tbuckley/cabot-search huggingface dataset:
Targeted next generation sequencing and identification of risk factors in <scp>W</scp>orld <scp>H</scp>ealth <scp>O</scp>rganization defined atypical chronic myeloid leukemia
Authors: Mrinal M. Patnaik, Daniela Barraco, Terra L. Lasho, Christy M. Finke, Kaaren Reichard, Katherine P. Hoversten, Rhett P. Ketterling, Naseema Gangat, Ayalew Tefferi
Journal: American Journal of Hematology (2017)

Atypical chronic myeloid leukemia (aCML) is an aggressive myeloid neoplasm with overlapping features of myelodysplastic syndromes (prominent granulocytic dysplasia) and myeloproliferative neoplasms (neutrophilic leukocytosis). We studied 25 molecularly-annotated and World Health Organization defined aCML patients; median age 70 years, 84% males. Cytogenetic abnormalities were seen in 36% and gene mutations in 100%. Mutational frequencies were, ASXL1 28%, TET2 16%, NRAS 16%, SETBP1 12%, RUNX1 12%, ETNK1 8%, and PTPN11 4%. Fifteen patients (60%) had >1 mutation, while 9 (36%) had ≥3. The median overall survival (OS) was 10.8 months and at last follow up (median 11 months), 17 (68%) deaths and 2 (8%) leukemic transformations were documented. On univariate analysis, survival was adversely impacted by advanced age (P = .02), low hemoglobin (P = .01), red blood cell transfusion dependence (P = .03), high white blood cell count (P = .02), TET2 (P = .03), NRAS (P = .04), PTPN11 (P = .02) mutations and the presence of ≥3 gene mutations (P = .006); ASXL1, SETBP1, and ETNK1 mutations did not impact OS. In multivariable analysis, advanced age (P = .003) [age >67: HR 10.1, 95% CI 1.3-119], low hemoglobin (P = .008) [HB< 10 gm/dL: HR 8.2, 95% CI 1.6-23.2] and TET2 mutations (P = .01) [HR 8.8, 95% CI 1.6-47.7] retained prognostic significance. We then used age >67 years, hemoglobin <10 gm/dL and the presence of TET2 mutations (each counted as one risk factor) to create a hazard ratio weighted prognostic model; effectively stratifying patients into two risk categories, low (0-1 risk factor) and high (≥2 risk factors), with median OS of 18 and 7 months, respectively.
Hard-wiring survivorship care plan delivery.
Authors: Lisa Barbarotta, Mae Anne Jauk, Anne C. Chiang, Tara Beth Sanft
Journal: Journal of Clinical Oncology (2017)

113 Background: As outlined by the Institute of Medicine (IOM) report, ASCO, the Commission on Cancer, survivorship care planning is an essential part of quality cancer care. Meeting SCP delivery standards is a challenge due to complex systems, difficulty identifying eligible patients, lack of clarity around roles and responsibilities, and time required to complete the care plans. Yale Cancer Center/Smilow Cancer Hospital is a NCI-designated comprehensive cancer center with 12 multidisciplinary cancer programs, a large cancer hospital and 10 care centers in the community. We have approximately 4000 early stage analytic cases per year. We set out to standardize SCP delivery. Methods: A group of multidisciplinary stakeholders convened to outline goals and identify needs. Based on gap analysis and review of national standards, a standard operating procedure for the creation and delivery of SCPs was developed. Models of care were outlined in the policy. Disease specific treatment summary and care plan templates for the most common cancer types were developed within our electronic medical record (EMR) based on ASCO standards and were vetted by disease team experts. The templates were built to minimize the need for manual entry of content. Automated alerts were developed within the EMR to trigger identification of eligible patients. An operational plan was developed for each clinical area to outline responsibilities for care plan creation and delivery. Results: Implementation of model survivorship care within each disease team and community site was performed over a period of one year. The number of care plans delivered has already increased by 20%. At least 10% of early stage analytic cases received SCPs in 2015. Conclusions: Meeting SCP standards in a large, single institution can be challenging. With a standard operating procedure, clear delineation of responsibility within teams, disease specific templates, and EMR tools to trigger visits, meeting these standards becomes an achievable goal. A systematic approach to developing comprehensive survivorship care in a large academic center can hardwire high quality patient care and compliance with standards.
Abstract 108: TALEN-mediated Gene-Editing in Zebrafish for Studying Titin Biology
Authors: YU-HUAN SHIH, Xiaolei Xu
Journal: Circulation Research (2013)

Background: Titin, the largest protein found in nature, has been found to be crucial for heart and muscle development and mutations on titin caused human diseases. Especially, truncated mutations on TITIN were found to be a major causative gene (more than 25%) for familiar dilated cardiomyopathy (DCM) but the mechanism is lacking. Due to the gigantic size and number of exons, genetic study of titin has been challenging. To facilitate genetic analysis of titin biology, we leveraged the Transcription Activator-Like Effects Nuclease (TALEN) technology in zebrafish to edit the titin gene directly. Results: We generated TALEN pairs targeting different domains of zebrafish titin, including Z-disc domain, N2B domain, and A domains. Because zebrafish contain two titin homologues, ttna and ttnb , TALEN pairs targeting the corresponding loci for both homologues were made. The mutations are efficiently introduced on the titin using TALENs. In addition to these truncated mutants, TALEN technology can also create internal deletions. The titin mutant fish were identified and further phenotypic analysis has been carried out. Conclusions: Combined with TALEN technology, zebrafish can provide a convenient vertebrate model for genetic studies of titin biology. Moreover, this gene-editing technology will facilitate the use of the zebrafish model as a powerful research tool for modeling human diseases and investigating their pathogenesis.
Oncogenetic Risk Classification Based on NOTCH1/FBXW7/RAS/PTEN Mutation Profiles Improves Outcome Prediction in Pediatric T-Cell Acute Lymphoblastic Leukemia, Treated According the Fralle 2000 T Guidelines
Authors: Arnaud Petit, Amélie Trinquand, Sylvie Chevret, Paola Fabiola Ballerini, Jean-Michel Cayuela, Nathalie Grardel, Aurore Touzart, Benoit Brethon, Hélène Lapillonne, Pascal Chastagner, Claire Berger, Gerard Michel, Claude Preudhomme, Jean Soulier, Judith Landman-Parker, Guy Leverger, Elizabeth Macintyre, Andre Baruchel, Vahid Asnafi
Journal: Blood (2016)
Abstract 86: Exercise Prevents Cardiac Injury and Improves Mitochondrial Biogenesis in Advanced Diabetic Cardiomyopathy With Pgc-1α and Akt Activation
Authors: Hui Wang, Yan Lu, Wei Sun, Junjie Xiao, Xiangqing Kong
Journal: Circulation Research (2015)

Background/Aims: Diabetic cardiomyopathy (DCM) represents the major cause of morbidity and mortality among diabetics. Exercise has been reported to be effective to protect the heart from cardiac injury during the development of DCM. However, the potential cardioprotective effect of exercise in advanced DCM remains unclear. Methods: Seven-week old male C57BL/6 wild-type or db/db mice were either subjected to a running exercise program for 15 weeks or kept sedentary. Cardiac function, myocardial apoptosis and fibrosis, and mitochondrial biogenesis were examined for evaluation of cardiac injury. Results: A reduction in ejection fraction and fractional shortening in db/db mice was significantly reversed by exercise training. DCM induced remarkable cardiomyocyte apoptosis and increased ratio of Bax/Bcl-2 at the protein level. Meanwhile, DCM caused slightly myocardial fibrosis with elevated mRNA levels of collagen I and collagen III. Also, DCM resulted in a reduction of mitochondrial DNA (mtDNA) replication and transcription, together with reduced mtDNA content and impaired mitochondrial ultrastructure. All of these changes could be abolished by exercise training. Furthermore, DCM-associated inhibition of PGC-1α and Akt signaling was significantly activated by exercise, indicating that exercise-induced activation of PGC-1α and Akt signaling might be responsible for mediating cardioprotective effect of exercise in DCM. Conclusion: Exercise preserves cardiac function, prevents myocardial apoptosis and fibrosis, and improves mitochondrial biogenesis in the late stage of DCM. Exercise-induced activation of PGC-1α and Akt signaling might be promising therapeutic targets for advanced DCM.
Minimal effect of initial TNM stage on follow-up intensity for rectal cancer patients
Authors: K. Ode, K. S. Virgo, W. E. Longo, R. A. Audisio, F. E. Johnson
Journal: Journal of Clinical Oncology (2007)

14508 Background: For rectal cancer patients, the risk of recurrence after curative-intent treatment is directly related to initial tumor stage. It is often assumed that more intensive follow-up is worthwhile in patients with high TNM stage lesions, while less intensive follow- up is sufficient for those with low TNM stage cancers. We carried out a survey of members of the American Society of Colon and Rectal Surgeons (ASCRS) to determine the surveillance strategies they use after primary curative-intent treatment for their own patients. This report describes the variation in surveillance intensity ascribable to initial TNM stage. Methods: We created a series of 4 vignettes succinctly describing generally healthy patients with rectal carcinoma (stage I treated with local excision, stage I treated with radical surgery, stage II treated with radical surgery, and stage III treated with radical surgery ± adjuvant therapy). We mailed a questionnaire based on the vignettes to all 1,795 members of ASCRS. Evaluable replies were entered into a computer database. The effect of TNM stage on follow-up intensity was analyzed using repeated-measures ANOVA. Results: There were 566 responses (32%), among which 347 (61%) were evaluable. The most frequent surveillance modality was office visit. In post-operative year 1 for patients with stage I lesions treated with local therapy, 3.8 ± 1.4 office visits (mean ± SD) were recommended, decreasing to 1.5 ± 0.8 in year 5. For patients with stage III lesions treated with radical surgery ± adjuvant therapy, 4.0 ± 2.8 office visits were recommended in year 1, decreasing to 1.7 ± 1.2 in year 5. Similar results were generated for all commonly used modalities on the questionnaire (3 blood tests, 2 endoscopic procedures, 8 imaging studies). Conclusions: The intensity of post-operative surveillance following curative-intent treatment for rectal cancer varies minimally by TNM stage. Because of this, a randomized trial of alternate follow-up strategies may be feasible without stratification according to stage. We will present the schema of such a trial at the meeting. No significant financial relationships to disclose.
Socioeconomic status and incidence of pediatric embryonal tumors in the United States.
Authors: Raquel Ataide Peres Silva, Tamara P. Pace-Emerson, Carlos Rodriguez-Galindo, A. Lindsay Frazier, Karina Braga Ribeiro
Journal: Journal of Clinical Oncology (2013)

10036 Background: Of the 13,000 children diagnosed with cancer each year in the United States (US), the embryonal solid tumors, neuroblastoma (NB), retinoblastoma (RB), Wilms tumors (WT), hepatoblastoma (HB), rhabdomyosarcomas (RMS) and germ cell tumors (GCT), account for over 30% of the cases. Social disparities in cancer are well studied for adults, but few studies have focused on children, mostly for leukemia. The aim of this study is to evaluate the differences in incidence of rare cancers according to socioeconomic status (SES). Methods: Cases aged 0-19 were identified from the Surveillance Epidemiology and End Results (SEER) cancer registries from 1992-2009. Using data from the US 2000 Census, the county of residence of the cases was categorized above or below the national average for SES measures including: % persons with&lt; high school education, % persons below poverty, % persons unemployed and % households with &gt; 1 person/room. Age standardized rates per million (ASR), rate ratios (RR) and 95% confidence intervals (CI) were obtained. The findings were validated using cases from the National Program of Cancer Registries (NPCR) from 1999-2009, analyzed with the same SES variables. Results: Among cases identified in SEER, rates of NB and WT are higher in counties with upper SES measures whereas RB and GCT occurred more frequently in counties with lower SES measures. No association was found between SES and rates of HB and RMS. The results were reproducible with NPCR cases. For instance, ASR of NB is lower (SEER: 5.86; NPCR: 7.48) in counties where &gt;19.6% of the population had not completed high school and higher (SEER: 8.41; NPCR: 8.47) in counties where ≤19.6% had not achieved a high school degree. (SEER: RR=0.69; 95%CI=0.62-0.77; NPCR: RR=0.88; 95%CI=0.84-0.93). Analysis of NB rates according to poverty, unemployment and crowding showed consistent results, with higher rates in counties with higher SES. Conclusions: The findings are suggestive of a relation between SES and cancer susceptibility that may be connected to environment and lifestyle. Understanding the role of contributing causes demands further studies to evaluate why cancer rates vary across cultural and ethnic groups as well as the magnitude of specific SE aspects.
Quality of Dutch integrated head and neck cancer care: Measurement and evaluation.
Authors: Lydia Francisca Jacoba van Overveld, Robert P. Takes, Jozé C.C. Braspenning, Matthias A.W. Merkx, Ludi E Smeele, Rosella P.M.G. Hermens
Journal: Journal of Clinical Oncology (2017)

173 Background: Oncologic care is very complex, and delivery of integrated care with optimal alignment and collaboration of several disciplines is crucial. To monitor and effectively improve high-quality integrated oncologic care, a dashboard of valid and reliable quality indicators (QIs) is indispensable. A set of QIs is developed specifically for head and neck cancer (HNC) patients from three perspectives: patients (development of indicators from patient perspective, including the first results, are described in the abstract "PROMs and PREMs in Dutch integrated head and neck cancer care: Measurements and evaluation"), medical specialist and allied health professionals. This presentation concerns the first results from medical and allied health professional perspective. Methods: QIs on process, structure and outcome of care, were developed using an evidence based method: the Rand modified Delphi method. Data was collected in nine Dutch hospitals nearly 1,500 patients (November 2014 - December 2016). Indicators were calculated on national and hospital level and corrected for case-mix using SPSS. Results: The final set contained 5 outcome indicators from both perspectives, 13 and 18 process indicators from the perspective of medical specialists and allied health professionals respectively, and three structure indicators from the perspective of allied health professionals. Besides, 10 case-mix factors were selected. Current practice assessment, in 1263 patients, produced high scores on integrated care indicators, e.g., the percentage of patients discussed in multidisciplinary team meeting before start of the treatment (93%) and availability of a treatment plan (99%). However, involvement of dental teams (range 57 – 100%) and malnutrition screening (range 8-35%) could be improved in most hospitals. In addition, most hospitals did not meet the standard of 80% on patients starting with treatment within 30 days. Conclusions: The quality of integrated multidisciplinary care for patients with head and neck cancer in the Netherlands is already high on some aspects, but varied between hospitals and shows room for improvement. This study can be an example for other oncologic diseases where integrated care is necessary.
Epidermal growth factor receptor (EGFR) status and prognosis in gallbladder cancer.
Authors: Sandro José Martins, Sérgio Renato Pais-Costa, Ricardo Artigiani-Neto, José Francisco de Mattos Farah, Maria Isete Fares Franco, Alberto Goldemberg
Journal: Journal of Clinical Oncology (2012)

e14657 Background: Studies from USA, Asia and Australia showed EGFR over-expression in gallbladder cancer (GC), and recent case reports suggest a role for EGFR targeted therapies in this disease. Methods: We studied the prognostic role of EGFR expression and its association with clinicopathologic features in forty-two GC patients surgically treated at our center, from 1995 to 2006. None received targeted cancer therapeutics. Tissue microarray blocks containing neoplastic tissue and tumor-adjacent non-neoplastic biliary epithelia were obtained and assessed for immunohistochemical (IH) expression of EGFR, cyclo-oxygenase-2 (COX2), E-cadherin and p53 protein. Nonparametric correlations were assessed by Spearman’s rho; survival analysis was performed using the Kaplan-Meier method and Cox regression; and p-values were computed for two-tailed tests. Results: EGFR IH scores 0, +1, +2, and +3 were observed in 48.7%, 23.1%, 17.9%, and 10.3%, respectively. They were correlated with p53 staining (rho=0.48; p=0.002); T-stage (rho=0.38; p=0.016); serum CA-19.9 (rho=0.48; p=0.016); and serum CEA (rho=0.56; p=0.004). Median overall survival (OS) was 8.0 months (95% C.I.: 5.6 to 10.3); 1-year and 2-year survival rates were 43.7% and 23.5%, respectively. OS were 18.0 months, 14.0 months, and 4.0 months for tumors with 0, 1+ and 2+ to 3+ EGFR staining, respectively. Univariate analysis suggested a worse prognostic significance for low serum albumin (p=0.001); elevated CEA (p=0.007) and CA-19.9 (p=0.007) levels; positive surgical margins (p=0.001); gallbladder fundus tumors (p=0.007); histologic grade 3 (p=0.003); positive nodes (p=0.001); lymphovascular invasion (p=0.001); tumoral necrosis (p=0.004); perineural invasion (p=0.002); and EGFR expression (p=0.004). In the multivariate analysis, low serum albumin (p=0.006), tumoral necrosis (p&lt;0.001) and EGFR expression (p&lt;0.001) predicted poor OS. Conclusions: We found tumor immunoreactivity for EGFR in nearly half of the cases and it was independently associated with poor survival in GC patients.
Italian observational study in patients with metastatic colorectal cancer (mCRC) treated with first-line cetuximab based regimen (ObservEr study).
Authors: Francesca Di Fabio, Gerardo Rosati, Ivan Roberto Lolli, Enzo Maria Ruggeri, Libero Ciuffreda, Daris Ferrari, Salvatore Tumolo, Giovanni Rosti, Paolo Tralongo, Raimondo Ferrara, Oscar Alabiso, Silvana Chiara, Giovanni Paolo Ianniello, Francesco Di Costanzo, Antonio Frassoldati, Carmelo Iacono, Mario Clerico, Lorenzo Pavesi, Giovanni Bernardo, Carmine Pinto
Journal: Journal of Clinical Oncology (2014)

e14600 Background: After the Italian Drug Agency (AIFA) approval of cetuximab in mCRC KRASwt, the ObsrvevEr Study was initiated to evaluated quality of life (QoL), skin toxicity management and compliance of cetuximab based regimens in first-line chemotherapy (CT) Methods: ObservEr is a non interventional, observational, prospective study. The primary end point is the evaluation of QoL. Data on QoL (Dermatology Life Quality Index/DLQI, EORTC QLQ-C30) is assessed at baseline and weekly for the first 8 weeks of treatment Results: Between April 2011-November 2012, 233 pts were enrolled in 29 Italian centers, with 229 evaluable pts. Pt characteristics were: 154(67.2%) M, 75(32.8%) F; median age 65y (39-81); ECOG PS-0 78.2%, PS-1 21.8%%; adjuvant CT 81(35.4%); only liver metastasis 98(42.8%). Median interval between request and result of KRAS test in all Italian regions was 10d. The CT regimens in combinations with cetuximab were: IRI-based 149(65.1%), OXA-based 67(29.3%). Capecitabine regimens were administered in 52(22.7%). Skin toxicity prophylaxis with vitamin K1 cream was performed in 164(71,6%), and reactive skin toxicity treatment included vitamin K1 cream in 60(26.2%). At 2 years 65.1% of pts were alive. Liver metastasis resection was performed in 34(14.8%; 34.7% in only liver metastasis). G1-3 skin toxicity was observed in 142(62.0%), G3 in 31(13.5%); no G4 was detected. No significant difference in G3 skin toxicity was observed between M vs F (15.7 vs 9.2%; p=0.177), age <75 vs ≥75 years (14.5 vs 8.3%; p=0.431), IRI vs OXA regimens (12.1 vs 17.9; p=0.252), 5-FU vs capecitabine regimens (16.1 vs 7.7; p=0.127); prophylactic vs reactive treatment (15.2 vs 13.5%; p=0.79). Median cetuximab treatment was 20w (1-85), with discontinuation skin toxicity-related in 9(3.9%). QoL assessed by DLQI and EORTC questionnaires was evaluable in 221 pts (96.5%) at baseline and in 201(87.8%) at week 8 (W8). No deterioration of QoL was observed from baseline to W8 both by DLQI and EORTC questionnaires Conclusions: In the first-line CT of mCRC the current management of skin toxicity had a favourable impact in the compliance of cetuximab based treatment. No deterioration of QoL was registered Clinical trial information: ID239.
CAHPS Cancer Care Survey: Development, testing, and final content of a survey of patient experience with cancer care.
Authors: Christian Evensen, Kathleen J. Yost, San Keller, Tamika Cowans, Elizabeth Frentzel, Sarah Jenkins, Jason Egginton, Neeraj K. Arora, Steven Garfinkel
Journal: Journal of Clinical Oncology (2017)

227 Background: The objective of this work was to develop a reliable and valid survey measuring aspects of cancer care important to patients to be used in both inpatient and outpatient settings, and that allows comparisons of patient experiences across treatment centers and treatment modalities (medical oncology, radiation, surgery). Other objectives included testing various modes of data collection and developing a standardized sampling methodology based on ICD diagnosis and procedure codes. Methods: We conducted focus groups with patients who had received cancer treatment and with family members of cancer patients. We convened a panel of experts representing quality improvement, oncology, shared decision-making, patient safety, and patient advocacy to obtain feedback on the development of the survey. We interviewed stakeholder groups representing oncology associations to obtain feedback on focal provider, attribution and sampling. We then conducted a field test of the survey among six cancer centers around the country, conducted psychometric analyses, revised the survey, conducted a second field test among four community oncology practices in CA, re-analyzed the data, and finalized the survey. Results: Final survey content was determined using results of the formative research, psychometric analyses, and input from the CAHPS Consortium. The core survey includes 56 questions, 23 of which map to eight composites: Provider Communication, Enabling Patient Self-management, Team Available to Provide Information, Access to Care, Care Coordination, and Office Staff. Supplemental item sets include seven items assessing Shared Decision Making, four items measuring Keeping Patients Informed, and two additional Access to Care items. Mail-only, mail-telephone mixed-mode, and web-mail mixed-mode are recommended methods of data collection. The survey and all recruiting materials are available in English and Spanish. Conclusions: The CAHPS Cancer Care Survey is a rigorously developed, well-tested, reliable and valid survey of patient experiences with their cancer care. The survey and supporting materials are available free of charge on the CAHPS website (www.ahrq.gov/cahps).