tbuckley/cabot-search huggingface dataset:
Data quality in clinical trials.
Authors: Knud Mejer Nelausen, Hanne Marie Michelsen, Birgitte Krogh Jensen, Lisa Sengeløv, Marie-Helene Olsen, Dorte Lisbet Nielsen
Journal: Journal of Clinical Oncology (2014)

e17610 Background: Ensuring correct and complete source data in clinical trials is of outmost importance. Journal audits in the Dept. of Oncology revealed that source data were not always complete and thus the need to identify specific areas and extent of deficiencies. Methods: Coupling of data from patient’s clinical records and electronic medicine ordering records with findings by research nurse at point of CRF data entry, thereby identifying areas with missing or erroneous data. A questionnaire was developed. Results: From June to September 2013, 382 patient visits were examined. 187 of these had at least one or more deficiency which corresponds to 49% of the total registrations. Of these, deficiencies regarding Adverse Events (AE) are the most common (77%). For AEs, deficiencies were found in three main groups: Omissions in completing forms registering AEs per patient/visit: 39.6%; omission to register relationship to IMP: 37.4%; omitting start/stop dates: 21.2%. Of the 278 AE registrations with error/omissions there were 26 potentially significant errors which correspond to 10.7% of the registrations. (Significant errors: a) should have led to dose modification, b) essential for patient safety, or c) should have triggered a medical treatment/examination). Most deficiencies (57%) were found in investigator initiated trials and 5 doctors of 55 were linked to 39% of deficient registrations. Conclusions: The findings were not satisfactory from an efficacy and quality point of view, but it did not have major effect on the trial conduction when monitored by external audit. Several causes could explain the findings: insufficient documentation tools; lack of time to perform protocol requirements etc., poor understanding of GCP in clinical trials. Multi-targeted interventions will be planned to improve the production/efficacy, pending further analyses. A review of source data in clinical protocols revealed one or more deficiency in approximately half of all registrations. Deficiencies did not seem to have any significant impact on trial conduction. The conducted survey is an important tool to improve efficacy and quality.
Reintroduction of oxaliplatin for patients with metastatic colorectal cancer refractory to standard chemotherapy regimens.
Authors: Tohru Sasaki, Mizutomo Azuma, Wasaburo Koizumi, Tomohisa Egawa, Atsushi Nagashima, Takeshi Kenmochi, Ken Shimada, Yasutaka Takinishi, Kouji Kobayashi, Yusuke Saito, Sotaro Akatsuka, Hitoshi Arioka, Norisuke Nakayama, Ken Nishimura, Seiichi Takagi, Atsushi Shirahata, Hitoshi Soda
Journal: Journal of Clinical Oncology (2014)

630 Background: Reintroduction of oxaliplatin seems to have clinical benefits for patients with metastatic colorectal cancer refractory to standard chemotherapy regimens. A interim analysis of RE-OPEN study reported 38.9% of disease control rate (DCR) in ASCO GI 2013, but it is still unknown who will receive benefits from reintroduction of oxaliplatin. Methods: Among patients in whom oxaliplatin was reintroduced in the 7 participating hospitals, we retrospectively studied patients who had previously received oxaliplatin and irinotecan and patients who had a response of stable disease or better during initial treatment with oxaliplatin. Results: From June 2009 through January 2013, oxaliplatin was reintroduced in 53 patients (31 men and 22 women). The median age was 64 years, and the performance status was 0 in 24 patients and 1 in 29. The reasons for discontinuing initial treatment with oxaliplatin were progressive disease in 36 patients, adverse events in 14 and others in 3. The response rate (RR), DCR, the median progression-free survival (PFS), and the median overall survival were 3.8%, 47.2%, 105 days, and 313 days, respectively. As for adverse events, allergic reactions to oxaliplatin (grade 1 or higher) occurred in 26% of the patients. RR, DCR, and PFS in 44 patients with the oxaliplatin-free-interval (OFI) over 6 months were 4.6%, 54.6%, and 119 days, respectively, and were statistically better than those in 9 patients with OFI less than 6 months (0%, 11.1%, and 84 days). Reintroduction of oxaliplatin with bevacizumab showed better PFS than that without bevacizumab (114 days and 78 days, respectively). Conclusions: Reintroduction of oxaliplatin was suggested to be one option for the management of colorectal cancer that is resistant to standard therapy, especially in patients with OFI over 6 months. Bevacizumab may enhance the results of reintroduction treatment.
Evaluation of NF-κB2 polymorphisms rs7897947, rs11574852 and rs12769316 in NSCLC: A case-control study.
Authors: Fotinos-Ioannis D Dimitrakopoulos, Anna G Antonacopoulou, Anastasia E Kottorou, Stella Maroussi, Ioulia Koukourikou, Chrisoula D Scopa, Dimitrios Dougenis, Helen Papadaki, Haralabos Kalofonos
Journal: Journal of Clinical Oncology (2014)

e22044 Background: Lung cancer remains the leading cause of cancer-related deaths in both men and women worldwide. Last years, NF-κB2 (p52) expression has been demonstrated to be deregulated in lung cancer, contributing to the progression of the disease. In this study, we assessed the clinical relevance of the NF-κB2 single nucleotide polymorphisms rs7897947 (T/G),rs11574852 (A/C), rs12769316 (G/A) with NSCLC and with the expression pattern of NF-κB2. Methods: We used 281 blood and FFPE normal tissue specimens from patients with NSCLC and 279 blood specimens from healthy donors. DNA isolation was performed using the “Qiagen DNA blood” and the “QIAamp DNΑ FFPE Tissue kits”. Samples were genotyped using real-time PCR. Immunohistochemical analysis for NF-κB2 was performed on 130 FFPE specimens (120 tumors and 10 tumor-adjacent normal tissues) from NSCLC patients. Results: Statistically significant was the difference in allele frequencies of rs7897947 between healthy controls and patients (p=0.024). In addition, rs7897947 was related to the pathological stage of the disease (p=0.016). Moreover, T allele carriers had bigger tumors compared with GG homozygotes (p=0.04). Importantly, relapse rates of patients were associated with the second polymorphism (rs11574852, p=0.045). The difference with the infiltration of regional lymph nodes and with two- and five-year survival did not reach in statistical significance, but there was a trend that requires further validation (p 0.065 and p=0,079 respectively). Polymorphism rs12769316 had also strong associations with histological subtype, tumor grade and smoking (p=0.036, p=0.004, p=0.05 respectively). Another strong association of rs12769316 genotype AA was with cytoplasmic expression of NF-κB2 (p<0.001). Stratifying according to tumor grade, we observed rs12769316 be associated with two-year survival (p=0.05). Conclusions: NF-κB2 genetic polymorphisms seem to play an important role in the development of NSCLC. Our findings suggest that examined SNPs may become useful as independent biomarkers, improving diagnosis, prognosis and treatment of NSCLC patients.
Enhancement of Eligibility Guidelines for Gemtuzumab Ozogamicin Therapy for Childhood Acute Myeloid Leukemia: A Report from Children's Oncology Group Protocol AAML0531
Authors: Laura Pardo, Lisa Eidenschink Brodersen, Jatinder K Lamba, Todd A Alonzo, Yi-Cheng Wang, Dana Paine, Alan S Gamis, E. Anders Kolb, Jessica A. Pollard, Todd M Cooper, Richard Aplenc, Soheil Meshinchi, Michael R. Loken
Journal: Blood (2018)
NHS long term plan: Care to be shifted away from hospitals in “21st century” service model
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The NHS in England will shift its emphasis from acute care hospitals towards a “new service model for the 21st century” based on community care, population health, and collaboration, service leaders have vowed.

The pledge is a key part of the much anticipated NHS long term plan, published on 7 January,1 which sets out how the NHS will use the extra £20.5bn (€23bn; $26bn) a year by 2023-24 it will receive from the government to drive improvements in the service over the next decade.

The …
Characteristics, Treatment Patterns and Outcomes Among Newly Diagnosed Patients (pts) with Acute Myeloid Leukemia (AML) Who Present with Hyperleukocytosis: Findings from a Large International Patient Cohort
Authors: Maximilian Stahl, Wei Wei, Pau Montesinos, Etienne Lengline, Rory M Shallis, Judith Neukirchen, Vijaya R. Bhatt, Mikkael A. Sekeres, Amir T. Fathi, Heiko Konig, Selina Luger, Irum Khan, Gail J. Roboz, Thomas Cluzeau, David Martínez-Cuadron, Emmanuel Raffoux, Ulrich Germing, Jayadev Manikkam Umakanthan, Sudipto Mukherjee, Andrew M. Brunner, Adam M. Miller, Christine M. McMahon, Ellen K. Ritchie, Rebeca Rodríguez-Veiga, Raphael Itzykson, Blanca Boluda, Florence Rabian, Mar Tormo, Evelyn Gloria Acuna Cruz, Emma Rabinovich, Brendan Yoo, Nikolai A. Podoltsev, Steven D. Gore, Amer M. Zeidan
Journal: Blood (2018)
FGFR1 overexpression and anti-FGFR compound sensitivity in renal cell carcinoma.
Authors: Ilya Tsimafeyeu, Evgenia Stepanova, Elina Zaveleva, Marat Gordiyev, Nigel Wynn
Journal: Journal of Clinical Oncology (2014)

e15544 Background: Fibroblast growth factor receptor 1 (FGFR1) plays a significant role in renal cell carcinoma (RCC) pathogenesis. There are several compounds targeting FGFR1 on the horizon. Here, we report changes in FGFR1 overexpression/mutation and anti-FGFR compound sensitivity in RCC. Methods: Twenty-eight female NCr nu/nu mice (6-12 weeks of age) were used for xenotransplantation of human clear cell renal carcinoma Caki-1 cell line. Mice with established FGFR1-expressing tumors (an average size of 80-120 mg) received intravenous OM-RCA-01 (humanized anti-FGFR1 monoclonal antibody, 10 mg/kg, twice a week; N=14) or oral ponatinib (pan-FGFR inhibitor, 30 mg/kg, daily; N=14). Tumor sizes were measured in a blind fashion twice a week with a vernier caliper. Additionally, primary tumor and metastatic lesion of 40 RCC patients were accessed. Animal and patient formalin-fixed, paraffin-embedded specimens of tumors were evaluated by immunohistochemistry with FGFR1 antibodies. FGFR1 mutations were assessed by PCR and direct sequencing. Results: At in vivo study termination day (Day 31), there were 6 (43%) and 5 (36%) tumors reached end-point volume of 2000 mm3 in OM-RCA-01 and ponatinib groups, respectively. Nine (82%) of these 11 resistant tumors had no FGFR1 expression (5 and 4 tumors in OM-RCA-01 and ponatinib groups). FGFR1 was highly expressed in all 17 tumors that responded to OM-RCA-01 or ponatinib. Intensity was 3+ in all cases. Expression of FGFR1 was observed in 92.5% (37/40) of primary tumors and in 65% (26/40) of metastasis in RCC patients. FGFR1 expression decreased in 32% (12/37) and increased in 67% (2/3) of metastasis in comparison with primary tumors. No FGFR1 mutations were detected in animal and patient tumors. Conclusions: FGFR1 overexpression could be different in primary RCC and metastasis of same patient. Expression of FGFR1 was found in 100% of renal tumors that responded to anti-FGFR therapy and in 18% of resistant RCC. Further translational studies will provide more information.
Clinical correlates and outcome associated with changes in 6‐minute walking distance in patients with heart failure: findings from the BIOSTAT‐CHF study
Authors: João Pedro Ferreira, Marco Metra, Stefan D. Anker, Kenneth Dickstein, Chim C. Lang, Leong Ng, Nilesh J. Samani, John G. Cleland, Dirk J. van Veldhuisen, Adriaan A. Voors, Faiez Zannad
Journal: European Journal of Heart Failure (2019)
Pattern of traditional Islamic medicine utilization among adult oncology patients in Saudi Arabia.
Authors: Nagwa Abdel Rahman Ibrahim, Ahmed Al Eid, Ashraf Al Alwan, Yazeed Al Ghawa, Maram Al Ghalbi
Journal: Journal of Clinical Oncology (2014)

e20603 Background: Traditional Islamic Medicine (TIM) is a diverse of health practice used by patients as an orientation to their own values and believes toward good health which might affect the conventional cancer therapy. This issue was not well studied in our adult cancer patients. The aim of this study is to determine the pattern of utilization of Traditional Islamic Medicine among adult cancer patients in Saudi Arabia. Methods: We conducted a cross sectional descriptive study using interview-administered questionnaire on patients with cancer in the Adult Oncology Department of Prince Sultan Military Medical City, Riyadh, Saudi Arabia. Patients were asked about Traditional Islamic Medicine use including dietary supplement (DS) and non DS remedies. Univariate and multivariate analysis were conducted to identify the predicting factors for TIM use. Results: A total of 104 adult oncology patients were enrolled in the study with a median age of 52.5 years, and the ratio of females to males was (52%/48%). Out of 104 patients 97.1% used different types of dietary supplements remedies. The highest percentage of DS remedies used was honey (57.7%), followed by Zamzam water (26%), Nigella and Fenugreek (25% each). The majority of patients (91%) used the remedies for religious nature explained by patients as ‘’following Quran and Al Sunnah Al Nabawiah for our Prophet Mohamed’’. Other reasons mentioned for remedies use are treatment of cancer, management of therapy side effects, improve immunity, enhance wellbeing or upon advice from family member, friend, or patient. Only 21% of patients consulted TIM use with their doctors. The univariate analysis revealed that only female gender is a predictor of TIM use. The female gender remained significant in a multivariate analysis, in addition to disease stage. Conclusions: Traditional Islamic Medicine usage is highly prevalent among Saudi cancer patients. It indicates the strong influence of religion on people behaviour mainly those diagnosed with cancer. Given the possible potential risk with some TIM therapies, it is essential oncology clinical pharmacists ask patients whether they use TIM to provide the appropriate counselling. Clinical trial information: 448.
Aggregation of Child Cardiac Progenitor Cells Into Spheres Activates Notch Signaling and Improves Treatment of Right Ventricular Heart Failure
Authors: David Trac, Joshua T. Maxwell, Milton E. Brown, Chunhui Xu, Michael E. Davis
Journal: Circulation Research (2018)

Rationale: Congenital heart disease can lead to life-threatening right ventricular (RV) heart failure. Results from clinical trials support expanding cardiac progenitor cell (CPC) based therapies. However, our recent data show that CPCs lose function as they age, starting as early as 1 year. Objective: To determine whether the aggregation of child (1–5-year-old) CPCs into scaffold-free spheres can improve differentiation by enhancing Notch signaling, a known regulator of CPC fate. We hypothesized that aggregated (3-dimensional [3D]) CPCs will repair RV heart failure better than monolayer (2-dimensional [2D]) CPCs. Methods and Results: Spheres were produced with 1500 CPCs each using a microwell array. CPC aggregation significantly increased gene expression of Notch1 compared with 2D CPCs, accompanied by significant upregulation of cardiogenic transcription factors (GATA4, HAND1, MEF2C, NKX2.5, and TBX5) and endothelial markers (CD31, FLK1, FLT1, VWF). Blocking Notch receptor activation with the γ-secretase inhibitor DAPT (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester) diminished these effects. To evaluate the therapeutic improvements of CPC aggregation, RV heart failure was induced in athymic rats by pulmonary artery banding, and cells were implanted into the RV free wall. Echocardiographic measurements 28 days postimplantation showed significantly improved RV function with 3D compared with 2D CPCs. Tracking implanted CPCs via DiR (1,1’-dioctadecyl-3,3,3’,3’-tetramethylindotricarbocyanine iodide)-labeling showed improved retention of 3D CPCs. Transducing 3D CPCs with Notch1-shRNA (short hairpin RNA) did not reduce retention, but significantly reduced RV functional improvements. Histological analyses showed 3D treatment reduced RV fibrosis and increased angiogenesis. Although 3D CPCs formed CD31 + vessel-like cells in vivo, these effects are more likely because of improved 3D CPC exosome function compared with 2D CPC exosomes. Conclusions: Spherical aggregation improves child CPC function in a Notch-dependent manner. The strong reparative ability of CPC spheres warrants further investigation as a treatment for pediatric heart failure, especially in older children where reparative ability may be reduced.
Sarcopenia as a marker of outcome in patients with metastatic non-small cell lung cancer: A retrospective review.
Authors: Keerti Munnalal Khandelwal, Carlos Prevegliano,, Runhua Shi, Guillermo Sangster, Eduardo Toledo Gonzalez, Syed Hasan Raza Jafri
Journal: Journal of Clinical Oncology (2014)

e14000 Background: Most patients with lung cancer at the time of diagnosis have stage IV or metastatic disease.Various prognostic markers like performance are associated with worse outcome. We wanted to study if sarcopenia is a marker of poor outcome in stage IV NSCLC patients. Methods: Patients with metastatic NSCLC at diagnosis managed at Feist weiller cancer center between Jan 1, 2000 to June 30, 2011 were retrospectively studied. Abdominal CT scan done within one month of diagnosis was reviewed to determine the skeletal muscle area (SMA) using MIPAV (Medical Image Processing, Analysis, and Visualization) software. SMA was calculated at L1-L2 level by two investigators who were blinded to patient outcome. Skeletal muscle index (SMI) was calculated as (SMA/height (m²)). Kaplan-Meier method was used to estimate progression free survival and overall survival. Log-rank test were used to compare the survivals among various factors. Multivariate Cox regression was used to perform survival analysis in order to estimate the hazards ratio for various factors. Results: 112 patient CT scans were included in the analysis. Range of SMI was 23 to 77. Using receiver operating characteristics (ROC) analysis SMI value of 40 was selected to divide the group into sarcopenic (SMI ≤40) and non-sarcopenic ( >40).There was no difference in race, sex, performance status, histology and number of metastatic sites between the two groups. Sarcopenic patients were less likely to have any response to chemotherapy. Using multivariate analysis adjusting for age, sex, race and histology sarcopenic patients were found to have adverse progression free survival (HR= 1.69,95% CI (1.12- 2.58),p value =0.013 ) and overall survival (HR=1.58,95% CI (1.04-2.41), p value= 0.032). Conclusions: Sarcopenia (SMI of ≤40) is a marker of poor outcome and response to chemotherapy in patients with stage IV NSCLC. This should be validated in a prospective study.
64cu-DOTA-Anti-CD33 PET-CT Imaging for Acute Myeloid Leukemia and Image-Guided Treatment
Authors: Srideshikan Sargur Madabushi, Darren Zuro, Jamison Brooks, Bijender Kumar, Liliana E Parra, Marvin Orellana, Indu Nair, Junie Chea, Kofi Poku, Ching-Cheng Chen, James Sanchez, John E. Shively, Daniel A. Vallera, Jeffrey Wong, Anthony S. Stein, David Colcher, Paul Yazaki, Susanta Hui
Journal: Blood (2018)
Impact of complementary and alternative medicine (CAM), religiosity, and evidence-based medicine (EBM) in advanced cancer patients.
Authors: Dragan Trivanovic, Nika Spasic, Stjepko Plestina, Renata Dobrilla-Dintinjana, Lidija Kocic
Journal: Journal of Clinical Oncology (2014)

e17509 Background: Oncology organisations highlighted the need to improve communications and decision making for pts with advanced cancer. The primary aim is to test the hypothesis that EBM had important role in survival despite the prevalent role of CAM and religiosity. Methods: 124 adult cancer pts who attended the outpatient clinic in General Hospital Pula between January 2011 and December 2013, were evaluated for demographics, socioeconomic, educational, functional and cognitive status, psycho-oncological characteristics and prevalence of use of CAM, religiosity, methods of self-healing and to importance of believing and consuming the EBM. Results: Median age was 62 (range 26-83) years, the majority being male (61.3%), 67% of patients declared as agnostic/atheist. Median FU was 13.1 and OS was 12.4 months. The most common primary cancer sites were lung (38, 31%), colorectal (35, 28%), breast (19, 15%) and other sites (32, 26%). Patients, in general, were highly satisfied how oncologist discussed and conducted diagnosis and treatment procedures. Usage of CAM, methods of self healing and religious practice was very prevalent but not corelated with survival. In univariate analysis, patients who had better functional status (ECOG PS 0 or 1) had better survival as we expected (P=0.001). We found also that patients who were satisfied with communication with oncologist and his team, and had performed complete diagnostic and therapy procedure in one hospital center had better survival (P=0.008; P=0.026 respectively). In multivariate Cox proportional-hazards regression analysis, two independent prognostic parameters were retained (ECOG PS and importance of oncologist communications-EBM). See Table. Conclusions: Despite the prevalent use of CAM, and religiosity, cancer pts actively seeking out-methods of EBM with cleary proven benefit. Understanding the influence of religiosity and metaphysical self-knowledge may be a tool to help providers get their pts appropriate cancer care. Variable HR 95% CI P ECOG PS ≥2 0.21 0.04-0.92 0.013 Importance of EBM 2.616 1.21-5.65 0.014 Diagnostic and treatment in >1 center 0.58 0.34-1.01 0.052
Efficacy and Safety of Tyrosine Kinase Inhibitors for Treatment of Newly Diagnosed Chronic Myeloid Leukemia: Results Using Data Obtained with the New Target System from the Japanese Registry
Authors: Naoto Takahashi, Masahiro Kizaki, Masatomo Miura, Tatsuya Kawaguchi, Ritsuro Suzuki, Kazuhito Yamamoto, Kazunori Ohnishi, Itaru Matsumura, Tomoki Naoe, Koichi Akashi
Journal: Blood (2018)
MLL-USP2: An Underestimated New Entity of MLL-Rearranged Leukemia Identified By NGS Analysis
Authors: Claus Meyer, Bruno Lopes, Aurélie Caye-Eude, Hélène Cavé, Chloé Arfeuille, Rosemary Sutton, Nicola Venn, Patrizia Larghero, Seung Hwan Oh, Grigory Tsaur, Marketa Zaliova, Jan Zuna, Vesa Juvonen, Renate Panzer-Grümayer, Grazia Fazio, Giovanni Cazzaniga, Mariana Emerenciano, Rolf Marschalek
Journal: Blood (2018)