tbuckley/cabot-search huggingface dataset:
Final results of the UGT1A1-based dose modification of irinotecan and its impact on rates of severe neutropenia and hospitalization.
Authors: Benjamin R. Tan, Ningying Wu, Andrea Wang-Gillam, Rama Suresh, Joel Picus, Joaquina Celebre Baranda, Albert C. Lockhart, Howard L. McLeod
Journal: Journal of Clinical Oncology (2014)

461 Background: UGT1A1 7/7 genotype has been associated with a 3-fold increase in severe neutropenia for patients treated with irinotecan (IRI) (Mcleod 2010, Liu 2013). UGT1A1 determination may tailor IRI therapy and reduce toxicities. However, the impact of the FDA-recommended IRI dose modification on outcomes is unclear. Methods: UGT1A1 genotyping was done for patients with various cancers wherein IRI therapy was planned and who consented to 1 of 3 IRB-approved registries. For patients with UGT1A1 7/7, a reduction in IRI doses was recommended per FDA and toxicities monitored during the first 2 doses. Results: 323/341 patients registered had UGT1A1 determined, of which 13% (42/323) had the 7/7 or 7/8 genotypes. Notably, a significantly higher proportion of African-Americans (AA) harbor these genotypes compared to Caucasians (C) (26.32% vs 10.08%, p=0.001). Among the 251 evaluable for toxicities, the incidence of grade 3-5 ANC for patients with 7/7 was not significantly different than those with 6/6 or 6/7 (Kendall's Tau-b coefficient p=0.494) (see Table). Among the 7/7 patients, 23/33 were treated at IRI doses of 150 mg/m 2 or higher. 30% of patients treated at the higher dosages still developed grade 3-5 neutropenia compared to 17-21% for those with other genotypes. 38 of 251 patients were hospitalized during their first 2 cycles of therapy. The proportion of hospitalized patients with 7/7 genotype was not significantly different than those with 6/6 or 6/7 (15% vs 17% vs 12.6%). Conclusions: UGT1A1 can be used to tailor IRI therapy and reduce toxicities. The incidence of severe neutropenia and rate of hospitalization is comparable among patients with all UGT1A1 genotypes when IRI dose is adjusted for those with UGT1A1 7/7. There is a higher incidence of UGT1A1 7/7 genotype among African-Americans comnpared to Caucasians, which warrants further evaluation. [Table: see text]
Allogeneic Stem Cell Transplantation after Conditioning with Treosulfan, Etoposide and Cyclophosphamide for Patients with Acute Lymphoblastic Leukemia (ALL) Not Eligible for TBI-Containing Regimens: A Phase II-Study on Behalf of the German ALL Study Group (GMALL) and the German Cooperative Transplant Study Group
Authors: Nicolaus Kröger, Martin Bornhäuser, Matthias Stelljes, Uwe Pichlmeier, Christoph Schmid, Renate Arnold, Gesine Bug, Ralf Georg Meyer, Wolfgang A. Bethge, Guido Kobbe, Dietrich Beelen
Journal: Blood (2014)
Preliminary results of a phase II study of neoadjuvant treatment with docetaxel (T), doxorubicin (A) and capecitabine (X) in locally advanced or inflammatory breast cancer (LABC)
Authors: G. Perez Manga, M. Méndez, M. I. Palomero, R. Quibén, J. Belón
Journal: Journal of Clinical Oncology (2006)

10678 Background: Previous studies suggest that combined treatment of chemotherapy + surgery + radiotherapy has a high survival rate in pts with locally advanced or inflammatory breast cancer. Primary objective was evaluate response rate. Secondary objectives were time to progression and toxicity profile of neoadjuvant chemotherapy T, A and X in pts with LABC. Methods: Eligibility criteria: Pts with histological confirmation of LABC, ECOG PS ≤ 2, age ≤ 75 years, LVEF &gt; 50%, and adequate bone marrow, renal and hepatic function. Prior systemic therapy, surgery or radiotherapy for breast cancer was not allowed. Pts with invasive bilateral breast cancer were not included. Treatment: T (30 mg/m 2 ) iv day 1, 8 and 15, A (50 mg/m 2 ) iv day 1 and X (1500 mg/m 2 o.d.) days 1–14, in a 4 weeks course. This scheme was repeated up to 4 cycles followed by surgery. According to investigator criteria pts receive a maximum of six cycles. Radiotherapy and hormonal treatment are allowed depending on molecular markers. Expression of markers was performed by inmunohistochemistry before chemotherapy. Results: 36 pts were included in this analysis, with a median age of 48 years (25–69). ECOG PS was 0 in 32% of pts and 1 in 68%. Hormonal receptor status was ER+ 43%, PR+ 34% and C-erb2+ 52%. A total of 131 cycles (median 4, range 1–4) were administered. Median relative dose intensity was 86% for T, 91% for A and 93% for X. Two patients are still undergoing treatment; of 34 evaluable pts for efficacy, 11 achieved CR, 22 PR and 1 PD resulting in an ORR of 97% (CI 95%: 92–100). Surgery was performed in 34 pts: 3 (9%) of them achieved pathological CR and one additional patient had non invasive carcinoma. Grade III/IV toxicity per patient was neutropenia (69%), leucopenia (53%), febrile neutropenia (8%), mucositis (14%), diarrhea (11%), nausea/vomiting (6%), dysgeusia (3%) and asthenia (3%). Median follow up time was 8.8 months. Conclusions: T, A and X every 28 days administered during 4 cycles as neoadjuvant chemotherapy in LABC is an active regimen with a manageable toxicity profile before surgery. No significant financial relationships to disclose.
High-Throughput Genomic Profiling of Adult Solid Tumors Reveals Novel Insights into Cancer Pathogenesis
Authors: Ryan J. Hartmaier, Lee A. Albacker, Juliann Chmielecki, Mark Bailey, Jie He, Michael E. Goldberg, Shakti Ramkissoon, James Suh, Julia A. Elvin, Samuel Chiacchia, Garrett M. Frampton, Jeffrey S. Ross, Vincent Miller, Philip J. Stephens, Doron Lipson
Journal: Cancer Research (2017)

Genomic profiling is widely predicted to become a standard of care in clinical oncology, but more effective data sharing to accelerate progress in precision medicine will be required. Here, we describe cancer-associated genomic profiles from 18,004 unique adult cancers. The dataset was composed of 162 tumor subtypes including multiple rare and uncommon tumors. Comparison of alteration frequencies to The Cancer Genome Atlas identified some differences and suggested an enrichment of treatment-refractory samples in breast and lung cancer cohorts. To illustrate novelty within the dataset, we surveyed the genomic landscape of rare diseases and identified an increased frequency of NOTCH1 alterations in adenoid cystic carcinomas compared with previous studies. Analysis of tumor suppressor gene patterns revealed disease specificity for certain genes but broad inactivation of others. We identified multiple potentially druggable, novel and known kinase fusions in diseases beyond those in which they are currently recognized. Analysis of variants of unknown significance identified an enrichment of SMAD4 alterations in colon cancer and other rare alterations predicted to have functional impact. Analysis of established, clinically relevant alterations highlighted the spectrum of molecular changes for which testing is currently recommended, as well as opportunities for expansion of indications for use of approved targeted therapies. Overall, this dataset presents a new resource with which to investigate rare alterations and diseases, validate clinical relevance, and identify novel therapeutic targets. Cancer Res; 77(9); 2464-75. ©2017 AACR.
Establishing an oncology quality dashboard for improvement.
Authors: Diane Denny, Danielle Gross
Journal: Journal of Clinical Oncology (2016)

223 Background: Cancer Treatment Centers of America (CTCA), a national network of five hospitals, formed a Quality Improvement Committee to bring together both clinical and administrative leadership (physician, nursing, pharmacy and quality) across the enterprise vested in the oversight of quality and patient safety. Tasked with facilitating and driving measurement and improvement the group established a Quality dashboard housing metrics of importance given current performance, evidence-based practice, and evolving external standards. The dashboard includes a mix of outcome, process, and structure measures with targets, both externally driven and CTCA established. Methods: The dashboard houses data sourced from a multitude of systems and is segmented into clinically relevant categories such as Infection Prevention, Nursing, Medication Management, and Medical Oncology to name a few. These categories are further broken down into specific measures, reported by quarter, and color-coded (red/yellow/green) to display progress. Targets are established based upon external benchmarks, where data is available. Each metric is also graphically displayed, trending the 6 most recent quarters of data as another visual reference. Finally, a glossary was created to standardize key measure details across the enterprise for accurate data collection including documentation of source, numerator, denominator, references, inclusions, exclusions and rationale. Data is updated monthly to reflect most current performance and promote timely intervention. Results: Since development of the Quality dashboard, CTCA has experienced various red to yellow to green progressions as well as upped its targets indicating significant advancement in performance. Standard data collection and visual identifiers within one repository has enabled CTCA to accurately focus time and resources where needed in order to continually improve care. Conclusions: The establishment of the enterprise-wide quality dashboard has led to great collaboration within CTCA’s network of hospitals. The display of the data allows both a focus upon individual and network strengths and opportunities for improvement as well as a mechanism for communicating shared goals.
Socioeconomic and clinical factors associated with delayed initiation of adjuvant chemotherapy for stage III colon cancer.
Authors: Alex Bernard Haynes, Y. Sabrina Chiang, Genevieve Marie Boland, Yan Xing, Nader N. Massarweh, George J. Chang, Y. Nancy You, Barry W. Feig, Janice N. Cormier
Journal: Journal of Clinical Oncology (2012)

173 Background: We have previously described an association between a greater than 8-week interval to initiation of adjuvant chemotherapy after resection of stage III adenocarcinoma of the colon and an approximately 20% increased risk of mortality. We sought to understand the factors that lead to delay in chemotherapy initiation. Methods: Patients who received adjuvant chemotherapy after resection of stage III colon cancer between 2003 and 2007 were identified from the National Cancer Data Base. Delayed chemotherapy was defined as the first date of chemotherapy administration being eight weeks or more after surgical resection. Comorbidity was categorized using the Charlson/Deyo index. Prolonged length of stay and unplanned readmission were used as surrogates for surgical complications. Multivariate logistic regression was performed to examine the associations between various clinical and socioeconomic variables and delay in the receipt of adjuvant chemotherapy. Results: 33,011 stage III colon cancer patients who received chemotherapy after surgery were identified. 8,036 (24.3%) initiated chemotherapy more than eight weeks after surgical resection. Unplanned readmission (OR 1.76, 95% CI 1.58-1.95), prolonged postoperative stay (OR 1.56, 95% CI 1.48-1.65), and comorbidity (OR 1.18, 95% CI 1.12-1.25) were all independent predictors of delay. Nonclinical factors, including African-American race (OR 1.34, 95% CI 1.24-1.45), lack of insurance (OR 1.63, 95% CI 1.43-1.87), and residence more than 100 miles from treating center (OR 1.23, 95% CI 1.01-1.51) were also independently associated with delayed chemotherapy. Conclusions: Delay in the initiation of adjuvant therapy for colon cancer beyond 8 weeks has previously been found to be an independent predictor of increased mortality. While some delays may result from patient frailty or postoperative complications, these data suggest that nonclinical factors may also contribute to delays. Increased focus on overcoming barriers to coordinated care should be prioritized to ensure that those patients who may benefit from adjuvant therapy receive it in a timely fashion to optimize survival advantages.
A Multicenter Case-Control Prospective Study to Assess the Risk of Immune Thrombocytopenia (ITP) Associated with Vaccines in Adults Using the PGRx-ITP Registry
Authors: Lamiae Grimaldi-Bensouda, Marc Michel, Jean-François Viallard, Daniel Adoue, Nadine Magy-Bertrand, Medhi Khellaf, Maya Hacini, Olivier Fain, Anne-Sophie Morin, Philippe Quittet, Brigitte Pan-Petesch, Bernard Bonnotte, Nathalie Chalumeau-Costeadoat, Michel Ruel, Pamela Leighton, Elodie Aubrun, Annick Alperovitch, Lucien Abenhaim, Bertrand Godeau
Journal: Blood (2011)
The Outcome of Autologous Stem Cell Transplantation and the Risk of Relapse in Myeloma and Lymphoma Patients Mobilized Using Plerixafor Compared to Standard Mobilization Regimen
Authors: Patrycja Zielinska, Malgorzata Krawczyk-Kulis, Miroslaw Markiewicz, Anna Koclega, Robert Liwoch, Monika Dzierzak-Mietla, Krzysztof Bialas, Slawomira Kyrcz-Krzemien
Journal: Blood (2011)
A panel of dynamic micromechanical biomarkers in the detection and differentiation of prostate cancer.
Authors: Daniel W. Good, Steven Hammer, Paul Scanlan, Grant Stewart, Robert L Reuben, Alan S McNeill
Journal: Journal of Clinical Oncology (2015)

38 Background: Elasticity devices enable quantitative measurements and can reduce the need for operator interpretation. Our dynamic assessment enables micromechanical markers to be identified: amplitude ratio [AR], phase lag [PL] and mean ratio [MR], at specific frequencies. Aim: To assess the efficacy of a panel of dynamic micromechanical biomarkers for the detection of prostate cancer (Primary endpoint) (and differentiation of significant from insignificant disease (secondary endpoint)) in ex-vivo prostates and in patients, using a direct elasticity assessment probe (E-finger). Methods: Patients undergoing surgery for prostate cancer were enrolled into a prospective clinical study; exclusion criteria (previous TURP, 5ARI). Ex-vivo prostates were systematically assessed at multiple points on posterior surface. In-vivo testing was done using the probe attached to the index finger and assessing the prostate via DRE using 12 -16 different areas. Measurement points were marked and noted on final pathology to allow correlation with final histology. CART was used to create a model of the micromechanical markers and regression analysis used to identify histopathological parameter associations. Results: 22 patients were recruited to the study to date, mean age was 64 (55 – 73), median PSA 7.5 (5.5 – 10), over 50% were cT1c, median weight 51g (44 – 68) and over 50% were pT3 on final pathology. Over 600 measurement points were assessed. The in-vivo marker panel was made up of: 10HzARA, 10HzPLA, 1HzPLC, 15HzMRB and 1HzARA. Sensitivity was 89%, specificity 87%, PPV 86%, NPV 88% for cancer detection in-vivo. That for the ex-vivo tests were Sen 71%, Spec 81%, PPV 80%, NPV 72% (primary outcome). For differentiation of clinically significant from insignificant areas sensitivity and specificity were 81% and 75% respectively (secondary outcome). Correlation of the marker panel with underlying tumour volume was strong (R 2 = 0.75). Conclusions: These results show the promise of micromechanical biomarkers in the detection of prostate cancer and in the differentiation of significant from insignificant disease. This study shows that these markers maintain their accuracy from the ex-vivo into the in-vivo environment.
Integrating Lean Six Sigma in the daily operations of an ICU to achieve safe, quality patient care.
Authors: Ann Marquis, Jacqueline Magurn, Joanne McGovern, Michelle Jetter, Sarah Beadling, Dorothy Gregoire
Journal: Journal of Clinical Oncology (2016)

230 Background: Developing and maintaining a culture of safety and quality in delivering patient care is critical in the intensive care unit (ICU) especially an oncology ICU. Incorporating the Lean Six Sigma program into daily operations of the ICU achieves, simplifies, and sustains continuous improvement in the delivery of safe quality patient care. This program engages the ICU team through visual management of quality, safety, and budget indicators including medication scanning, falls, sharps exposure, infection prevention including blood stream, catheter, hospital and ventilator acquired pneumonias, venous embolism prevention, and staffing compliance. Methods: The initiative focused on stakeholder development to increase professional certifications, improve engagement through development and implementation of educational events, and enhance participation in monthly journal club. Discussion of evidence-based research projects aligned each shift with data, metrics, and outcomes. Cost containment through charge capture, reduction in wasted supplies, and appropriate level of care order was implemented. With the support of Lean Six Sigma, the lean daily management board came to life each shift. Results: Outcomes included medication scanning rates increasing from 94% to 99.5%. Hospital acquired infection and pressure ulcer rates remained 0%. Venous thromboembolism prophylaxis rates increased form 77% to 100%. Staffing compliance increased from 90% to 100%. The number of chemotherapy certified nurses increased from 56% to 71%. The number of nurses with specialty certification improved from 28% to 47%. Stakeholders engaged in 32 professional educational events, and 12 journal clubs were led by the ICU nurses. Product charge capture began at $0 ending in an average of $1342 per month from 0% charge capture to 100% charge capture each month. Conclusions: Team alignment around daily production, patient flow, and staff development enables real-time problem solving around the daily issues of safety, quality, productivity, and stakeholder development. In this oncology critical care unit it has not only enhanced daily communication but every twelve hour shift engagement as well.
Fatigue symptom clusters—A reality or myth?
Authors: S. Yennurajalingam, D. Urbaeur, R. Chacko, K. Busby, V. Poulter, E. Bruera
Journal: Journal of Clinical Oncology (2008)

20564 Background: There is controversy of the existence and nature of Fatigue symptom clusters in patients with advanced cancer. Characterization of the fatigue symptom cluster would lead to improved multidimensional evaluation and management of fatigue and guide clinical research. Methods: Consecutive patients with advanced cancer presenting in the palliative care clinic in a comprehensive cancer center over a 2 year period, with a complete Edmonton symptom assessment scale (ESAS) and Memorial Delirium assessment scale(MDAS) at initial and subsequent visit and with frequency of significant fatigue(SF) (≥4 on 0–10 on ESAS fatigue scale) were analyzed retrospectively. Demographics, primary cancer type, characterization of fatigue symptom cluster and change in fatigue with treatment were analyzed. Results: A total of 70 evaluable patients were analyzed. The median age was 60 years; males were (54%). The most common primary cancer types were H&N and Lung (31%). The mean time between the initial and subsequent visit was 19 days. Mean (SD) fatigue score was 6.6(1.81). The mean change (improvement) in symptom composite score and fatigue were -6.6 (p=0.006) and -1.1 (p=0.002) respectively. Correlation between initial and follow up symptoms was: sleep r=0.60, p=<0.0001, drowsiness r=0.48, p=<0.0001, depression r=0.45, p=0.0001, pain r=0.43, p=0.0002, appetite r=0.33, p=0.005, MDAS r=0.15, p=0.2. The cluster analysis of baseline data indicates that there were distinct clustering for fatigue, drowsiness, sleep and well being. In the subsequent visit this clustering was maintained. Anxiety, depression, pain and MDAS (delirium) symptoms were not part of the initial clustering in both cohorts. Conclusions: Our findings confirm a symptom cluster of fatigue, drowsiness, sleep and well being in outpatient palliative care patients. Anxiety, depression, pain and MDAS (delirium symptoms) were not part this cluster. No significant financial relationships to disclose.
Analysis of EGFR status in metastatic colorectal cancer patients treated with cetuximab monotherapy
Authors: A. W. Pippas, H. J. Lenz, R. J. Mayer, B. Mirtsching, A. L. Cohn, P. Windt, E. van Cutsem
Journal: Journal of Clinical Oncology (2005)

3595 Background: Erbitux (Cetuximab), an IgG1 monoclonal antibody, has demonstrated activity in patients with colorectal cancer (CRC), both as a single agent and in combination with irinotecan. This phase II study explored the activity of cetuximab in patients with metastatic CRC, who progressed following treatment with a fluoropyrimidine, irinotecan, and oxaliplatin. Methods: Prior to study entry, patients were screened for EGFR expression with the DakoCytomation EGFR pharmDx test kit. EGFR status was classified as undetectable, 1+, 2+, or 3+. Patients received cetuximab at an initial dose of 400 mg/m2, followed by weekly doses at 250 mg/m2, until disease progression or unacceptable toxicity. Results: Of 346 treated patients, the median number of prior regimens was 4 (range 2–9). 12% of patients achieved a PR (95% CI 8% - 15%) with a median survival of 6.6 months (95% CI 5.6–7.6 months). Conclusion: EGFR staining intensity does not appear to correlate with increased survival in patients treated with cetuximab. This appears to differ from results with erlotinib (Tarceva), which demonstrated prolonged survival in EGFR+, but not EGFR-negative patients.(Erlotinib Package Insert 2004). EGFR staining might be a more relevant determinant of activity for small molecules than for Mabs. Due to the limited size of the data set, further investigation is warranted and a clinical trial investigating EGFR undetectable patients is being conducted to determine if the trend observed in this study is maintained in a larger population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Chiron, Response Genetics, Genentech Bristol-Myers Squibb, Roche, Pfizer, Lilly, Sanofi Bristol-Myers Squibb, NCI, NIH
Vantage 088: Vorinostat in Combination with Bortezomib in Patients with Relapsed/Refractory Multiple Myeloma: Results of a Global, Randomized Phase 3 Trial
Authors: Meletios Athanasios Dimopoulos, Sundar Jagannath, Sung-Soo Yoon, David S. Siegel, Sagar Lonial, Roman Hajek, Thierry Facon, Laura Rosiñol, Hilary Anne Blacklock, Hartmut Goldschmidt, Vania Hungria, Andrew Spencer, Antonio Palumbo, Donna E. Reece, Thorsten Graef, Jennifer Houp, Linda Sun, Joseph E. Eid, Kenneth C. Anderson
Journal: Blood (2011)