tbuckley/cabot-search huggingface dataset:
Improving care with portfolio of physician-led cancer quality measures at an academic center.
Authors: Julie Porter, Andrea Segura Smith, Marcy Winget, Eben Lloyd Rosenthal, Sridhar Belavadi Seshadri, Yohan Vetteth, Eileen F Kiamanesh, Amogh Badwe, Ranjana H. Advani, Mark K. Buyyounouski, Steven Coutre, Oliver Dorigo, Kristen N. Ganjoo, Laura J. Johnston, Lawrence David Recht, Joseph B Shrager, Eila C. Skinner, Susan M. Swetter, Brendan C. Visser, Douglas W. Blayney
Journal: Journal of Clinical Oncology (2017)

49 Background: Development and implementation of robust reporting processes to systematically provide quality data to care teams in a timely manner is challenging. National cancer quality measures are useful, but the required manual data collection is slow and resource-intensive. We designed a largely automated measurement system with our multidisciplinary cancer care programs (CCP). Methods: CCP physician leaders (MD) identified two measures that were meaningful to their team and patients. The quality team worked with hospital and university analytics teams to develop metrics and reports. Hospital leadership provided financial incentives (FI) for each CCP if jointly set targets were met. Results: 16 metrics were identified and measured for 13 CCPs (Table). Measures spanned from new diagnosis (ND) through end of life or survivorship care, and were a mix of process and outcome measures. To build and manage metrics required 2 full-time equivalent data analysts and quality specialists over 12 months. CCP MDs received monthly reports for dissemination to their team. Almost all measures improved or maintained initial high levels (*). FI awards will be used for quality improvement, education, and team-building, as determined by CCP MDs. Conclusions: A successful quality reporting system with measured improvements takes considerable engagement and resources, including FI, data systems, and staff to build, manage, and improve measures. This may not be feasible or sustainable for centers in the current fiscal environment. [Table: see text]
Enhanced anti-tumor effect via combination of Triptolide with ionizing radiation
Authors: Wei Wang, Shanmin Yang, Ying Su, Zhenyu Xiao, Hengshan Zhang, Paul Okunieff, Lurong Zhang
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4720 

Aim: Pancreas cancer is among the most resistant cancer to any therapy. The lack of effective treatment results in a very low survival rate, with median survivals of only about 6 month. This study is to explore the enhancement of therapeutic effect on human pancreatic cancer via combination of triptolide (TPL) and ionizing radiation (IR). Methods: AsPC-1 human pancreatic cancer cells cultured in 96 well plates were treated in vitro with different concentrations (0, 6, 12, 25 nM) of TPL alone or TPL plus 4 Gy IR one day later. The positive control is gemcitabine, a first line drug against pancreatic cancer. On day 4, the cell proliferation in anchorage-dependent conditions was analyzed by the sulforhodamine B (SRB) method. In addition, AsPC-1 cells treated with TPL or TPL plus IR were analyzed for their clonogenic survival. Finally, the extent of apoptosis induced by the above treatments were analyzed by Annexin V-FITC / propidium iodide (PI) staining as well as other apoptotic indices. In vivo, the AsPC-1 tumor xenografts were treated with 0.2 mg/kg TPL or 10 Gy IR or 100 mg/kg gemcitabine along or TPL plus IR. The tumor size was measured with Vernier calipers twice a week and the tumors were excised and weighed at the end of the experiment. The alterations of VEGF upon different treatments were determined by ELISA. Results: In vitro , TPL exerted a great inhibitory effect on growth of AsPC-1 cells, which was much more potent than gemcitabine (ID50 25 nM vs. >200 nM). The combination of TPL with IR shifted the ID50 of TPL from 25 nM to 12.5 nM (anchorage dependant phase cells) and reduced clonogenic survival of AsPC-1 cells (exponential growth phase cells). Cells treated with TPL plus IR exhibited a greater apoptosis as evidenced by stronger Annexin V/PI staining ratio, higher levels of cleaved caspases and increased DNA fragmentation as compared with TPL or IR alone. In vivo , the tumor growth of AsPC-1 xenografts was much slower in the group treated with TPL plus IR compared to the TPL or IR or gemcitabine alone groups. Importantly, 2 of 5 mice had prolonged complete responses (14 days). The VEGF level of AsPC-1 cells was greatly reduced upon treatment with TPL plus IR. Conclusion: 1) TPL possesses a potent therapeutic effect on pancreatic cancer, which seems superior to a current first line drug, gemcitabine; 2) the combination of TPL with IR enhances the therapeutic effect both in vitro and in vivo ; and 3) the inhibitory effect of TPL plus IR on pancreatic cancer is associated with induction of apoptosis and reduction of VEGF.
Mastering the design for rehabilitation strategies in ICU survivors
Authors: Peter E Morris, Ashley Montgomery-Yates
Journal: Thorax (2017)

Although the data from several recent trials have informed our understanding of early intensive care unit (ICU) exercise treatment. There remains a distinct lack of clarity in terms of the dose, duration, and frequency of exercise therapy that should be provided to the ICU survivor.1–4 Indeed, the coordination and integration of care for the critically ill patient, from early ICU exercise therapy and mobilisation to post-ICU rehabilitation, will be key going forward. In Thorax , McDowell et al 5 report on the REVIVE trial, which provides insight into the management of the post-ICU survivor and, in particular, the effectiveness of exercise on physical function (PF) in patients discharged from hospital following critical illness. The target population had received invasive ventilation for at least 4 days in the ICU with the exercise intervention delivered in the outpatient setting after hospital discharge. As with all outpatient-based UK exercise training programmes, the majority of sessions were supervised by a rehabilitation physiotherapist. It was delivered as a bespoke and personalised intervention that was modified based on the response of the individual patient to exercise. The intervention consisted of two directly supervised exercise sessions and one independent unsupervised session per week over 6 weeks. Importantly, there was a standard operation procedure for delivery of the multimodal exercise therapies to ensure uniform delivery of the intervention. More specifically, the training schedule for the rehabilitation physiotherapists included targeted exercise treatments based on the physical capability of the patient with an instruction to deliver goal-directed therapy and progress the patient through the exercises over multiple sessions. The detail of the dose, duration and frequency of the exercise therapy were recorded to permit the investigators to interpret the relationship between these factors and outcome in terms of PF. This is the strict controlled approach …
Survival and toxicity in patients with disseminated germ-cell cancer above 40 years of age.
Authors: Frederik Birkebæk Thomsen, Mikkel Bandak, Maria Ferløv Thomsen, Jakob Lauritsen, Ib Jarle Christensen, Kirsten Gedske Daugaard
Journal: Journal of Clinical Oncology (2013)

4532 Background: The aim was to analyze treatment related toxicity and survival in patients aged 40 years or above (40+) treated with standard chemotherapy for germ-cell cancer (GCC). Methods: The study population comprised 135 40+ patients with disseminated GCC treated between 1984 – 2011 with either 3 or 4 cycles bleomycin, etoposide and cisplatin (BEP). A control-group of 135 patients aged 18-35 years was randomly selected matched on year of BEP treatment. All patients were followed until death or October 1 st 2011. Cumulated doses of BEP as well as bone-marrow toxicity, renal- and lung functions were recorded before, during and after termination of treatment. The expected mortality was calculated by extracting survival data for each patient matched on the date and age at the time of diagnosis. The cause of death was categorized as GCC, other malignancy or other. Results: The cumulated doses of BEP were comparable between the two groups and, generally, BEP was equally well tolerated. 40+ patients had increased cancer specific mortality, HR = 4.8 (P = 0.005). Especially patients with disease progression after first line chemotherapy had increased mortality (P = 0.015). The year of treatment (P = 0.32), histology (P = 0.30), CCI (P = 0.99), tobacco use (P = 0.16), alcohol consumption (P = 0.21), prophylactic G-CSF (P = 0.61), reduced doses of bleomycin (P = 0.11) and decreased renal function (P = 0.18) were not significantly associated with GCC mortality. However, patients with impaired lung function (&lt;80% of expected) prior to treatment had an increased risk of GCC mortality (FVC (P = 0.03), DLCO (P = 0.01) and FEV 1 (P = 0.05)). Moreover, the 5-year overall survival in the 40+ group was 82.5% compared to the expected 5-year survival of the background population of 96.2% (P &lt;0.001) and the estimated 5-year survival of 97.0% in the control-group (P &lt;0.001). Conclusions: Reduced treatment intensity, or treatment related toxicity could not explain the increased mortality in 40+ GCC patients compared to a younger control-group. The 40+ group has a significantly lower response rate to BEP and a significantly higher mortality in case of disease progression. The worse prognosis could be related to tumor biology or increased co-morbidity.
The docetaxel (DOC) and gemcitabine (GEM) combination as adjuvant chemotherapy in patients with non-small cell lung cancer (NSCLC): A multi-institutional phase II trial
Authors: M. Kawamura, K. Eguchi, Y. Izumi, K. Kobayashi, H. Sakaguchi, T. Koike
Journal: Journal of Clinical Oncology (2006)

17157 Background: As clinical phase II studies with non-platinum doublet for adjuvant chemotherapy after complete resection of NSCLC has been scarcely reported, this clinical study was designed to evaluate the toxicity profile and the efficacy of the adjuvant chemotherapy with non-platinum doublet of DOC+GEM. Methods: Eligibility criteria included: completely resected NSCLC, pathological stage II and IIIA, younger than 76 years old, and performance status 0–1. Patients treated preoperatively were excluded. Treatment consisted of DOC, 60 mg/m 2 , on day 8, and GEM, 1000 mg/m 2 , on day 1, 8, and 15 every 4 week (4 cycles). Dose of GEM was decreased to 800 mg/m 2 after the initial 21patients because interstitial pneumonitis (IP) occurred in 3 among them. Results: Between August 2000 and August 2002, 35 patients (M/F: 21/14) were enrolled. The median age was 62 years (range 47–74) were enrolled with 5 patients (14.3%) over the age of 70. 34 patients had ECOG PS of 0. 28 patients had adenocarcinomas, 6 had squamous cell carcinomas, and one had adenosquamous carcinoma. Pathological stages were stage IIA in 5 patients, stage IIB in 1 and stage IIIA in 29 (82.9%). All patients received at least one cycle of chemotherapy. 29 patients received 3 cycles of chemotherapy and 23 (66%) completed 4 cycles. The main grade 3/4 toxicity (according to WHO scale) consisted of leukocytopenie (n = 19, 54.3%), thrombocytopenia (n = 3, 8.6%), appetiteloss (n = 4, 11.4%), dyspnea (n = 3, 8.6%), and vomiting (n = 1, 2.9%). IP, which caused dyspnea in these 3 patients, were well treated with steroid and suspension of chemotherapy. There was no treatment related death. Median follow-up period was 52 months. The 4 year recurrent free survival rate was 42.9% and the 4 year survival rate was 65.8%. Conclusions: Non-platinum doublet regimen with DOC+GEM as adjuvant chemotherapy for the NSCLC patients with complete resection was feasible and showed good compliance besides IP. No significant financial relationships to disclose.
Correcting a 25‐year old error: Preanalytical conditions affect determination of von Willebrand factor variability as a function of menstrual cycle
Authors: Margareta Blombäck
Journal: American Journal of Hematology (2017)

In 1992, my coworkers and I published a paper in the American Journal of Hematology entitled “On the laboratory problems of diagnosing mild von Willebrand's disease” and elsewhere another report “On the intraindividual and gender variability of hemostatic components.”1, 2 Data in both papers were based on fifteen young healthy women, sampled 10-16 times during one month (one menstrual cycle) and on six young men sampled six times during one month. Considerable variations were found in the values of FVIII activity (FVIIIc), VWF:Ag, and VWF ristocetin cofactor (VWF:Rcof) activity, in both genders. In 3 of the 15 female volunteers, the VWF Ag values on some samples were so low that they could be suspected to have a mild form of von Willebrand's disease (VWD) although they had no history of bleeding; this was associated with high individual variability in VWF:Ag. In one of these females, VWF:Ag varied from a low of 0.25 IU/mL to a high of 1.4 IU/mL (see Fig 1 in reference # 1). In 2001 Önundarsson et al. investigated VWF activity ((Rcof), VWFAg, and FVIIIc during one menstrual cycle (early, middle, and late phase), in 95 young healthy women but found no comparable variation of these three parameters.3 Subsequently, we learned that the subjects with the highest VWF variability had run before the blood sampling took place. In our 1992 study, we failed to inform the volunteers that physical and mental stress could influence the results.4-6 In 2002 Miller et al.7 studied 175 women sampled during one cycle and found lowest levels of all three parameters VWF:Ag, VWF:Rcof, and FVIIIc during days 1-4 and highest during days 5-11. In 2007 we and others on behalf of ISTH/SSC8 summarized key preanalytical requirements such as abstain from physical exercise for at least 24 h; abstain from fatty food and smoking before sampling; take samples in morning hours after sitting in a relaxed position and environment for 20-30 min for equilibration of the hydrostatic pressure. In addition, for the diagnosis of VWD in fertile women, samples should be obtained on cycle days 1-4. Thus, I feel that the limitations of our 1992 study provide an explanation for its discrepant values, and I welcome the opportunity to correct the records. Nothing to report.
Specific splicing regulatory protein human hTra2-beta but not hTra2-alpha is overexpressed in invasive human breast cancer
Authors: E. Stickeler, D. Watermann, S. Stamm, I. B. Runnebaum
Journal: Journal of Clinical Oncology (2004)

9621 Background: The two human dTra2 orthologs hTra2-alpha and hTra2-beta 1, members of the extended family of serine-argenine-rich (SR) splicingfactors, regulate alternative splicing of exons with C/A-rich enhancer sequences. The CD44 gene, encoding for an extracellular matrix protein, undergoes extensive alternative splicing of at least 10 variable exons. Alternative exons v4-v6 which contain these C/A-rich enhancer sequences have increased inclusion levels in breast cancer. They are thought to be involved in tumor progression and metastasis. Recently, we demonstrated that alternative exon v4 inclusion is increased upon over-expression of the DNA and RNA binding protein YB-1 and Tra2 in a mouse model of breast cancer development. Material and Methods: In this study we investigated expression levels of hTRa2-alpha and hTra2-beta 1 in a matched pair analysis of tumor samples and normal tissues of patients with invasive breast cancer by Western Blot and RT-PCR analysis. In addition, we performed in vivo splicing assays to examine the functional effects of human Tra2 on CD44 splicing. Results: Western Blot and RT-PCR revealed a marked induction of hTra2-beta 1 but not - hTra2-alpha expression in adenocarcinomas of the breast in comparison to physiological tissue samples of the same patient. The in vivo splicing assays showed, that human Tra2 specifically affected the in vivo inclusion of CD44 exon v4. Conclusions: Our results suggest that involvement of hTra2 in CD44 exon recognition and alternative splicing may be important to over-expression of these CD44 alternative protein isoforms in invasive breast cancer leading to tumor progression and metastasis No significant financial relationships to disclose.
Risk and cost of anthracycline-induced cardiotoxicity among breast cancer patients in the United States
Authors: J. C. Choi, J. D. Chang, B. Seal, M. Tangirala, C. D. Mullins
Journal: Journal of Clinical Oncology (2009)

1037 Background: Onset of anthracycline-induced cardiotoxicity is well documented. However, information regarding the time of onset varies depending on literature. The purpose of this study was to compare the risk of cardiotoxicity among three cohort groups: anthracycline-containing-chemotherapy (ACC), no-anthracycline-containing-chemotherapy (NACC), and no-chemotherapy (control) groups. Methods: A retrospective cohort study was designed using commercial managed care claims database. Adult subjects (≥18) diagnosed with breast cancer, between January 1, 2002 to December 31, 2005, (index-period) were followed for 24 months. Subjects with a previous cardiotoxic events (CE), breast cancer diagnosis, or anthracycline-use 12-months prior to index date were excluded. Index date was the first chemotherapy claim date for ACC and NACC and non-chemotherapy medication claim date for controls. Cohorts were matched by index date and year of birth. CE was defined based on ICD-9-CM and Healthcare Common Procedure Coding System codes. Risk of CE was evaluated using a logistic model with and without adjusting for confounders. Results: 21,106 subjects were classified as ACC (n = 3,428), NACC (n = 7,125), and controls (n = 10,553). NACC cohort was significantly (p &lt; 0.01) older (mean age: 62 years ±12.5) compared to ACC (53±9.7) or control cohorts (59±12.5). ACC cohort had a higher (p &lt; 0.01) average degree of comorbidity, (1.8±0.8) compared to NACC (1.6±0.9) or control (1.3±0.8) as measured by Charlson comorbidity-index. Higher rates of CE were found within the ACC group compared to NACC and controls as early as month 3 post index-date and remained consistent over 24 months. At month 12 post index-date, 14% (n = 485) of ACC and 5% (n = 381) of NACC had CE compared to 3% (n = 310) of controls. After adjusting for all baseline differences, the odds ratio of CE compared to controls was 3.98 (95% CI: 3.27–4.85), and 1.31 (95% CI: 1.11–1.54) for ACC and NACC cohorts, respectively. The total mean costs were $59,287, $20,528, and $11,600, among ACC, NACC, and control cohorts respectively. Conclusions: Compared to NACC and controls, ACC cohorts had significantly higher risk of cardiotoxic events and seen as early as month 3 post treatment initiation. [Table: see text]
Predictors of complete response following disease recurrence in gastrointestinal stromal tumor (GIST) patient: A retrospective patient chart review analysis.
Authors: Anthony Paul Conley, Annie Guérin, Medha Sasane, Geneviève Gauthier, Frances Annelies Schwiep, Christopher Hunt Keir, Matt Magestro, Eric Q. Wu
Journal: Journal of Clinical Oncology (2013)

10545 Background: Adjuvant imatinib (IM) treatment reduces the risk of GIST recurrence and improves survival particularly when IM is used for a longer duration among moderate to high risk patients. However, among patients who recur, little is known about the factors impacting the probability of achieving complete treatment response (CR). This study identifies factors associated with the probability of achieving CR among patients who had a recurrence following cessation of initial adjuvant IM treatment for a KIT + GIST. Methods: An online tool was used to retrieve clinical data on 410 patients who were treated with adjuvant IM for ≥6 months for primary resectable KIT+GIST, discontinued, had a recurrence after discontinuation, and then restarted IM or initiated sunitinib. Tumor and treatment characteristics were collected at primary diagnosis and disease recurrence. Patient response status was assessed by physicians based on different measures (e.g., RECIST, Choi, other subjective measures). Predictors of CR were identified using logistic regression models. Results: Among the 410 (IM = 314, sunitinib = 96) patients treated for GIST recurrence, 22.4% achieved CR (25.2% of pts on IM and 13.5% of patients on sunitinib). On average, CR was achieved after 11 weeks of treatment and only 2% of patients had a subsequent disease progression/recurrence. RECIST criteria were most widely used for CR evaluation in 68% of patients followed by subjective measures (29%) and Choi criteria (17%), respectively. Patients with a unifocal tumor (Odds Ratio[OR]=2.61; p&lt;.001 ), small tumor size (≤2cm) (OR=2.16; p=.023), lower mitotic rate ≤5/50 HPF (OR=1.87; p=.017) at recurrence, or tumor recurrence inside gastrointestinal system (OR=2.27; p=.036) were more likely to achieve CR. Conclusions: Among study patients, 22.4% achieved CR following disease recurrence. The main predictors of CR were tumor focality, size, location, and the mitotic rate at recurrence. This suggests that detecting recurrence at an early stage and managing disease with re-initiation of KIT inhibitor therapy may improve the probability of achieving CR following recurrence.
Effect of the establishment of a hematological multidisciplinary oral chemotherapy clinic at a community hospital on the number of emergency department visits.
Authors: Patricia Disperati, Dalia Kagramanov, Hannah Bjorkman, Rose Horsley, Katie Thede
Journal: Journal of Clinical Oncology (2017)

50 Background: Oral chemotherapy is an efficacious albeit toxic treatment of Malignant Hematological diseases. Multidisciplinary oral chemotherapy clinics (MOCC) have been proven to improve care in patients with solid tumors such as prostate and gastrointestinal cancer but there is little data in the Hematological setting. A MOCC was formed to determine if it would lead to a 20% decrease in emergency department (ED) visits and hospital admission over a 10-month period after implementation in patients with Malignant hematological disease on oral chemotherapy. Methods: A chart review of patients on oral Hematological drugs was performed for baseline data. A MOCC consisting of a nurse and a pharmacist was established, with physician backup. Checklists that were drug and disease specific were created for 5 different drugs (Lenalidomide, Ibrutinib, Dasatinib, Nilotinib and Idelalisib) for treatment initiation, follow-up and monitoring and incorporated into the electronic health record. This model was piloted and outcomes were measured to determine improvements in medicine reconciliation, documentation of adverse events, dose modification, patient compliance, unscheduled MD assessments and ED visits. Qualitative interviews were performed with patients and nurses to assess satisfaction with this team approach. Results: 30 patients with Hematological malignancies were enrolled sequentially during the 10-month period. After a median follow up of 7 months, there was 100% medicine reconciliation and 92% compliance with treatment protocols; 47% of patients had interventions requiring dose modifications that would not previously have been documented or addressed. There was a 20% increase in unscheduled MD assessments and a 33% decrease in ED visits and hospital admission from baseline. Both patients and nursing staff were satisfied with the team approach. Conclusions: In a community setting, the implementation of MOCC resulted in early recognition of AE and reduced ED visits. In addition, the new model lead to improved patient and staff satisfaction.