tbuckley/cabot-search huggingface dataset:
Impact of computerized provider order entry on medication errors in outpatient chemotherapy administration.
Authors: Lyudmila Bazhenova, Patricia A. DeMoor
Journal: Journal of Clinical Oncology (2012)

295 Background: Computerized provider order entry (CPOE) reduces medication errors (ME) in ambulatory and hospital settings. We conducted a study to assess the effect of CPOE on ME in an outpatient NCI designated infusion center (IC). Methods: Both actual and prevented ME were prospectively reported by clinical staff as part of IC Standard Operating Procedure using the electronic Quality Variance Reporting (eQVR, Incident Reporting 2.0, University of California) system. Reported ME from 10/2007 to 03/2011 were reviewed by 2 investigators and classified into categories by consensus: wrong medication given (WM), medication missed (MM), wrong timing/rate (T/R), wrong dose (WD), unmet chemotherapy parameters (UP) and other (O). Classifications were further categorized by preventable or facilitated by CPOE. We compared ME 18 mo. pre and post implementation. The 6 month go live period was reviewed separately to examine ME related to a learning curve (LC). Results: 40,366 patients were seen pre-implementation, 47,460 post, and 14,343 during go live. The total ME per pt was similar pre and post (see table). There were dramatic rate differences in WM and MM, but no effect on T/R, WD, UP. In the pre period 66% of ME were felt preventable by CPOE. In turn 35% of ME were facilitated by CPOE. Preventability rates differed between categories. During go live 100% of CPOE facilitated ME were related to user and designer LC. Post implementation 58% of CPOE facilitated ME were still accounted by LC with the rest felt related to the complexity of CPOE. Conclusions: ME are rare in our outpatient IC. CPOE did not change the total number of ME but significantly decreased the rate of WM. Complexities of CPOE resulted in increased MM. LC related errors still occur 24 mo. after implementation of CPOE and require constant monitoring and education. CPOE increased the rate of serious ME felt due to the change in workflow and adding an extra layer of complexity. Human errors cannot be fixed with CPOE and generally encompassed the ME in T/R, WD, and UP classifications [Table: see text]
A retrospective study of FOLFOX in the treatment of patients with advanced duodenal adenocarcinoma: A Japanese single-center experience.
Authors: Ikuhiro Yamada, Masato Ozaka, Hiroshi Ishii, Naoki Sasahira, Kouichi Takano, Masato Matsuyama, Takashi Sasaki, Kei Saito, Hiroki Osumi, Mitsukuni Suenaga, Masahiro Igarashi
Journal: Journal of Clinical Oncology (2015)

457 Background: Duodenal adenocarcinoma is a rare tumor with poor prognosis. There is little data on the efficacy of chemotherapy for this disease. Methods: The current study included data from all consecutive patients who were diagnosed as having duodenal adenocarcinoma at our hospital between October 2008 and December 2013. Selection criteria were as follows: patients who 1) had histologically confirmed duodenal adenocarcinoma, 2) were diagnosed as having unresectable or recurrent disease, and 3) received first-line chemotherapy with infusional 5-FU, leucovorin and oxaliplatin (FOLFOX). We examined efficacy and toxicity of FOLFOX therapy from the case cards and analyzed their survival data. Results: There were 20 patients who met the selection criteria. The median age was 67.5 years (range, 35-76). Of the 20, 11 (45%) were male, 17 (85%) had a good performance status, 15 (75%) had received resection of the primary tumor, and 13 (65%) had a liver metastasis. They received median of 8 (range, 1-32) chemotherapy cycles. There was no complete response. Of the 20, 4 (20%) achieved partial response, 9 (45%) remained stable disease, 6 (30%) showed progressive disease and the remaining one did not have a CT evaluation. The median progression free survival and overall survival months from the initiation of FOLFOX therapy were 5.0 and 11.7, respectively. Grade 3/4 toxicities were observed in 9 (45%). Although there was no febrile neutropenia, grade 3/4 neutropenia was observed in 7 (35%). Treatment-related death due to pneumonitis was documented in one. Whereas prognostic factor was not found in multivariate analysis, a peritoneum metastasis tended to be associated with poor progression free survival (p=0.06). Conclusions: The FOLFOX therapy shows moderately activity with acceptable toxicities for the treatment of advanced duodenal adenocarcinoma.
Androgen deprivation with or without radiation therapy for clinically node-positive prostate cancer.
Authors: Jason Alexander Efstathiou, Chun Chieh Lin, Phillip John Gray, Ahmedin Jemal
Journal: Journal of Clinical Oncology (2015)

198 Background: Clinically lymph node positive (cN+) prostate cancer (PCa) is an often fatal disease. Its optimal management remains largely undefined given a lack of prospective, randomized data to inform practice. We sought to describe modern practice patterns in the management of cN+ PCa and assess the effect of adding radiation therapy (RT) to androgen deprivation therapy (ADT) on survival using the National Cancer Data Base. Methods: Patients with cN+ PCa with no distant metastases diagnosed between 2004-2011 were included. Five-year overall survival for patients diagnosed between 2004-2006 and treated with ADT alone or ADT+RT were compared. Propensity score (PS) matching was used to balance baseline characteristics and Cox multivariate regression analysis was used to estimate hazard ratios (HRs) for all-cause mortality. Results: 3,540 patients were included. 32.2% were treated with ADT alone and 51.4% received ADT+RT. Patients aged &lt;65, those with private insurance, lower comorbidity scores, higher Gleason scores, and lower PSA values were significantly more likely to receive ADT+RT (p&lt;.05). After PS matching, 318 patients remained in each group. Compared to ADT alone, ADT+RT was associated with a 50% decreased risk of five-year mortality (HR: 0.497, 95% CI: 0.37-0.67, p&lt;.001). Conclusions: Using data recorded in a large national database, we have identified a significant survival benefit for patients with cN+ PCa treated with ADT+RT. These data, if appropriately validated, suggest that a significant proportion of such patients at high risk for prostate cancer death may be undertreated warranting a re-evaluation of current practice guidelines.
Palliative care training: A national survey of U.S. hematology/oncology fellows.
Authors: Brendan F. Curley, Roby Antony Thomas, Sijin Wen, Jianjun Zhang, Jame Abraham, Alvin Howard Moss
Journal: Journal of Clinical Oncology (2013)

28 Background: The American Society of Clinical Oncology (ASCO) has recommended integration of palliative care into oncology practice at the time of diagnosis of advanced cancer. The attitudes, knowledge, and skills of Hematology/Oncology fellows in palliative medicine to implement this recommendation have not been assessed. Methods: In 2013 we surveyed current US Hematology/Oncology fellows to assess their attitudes and the quality of teaching in palliative care received during fellowship and their perceived preparedness to care for patients at End of Life (EOL). Trainees at all US programs were surveyed via Research Electronic Data Capture. The survey was IRB approved, anonymous and voluntary. Results: 176 surveys were collected. Statistical analysis was performed with t-test for numeric and Fisher’s exact test for categorical variables. 98% of respondents felt that providing care for dying patients was important. 99% indicated that physicians have a responsibility to help patients at EOL. Fellows felt their overall training in fellowship was superior to their quality of training (p&lt;0.0001) or teaching (p &lt;0.0001) on EOL. Pearson correlation showed that those with training in palliative care felt more prepared caring for patients at EOL (p &lt;0.0001). Fellows who had training in palliative care during fellowship (45.4% of those surveyed) felt they had better teaching on managing a patient at EOL than those who did not (p&lt;0.0001). There was no statistical significance noted with self-identified roles of spirituality or religion in attitudes, knowledge, or skills. 64% reported having conducted over ten family meetings regarding EOL. Only 18.9% were supervised (p&lt;0.0001) and only 13.1% were given feedback more than ten times (p&lt;0.0001). 89.7% of fellows surveyed stated they have disagreed with treatment without palliative care on at least one occasion. 40% of respondents did not know how to respond to a request to stop chemotherapy. Conclusions: Hematology/Oncology fellows believe that EOL care is important. Education about EOL is not at the same level of their overall fellowship training despite the recognition of the benefit of palliative care in Oncology. Educational initiatives need to be introduced to improve training on EOL care.
Did multiagent chemotherapy improve clinical outcomes of advanced pancreatic cancer? A single center experience of 408 cases.
Authors: Yousuke Nakai, Hiroyuki Isayama, Kazunaga Ishigaki, Naminatsu Takahara, Tsuyoshi Hamada, Suguru Mizuno, Hirofumi Kogure, Saburo Matsubara, Natsuyo Yamamoto, Minoru Tada, Kazuhiko Koike
Journal: Journal of Clinical Oncology (2016)

293 Background: We previously reported the introduction of S-1 improved overall survival (OS) in advanced pancreatic cancer (PC), but in a pooled analysis of 3 RCTs, a combination of gemcitabine and S-1 (GS) improved OS in locally advanced PC (LAPC), but not in metastatic PC (MPC), compared to gemcitabine (Gem) alone. More recently, FOLFIRINOX, a multiagent chemotherapy, is shown to improve OS in MPC. We conducted clinical trials of a combination of Gem, S-1 and leucovorin (GSL) to further enhance antitumor effects. Herein, we retrospectively studied whether these multiagent regimens, GSL &amp; FOLFIRINOX, affected the prognosis of APC, especially MPC. Methods: A total of 408 pts with APC receiving chemotherapy were grouped by treatment era into 3 groups: Group 1 (Years 2001-5: 53 pts prior to S-1 introduction), Group 2(Years 2005-11: 240 pts post S-1 introduction) and Group 3 (2012-14: 115 pts post multiagent treatment introduction), and clinical outcomes were compared. Results: Patient characteristics and protocol are shown in Table 1. Treatment protocol was single in 233, dual 142, and multiagent in 33. Response rate &amp; disease control rate in Groups 1/2/3 were 2/8/17% &amp; 26/67/73%. In LAPC, PFS was 6.2/8.9/7.9 &amp; OS was 13.4/17.2/19.7 months in Groups 1/2/3. Meanwhile, in MPC, PFS was 2.0/3.5/4.8 &amp; OS was 6.7/8.6/9.6 months in Groups 1/2/3. When treatment protocols were compared, in LAPC, PFS &amp; OS were 7.0/11.7/8.8 &amp; 13.6/22.6/22.6 months in singe/dual/multiagent chemotherapy. In MPC, PFS &amp; OS were 3.1/3.5/6.0 &amp; 8.3/8.1/13.7 months in single/dual/multiagent chemotherapy. Conclusions: While the introduction of S-1 led to longer OS in LAPC, recent introduction of multiagent chemotherapy appeared to improve OS in MPC. Whether multiagent chemotherapy would lead to longer OS than dual chemotherapy in LAPC needs further investigation. Table 1. [Table: see text]
Phase I trial with weekly docetaxel, capecitabine and carboplatin followed by concomitant capecitabine and radiation in patients with locally advanced esophageal cancer
Authors: S. Rao, B. Oelschlager, W. J. Koh, D. Mabe, J. Huang, M. Saunders, C. Pellegrini, A. R. Shustov, M. P. Upton
Journal: Journal of Clinical Oncology (2008)

15501 Background: The combination of docetaxel,capecitabine and carboplatin has been reported to have activity in metastatic esophagogastric tumor. This phase I study with dose escalation of weekly docetaxel was undertaken to evaluate its safety in the neoadjuvant setting and secondarily to assess pathologic response to this combination. Methods: Patients with T3N0M0 or any TN1M0 esophageal or GE junction tumor who were resection candidates were eligible. Two cohorts of patients were treated with weekly docetaxel:20 mg/m2(cohort1) or docetaxel 25mg/m2(second cohort)on day 1,8, 15 every 28 days with carboplatin AUC=2 on day1, 8, 15 every 28 days and capecitabine 500 mg/m2 po bid days 1–21 q28days. Patients were treated for two cycles followed by capecitabine 650 mg/m2 p.o. bid days 1–42 with radiotherapy (1.8Gy daily days 1–40). This was followed by surgery if there was no evidence of progression. Results: In both cohorts, the most common toxicities were grade I/II toxicities(mucositis, diarrhea,nausea,fatigue). Hematologic toxicity was mild(grade I/II). No grade III/IV toxicity seen. One patient in the second cohort had an active wound infection prior to iniation of treatment and developed sepsis. This patient should have been ineligible due to active infection at the time of entry to the study. Three additional patients at this dose level at this dose level have been studied without any significant toxicity. Eight patients are evaluable for response. Three patients had a near complete pathologic response with rare foci of tumor, five patients had evidence of ulceration/sclerosis at tumor site with microscopic residual disease. Conclusions: The treatment with weekly docetaxel, carboplatin and capeciabine was well tolerated with no patients having grade III/IV toxicity and majority of patients with objective pathologic response including near CR with rare foci of tumor 3/8(38%); and pathologic downstaging in 4/8 (50%). Due to excellent tolerance and efficacy, this combination warrants further clinical study and dose escalation of docetaxel to 30mg/m2 is planned. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche, sanofi-aventis
Selective inhibition of proliferating endothelial cells: A phase I study of the novel organoarsenical compound GSAO in patients with advanced solid tumors.
Authors: G. Kumaran, M. R. Middleton, Y. K. Zee, L. McGuigan, A. R. Clamp, P. J. Hogg, A. Jackson, G. J. Parker, A. L. Harris, G. C. Jayson
Journal: Journal of Clinical Oncology (2010)

TPS167 Background: 4-(N-(S- glutathionylacetyl)amino)phenylarsonous acid (GSAO) is a new water-soluble organoarsenical that selectively inhibits proliferating endothelial cells (EC) in vitro and angiogenesis and tumor growth in human tumor xenografts in vivo. The prodrug GSAO is cleaved by γ-glutamyl transpeptidase (γGT), which is commonly overexpressed on the surface of cancer cells before entering surrounding ECs where it interacts with its mitochondrial target, adenine nucleotide translocase (ANT). ECs are specifically sensitive to GSAO due to their low expression of the multidrug resistance-associated proteins 1 and 2 (MRP 1/2), whereas cancer cells are less sensitive because of higher MRP 1/2 expression. This phase I dose escalation study aims to establish the maximum tolerated dose (MTD) of GSAO, to assess the safety and toxicity profile and to identify the dose limiting toxicity (DLT). Methods: Patients with solid cancers refractory to standard therapy are eligible for the study. Three patients are recruited per dose level with a planned expansion to 6 patients if a DLT occurs. The MTD is the highest dose at which 1 of 6 patients in a cohort experience DLT. Intravenous infusions of GSAO are administered on days 1-5 and 8-12 in a 21-day cycle. Radiological response is assessed after 2 cycles. The pharmacokinetics of GSAO are evaluated by measuring plasma levels using liquid chromatography/mass spectrometry. Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) is used to determine blood flow parameters (Ktrans, ve, vp, IAUC60). Plasma markers of angiogenesis (VEGF, VEGFR1, VEGFR2 and CD105), cell death (Cytokeratin 18 [CK18] fragments) and apoptosis (CK18asp396) are measured in samples before and after GSAO administration. Tumor tissue γGT, measurement of circulating ECs, and protein phosphorylation (Hic-5) in blood samples serve as exploratory biomarkers. To date 18 patients have been recruited into 5 dose levels (1.3 mg/m2/day–9.3 mg/m2/day). GSAO has been well tolerated with no observed DLTs. Preliminary evidence of antivascular activity was detected by DCE-MRI and soluble biomarkers. Recruitment is ongoing. No significant financial relationships to disclose.
Erratum for the Research Article: “Tracking genetically engineered lymphocytes long-term reveals the dynamics of T cell immunological memory” by G. Oliveira, E. Ruggiero, M. T. L. Stanghellini, N. Cieri, M. D’Agostino, R. Fronza, C. Lulay, F. Dionisio, S. Mastaglio, R. Greco, J. Peccatori, A. Aiuti, A. Ambrosi, L. Biasco, A. Bondanza, A. Lambiase, C. Traversari, L. Vago, C. von Kalle, M. Schmidt, C. Bordignon, F. Ciceri, C. Bonini
Journal: Science Translational Medicine (2015)
Altretamine for recurrent ovarian cancer or as maintenance after response to second-line therapy.
Authors: C. Mendiola, N. Valdiviezo, E. Vega, A. Sanchez Munoz, E. M. Ciruelos, L. Manso, I. Ghanem, M. Dorta, R. Manneh, C. J. Flores, H. Cortes-Funes
Journal: Journal of Clinical Oncology (2011)

e15589 Background: Altretamine is an oral drug with alkylating activity and low toxicity profile including no alopecia and scarce hematologic toxicity. Its activity in recurrent ovarian cancer is well known but new drugs with more activity have reduced its use. Methods: We present a retrospective study with altretamine in patients with recurrent ovarian cancer failing to the standard second line treatments or as maintenance after achieving a response to second line therapy. The dose used was 400 mg daily, during fourteen days every four weeks, until toxicity or disease progression.Our objective was to evaluate the activity and toxicity profile of altretamine in the second line setting of ovarian cancer patients. Results: Median age was 53years old. Eight patients were treated with altretamine as maintenance after achieving a complete or a partial response with a standard second line regimen to prolong the PFS. 76.5% of the patients have received 3 or more previous lines of chemotherapy. Excluding the eight patients treated for maintenance, 33% achieved complete or partial response, 25% stable disease and 42% progression. The more frequent toxicities were: nausea in 40% of patients, other gastrointestinal disorders in 40% and dizziness in 30%. The median PFS for all the group was 12,1 months and for the maintenance group of patients 18,1 months. The maintenance group has received between 4+ and 61+ cycles. Conclusions: Altretamine is an oral drug with manageable toxicity and with activity in patients with recurrent ovarian cancer being another option to be considered after the standard second lines. Also can be used as a maintenance drug for patients in response to prolong the PFS.
Impact of endocrine therapy in early-stage breast cancer on time to locoregional recurrence.
Authors: Ines B. Menjak, Ellen Maki, Hal K. Berman, Caroline Chung, David R. McCready, Srikala S. Sridhar
Journal: Journal of Clinical Oncology (2013)

64 Background: Locoregional recurrence (LR) remains a major source of morbidity and mortality in breast cancer. Our primary aim was to evaluate the impact of endocrine therapy (ET) on time to LR. Methods: A retrospective chart review of breast cancer patients (pts) treated with lumpectomy and locoregional radiation from 1999-2005 at the Princess Margaret Cancer Centre was carried out. LR was defined as ipsilateral breast or lymph node recurrence. Kaplan-Meier estimates of survival and univariate analyses were performed for age, menopausal status, tumor and nodal stage, grade, receptor status, adjuvant chemotherapy (AC) and ET. Results: Of 440 pts evaluated, the mean age at primary resection was 56 years (yrs) (range 40-79), and 67% were postmenopausal. The majority had ductal carcinomas (87%) and grade 1-2 (68%) tumors. Tumor distribution was 315 (72%) T1, 120 (27%) T2, 4 (1%) T3; 138 (31%) were node positive. Receptor status was ER/PR+HER2- 206 (47%), ER+PR+HER2unknown 80 (18%), ER-PR-HER2unknown 41 (9%), and triple negative 37 (8%). AC was used in 190 (43%). ET (tamoxifen and/or aromatase inhibitors) was initiated in 294 (84%) eligible pts, and 267/294 (91%) completed a minimum duration of ≥2 yrs. Overall, LR occurred in 24 (5%) pts, and 8/24 (33%) pts with LR also had distant metastases. Average time from surgery to LR was 5.4 yrs (range 8 months-12 yrs). The average duration of ET in pts with LR was 4.3 yrs (range 0-8), and 5.8 yrs (range 0-12) without LR. Of ER/PR+ pts with LR, 3/15 (20%) did not receive ET. At the time of LR, 5 (33%) pts were receiving ET. After stopping ET, 2 (13%) recurred 0-2 yrs, 3 (20%) at 4-5 yrs, and 2 (13%) at 7-8 yrs. Treatment with at least 2 yrs of ET predicted for fewer recurrences: at 2 yrs LR-free rate was 100% vs 90% for &lt;2 yrs ET; at 5 yrs 99.6% vs 84%; and at 8 yrs 98.2% vs 84% (p=0.0092). ER/PR+HER2- pts had lower LR risk (p=0.028), and ER-/PR-/HER+ had higher LR risk (p=0.029). The remaining variables were not associated with risk of LRs. Survival post-LR was 90% (95%CI 64-97%) at 2 yrs and 65% (95%CI 34-84%) at 5 yrs. Conclusions: Pts who completed at least 2 yrs of ET had significantly lower risk of LR. The average time to LR was 5.4 years, and pts with LR had decreased survival at 5 yrs post-recurrence.
Local versus central laboratory discrepancies in the determination of triple-negative breast cancer (TNBC) status in a large phase III (CIBOMA/2004-01/GEICAM/2003−11) trial assessing adjuvant capecitabine (C) maintenance therapy after standard chemotherapy (CT) in early breast cancer (EBC) patients (pts).
Authors: M. Ruiz-Borrego, C. H. Barrios, A. Lluch, J. Bines, J. G. M. Segalla, A. Ruiz, L. Torrecillas, A. Llombart-Cussac, R. Torres, J. Á. Garcia Saenz, J. A. Lopez Garcia-Asenjo, H. L. Gomez, J. R. De la Haba, S. Reyes, E. Martinez, J. M. Baena, L. Perez-Michell, A. Rodriguez-Lescure, A. Anton, M. Martin
Journal: Journal of Clinical Oncology (2011)

1022 Background: Appropriate determination of immunohistochemistry (IHC) to define EBC subtypes is crucial for an adequate treatment recommendation. A number of studies have raised questions about the reproducibility of IHC results when comparing local and central laboratories. In this report we explore the differences between local and central determinations of TNBC status in a multinational randomized phase III trial that focuses on adjuvant C maintenance after conventional induction CT in early TNBC: CIBOMA/2004−01/GEICAM/2003−11. Methods: A total of 1.441 specimens of pts locally defined as TNBC were registered and sent to Spain for central laboratory confirmation of negative results for both Estrogen (ER) and Progesterone Receptors (PR) by IHC (<1%) using Clone 1D5 (ER) and Clone PGR 636 (PR), and HER−2 by HercepTest and FISH (HercepTest 2+). CK 5/6 and EGFR status were also assessed. 854 (59%) samples came from Spain and 587 (41%) from 7 Latin American (LA) countries. Results: In 18 (1%) cases it was not possible to centrally assess TNBC status due to lack of tumour tissue in the specimen. In 130 cases (9%) tumours were found not to be TNBC by central determination. 74 (13% of LA samples) discordant cases came from LA countries while 56 (7% of Spanish samples) came from Spain (p<0.0001). Most of the discrepant results involved ER or PR status (71%) while HER-2 discrepancies represented 22% of cases. Conclusions: The considerable emphasis modern management strategies places in an individualized treatment assignment needs to take into consideration the significant discrepancies that are seen between local and central laboratory IHC determinations. In this large trial up to 9% of pts were erroneously diagnosed as TNBC. The translation of these results into routine clinical practice indicates that a significant portion of pts may not receive appropriate therapy due to faulty IHC testing. We need to improve the methodological standards for ICH testing.
Activity of RN-1, an LSD-1 Inhibitor, on Fetal Globin Expression in Sickle Mice and Sickle Erythroid Progenitors
Authors: Shuaiying Cui, Jose Sangerman, Seyed Mehdi Nouraie, Yan Dai, Oluwakemi Owoyemi, Robert E. Taylor, Susan P. Perrine
Journal: Blood (2015)