tbuckley/cabot-search huggingface dataset:
Evaluation of putative prognostic tissue biomarkers in pancreatic ductal adenocarcinoma.
Authors: J. M. Winter, L. H. Tang, D. S. Klimstra, M. F. Brennan, E. M. O'Reilly, W. R. Jarnagin, P. J. Allen
Journal: Journal of Clinical Oncology (2011)

4020 Background: Thousands of transcripts and proteins have been reported as overexpressed in pancreatic cancer, although their prognostic significance remains uncertain. Methods: Representative sections of paraffin embedded tumor were sampled and tissue microarrays (TMA) were prepared. Candidate proteins were selected based on the number of publications cited in a central repository of pancreatic cancer biomarkers (PLoS Med. 2009 Apr 7;6(4):e1000046) as well as the availability of optimized antibodies. Patients were included in the TMA if they had previously undergone resection of their primary tumor and had either a short (<1 year) or long (>30 months) cancer-specific survival. Patients who died as a result of non-disease related causes or had an intermediate survival (>1 year and <30 months) were excluded from this study. Results: Since 2000, 671 pancreatic resections were performed. Early cancer-specific death occurred in 87 patients (13%) and >30 month survival in 115 patients (17%). Tissue was available for a TMA in 66 patients in the early cancer-specific death group and in 85 patients in the long-term survival group. In an initial biomarker screen, the TMA’s were tested with antibodies against MUC1, p53, cyclin D1, mesothelin, and EGFR. In the univariate analysis, MUC1 (OR 5.1, p<0.001), mesothelin (OR 3.7, p<0.001), and p53 (OR 2.0, p=0.04) expression were associated with early cancer-specific mortality, while cyclin D1 and EGFR expression were not informative. In a multivariate analysis, expression of MUC1 and mesothelin were superior to positive lymph node status and poor differentiation as prognostic markers (Table). Conclusions: In the current study of 151 patients who underwent resection for pancreatic adenocarcinoma, MUC1 and mesothelin expression were superior to conventional pathologic features at predicting prognosis. Incorporation of additional antibodies may allow the development of a highly accurate molecular test for early recurrence following resection. Risk of early cancer-specific mortality. <1yr > 30 months Hazard ratio P value Positive regional lymph nodes, n=151 82% 65% 2.9 0.02 Poorly differentiated, n=151 48% 22% 2.7 0.01 Mesothelin and MUC1 expression, n=148 51% 16% 5.1 <0.001
Neoadjuvant rectal cancer (RC) score to predict survival: Potential surrogate endpoint for early-phase trials.
Authors: Greg Yothers, Thomas J. George, Nicholas J. Petrelli, Michael J. O'Connell, Robert W. Beart, Carmen Joseph Allegra, Mark S. Roh, Samia H. Lopa, Saima Sharif, Norman Wolmark
Journal: Journal of Clinical Oncology (2014)

384 Background: Valentini, et al. (J Clin Oncol 29: 2011, 3163-72) developed nomograms for predicting overall survival (OS) based on clinical factors available after neoadjuvant therapy (tx). Pathologic T-stage (pT), N-stage (pN), and clinical T (cT) were the most important independent predictors of OS. We developed a neoadjuvant RC score (NAR score) using pN and downstaging of T (cT – pT) based on relative weights suggested by the nomograms. NSABP’s R-04 trial presents an opportunity for independent validation of the NAR score. Methods: Pts with clinical stage II/III RC undergoing preoperative RT (4,500cGy in 25 fractions over 5 wks + boost of 540-1,080cGy in 3-6 daily fractions) were randomized to one of four regimens in a 2x2 design: CVI 5-FU (225mg/m 2 5 days/wk), with or without oxaliplatin (Ox) (50mg/m 2 /wk x 5) or oral capecitabine (825 mg/m 2 BID 5 days/wk), with or without Ox. The NAR score is computed as [5 pN – 3 (cT – pT) + 12] 2 / 9.61 where: cT in {1, 2, 3, 4}, pT in {0, 1, 2, 3, 4}, and pN in {0, 1, 2}. The NAR score takes values from 0 to 100; higher scores indicate poorer prognosis. Analyses based on the score should be stratified by cT. NAR score is compared to pathologic complete response (ypCR) by Akaike’s information criterion (AIC) to determine the better predictor of OS. Results: 1,479 pts had data for the NAR score and follow-up for OS. Continuous NAR score was significantly associated with OS (HR/unit 1.04 95% CI 1.03-1.05, p&lt;0.0001). Pts were grouped into low, intermediate, and high risk of death categories based on tertiles of the NAR score. Categories were significantly associated with OS (p&lt;0.0001) with 5yr OS values of 92, 89, and 68%, respectively. ypCR was also significantly associated with OS (HR 0.37 95% CI 0.24-0.58, p&lt;0.0001). Continuous NAR score had a much lower AIC (2,902.49) than ypCR (2,987.08) suggesting stronger association with OS. Conclusions: The NAR score has been validated as a predictor of OS after neoadjuvant tx for RC. AIC of the continuous NAR score suggests it is a better predictor of OS than dichotomous ypCR. NAR score could be used in place of ypCR as a surrogate endpoint for OS in early phase neoadjuvant rectal trials. Support: U10-CA-12027, U10-CA-37377, U10-CA-69651, U-10-CA-69974; Sanofi; Roche. Clinical trial information: NCT00058474.
Patients with metastatic chromophobe renal cell carcinoma treated with sunitinib therapy: Analysis of an international database regarding outcome and comparison to clear cell histology (mccRCC).
Authors: Daniel Keizman, David Sarid, Jae-Lyun Lee, Maya Gottfried, Natalie Maimon, Hans J. Hammers, Mario A. Eisenberger, Michael Anthony Carducci, Victoria J. Sinibaldi, Victoria Neiman, Eli Rosenbaum, Eli Gez, Avivit Peer, Wilmosh Mermershtain, Keren Rouvinov, Raanan Berger, Ibrahim Yildiz
Journal: Journal of Clinical Oncology (2015)

429 Background: Sunitinib (Su) is a standard therapy (tx) for mccRCC. Data on its activity in the rare variant of metastatic chromophobe renal cell carcinoma (mchRCC) are limited by very small or heterogeneous (mixed histology with papillary type, or mixed targeted therapies) studies. We analyzed the activity of Su in a relatively large and homogenous international cohort of mchRCC pts, in terms of outcome and comparison to mccRCC. Methods: Records from mchRCC pts treated with first-line Su in 9 centers across 4 countries were retrospectively reviewed. Univariate and multivariate analyses of association between clinicopathologic factors and outcome were performed. Subsequently, mchRCC pts were individually matched to mccRCC pts. We compared the response rate (RR), progression free survival (PFS), and overall survival (OS) between the groups. Results: Between 2004-2014, 33 pts (median age 64, 45% male) with mchRCC were treated with Su as first-line tx. 76% had a prior nephrectomy. HENG risk was good 27%, intermediate 55%, and poor 18%. 33% were active smokers, and 30% users of angiotensin system inhibitors (ASIs). 55%, 27%, and 33% had lung, liver, and bone metastases, respectively. 48% had a pre-tx neutrophil to lymphocyte ratio (NLR) &gt;3. 42% had dose reduction/tx interruption (DR/TI). Su-induced hypertension (HTN) occurred in 48%. 75% achieved a clinical benefit (partial response + stable disease), while 25% had disease progression within the first 3 months of tx. Median PFS and OS were 10 and 26 months, respectively. Factors associated with PFS were the HENG risk (HR 3.8, p=0.025) and pre-tx NLR &gt;3 (HR 0.6, p=0.012). Factors associated with OS were the HENG risk (HR 4.27, p=0.027), liver metastases (HR 4.6, p=0.029), and pre-treatment NLR &lt;3 (HR 0.5, p=0.04). Tx outcome was not significantly different between mchRCC pts and mccRCC pts, who were individually matched by HENG risk, nephrectomy/smoking status, pre-tx NLR, use of ASIs, DR/TI, and Su induced HTN. In mccRCC pts (p value versus mchRCC), 70% achieved a clinical benefit (p=0.58), and median PFS and OS were 9 (p=0.7) and 24 (p=0.6) months, respectively. Conclusions: In mchRCC pts, Su tx may have similar outcome to mccRCC pts.
A phase II study of intermittent sorafenib with bevacizumab in bevacizumab-naive epithelial ovarian cancer (EOC) patients.
Authors: E. C. Kohn, J. Lee, C. M. Annunziata, L. M. Minasian, J. Zujewski, S. A. Prindiville, H. L. Kotz, J. Squires, N. D. Houston, H. X. Chen, J. J. Wright
Journal: Journal of Clinical Oncology (2011)

5019 Background: We targeted the VEGF pathway at multiple points by combining the VEGFR2/Raf kinase inhibitor sorafenib (S) with bevacizumab (B), a selective anti-VEGF antibody. We hypothesized that this combination would suppress angiogenesis and tumor growth, and yield clinical benefit in B-naïve EOC pts. Methods: Eligible pts had recurrent EOC, ECOG PS 0-1, good end organ function, and no prior exposure to S or B (NCT00436215). All pts received S 200mg twice daily days 1-5 /wk and B 5mg/kg q 2 weeks in 4 wk cycles. Primary endpoints of response and safety were evaluatedand every other cycle by reassessment imaging and every cycle, respectively. Vascular permeability (Ktrans) was measured by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and metabolic activity by 18FDG-PET scans performed pretreatment, day 3, and at 6 wks. quality of life (QoL) was assessed at every other cycle. Results: 30pts with B naïve EOC were evaluable for toxicity and 25 for response. Clinical benefit occurred in 22/25 (88%); 6/25 pts had partial responses lasting a median of 15.5 mo (mean 15, range 5-22) and 16/25 pts stabilized disease (median 5 mo; mean 6.8; 4+-18 mo). Therapy related gr 3-4 toxicities included hypertension (47%), thrombosis (13%; DVT [3pts] and PE [1pt]), elevated liver enzymes (7%), anal fissure (3%), headache (3%), and hand-foot syndrome (HFS; 3%). Most gr 3-4 toxicities and gr 2 HFS occurred within the first 4 mo and most other gr2-3 toxicities occurred at 5-18mo (hypertension [7%], anal fissure [3%], headache [7%], elevation of amylase/lipase [7%], DVT [7%]). HFS gr 2 toxicity was common (80%); all others were ≤10%. S dose reduction was due to HFS in 73% of pts with S dose reduction to 200mg daily at median 2 cycles (range 1-7). DCE-MRI and PET were done to evaluate predictive biomarker potential and will be presented; QoL indices and correlative studies are under analysis. Conclusions: S+B yields promising clinical benefit in B-naïve EOC pts, with manageable toxicity. Phase II intermittent dosing of S+B yielded similar clinical benefit compared to our phase I continuous dosing S+B (NCT00098592) experience (88% v 85% [11/13]) in B-naïve EOC. Most gr3/4 toxicities were early and manageable.
Second interim analysis of GIDEON (Global Investigation of Therapeutic Decisions in Unresectable HCC and of Its Treatment with Sorafenib): Sorafenib treatment and safety in U.S. patients with Child-Pugh B status.
Authors: Bilal Piperdi, Brendan McGuire, Parvez Mantry, Robert C. G. Martin, Pierre Michel Gholam, Jorge A. Marrero, Jeff H. Geschwind, Alan Paul Venook, Arun Sanyal
Journal: Journal of Clinical Oncology (2012)

282 Background: Sorafenib (SOR) is the first systemic therapy to demonstrate a survival benefit in patients (pts) with late-stage hepatocellular carcinoma (HCC). GIDEON is an ongoing, global, prospective, noninterventional study of HCC pts receiving SOR in real-life practice. We present results from the second interim analysis, describing dosing and safety of SOR in HCC pts with Child-Pugh (CP)-B status in the US. Methods: From Jan 2009 – Nov 2010, 326 pts were enrolled (n = 313, safety population) and followed ≥4 months at 92 US centers. Eligible pts had unresectable HCC and were treated with SOR. Demographics, initial dose, treatment duration (TD), dose modifications (mods), and adverse events (AE) were analyzed in pts with available CP status. Results: 119 (38%) pts were CP-A and 100 (32%) were CP-B. 94 (30%) pts were excluded (Table). Median (med) SOR dose was 580 mg/d in CP-A pts and 577 mg/d in CP-B pts. Med TD was 14.4 weeks (wks) in CP-A pts and 10.1 wks in CP-B pts. TD was &lt;4 wks, 4-12 wks, and &gt;12 wks in 14%, 29%, and 56% of CP-A pts, and 22%, 36%, and 39% of CP-B pts, respectively. Treatment-emergent (TE) drug-related AE (all grades) were similar between groups, but more CP-B pts discontinued SOR due to AE (Table). In CP-A and -B pts, all-grade AE were as follows: hand-foot skin reaction (HFSR) (28% vs 19%), diarrhea (28% vs 27%), and fatigue (15% vs 16%). All-grade elevations in ALT, AST, and bilirubin were 2.5%, 2.5%, and 3.4% in CP-A pts and 3%, 1%, and 4% in CP-B pts. Conclusions: These interim US data suggest that SOR safety may be similar in HCC pts with CP-A and CP-B status. Med SOR dose was similar, but med TD was shorter in CP-B pts. AEs were as expected, although HFSR may be underreported in CP-B pts. Limitations of an observational registry must be considered. [Table: see text]
The Impact of Developmental Stage of Osteoblasts and Collagen Fibril Matrix Properties On Hematopoietic Stem Cell Function.
Authors: Brahmananda Reddy Chitteti, Ying-Hua Cheng, Eric Brandner, Bradley Poteat, S.L. Voytik Harbin, Melissa Kacena, Edward F. Srour
Journal: Blood (2009)
Impact of early engagement of patients with clinical trial information in a system-based multidisciplinary breast cancer clinic on clinical trial enrollment.
Authors: Minggui Pan, Anita T. C. Lee, Samantha A. Seaward, Aaron Ilano, Karen House, Esther Duran, Mark DuLong, Maihgan Kavanagh
Journal: Journal of Clinical Oncology (2012)

149 Background: Cancer clinical trial enrollment is low at approximately 3% in the U.S., and there is an urgent need for improvement. Informing patients clinical trial information early at their initial appointment after the diagnosis of cancer may improve clinical trial enrollment. To this goal, we have developed a system-based multidisciplinary breast cancer clinic (MDBCC) that evaluates all newly diagnosed breast cancer cases and discuss with all patients eligible clinical trials at their initial appointment. Methods: Our MDBCC team consists of a medical and radiation oncologist, breast surgeon, mammographer, pathologist, geneticist, and breast cancer coordinators, who review all newly diagnosed cases in the tumor board (multidisciplinary breast cancer tumor board) prior to patient’s MDBCC appointment. During the MDBCC visit, each individual patient meets separately with a medical oncologist, a radiation oncologist, and a surgeon to discuss their treatment options. Eligible clinical trials are discussed and presented to patients with informed consent. Clinical trial nurses are dedicated for patients to call and meet for further discussion on the eligible trials after the MDBCC visit. Results: The average annual clinical trial enrollment for breast cancer was 9 cases (approximately 3%) between 2000 and 2006 prior to initiating the MDBCC, improved to 53 (approximately 17%) between 2007 and 2011 after the MDBCC was formed. The enrollment into the NSABP and SWOG trials accounts for the large portion of the accrual. Conclusions: Early engagement of patients with clinical trial information in a system-based MDBCC for all newly diagnosed breast cancer patients dramatically improves clinical trial enrollment.
RTOG 0118: A phase III study of conventional radiation therapy alone vs. conventional radiation therapy plus thalidomide for multiple brain metastases
Authors: J. P. S. Knisely, B. A. Berkey, A. Chakravarti, W. K. A. Yung, W. J. Curran, H. I. Robins, B. Movsas, D. G. Brachman, R. H. Henderson, M. P. Mehta
Journal: Journal of Clinical Oncology (2005)

1500
Improving nurse practitioner documentation of QOPI symptom management and end-of-life care measures by using "Smart Text" in electronic health records.
Authors: Peg Esper, Suzette Walker
Journal: Journal of Clinical Oncology (2012)

328 Background: Nurse practitioners (NPs) play a significant role in symptom management, yet the literature is lacking in their role in implementation of quality measures for supportive care, symptom management, and end-of-life care. Previous research, however, has described the importance of oncology NPs in providing palliative care and symptom management. Evidence of ASCO’s Quality Oncology Practice Initiative (QOPI) measures for symptom management and end-of-life care have not been well documented in patient medical records. The objective of this project is to improve NP documentation of these quality measures by incorporating use of “Smart Text” with a new electronic medical record system. The research question is, “Do NPs caring for adult medical oncology patients in the ambulatory care setting demonstrate increased documentation of symptom management quality measures following an educational intervention (EI) as compared to pre-intervention chart audits?” Improved documentation of these measures can positively impact patient outcomes. Methods: This quantitative study utilizes pre- and post-EI chart audits. The pre-intervention chart audit will evaluate 100 charts of oncology patients seen by oncology NPs in an academic cancer center for documentation of symptom management and end-of-life care QOPI measures. Pre-chart analysis will be used to develop the EI. The EI will include development of specific “Smart Text” which include information specific to symptom management and end-of-life care QOPI measures. Following the EI, a post- chart audit will be completed to evaluate improvement in NP documentation of these measures. SPSS software will assist researchers in developing descriptive statistics, graphs and analyses to be used in interpretation of findings. The project has been approved and given exempt status by the institution’s IRB. Results: This study is in process and preliminary results are expected by the time of this meeting taking place. Conclusions: If this intervention proves to be successful, it has the potential to be incorporated by not only nurse practitioners, but by all clinicians in oncology settings across the country.
A patient-centered outcome measurement approach for bundled payments in cancer care.
Authors: Tracy Spinks, Seohyun Lee, Kevin Shah, Alexis B. Guzman, Thomas W. Feeley
Journal: Journal of Clinical Oncology (2014)

266 Background: The project aims are to: 1) apply a patient-centered approach to evaluate quality of care in a bundled payment pilot for head &amp; neck cancer; and, 2) measure quality at the condition-level; and, 3) incorporate patient-reported outcomes (PRO) in routine quality assessments. A three-tiered outcomes hierarchy developed by Michael Porter of Harvard Business School is used to define outcome measures, to be used for quality improvement and reporting during the pilot. Porter’s model evaluates outcomes over the full cycle of care, examining: (1) health status achieved/retained; (2) recovery process; and, (3) health sustainability. [Porter, M.E. (2010). What is value in health care? N Engl J Med, 363(26), 2477-2481. doi: 10.1056/NEJMp1011024.] Methods: An 11-member team of clinical, quality, data, and IT experts identified measure concepts, developed measure specifications, and implemented reporting. The project lead interviewed clinical experts to gain consensus around a focused set of measures and benchmarks. Measures were evaluated for importance to patients using feedback from patient focus groups. The team defined the measure specifications (numerator, denominator, etc.), selected a validated PRO instrument, and developed the work flow and tools for data collection and reporting. Process maps were created for training and reference purposes, and clinic staff trained. Testing was completed prior to implementation, with periodic process checks and additional staff training, as needed. Results: Measure development and implementation were completed using a streamlined approach over a 6-month period and required 12 team meetings before implementation. The project leveraged existing data streams, where possible, and IT development focused on quick-turnaround solutions. Conclusions: The project demonstrated that patient-centered outcomes measures can be developed and implemented in a compressed time frame. With provider and patient input, the measures focused on outcomes that are important to patients and actionable by clinicians. This created a scalable framework to be implemented in other disease sites and integrated into our EHR.
Effects of structured patient education in adults with atopic dermatitis: Multicenter randomized controlled trial
Authors: Annice Heratizadeh, Thomas Werfel, Andreas Wollenberg, Susanne Abraham, Sibylle Plank-Habibi, Christina Schnopp, Michael Sticherling, Christian Apfelbacher, Tilo Biedermann, Kristine Breuer, Isabel Fell, Regina Fölster-Holst, Guido Heine, Jennifer Grimm, Lars Hennighausen, Claudia Kugler, Imke Reese, Johannes Ring, Knut Schäkel, Jochen Schmitt, Kurt Seikowski, Esther von Stebut, Nicola Wagner, Anja Waßmann-Otto, Ute Wienke-Graul, Elke Weisshaar, Margitta Worm, Uwe Gieler, Joerg Kupfer, Katrin Brauner, Sabine Dölle, Laura Ehmann, Ute Hagmaier, Susanne Eberlein, Julia Kroth, Katja Lämmerhirt, Rosemarie Landleiter, Ute Lorenz, Anja Lüdemann, Uwe Matterne, Heidrun Mitzel-Rink, Margarete Niebuhr, Tessa Rehberg, Sandra Vogel, Katja Wichmann
Journal: Journal of Allergy and Clinical Immunology (2017)
Adding Mercaptopurine and Methotrexate to Alternate Week ATRA Maintenance Therapy Does Not Improve the Outcome for Adults with Acute Promyelocytic Leukemia (APL) in First Remission: Results From North American Leukemia Intergroup Trial C9710
Authors: Bayard L. Powell, Barry K Moser, Wendy Stock, Robert E. Gallagher, Cheryl L Willman, Richard M. Stone, Jacob M. Rowe, Steven E. Coutre, James H. Feusner, John Gregory, Stephen Couban, Frederick R. Appelbaum, Martin S. Tallman, Richard A. Larson
Journal: Blood (2011)
Second neoplasms in survivors of childhood acute lymphoblastic leukemia treated with both chemotherapy and radiotherapy.
Authors: Wen Shen Looi, Jia Wen Janine Cynthia Koh, Francis Chin, Yi Hui Jonathan Teh, Mei Yoke Chan, Ah Moy Tan
Journal: Journal of Clinical Oncology (2016)

e293 Background: Second malignant neoplasms (SMNs) are a concern in survivors of childhood cancer. Chemotherapy forms the mainstay of treatment for acute lymphoblastic leukaemia, but radiotherapy is used in certain situations. As both chemotherapy and radiotherapy can be carcinogenic, patients treated with both modalities may be at a higher risk of SMNs. This study aims to investigate the incidence of SMNs in patients treated with both chemotherapy and radiotherapy. Methods: Children aged 16 years and below diagnosed with acute lymphoblastic leukaemia from 1993 to 2014 were identified in the Childhood Cancer Registry. Manual and electronic medical records were reviewed for information on demographics, management and SMNs. Results: A total of 64 patients treated with both chemotherapy and radiotherapy were identified. Seventeen (26.6%) were female and 47 (73.4%) were male. The median follow-up was 9.2 years (range, 1.1-22.0 years). The median age at diagnosis was 5.3 years, (range, 0.3-14.6 years). The median age at which radiotherapy was given was 6.6 years (range, 2.9-15.4 years). SMNs were noted in 3 of 64 (4.7%) patients. Two of 3 patients had a SMN within the radiation field (both cranial). The histological diagnoses were basal cell carcinoma and cerebral PNET. The remaining patient had an ovarian immature teratoma outside the radiation field. The latency period ranged from 8.3 years to 13.3 years (median 9.4 years) from date of diagnosis to development of SMN. The estimated 10-year cumulative incidence was 4.3%, 95% CI [0.01, 0.13] using a competing risks analysis. Radiotherapy data was available in 63 patients. Fifty-one of 63 (81.0%) received cranial irradiation, of which 3 (5.9%) also received spinal irradiation. Total body irradiation was performed in 20 of 63 (31.7%), and testicular irradiation in 17 of 63 (27.0%) patients. The orbit was targeted in 3 of 63 (4.8%) patients. Conclusions: Long term survivors of acute lymphoblastic leukaemia treated with both chemotherapy and radiotherapy may have a significant risk of second malignant neoplasms, which may occur years after the initial diagnosis.