tbuckley/cabot-search huggingface dataset:
Validity and reliability of the patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE).
Authors: Amylou C. Dueck, Tito R. Mendoza, Sandra A. Mitchell, Bryce B. Reeve, Kathleen M. Castro, Andrea Denicoff, Ann M. O'Mara, Lauren J. Rogak, Steven B. Clauser, Donna M. Bryant, Theresa A. Gillis, James D. Bearden, Robert D. Siegel, Jay K. Harness, Diane B. Paul, Charles S. Cleeland, Jeff A. Sloan, Deborah Schrag, Lori M. Minasian, Ethan M. Basch
Journal: Journal of Clinical Oncology (2012)

9047 Background: Symptomatic adverse events (AE) in cancer trials are reported by clinicians using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE). To integrate the patient perspective into AE reporting, NCI contracted (HHSN261201000043C) to create a patient-reported outcomes companion tool (PRO-CTCAE). We report the validity and reliability of PRO-CTCAE’s 124 items reflecting 78 symptomatic AEs. Methods: English-speaking subjects (n=869; 44% male; median [mdn] age 59; 32% racial/ethnic minority; 34% high school or less; 17% ECOG Performance Status [PS] 2-4) receiving treatment for a range of cancers at 4 NCI-designated cancer centers and 5 sites in NCI's Community Cancer Centers Program completed a web-based survey in clinic including PRO-CTCAE and EORTC QLQ-C30. Pearson correlations were computed between PRO-CTCAE items and QLQ-C30 scales. Differences in PRO-CTCAE item scores between clinician-reported ECOG PS (0-1 vs 2-4) groups were computed. Test-retest reliability of 48 prespecified items was evaluated in a subset (n=79). Results: Correlations in the expected direction were observed for 116/124 PRO-CTCAE items with the QLQ-C30 global health scale (mdn r=-.21; range .08 to -.57). Stronger correlations were seen for PRO-CTCAE items with conceptually related QLQ-C30 domains: fatigue with physical, role and social functioning (-.54 to -.66); anxiety and depression with emotional functioning (-.54 to -.70); and concentration and memory problems with cognitive functioning (-.62 to -.72) [all p &lt;0.001]. Fatigue, nausea, vomiting, pain, dyspnea, insomnia, appetite loss, constipation and diarrhea items strongly correlated with corresponding QLQ-C30 symptom scales (.69 to .79, all p &lt;0.001). Scores for 98/124 PRO-CTCAE items were higher in the ECOG PS 2-4 vs 0-1 group (mdn effect size .3). Test-retest reliability was observed across all tested items (mdn intraclass correlation coeff .77; range .53 to .96). Conclusions: Results demonstrate favorable validity and reliability of PRO-CTCAE in a large, heterogeneous sample of patients undergoing cancer treatment. Further testing in multicenter treatment trials is underway.
A phase II study of weekly 24-hour infusion with high-dose fluorouracil with leucovorin in colorectal carcinoma.
Authors: B Ardalan, L Chua, E M Tian, R Reddy, K Sridhar, P Benedetto, S Richman, A Legaspi, S Waldman, L Morrell
Journal: Journal of Clinical Oncology (1991)

Twenty-two patients with advanced colorectal carcinoma were enrolled in this study. Ten patients had received prior chemotherapy that included the combination of fluorouracil (5-FU) and leucovorin (LV). All patients required subcutaneous port insertion and portable external infusion pumps to allow outpatient treatment. 5-FU (2,600 mg/m2) was administered concurrently with LV (500 mg/m2) over 24 hours of continuous infusion. The mean steady-state plasma concentration of 5-FU was 10 mumol/L (range, 7 to 14 mumol/L). The 5-FU dose was based on our previous phase I study, in which maximum-tolerated dose (MTD) of 5-FU was determined to be 2,600 mg/m2 in combination with a fixed dose of LV at 500 mg/m2. The treatment was repeated weekly. Twenty-two patients received a total of 560 courses of treatment. Eleven instances of grade 2-3 toxicity were observed: diarrhea (five), stomatitis (three), hand/foot syndrome (three). The overall objective response was 45% (10 of 22) and among previously untreated patients was 58%. Three of the responders achieved complete response (CR), with lung and liver as the metastatic sites. The median duration of survival for the previously untreated patients was not reached at 22 months, and was 10 months for the previously treated patients. These results suggest that short-term infusional therapy of 5-FU and LV in patients with advanced metastatic colorectal cancer generates acceptable toxicity, with equivalent or superior survivability in previously treated and untreated patients versus alternative methods of administration of the two agents.
Comparison of the American PPCM Registry Data With International Registries
Authors: Denise Hilfiker-Kleiner, Karen Sliwa, Johann Bauersachs
Journal: Journal of the American College of Cardiology (2016)

We congratulate McNamara et al. [(1)][1] for these exciting new data on a cohort of 100 women diagnosed with peripartum cardiomyopathy (PPCM). This study adds important information with regard to ethnic differences and prognosis as the current management allows it.

However, we noted that several
The King's brief interstitial lung disease quality of life questionnaire (K-BILD) for patients with IPF and other ILDs
Authors: Amit S. Patel, Richard Siegert, Kate Brignall, Sabrina Bhajwah, Sujal R. Desai, Athol U. Wells, Irene J. Higginson, Surinder S. Birring
Journal: European Respiratory Journal (2011)

We set out to develop a brief ILD specific health related quality of life (HRQOL) questionnaire for patients with idiopathic pulmonary fibrosis (IPF) and other ILDs. Items were generated from patient interviews (n=10), literature review and a multi-disciplinary team meeting. A preliminary questionnaire consisting of 71 items and a 7 point Likert response scale was tested in 173 patients (49 IPF). The following items were removed: 1) floor effect: >60% of participants responded “rare” or “never” (25 items), 2) inter-item correlations of r>0.8 (7 items), 3) Exploratory factor analysis (FA): items loading <0.5 on each factor (5 items). A scree plot suggested a 4 factor solution. 4) Items that did not fit unidimensional scales following Rasch analysis (9 items). The remaining 25 items were pooled together and subjected to further Rasch analysis to eliminate items that did not conform to a unidimensional overall HRQOL scale (10 items removed). A repeat FA was performed to confirm the remaining items conformed to the original factor solution. The fourth factor consisted of 1 item which was considered too small to constitute a health domain but remained in the questionnaire to generate an overall HRQOL score. The final King's Brief ILD questionnaire (K-BILD) comprises of 15 items which generate an overall and 3 health domain QOL scores (Psychological (7items), Breathlessness and Activities (4 items) and Physical Symptoms (3 items). The K-BILD is currently undergoing evaluation of repeatability and responsiveness.
Filaggrin inhibits generation of CD1a neolipid antigens by house dust mite–derived phospholipase
Authors: Rachael Jarrett, Mariolina Salio, Antonia Lloyd-Lavery, Sumithra Subramaniam, Elvire Bourgeois, Charles Archer, Ka Lun Cheung, Clare Hardman, David Chandler, Maryam Salimi, Danuta Gutowska-Owsiak, Jorge Bernardino de la Serna, Padraic G. Fallon, Helen Jolin, Andrew Mckenzie, Andrzej Dziembowski, Ewa Izabela Podobas, Wojciech Bal, David Johnson, D. Branch Moody, Vincenzo Cerundolo, Graham Ogg
Journal: Science Translational Medicine (2016)

Lack of the skin barrier protein filaggrin worsens atopic dermatitis by allergenic activation of CD1a-reactive T cells.
Use of peripheral blood mRNA signatures to distinguish colorectal cancer patients from colonoscopy-negative patients.
Authors: Y. Xu, S. Ni, Q. Xu, F. Liu, F. Wu, X. Ye, X. Meng, B. Mougin, X. Du, S. Cai
Journal: Journal of Clinical Oncology (2010)

10564 Background: Colorectal cancer (CRC) represents the 4th common cancer in China with more than 170,000 new cases annually. In Shanghai, CRC increased rapidly during the latest decade (second most common cancer), and its early detection remains a major public health challenge. Fecal occult blood testing and colonoscopy aim to identify CRC patients from symptomatic or asymptomatic people, but both require heavy logistics. A simpler blood-based test would represent an interesting alternative. DNA-microarrays and PAXgene are used to study the gene expression repertoire in peripheral blood samples, suitable for new biomarker discovery. Methods: 119 CRC patients without previous radiotherapy or chemotherapy and 101 colonoscopy-negative controls without polyps or CRC were enrolled in our study. RNA extracted from peripheral blood samples collected in PAXgene tubes, were analysed after NuGEN WT-Ovation RNA amplification, using Affymetrix GeneChip HG-U133 Plus 2.0 Array. Molecular signature analysis was performed based on 5-fold cross validation process. In each iteration, 95 CRC and 80 control samples were randomly assigned to training set for gene selection and classification model training. The retained 24 CRC and 21 control samples were used as test set to assess the classification model performance. The process was repeated for 1000 iterations. Eventually, accuracy, sensitivity and specificity were used to assess the overall performance. Results: One thousand of 100-gene based SVM classifiers were studied. The performance observed was overall accuracy 0.93 (95%CI: 0.928-0.932), sensitivity 0.93 (95%CI: 0.926-0.934) and specificity 0.92 (95%CI: 0.916-0.924). The majority of selected genes represent cell death, cell adhesion, immune system development and signal transduction information, indicating the molecular changes occurring during colorectal cancer progression. Conclusions: Our results demonstrate the feasibility of gene expression profiling in peripheral whole blood for biomarker discovery for early detection of colorectal cancer. Validation of these findings in larger independent series are ongoing, strongly motivated by the performance observed at this stage. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration bioMerieux
Randomized comparison of 36-hour intermediate-dose versus 4-hour high-dose methotrexate infusions for remission induction in relapsed childhood acute lymphoblastic leukemia.
Authors: C Wolfrom, R Hartmann, R Fengler, S Brühmüller, A Ingwersen, G Henze
Journal: Journal of Clinical Oncology (1993)

PURPOSE Pharmacokinetics, toxicity, and therapeutic efficacy of two different methotrexate (MTX) infusions for remission induction of relapsed childhood acute lymphoblastic leukemia (ALL) were investigated in a randomized multicenter trial. PATIENTS AND METHODS Sixty patients with early bone marrow relapse received a polychemotherapy induction protocol starting with either 12 g/m2 MTX as a 4-hour infusion (high-dose [HDM]) or 1 g/m2 as a 36-hour infusion (intermediate-dose [IDM]). In HDM, leucovorin (LCV) was administered orally (12 times, 15 mg/m2 every 6 hours), beginning at hour 24. In IDM, only two doses were administered at hours 48 and 54. RESULTS Median serum MTX concentrations during infusion were 716 mumol/L in HDM and 7.2 mumol/L in IDM. In HDM, MTX serum levels at hour 24 (median, 2.8 mumol/L) were significantly less than steady-state levels of IDM. Concentrations greater than 1 mumol/L were maintained for 36 hours with HDM and 45 hours with IDM. General tolerance to treatment was better in the HDM group. Mucosal lesions occurred significantly more often and were more severe after IDM treatment. A median treatment delay of 3 days was required in the IDM group but not in the HDM group. At day 15, complete remission (CR) was documented in 45% of IDM- and 48% of HDM-treated patients. Persistent blasts (&gt; 5%) appeared more frequently in HDM than in IDM (35% v 19% of patients; P = NS). After completion of induction therapy, 28 of 30 patients in each group achieved CR. CONCLUSION Both regimens produced the same remission rates. The tendency to better antileukemic activity of IDM was accompanied by more severe side effects as a consequence of long-lasting cytotoxic MTX levels. Hence, long-term infusion of IDM followed by low-dose LCV is an effective treatment for recurrent ALL.
Abstract A2-02: SF3B1 mutations constitute a novel therapeutic target in breast cancer
Authors: Sarah Maguire, Andri Leonidou, Patty Wai, Caterina Marchio, Charlotte Ng, Ana Sapino, Anne Vincent-Salomon, Jorge Reis-Filho, Britta Weigelt, Rachael Natrajan
Journal: Cancer Research (2015)

Abstract Mutations in genes encoding proteins involved in RNA splicing have been found to occur at relatively high frequencies in several tumour types including myelodysplastic syndromes, chronic lymphocytic leukaemia, uveal melanoma, pancreatic cancer and at lower frequencies in breast cancer. To investigate whether dysfunction in RNA splicing is implicated in the pathogenesis of breast cancer, we performed a re-analysis of published exome and whole genome sequencing data. This analysis revealed that mutations in spliceosomal component genes occurred in 5.6% of unselected breast cancers, including hotspot mutations in the SF3B1 gene, which were found in 1.8% of unselected breast cancers. SF3B1 mutations were significantly associated with ER-positive disease, AKT1 mutations and distinct copy number alterations. Additional profiling of hotspot mutations in a panel of special histological subtypes of breast cancer showed that 16% and 6% of papillary and mucinous carcinomas of the breast harboured the SF3B1 K700E mutation. RNA sequencing identified differentially spliced events expressed in tumours with SF3B1 mutations including the protein coding genes TMEM14C, RPL31, DYNL111, UQCC and ABCC5 and the long non-coding RNA CRNDE. Moreover, SF3B1 mutant cell lines were found to be sensitive to the SF3b complex inhibitor spliceostatin A and treatment resulted in perturbation of the splicing signature. Our findings indicate that albeit rare, SF3B1 mutations result in alternative splicing events, and may constitute drivers and a novel therapeutic target in a subset of breast cancers. Citation Format: Sarah Maguire, Andri Leonidou, Patty Wai, Caterina Marchio, Charlotte Ng, Ana Sapino, Anne Vincent-Salomon, Jorge Reis-Filho, Britta Weigelt, Rachael Natrajan. SF3B1 mutations constitute a novel therapeutic target in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-02.
Can clinical data help to screen patients with lymphoma for MR imaging of bone marrow?
Authors: A.A. Tardivon, J.-N Munck, L.G. Shapeero, S. Koscielny, J. Bosq, F. Dhermain, R. Gilles, M. Hayat, D. Vanel
Journal: Annals of Oncology (1995)

Previous studies have suggested combining magnetic resonance (MR) imaging and biopsy in patients with lymphoma but association between MR results and clinical symptoms have never been investigated. The purpose of this retrospective study was to better delineate patients profiles requiring bone marrow (BM) imaging in lymphoma.50 MR studies and blind biopsies (BB) were reviewed in 40 patients with lymphoma. MR results were compared to clinical, laboratory-based and BM follow-up data to determine potential associations between MR results and these parameters.46% of MR studies were abnormal with a normal BB; 2% were normal with an abnormal BB. Abnormal MR results were significantly associated with subsequent bone marrow involvement (p < 0.01). Abnormal MR studies were significantly associated with constitutional symptoms, bone pains (p < 0.05) and an elevated alkaline phosphatase level (p < 0.01). MR imaging excluded malignancy in three patients and caused therapy to be modified in three.Abnormal clinical and laboratory-based data should be used to screen patients with normal BB for MR imaging, especially in patients with Hodgkin's disease and high grade non-Hodgkin's lymphoma.
How We Treat Chronic Myeloid Leukemia Patients During Daily Practice? Case Studies From The Real Life Experience Of Two Genoa Centers Of Hematology
Authors: Laura Mitscheunig, Micaela Bergamaschi, Raffalla Grosso, Maurizio Miglino, Marino Clavio, Filippo Ballerini, Letizia Canepa, Riccardo Varaldo, Roberto Lemoli, Marco Gobbi, Ivana Pierri
Journal: Blood (2013)
Tuberculosis-related mortality in people living with HIV in Europe and Latin America: an international cohort study
Authors: Daria N Podlekareva, Anne Marie W Efsen, Anna Schultze, Frank A Post, Alena M Skrahina, Alexander Panteleev, Hansjakob Furrer, Robert F Miller, Marcelo H Losso, Javier Toibaro, Jose M Miro, Anna Vassilenko, Enrico Girardi, Mathias Bruyand, Niels Obel, Jens D Lundgren, Amanda Mocroft, Ole Kirk
Journal: The Lancet HIV (2016)
Cell-Mediated Immune Status of Breast Cancer Patients: Evaluation by Skin Tests, Lymphocyte Stimulation, and Counts of Rosette-Forming Cells23
Authors: Takuma Nemoto, Tin Han, Jun Minowada, Vishudi Angkur, Alice Chamberlain, Thomas L. Dao
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Cell-Mediated Immune Status of Breast Cancer Patients: Evaluation by Skin Tests, Lymphocyte Stimulation, and Counts of Rosette-Forming Cells Get access Takuma Nemoto, M.D., Takuma Nemoto, M.D. 4Department of Breast Surgery, Roswell Park Memorial Institute (New York State Department of Health), 666 Elm St., Buffalo, N.Y. 14203. Search for other works by this author on: Oxford Academic PubMed Google Scholar Tin Han, M.D., Tin Han, M.D. 5Department of Medicine B, Roswell Park Memorial Institute. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jun Minowada, M.D., Jun Minowada, M.D. 6Department of Immunology and Immunochemistry Research, Roswell Park :Memorial Institute. Search for other works by this author on: Oxford Academic PubMed Google Scholar Vishudi Angkur, M.D., Vishudi Angkur, M.D. 7Now in private practice in Rome, N. Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar Alice Chamberlain, Alice Chamberlain 8Department of Biostatistics, RosweIl Park Memorial Institute. Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas L. Dao, M.D. Thomas L. Dao, M.D. 4Department of Breast Surgery, Roswell Park Memorial Institute (New York State Department of Health), 666 Elm St., Buffalo, N.Y. 14203. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 3, September 1974, Pages 641–645, https://doi.org/10.1093/jnci/53.3.641 Published: 01 September 1974 Article history Received: 19 March 1974 Accepted: 09 May 1974 Published: 01 September 1974
Cisplatin in non-small cell lung cancer (NSCLC)—Reducing the most prominent toxicity, emesis: Results of a meta-analysis with 1527 patients in randomized clinical trials (RCTs) testing the addition of an NK1 antagonist
Authors: R. J. Gralla, H. Raftopoulos, E. Bria, P. J. Hesketh
Journal: Journal of Clinical Oncology (2008)

8064 Background: Three meta-analyses (MA) demonstrated modest but significant survival and response advantages of cisplatin over carboplatin with ‘3rd-generation’ regimens. Large RCTs (Kelly JCO 2001, Fossella JCO 2003) did not show quality of life benefits favoring carboplatin even in stage IV patients (pts). Neuro- and nephrotoxicity were more prominent with cisplatin (by 1%) whereas thrombocytopenia occurred more with carboplatin. A 2-fold increase in grade 3–4 emesis (18% cisplatin, 8% carboplatin) (Ardizzioni, JNCI 2007) represents the most compelling toxicity barrier in selecting the more effective platinum agent. With recent availability of the NK1 antagonist aprepitant, we investigated whether addition of this agent would offset the emesis of cisplatin and if heterogeneity (het) of RCTs would be a factor in interpretation. Methods: 3 large RCTs with 1527 pts have been reported in previously untreated pts receiving cisplatin > 70 mg/M2. NSCLC was the most common single diagnosis. All pts were given ondansetron + dexamethasone; half were randomized to receive aprepitant as well. In one study pts not given aprepitant received ondansetron also for delayed emesis. MA was conducted with Peto-Odds Ratio (OR) with 95% confidence interval (CI) derived through fixed- and random- effect models. CMA software v.2 (Biostat, NJ) was used for calculations. Results: Results of this MA are in the table below. Complete control of acute emesis in the 763 pts assigned to the aprepitant 3-drug regimen was 88%, with a 5-day no emesis rate of 74%. Conclusions: This meta-analysis shows a clear benefit in complete control of emesis and nausea with the addition of aprepitant. No het was seen. The magnitude of this benefit and the observed control rate demonstrate that this regimen markedly reduces cisplatin acute and delayed emesis allowing the use of cisplatin with little more toxicity than reported with carboplatin. OR (95% CI) p Heterogeneity (p) Acute Emesis: Complete Control 2.16 (1.66, 2.80) <0.0001 0.84 Delayed Emesis: Complete Control 2.58 (2.04, 3.13) <0.0001 0.45 5-day no emesis rate 2.38 (1.92, 2.93) <0.0001 0.44 No significant nausea - 5 days 1.31 (1.05, 1.63) 0.015 0.84 No significant nausea - delayed 1.36 (1.08, 1.70) 0.007 0.76 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline, Merck Merck Merck
Corrected area under prostate-specific antigen (PSA) curve and PSA half-time dynamics during chemotherapy. A new prognostic classification for hormone-refractory prostate cancer (HRPC) patients
Authors: P. Beuzeboc, E. Banu, Y. Goubely Brewer, A. Banu, M. Zerbib, T. Flam, M. Peyromaure, F. Scotte, J. M. Andrieu, S. Oudard
Journal: Journal of Clinical Oncology (2005)

4641 Background: The PSA half-time (PSA HT) dynamics and corrected area under PSA curve (PSA c-AUC) during chemotherapy (CT) predict overall survival (OS) probability among metastatic HRPC patients (ASCO 2003, abstract 1673; ASCO 2004, abstract 9579). This has motivated the search of a new prognostic classification to identify these patients (pts) at risk, with a poor outcome. The manner in which these parameters were combined could have a major survival impact. Methods: Based on their PSA c-AUC values (< 60 or ≥ 60 ng/mL) and PSA HT categories [initial progressers (IP), late progressers (LP) and responders (R)], a new prognostic classification was defined (Table). Analysis was done according to the OS as primary end point, stratified by first-line CT regimen. Log-rank test was used to determine the equality of the groups over the survival distribution estimates. Results: Two hundred-eighteen metastatic HRPC pts treated with docetaxel (77%) or mitoxantrone (23%) based CT were included in this exploratory analysis. Pts characteristics: median age 68 years (range 51–91 years), median PSA follow-up duration of 26.8 months (range 2–184 months). The 3-year OS for the entire cohort was 26% with a median of 20 months [95% confidence interval (CI) 17.5–22.5 months)]; 137 (73%) pts have died. Our classification identified three major risk groups with predicted 3-year survival rates of 45%, 28% and 16% (Table). There was an significant difference in OS (log-rank, P=0.00003) according to prognostic groups. Conclusions: The PSA c-AUC and PSA HT are predictive factors for overall survival independently of chemotherapy regimen. Combination of both parameters is more powerful, being capable to stratify patients according to survival probabilities. Such model could assist in assessing the results of newer therapies, by comparing predicted survival to achieved survival. No significant financial relationships to disclose.