tbuckley/cabot-search huggingface dataset:
Chemotherapy ordering in a computerized physician order entry (CPOE) environment: A longitudinal analysis of defects from oncologist to patient
Authors: W. C. Mertens, L. J. Cassells, D. E. Brown, V. Koertge, L. Cabana, R. Parisi, D. Naglieri-Prescod, D. J. Higby
Journal: Journal of Clinical Oncology (2006)

6040 Background: While published data suggest low chemotherapy error rates, the rate of chemotherapy ordering process defects and who detects them remains uncertain. Methods: Outpatient treatment plans/orders were prospectively evaluated by pharmacy prior to preparation, then by nursing prior to administration. Data collected included the nature of defects, how detected, utility of regimen-specific care sets (facilitating antineoplastic dose calculation and adjunct agent selection), and patient impact. Results: Pharmacy recognized problems with 36% of orders (comprising 1,082 cycles/4,600 drugs), with 34% incomplete (absent orders 17%; missing cycle number 12.5%; other items 4%). Pharmacy identified incorrect orders in 6% (dose calculation 2%; cycle number 1.5%; other items 2.5%). Incomplete orders were more likely to have incorrect items (11.6% v. 3.5% if complete, p &lt; .001). Care set use (76% of cycles) was associated with fewer overall problems and incomplete orders (both p &lt; .001), with reduced absent orders and missing antiemetics, but not antineoplastics. Care set orders exhibited a trend for fewer incorrect items (p=.06). Nursing recognized problems with 14.6% of orders, again most commonly incomplete orders (10%; absent orders 7%; missing antiemetic or antineoplastic drug 4.6%); fewer missing items resulted from care set use (p &lt; .001). Nursing detected fewer orders with problems and missing items but more instances of missing antineoplastic and antiemetic agents (all p &lt; .001) despite prior pharmacy review. Nursing identified incorrect orders in 5% (wrong dosage 3.4%; wrong drug 2.5%) and classified 4% of cycles as having an error (“near miss” 3.3%; more serious error reaching the patient 0.6%). Conclusions: Defects in chemotherapy orders are common despite the relatively low error rate. The predominant defects–incomplete orders–are associated with incorrect items. Both care sets and pharmacy review reduce but do not eliminate incomplete orders; the effect on incorrect orders is smaller. Even with CPOE, sequential pharmacy and nursing review remain critical to reducing order defects; additional software enhancements are needed to further reduce defects. No significant financial relationships to disclose.
Additional value of EGFR downstream signaling phosphoprotein expression to <i>KRAS</i> mutation for response prediction to cetuximab in colorectal cancer (CRC)
Authors: J. L. Merlin, G. Perkins, A. Lièvre, C. Ramacci, J. F. Emile, V. Boige, F. Bibeau, O. Bouché, F. Penault-Llorca, P. Laurent-Puig
Journal: Journal of Clinical Oncology (2008)

4126 Background: KRAS mutations have been implicated in the resistance of CRC to cetuximab (Lievre et al, J Clin Oncol, 2007) and key mechanisms involved in the resistance to anti-EGFR therapy appear to come from the constitutive activation of EGFR downstream signaling. Methods: EGFR downstream signaling phosphoproteins expression, belonging to MAP kinase (p-MEK, p- ERK1/2) and AKT (p-AKT, p-GSK3, p-P70S6K) pathways were analyzed using Bioplex phosphoprotein array in 42 patients treated for advanced CRC by cetuximab (41) or panitumumab (1) then confronted to KRAS mutation previously analyzed. Results: Among the 42 patients analyzed (M/F: 24/18; mean age: 61.8 years), 12 (28.5%) had an objective response to anti EGFR antibodies (CR: 1, PR: 11), administered in monotherapy (n=3) or in combination with irinotecan (alone, n=37; FOLFIRI regimen, n=2). Median progression-free survival (PFS) was 15.3 weeks. KRAS mutations were observed in 45.2% of the cases (n=19) and were significantly associated with the absence of response to cetuximab (0 responder among the 19 mutated patients versus 12 (52%) among the 23 non-mutated patients; p<10-4). In univariate analysis, PFS was longer when tumor was not mutated (median: 32 vs 8.6 weeks, Log-rank p<10-5). Expression of p-P70S6K was lower in responder than in non-responder patients (p=0.02). In Cox univariate analysis adjusted on age and gender progression free survival (PFS) was longer for patients with low expression of p-P70S6K and p-MEK with an hazard ratio (HR) of 2.44 (p=0.007) and 1.89 respectively (p=0.025). In a stepwise estimation of a Cox proportional hazard model including the 5 phosphoprotein tested p-MEK was the only retained protein to predict PFS. p-MEK expresion was higher in KRAS mutated tumors than in non mutated tumors (p<.04). In Cox multivariate analysis adjusted for age and gender KRAS and pMEK are two independent prognostic markers of patients treated by anti-EGFR antobodies (HR 4.4, P<10-3 and 2.15, p=0.03 respectively). Conclusions: This study shows the interest of measuring EGFR downstream signaling phosphosproteins expression in CRC. Adding functional data to KRAS mutation analysis, such data could be helpful to predict response to cetuximab and PFS in CRC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Merck
The prognostic value of pain scores for clinical outcomes in advanced breast cancer and prostate cancer
Authors: P. P. Major, D. Habr, R. J. Cook
Journal: Journal of Clinical Oncology (2008)

22120 Background: In patients (pts) with advanced cancer, bone metastases (mets) are the most common source of chronic cancer-related pain. Pts with untreated bone mets typically have pain clustered with fatigue, increased use of analgesics, and a reduced sense of overall well-being; however, residual pain despite treatment can be viewed as an independent outcome. Pain scores may therefore provide prognostic insight into risks of skeletal-related events (SREs) and death in these pts. To evaluate this, we conducted a retrospective analysis in 2 large zoledronic acid (ZOL) clinical trials in pts with bone mets from breast cancer (BC) or prostate cancer (PC). Methods: Pts treated with ZOL who had BC (n = 664 at baseline) or PC (n = 376 at baseline) and complete pain, lesion site, lesion #, and SRE history data for the respective time points were included. At baseline and 6 and 12 mo, pts were categorized by their Brief Pain Inventory (BPI; 1 to 10 scale) as group A (< 2.5), group B (2.5 to 5.0), group C (5.0 to 7.5), and group D (≥ 7.5). Univariate analyses were performed for relative risks of first SRE and death for each group vs group A. Results: Group D contained <10% of pts at each time point, and is not reported herein. For BC, many pts transitioned from higher-pain to lower-pain groups during treatment, whereas pain was persistent among PC pts. For BC, at each time point groups B and C had ∼2-fold increased risks of first SRE vs group A (P < .05 for all). Groups B and C consistently had increased risks of death vs group A at each time point, although the magnitude and significance of the differences varied throughout the study. For PC, Group B and C had increased risks of death and first SRE, respectively, vs group A at baseline (P < .003 for each). During therapy (6 and 12 mo), group C had ∼2-fold increased risks of first SRE and death vs group A, and group B also had ∼2- fold increased risk of first SRE vs group A (P < .02 for both 6 and 12 mo), but correlations with overall survival were inconsistent. Conclusions: These analyses suggest that the time course of pain levels may provide important prognostic information during ZOL therapy in pts with bone mets from BC or PC. Therefore, residual pain level may not only be an indicator to increase palliative care but should also play a role in evaluating overall treatment options. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Pharmaceuticals Corporation Novartis Pharmaceuticals Inc. Novartis Pharmaceuticals Inc. Novartis Pharmaceuticals Inc.
Transdermal gels: A novel delivery system for rescue of delayed nausea and vomiting
Authors: P. T. Silberstein, A. Bhaskara
Journal: Journal of Clinical Oncology (2005)

8201 Several recent studies have shown that despite modern antiemetic regimens, 40% to 60% of patients continue to experience delayed nausea and vomiting. We have studied the use of transdermal gel compounds as an alternative rescue medication for delayed nausea and vomiting compared to oral medications and rectal suppositories. We were unable to locate any trial measuring the effectiveness of rescue medications once patients are experiencing nausea and vomiting at home in the literature. In our clinic, patients receiving outpatient treatment are sent home with a prescription of the Ativan, Benadryl, and Haldol (ABH) transdermal gels, which are formulated at several outpatient pharmacies. The ABH gel is constituted in 5 cc of plurionic lecithin organogel (PLO) and is rubbed into the palmar aspect of the wrist for approximately one minute. These gels may be used up to four times a day. We contacted twenty-four patients who were prescribed these gels after receiving outpatient chemotherapy. The patients were asked a series of questions to determine their response to and side effects from the transdermal gels. Only three patients noted sedation while using the transdermal gels. Eighty-seven percent of patients surveyed were also prescribed standard agents for the prevention of both acute and delayed nausea and vomiting including dexamethasone and 5-HT3 antagonists. A majority of surveyed patients expressed satisfaction with the transdermal gels. The survey showed the transdermal gels were helpful as a rescue medication for chemotherapy induced delayed nausea and vomiting. No significant financial relationships to disclose.
Correlation of hENT1 expression with response and survival in non-small cell lung cancer patients treated with gemcitabine-containing chemotherapy
Authors: T. Oguri, H. Achiwa, H. Ozasa, M. Nakao, T. Uemura, C. Ohta, O. Takakuwa, M. Miyazaki, K. Maeno, S. Sato, R. Ueda
Journal: Journal of Clinical Oncology (2009)

e22032 Background: The most active gemcitabine uptake has been found via the human equilibrative nucleoside transporter 1 (hENT1). This study was to explore the prognostic impact of the hENT1 on response and survival in Non-small lung cancer (NSCLC) patients treated with gemcitabine-containing chemotherapy. Methods: We developed polyclonal antibody for hENT1. Then we stained hENT1 expression by immunohistochemical analysis in 24 biopsy samples of NSCLC which was formaline-fixed, paraffin- embedded tissues. We were treated with gemcitabine alone or gemcitabine-containing chemotherapy until third-line regimen. Results: They comprised 16 males and 8 females with a median age of 63 years (range 45–82 years). Seventeen patients had adenocarcinomas, six had squamous-cell carcinomas, and one had a large-cell carcinoma. All patients were treated with gemcitabine- containing chemotherapy, with 9, 12, and 3 patients receiving this as a first-, second-, and third-line therapy, respectively. The hENT1-positive staining in NSCLC samples was significantly associated with response to gemcitabine-containing chemotherapy (Fisher's exact test, P&lt;0.05). Responses to gemcitabine-containing chemotherapy were evident in none of the seven patients with no hENT1 expression. Further 3 years survival differed by hENT1 staining: 714 days for hENT1-positive, 316 days for hENT1-negative (HR 2.86; 95%CI 1.13–15.16, P&lt;0.05). Conclusions: While there are some determinants for gemcitabine sensitivity, hENT1 expression may be a predictive maker for the response and survival to gemcitabine-containing chemotherapy in NSCLC. No significant financial relationships to disclose.
Preclinical testing of the PARP inhibitor ABT-888 in microsatellite instable colorectal cancer
Authors: E. Vilar Sanchez, A. Chow, L. Raskin, M. D. Iniesta, B. Mukherjee, S. B. Gruber
Journal: Journal of Clinical Oncology (2009)

11028 Background: Microsatellite instability (MSI) represents approximately 15% of colorectal cancer (CRC) cases. MSI due to hypermethylation or mutation in DNA mismatch repair genes leads to genetic instability and a mutator phenotype. Genetic instability is particularly high at repetitive sequences such as those located in MRE11, RAD50, CtIP and MBC. Each of these genes are implicated in the double strand break (DSB) repair pathway. PARP inhibitors induce single strand breaks that remain unrepaired and then will be converted to DSB during DNA replication. Our objective was to assess the preclinical activity of a novel PARP inhibitor ABT-888 in MSI cell lines deficient in the DSB repairing pathway and compare it to Microsatellite Stable (MSS) lines. Methods: We used the systems biology tool “Connectivity Map” to synthesize data from 5 different published studies of expression profiling of MSI CRC phenotype and to identify target compounds. We assessed the mutational status of MRE11, RAD50, CtIP and MBC in a panel of 10 CRC cell lines displaying either MSI or MSS, and measured the expression of MRE11 by quantitative RT-PCR. We tested the cytotoxic activity of single-agent ABT-888 for 6 days in MSS and MSI cell lines, stratified by mutational status. Flow cytometry was performed after 24 hours. Results: Systems biology studies identified PARP inhibitors as a candidate compound relevant for MSI CRC. Mutational status of MRE11 was perfectly correlated with MSI status. ABT-888 shows a preferential activity on those MSI cell lines harboring mutations in both MRE11 and RAD50 genes compared to MSS cell lines (wild-type for both genes). A significant correlation exists between MRE11 expression levels and cytotoxicity to ABT-888 at 10 μM (R 2 =0.915, P&lt;0.001). Flow cytometry analyses show a G1 arrest following to the treatment with ABT-888 that is higher in MSI cell lines with mutations in MRE11 and RAD50 compared to MSS cell lines. Conclusions: This is the first report of the preclinical activity of a PARP inhibitor in CRC models. MSI colorectal tumors deficient in DSB repair show a higher sensitivity to PARP inhibition. Further clinical investigation of ABT-888 as a single agent or in combination with other chemotherapy drugs inducing DSB is warranted in MSI CRC with mutations in MRE11 and RAD50. No significant financial relationships to disclose.
Improving data collection procedures in multi-center clinical trials: Evaluation of an electronic system in the URCC CCOP research base
Authors: S. L. Ranson, G. R. Morrow, S. Dakhil, M. Good, P. J. Kuebler, D. Halk, L. Yee, D. H. Vesole, M. Hofman, J. Yates
Journal: Journal of Clinical Oncology (2004)

6084 Background: The URCC CCOP Research Base studied ways to improve the quality of data collection for patient feedback-driven clinical trials by reducing the time between when data is requested and the receipt of that data. The previous system used paper forms mailed to participating CCOP sites across the country. Since much of the cancer control data collected at the URCC CCOP depends on time-points during cancer treatment, delay in data recovery contributes to a higher rate of unusable or lost data. Methods: Three test sites were chosen based on high numbers of queries for missing or incomplete data generated last year, willingness to provide feedback, and geographical location. The sites were observed without intervention for three consecutive months as a baseline measure. The sites were introduced to the E-query system for one month to test the program and finalize the design. Intervention data were then collected for another consecutive three months for comparison with the baseline. Results: The mean number of days for the return of queries during baseline was 37.0 days. After intervention, the mean number of days for the return of e-queries was 28.6 days. This 23% reduction in mean time for data request responses was found to be statistically significant (p < .05). When data were examined by individual test sites, two of the three showed statistically significant improvement. Conclusions: Data timeliness, (defined as proper response to data requests within the 21-Day period used in URCC CCOP protocols) improved overall by 45.3%. Per site, the improvement was 85.6%, 53.4% and 10% improvement over time. The use of E-queries reduced the time between data request and data receipt and were found to improve data quality at URCC CCOP. Some sites responded better to E-queries than others over time. Additional benefits included: reduction of paper waste, elimination of accidental paper query loss, and a reduction of steps between data request and data report generation. Based on these findings, the remaining 17 URCC affiliated CCOP members were added to the E-query system on June 1st. No significant financial relationships to disclose.
Changes in symptoms and inpatient mortality among advanced cancer patients admitted to a palliative care unit in a comprehensive cancer center.
Authors: M. Mori, H. A. Parsons, M. De la Cruz, A. F. Elsayem, S. L. Palla, J. Liu, Z. Li, J. L. Palmer, E. Bruera, N. A. Fadul
Journal: Journal of Clinical Oncology (2010)

9065 Background: Accurate prediction of hospital death in advanced cancer patients would allow oncologists and palliative care specialists to share more appropriate care plan with patients and families. Although several symptoms have been shown to predict survival, little is known of the association between changes in symptoms and inpatient mortality. Methods: This is a retrospective study approved by the institutional review board. We reviewed the medical records of 166 consecutive cancer patients admitted to our palliative care unit (PCU) from the emergency center (EC) or clinic from 06/2006 to 12/2007. We recorded symptoms as rated by Edmonton Symptom Assessment Scale and the presence of delirium as determined by Memorial Delirium Assessment Scale both on admission (baseline) and on the 3rd, 4th, or 5th day, whichever appeared first (follow-up). The primary end point was the vital status at discharge. Paired T test was used to test changes in symptoms over time. Univariate (UVA) and multivariate analyses (MVA) were used to estimate the odds of dying in PCU between various patient groups. Results: 134 patients (80.7%) were discharged alive and 32 (19.3%) died in PCU. All symptoms significantly improved at follow-up. In UVA, persistent delirium over time was significantly associated with inpatient mortality (odds ratio [OR] 2.59, 95% confidence interval [CI] 1.09-6.17, p=0.031), though presence of delirium at baseline was not. MVA revealed that greater risk of dying was jointly correlated with a high level of baseline dyspnea (OR 1.35, 95% CI 1.13-1.61, p=0.001), a high level of baseline drowsiness (OR 1.25, 95%CI 1.04-1.50, p=0.02), transfer from the EC (OR 6.78, 95%CI 1.99-23.14, p=0.002) and a decreasing level of baseline anxiety (OR 0.83, 95%CI 0.70-0.99, p=0.038). Worsened depression over time was significantly related with death in UVA (OR 1.30, 95%CI 1.08-1.56, p<0.001), but not in MVA. Conclusions: We observed a significant association of certain factors with increased likelihood of PCU death in advanced cancer patients. Changes in certain symptoms, such as worsened depression and persistent delirium, were suggested as important predictors of inpatient death. No significant financial relationships to disclose.
The <i>JEM</i> and the <i>JCB </i>
Authors: Ralph M. Steinman, Ira Mellman
Journal: The Journal of Experimental Medicine (2004)

We live in a scientific universe in which subject boundaries are increasingly porous. Department definitions in many institutions are either close to meaningless or nonexistent, and many faculty count themselves as active participants in at least two, if not more, of the major disciplines of biology
Inadequate BCR-ABL monitoring in imatinib-treated patients with chronic myelogenous leukemia
Authors: E. Stanek, R. E. Aubert, C. Sanders, F. W. Frueh, J. Yao, R. S. Epstein
Journal: Journal of Clinical Oncology (2009)

7077 Background: Recommendations for baseline and quarterly measurement of the BCR-ABL fusion transcript to monitor imatinib response in patients with chronic myelogenous leukemia (CML) were formally introduced in October 2006, and have been incorporated into nationally recognized treatment guidelines. Methods: To assess BCR-ABL testing rates, we conducted a retrospective cohort analysis using a &gt;10 million-member health plan database comprised of integrated pharmacy and medical claims. The study cohort was defined as patients with an index imatinib pharmacy claim from July 1, 2006, to December 31, 2006, who had a CML diagnosis (ICD-9 205.1X; N = 504), and a minimum of 3 months continuous follow-up by claims history (N = 465). Over a period of up to four quarters from the index imatinib prescription date, BCR-ABL testing in each quarter was assessed by the presence of any of a set of 19 CPT-4 codes. BCR-ABL testing rates in each individual quarter and in consecutive quarters were measured. Results: The overall study cohort was 57% male; mean (±SD) age was 52±14 y/o, with 26% 19–44 y/o, 57% 45–64 y/o, and 15% ≥65 y/o. Median duration of f/u was 559 days (interquartile range 302–628 days), and a cohort of 359 patients had 4 quarters of f/u. At least one BCR-ABL test was recorded in 60% of patients. The rate of first quarter BCR-ABL testing was 40%, and remained at 42%-43% in quarters 2 thru 4. Consecutive quarterly testing rates were 24% through the second quarter, 18% through the third quarter, and 14% through the fourth quarter. Conclusions: In this retrospective claims database analysis, only 14% of a large cohort of CML patients treated with imatinib had BCR-ABL testing recorded in each of 4 consecutive quarters. Inadequate compliance with recommended BCR-ABL testing can delay treatment decisions, and may be associated with poor clinical outcome. [Table: see text]