tbuckley/cabot-search huggingface dataset:
Results from the first-in-human (FIH) phase I study of RO5520985 (RG7221), a novel bispecific human anti-ANG-2/anti-VEGF-A antibody, administered as an intravenous infusion to patients with advanced solid tumors.
Authors: Manuel Hidalgo, Christophe Le Tourneau, Christophe Massard, Valentina Boni, Emiliano Calvo, Joan Albanell, Alvaro Taus, Marie-Paule Sablin, Andrea Varga, Ratislav Bahleda, Oliver Krieter, Lada Markovtsova, David Carlile, Angelika Lahr, Tapan Nayak, Katharina Lechner, Astrid Koehler, Ingrid Van Uffelen, Maria Martinez Garcia
Journal: Journal of Clinical Oncology (2014)

2525 Background: RO5520985 is a novel bi-specific human IgG1 antibody, acting as a dual- targeting inhibitor of the two key angiogenic factors VEGF-A and Ang-2. RO5520985 led to strong inhibition of angiogenesis with enhanced vessel maturation and demonstrated potent tumor growth inhibition, superior to single pathway inhibitors in a panel of preclinical models. Methods: This is a 3-part FIH phase I study: Part 1 explores the safety/ tolerability, PK, PD and anti-tumor activity, to establish the recommended phase 2 dose (RP2D) and schedule, part 2 will assess PD effects in tumor tissues and part 3 the efficacy and safety in patients (pts) with rec. ovarian cancer. Results of part I are presented here, where pts were treated on a bi-weekly (Q2W) or weekly (QW) schedule at escalated dose levels (DLs). A Bayesian logistic regression model with overdose control guided the dose escalation. Results: 42 pts (18m/24f) were treated on 7 DLs: Q2W 3mg/kg (1pt), 6 (3), 12 (4), 19 (8), 30 (6); QW 10mg/kg (4), 20 (4), 30 (12). Median age: 63 years (range 25-76). Plasma concentrations (Cmax and AUC) increased proportionally, with low inter-individual variability for both schedules. The elimination t1/2 was 7-9 days, based on Q2W. DCE-MRI of tumor lesions demonstrated moderate to significant reduction of vascular characteristics in 22/34 pts; within Q2W sustained effects were associated with 30 mg/kg. DW-MRI showed signs of on treatment necrosis and decreased cell density in 7 pts, particularly at 30 mg/kg. Depletion of circulating targets Ang-2 and VEGF-A was evident and apparently independent of dose and schedule. The most frequent AE of any grade (G) were hypertension (50%), asthenia (36%), headache (29%) and fatigue (19%). Most common AE ≥ G3 was hypertension (19%), predominantly associated with the weekly regimen (QW 30% vs. 9% Q2W). One DLT of pulmonary hemorrhage G5 occurred at 19mg/kg Q2W; a MTD was not reached. The progression-free rate at 8 weeks was 67% (Q2W) and 53% (QW). Conclusions: The RP2D and schedule was determined at 30mg/kg Q2W, where RO5520985 demonstrated an acceptable safety profile with favorable PK and PD effects. Clinical trial information: NCT01688206.
Prognostic factors for survival in renal cell cancer patients undergoing allogeneic stem cell transplantation: A report from the EBMT Solid Tumours Working Party
Authors: M. Bregni, J. Peccatori, L. Barkholt, O. Ringden, P. Pedrazzoli, R. Martino, S. Lenhoff, P. Corradini, T. Demirer, D. Niederwieser
Journal: Journal of Clinical Oncology (2004)

6666 Background: An immune-mediated graft-versus-tumor (GVT) effect has been reported to occur in patients with metastatic renal carcinoma receiving allogeneic transplantation. However, the onset of GVT effect is typically delayed by months from the time of the transplant, and usually follows cyclosporine withdrawal. Indeed, most patients show a tumor progression soon after the transplant, and it is questionable if patients with rapidly progressive tumor should be included in allografting protocols. Methods: We identified poor prognosis patients as those with four or more out of ten analysed prognostic factors. Prognostic factors examined were: ECOG PS; time interval from diagnosis to occurence of metastases; number of metastatic sites; liver metastases; mediastinal metastases; Hb; CRP; LDH; neutrophils; and calcium. We report the data on 53 patients with clear-cell renal carcinoma transplanted in Europe with various fludarabine-based, reduced-intensity conditioning regimens. Survival was measured from transplant date to death or last follow-up. Results: Median survival for poor-prognosis patients was 140 days, vs 820 days for good-prognosis patients. Conclusions: Identification of prognostic subgroups can assist in result evaluation and clinical decision making about allografting in renal cell carcinoma. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Funded by the Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research), a non-profit cancer-funding agency
Institute for Medical Ethics faces up to flood of dilemmas
Authors: Linda Emanuel
Journal: BMJ (1997)

After a long career in research and teaching in ethics at Harvard Medical School, Dr Emanuel came to the American Medical Association (AMA) in 1996 as vice president of the ethics standards division. She began working on a framework for creating the Institute for Medical Ethics as a place to design practical, accessible methods for incorporating ethics into–or back into–medical professionalism. “The AMA allows us to be advocates for professionalism,” said Dr Emanuel. “Ethics provide a moral anchor for physicians,” she added, “without them, physicians become unanchored.”

The doctor and patient relationship has never before been confronted with such ethically challenging issues as those that have emerged in the past 10 years, said Dr Emanuel. Medical technologies barely imaginable two decades ago can now prolong a life artificially, long after the brain has shut down, forcing difficult decisions about end of life care. Similarly, the advancement of the delivery of health care towards a market driven system in the United States has raised new issues about the accountability and responsibility of doctors. These are just two of the biomedical and social issues that the institute wants to address, but they are issues that Dr Emanuel has been thinking about for …
Predictors of pathological response and tumor regression following neoadjuvant therapy in advanced gastric cancer patients.
Authors: Ulysses Ribeiro, Marcus Fernando Kodama Pertille Ramos, Marina Alessandra Pereira, André Roncon Dias, Osmar Kenji Yagi, Sheila Faraj, Evandro Sobroza de Mello, Amir Zeide Charruf, Guilherme Luiz Stelko Pereira, Bruno Zilberstein, Paulo Marcelo Hoff, Ivan Cecconello
Journal: Journal of Clinical Oncology (2017)

206 Background: Neoadjuvant chemotherapy (NACT) has became the standard approach for patients with advanced gastric cancer. Clinicopathological characteristics can be utilized to evaluate the effect of NACT, and may be a useful tool to identify responsive patients. Methods: We retrospectively reviewed all patients with GC treated with NACT and R0 resection between 2009 and 2015 from a prospective collected database. Histopathological response to the treatment was graded from 0% to 100% and the clinicopathological characteristics assessed to identify predictors of tumor response. A threshold of 50% histopathological response was used for the analysis. Results: NACT was performed in 45 patients. Cisplatin-irinotecan therapy was used in 64.4% of patients and 11 (24.4%) tumors were located in the proximal stomach. Ten (22.2%) patients demonstrated a tumor regression of at least 50% and one patient had complete response. The mean number of lymph node retrieved was 38.1 and 66.7% patients had lymph node metastasis (LNM). Factors associated with &gt; 50% of response by univariate analyses included lower neutrophil-lymphocyte ratio (NLR) ( p = 0.035), diffuse/mixed Lauren type ( p = 0.007), lower depth of tumor invasion ( p = 0.043) and non cisplatin-irinotecan therapy (p = 0.01). A slight tendency of poorly differentiated tumors respond better to NACT than differentiated type was observed ( p = 0.05). There was no significant difference regarding the presence of mucin, calcification and/or necrosis and the tumor response. Multivariate analysis identified NLR and diffuse/mixed tumors as independent predictors of pathologic response. Median follow-up for all patients was 26.5 months and recurrence-free survival (RFS) rate was 74.3% and 60% for patients with &gt; 50% and &lt; 50% of response, respectively ( p= 0.08). RFS was significantly different in patients without LNM compared to patients who have LNM (100% vs. 55.2%, p = 0.01), and in patients with fibroinflammatory/inflammatory stroma infiltration compared to patients with only fibrotic stroma (80% vs. 53.3%, p = 0.015). Conclusions: Diffuse/mixed histopathological type and lower NLR are independently predictors of tumor response after NACT.
Relationship between pharmacokinetics and safety of tremelimumab in patients with melanoma
Authors: E. Wang, D. Kang, D. Wang, C. Bulanhagui, P. Hsyu
Journal: Journal of Clinical Oncology (2009)

3049 Background: Tremelimumab is a fully human anti-CTLA4 monoclonal antibody that has antitumor activity in some patients with advanced melanoma. The most common adverse event associated with tremelimumab is diarrhea/colitis. This analysis investigated the relationship between pharmacokinetics (PK) and diarrhea or colitis in 450 patients enrolled in four phase I or II clinical studies. Methods: PK parameters including AUC during the first 90 days (AUC90), C max , concentration at day 29 (C29), and AUC of concentration &gt;30 μg/mL (AUCG30) of tremelimumab were determined using nonlinear mixed-effect modeling. Severity and frequency of diarrhea and colitis during the 90 days after the first dose were considered in relation to each individual PK parameter. Frequency of diarrhea was further analyzed by logistic regression analysis. Frequencies of diarrhea and colitis were combined for logistic analysis. Results: The PK/safety analysis included 450 patients (445 with advanced melanoma). In this analysis, the severity of diarrhea and colitis appeared to be independent of PK (AUC90, C max , C29, and AUCG30) of tremelimumab. Although frequency of diarrhea was positively related to AUC (AUC or AUCG30), C max , and C29, AUC appeared to be best correlated to frequency of diarrhea. Logistic regression analysis of change in AUC on probability of having diarrhea indicated that the frequency of diarrhea increased initially with increasing AUC, but reached a plateau quickly at approximately AUC value of 50,000 μg × hr/mL (20th percentile). Results of the combined diarrhea and colitis analysis were similar to those of diarrhea alone. Conclusions: Severity of diarrhea and colitis is independent of AUC in patients with melanoma treated with tremelimumab. Frequency of diarrhea and colitis initially increases with increasing AUC, but plateaus quickly. [Table: see text]
Idelalisib is effective in patients with high-risk follicular lymphoma and early relapse after initial chemoimmunotherapy
Authors: Ajay K. Gopal, Brad S. Kahl, Christopher R. Flowers, Peter Martin, Stephen M. Ansell, Esteban Abella-Dominicis, Brian Koh, Wei Ye, Paul M. Barr, Gilles A. Salles, Jonathan W. Friedberg
Journal: Blood (2017)
A randomised phase IIb trial of BEvACizumab added to Temozolomide ± IrinOtecan for children with refractory/relapsed Neuroblastoma - BEACON-Neuroblastoma, a European Innovative Therapies for Children with Cancer (ITCC) - International Society of Paediatric Oncology Europe Neuroblastoma Group (SIOPEN) trial.
Authors: Lucas Moreno, Jennifer Laidler, Veronica Moroz, Cormac Owens, Herve Rubie, Pablo Berlanga, Aurora Castellano, Karsten Nysom, Ruth L Ladenstein, Jochen Rossler, Christian M. Zwaan, Martin Elliott, Guy Makin, Dermot Murphy, Susan A Burchill, Neil Jerome, Raphael F. Rousseau, Pamela Kearns, Keith Wheatley, Andrew DJ Pearson
Journal: Journal of Clinical Oncology (2015)

TPS10082 Background: Current therapy for relapsed/refractory high-risk neuroblastoma is not evidence based and long-term disease control is poor. Advances in frontline therapy have been achieved through randomised clinical trials. BEACON-Neuroblastoma trial is designed to identify a backbone chemotherapy regimen to be combined with targeted agents and determine if inhibiting angiogenesis with bevacizumab(B) adds to the activity of chemotherapy. It is the first randomized European study for refractory/relapsed neuroblastoma Methods: BEACON-Neuroblastoma is a factorial phase 2, multicentre, international, randomized clinical trial (EudraCT 2012-000072-42, sponsored by the University of Birmingham). Patients 1-21 years with relapsed/refractory high-risk neuroblastoma are randomised to 1 of 4 arms: T (temozolomide), IT (irinotecan-temozolomide), BT (B-T) or BIT (B-IT). The trial tests whether B added to chemotherapy (T or IT) demonstrates activity and whether the addition of I to T increases activity. Primary endpoint is best response at any time during trial treatment. During 2015, whether the addition of topotecan to T increases activity will be addressed by changing to 3 x 2 design with 6 arms and requiring 160 patients. The trial incorporates functional imaging (FI) to elucidate the role of anti-angiogenic therapy in neuroblastoma; a biomarker study measuring neuroblastoma mRNAs and molecular characterisation. This work is supported by Cancer Research UK [grant number CRUK/11/056] and Imagine for Margo. 21 sites in 7 countries are open (11 further sites are to open). From Jul-2013 to Jan-2015, 30 patients have been included. BEACON-Neuroblastoma is the recommended approach for relapsed/refractory neuroblastoma in SIOPEN/ITCC. The trial will answer 2 randomised questions in a small population and has developed a European network of centres performing biomarker and FI studies. It will be the foundation of a European multi-arm multi-stage trial to evaluate new drugs in the future Clinical trial information: NCT02308527.
ALTERACIONES ESOFAGOGÁSTRICAS EN PACIENTES CON OBESIDAD MÓRBIDA TRAS LA COLOCACIÓN ENDOSCÓPICA DE BALÓN INTRAGÁSTRICO COMO TRATAMIENTO DE OPTIMIZACIÓN PREQUIRÚRGICA
Authors: S Sevilla Ribota, M Gómez Rubio, P Monasterios Maestra, G Castillo López, I Alía Moreno, JC Ruiz De Adana, A Hernández
Journal: Endoscopy (2015)

El balón intragástrico (BIG) se emplea en la optimización prequirúrgica de pacientes con obesidad mórbida. La disminución de peso que consigue puede mejorar la morbilidad perioperatoria y facilitar la técnica quirúrgica. No se conoce adecuadamente si el BIG ocasiona lesiones esofagogástricas en estos enfermos.
Utilization of patient pager for preservation of privacy in clinic waiting room.
Authors: Tasneem Kaleem, Daniel Miller, Maresciel Yanez, Steven J. Buskirk
Journal: Journal of Clinical Oncology (2017)

192 Background: Patient privacy is of the utmost importance for the emotional needs of a cancer patient and their family. As an effort to improve privacy, quality, and coordination of care within our Radiation Oncology department, in 2016 a patient pager system was devised to inform patients to prepare for daily treatment rather than verbally call the patient's name in waiting rooms. Methods: During June 2016, patients undergoing daily radiation therapy participated in a six-question survey addressing various aspects of the paging service, privacy prior to pager use, and demographics. Six radiation therapists also participated in a 7-question survey addressing privacy and workflow. Participants rated their experience on a scale of 1 to 5 (1 being poor, 5 being excellent). Surveys were collected and retrospectively reviewed. Results: 42 patients completed the survey. Patients rated "Very Good" to "Excellent" for the following categories: “Paging system more convenient than being called”(4.6), “Protection of privacy”(4.6), “Easiness”(4.7) and whether “Pager should be utilized for all appointments” (4.3). Patients rated “Patient privacy when name is called” as "Good" to "Very Good" (3.7). Seven patients also underwent therapy prior to pager implementation and rated the new system in comparison as "Very Good" to "Excellent" for “Privacy protection”(4.6), “Efficiency” (4.6), and “Satisfaction” (4.6). Only 24 filled out demographic information. Of the 24 patients, 54% of patients were female, 87% were above the age of 50, and all patients were receiving at least 10 treatments. Staff rated "Fair" to "Very Good" for “More preparation time” (2.8), “Patient use difficulty”(3.2), “Patient positive feedback”(2.3), “Receiving patients” (2.2) and “Workflow” (2). However, “Patient privacy” was rated as "Very Good" to "Excellent" (4.2). Conclusions: Overall, patients and staff highly rated the paging system for protecting privacy in the waiting room. Patients who experienced waiting room procedure prior to pager implementation display greater satisfaction with a paging system. However, it did not change overall workflow. Our study shows clinics should prioritize patient privacy in the waiting room to improve the emotional needs of the patient.
Vasomotor (VM) and musculoskeletal (MSK) symptoms and association with outcomes on extended adjuvant letrozole therapy: Analyses from NCIC CTG MA.17.
Authors: Pedro Emanuel Rubini Liedke, Yanin Chavarri-Guerra, Lois E. Shepherd, Dongsheng Tu, Kathleen I. Pritchard, Paul Edward Goss
Journal: Journal of Clinical Oncology (2012)

524 Background: Surrogate markers of clinical outcomes can potentially guide cancer therapy. New onset MSK symptoms and VM symptoms on aromatase inhibitors (AI) for hormone receptor positive (HR+) early breast cancer (EBC) have been investigated as markers of clinical outcomes, but results have been conflicting. MA.17 showed improved disease free survival (DFS) with letrozole (L) as extended adjuvant therapy after 5 years of tamoxifen (T). We performed this exploratory analysis of new onset symptoms and their association with clinical outcomes in the MA.17 trial. Methods: Patients (pts) with HR+ EBC were randomized to receive L or placebo (P) for 5 years after 5 years of T. Symptoms were collected according to CTC v. 2.0 at baseline, 1 month (mo), 6 mos, and every 12 mos thereafter. Analyses included pts with new symptoms of any grade who received therapy and excluded pts with baseline symptoms, EBC not HR+, and deaths/ relapses prior to each time point. Symptoms were categorized as VM - hot flashes/flushes, flushing, or sweating; and MSK - arthritis, arthralgia, myalgia, bone pain, or MSK other. Multivariate Cox Models adjusting for age, nodal status, duration of T and prior chemotherapy were used for analysis of DFS, distant DFS (DDFS), and overall survival (OS) assessed before unblinding. Hazard Ratios [HR] and 95% confidence intervals (CI) for patients with either VM or MSK symptoms are presented below for L using pts with no symptoms as controls. Results: Emergent VM symptoms were associated with improved DFS and DDFS on L (Table). No association was found for MSK symptoms at any time point. No association between either MSK or VM and OS was found at any time point. Conclusions: New VM symptoms initiating with extended letrozole were associated with improved outcomes. Similar findings have been seen with up-front AI therapy. Our results should be confirmed as they are of potential significance in guiding therapy. [Table: see text]
Accuracy and completeness of diagnosis codes for cancer metastasis on Medicare claims.
Authors: Neetu Chawla, K. Robin Yabroff, Angela Mariotto, Timothy S. McNeel, Deborah Schrag, Joan L Warren
Journal: Journal of Clinical Oncology (2013)

6521 Background: Researchers are increasingly using diagnosis codes from administrative claims for cancer patients to identify metastatic disease at initial diagnosis or recurrence. However, the validity of metastasis codes on claims has not been established. We used the linked SEER -Medicare data to assess the completeness and validity of metastasis codes from Medicare claims for three common U.S. cancers. Methods: The study included 80,052 breast, lung, and colorectal cancer patients diagnosed with localized, regional, or distant disease in the SEER data between January 1, 2005 and December 31, 2007. From Medicare claims, patients were classified as having regional or distant disease at diagnosis if they had one hospital claim or two physician claims with metastasis codes within 3 months of diagnosis. Patients without claims with metastases codes were classified as having local disease. Using SEER data as the gold standard, we calculated sensitivity, specificity, positive and negative predictive values of metastasis codes on Medicare claims. We conducted multivariate logistic regression analysis to evaluate patient factors associated with stage misclassification for each cancer site. Results: For patients with distant disease per SEER data, the sensitivity and PPV of the claims to identify distant disease was: breast (50.6%, 67.3%), colorectal (72.2%, 68.8%) and lung cancer (42.1%, 88.6%). None of the measures for stage simultaneously exceeded 80% for sensitivity, specificity, and PPV for any of the cancer sites. In adjusted analysis, older, lower-income, and African American patients were more likely to have stage at diagnosis misclassified from Medicare claims. Conclusions: Use of diagnosis codes alone in Medicare claims will misclassify stage at diagnosis for cancer patients, particularly for patients with metastatic disease. Our findings also suggest that using diagnosis codes for metastasis to define recurrence in Medicare claims will be limited.
Dystroglycan expression correlates with tumor grade and with outcome in renal cell carcinoma patients
Authors: A. Sgambato, A. Camerini, F. De Luca, G. Genovese, C. Valsuani, G. Tartarelli, O. Garrone, M. Cecchi, A. Cittadini, D. Amoroso
Journal: Journal of Clinical Oncology (2007)

15554 Background: The dystroglycan (DG) complex is a transmembrane glycoprotein that forms a continuous link from the extracellular matrix to the actin cytoskeleton. Deregulated expression of DG has been reported in a variety of human malignancies and related to tumor differentiation and aggressiveness. Methods: In this study, the expression of the a-subunit of DG was evaluated by immunostaining in a series of 125 renal cell carcinomas (RCCs) and its relation with disease progression and cancer-specific survival was evaluated. Results: to date, median follow-up is 19 months (range 1–96). We found that a-DG expression was lost in a significant fraction of tumors (66%) with 18% being the mean percentage of positive cells (median = 0; range = 0–80%). Loss of DG staining correlated with higher tumor grade (p=0.039) but not with tumor stage or size. Recurrence (p=0.014) and death (p=0.041) from RCCs were significantly more frequent in patients whose tumors displayed reduced staining for DG compared with patients whose tumors were positive for a-DG expression. Kaplan-Meier analysis showed a significant separation between high vs low a-DG expression for both disease-free (p=0.0094) and overall (p=0.0023) survival. In a multivariate analysis, loss of a-DG expression was the only independent risk predictor for recurrence (HR=6.509, p=0.0012) and death (HR=4.701, p=0.012) from RCCs when tumor size as well as tumor grade and stage were included in the model. Conclusions: These findings demonstrate that loss of a-DG expression, which correspond to loss a functional DG complex, is a frequent event in human renal tumorigenesis and is associated with an aggressive phenotype of the disease. They also suggest that evaluation of DG expression has the potential to offer important prognostic information and warrant further studies to better understand the role(s) of this molecule in term of renal cancer development and as a new prognostic marker for RCC patients. No significant financial relationships to disclose.