tbuckley/cabot-search huggingface dataset:
Trial prospector: An automated clinical trials eligibility matching program.
Authors: Andrew J. Parchman, Guo-Qiang Zhang, Patrick Mergler, Jill Barnholtz-Sloan, Robert Lanese, Dawn M. Miller, Chris Opper, Satya Sahoo, Shiqiang Tao, Joseph Teagno, James Warfe, Neal J. Meropol
Journal: Journal of Clinical Oncology (2013)

6538 Background: Clinical trials are the evidence base for improving cancer treatment. Unfortunately, only approximately 5% of cancer patients (pts) take part in clinical research studies. Even in settings where clinical trials (CTs) are available, pt participation remains low. We hypothesize that the time required to identify appropriate studies for individual pts is a significant barrier to clinical trial accrual. Methods: Our multidisciplinary team developed Trial Prospector (TP), an innovative and flexible computer-based system that utilizes artificial intelligence and natural language processing to automatically extract information (e.g. demographics, pathologic diagnosis, stage, labs) from multiple clinical data systems and then match it to CT eligibility criteria. A user-friendly interface allows physician perusal of relevant CTs and eligibility checklists at the point of care without requiring manual data entry. We pilot tested TP in our cancer center GI oncology subspecialty clinics. TP was deployed for consecutive new pts, and oncologists (oncs) completed surveys after each visit to assess the usability and impact of TP. Results: Eleven medical oncologists (6 attendings and 5 fellows) participated in the pilot study. TP was deployed during 60 new pt visits. Of the 15 relevant GI/phase I CTs, TP identified a mean of 7 ± 2.7 eligible trials per patient. The most common reasons for ineligibility were pathologic diagnosis and labs. CTs were considered by the treating onc for 66.7% of the pts. 95% of participating oncs reviewed the TP output at the point of care with 70% spending 0-5 minutes assessing eligibility. Of the pts considered for CTs, a TP report was reviewed 72.5% of the time. Oncs reported that TP saved time identifying potential CTs during 57.1% of the visits. The reports were manually reviewed, and the TP matching algorithm was 100% accurate. 90.9% of the oncs recommended TP for CT screening. Conclusions: These results indicate that Trial Prospector is a feasible, accurate, and effective means to identify CTs for individual pts during a busy outpatient oncology clinic. Ongoing refinements will expand clinical data extraction and CT warehouse to improve precision and applicability across diseases.
Testing targeted demethylation to overcome resistance to epidermal growth factor receptor (EGFR) blocking agents in wild-type (wt) <i>KRAS</i> metastatic colorectal cancer patients (mCRC).
Authors: Ignacio Garrido-Laguna, Kimberly McGregor, Mark Wade, John R. Weis, Laura Burr, Raffaella Soldi, Cynthia Davidson, Loni Jakubowski, Glen Morrell, Jeffrey Olpin, David Jones, Sunil Sharma
Journal: Journal of Clinical Oncology (2012)

3057 Background: Panitumumab, a monoclonal antibody against EGFR, led to improved progression-free survival (PFS) in patients with (wt)KRAS mCRC. However, the benefit of panitumumab is limited to a not yet identified small subset of (wt)KRAS patients. The CpG island methylator phenotype (CIMP-high) is present in 15-20% of CRC patients. Epigenetic silencing through methylation of PTEN and/or genes in the EGFR pathway might play a role in resistance to therapy. We assessed whether decitabine (a hypomethylating agent) reverted resistance to anti-EGFR therapies. Methods: Patients (n=19) with (wt)KRAS mCRC previously treated with anti-EGFR therapies were enrolled. Patients were treated with decitabine 45mg/kg IV on day (d)1 and d15 and panitumumab 6mg/kg IV on d8 and d22 q28days. Peripheral blood, skin biopsies and buccal smear samples were collected on d1, d8, d15 and d22 to assess methylation changes in PTEN, RASSF1A and SOCS-1 in response to therapy. Tumors were analyzed for PIK3CA mutations using PCR-based DNA sequencing of exon 9 and 20 by PCR as well as for PTEN by immunohistochemistry. Results: Median age was 53 (range 31-72). Eleven (58%) patients were female; 15 (79%) had ECOG PS 1; 3 (16%) had ECOG PS 2; and 1 had ECOG PS 0. Median number of previous therapies was 4. The most common toxicities were rash (68%), hypomagnesemia (26%) and neutropenia (10%) (all grade 1-2). The most common grade 3-4 toxicities were neutropenic fever (5%) and hypomagnesemia (5%). Of 19 (wt)KRAS mCRC patients previously treated with anti-EGFR therapies, 2 (11%) had a partial response (PR) (-50% and -30%, respectively) and 3 (16%) had stable disease (SD) &gt;4 months (7.8, 5.9 and 4.2 months). Both responders were (wt)PIK3CA and (wt)PTEN. Clinical benefit rate (PR+SD) was 27%. Median PFS was 60 days (95% CI 45.4-74.5), similar to median PFS after last anti-EGFR therapy, 61d (95% CI 50.6-71.3). Conclusions: Panitumumab + decitabine is an active combination in a subset of patients with mCRC previously treated with anti-EGFR therapies (2 PRs in this population). Efficacy assessment in an anti-EGFR therapy naïve population is warranted. Methylation studies are ongoing.
Arthur Jores 1901–1982
Authors: Herbert Weiner, Adolf-Ernst Meyer, W. Senf, H. Kordy, M. von Rad, W. Bräutigam, Peter E. Sifneos, Cairns Aitken, Chase Patterson Kimball, Alec Ramsay, Michael von Rad, Johannes Siegrist, Adolf-Ernst Meyer, Herbert Weiner, Adolf-Ernst Meyer, Hubert Speidel, W. Bräutigam, M. von Rad, Adolf-Ernst Meyer, Antje Haag, Christian Müller, Volker Tschuschke, Walter Volk, Reinhard Költzow, Fritz A. Muthny, Adam J. Krakowski, A. Heerlein, G. de la Parra, S. Aronsohn, F. Lolas, W. Ehlers, D. Czogalik, E. Gaus, M. Klingenburg, K. Köhle, Hertha Appelt, Bernhard Strauss, K.W. Bash, Hans-Werner Künsebeck, Wolfgang Lempa, Hellmuth Freyberger, Eike G. Fischer, Nora E. Falke, Antje Haag, Adam J. Krakowski, M.A. Rea, D.H. Hellhammer
Journal: Psychotherapy and Psychosomatics (1984)
Overweight as a risk factor for triple-negative breast cancers in premenopausal women.
Authors: Yin Liu, Shuang Hao
Journal: Journal of Clinical Oncology (2014)

e12038 Background: Triple-negative breast cancer (TNBC) is a subtype of breast tumor with unique characteristics in terms of clinical-pathological presentation, prognosis, and response to therapy. Obesity is associated with poorer outcomes in patients with hormone receptor-positive breast cancers. This association is not well established for women with TNBC. In this study, the prognostic effects of body mass index on clinical outcome were evaluated in patients with TNBC. Methods: A total of 1,106 patients who met the inclusion criteria were identified from January 2002 to June 2012. Clinical and biological features were collected to evaluate the relation between body mass index (BMI) and breast cancer specific survival (BCSS) after controlling for other clinically significant variables by cox proportional hazard model. Results: Six hundred and fifty-six patients (59.3%) were normal/underweight (BMI ≤24 kg/m2), 450 patients (40.7%) were overweight (BMI >24 kg/m2). The median follow-up time was 44.8 months.The 5-year BCSS was 87%. Compared with normal/underweight patients, the multivariate hazard ratio (HR) for BCSS was 1.18 (95% confidence interval [CI], 0.97-1.44) for overweight patients in the whole population. Similarly, BCSS was not associated with BMI category in postmenopausal women; overweight patients had an HR of death of 0.94 (95% CI, 0.74-1.21) compared with normal/underweight patients. In contrast, the multivariate hazard ratio (HR) for BCSS was 1.46 (95% confidence interval [CI], 1.03-2.07; p =0.04) for overweight patients in premenopausal women. A Cox regression analysis identified overweight (HR, 1.46; 95% CI, 1.03-2.07), positive nodal involvement (HR, 12.43; 95% CI, 4.32-35.78), and tumor size larger than 5 cm (HR, 2.53; 95% CI, 1.71-3.73) as independent prognostic factors for BCSS in premenopausal women. Conclusions: According to this analysis, overweight women with TNBC are at a greater risk of poorer prognosis than normal/underweight women in premenopausal population. If validated, these findings should be taken into consideration for the development of targeted preventive programs.
No evidence for microsatellite instability in acute myeloid leukemia
Authors: C J Walker, A-K Eisfeld, L K Genutis, M Bainazar, J Kohlschmidt, K Mrózek, A J Carroll, J E Kolitz, B L Powell, E S Wang, R M Stone, R Bundschuh, A de la Chapelle, C D Bloomfield
Journal: Leukemia (2017)
Shift to a New Donor Does Not Improve the Outcome After Second Allogeneic Stem Cell Transplantation (alloSCT) in Acute Leukemia Relapse After a First Allosct – a Risk Factor Analysis by the German Stem Cell Registry (DRST).
Authors: Maximilian Christopeit, Ulrike Feldmann, Juergen Finke, Donald W. Bunjes, Dietrich W. Beelen, Martin Bornhaeuser, Christoph Faul, Rainer Schwerdtfeger, Hans-Jochem Kolb, Martin Gramatzki, Hans Martin, Stefan O Schoenland, Christof Scheid, Lutz Uharek, Axel R. Zander, Arnold Ganser, Guido Kobbe, Ernst Holler, Axel A Fauser, Joachim Kienast, Hermann Einsele, Herbert G. Sayer, Ralph Mayer, Gerhard Behre, Hellmut Ottinger, Hubert Schrezenmeier, Christoph Schmid
Journal: Blood (2009)
Piloting breast cancer survivorship care planning in a safety net hospital.
Authors: Sofia F. Garcia, Katy Wortman, Yanina Guevara, Elizabeth A. Hahn, Maria E. Corona, Shakuntala Shrestha, Paramjeet Khosla
Journal: Journal of Clinical Oncology (2017)

65 Background: Survivorship care plans (SCPs) include treatment summaries and follow-up care recommendations intended to improve patient care and well-being after cancer treatment. Limited research has yielded mixed results regarding SCPs' impact on patient and system outcomes, but emphasized provider burden as an implementation barrier. We created a patient-centered SCP template and implemented its delivery at a safety net hospital that serves primarily racial/ethnic minority patients. Methods: In a single-arm feasibility study, oncologists and advanced practice nurses used the template to deliver SCPs to post-treatment breast cancer survivors (BCS) in consultation visits. We assessed changes in patient-reported outcomes from baseline (pre-SCP) to a 3-month follow-up, as well as provider time burden. Results: Female BCS participants (n = 75; mean age = 58.5 years) were primarily African-American (73%) and had high school/GED education or less (61%). Average time since diagnosis was 3.7 years (SD = 3.8); all received surgery; most received radiation (84%), hormone (77%), and/or chemotherapy treatment (73%). At follow-up, a majority rated their SCPs as good to excellent (92%), easy or very easy to understand (84%), a good to excellent summary of their treatment (92%) and as motivation for healthy lifestyles (88%). BCS follow-up scores improved significantly from baseline on breast cancer knowledge (p = .02), self-efficacy (p = .03), the QLQ-INFO25 (p &lt; .01), and the FACIT TS-PS satisfaction with health care staff communication subscale (p &lt; .01). No significant differences between baseline and follow-up scores (p &lt; .05) were found for overall treatment satisfaction, health behaviors, and health-related quality of life. Preparing and delivering SCPs took providers considerable time (M = 54 &amp; 22 minutes, respectively). Conclusions: This pilot study is limited by a single-arm design, but results suggest that SCPs may be related to improved survivor knowledge, information, self-efficacy and communication with health care staff. The individualized, comprehensive SCPs were well received by BCS in a safety net hospital but delivery was time-intensive. These findings will inform future research trials and clinical care initiatives.
Nimotuzumab plus paclitaxel and cisplatin as first-line treatment for esophageal squamous cell cancer: Final results of a single-center prospective clinical trial.
Authors: Ming Lu, Xicheng Wang, Zhihao Lu, Jian Li, Jie Li, Yan Li, Xiaotian Zhang, Jun Zhou, Jifang Gong, Jun Jia, Jing Yu, Yan Cui, Lin Shen, Xiaodong Zhang
Journal: Journal of Clinical Oncology (2014)

4070 Background: Nimotuzumab (N) was a humanized anti-EGFR monoclonal antibody. We conducted a prospective, single-armed, open label phase II study to evaluate the efficacy and safety of paclitaxel (T)/cisplatin (C)/ Nimotuzumab (N) as first-line treatment in advanced ESCC. Methods: Patients with pathologic confirmed unresectable local-regional advanced or metastatic ESCC were treated with the TPN regimen: Nimotuzumab 200mg weekly, Paclitaxel 175mg/m2 on d1, and Cisplatin 30mg/m2 on day1 and 2, repeat cycle every 3 weeks for six cycles. Local-regional advanced disease was defined as tumor lesion limited in 1 radiation field without organ metastasis. Metastatic disease was defined as organ (liver, lung et al) metastasis or lymph nodes metastasis exceeding 1 radiation field. Radiotherapy was allowed to be admitted after 4 cycle of TPN treatment.The primary endpoint is the objective response rate (ORR) and the safety. The secondary endpoint is the progression free survival (PFS) and the overall survival (OS). Results: 59 pts were enrolled from 2011 to 2013 and 56 were eligible. 29 pts were local-regional advanced disease and 27 pts were metastatic disease. Overall RR was 51.8%(29/56) and DCR was 92.9%(52/56). As a median follow-up of 24 months, 33 pts had progressed, of which 22 pts were metastatic disease. The median PFS for patients with metastatic disease and local-regional advanced disease were 8.2 months (95% CI 5.3 to 11.2 months) and more than 23 months (95% CI: 9.0 to 37.1).The overall survival for patients with metastatic disease was 13.9 months (95% CI: 6.8 to 21.2). The most common G3/4 toxicities were Neutropenia (58.9%), Leukopenia(32.1%), Nausea/Vomiting (7.1%), Anorexia (5%). Febrile neutropenia was reported in 3.6% of patients. No chemotherapy related death occurred. Conclusions: The TPN regimen, as first-line chemotherapy, was a more active treatment option in patients with advanced ESCC compared to other regimens published in previous studies. The addition of anti-EGFR treatment of nimotuzumab to standard chemotherapy was well tolerated with no serious AEs. Clinical trial information: NCT01336049.
Selective Loss of Smaller Spines in Schizophrenia
Authors: Matthew L. MacDonald, Jamil Alhassan, Jason T. Newman, Michelle Richard, Hong Gu, Ryan M. Kelly, Alan R. Sampson, Kenneth N. Fish, Peter Penzes, Zachary P. Wills, David A. Lewis, Robert A. Sweet
Journal: American Journal of Psychiatry (2017)

Objective: Decreased density of dendritic spines in adult schizophrenia subjects has been hypothesized to result from increased pruning of excess synapses in adolescence. In vivo imaging studies have confirmed that synaptic pruning is largely driven by the loss of large or mature synapses. Thus, increased pruning throughout adolescence would likely result in a deficit of large spines in adulthood. Here, the authors examined the density and volume of dendritic spines in deep layer 3 of the auditory cortex of 20 schizophrenia and 20 matched comparison subjects as well as aberrant voltage-gated calcium channel subunit protein expression linked to spine loss. Method: Primary auditory cortex deep layer 3 spine density and volume was assessed in 20 pairs of schizophrenia and matched comparison subjects in an initial and replication cohort (12 and eight pairs) by immunohistochemistry-confocal microscopy. Targeted mass spectrometry was used to quantify postsynaptic density and voltage-gated calcium channel protein expression. The effect of increased voltage-gated calcium channel subunit protein expression on spine density and volume was assessed in primary rat neuronal culture. Results: Only the smallest spines are lost in deep layer 3 of the primary auditory cortex in subjects with schizophrenia, while larger spines are retained. Levels of the tryptic peptide ALFDFLK, found in the schizophrenia risk gene CACNB4, are inversely correlated with the density of smaller, but not larger, spines in schizophrenia subjects. Consistent with this observation, CACNB4 overexpression resulted in a lower density of smaller spines in primary neuronal cultures. Conclusions: These findings require a rethinking of the overpruning hypothesis, demonstrate a link between small spine loss and a schizophrenia risk gene, and should spur more in-depth investigations of the mechanisms that govern new or small spine generation and stabilization under normal conditions as well as how this process is impaired in schizophrenia.
Does stage migration exist in active multiple myeloma (MM)?
Authors: Prashant Kapoor, Shaji Kumar, Morie A. Gertz, Martha Lacy, David Dingli, Stephen J. Russell, Francis Buadi, Steven R. Zeldenrust, John Anthony Lust, Suzanne R. Hayman, Robert A. Kyle, Vincent Rajkumar, Angela Dispenzieri
Journal: Journal of Clinical Oncology (2012)

8105 Background: Tumor stage migration can artifactually inflate cancer survival rates and overestimate benefits of newer therapies. We have previously shown a favorable impact of widely used novel agents in MM patients. However, it is not known whether use of well tolerated and easily administrable novel agents results in their introduction at lower levels of MM burden (and therefore add to improved outcome). Our goal was to assess for stage migration in newly diagnosed active MM patients. Methods: We reviewed records of 1,467 patients with active MM at Mayo Clinic, at initiation of therapy from 3 consecutive 5-year intervals: 01/1996-12/2000 (Group 1), 01/2001-12/2005 (Group 2), 01/2006- 12/2010 (Group 3). These intervals reflect the practice changing approaches at our center transitioning from the use of alkylator-based to novel agent-based initial therapy. Traditional parameters and staging systems were used to estimate tumor burden. We performed one way analysis of variance (ANOVA) to assess for differences in these parameters among the groups. A p-value of &lt;0.05 was considered significant. Results: Group 3 shows an upward trend for hemoglobin (Hgb), and lower creatinine and bone marrow plasma cell (BMPC) percent. Compared to other groups, a greater proportion of Group 3 patients are assigned to lower Durie Salmon (DS) stages (Table) suggesting reduced tumor burden at therapy initiation. In contrast, the International Staging System (ISS) which is not used for decisions regarding therapy initiation divides cohorts in similar proportions. Conclusions: Stage migration is evident in our cohort of active MM patients presenting in the time periods of evolving initial therapeutic strategies. Future studies should take into account the bias introduced by this phenomenon in interpreting survival analysis of MM patients. [Table: see text]
Analysis of serum protein biomarkers and circulating tumor (ct) DNA for activity of dovitinib in patients (pts) with tyrosine kinase inhibitor (TKI)-refractory gastrointestinal stromal tumors (GIST).
Authors: Changhoon Yoo, Min-Hee Ryu, Baek-Yeol Ryoo, Sook Ryun Park, Shinkyo Yoon, Young-Soon Na, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2014)

10550 Background: Dovitinib is a multikinase inhibitor targeting VEGFR, FGFR, PDGFR beta, and KIT. Serum protein biomarkers and ctDNA were analyzed for the correlation with the outcomes of dovitinib in a phase II study for TKI-refractory GIST (Br J Cancer 2013;109:2309). Methods: In total of 30 pts, predose serum samples were collected at day 1 of cycle 1 (n=30) and cycle 2 (28). Eight serum proteins were assessed by ELISA (Table 1). Mutation analysis was performed via BEAMing from ctDNA, isolated from baseline samples. Pts were classified by quartiles (Q) of biomarker levels and grouped as appropriate for the analyses. Results: With dovitinib treatment, FGF23, VEGF, VEGF-A, PIGF, and IL-8 increased by 1.5 fold (p=0.02), 1.3 (p=0.006), 1.3 (p=0.004), 6.0 (p=0.002), and 1.8 (p=0.04), respectively, and sVEGFR2 decreased by 0.8 fold (p=0.001) from baseline. Although baseline serum proteins were not associated with efficacy outcomes, pts whose sVEGFR2 decreased more (Q1-Q3) with dovitinib treatment showed better progression-free survival (PFS) than those with a smaller decrease (Q4; median 4.2 months [mo] vs 2.7 mo; p=0.02). Primary KIT mutations were identified via serum in 5 pts (2 for exon 11, and 3 for exon 9), and 100% concordant with results via tissue. Secondary KIT mutations were detected in 11 pts (37%) via serum: 10 had mutations on exon 17/18 and one on both exon 13 and 17. The presence of secondary mutations showed a tendency for shorter PFS (median 3.4 mo vs 4.2 mo; p=0.11) and significantly associated with shorter overall survival (median 5.5 mo vs 9.8 mo; p=0.02). Conclusions: Dovitinib modulates serum levels of circulating proteins involved in VEGF and FGF signaling. The change of sVEGFR2 might predict the outcomes of dovitinib. Secondary KIT mutations could be successfully detected from ctDNA and was associated with poor prognosis. Protein name Abbreviation Soluble vascular endothelial growth factor receptor 1-2 sVEGFR 1-2 Vascular endothelial growth factor and type A VEGF, VEGF-A Placental growth factor PIGF Basic fibroblast growth factor bFGF Fibroblast growth factor 23 FGF 23 Interleukin 8 IL-8
Phase II study of panitumumab, nab-paclitaxel, and carboplatin followed by FEC neoadjuvant chemotherapy for patients with primary HER2-negative inflammatory breast cancer.
Authors: Naoko Matsuda, Xiaoping Wang, Savitri Krishnamurthy, Ricardo H. Alvarez, Jie S. Willey, Bora Lim, Charla A. Parker, Gildy Babiera, Daniel J. Booser, James L. Murray, Banu Arun, Abenaa M. Brewster, James M. Reuben, Michael Charles Stauder, Wendy A. Woodward, Anthony Lucci, Sarah Marie DeSnyder, Debu Tripathy, Vicente Valero, Naoto T. Ueno
Journal: Journal of Clinical Oncology (2016)

1087 Background: EGFR overexpression is an independent poor prognostic factor in patients with inflammatory breast cancer (IBC). Our IBC animal model indicated that EGFR-targeted therapy inhibited IBC tumor progression via reversing EMT and suppression of CSC phenotype. We hypothesized that the combination of an anti-EGFR monoclonal antibody to neoadjuvant chemotherapy for IBC produce higher pathological complete response (pCR; including breast and axilla) rates compared with our historic rates (triple-negative [TN], 12%; HR+/HER2-, 7%) of 527 patients. Methods: In this single-arm, phase II study (47 patients enrolled, closed in June 2015), patients received 1 dose of panitumumab in a window period followed by 4 cycles of the combination of panitumumab (2.5 mg/kg), nab-paclitaxel (100 mg/m2), and carboplatin (AUC 2) on a weekly (PNC) followed by 4 cycles of FEC (5-fluorouracil, 500 mg/m2; epirubicin, 100 mg/m2; cyclophosphamide, 500 mg/m2) was administered, followed by surgical resection, radiation, and hormonal therapy (HR+). The primary end point was the pCR and the secondary objectives were safety and the identification of predictive biomarkers using RNA sequencing and IHC staining. Results: Our analysis included 35 patients. The median age was 54 years (23-68 years). Sixteen patients had TN and 19 had HR+/HER2-. The median follow-up time was 17.8 months (0.5-48.8 months). The pCR rate was 29% (95% CI: 0.15-0.46); seven patients with TN (44%; 95% CI: 0.20-0.70) and 3 with HR+/HER2- (6%, 95% CI: 0.03-0.40). Twelve patients experienced recurrence or death. Grade 3 or 4 hematologic adverse events (AEs) were observed in 25 patients (71%), grade 3 nonhematologic AEs were observed in 11 patients (31%; the most frequent was rash, n = 4), and no grade 4 nonhematologic AEs were observed during the PNC regimen.Comparing changes in gene expression before and after treatment with panitumumab, we identified candidate gene expression changes that might predict the pCR. The validation of these candidate is ongoing. Conclusions: Our data showed that our novel NAC regimen was well tolerated and produced unprecedentedly high pCR rates in primary TN-IBC. Clinical trial information: NCT01036087.
RESULTS of Allogeneic TRANSPLANTATION for Polycythemia VERA and Essential Thrombocythemia
Authors: Karen K Ballen, Mukta Arora, Xiaochun Zhu, Manza Agovi, Matt Kalaycio, Richard T Maziarz, Jorge E. Cortes, Ann Woolfrey, Mary M. Horowitz, Wael Saber
Journal: Blood (2010)