tbuckley/cabot-search huggingface dataset:
A phase III, randomized, open-label study of isatuximab (SAR650984) plus pomalidomide (Pom) and dexamethasone (Dex) versus Pom and Dex in relapsed/refractory multiple myeloma.
Authors: Paul G. Richardson, Michel Attal, Jesus San Miguel, Frank Campana, Solenn Le-Guennec, Ai-Min Hui, Marie-Laure Risse, Kenneth Carl Anderson
Journal: Journal of Clinical Oncology (2017)

TPS8057 Background: Treatment for refractory or relapsed and refractory multiple myeloma (MM) remains an unmet need. Isatuximab (ISA), an anti-CD38 monoclonal antibody with multiple mechanisms of tumor killing, has shown efficacy and an acceptable tolerability profile in Phase 1/2 studies in patients with refractory or relapsed and refractory MM (RRMM) (Richter et al. ASCO 2016; Vij et al. ASCO 2016). Methods: This Phase III, prospective, multicenter, randomized, open-label study (NCT02990338; ICARIA-MM) is being conducted to evaluate the clinical benefit of ISA in combination with Pom and low-dose Dex (Pom/Dex) versus Pom/Dex for the treatment of adult patients with RRMM and demonstrated disease progression within 60 days of the last therapy, and who have received at least 2 prior lines of therapy, including lenalidomide and a proteasome inhibitor (bortezomib, carfilzomib, or ixazomib) alone or in combination. Patients will be randomly assigned in a 1:1 ratio to either ISA (10 mg/kg IV on Days 1, 8, 15, and 22 in the 1st cycle; Days 1 and 15 in subsequent cycles) plus Pom (4 mg on Days 1–21) and Dex (40 mg for patients &lt; 75 years of age and 20 mg for patients ≥75 years of age, on Days 1, 8, 15, and 22) or Pom and Dex. Treatment cycles will be 28 days each. Patients will continue therapy until disease progression, occurrence of unacceptable adverse events (AEs), or their decision to discontinue the study, whichever comes first. The primary endpoint is progression-free survival (PFS), i.e. time from randomization to progressive disease or death from any cause. Response will be determined by IMWG criteria (2016). Key secondary endpoints include overall response rate and overall survival (OS). Safety evaluations include treatment-emergent AEs/serious AEs (including infusion-associated reactions), laboratory parameters, vital signs and assessment of physical examination. Statistical analyses will be conducted according to a pre-specified plan; approximately 300 patients (150 in each arm) are expected to be enrolled in this study. The first patient was recruited in January 2017. Study funding: Sanofi. Clinical trial information: NCT02990338.
An Adaptation of the Transparent-Chamber Technique to the Mouse
Authors: Glenn H. Algire
Journal: JNCI Journal of the National Cancer Institute (1943)

Journal Article An Adaptation of the Transparent-Chamber Technique to the Mouse Get access Glenn H. Algire Glenn H. Algire National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 4, Issue 1, August 1943, Pages 1–11, https://doi.org/10.1093/jnci/4.1.1 Published: 01 August 1943
Association of ERP29 genetic polymorphism in microRNA-binding site with oropharynx cancer risk and prognosis
Authors: J. Carron, E. Costa, L. Lopes-Aguiar, B. Sá Carvalho, J.A. Rinck-Junior, A.P. Dalla Costa, M. Ortega, C.S.P. Lima, G.J. Lourenço
Journal: Annals of Oncology (2017)
Brentuximab Vedotin for Patients With Refractory Lymphomatoid Papulosis
Authors: Daniel J. Lewis, Rakhshandra Talpur, Auris O. Huen, Michael T. Tetzlaff, Madeleine Duvic
Journal: JAMA Dermatology (2017)

Brentuximab vedotin is a monomethyl auristatin E-conjugated monoclonal antibody directed against CD30. It represents a potential treatment for the CD30+ lymphoproliferative disorder lymphomatoid papulosis (LyP), which currently has no approved treatment.To assess the efficacy and safety of brentuximab vedotin for the treatment of LyP.In this study conducted at The University of Texas MD Anderson Cancer Center from May 10, 2011, to March 31, 2017, a total of 12 patients with LyP received brentuximab vedotin. All patients were 18 years or older with a diagnosis of LyP and were also required to have scarring, more than 10 lesions, or active lesions on the face, hands, or feet. Nine patients were enrolled in a physician-initiated, open-label, single-center, phase 2 clinical trial of brentuximab vedotin for CD30+ cutaneous T-cell lymphomas and LyP from 2011 to 2013. Three patients were later treated outside of the trial from 2013 to 2017. Five patients continued to be followed up as of March 2017.Intravenous brentuximab vedotin 1.8 mg/kg infused over 30 minutes every 21 days.The primary end point was the overall response rate. Complete response was defined as zero lesions, and partial response was defined as a 50% or greater reduction in lesion count from baseline. A relapse was defined as loss of partial response.All 12 patients (8 men and 4 women; median age, 46 years) responded to brentuximab vedotin, and 7 exhibited a complete response. Time to response was 3 weeks in all patients. The median duration of response was 20 weeks (range, 6-103 weeks). For 5 patients who relapsed, the median time to relapse was 12 weeks (range, 6-41 weeks). One patient who relapsed was retreated and has remained in partial response for more than 23 months. Grade 1 to 2 neuropathy occurred in 10 patients but resolved in 5. Adverse events of grade 3 or higher were neutropenia (n = 2) and dizziness/vertigo (n = 1). Three patients withdrew owing to adverse events.Brentuximab vedotin is effective in treating LyP (overall response rate, 100%; complete response rate, 58%), but its use should be reserved for patients with truly severe and refractory LyP. More work is needed to optimize its dosing to minimize adverse events, such as peripheral neuropathy.clinicaltrials.gov Identifier: NCT01352520.
Interruption of the Inferior Vena Cava With Azygos Continuation
Authors: Chien-Wei Kuo, Nan-Jing Peng, Yu-Li Chiu
Journal: Clinical Nuclear Medicine (2017)

This report describes a 19-year-old man with interruption of the inferior vena cava with azygos continuation. Both radionuclide venography and MRI clearly showed venous return of the lower limbs through prominent collateral systems.
A novel pre-clinical mouse model of systemic metastatic cancer
Authors: Leanne Huysentruyt, Laura Shelton, Thomas Seyfried
Journal: Cancer Research (2008)

1163   Metastasis is the process by which cancer cells disseminate from the primary tumor and invade surrounding tissues, and is the primary cause of morbidity for cancer patients. Most conventional cancer therapies are ineffective in managing tumor metastasis. This has been due in large part to the absence of pre-clinical models that represent the full spectrum of metastatic disease. We recently identified a new tumor (VM-M3), which arose spontaneously in the brain of an inbred VM mouse. VM-M3 expresses all major biological processes of metastasis to include local invasion, intravasation, immune system survival, extravasation, and secondary tumor formation involving lung, liver, kidney, spleen, lung and brain. The VM-M3 tumor also expresses multiple properties of macrophages similar to those described previously in a variety of human metastatic cancers including skin, breast, lung, and some brain tumors. We used VM-M3 tumor cells that were transduced with a lentiviral vector expressing luciferase (VM-M3/Fluc). The cells were grown in the flank of the immunocompetent and syngeneic VM mouse host. We evaluated the anti-metastatic effects of methotrexate (25mg/kg) and cisplatin (10-15mg/kg) administered by single i.p. injections once/wk for three weeks. Bioluminescent imaging was used to measure VM-M3/Fluc growth and metastasis, while body weight and food intake were used to evaluate toxicity. All (12/12) untreated mice developed systematic metastatic cancer within 21 days of VM-M3/Fluc implantation. Although methotrexate did not inhibit VM-M3/Fluc primary tumor growth, it reduced lung and liver metastasis by 50% and completely inhibited metastasis to kidneys, spleen, and brain. In contrast, cisplatin significantly reduced primary tumor growth and also blocked metastasis to lung, liver, kidney, spleen, and brain in all treated animals. Our findings show that the VM-M3/Fluc tumor is a quick and reliable pre-clinical model for evaluating therapies for systematic metastatic cancer.
ATTRACTION-04 (ONO-4538-37): A randomized, multicenter, phase 2/3 study of nivolumab (Nivo) plus chemotherapy in patients (Pts) with previously untreated advanced or recurrent gastric (G) or gastroesophageal junction (GEJ) cancer
Authors: L-T. Chen, Y-K. Kang, M. Tanimoto, N. Boku
Journal: Annals of Oncology (2017)
Inclusion of older patients with colorectal cancer in clinical trials: the SAGE prospective multicenter cohort study
Authors: F. Canouï-Poitrine, A. Lievre, F. Dayde, D. Lopez-Trabada-Ataz, I. Baumgartner, O. Dubreuil, F. Brunetti, T. Aparicio, R. Coriat, K. Maley, O. Colussi, C. Tournigand, E. Paillaud, S. Bastuji-Garin
Journal: Annals of Oncology (2017)
Abstract 16703: Decompensated Heart Failure Patients with Preserved and Reduced Ejection Fraction who Require Ultrafiltration Therapy have Similar Morbidity and Mortality
Authors: Niyada Naksuk, Monica Colvin-Adams, Prangthip Charoenpong, Michael Petty, Marc Pritzker, Sofia C Masri
Journal: Circulation (2012)

Introduction:  Ultrafiltration therapy (UF) has been increasingly used for acute decompensated heart failure (ADHF) patients who failed diuretic therapy. However little is known about the outcomes of UF in heart failure patients refractory to standard medical therapy with preserved ejection fraction (pEF). Hypothesis: Patients with pEF who require UF therapy experience morbidity and mortality similar to heart failure patients with reduced EF (rEF).   Method:  We retrospectively studied 57 consecutive ADHF patients who required UF at University of Minnesota Medical Center from 2006 to 2011. All patients had a trial of loop diuretics. Selection of UF as the treatment method was made by the attending cardiologist. Subjects were divided into two groups: pEF (EF>0.45) and rEF (EF   Results:  Of a total of 57 patients, mean age was 67±14 years. Seventeen (30%) had pEF. Mean EF was 0.57±0.06 in the pEF group versus 0.25±0.11 in the rEF group (p    Conclusions:  ADHF patients who are not responsive to conventional medical therapy have a high 90-day readmission rate and mortality despite improvement in weight and fluid removal with UF. Interestingly, these outcomes are similar among heart failure patients with pEF and rEF. Further studies are required to clarify the role of UF in patients refractory to conventional treatment since it is unlikely to change the natural history of ADHF.
N-DUR: Matched pair pharmacodynamics study of neoadjuvant durvalumab in combination with chemotherapy in frontline ovarian cancer
Authors: J. Taylor, S. Westin, S. Sharafi, A. Jazaeri, M. Frumovitz, P. Soliman, A. Sood, K. Lu, K. Savelieva, G. Mills, A. Vergara-Silva, R. Coleman
Journal: Annals of Oncology (2017)
Improving Blood Pressure Control and Health Systems With Community Health Workers
Authors: Mark D. Huffman, Dike Ojji, Donald M. Lloyd-Jones
Journal: JAMA (2017)

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A phase I study of the EZH2 inhibitor tazemetostat in pediatric subjects with relapsed or refractory INI1-negative tumors or synovial sarcoma.
Authors: Susan N. Chi, Geoffrey Brian McCowage, Lindsey Hoffman, Margaret Macy, Susan Doleman, Stephen J Blakemore, Alicia Clawson, Scott Daigle, Jeanie Tang, Maria Roche, Peter T.C. Ho
Journal: Journal of Clinical Oncology (2016)

TPS10587 Background: Tazemetostat is a potent and selective inhibitor of the histone methyltransferase enhancer of zeste-homolog 2 (EZH2), the catalytic subunit of the polycomb repressive complex 2 (PRC2). EZH2 is responsible for trimethylation of lysine 27 on histone H3, which results in chromatin remodelling and repressed transcription. Aberrant EZH2 activity has been implicated as an oncogenic driver in non-Hodgkin lymphoma and other malignancies. The SWI/SNF complex also remodels chromatin, activates transcription, and acts in opposition to PRC2. Oncogenesis from mutation and/or loss of the SWI/SNF subunit INI1 in cancers such as malignant rhabdoid tumor (MRT) or SMARCA4 loss in ovarian “small cell carcinoma, hypercalcemic type” is associated with anticancer activity of EZH2 inhibition in preclinical models. This has translated into objective responses of promising durability in subjects (subjs) whose solid tumors exhibited either INI1 or SMARCA4 loss in the tazemetostat phase I adult study. Methods: This phase I, multi-center dose escalation (DEsc) and dose expansion (DExp) study administers tazemetostat twice daily (BID) using an oral suspension formulation in pediatric subjs age 6 months to 21 years. Approximately 24 subjs will be dosed using a “Rolling 6” DEsc design at a starting dose of 240 mg/m2 BID. Following DEsc, a DExp cohort will enroll up to 20 subjs. Eligible malignancies includerhabdoid tumors (MRT, atypical teratoid rhabdoid tumor, rhabdoid tumor of the kidney, MRT of ovary) that are INI1 or SMARCA4 negative, synovial sarcoma, and other INI1 negative tumors including epithelioid sarcoma, renal medullary carcinoma, myoepithelial carcinoma, and others. Response assessments are evaluated every 8 weeks using RANO or RECIST 1.1. Primary endpoints include dose-limiting toxicities/maximum tolerated dose (DEsc) and overall response rate (ORR) (DExp). Secondary endpoints include ORR (DEsc), progression-free survival, overall survival, safety/tolerability, PK and duration of response for confirmed responders. The first subj was dosed in January 2016 in the US with additional sites to be opened in Canada, the EU and Australia (NCT02601937). Clinical trial information: NCT02601937.
Substantial underreporting of tuberculosis in West Greece - implications for local and national surveillance
Authors: E Jelastopulu, E C Alexopoulos, D Venieri, G Tsiros, G Komninou, T C Constantinidis, K Chrysanthopoulos
Journal: Eurosurveillance (2009)

In order to estimate the reliability of the officially reported national tuberculosis (TB) incidence rates we performed a retrospective review of data collected in regional and national public health framework. TB notifications for the period 2000-2003 were obtained from two major hospitals and three relevant Public Health Departments (PHDs) in the region of West Greece, and subsequently compared with the data reported to the Hellenic Centre for Diseases Control (KEELPNO). During the four-year study period a total of 161 cases of TB were reported to the PHDs in West Greece; 70% of these cases were reported to the KEELPNO. Furthermore only 72 (38.7%) out of the 186 cases of TB identified in the two hospitals were notified to the PHDs. Assuming that the degree of undernotification observed for the two hospitals is the same throughout the region, we estimated that the case detection rate was 14 cases per 100,000 persons per year, i.e. 3.7 times higher than the rate officially reported for the period 2000-2003. Male predominance (2.1, male/female ratio) and an increased incidence in the elders (older than 60 years) and adolescents (10-14 years old) were also evident. The study demonstrated a substantial underestimation of TB burden in West Greece. In the face of the massive influx of immigrants and refugees coming from regions with high TB incidence and the increase of the number of drug-resistant cases a reliable and complete notification of TB is crucial in the planning of programs and development of appropriate control policies.
Genomic Subtypes of Nucleophosmin (NPM1) Mutations Are Associated with Clinical Outcome in AML - a COG and SWOG Intergroup Collaboration
Authors: Dalia Selim, Todd A. Alonzo, Megan Othus, Robert Gerbing, Fabiana Ostronoff, Katherine Tarlock, Matthew A. Kutny, Richard Aplenc, E. Anders Kolb, Jerald P. Radich, Frederick R. Appelbaum, Alan S. Gamis, Derek L. Stirewalt, Soheil Meshinchi
Journal: Blood (2016)
Survival prediction using time-evolving tumor load: An approach to rationally design treatment sequencing, staging, and dosing strategies for oncology combinations.
Authors: James Dunyak, Dmitry Onishchenko, Eric Masson, Gabriel Helmlinger, Helen Tomkinson, Kald Abdallah, Donald Stanski, Nidal Al-Huniti
Journal: Journal of Clinical Oncology (2017)

e20040 Background: Longitudinal tumor burden has long been used for the clinical diagnosis, staging, prognosis and treatment of non-small cell lung cancer (NSCLC). Tumor burden and growth rate correlate directly with survival and RECIST (measurement of tumor) is widely used as a surrogate endpoint. RECIST doesn’t take into account the impact of the therapy on the speed of growth over time, and poorly correlates with survival, especially in IO therapies. Surrogate endpoints such as progression-free survival (PFS) or dichotomous RECIST-based overall response rate (ORR) allow early assessment of efficacy based on reduced study population size. Unfortunately, ORR and PFS are poorly predictive of OS in NSCLC. This well-known loss of information during categorization emphasizes the potential benefits of continuous tumor load modeling. Methods: This research provides a statistically valid basis for modeling and interpretation of longitudinal response dynamics, in the context of time-to-event (survival) censoring, through development of a joint longitudinal/event model. Using clinical data from the Phase 3 IPASS study of Iressa (gefitinib), we build a generalizable model relating tumor load dynamics to a time-evolving hazard of progression. Results: Using longitudinal data from other smaller and shorter studies, we identify the time-progression of patient’s risk, including post-treatment time of minimum hazard of progression and the time when hazard rapidly increases. This is applied at both the population strata and individual patient level to assess different treatment paradigms. The model shows that EGFR-mutated patients on gefitinib have stable hazard of progression for about 8 months, as which point hazard increases rapidly. EGFR-mutated patients treated with carboplatin/paclitaxel started with a 72% higher initial progression hazard which then increased rapidly after 4 months. Conclusions: Because of their continuous-in-time nature, joint longitudinal/event models provide a basis for exploring the complex timing issues in oncology treatment sequencing, treatment staging strategies for combinations, and dosing regimes.
Treatment outcome according to tumor RAS mutation status in TRICOLORE trial: A randomized phase 3 trial of S-1 and irinotecan plus bevacizumab versus mFOLFOX6 or CapeOX plus bevacizumab as first-line treatment for metastatic colorectal cancer
Authors: Y. Komatsu, A. Takashima, T. Denda, M. Gamoh, I. Iwanaga, H. Shimodaira, M. Nakamura, T. Yamaguchi, H. Takahashi, K. Kobayashi, M. Tsuda, Y. Kobayashi, H. Baba, M. Kotake, C. Ishioka, A. Sato, S. Yuki, S. Morita, S. Takahashi, K. Shimada
Journal: Annals of Oncology (2017)
Comparison of stem cell signaling pathways in long-term responders (LR) versus primary refractory (PR) patients with metastatic clear-cell renal cell carcinoma (ccRCC) under sunitinib (SU) treatment (SULONG study).
Authors: Javier Puente, Nuria Laínez, María José Méndez-Vidal, Emilio Esteban, Daniel E. Castellano, Laura Basterretxea, María José Juan Fita, Luis Antón Aparicio, Luis León Mateos, Julio Jose Lambea- Sorrosal, Begoña Perez-Valderrama, Sergio Vazquez-Estevez, Cristina Suárez, Xavier Garcia del Muro, Enrique Gallardo, Pablo Maroto, Maria Victoria Bolós, Marina Morán, Julian Sanz
Journal: Journal of Clinical Oncology (2014)

4578 Background: Deregulation of stem cell signaling pathways, such as Notch and Sonic Hedgehog (SHH) seems necessary for tumor initiation, maintenance and progression. Preclinical evidence supports that they may play an oncogenic or tumor suppressor role depending on the tumor type. Methods: Retrospective, observational and multicenter study of patients (pts) treated with SU under clinical practice aimed to compare clinical and molecular characteristics in two groups of pts: Metastatic ccRCC pts who achieved progression free survival ≥ 22 months (LR), and pts who showed progressive disease at first radiological evaluation (PR). Tumour expression of different Notch (Jagged-1, Notch-1, nuclear N1ICD) and SHH (SFU-SHH suppressor and GLI-1) signalling components was evaluated by immunohistochemistry and correlated with treatment outcome. This study was approved by the Regulatory Authorities. Results: From a total of 123 pts, 97 were identified as LR and 26 as PR. Pts with higher Fuhrman grade, metastasis at diagnosis, shorter time from primary to metastatic diagnosis, no nephrectomy and brain, lung and hepatic metastasis were significantly higher in the PR cohort. So far, 47 tumor samples have been analyzed, 36 of LR and 15 of PR. Expression of Jagged-1 (p<0.001) and SFU (p<0.001) was significantly correlated with PR; as well as the join expression of Jagged-1/Notch-1+ and Jagged-1/N1ICD+ (p<0.001) confirming the activation of the pathway in this group. Jagged-1 expression was also significantly correlated to Furhman G4 (p<0.05) in the PR group, metastasis at diagnosis (p<0.001) in LR and poor risk group by Heng’s criteria (p<0.05) in the overall population. The ongoing molecular analysis of the remaining tumour samples and their correlation with PFS and OS in the LR group is warranted to confirm their predictive value under SU treatment. Conclusions: These preliminary results suggest that Notch signaling activation predicts poor outcome in metastatic ccRCC. By contrast, SHH seems to be activated in the LR group suggesting an opposite role for both pathways in this tumor.