Self-rating Depression Scale (SDS), and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30. Results: Of 399 patients, 299 completed the baseline questionnaire (response rate, 74.9%) and 212 completed at 12 months after diagnosis (70.9%). Compared with the general population, social support at baseline in patients was similar and significantly lower at 12 months (p<0.01). On the other hand, compared with the general population, baseline depression in patients was significantly higher (p<0.001) and depression at 12 months was similar. Multivariate analysis showed that the change of social support between baseline and 12 months from diagnosis was negatively associated with change of depression. More social supports the patients had during the treatment period, better improved their depression was. The change of depression was negatively associated with changes of QoL functioning in all subscales in QLQ-C30. Conclusion: Although depression in patients with breast cancer improves at 1 year after diagnosis when acute treatment effects are declined, deficits in social support are predictors of depression during the treatment period. The results indicate that high level of depression may need interventions that target their needs related to social support. It may also improve breast cancer patient’s QoL functioning. We suggest that further study on the association between social support and depression is required. No significant financial relationships to disclose.
Prognostic significance of Wnt signaling pathway molecules in nongastric GIST patients: A tissue microarray-based (TMA) analysis.
Authors: Javier Martin Broto, Rafael Ramos, Javier Martinez-Trufero, Silvia Calabuig, Carlos Horndler, Antonio Casado, Luis Ortega, Luis Miguel Gonzalez de Sande, Francisco Izquierdo, Antonio Gutierrez, Angeles Sala, Aitziber Ugalde, Claudia María Valverde, Ines de Torres, Ferran Losa, Remei Blanco, Rosa Maria Sanchez Gomez, Ricardo Cubedo, Juan Antonio Carrasco, Carmen Balañá
Journal: Journal of Clinical Oncology (2013)

10529 Background: Pathogenesis in GIST could be related to cancer stem cell hypothesis (highly chemo resistant, very uncommon complete responses, kit is stem cell marker) even though no stem cell component in GIST has been yet demonstrated. Wnt signaling regulates proliferation in some normal and cancer stem cells as it occurs with intestinal epithelium. We have explored the prognostic significance of several Wnt signaling pathway and related molecules. To investigate the prognostic significance of β-Catenin, CDC25A, ROR2, p53, CUL4A, AKT-p and VEGFR-3 by immunohistochemical (IHC) analysis in TMA specimens of 101 non-gastric GIST. Methods: Data of diagnostic, therapeutic and follow-up procedures stem from the GIST Registry of GEIS. Cytoplasmic and/or membrane staining was deemed positive for ROR-2, VEGFR-3 and p-AKT antibodies whereas nuclear staining was positive for β-Catenin, CDC25A, CUL4A and p53 antibodies. IHC positive cases were considered if they displayed staining in at least 10% of cells. Statistical analyses for correlation of protein expression with known prognostic variables (mitoses, size) were performed with Mann-Whitney U test. Results: A subset of 101 non-gastric localized GIST patients was selected (90 intestinal, 15 others: mainly rectum and omentum). The median age was 62 y with gender distribution of 59M/42F and the median of follow-up was 36 months. The positivity for each protein was distributed as follows: ROR-2 63%, p-AKT 55%, β-Catenin 53%, VEGFR-3 22%, CDC25A 20%, p53 8% and CUL4A 7%. A statistically significant correlation was found between mitoses and β-Catenin (median 5 if negative/ 10 if positive, p=0.028); VEGFR-3 (median 5 if negative/21 if positive, p=0.002); CUL4A (median 6 if negative/60 if positive, p= 0.027). Additionally, tumor size was statistically correlated with VEGFR-3 (median 7 if negative/11 if positive, p=0.007). Conclusions: VEGFR-3, β-Catenin and CUL4A are correlated with the highest proliferative non-gastric GIST. These findings deserve further analysis and lead to potential new molecular therapeutic targets in GIST. This study was partially granted by Buesa Grant of GEIS.
Sensitivity and specificity of signs and symptoms to determine the risk of death associated with gastric cancer patients.
Authors: Gustavo A. Rojas Uribe, Jose Martinez, Paula Londono
Journal: Journal of Clinical Oncology (2016)

26 Background: Risaralda (Colombia) has an irregular pattern in the risk of death for gastric cancer; for these reasons, the survival analysis was made with the information of gastric cancer patients treated in Oncólogos del Occidente clinic during 2014. Methods: A cross-sectional study was done with oncologic patients in order to evaluate the replicability of a binary list of signs and symptoms of gastric cancer, also its corresponding principal component factors for the proper identification of their dimensions. A sum of the set of signs and symptoms was done. This total sum of signs and symptoms was used to identify the sensitivity and specificity of each of cut-off related to the patient’s death condition. This evaluation was established by the ROC (Receiver Operating Characteristic) methodology, which is a graphic representation of the sensitivity in front of the specificity for a classifying binary system that may vary the threshold of rejection. The analysis was done in Stata. Results: There were 173 patients, of whom 69.9% were males; the group with the highest incidence was the 60-69 years old group (32%); These patients referred 5 signs and symptoms that conformed the list from which every single item behaved as a binary variable. Cronbach’s alpha was 0.62 and the analysis of principal components factors defined only one dimension. The ROC curve established a sensitivity of 65% and a specificity of 72% for the determination of the risk of death with a score equal or higher to 4 in the sum of the list of signs and symptoms. Adding the gender, the sensitivity increased to 66%. In the ≥ 80 years old group the sensitivity was 70.9%, meanwhile the group of ≥ 40 years old the sensitivity was 93%. Conclusions: The list of signs and symptoms could be a diagnostic technology relevant for unspecific clinical but has an important high frequency in Colombia for gastric cancer patients. The sensitivity was very variable according to the age range, being more sensible and specific for the patients of the ≥ 40 years old group.
Development of a Web-based community cancer survivorship program.
Authors: M. Pan, A. T. C. Lee, E. Ahmed
Journal: Journal of Clinical Oncology (2011)

e19573 Background: The rising population of cancer survivors demands more efficient and effective delivery of cancer survivorship care that integrates multiple disciplines and novel communication methods, especially in community settings where eight-five percent of cancer patients receive their cancer care. In response to the diverse cultural and ethnic backgrounds of our patients within Northern California Kaiser Permanente, a web-based cancer survivorship program was developed, with educational classes and workshops to reinforce the adherence of cancer survivorship care. Methods: A cancer survivorship program was developed within a comprehensive cancer website of over 500 pages, including: managing short and long-term side effects related to cancer treatment, ways to reduce risk of cancer relapse, management of social and emotional issues, complementary and alternative medicine, as well as palliative care, and others. Each category covers a broad range of issues such as nutrition, vitamins, supplements and food in cancer management and prevention; physical activities and reduction of cancer relapse; smoking and alcohol cessation, antioxidants and anti-inflammatory drugs; cancer prevention, and others. We also developed cancer survivorship workshops to educate cancer patients and their families regarding healthy lifestyles and its importance in cancer prevention and reduction of recurrence. We used the web-based program as a tool to develop additional classes to further promote understanding of medication compliance and palliative care. Results: A steady monthly increase in unique visitors and visits were observed after the launch of the web-based program. In 2010, visits ranged from an initial 550 to a peak of more than 2200 visits per month. In the 12 months after its launch, our cancer survivorship website generated a broad readership with 9089 unique visitors, 16,500 total visits, 62,600 pages viewed, 321,000 hits and much accolade from others who aspire to duplicate this website. Conclusions: A web-based community cancer survivorship program coupled with classes and workshops is a practical and effective method for delivering care to our cancer survivors. The web-based program will be demonstrated during the presentation.
Regulation of Dietary Supplements
Journal: JAMA (1993)

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The relationship between circulating VEGF level and outcome of advanced Chinese NSCLC treated with gefitinib
Authors: Y. Y. Zhao, C. Q. Zhang, L. P. Lin, X. Wu, J. X. Wu, F. H. Wang, H. Y. Zhao, Z. Z. Guan, L. Zhang
Journal: Journal of Clinical Oncology (2008)

19074 Background: VEGF represents a novel molecular target in NSCLC. We aimed to evaluate the association between VEGF plasma concentration, and response, overall survival of Chinese NSCLC patients treated with orally gefitinib (250 mg). Methods: Twenty patients’ blood samples were obtained from Chinese registration trial of gefitinib in NSCLC. Plasma VEGF before treatment (D0) and after treatment on D7, D14 was measured using a commercially available VEGF enzyme-linked immunosorbent assay kit (Quantikine human VEGF, R&D Systems, Minneapolis, MN) according to the manufacturer’s instructions. One-Way ANOVA, Kaplan-Meier method and Cox Regression were used in the statistical analysis. Results: Averaged plasma VEGF concentration on baseline (D0) and D7 and D14 were 92.68 ± 11.91 pg/mL, 112.36 ± 19.12 pg/mL and 159.14 ± 59.71 pg/mL respectively (P=0.406). VEGF concentration on D0 for the patients with CR+PR, SD, and PD were 124.55 pg/mL, 90.18 pg/mL and 74.32 pg/mL respectively (P=0.226) and changed to 66.36 pg/mL, 75.91 pg/mL, 237.37 pg/mL on D14 respectively (P=0.406). D14/D0 rate was categorized by <1 and ≥1. Univariate analysis showed patients with D14/D0 <1 (MST 14.17 months) had a longer overall survival than patients with D14/D0 ≥1 (MST 1.60 months) with P value 0.0008. Multivariate analysis showed that OS was associated with D14/D0 rate (P=0.09), gender, histology and smoking history were not significant. Conclusion: D14/D0 <1 was independently associated with better OS in gefitinib-treated NSCLC patients. Our findings suggest that plasma VEGF maybe another effective predictive factors of overall survival of gefitinib in NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline, Lilly, Roche Bayer, Novartis
Change in <i>MGMT</i> methylation status between first and second surgery for recurrence: Clinical implications
Authors: A. A. Brandes, E. Franceschi, A. Tosoni, A. Fioravanti, R. Agati, A. Andreoli, V. Mazzocchi, L. Morandi, S. Bartolini, M. Ermani
Journal: Journal of Clinical Oncology (2009)

2027 Background: MGMT promoter methylation status is known to be a potent prognostic factor in newly diagnosed glioblastoma (GBM) patients (pts). However, it is not yet clear whether and, if so, how MGMT methylation status may change; nor is it known whether the prognostic role of this epigenetic feature is retained during the disease course. Methods: A retrospective analysis was made using a database of 614 GBM pts treated prospectively from January 2000 to August 2008. We evaluated only patients who met the following inclusion criteria: age ≥18; PS 0–2; two distinct surgical procedures; histological diagnosis of GBM both at first and at second surgery for recurrence; postoperative treatment consisting of: a) radiotherapy (RT) followed by temozolomide (TMZ) until 2005, and b) TMZ concurrent with and adjuvant to RT after 2005; a time interval ≥3 month between first and second surgery. The study aim was to evaluate changes of MGMT status during the course of GBM. The log-rank test was employed to evaluate the significance of the prognostic variables. The percentages of MGMT methylated cases at first and second surgery were compared using the McNemar test. Results: MGMT status, evaluated at first and second surgery in all 44 pts (M:F 32:12, median age: 49 years, range: 27–67), was assessable in 38 (86.4%) cases: MGMT promoter was methylated in 13 (34.2%) pts at first surgery. MGMT methylation status, unchanged in 63.2% of second surgery samples, changed more frequently in methylated than in unmethylated pts (61.5% vs 24%, p = 0.03). The median survival was 24.3 months (95% CI: 20.8–27.7), being 35.2 months (95% CI: 10.1–60.2) and 21.9 months (95% CI: 17.3–26.5) for pts with methylated and unmethylated MGMT assessed at first surgery, respectively (p = 0.04). However, MGMT status at second surgery was no longer prognostic for survival (p = 0.1). Conclusions: Significant changes in MGMT methylation status during the course of GBM occur more frequently in MGMT methylated than unmethylated cases. Moreover, while MGMT methylation status is prognostic at first surgery, it appears to be of no prognostic utility at the time of second surgery. No significant financial relationships to disclose.