tbuckley/cabot-search huggingface dataset:
Phase III Prospective Randomized Comparison Trial of Depot Octreotide Plus Interferon Alfa-2b Versus Depot Octreotide Plus Bevacizumab in Patients With Advanced Carcinoid Tumors: SWOG S0518
Authors: James C. Yao, Katherine A. Guthrie, Cesar Moran, Jonathan R. Strosberg, Matthew H. Kulke, Jennifer A. Chan, Noelle LoConte, Robert R. McWilliams, Edward M. Wolin, Bassam Mattar, Shannon McDonough, Helen Chen, Charles D. Blanke, Howard S. Hochster
Journal: Journal of Clinical Oncology (2017)

Purpose Treatment options for neuroendocrine tumors (NETs) remain limited. This trial assessed the progression-free survival (PFS) of bevacizumab or interferon alfa-2b (IFN-α-2b) added to octreotide among patients with advanced NETs. Patients and Methods Southwest Oncology Group (SWOG) S0518, a phase III study conducted in a US cooperative group system, enrolled patients with advanced grades 1 and 2 NETs with progressive disease or other poor prognostic features. Patients were randomly assigned to treatment with octreotide LAR 20 mg every 21 days with either bevacizumab 15 mg/kg every 21 days or 5 million units of IFN-α-2b three times per week. The primary end point was centrally assessed PFS. This trial is registered with ClinicalTrials.gov as NCT00569127. Results A total of 427 patients was enrolled, of whom 214 were allocated to bevacizumab and 213 to IFN-α-2b. The median PFS by central review was 16.6 months (95% CI, 12.9 to 19.6 months) in the bevacizumab arm and was 15.4 months (95% CI, 9.6 to 18.6 months) in the IFN arm (hazard ratio [HR], 0.93; 95% CI, 0.73 to 1.18; P = .55). By site review, the median PFS times were 15.4 months (95% CI, 12.6 to 17.2 months) for bevacizumab and 10.6 months (95% CI, 8.5 to 14.4 months) for interferon (HR, 0.90; 95% CI, 0.72 to 1.12; P = .33). Time to treatment failure was longer with bevacizumab than with IFN (HR, 0.72; 95% CI, 0.58 to 0.89; P = .003). Confirmed radiologic response rates were 12% (95% CI, 8% to 18%) for bevacizumab and 4% (95% CI, 2% to 8%) for IFN. Common adverse events with bevacizumab and octreotide included hypertension (32%), proteinuria (9%), and fatigue (7%); with IFN and octreotide, they included fatigue (27%), neutropenia (12%), and nausea (6%). Conclusion No significant differences in PFS were observed between the bevacizumab and IFN arms, which suggests that these agents have similar antitumor activity among patients with advanced NETs.
Trends in survival and costs among U.S. patients with multiple myeloma.
Authors: Eric Maiese, Kristin Evans, Bong-Chul Chu, Debra E. Irwin
Journal: Journal of Clinical Oncology (2017)

12 Background: Survival among patients with multiple myeloma (MM)has improved over time, but little is known about concurrent changes in health care costs. This study examined trends in both survival and health care costs over the same time periods in U.S. patients with MM. Methods: The MarketScan Commercial and Medicare claims dataset was used to identify 5199 adult patients diagnosed with MM from Jan. 2006 to Dec. 2014. Patients had no prior evidence of cancer, were continuously enrolled for ≥ 12 months prior to MM diagnosis, and were followed through the earliest event (death, end of enrollment, or end of the study period (9/30/2015)). Multivariate GLM and Cox proportional hazards models estimated health care costs and survival probabilities, respectively, for two time periods during which patients were diagnosed with MM (2006-2010 vs. 2011-2014) while controlling for demographic and clinical characteristics. The recycled prediction method was used to calculate the incremental cost estimates between the time periods. Results: Patients diagnosed in 2011-2014 had a 35% lower risk of death compared to those diagnosed in 2006-2010 (HR [95% CI] = 0.65 [0.57-0.74]). Patients diagnosed in 2011-2014 had 18% (95% CI: 6-31%) higher all cause and 26% (95% CI: 6-50%) higher MM-related per patient per month costs compared to those diagnosed in 2006-2010 (see table). Conclusions: Among patients with MM, survival has improved at a greater rate than the increase in health care costs. In addition to improvements in MM treatment, changes in overall disease management may have contributed to both the increased expenditures and survival improvements observed in this study.[Table: see text]
Induction therapy for non small cell carcinoma (NSCLC) using the principle of radiation therapy induced sensitization to chemotherapy: A phase II study
Authors: H. Takita, A. Y. Soh, K. H. Shin, G. E. Wilding
Journal: Journal of Clinical Oncology (2004)

7317 Background: Previously we reported an enhanced effectiveness of chemotherapy in induction therapy of stage III lung cancer following a relatively low dose(20 Gy) of radiation therapy (Proc ASCO 18:524a, 1999): The response rate was 91 % (11/12 patients). Methods: Newly diagnosed patients with stage IB – IIIB NSCLC entered the study. The treatment consisted of 20 Gy of radiation therapy in 10 fractions to the primary and the mediastinum. This was followed by 2 courses of chemotherapy with taxol 180 mg/m2 intravenously (IV) in 3 hours; cisplatin 45 mg/m2 IV in 6 hours; and ifosfamide 1,000 mg/m2 IV in 6 hours. The patients were reassessed and if suitable the surgical therapy was advised. Results: From March 2000 to July 2003, thirty two patients entered the study.They were 11 patients with stage IB-IIB, and 21 patients with stage IIIA and B. The age ranged from 40 to 78 years.The performance status was 0 and 1. Grade ¾ leukopenia noted in 9 patients (one grade 4). Five patients received granulocyte colony stimulating factor. In 27 patients (84.38%) response was noted (confidence interval,CI 67.21 – 94.72%). Complete response (CR) was in 7 patients (21.88 %) (CI 9.28 – 39.97 %). In addition, 3 patients had a pathological CR of the surgically removed specimen thus the CR (clinical + pathological) rate was 10/32 (31.25%) (CI 16.12 – 50.01 %). Twenty two patients subsequently had the surgical therapy. Seven patients with CR and ten patients post operatively completed the remaining course of radiation therapy (45 Gy). There was no surgical mortality, one patient died of pulmonary toxicity after completing the full course of radiation (stage IIIA).The median follow up time is 21 months and the median survival was not observed but is estimated to be greater than 46 months. The 2 year survival of patients with stage IB – IIB is 57.14 %, and that of stage III (A and B) is 61.54 %. Conclusions:Induction therapy using radiation induced sensitization of chemotherapy produced a high response rate with a low treatment related mortality (3.7 %), and appears to be a suitable regimen for induction therapy for the locoregional NSCLC including earlier stage. No significant financial relationships to disclose.
Radioimmunotherapy of B-lineage non-Hodgkin's lymphoma using anti-CD19 and anti-CD20 conjugates
Authors: S. W. Heeger, G. Moldenhauer, J. M. Flynn, G. Egerer, T. Nikula, C. Apostolidis, M. Brechbiel, U. Haberkorn, A. D. Ho, R. Haas
Journal: Journal of Clinical Oncology (2004)

2625 Background: Radioimmunotherapy of non-Hodgkin's lymphoma has proven effectiveness when using anti-CD20 radioconjugates. So far, two different constructs are approved by the FDA: Zevalin and Bexxar. These substances reveal strong cytotoxicity taking advantage of the beta-emitting radioisotopes Yttrium-90 and Iodine-131 respectively. Due to the long range of these two radionuclides, they are probably most useful to treat large tumour burden as they exhibit the so-called "crossfire"-effect. This trait, however, is associated with non-specific cytotoxicity of healthy tissue and responsible for the dose limiting toxicity (DLT) in case of myelosuppression. We are currently evaluating anti-CD19 and anti-CD20 radioconjugates coupled to either Lutetium-177 or Bismuth-213. Lutetium-177 represents a beta-emitting radioisotope with a short path length and therefore a potentially more tumour-selective candidate for RIT. Even more effective and shorter in range are alpha-emitters such as 213Bi. These properties make them especially suitable to eradicate minimal residual disease. Methods: In vivo stability, biodistribution and toxicity of anti-CD19-CHX-A"- and anti-CD20-CHX-A"-Bismuth-213 were investigated in Balb/c mice. In CD19 transgenic mice bearing CD19 positive murine lymphoma biodistribution of anti-CD19-radioconjugates were evaluated with and without prior pretreatment with cold antibody. Results: Tissue-to-blood ratios were less than 0.3 indicating that there is no nonspecific uptake in mouse tissue or degradation of the Bismuth compounds As expected, DLT was myelosuppression, whereas other organs were not affected. Injections of cold antibody prior to the injection of the radioconjugates resulted in a decrease of the uptake in the spleen from 48% to 16% of the injected dose per gram organ weight after six days. A phase I dose escalation trial was conducted to determine safety and feasibility of anti-CD20-CHX-A"-Bismuth-213. Conclusions: Both Bismuth-213-and Lutetium-177-labelled anti-CD19 and anti-CD20 antibody conjugates might evolve as a promising strategy to improve therapy of refractory B-cell malignancies. No significant financial relationships to disclose.
Phase II, multicentre study evaluating cisplatin (P), epirubicin (E) and vinorelbine (V) as first line chemotherapy (CHT) in advanced breast cancer (ABC): A new promise
Authors: S. Barni, M. T. Ionta, R. Labianca, A. Zaniboni, A. Ardizzoia, B. Massidda, C. Tondini, D. Capra, C. Demontis, M. E. Cazzaniga
Journal: Journal of Clinical Oncology (2004)

761 Background: ABC is an incurable disease and CHT has only a palliative aim. Our previous studies demonstrated that PEV regimen is an active and well tolerated treatment both in locally advanced BC and as neoadjuvant therapy. Taking in mind those results we planned a multicenter Phase II study aimed to investigate the activity and tolerability of PEV regimen as front line CHT in ABC patients (pts). Methods: After informed consent, 46 unselected pts entered the study, of whom 14 were metastatic at diagnosis. Median age was 41 (27–72) and median DFI was 32.5 months. Fourteen pts out of 46 (30.4%) had received an anthracycline-based adjuvant CHT. More than half of the pts (25; 54.3%) presented 2 or more mestastatic sites. CDDP was administered at the dose of 50 mg/sqm, EPI 100 mg/sqm and VNB 25 mg/sqm, every 21 days. A total of 235 cycles were delivered (4, range 2–6). Results: We obtained 4 CR and 18 PR (ORR 47.8%), whereas 15 pts had SD (32.6%). Median duration of OR was 5.5 months, while median time to progression (TTP) was 10.5 months. Grade 3/4 toxicities were neutropenia (80/235, 34%), leucopenia (56, 23.8%) and anemia (14, 5.9%). Only one pt developed febrile neutropenia. No cardiac toxicity was observed. Dose-intensity of PEV regimen were 94.9, 90.4 and 94.9 for CDDP, EPI and VNB respectively. Conclusion: In conclusion, PEV is an active, low cost and well tolerated front-line CHT regimen for pts with ABC. Dose-limiting toxicity is represented by haematological toxicity, mainly neutropenia. A comparison with taxane-based CHT is needed. No significant financial relationships to disclose.
The Impact of Open Access upon Public Health
Journal: PLoS Medicine (2006)

A rthur Amman, President of Global Strategies for HIV Prevention (http:⁄⁄www.globalstrategies.org),tells this story:"I recently met a physician from southern Africa, engaged in perinatal HIV prevention, whose primary access to information was abstracts posted on the Internet.Based on a single abstract, they had altered their perinatal HIV prevention program from an effective therapy to one with lesser effi cacy.Had they read the full text article they would have undoubtedly realized that the study results were based on shortterm follow-up, a small pivotal group, incomplete data, and unlikely to be applicable to their country situation.Their decision to alter treatment based solely on the abstract's conclusions may have resulted in increased perinatal HIV transmission."Amman's story shows the potentially deadly gap between the informationrich and the information-poor.This gap is not the result of lack of technology or of money, but of a failure of imagination.We live in the most information-rich era of history, when the Internet allows immediate global dissemination of crucial health information, and the interlinking of online information creates an integrated, living body of information-the ultimate vision of which is the semantic Web (http:⁄⁄www.w3.org).What is preventing such a living Web?For scientifi c and medical information, two obstacles are vested interests and traditions.The role of copyright, which was developed when the dissemination of work was on paper, is crucial.Initially, applying copyright to medical articles protected both the intellectual investment of authors and the commercial investment of publishers.Authors of scientifi c articles handed over their
eIF5A-PEAK1 Signaling Regulates YAP1/TAZ Protein Expression and Pancreatic Cancer Cell Growth
Authors: Jan Strnadel, Sunkyu Choi, Ken Fujimura, Huawei Wang, Wei Zhang, Meghan Wyse, Tracy Wright, Emilie Gross, Carlos Peinado, Hyun Woo Park, Jack Bui, Jonathan Kelber, Michael Bouvet, Kun-Liang Guan, Richard L. Klemke
Journal: Cancer Research (2017)

In pancreatic ductal adenocarcinoma (PDAC), mutant KRAS stimulates the translation initiation factor eIF5A and upregulates the focal adhesion kinase PEAK1, which transmits integrin and growth factor signals mediated by the tumor microenvironment. Although eIF5A-PEAK1 signaling contributes to multiple aggressive cancer cell phenotypes, the downstream signaling processes that mediate these responses are uncharacterized. Through proteomics and informatic analyses of PEAK1-depleted PDAC cells, we defined protein translation, cytoskeleton organization, and cell-cycle regulatory pathways as major pathways controlled by PEAK1. Biochemical and functional studies revealed that the transcription factors YAP1 and TAZ are key targets of eIF5A-PEAK1 signaling. YAP1/TAZ coimmunoprecipitated with PEAK1. Interfering with eIF5A-PEAK1 signaling in PDAC cells inhibited YAP/TAZ protein expression, decreasing expression of stem cell-associated transcription factors (STF) including Oct4, Nanog, c-Myc, and TEAD, thereby decreasing three-dimensional (3D) tumor sphere growth. Conversely, amplified eIF5A-PEAK1 signaling increased YAP1/TAZ expression, increasing expression of STF and enhancing 3D tumor sphere growth. Informatic interrogation of mRNA sequence databases revealed upregulation of the eIF5A-PEAK1-YAP1-TEAD signaling module in PDAC patients. Taken together, our findings indicate that eIF5A-PEAK1-YAP signaling contributes to PDAC development by regulating an STF program associated with increased tumorigenicity. Cancer Res; 77(8); 1997-2007. ©2017 AACR.
Inferior Vena Caval Filter Insertion in Trauma Patients—Reply
Authors: Shayna Sarosiek, Denis Rybin, George Kasotakis
Journal: JAMA Surgery (2017)

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Vitreous microRNA levels as diagnostic biomarkers for vitreoretinal lymphoma
Authors: Vinodh Kakkassery, Roland Schroers, Sarah E. Coupland, Marc-Ilan Wunderlich, Marc Schargus, Carsten Heinz, Susanne Wasmuth, Arnd Heiligenhaus, Guido Ahle, Patrick Lenoble, Uwe Schlegel, Wolff Schmiegel, H. Burkhard Dick, Alexander Baraniskin
Journal: Blood (2017)
Immunohistochemical approach of microsatellite instability (MSI) and intratumoral microvessel density (IMD) in sporadic gastric cancer (sGC): Correlation with clinicopathological parameters and survival rates
Authors: S. Meditskou, T. Toliou, P. Makrantonakis, P. Stravoravdi, G. Geromichalos, K. Dimitriadis
Journal: Journal of Clinical Oncology (2004)

9675 Background: Defects of the mismatch repair (MMR) system leading to MSI are important in gastric carcinogenesis. High IMD is associated with poor prognosis. Few studies correlate IMD with MMR genes in sGC. We investigated the MLH1and MSH2 proteins (MMR gene products), and IMD and correlated their expression with clinicopathological parameters and survival. Methods: Gastric adenocarcinomas from 45 pts (M/F: 29/16; mean age: 59; 8 of them <50 years old) were analyzed. The histological type was evaluated according to Lauren as: intestinal 28 (62.2%); diffuse:17 (26.4%) and to Carneiro as: glandular 14 (31.1%), isolated 12 (20.7%) and mixed 19 (42.2%). TNM stage was: 3 stage I; 17 II; 17 III; and 6 stage IV. The pts were followed up for a maximum of 10-yrs. MSI was assessed on paraffin sections of tumor and adjacent normal mucosa (using monoclonal antibodies) against MSH2–1, MSH2–2 and MLH1 proteins. Tumors with loss of at least one protein expression were defined as MMR(-). IMD (MoAb CD 34) was evaluated by an interactive image analysis morphometric program (vessels /mm3). Results: MMR(-) cases were correlated with younger age (mean age 52.5 vs. 62.5, p<0.05). MMR negativity was verified in 17% of pts; 75% of these cases were of the diffuse type (p<0.05) and 87.5% of the isolated (75%) or mixed (25%) type (p<0.05). High IMD was noticed in sGC of the diffuse type (p<0.01) and isolated or mixed type (p<0.007). No significant differences were documented between survival and MMR gene products. IMD did not correlate alone with survival and was not an independent prognostic factor. In multivariate analysis TNM stage and vessel invasion were independent prognostic factors (p<0.02). Conclusions: MMR(-) cases constitute a particular group of sGC with different prognosis, distinct clinicopathological characteristics and high IMD. The detection of MSI and IMD in sGC may have clinical and prognostic implications. No significant financial relationships to disclose.
Impact of baseline BMI and weight change in CCTG adjuvant breast cancer trials
Authors: R. Yerushalmi, B. Dong, J.W. Chapman, P.E. Goss, M.N. Pollak, M.J. Burnell, M.N. Levine, V.H.C. Bramwell, K.I. Pritchard, T.J. Whelan, J.N. Ingle, L.E. Shepherd, W.R. Parulekar, L. Han, K. Ding, K.A. Gelmon
Journal: Annals of Oncology (2017)
Development of a registry to evaluate hospital admissions related to chemotherapy toxicity in a community cancer center
Authors: M. K. Krzyzanowska, J. T. Treacy, B. A. Maloney, A. Lavino, J. O. Jacobson
Journal: Journal of Clinical Oncology (2004)

6062 Background: While most chemotherapy (CT) administration occurs in routine care settings, there is a lack of data on toxicity (TOX) outside of clinical trials. After developing a mechanism for identifying all patients with CT-related hospitalizations in our center we created a prospective registry of such admissions in order to examine trends in TOX, modify practice, and establish benchmarks for severe TOX in a community cancer center. Methods: The North Shore Cancer Center is a community-based cancer facility in Peabody, MA. Eligible population consisted of all adult patients admitted to hospital within 30 days of their last CT administration. Each admission was reviewed by a panel of hospital staff to determine whether it was treatment-related; admission information was collected using a standard form. Results: Between 10/01/2001 and 10/31/2003 there were 335 hospitalizations among patients receiving CT, 110 (33%) of which were deemed CT-related. During this time period 7,632 patient months of parenteral CT were administered. The median time from last CT administration to admission was 7 d. Median age of the cohort was 67 (range 21–93) and 43% were male. NHL (25%) and colorectal cancer (17%) were the most frequent diagnoses. Approximately 54% of patients were receiving CT with palliative intent. Most common reasons for admission were infection or gastrointestinal TOX (37% each). Platinum- (25%) or fluorouracil-based (22%) regimens and CHOP (22%) resulted in the greatest number of admissions. The mean length of stay was 7.3 d (range 0–49); 6 patients died during hospitalization (5%). When the registry was reviewed to identify areas where care may be improved, several admissions for decadron-related hyperglycemia in non-diabetic patients with myeloma were identified. This resulted in introduction of glucose monitoring guidelines with no subsequent admissions for this TOX since then. Conclusions: About one third of hospital admissions in patients receiving CT are treatment-related and most occur in patients with advanced cancer. Collection of data on toxicity is feasible in the routine setting and can facilitate quality improvement. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho Biotech