tbuckley/cabot-search huggingface dataset:
Renal function in advanced renal cell carcinoma patients treated with sorafenib: Subset analyses of post-marketing surveillance in Japan with over 3,200 consecutive cases.
Authors: Mototsugu Oya, Koki Kabu, Masatoshi Adachi, Yuichiro Ito, Hideyuki Akaza
Journal: Journal of Clinical Oncology (2016)

518 Background: Patients with advanced renal cell carcinoma (RCC) are predisposed to impaired renal function due to prior nephrectomy and existing renal mass. Moreover, treatment with molecular targeted agents may also affect renal function. We retrospectively analyzed post marketing all-patients surveillance to assess the effect of sorafenib on the renal function of advanced renal cell carcinoma (RCC) in real-world use. Methods: We have collected safety/efficacy data of over 3,200 consecutive Japanese patients with advanced RCC treated with sorafenib under daily medical practice (1). Using this database, the effect of sorafenib on renal function was analyzed in a post-hoc manner, by calculating estimated glomerular filtration rate (eGFR) from age, gender, and serum creatinine at each time point. Results: The eGFRs at baseline (n=2,943), 12 months after sorafenib treatment (n=636, and the time of discontinuation (n=1712) of all patients were 54 ± 21, 57 ± 24, and 59.6 ± 31.8 mL/min/1.73 mm 2 , respectively, and showed no significant differences. The mean eGFRs of each segment at baseline and 12 months were 110 ± 26 and 96 ± 39 in G1(eGFR ≥90), 70 ± 8 and 73 ± 23 in G2 (eGFR ≥60 and &lt;90), 52 ± 4 and 57 ± 15 in G3a (eGFR ≥45 and &lt;60), 39 ± 4 and 43 ± 11 in G3b (eGFR ≥30 and &lt;45), 24 ± 4 and 30 ± 10 in G4 (eGFR ≥15 and &lt;30), 7 ± 3 and 11 ± 12 in G5 (eGFR &lt;15), respectively. The median daily dose were 726mg (G1), 522mg (G2), 524mg (G3a), 517mg (G3b), 483mg (G4), and 400mg (G5). The incidence of renal AEs seemed to be higher in G4 and G5 (14% and 6%, respectively) than the other groups. The objective response rate ranged from 29.2% in G3a to 18.3% in G5, and the overall survival were higher in G3a and G3b (1 year survival rate: 81.5% and 78.4%, respectively), and lower in G1 (1 year survival rate: 50.2%). Conclusions: This study demonstrated that little impact on renal function of advanced RCC patients treated with sorafenib during observational period with sufficient clinical response and safety irrespective of the baseline eGFR value.
Development and Characterization of a Novel CD34 Monoclonal Antibody That Identifies Sheep Hematopoietic Stem/Progenitor Cells.
Authors: Christopher D. Porada, Dee Harrison-Findik, Chad Sanada, Vincent Valiente, Paul J. Simmons, Graça Almeida-Porada, Esmail D. Zanjani
Journal: Blood (2007)
P10-1 open-label, multicenter study of sipuleucel-T in metastatic castrate-resistant prostate cancer (mCRPC) patients (pts) previously treated with sipuleucel-T: Evaluation of antigen-presenting cell (APC) activation.
Authors: Tomasz M. Beer, L. Michael Glode, Raymond Lance, Richard Greengold, Robert Brownell Sims, Yang Wang, Nadeem A. Sheikh, John M. Corman
Journal: Journal of Clinical Oncology (2013)

147 Background: Sipuleucel-T is an autologous cellular immunotherapy that has demonstrated an improvement in survival among men with asymptomatic or minimally symptomatic mCRPC. P10-1 (NCT01338012) is an open-label, multicenter study of sipuleucel-T in men with mCRPC previously treated with sipuleucel-T in the androgen-dependent setting on the PROTECT trial (a prospective, randomized, controlled Phase III study of sipuleucel-T in men with prostate-specific antigen recurrence following radical prostatectomy; NCT00779402). This preliminary analysis of P10-1 evaluates the pattern of APC activation in pts re-treated with sipuleucel-T after progression to mCRPC. Methods: Eligible pts include those previously treated with at least one infusion of sipuleucel-T on PROTECT and who progressed to the mCRPC state. Pts receive up to three additional infusions of sipuleucel-T. APC activation is assessed by CD54 upregulation expressed as the ratio of the average number of CD54 molecules on post-culture vs. pre-culture cells. Results: As of September 14, 2012, 7 pts have been enrolled and have received an infusion of sipuleucel-T. The median interval between the last infusion in PROTECT and the first infusion in P10-1 was 8.6 years. The Table shows a higher fold change in CD54 expression in the first P10-1 treatment compared with the initial infusion in PROTECT. Conclusions: This is the first report of pts re-treated with sipuleucel-T after prior treatment in an earlier disease setting. These preliminary data are consistent with the presence of an immunological memory response to the immunizing antigen several years following initial treatment. Clinical trial information: NCT01338012. [Table: see text]
Phase II study to evaluate efficacy and safety of irinotecan, capecitabine, and bevacizumab in metastatic colorectal cancer (mCRC) patients.
Authors: Pilar Garcia Alfonso, Manuel Chaves-Conde, Andres Munoz, Antonia Salud, Carlos Garcia-Giron, Cristina Gravalos Castro, Bartomeu Massuti, Encarnación González Flores, Bernardo Queralt, Amelia Lopez Ladron, Ferran Losa, Amparo Oltra Ferrando, Maria Jose Gomez Reina, Rocio Garcia-Carbonero, Ignacio Garcia-Escobar, Enrique Aranda
Journal: Journal of Clinical Oncology (2013)

501 Background: XELIRI regimen biweekly (combination of capecitabine and irinotecan) is an active and well tolerated treatment for mCRC. Bevacizumab provides significant clinical benefits in previously treated patients with mCRC. On this basis, the aim of this study is to evaluate the efficacy and safety of this combination. Methods: Multicentric, prospective, open-label phase II trial. Treatment scheme: irinotecan (iri) (175mg/m 2 d1 q2w) + capecitabine (xel)(1,000mg/m 2 bid d 2-8) + bevacizumab (bev) (5mg/kg, d1 q2w). Results: 77 patients (p) were evaluated (66.2%, male) with a median age of 65.1 years (41.1-81.1). ECOG performance status was ≤1 in 96.1%. Primary tumor locations were: colon (53.2%), rectum (31.2%), and rectum/colon (15.6%). 27 p (35.1%) received adjuvant chemotherapy. Metastases were detected in liver (62.3%) and lung (54.5%). Mean time in treatment was: 7.1±4.9 months and median of cycles administered was 12(1-43). Median relative dose intensity was 89% for xel and bev and 85% for iri. Best response confirmed were: complete response (5.2%), partial response (32.5%), stable disease (46.8%). After a median of follow-up of 23.3 (0.4-39.6) months, median overall survival (OS) and progression free survival (PFS) was 24.8 and 11.8 months respectively. Analysis on Kras status was done in 71 p. There were no significant differences in OS or in PFS between WT and MUT p. 17 p (22.1%) underwent salvage surgery, 12 of whom had an R0 resection. The most frequent G3-4 toxicities were: diarrhea (18.2%), asthenia (16.9%), pulmonary embolism (13%; in eight of 10 p were asymptomatic), neutropenia (10.4%), febrile neutropenia (6.5%) and HFS (5.2%). Three treatment related deaths were reported (2 cases of multi-organ failure, and 1 case of intestinal perforation). Conclusions: Bevacizumab combined with biweekly XELIRI is an active first-line regimen for mCRC treatment with a feasible and manageable safety profile. Bevacizumab treatment efficacy was independent on Kras status. Clinical trial information: NCT00875771. [Table: see text]
Bendamustine in Chronic Lymphocytic Leukemia (CLL): Outcome According to Different Clinical and Biological Prognostic Factors in Everyday Practice
Authors: Francesco Zaja, Michael Mian, Carlo Visco, Cinzia Sissa, Ilaria Nichele, Monica Castelli, Achille Ambrosetti, Simona Puglisi, Renato Fanin, Sergio Cortelazzo, Giovanni Pizzolo, Livio Trentin, Francesco Rodeghiero, Rossella Paolini, Paolo Vivaldi, Rosaria Sancetta, Gianpietro Semenzato
Journal: Blood (2012)
Favorable outcome in treating pediatric and adolescent patients with locally advanced nasopharyngeal cancer.
Authors: T. M. Khattab, A. a. Baothman, N. b. Safadi, M. m. Kesudeen
Journal: Journal of Clinical Oncology (2011)

e20004 Background: Nasopharyngeal carcinoma (NPC) is extremely rare in pediatric population. Survival of patient with early lesions is excellent with local control rate of 80%. Prognosis of patients with advanced lesions when treated with Radiotherapy (RT) alone is less favorable. Methods: Objectives: To retrospectively review outcome of all registered children and adolescent (20 year or less) with locally advanced NPC (LANPC) at our institution. January 2002 to December 2008, nine patients with LANPC were identified. Three pediatrics and 6 adolescents. Tumors classified according to the AJCC (TNM) 6th edition staging system. Pediatric patients received Induction Chemotherapy (IC) using cisplatin and 5-fluorouracil (5-FU) for 3 to 6 cycles. Adolescent patients were treated with IC consisting of Docetaxel, cisplatin, and 5-FU for 3 cycles. Seven patients received conventionally fractionated RT (median dose 6,600 cGy in 35 fractions) with concomitant chemotherapy using cisplatin or Carboplatin. The remaining two patients received hyperfractionated RT with concomitant Cisplatin. RT was delivered with 3-D conformal technique in all patients. Results: Median age of the whole group was 16 (range 7-20). Male to female ratio 2:1. All pediatric patients (3) had stage IVA. Adolescent patients, 2 had stage IVA, 2 stage IVB, and 2 had stage III. Eight patients (88%) had Undifferentiated Carcinoma (WHO type III) and one patient (12%) had nonkeratinizing squamous cell carcinoma (WHO type II). Median follow-up of 66 month, overall survival was 100%; event-free survival was 88%. One pediatric patient treated with low dose hyperfractionated RT (6,000 cGy in 50 fractions twice-a-day) for close proximity of optic pathway, developed local recurrence 10 month following RT. For 13 months, he showed favorable response to salvage therapy including gemcitabine and docetaxel. Conclusions: LANPC in children and adolescents has favorable outcome when treated with a combination of chemotherapy and radiotherapy. Future development must focus on reducing acute and late treatment morbidity while maintaining efficacy. Patients with complete response to IC might benefit from reduced doses of Intensity Modulated RT (IMRT).
Concordance with the ASCO Provisional Clinical Opinion on the integration of palliative care into standard oncology care in Ontario.
Authors: Victoria Zwicker, Katharina Forster, Angelika Gollnow, Amy Liu, Jingxian Sun, Reena Tabing, Ashley Tyrrell, Sara Urowitz, Kirsten Wentlandt
Journal: Journal of Clinical Oncology (2015)

170 Background: In 2012, ASCO released a Provisional Clinical Opinion for patients with stage IV non-small cell lung cancer (NSCLC) and the need for integration of palliative care services concurrent with standard treatment from the time of diagnosis. To understand if this recommendation is being followed in Ontario, provincial administrative data was used to explore concordance. Methods: Various aspects of concordance were considered including: whether and when in the treatment trajectory patients received palliative care, and how much care was received. For Phase 1 of the analysis, a provincial database of outpatient cancer care was used to identify services received within Ontario’s regional cancer centers (RCCs) and select partner hospitals. The Ontario Cancer Registry and Staging databases were used to identify the patient cohort. The cohort included patients diagnosed with stage IV NSCLC between January 1, 2012 and December 31, 2013. Results: Phase 1 results indicate that 41% of patients received palliative and/or psychosocial oncology care at the RCC or partner hospital after diagnosis. Those receiving palliative care first received services an average of 148 days after diagnosis. See Table below for detailed results. Conclusions: A growing body of literature has identified the benefits of concurrent palliative care. Knowing whether these services are being provided for the NSCLC population is a promising start to understanding and improving the delivery of palliative care in Ontario. Initial results suggest that there is a need for quality improvement in this area. Future phases will expand the analysis to include services received in additional settings such as hospitals and community. [Table: see text]
Tumor and plasma biomarker analysis from the randomized controlled phase II trial (RCT) of tivantinib in second-line hepatocellular carcinoma (HCC).
Authors: Lorenza Rimassa, Giovanni Abbadessa, Nicola Personeni, Camillo Porta, Ivan Borbath, Bruno Daniele, Jean-Luc Van Laethem, Hans Van Vlieberghe, Jorg Trojan, Enrico de Toni, Markus Peck-Radosavljevic, Richard S. Finn, Jean-Luc Raoul, Aiwu Ruth He, Maria Lamar, Yunxia Wang, Reinhard W. Von Roemeling, Brian E. Schwartz, Jordi Bruix, Armando Santoro
Journal: Journal of Clinical Oncology (2016)

197 Background: Tivantinib, an oral MET inhibitor, showed activity in patients (pts) MET-High at immunohistochemistry (IHC) in randomized, placebo controlled studies in HCC, NSCLC, CRC, and prostate cancer. ARQ 197-215 was a RCT of tivantinib in second-line HCC. The study randomized 107 pts 2:1 to tivantinib capsules or placebo, reached the primary endpoint of time to progression in the intent-to-treat population and the pre-specified secondary efficacy endpoints, including OS, in MET-High pts. Tumor MET was also found to be a strong independent prognostic factor. This analysis aims to study prognostic and predictive value of tumor and circulating biomarkers. Methods: Circulating MET, HGF, and AFP were centrally analyzed by ELISA and median values were used as cut-offs to determine High or Low status except for AFP, where the 75th percentile was also used. Tumor MET was centrally analyzed and considered High if staining was &gt;2+ in &gt;50% of cells at IHC. Results: Circulating MET was prognostic (N=102; OS: 4.6 vs 8.9 months in High vs Low, HR=0.61, p=0.023) and trended towards predicting tivantinib’s activity. MET was also a pharmacodynamic marker: pts on tivantinib with a MET reduction over time survived longer; MET was reduced in pts stable on tivantinib but not on placebo. Circulating HGF was prognostic (N=102; OS: 5.0 vs 9.0 months in High vs Low, HR=0.6, p=0.02) and changes over time correlated with outcome. AFP by the 75th percentile was prognostic (N=104; OS: 3.0 vs 7.9 months in High vs Low, HR=0.36, p&lt;0.0001). Median IHC score (H-Score) was 175 for tumor MET-High, 40 for MET-Low pts (N=77). MET was highly expressed in 40% of biopsies taken before and in 82% of biopsies taken after sorafenib. A significant interaction between tivantinib and tumor MET in terms of OS was observed (p=0.039). No biomarker except for tumor MET was predictive of response to tivantinib. Conclusions: A clear prognostic value was found for circulating MET, HGF, and AFP by the 75th percentile. Tumor MET was highly prognostic and predictive. IHC results on over 900 tumor samples analyzed in the ongoing METIV-HCC phase 3 study will also be presented. Clinical trial information: NCT00988741.
Identification of common and distinct epigenetic reprogramming properties of RUNX1 fusion proteins in acute myeloid leukaemia
Authors: Justin Loke, Salam Assi, Maria Imperato, Anetta Ptasinska, Pierre Cauchy, Manoj Raghavan, Ruud Delwel, Peter Cockerill, Olaf Heidenreich, Constanze Bonifer
Journal: The Lancet (2017)
Deep sequencing of sarcomatoid renal cell carcinoma (sRCC) and identification of aurora kinases and mTOR as potential therapeutic targets.
Authors: Sumanta Kumar Pal, Tommy Tong, Miaoling He, Huiqing Wu, Xueli Liu, Rebecca A. Nelson, Xiwei Wu, Sabina Signoretti, Toni K. Choueiri, Jeremy Jones
Journal: Journal of Clinical Oncology (2014)

411 Background: The presence of sarc elements in pts with RCC portends a poor prognosis. Some studies have focused on epithelial-to-mesenchymal transition (EMT) as a driver of sarc ccRCC; however, the potential role of other targetable entities is unknown. Methods: From an institutional database, we identified 13 pts with metastatic sarc ccRCC and 13 pts with metastatic ccRCC lacking sarc elements matched by age and risk group. All patients had available FFPE tissue derived from nephrectomy. For a limited sample of 5 pts with sarc ccRCC, RNA sequencing was performed on microdissected cc, sarc, and benign renal cortical sections from FFPE blocks. Reads were aligned to hg19 genome with Tophat v2.0. IHC was used to explore expression of implicated genes in the entire matched cohort of 26 pts. Results: With respect to RNA sequencing analysis for 5 pts with sarc ccRCC, reads had between 4% and 24% exon coverage. Hierarchical clustering demonstrated that most samples were clustered by patient, not by disease state (i.e., sarc vs non-sarc), suggesting that inter-patient variation is large. However, comparisons between cc and sarc components for these 5 pts demonstrated a significant increase in cell growth pathways, with the most highly enriched gene ontology pathways being M-phase, cell cycle, mitosis and aurora kinase pathways. No EMT-related pathways were found to be enriched. IHC assessments of VEGF and mTOR pathways were performed, given their purported role in RCC cell growth. While no differences were noted in pVEGFR2, higher pS6K staining was noted in both the sarc and non-sarc components of pts with sarc ccRCC relative to pS6K staining in tumor tissue derived from ccRCC pts lacking sarc elements (p&lt;0.05 for both). No differences in EMT marker expression were noted (specifically, E-cad, N-cad and Twist); IHC assessments for aurora kinases A and B will be reported. Conclusions: Although cytotoxic agents and VEGF-directed therapies have been explored in sarc ccRCC, the finding of mTOR pathway activity underscores the need to examine mTOR inhibitors in this disease. Furthermore, emerging agents targeting aurora kinases may have a role in sarc ccRCC.
Prognostic value of blood-borne epithelium-derived c-erbB2 oncoprotein-positive clustered cells from the peripheral blood of breast cancer patients
Authors: P. Wülfing, J. Borchard, S. Heidl, K. S. Zänker, L. Kiesel, B. Brandt
Journal: Journal of Clinical Oncology (2005)

9625 Background: Clinical studies have demonstrated that amplification and overexpression of c-erbB2 in breast carcinomas indicates poor clinical outcome. Previously, we reported the detection of cytokeratin-/c-erbB2 double-positive clustered cells in the peripheral blood of breast cancer patients. The objective of this study was to evaluate the prognostic value of blood-borne c-erbB2-positive cells in breast cancer patients. Methods: Blood-borne epithelium-derived clustered cells that express c-erbB2 were separated from the peripheral blood of 35 breast cancer patients applying a combined buoyant density gradient and immuno-magnetic separation technique. Co-expression of c-erbB2 and cytokeratin by the captured cells was detected using an immunocytochemical double staining protocol. Correlations between c-erbB2-positive cells and staging/grading, hormone receptor status were tested for statistical significance by Chi-square test. Kaplan-Meier estimates were generated for survival analysis and compared by log-rank test. Results: Mean follow-up was 75.5 months. In total, 17 patients (48.6%) had cytokeratin/c-erbB2-positive clustered cells in their peripheral blood. Presence of c-erbB2-positive cells was associated with both a significantly decreased disease-free (p=0.007) and overall survival (p=0.024), respectively. Moreover, a correlation between c-erbB2-positive clustered cells in the peripheral blood with larger tumor size (p=0.006), lymphovascular invasion (p=0.042) and lack of estrogen receptor expression (p=0.039) was found. Conclusions: Our findings suggest that blood-borne epithelium derived c-erbB2 positive clustered cells are conceivable precursor cells indication systemic tumor spread and responsible for the formation of distant metastases. Determination of c-erbB2 positive cells in the peripheral blood of breast cancer patients may serve as a prognostic marker for identifying high risk patients for early metastases and decreased survival. No significant financial relationships to disclose.
Effect of palliative care on aggressiveness of end-of-life care in patients with advanced colon cancer.
Authors: Jessica Ann Reifer Hildebrand, Renuka Bhan
Journal: Journal of Clinical Oncology (2013)

168 Background: Recent studies have observed that starting Palliative Care (PC) soon after diagnosis for patients with advanced cancer improves quality of life, end of life (EOL) care, and possibly survival. Consequently, it has been recommended that combined standard oncology care and PC should be considered early in the course of illness for patients with advanced cancer. It has been posited that patients enrolled in early PC receive less aggressive care at the EOL and consequently spend fewer healthcare dollars. We sought to compare the aggressiveness of care received by those enrolled in early PC to those enrolled in late PC. Methods: A retrospective chart review of patients diagnosed with stage III or IIII colorectal cancer (CRC) at New Hanover Regional Medical Center between 2009 through 2011 was performed. Patients who were enrolled in PC within 30 days of diagnosis were compared to those enrolled later. Aggressiveness of care given during the last 30 days of life was assessed by: hospitalizations, ED visits, days spent in the ICU, chemotherapy received in the last 14 days of life, and death in the hospital. Results: 186 patients were identified for the study, and 89 met inclusion criteria. We found no significant difference in the aggressiveness of care received by those enrolled in early PC (46.7%) versus later PC (47.8%) (p = 1.00). In fact, almost half of all patients with advanced cancer received some form of aggressive care within the last 30 days of life. While those enrolled in late PC more frequently received chemotherapy, were admitted to the ICU, and died in the hospital, the differences were not statistically significant. Whether or not these differences account for cost savings in the early PC group has yet to be determined. Conclusions: Our study found that patients were just as likely to receive aggressive care at the EOL regardless of whether or not they were enrolled in early PC. This finding was unexpected given the goals and philosophy of PC groups. While early PC has been recommended as a quality care measure, patient and physician factors may limit its effectiveness. For example, patients, while receptive to certain aspects of PC, still desire a cure. Similarly, physicians feel compelled to treat patients aggressively.