tbuckley/cabot-search huggingface dataset:
Lack of concordance between I-111 pentreotide (PEN) status and immuno-histochemistry (IHC) status for somatostatin receptors type 1, 2, and 3 in neuroendocrine tumors (NET)
Authors: A. C. Palhares, F. P. Costa, A. J. Belfer, C. E. Bacchi, S. H. Jokh, P. M. Hoff, A. C. Buzaid, F. C. Maluf, R. J. Marques, C. Dzik, L. F. Lopes
Journal: Journal of Clinical Oncology (2007)

15060 Background: The use of somatostatin analogues (ST) in the treatment of NET is recommended for functional and non- function slow progressing tumors that present with positive PEN. The goal of the study was to determine if expression of ST receptors type 2, 3 and 1 in NET tumors by IHC predict the PEN status and response to ST. Methods: Retrospective analysis of paraffin blocs from primary or metastatic sites and PEN imaging from 39 patients with a diagnosis of NET confirmed by independent pathology review. IHC analysis was performed in a central laboratory using antibody ST receptor type 1 from Neomarkers and type 2 and 3 from Affinity Bio Reagents. Status for each receptor type was reported as positive or negative, diffuse or focal and by % of positive cells. All slides were reviewed by the same pathologist. PEN images were submitted to an independent radiology review and reported as positive or negative and the signal intensity was graded from 1 to 4. Investigators were blinded to receptor and PEN status. This concordance analysis study was designed with a power to detect at least 60% correlation between receptor and PEN status with type I error of 5% and a type II error of 20%. Results: There was no correlation between receptor and PEN status ( Table ). Furthermore, there was no significant correlation between PEN and receptor types 3 and 1 in receptor type 2 negative patients (p=0,54, p=0,14, respectively). There was no correlation between receptor type status and PEN positive intensity. No independent or multivariate characteristics by IHC can correlate to PEN status in this cohort. Conclusions: Commonly used antibodies for IHC detection of receptors type 2, 3 and 1 used in this study failed to correlate with PEN. These results do not support the use of IHC as a substitute for PEN with respect to prediction of ST activity in NET. [Table: see text] No significant financial relationships to disclose.
Solitary fibrous tumor: A retrospective analysis on 65 patients from a reference center
Authors: E. Palassini, S. Stacchiotti, P. Collini, S. Pilotti, U. Pastorino, G. Cantù, M. Fiore, A. Gronchi, P. G. Casali
Journal: Journal of Clinical Oncology (2009)

10572 Background: Solitary fibrous tumors (SFT) are very rare mesenchymal tumors with an unpredictable malignant potential. We retrospectively reviewed the long-term outcome of patients operated on at the Istituto Nazionale Tumori (INT), Milan, in a 18-year time span. Methods: All patients who underwent surgery at INT from 1990 to 2008 for primary SFT or first local relapse were retrospectively reviewed. Clinical and pathologic data were recorded. Local recurrence, distant metastases and overall survival were analyzed both from time of diagnosis and from time of local recurrence/distant metastasis. Biomolecular studies are ongoing for those cases whose frozen material is available. Results: 65 patients were identified (M/F: 33/32 - age: mean 54 yrs, range 19–85 yrs - site: peritoneum 45%, pleura 21%, lower-limb 17%, other 18% - extension at diagnosis: localized 94%, locally-advanced/unresectable 3%, metastatic 3% - size: median 11 cm, range 2–40 cm). The median follow-up was 54 months (range 0–185 months). The overall 5/10-year survival (OS), local relapse-free survival (LRFS) and metastasis-free survival (DRFS) were, respectively, 92/91%, 89/86%, 94/89%. The 5-year OS, LRFS, DMRFS after the first local relapse were, respectively, 100%, 67%, 89%. The overall incidence of metastases was 17% (lung was the commonest site). The 5-year post-metastasis OS was 45%. Multivariate analysis on clinical and pathologic/molecular prognostic factors is ongoing. Conclusions: SFT arise from a variety of anatomic sites. Surgery is curative in most patients, and local relapse has a limited impact on prognosis. Pathologic prognostic factors are under investigation to help identify the minority of patients with a poor clinical outcome. No significant financial relationships to disclose.
Impact of cytidine deaminase genetic polymorphisms on gemcitabine kinetics and toxicity in Japanese cancer patients
Authors: H. Ueno, T. Okusaka, N. Saijo, J. Furuse, H. Ishii, T. Yoshida, E. Sugiyama, S.-R. Kim, N. Kaniwa, J.-I. Sawada
Journal: Journal of Clinical Oncology (2005)

2009 Background: Gemcitabine is an anti-cancer drug effective against solid tumors. It is rapidly metabolized to its inactive metabolite 2’,2’-difluorodeoxyuridine (dFdU) by cytidine deaminase (CDA), for which several genetic polymorphisms are known. We investigated the impact of genetic polymorphisms of CDA on gemcitabine pharmacokinetics and toxicities. Methods: Two hundred fifty-two Japanese cancer patients who had not previously received gemcitabine were given a 30-min i.v. infusion of the drug at either 800 or 1000 mg/m2, and blood samples were collected before the infusion, at 3 min before the end of the infusion, and 15, 30, 60, 90, 120, and 240 min after the end of the infusion. Plasma levels of gemcitabine and its metabolite were measured by HPLC. Plasma CDA activity was also measured using gemcitabine as a substrate. Polymorphisms of the CDA gene were detected by a dideoxy sequencing method using genomic DNA obtained from peripheral blood leukocytes. Results: Two non-synonymous genetic polymorphisms of CDA - 79A>C (*2, K27Q) and 208G>A (*3, A70T) were found, and their allele frequencies were 0.207 and 0.037, respectively. Pharmacokinetic parameters and plasma CDA activities were significantly dependent on the *3 allele (Results of preliminary analysis are summarized in the Table. The data will be fixed by the meeting). In a patient homozygous for *3, very severe toxicities including grade 4 neutropenia, grade 4 thrombocytopenia, and grade 3 rash were observed. The *2 allele had no marked effects on the pharmacokinetics or toxicities of gemcitabine. Conclusions: Carriers of the CDA *3 allele have decreased clearance of gemcitabine. Attention should therefore be given to patients with the CDA *3 allele before commencing gemcitabine treatment. No significant financial relationships to disclose.
Trimodality therapy for locally advanced non-small cell lung cancer.
Authors: R. P. Lackner, A. Ganti, W. Zhen, M. S. Copur, I. A. Vaziri, M. Bolton, T. Hlavaty, K. P. Trujillo, M. A. Kessinger
Journal: Journal of Clinical Oncology (2010)

e17529 Background: Management of locally advanced non-small cell lung cancer (LA-NSCLC) lacks consensus. Trimodality therapy is promising, but concerns about its safety and deliverability persist. A retrospective analysis of patients treated with trimodality therapy for LA-NSCLC at our institution to determine outcomes was conducted. Methods: All patients with LA-NSCLC treated with neoadjuvant chemoradiation (2-3 cycles of a platinum-based doublet with 45 Gy concurrent thoracic radiation) followed by resection performed by one of two thoracic surgeons (RL, KT). Two cycles of the same chemotherapy regimen were planned post-resection. Age at diagnosis, gender, smoking history, disease stage, treatment received, surgical complications and overall survival were collected. Outcomes were compared using log- rank test. Results: This analysis includes 35 patients who met the inclusion criteria. Median age of the patients was 63 years (range: 39-84 years). Clinical stage at diagnosis was IB – 1; IIB – 1; IIIA - 23; IIIB – 9; IV – 1 (resected brain metastasis). Carboplatin/paclitaxel was administered to 27 patients. Of these 23 received standard doses (AUC 5 and 175 mg/m2 respectively), while 4 received low-dose weekly therapy. Other regimens were carboplatin/gemcitabine (n=1), cisplatin/vinblastine (n=1), cisplatin/etoposide (n=3), carboplatin/etoposide (n=1), cisplatin/VP16 (n=1). Data on 1 patient was unavailable. Resection included pneumonectomy (n=5), bilobectomy (n=3) and lobectomy (n=27). Post-operative complications were atrial fibrillation (11), pneumonia (4), ARDS (4), air leak and recurrent laryngeal nerve injury (3 each). Surgical mortality at 28 days was 8.6% (n=3). Survival ranged from 4-54.6 months (median: 15.6 months). Median survival of 27 patients (77%) receiving postoperative chemotherapy was 31.9 months. Survival at 1, 2 and 3 years was 60%, 29% and 17% respectively. Conclusions: Trimodality therapy is feasible in locally advanced NSCLC. Patients who received their entire planned treatment had a prolonged median survival. Studies evaluating proper patient selection for trimodality therapy for LA-NSCLC are needed. No significant financial relationships to disclose.
Serum level of vascular endothelial growth factor (VEGF) as an independent prognostic factor in metastatic renal cell carcinoma (MRCC)
Authors: S. Negrier, S. Chabaud, B. Escudier, A. Ravaud, C. Chevreau, J. Y. Blay, R. Delva, C. Biota, D. Perol, C. Menetrier- Caux
Journal: Journal of Clinical Oncology (2007)

5044 Background: The French Immunotherapy Group previously showed that circulating interleukin-6 (IL-6) and VEGF correlate with survival in MRCC patients (pts) (Négrier JCO 2004). We aimed to confirm the prognostic value of IL-6 and VEGF, and to test that of macrophage colony-stimulating factor (M-CSF) and macrophage inflammatory protein 3-alpha (MIP-3a) for survival in MRCC pts of good and intermediate prognoses. Patients and Methods: Pre-treatment samples were obtained from 302 MRCC pts enrolled in 2 parallel multicenter randomized cytokine trials. Baseline serum levels of IL-6, M-CSF, VEGF, and MIP3a were determined by immunoassays; their prognostic value for progression-free survival (PFS) and overall survival (OS) was tested. Characteristics of pts with a 0.15 significance level in univariate analysis (ECOG PS, prior therapy, metastatic sites and biological parameters) were entered in a multivariate Cox model. A backward stepwise procedure discriminated non-influential variables at 0.05 level. Results: Median IL6, VEGF, M-CSF and MIP3a levels were respectively 7.3 (range 0–392 pg/mL), 0.5 (0–2.3 ng/mL), 406 (0–4,785 pg/mL) and 0 (0–1,705 ng/mL). IL6 or M-CSF and VEGF (p&lt;0.0001), or IL6 and M-CSF (p=0.0005) were significantly correlated. Death occurred in 192/302 pts, with 20.9 month median OS. OS was highly correlated with IL6, VEGF and M-CSF (p &lt;0.001) but not with MIP3a (p=0.06) in univariate analysis. Only VEGF remained independently prognostic for OS in multivariate analysis (39% increased probability of death if VEGF level doubled) after adjustment on PS, time from diagnosis to metastasis, number of metastatic sites, pleural metastasis, abnormal sedimentation rate, haemoglobin and LDH levels. Similar results were found for PFS, with a hazard ratio of 1.19 for a 2-fold VEGF increase. Conclusions: The independent prognostic value of serum IL6 level is not confirmed in our cohort that excluded pts with poor outcome, but serum VEGF level appears as an independent prognostic factor, thus supporting the therapeutic interest for these pts of newly available drugs targeting VEGF receptors. No significant financial relationships to disclose.
Palonosetron (PALO) versus ondanestron/dolasetron (OND/DOL) in preventing chemotherapy-induced nausea and vomiting (CINV) in elderly patients: Combined results from 2 phase III trials
Authors: M. S. Aapro, A. Macciocchi
Journal: Journal of Clinical Oncology (2004)

8049 Background: The majority of cancer patients (pts) are elderly (age ≥ 65 yrs) with age-related increases in mortality, comorbidity, and potential for treatment complications. Therefore, simple, convenient treatment regimens are desirable in this population. PALO is a pharmacologically distinct 5-HT3 receptor antagonist which offers multiday prevention of CINV with a single 0.25-mg IV dose. To assess efficacy/safety of PALO in elderly pts, a retrospective subset analysis of randomized studies (N = 754) in pts receiving moderately emetogenic CT was conducted. Methods: The subset consisted of pts (n = 165) ≥ 65 yrs in the pooled data from 2 phase III, multicenter, randomized, double-blind trials comparing single IV doses of PALO 0.25 mg, OND 32 mg, or DOL 100 mg. Concomitant dexamethasone was administered in 3% of pts. Endpoints included complete response rates (CR: no emetic episodes [EE] & no rescue therapy) and % of pts with no EE through 5 days post-CT. Results: A greater proportion of PALO-treated pts had a CR or were emesis-free compared with those treated with OND/DOL during the 5 days post-CT. *P = 0.01 Pts in the PALO group experienced a longer time to treatment failure than pts in the OND/DOL group (P = 0.01). Fewer PALO-treated pts experienced the most common adverse events of constipation (9.8% vs 13.5%) and headache (6.1% vs 12.4%) compared with OND/DOL-treated pts; cardiac adverse events were similar and infrequent (<3%) in both groups. The adverse event profile was similar to that seen in the pts < 65 yrs. Conclusions: A single dose of PALO was more effective than OND/DOL in preventing CINV over 5 days post-CT in elderly patients. PALO's longer half-life and improved control make it a more convenient and appropriate 5-HT3 receptor antagonist for use in elderly cancer patients receiving emetogenic CT. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Helsinn Healthcare Helsinn Healthcare Helsinn Healthcare Helsinn Healthcare
Proposal of a prognostic score system for the Brazilian Osteosarcoma Treatment Group (BOTG) patients.
Authors: M. Cypriano, A. Ferraro, C. M. J. Costa, V. Odone, D. Lustosa, M. L. Borsato, A. L. Brunetto, L. M. Calheiros, J. H. Barreto, S. Epelman, E. Carvalho, W. V. Pereira, E. M. Pontes, R. J. Garcia Filho, M. T. d. S. Alves, C. R. Macedo, O. P. de Camargo, P. Pericles, V. Penna, A. S. Petrilli
Journal: Journal of Clinical Oncology (2011)

9528 Background: To identify prognostic factors in the OS patients enrolled in the BOTG studies III, IV and V. Methods: A total of 604 patients younger than 30 years of age with high grade OS (metastatic and nonmetastatic) were prospectively enrolled onto the BOTG studies III, IV and V and were retrospectively evaluated according to sex, age, time from the onset of symptoms to diagnosis, primary tumor site, presence or absence of metastases at diagnosis, tumor size (≤ 12 cm or > 12 cm), type of surgery (limb-sparing or amputation), treatment protocol, and histological response. These variables were correlated with survival and a risk score system reflecting hazard ratios of the prognostic factors was created classifying patients into three subgroups. Results: The estimated 5-year overall survival and event-free survival (EFS) rates for the 553 eligible patients were 49% and 39%, respectively. Metastases at diagnosis, primary tumor site, tumor size, type of surgery, and histological response significantly correlated with overall survival and EFS in a univariate analysis. In the multivariable analysis, metastatic disease at diagnosis, grade of necrosis, surgery type and tumor site were independently associated with survival and EFS, whereas tumor size lost prognostic significance. A risk score system reflecting hazard ratios of the prognostic factors above was created to classify patients into three subgroups (low-risk group: score 1, intermediate-risk group: score 2 and high-risk group: score 3) (Table). The significant difference of EFS and overall survival was detected among these three different subgroups of patients (p<0.001). Conclusions: We propose the risk score system, which incorporated metastases at diagnosis, histological response and surgery type in order to predict postoperative clinical course of OS patients; this score will be tested prospectively in future BOTG trials. N Metastasis Grade of necrosis Type of surgery Score Overall survival EFS 92 – III or IV Limb-sparing 1 83% 67% 157 – I or II Limb-sparing 2 54% 42% 12 – III or IV Amputation 2 39 – I or II Amputation 2 21 + III or IV Limb-sparing 2 38 + I or II Limb-sparing 3 17% 14% 6 + III or IV Amputation 3 29 + I or II Amputation 3
Silencing or inhibition of endoplasmic reticulum aminopeptidase 1 (ERAP1) suppresses free heavy chain expression and Th17 responses in ankylosing spondylitis
Authors: Liye Chen, Anna Ridley, Ariane Hammitzsch, Mohammad Hussein Al-Mossawi, Helen Bunting, Dimitris Georgiadis, Antoni Chan, Simon Kollnberger, Paul Bowness
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objective</h3> Human leucocyte antigen (HLA)-B27 and endoplasmic reticulum aminopeptidase 1 (ERAP1) are strongly associated with ankylosing spondylitis (AS). ERAP1 is a key aminopeptidase in HLA class I presentation and can potentially alter surface expression of HLA-B27 free heavy chains (FHCs). We studied the effects of ERAP1 silencing/inhibition/variations on HLA-B27 FHC expression and Th17 responses in AS. <h3>Methods</h3> Flow cytometry was used to measure surface expression of HLA class I in peripheral blood mononuclear cells (PBMCs) from patients with AS carrying different ERAP1 genotypes (rs2287987, rs30187 and rs27044) and in ERAP1-silenced/inhibited/mutated HLA-B27-expressing antigen presenting cells (APCs). ERAP1-silenced/inhibited APCs were cocultured with KIR3DL2CD3ε-reporter cells or AS CD4+ T cells. Th17 responses of AS CD4+ T cells were measured by interleukin (IL)-17A ELISA and Th17 intracellular cytokine staining. FHC cell surface expression and Th17 responses were also measured in AS PBMCs following ERAP1 inhibition. <h3>Results</h3> The AS-protective ERAP1 variants, K528R and Q730E, were associated with reduced surface FHC expression by monocytes from patients with AS and HLA-B27-expressing APCs. ERAP1 silencing or inhibition in APCs downregulated HLA-B27 FHC surface expression, reduced IL-2 production by KIR3DL2CD3ε-reporter cells and suppressed the Th17 expansion and IL-17A secretion by AS CD4+ T cells. ERAP1 inhibition of AS PBMCs reduced HLA class I FHC surface expression by monocytes and B cells, and suppressed Th17 expansion. <h3>Conclusions</h3> ERAP1 activity determines surface expression of HLA-B27 FHCs and potentially promotes Th17 responses in AS through binding of HLA-B27 FHCs to KIR3DL2. Our data suggest that ERAP1 inhibition has potential for AS treatment.
Phase I study of intravenous CCI-779 in combination with bryostatin-1 in solid tumors
Authors: N. B. Haas, N. Lewis, R. B. Cohen, L. Malizzia, M. B. Einarson, M. A. Walker, T. Kim, M. Von Mehren, G. R. Hudes
Journal: Journal of Clinical Oncology (2006)

3067 Background: mTOR regulates translation of messenger RNA critical for angiogenesis and cell growth. CCI-779 inhibits mTOR signaling through p70S6 kinase (S6K), which phosphorylates the ribosomal S6 protein (S6). CCI-779 is active in renal carcinoma (RCC) and other solid tumors. Based on our finding that bryostatin-1 (bryo) inhibits S6K, and that CCI-779 + Bryo additively inhibit S6K and RCC growth in vitro, we initiated a phase I trial to determine the maximum tolerable (MTD) doses and dose-limiting toxicities of this novel combination in patients with solid tumors. Methods: Bryo (20 μg/m 2 ) was administered over 60 minutes IV followed by CCI-779 (10 and 15 mg, planned escalation to 75 mg) IV over 30 minutes, both weekly for 3 of 4 weeks. Serum and peripheral blood mononuclear cell (PBMC) samples were collected for analysis of pharmacokinetics and markers of mTOR inhibition (phospho-S6 and p21waf1). Results: Nine patients (median age 57, 6 RCC, 2 sarcoma and 1 neuroendocrine) are evaluable for toxicity (total cycles=27 cycles, median 4, range 1–7) at the initial 2 dose levels (Bryo 20 μg/m 2 , CCI-779 10 mg and 15 mg). Cycle 1 toxicity includes grade 3 hypophosphatemia and myelosuppression in one patient each and grade 2 fatigue, stomatitis, and anemia. One patient developed reversible grade 3 pneumonitis after 7 cycles. Of 7 patients with therapy-resistant disease, 5 (4 RCC and 1 sarcoma) had stable disease lasting up to 7 months. A therapy-naive patient with RCC has 23% tumor reduction after 2 cycles at dose level 2 (CCI-779=15 mg). PBMC proteins from 5 patients show consistent decreases in phospho-S6 at 2–6 hours-post treatment compared with pre-treatment baseline measurement, with recovery by 24–72 hours after dosing. In parallel with inhibition of phosphorylation of S6, PBMC levels of p21waf1 were completely inhibited in all 5 patients. Conclusions: The combination of bryo and CCI-779 is feasible, with antitumor activity in RCC and mTOR pathway inhibition observed at submaximal doses. Dose escalation is continuing. No significant financial relationships to disclose.
14-3-3 sigma expression and prognostic value in patients with epithelial ovarian carcinoma
Authors: P. Mhawech-Fauceglia, F. R. Herrmann, C. Andrews, S. Lele, K. Odunsi
Journal: Journal of Clinical Oncology (2008)

16597 Background: 14–3-3σ is a potential tumor suppressor gene that is inactivated by CpG methylation. Previously, we showed hypermethylation of 14–3-3σ in human ovarian cancer and ovarian cancer cell lines, and a correlation between hypermethylation and loss of its expression by immuhistochemistry. Herein, our aim is to determine the value of 14–3-3σ in predicting disease outcome inseries of patients with epithelial ovarian cancer. Methods: We performed an immunohistochemical analysis using 14–3- 3σ on tumor tissue microarray. Its expression was correlated with age, tumor types, grade, stage, volume of residual tumor, response to therapy, overall survival (OS) and disease-free survival (DFS). Results: Significant associations between 14–3-3σ and age (p=0.08) and volume of residual tumor (p=0.04) were seen. There was no association between loss of 14–3-3σ expression and any of stage, grade, tumor subtypes, and clinical response to therapy. Survival analysis according to Kaplan-Meier method showed that loss of 14–3-3σ expression was not associated with OS or DFS (p=0.78 and p=0.11 respectively). Conclusions: We concluded that 14–3-3σ is involved in ovarian tumorigenesis, but it might not be an independent maker to predict patients’ outcome. No significant financial relationships to disclose.