tbuckley/cabot-search huggingface dataset:
A quality verification tool to assure complete pre-treatment electronic medical records (EMR) for patients undergoing radiation therapy.
Authors: Timothy Barnes, Eleanor Elizabeth Harris, Michael Holloman, Hyder Husain Arastu, Clinton Leinweber, Andrew Wenhua Ju, James Naves
Journal: Journal of Clinical Oncology (2017)

103 Background: Complete medical records are critical for correct implementation of the intended care plan. Sentinel items include pathological reports, tumor staging, complete history and physical, pre-treatment performance and pain assessment, documented informed consent, and written directive/plan of care. The advent of electronic medical records and expanded use of technology have necessitated methodology to assure medical record completeness and quality. The technical portions of radiation oncology practice require unique EMR systems that are often used in addition to other institutional systems. The complete patient record is the aggregate of all systems. Methods: We developed a list of sentinel items that compose a complete pre-treatment radiation oncology medical record. This list was developed into an electronic spreadsheet and is recorded for each patient and his/her attending radiation oncologist. This tool is completed at the pre-treatment peer-review presentation and recorded for completeness and deficiencies. Any deficiencies were noted for resolution and tracked as a continuous quality improvement (CQI) activity to identify deficit root cause, interventions, and effectiveness of action(s). Results: Accumulative data showed the number and percentage of variances from standard practice as recorded at the time of initial peer review case presentation. Generally, the data showed improvement in completeness of the pre-treatment EMR by physician for the period February, 2015- November 2015. An initial 16% variance rate was recorded upon observation only in February of 2015. Variances over 5% were addressed and improvement programs instituted as needed. A final variance rate of 2.3% recorded in November 2015. Conclusions: Ongoing monitoring is an important strategy to assure complete pre-treatment medical records. The reasons for deficits are multi-factorial. Physician compliance and data availability, particularly for patients referred from outside facilities, were especially notable but resolution strategies have improved the system’s performance. These lessons will be part of the implementation plan for new EMRs over the upcoming months.
Results of a phase I trial combining ridaforolimus (mTOR inhibitor) and MK-0752 (Notch inhibitor) in patients with advanced solid tumors.
Authors: Sarina Anne Piha-Paul, Pamela N. Munster, Antoine Hollebecque, Guillem Argiles, Olav Dajani, Jonathan D. Cheng, Ruixue Wang, Ann M. Swift, Alessandra Tosolini, Shilpa Gupta
Journal: Journal of Clinical Oncology (2014)

2601 Background: The PI3K/AKT/mTOR signaling pathway is aberrantly activated in a variety of cancers. Ridaforolimus (R) is an mTOR inhibitor with activity in a broad range of cancers. MK-0752 inhibits the Notch receptor through its significant inhibition of gamma secretase and has evidence of antiangiogenic effects. R + MK-0752 may lead to complementary blockade of the PI3K pathway. Methods: The primary objective of this Phase I dose-escalation study (NCT01295632) was to define the dose limiting toxicities (DLTs) and maximum tolerated dose (MTD); a secondary objective was assessment of antitumor activity. Patients (pts) received a 5-day lead-in of R as monotherapy before beginning combination dosing. Rising doses of R were orally administered 5 days/week. MK-0752 dosing was fixed at 1800 mg given orally once per week. Results: For the 28 treated pts R doses were escalated from 20 to 30 mg/d. The MTD was determined to be 20 mg qd R 5 days/week + 1800 mg weekly MK-0752 (dose level 1). Among the 14 evaluable patients at the MTD, one DLT was reported: Grade 2 stomatitis, second episode. Among the 8 evaluable patients in dose level 2 (R=30mg), three DLTs were reported: 1 patient each with Grade 3 stomatitis, Grade 3 diarrhea, and Grade 3 asthenia. Other ≥G3 treatment-related adverse events (AEs) at the MTD were anemia (2 pts), stomatitis (2pts), diarrhea (1 pt), fatigue (1 pt), ALT elevation (1 pt), AST elevation (1 pt), hypokalemia (1 pt), hemoglobin decreased (1 pt) and hypophosphatemia (1 pt) (all Grade 3). The most common treatment-related Grade 2 toxicities at the MTD were: stomatitis (3 pts) and diarrhea (2 pts). One pt (squamous cell carcinoma [SCC] of the head/neck) had confirmed partial response (PR). Stable disease (SD) ≥6 mo was seen in 2 pts with SCC of the head/neck, including 1 pt with SD > 20 mo. Conclusions: The combination of R + MK-0752 shows activity in SCC of the head/neck (3/14). This combination resulted in disease responses though there were tolerance issues. The most common drug-related AEs occurring in >20% of patients treated at the MTD were diarrhea (32%), stomatitis (32%) and decreased appetite (32%) with 42% of patients experiencing Grade 3 drug-related AEs of any kind at this dose. Clinical trial information: NCT01295632.
Low periostin levels in adult patients with Langerhans cell histiocytosis are independently associated with the disease activity
Authors: Athanasios D. Anastasilakis, Stergios A. Polyzos, Marina Tsoli, Athanasios Papatheodorou, Panagiotis Kokkoris, Gregory Kaltsas, Evangelos Terpos, Polyzois Makras
Journal: Metabolism (2017)
Phase II study of gemcitabine, cisplatin, folinic acid (FA) and infusional 5-fluorouracil (5-FU) in patients with inoperable esophageal cancer (IEC)
Authors: A. Hilbig, J. Stieler, U. Pelzer, J. Okenga, R. Hintze, L. Roll, M. Gövercin, M. Arning, H. Riess, H. Oettle
Journal: Journal of Clinical Oncology (2004)

4238 Background: Our previous phase I study has shown that combination chemotherapy with gemcitabine, 5-FU/FA, and cisplatin (GFFC) is feasible and has encouraging activity in IEC. Therefore, we initiated a multicenter phase II study of outpatient GFFC treatment for IEC. Methods: A two-stage design was used, 11 or more of the first 25 evaluable patients (pts) were required to achieve at least SD to complete enrolment to a total of 66 pts. Treatment consists of cisplatin 30 mg/m2 (90 min), gemcitabine 1000 mg/m2 (30 min), FA 200 mg/m2 (30 min), and 5-FU 750 mg/m2 (24h) on days 1 + 8 q3w. Results: Forty-one pts have been included to date. There were 32 males and 9 females, 28 had squamous cell and 13 adenocarcinoma. Median Karnofsky index was 90 (60–100), median age was 65 years (22–77). Two pts had stage IIB, 17 stage III, 9 stage IVA and 13 stage IVB. Among the first 25 evaluable patients we observed 1 CR, 7 PR, 12 SD and 5 PD, for an objective response rate of 32% (CR+PR+SD 80%). We therefore opened the second stage of our study, and recruitment is ongoing. All 41 pts are evaluable for toxicity. They received a total of 192 cycles (median 5, range 1–8). WHO grade 3/4 toxicity occurred in 18/10 pts (44%/24%). Hematologic toxicities grade 3/4 were (anaemia 7/1, neutropenia 5/1 and thrombopenia 3/0). 3 pts showed non-hematologic toxicities grade 3, 8 pts had non-hematologic toxicities grade 4 including 4 urea, 2 AP, 2 transaminases. Conclusion: Our preliminary phase II data indicate that the GFFC regimen has manageable toxicity and is active in patients with IEC. Updated results will be available at the time of the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Co. Eli Lilly, Germany
Replacing the Affordable Care Act
Authors: Jonathan S. Skinner, Kevin G. Volpp
Journal: JAMA (2017)

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Alteration of the p53 and Rb tumor suppressor pathways by p16/INK4a and p14/ARF promoter methylation and loss of protein expression in recurrent and nonrecurrent meningiomas.
Authors: Juan Carlos Martinez, Santiago Ropero, Concepcion Mateos, Maria DEL VAL Toledo, Rafael Samaniego, Silvia Sacristan, Manel Esteller
Journal: Journal of Clinical Oncology (2013)

2064 Background: Promoter methylation inactivates tumor suppressor genes (TSG). The INK4a/ARF locus encodes p16INKa and p14ARF cell cycle regulatory proteins, which control Rb and p53 TSG pathways. Most meningiomas are slow growing tumors, but in spite of complete surgical removal, the recurrence rate at 5 years is 5%, rising to 19% in long-term follow-up. However, there are no markers predictive of this evolution. Epigenetic changes in low-grade meningiomas have not been previously addressed. To get insights into the possible role of p16INK4a and p14ARF TSG alterations in grade 1 meningiomas, we study the methylation status and protein expression of these genes in 140 specimens of meningiomas: 29 nonrecurrent and 57 recurrent in one, two or three times. Methods: Methylation specific PCR and bisulfate modification followed by bisulfate genomic sequencing of CpG islands and staining with p16INKa and p14ARF antibodies (Ab’s). Results: Our data show p16INK4a and p14ARF methylation in 43.4% and14.2% meningiomas respectively. Methylation of p16INK4a is found in a similar proportion in non-recurrent meningiomas (37.9%) and the first biopsy of recurrent cases (38.8%) and increases to a 52.3% in successive biopsies of recurrent cases. Methylation of p14ARF occurs in 13.8% of nonrecurrent vs. 9.6% recurrent meningiomas (first biopsy) and 19.6% of successive recurrent meningiomas. Loss of p16INK4a and p14ARF protein expression was shown in 52.7% and 18.6% of meningiomas respectively. p16INK4a and p14ARF methylation was associated with loss of protein expression in 54.7% and 18.8% of meningiomas. Loss of p16INK4a and p14ARF expression was associated with unmethylated promoters in 52.9% and 17.6% of cases respectively. Conclusions: Epigenetic changes of p16INK4a and p14ARF genes and loss of protein expression leading to Rb and p53 TSG pathways alterations, may have a pathogenic role in human meningiomas. Loss of p16INK4a and p14ARF protein expression associated with unmethylated promoters, could be due to loss of heterozigosity or gen mutation. Increase of p16INK4a and p14ARF methylation along the following biopsies of recurrent cases suggests a possible role of methylation in tumor progression.
Therapeutic targeting of microRNA-31 in lung cancer.
Authors: Monic Roengvoraphoj, Yongli Guo, Tian Ma, Radu V. Stan, Susanna Obad, Sakari Kauppinen, Ethan Dmitrovsky, Sarah J. Freemantle
Journal: Journal of Clinical Oncology (2012)

e13567 Background: MicroRNAs (miRs) have emerged as powerful regulators of cellular processes and are frequently deregulated in cancer. Our previous work showed that miR-31 was overexpressed in human and murine lung cancers and repression of miR-31 inhibits lung cancer proliferation and tumorigenesis. Novel miR-31-targeting compounds were developed using a locked nucleic acid (LNA) drug platform. Compounds were tested in cell-based assays to assess levels of miR-31, miR-31-target genes and cell proliferation. A lead compound was chosen and we are currently examining its in vivo activity in human lung cancer cells and in murine transgenic lung tumor models. Methods: We previously developed a murine model of lung cancer by specifically overexpressing human cyclin E in the lung (CEO mice). The ED1 cell line was derived from a CEO mouse lung tumor. ED1 cells were transfected with the miR-31-LNA-targeting compounds and miR-31 levels and target genes quantified versus controls using RT-PCR assays. Cell proliferation was assessed using the CellTiter-Glo assay. Microarray analysis was performed to further investigate novel miR-31 target genes that were validated using independent RT-PCR assays. A pharmacodynamic study (5 daily tail vein injections) was performed in CEO mice that develop lung tumors spontaneously. Lung tissues were harvested 24 hours after the final dose and analyzed for immunohistochemical biomarkers of drug response (Ki67 and cyclin E). Results: Novel LNA anti-miR-31 compounds decreased miR-31 levels and proliferation rates in murine and human lung cancer cells. The compound, as expected, augmented expression of a known miR-31 target, LATS2. The microarray analysis identified over 100 genes with 2-fold elevated expression in anti-miR-31 treated cells. Validated novel miR-31 targets include GADD45a, Trp53inp1, Txnip and Slc40a1. Preclinical studies in mouse models are ongoing. Conclusions: Targeting miR-31 using LNA–based therapy inhibits cell growth in lung cancer cells and is a promising therapeutic approach for the treatment of lung cancer. Successful preclinical activity of these compounds will warrant translation into the clinic in proof of principle trials to assess pharmacodynamic and pharmacokinetic outcomes.
Scoring system for prediction of having three or more involved axillary nodes for breast cancer.
Authors: Soo Kyung Ahn, Ji sun Kim, Jee Man You, Hee-Chul Shin, Hyeong Gon Moon, Wonshik Han, Dong Young Noh
Journal: Journal of Clinical Oncology (2012)

1133 Background: Completion axillary lymph node dissection (ALND) is currently the standard of care in the event of a positive sentinel lymph node biopsy (SLNB). However, result from Z0011 indicate that women with a one or two involved axillary nodes and clinical T1-T2 tumors undergoing lumpectomy with radiation therapy followed by systemic therapy do not benefit from completion of ALND in terms of survival. The purpose of this study was to define possible predictors of having three or more involved axillary node to provide information for surgeons making decision about sparing intraoperative frozen section analysis of sentinel lymph node and completion ALND. Methods: We reviewed the records of 1215 patients with clinical T1-T2 invasive breast cancer. None of these patients were in situ cancer on initial gun biopsy nor received neoadjuvant chemotherapy. Factors associated with having three or more involved axillary nodes were evaluated by univariate and multivariate logistic regression analysis. Results: Among 1215 patients, 321 patients had three or more positive nodes. On a multivariate analysis, having three or more positive nodes was associated with primary tumor size by breast US, axillary LN grade according to cortical thickness by US, presence of axillary LN enlargement on chest CT and age. A scoring system to predict the probability of having three or more nodes based on patients’ data and preoperative image findings was developed from the multivariate logistic regression model. The area under the ROC curve was 0.827 (95% CI: 0.793-0.860), and negative predictive value was 90.2% for a score ≤2.7. Similar findings were observed for a validation dataset of 505 patients. Conclusions: Patients with a low probability of having three or more positive nodes can be identified from preoperative image finding. The scoring system developed will be helpful to surgeons making decision about sparing intraoperative frozen section analysis of sentinel lymph node and completion ALND.
A priority educational program at Princess Margaret Cancer Centre.
Authors: Jasmine Grant, Susanna Sellmann, Julie Gundry, Pamela Degendorfer
Journal: Journal of Clinical Oncology (2017)

189 Background: The clinical research environment is consistently evolving with new methodology, complexity and regulatory stringency. With this evolution, the need for a well-educated clinical research team is critical. There are approximately 300 clinical research staff at Princess Margaret, 100 Principal investigators. The Cancer Clinical Research Unit (CCRU) is a support department within the Princess Margaret Cancer Program and provides two dedicated staff to implement and facilitate clinical research education across the program. Methods: CCRU Education currently offers 50 unique education sessions with an average of 45 sessions per quarter. Starting in 2010, 9275 attendees have attended 892 CCRU in-class sessions. Since 2015, 224 sessions have been attended by 25 sites through teleconference. The CCRU has implemented an “Orientation Pathway” for new clinical research staff to provide clear guidance on mandatory research training activities, as well as role and task-specific training activities. In 2016, CCRU has included more workshop-style courses, providing scenario-based learning models. The CCRU uses a blend of online, in-class, and case-based learning sessions to promote critical thinking and stimulate vibrant group discussion. Interactive sessions and evaluation ensure learning needs are met. Results: Since implementing the interactive sessions, and the Orientation Pathways, the CCRU Quality Assurance department has seen a reduction of insufficient documentation findings. To measure this, the total number of Quality Assurance Review (QAR) findings on insufficient and/or incomplete documentation of the consent process was averaged and compared in 2014 and 2015 and a 25% decrease was noted. In addition, staff feedback is regularly collected through an online methods and is reviewed by the CCRU Quality-Education committee for training quality improvement. Conclusions: Positive staff feedback and a reduction of QAR findings has encouraged CCRU Education to continue creating workshop-based training sessions that are interactive, timely and effective. Efforts will continue to include CCRU-QA findings in the development of new course content to ensure staff are well trained and overall quality continues to improve.
Improving survivors' outcomes in cancer survivorship clinics.
Authors: Guadalupe R. Palos, Katherine Ramsey Gilmore, Patricia Chapman, Paula A. Lewis-Patterson, Maria Alma Rodriguez
Journal: Journal of Clinical Oncology (2017)

93 Background: A core measure of the ASCO Quality Oncology Practice Initiative and Commission on Cancer Program Standard is adherence to use of written treatment summaries (TSs) and care plans (CPs) for cancer survivors. Previous data from ASCO’s quality improvement (QI) studies indicate inconsistent use and distribution of treatment summaries and care plans. Audits conducted of adherence rates among our survivorship providers indicated use varied across clinics. We developed a plan to improve use of TSs and CPs among providers and improve survivors’ outcomes. Methods: The Plan-Do-Study-Act QI model was used to identify gaps in performance and process failures that led to those gaps. The project used stratified purposive sampling to select clinics. Based on the disease site, staffing structure, and clinical infrastructure, the breast, genitourinary, and head/neck survivorship clinics were chosen. First, we identified primary elements of the processes detailed in clinical practice algorithms specific to each site. Next qualitative interviews were conducted with providers to identify strengths and barriers to the use of TSs and CPs. Interviews were audio-recorded, transcribed verbatim and analyzed to confirm themes. Descriptive statistics were used to summarize demographic and clinical data. Results: A total of 16 members of the 3 clinics were interviewed. Of these, 37.5% were providers, 31.3% administrators, 18.8% support staff, and 12.4% faculty champions. Major themes identified as hindering adherence rates centered on cumbersome scheduling processes i.e. “there’s so many people that have to “touch an order” to get it to happen”, fragmentation among electronic medical records systems, i.e. “the way to fix it would be if it was a smart automated document that took the information…there in the chart," limited support among other health care professionals about survivorship care, i.e. “when push comes to shove Survivorship gets pushed. That’s the nature of the beast.” Conclusions: The barriers identified can be used to develop feasible solutions to improve adherence rates among survivorship clinic providers. Findings from this QI project contribute to deeper understanding of the complex issues involved in improving outcomes for survivors.
Prostate cancer (PC) mortality rates: Manual versus ACME (Automated Classification of Medical Entities) coding
Authors: E. Hernes, L. A. Johansson, S. D. Fosså, S. Harvei, F. Gjertsen, E. Glattre
Journal: Journal of Clinical Oncology (2004)

4699 Background: Norway has one of the highest PC mortality rates world-wide. Two processes affect the quality and comparability of cause of death statistics: the information basis and handling of the information (codification process). In Statistics Norway (SN) the codification process is manual and information both from the death certificate, autopsy reports, queries to physicians and routinely collected information from the national Cancer Registry of Norway is used. To investigate the impact of SN registration routines on the Norwegian PC mortality rates we compared the underlying cause of death (UCOD) selected by SN to the UCOD selected by ACME. Methods: From the files of SN and Cancer Registry of Norway a total of 2012 Norwegian men with a diagnosis of PC and who died in 1996 were identified. Death certificates were collected from SN and recoded according to ACME specifications with use of death certificate information only. The UCOD selected by ACME was compared to the UCOD selected by SN. Age standardized PC mortality rates (World Population) were calculated. Results: In only 29 cases ACME could not select an UCOD. These cases were coded manually. Using ACME as described the age standardized (World Population) PC mortality rate in Norway for 1996 would have been 24.0 as compared to the figure of 24.8 based on UCODs identified by SN. Overall, ACME selected PC as UCOD in 1124 cases as compared to 1161 according to SN. In 1081 cases both ACME and SN selected PC as UCOD. Conclusions: On a case level there are noticeable differences between the automated coding system ACME and Statistics Norway regarding selection of PC as underlying cause of death. Overall, however, the registration routines do not fully explain the high PC mortality rate in Norway. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Norway
Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis
Authors: Karine Crozat, Kasper Hoebe, Sophie Ugolini, Nancy A. Hong, Edith Janssen, Sophie Rutschmann, Suzanne Mudd, Sosathya Sovath, Eric Vivier, Bruce Beutler
Journal: The Journal of Experimental Medicine (2008)