tbuckley/cabot-search huggingface dataset:
Learning from near misses: Addressing nursing chemotherapy verification fatigue.
Authors: Meghan Shea, Aya Sato-DiLorenzo, Danielle Wright, Erika Coletti, Michael Carvalho, Jessica A. Zerillo
Journal: Journal of Clinical Oncology (2017)

70 Background: Administration of chemotherapy is high-risk, requiring multiple safety checks, including pre-treatment laboratory value verification by nursing. A recent series of near misses in our event reporting system highlighted that nurses verified chemotherapy orders with pending pre-treatment or abnormal labs, such as grade 2 hyperbilirubinemia and grade 4 neutropenia. Such laboratory results would normally require holding or modifying planned treatment doses. Methods: Nurses treating patients in the outpatient chemotherapy infusion units were surveyed regarding barriers to pre-treatment lab verification. A team of clinicians, nurses, and pharmacists outlined a process map of the order verification process from acknowledging patient assignment and looking at patient oncologic history to sending the physician order to pharmacy. Pharmacists collected baseline data by tracking near-miss incidents. Results: The survey response rate of outpatient treatment nurses was 18 of 32 (56%). Nurses ranked inconsistent notation of treatment criteria in orders, long lab processing time, and patient frustration with a long wait as the most common barriers to lab verification. At baseline, in six non-consecutive weeks from August-October 2016, 31 of 947 (3%) orders were inappropriately verified by nursing in which pre-treatment lab results were pending or lab results did not meet parameters in the chemotherapy order. The team’s aim is by February 1, 2017, to reduce the number of chemotherapy orders sent to pharmacy without proper lab verification by 50%. Conclusions: Chemotherapy verification fatigue, specifically pre-treatment lab near misses, was identified as an area for improvement from recent patient safety reports. Barriers for nurses include inconsistent notation of treatment criteria in orders, long lab processing time, and patient frustration with a long wait. Interventions are underway to improve nursing adherence to pre-treatment lab verification.
Prolonged administration of low-dose interleukin-2 in human immunodeficiency virus-associated malignancy results in selective expansion of innate immune effectors without significant clinical toxicity
Authors: ZP Bernstein, MM Porter, M Gould, B Lipman, EM Bluman, CC Stewart, RG Hewitt, G Fyfe, B Poiesz, MA Caligiuri
Journal: Blood (1995)
Sixty seconds on . . . computer games
Authors: Anne Gulland
Journal: BMJ (2017)

Well, no, actually a new study has found that computer games can have positive effects. Tetris, the Russian designed game much loved by nerdy teenagers in the 1980s and 1990s, can help people who have experienced traumatic events.

I’m not sure about that. Researchers at Oxford University and the Karolinska Institute in Sweden asked people …
Efficacy and safety of panobinostat (LBH-589), a histone-deacetylase inhibitor (HDACi), in patients (pts) with advanced, previously treated soft tissue sarcoma (STS) and sex cord tumors (SCT): A study from the French Sarcoma Group.
Authors: Philippe Alexandre Cassier, Anne Lefranc, Nicolas Penel, Christine Chevreau, Binh Bui Nguyen, Axel Le Cesne, Isabelle Laure Ray-Coquard, Sylvie Chabaud, Eric Amela, Yann Berge, Julien Domont, Antoine Italiano, Florence Duffaud, Anne Claire Cadore, Valentine Polivka, Jean-Yves Blay
Journal: Journal of Clinical Oncology (2012)

10027 Background: Treatment options are limited for pts with advanced pretreated STS. HDACi have shown activity in preclinical models of STS and SCT Methods: Pts with advanced pretreated STS and SCT were enrolled in this open label, single arm, multicenter phase II study. Panobinostat was given orally, 40 mg thrice per week. The primary end-point was 3-month progression-free rate according to RECIST 1.1 using central review. Fleming-A’Hern single-stage design for phase II trials was used, and assuming a type I error alpha of 5% with 90% power, 15/47 pts were needed to be progression free at 3 months to reject a rate of 20%. Results: Fifty three pts were enrolled between January 2010 and January 2011. Median age was 59 (range 21-79) years, and 22 (42%) pts were males, 13 had translocation-related sarcoma (TRS) and 4 had SCT. All but 5 pts had metastatic disease. The most common sites were the lung and the liver. All but one pt had documented disease progression prior to study entry. The median number of prior lines of therapy was 2 (range 1-7). Panobinostat dose was lowered to 20 mg thrice a week after 11 pts were enrolled based on the recommendation of an independent safety committee. Fifty-two pts were evaluable for toxicity (1 pt never received treatment), 48 pts (92%) reported at least one adverse event (AE) and 22 (42%) reported at least one treatment-related grade 3 or 4 AE. The most common grade 3/4 AEs were thrombocytopenia, fatigue and anemia. Fifty pts were evaluable for the primary end-point, of these, 12 pts (24%, 95%CI[13-38%]) were progression-free at 3 months, including 4/13 pts (31%, 95%CI[9-61%]) with TRS and 2/4 pts (50%, 95%CI[7-93%]) with SCT. No CR was seen, two patients (4%) with SCT had a PR and 19 pts (37%) had SD as their best response. Seven pts were progression-free at 6 months: 2 pts with SCT, 2 with TRS, 1 with liposarcoma, 1 with malignant solitary fibrous tumor and 1 with leiomyosarcoma. Conclusions: Panobinostat was poorly tolerated at 40 mg thrice a week. Efficacy in unselected advanced STS was limited although some patients had prolonged SD. Activity in pts with SCT warrants further investigation.
Low HER2-expression to predict impaired activity of endocrine therapy in patients with estrogen-receptor (ER) positive metastatic breast cancer (MBC).
Authors: Cornelia Sparber, Anna Sophie Berghoff, Margaretha Rudas, Peter Christian Dubsky, Catharina DeVries, Christoph Minichsdorfer, Claudia Sattlberger, Robert M Mader, Zsuzsanna Bago-Horvath, Florian Fitzal, Michael Gnant, Andrea Rottenfusser, Christoph Zielinski, Matthias Preusser, Guenther G. Steger, Rupert Bartsch
Journal: Journal of Clinical Oncology (2013)

573 Background: ER cross-activation by growth-factor signalling causes resistance to endocrine therapy (ET) in patients (pts) with Her2-positive MBC. Moreover, low levels of Her2-expression (Her2 1+; Her2 2+ without gene amplification), may result in reduced efficacy of ET in early breast cancer pts. In a recently published study, these tumours had a less favourable outcome as compared to tumours with a Her2-score of 0. Here, we investigated if low levels of Her2-expression could predict for shorter progression-free survival (PFS) in MBC pts on ET. Methods: PFS on first-line ET was chosen as primary endpoint and estimated with the Kaplan-Meier method. To test for differences between PFS curves, the log-rank test was used. Association of the following variables with PFS was investigated: low Her2-expression, grading, level of ER-expression, progesterone-receptor status, Ki67 (cut-off ≤20%), prior adjuvant ET, and presence of visceral metastases. For an estimated superiority of 40% in terms of PFS in favour of the Her2-negative group, a sample of 130 pts in two groups was needed in order to rule out the null-hypothesis with a 80% power and a two-sided α of 0.025. Results: A total number of 320 ER-positive MBC pts were identified from a breast cancer database; 170 pts were available for this analysis. Median PFS on first-line ET was 11 months (m) (8.56-13.44), corresponding numbers for second-line were 6 m (4.65-7.36), and third-line 4 m (1.52-6.48), respectively; median OS from diagnosis of MBC was 58 m (48.15-67.86). None of the variables investigated were significantly associated with first-line PFS. Second-line PFS, however, was significantly shorter in pts with grade 3 tumours and prior adjuvant ET; a trend towards shorter PFS was observed in high proliferating tumours. Conclusions: In this chart review, low levels of Her2 expression did not predict for shorter PFS in pts receiving ET; PFS in different treatment lines was well in line with data from clinical trials. High tumour grading and prior adjuvant ET were associated with accelerated onset of resistance, rendering those patients candidates for early combination of ET with targeted treatment approaches.
Intermittent noninvasive ventilation after extubation in patients with chronic respiratory disorders: a multicenter randomized controlled trial (VHYPER)
Authors: Frédéric Vargas, Marc Clavel, Pascale Sanchez-Verlan, Sylvain Garnier, Alexandre Boyer, Hoang-Nam Bui, Benjamin Clouzeau, Charline Sazio, Aissa Kerchache, Olivier Guisset, Antoine Benard, Julien Asselineau, Bernard Gauche, Didier Gruson, Stein Silva, Philippe Vignon, Gilles Hilbert
Journal: Intensive Care Medicine (2017)
Community use of anthracyclines in metastatic breast cancer (MBC).
Authors: James Edward Krook, Akhil Kumar, Marc L. Fishman, William S. Shimp, Laura Rose Bobolts, Val Fishman, Sharon Davis, Dinah Huff, Carol Anthony, Robert Walton, William J. Hrushesky
Journal: Journal of Clinical Oncology (2013)

1080 Background: For decades, anthracyclines have been among the most useful treatments for women with MBC. Though recent publications have confirmed an overall decline in the use of anthracyclines in BC, most of that decline was felt to be due to its diminished utilization in the adjuvant management of BC. Current community anthracycline usage pattern in MBC is not known. We investigate and report, herein, how community oncologists in the southeast USA are currently utilizing anthracyclines for MBC. Methods: All chemotherapy treatment requests for HER2+ and HER2- Stage 4 BC were examined, from 2009 through 2012. Chi-Square test was performed for interaction between age and anthracycline utilization, with p-value less than 0.05 considered significant. The proportion of women who had been treated previously in the adjuvant setting with low cumulative doses of anthracyclines, which would have some effect upon subsequent use, was not retrievable. Results: During this span, 420 unique chemotherapy requests were initiated for 247 patients. These included 54 anthracycline requests for 50 MBC patients. The use of anthracyclines for metastatic HER2+ BC was virtually absent (one in 63 requests among 42 patients). The remaining 357 chemotherapy requests were for treatment of 205 HER2- MBC patients. Anthracyclines were employed in 22% of women under 65 years of age and in 25% of those older than 65 (p = 0.77). Approximately 83% (45/54) of anthracycline-requests were for conventional doxorubicin, either alone or in combination with other agents. The rest were for liposomal doxorubicin (6/54) or epirubicin (3/54). Conclusions: Data from the southeast USA identifies that anthracyclines are virtually never used in HER2+ MBC. Even in HER2- MBC, anthracyclines are used in only one out of 4 patients suffering from this disease. The effect of this unheralded alteration in oncology practice must be carefully considered when trends in metastatic breast cancer control are examined. [Table: see text]
The factors affecting pathologic complete response after neoadjuvant chemotherapy and the role of 18-FDG-PET/CT in patients with locally advanced breast cancer.
Authors: Faysal Dane, Serap Kaya, Hatice Odabas, Aydin Aytekin, Nilgun Yildirim, Ezgi Coban, Teoman Sakalar, Dincer Aydin, Mehmet Bilici, Mustafa Benekli, Perran Fulden Yumuk, Mahmut Gumus
Journal: Journal of Clinical Oncology (2016)

e12539 Background: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) has been shown to provide survival advantages in breast cancer. Here, we investigated the role of 18-FDG-PET/CT and other possible factors in predicting pCR after NAC. Methods: The patients who had 18-FDG-PET/CT before NAC in 6 different centers enrolled in this study. SUV max values of the primary tumor and axilla, age, menapousal status, postoperative histopathological characteristics as hormonal receptor status, presence of Her2 expression, vascular, lymphatic and perineural invasion, grade and molecular subtypes of the tumor of the patients were recorded. Receiver-operating curve (ROC) analysis was done to find out the cut-off SUV value for predicting pCR. The effects of all these factors on pCR were determined by chi-square test. Results: In this study, 317 patients were evaluated. Ten percent of the patients were below 35 years of age, 52% was premenapousal, 89% had ECOG performance status 0, 42.9% had Her2 positive disease. Triple negative subtype was detected in 8.2% of the patients. ORR was 87.1% while pCR was achieved in 29.7% of the patients. The predictive cut-off SUV value of 18-FDG-PET/CT for pCR was found as 7.7 by ROC analysis. The sensitivity and specificity for this value were 57% and 64% respectively (AUC = 0.606; p = 0.0018). There was no significant association between pCR and menapousal status, performance status, perineural invasion or grade (p > 0.05). The pCR was found to be significantly higher in patients with hormone receptor negative tumors, patients with Her2 positive tumors, patients with triple negative tumors , patients without vascular and lymphatic invasive tumors and in patients with mean SUV values over 7.7 (p = 0.009, 0.038, 0.047, 0.000, 0.001 respectively). Conclusions: High levels of mean SUV value 18-FDG-PET/CT and some histopathologic parameters may have a role in predicting pCR after NAC in breast cancer patients, and thus give us the clues about the survival of the patients
Early Feasibility Study of a Transcatheter Tricuspid Valve Annuloplasty
Authors: Rebecca T. Hahn, Christopher U. Meduri, Charles J. Davidson, Scott Lim, Tamim M. Nazif, Mark J. Ricciardi, Vivek Rajagopal, Gorav Ailawadi, Mani A. Vannan, James D. Thomas, Dale Fowler, Stuart Rich, Randy Martin, Geraldine Ong, Adam Groothuis, Susheel Kodali
Journal: Journal of the American College of Cardiology (2017)
Should we have a royal commission on the NHS?
Authors: Maurice Saatchi, Paul Buchanan, Nigel Crisp
Journal: BMJ (2017)

A high level inquiry could detoxify the radical changes needed and command wide support, say <b>Maurice Saatchi</b> and <b>Paul Buchanan</b>; but <b>Nigel Crisp</b> thinks that a less formal, more flexible and collaborative approach could be quicker
Modulation of Bax and mTOR for Cancer Therapeutics
Authors: Rui Li, Chunyong Ding, Jun Zhang, Maohua Xie, Dongkyoo Park, Ye Ding, Guo Chen, Guojing Zhang, Melissa Gilbert-Ross, Wei Zhou, Adam I. Marcus, Shi-Yong Sun, Zhuo G. Chen, Gabriel L. Sica, Suresh S. Ramalingam, Andrew T. Magis, Haian Fu, Fadlo R. Khuri, Walter J. Curran, Taofeek K. Owonikoko, Dong M. Shin, Jia Zhou, Xingming Deng
Journal: Cancer Research (2017)

Abstract A rationale exists for pharmacologic manipulation of the serine (S)184 phosphorylation site of the proapoptotic Bcl2 family member Bax as an anticancer strategy. Here, we report the refinement of the Bax agonist SMBA1 to generate CYD-2-11, which has characteristics of a suitable clinical lead compound. CYD-2-11 targeted the structural pocket proximal to S184 in the C-terminal region of Bax, directly activating its proapoptotic activity by inducing a conformational change enabling formation of Bax homooligomers in mitochondrial membranes. In murine models of small-cell and non–small cell lung cancers, including patient-derived xenograft and the genetically engineered mutant KRAS-driven lung cancer models, CYD-2-11 suppressed malignant growth without evident significant toxicity to normal tissues. In lung cancer patients treated with mTOR inhibitor RAD001, we observed enhanced S184 Bax phosphorylation in lung cancer cells and tissues that inactivates the propaoptotic function of Bax, contributing to rapalog resistance. Combined treatment of CYD-2-11 and RAD001 in murine lung cancer models displayed strong synergistic activity and overcame rapalog resistance in vitro and in vivo. Taken together, our findings provide preclinical evidence for a pharmacologic combination of Bax activation and mTOR inhibition as a rational strategy to improve lung cancer treatment. Cancer Res; 77(11); 3001–12. ©2017 AACR.
Impact of Karnovsky performance status (KPS) on outcome of elderly patients (pts) with glioblastoma (GBM) and activity of temozolomide (TMZ) as first line therapy: Retrospective analysis of a cohort
Authors: O. Chinot, M. Barrie, B. Calissi, S. Fuentes, P. Metellus, S. Honore, C. Boucard, A. Loundou, D. Figarella-Branger, H. Dufour
Journal: Journal of Clinical Oncology (2006)

1515 Background: Due to increasing incidence of GBM in the elderly, prognostic factors and therapeutic strategies need to be considered in this population. Recently radiotherapy has shown survival improvement in patients with KPS ≥ 70 (ANOCEF, EANO 2005), while chemotherapy with TMZ may be considered as a therapeutic option (Chinot at al, Cancer 2003). Methods: We analyzed retrospectively all pts above 70 years old with GBM, who were referred to our institution from May 1998 to October 2004; all responses to TMZ were reviewed. Results: We identified 136 pts registered. Median age was 74 (range 70–87), and 43% had a KPS &lt; 70. Surgery consisted of stereotactic biopsy (SB), 29% ; partial surgery (PS), 12%; and gross total removal (GTR), 29% of pts. Diagnosis was strongly suggested by neuroradiology in 30% of cases. Treatment consisted of TMZ (5 days standard schedule) (group A) as first-line treatment in 89 pts (65%), radiotherapy and/or nitroso-urea based regimens in 40 pts (30%) (group B) and best supportive care in 7 (5%) pts. For the all cohort, median of overall survival (OS) was 7 months (m), strongly impacted by KPS (3.9 vs 8.7 m, p&lt;0.0001 for KPS &lt; 70 and ≥70 respectively) and age (8.2 vs 6.0 m, p&lt;0.007 for age &lt; 75 years vs. ≥ 75). OS was 6.6, 7.3, and 8.4 mos in the case of SB, PS, and GTR respectively and was 5.2 for neuroradiologic diagnosis. In group A, median time to tumour progression (TTP) and OS were 4.7 &amp; 7.3 m. KPS impacted TTP (2.9 vs. 5.1 m, p=0.0002) and OS (4.9 vs. 8.7 m, p&lt;0.0001) for KPS &lt; and ≥ 70 respectively. Response rates (RR) were for 71 pts evaluable 28%; SD 35%; PD 37% associated with an OS of 11.7, 7 and 3.2 m respectively. RR was 34% for histologically proven GBM, vs 22% in cases of neuroradiologic diagnosis. In group B, TTP and OS were 4.3 &amp; 6.7 m respectively. Conclusions: KPS appeared to have a major impact on outcomes in elderly patients with GBM. Future trials designs should take this impact into consideration. TMZ appeared to be effective in elderly patients with newly diagnosed GBM. This alternative approach is currently being tested against RT alone in international trials. Impact of MGMT status in the TMZ population will be presented. No significant financial relationships to disclose.
Phase I trial of bi-weekly docetaxel combined with carboplatin for patients with non-small cell lung cancer
Authors: A. Inoue, T. Ishida, Y. Saijo, M. Maemondo, T. Suzuki, Y. Kimura, S. Ohkouchi, T. Nukiwa
Journal: Journal of Clinical Oncology (2004)

7241 Background: Docetaxel (D) combined with carboplatin (C) is widely used regimen for advanced non-small cell lung cancer (NSCLC). We conducted this trial to determine the maximum tolerated dose (MTD) of bi-weekly D combined with C and to assess toxicities of this regimen. Methods: Histologically proven chemotherapy-naïve NSCLC patients were entered to this study. Other entry criteria were (1) age equal or less than 75, (2) ECOG PS 0–1, (3) WBC ≥ 4000, Neut ≥ 2000, Plts ≥ 100000, Hb ≥ 9.0, GOT, GPT ≤ 1.5 upper limit, Ccr ≥ 40, PaO2 ≥ 60, (4) life expectancy more than 3 months, and (5) written informed consent. C was administered on day 1 and D was administered on day 1 and 15 every 4 weeks. Doses of agents were planned to increase from level 1 (C: AUC 5.0, D: 30 mg/m2) to level 2 (C: AUC 5.0, D: 35 mg/m2) and level 3 (C: AUC 6.0, D: 35 mg/m2). The level where dose limiting toxicities (DLT) such as Grade 4 neutropenia lasting for 4 days, needs for platelet transfusion, Grade 3 or more non-hematological toxicities were observed in 3/3 or 3/6 or more patients was determined as MTD. Results: Ten patients were enrolled in this study. No patient experienced DLT in each level. Hematological toxicities were moderate and no neutropenic fever was observed (Table). Non-hematological toxicities were also mild and no Grade 3/4 non-hematological toxicities were observed. Two patients experienced Grade 2 vertigo and another patient suffered from Grade 2 infection. Overall response rate was 20 % (2/10). Conclusions: Bi-weekly D combined with C may be effective for NSCLC with quite moderate toxicities. We are now conducting a phase II trial of this regimen. No significant financial relationships to disclose.
Local recurrence after rectal cancer resection is strongly related to the plane of surgical dissection and is further reduced by pre-operative short course radiotherapy. Preliminary results of the Medical Research Council (MRC) CR07 trial
Authors: P. Quirke, D. Sebag-Montefiore, R. Steele, S. Khanna, J. Monson, A. Holliday, L. Thompson, G. Griffiths, R. Stephens
Journal: Journal of Clinical Oncology (2006)

3512 Background: The MRC CR07 trial compared routine short course pre-operative radiotherapy (PRE) with selective post-operative chemo-radiation if there was involvement of the circumferential resection margin (CRM) (POST) and included a prospective pathological assessment of the quality of resection of the surgical specimen. Methods: A total of 1350 patients were randomised from 52 centres between March 1998 and August 2005. Median follow-up is 3 years. Trial pathologists were trained in histopathological assessment and reporting of the involvement of the CRM and plane of surgery (PoS) according to pre-set criteria describing the plane of dissection (Grade 1-muscularis plane: 2-intramesorectal plane: 3-mesorectal plane). 1232 patients were prospectively assessed for CRM and 1119 for PoS. Results: The CRM was involved (tumour ≤1mm) in 139 (11%) of resected specimens, and for these patients the 3-year local recurrence (LR), disease-free survival (DFS) and overall survival rates were 18%, 50% and 57%. For the 1093 patients with CRM-ve the respective rates were 7%, 81% and 84%. LR and DFS rates were associated with PoS (log-rank test p=0.0019 and p=0.0506 respectively), and in addition there was clear evidence of a reduction in LR and improvement in DFS rates in favour of PRE for all grades of quality of surgical assessment as shown in the table . Conclusions: The results indicate a strong association between the quality of surgery and the rates of local recurrence and disease-free survival, as well as a clear benefit from the addition of PRE to all grades of surgical dissection. Thus for patients with rectal cancer short-course pre-operative radiotherapy and good quality surgery can almost completely eliminate local recurrence. [Table: see text] No significant financial relationships to disclose.
Struma Ovarii With Hyperthyroidism
Authors: Lynn P. Ang, Anca M. Avram, Richard W. Lieberman, Nazanene H. Esfandiari
Journal: Clinical Nuclear Medicine (2017)

We report the case of a 61-year-old woman with persistent thyrotoxicosis for 7 years despite low thyroidal radioiodine uptake and methimazole treatment. Her initial 123I whole-body scan (WBS) was read as negative. Upon evaluation in our institution, she remained hyperthyroid after discontinuation of methimazole. Repeat WBS with SPECT/CT revealed low 24-hour thyroidal uptake (RAIU = 2%) and intensely focal radioiodine uptake in a large heterogeneous left pelvic mass, consistent with left adnexal struma ovarii. Resection of this mass confirmed benign struma ovarii. This case illustrates the advantage of fusion SPECT/CT imaging with planar 123I-WBS for diagnosis of extrathyroidal thyrotoxicosis.