tbuckley/cabot-search huggingface dataset:
Next-generation sequencing yields promising targets in advanced cholangiocarcinoma (CCA).
Authors: Rachna T. Shroff, Chaitanya Churi, Asif Rashid, Lopa Mishra, Mingxin Zuo, Ahmed Omar Kaseb, Filip Janku, Thomas A. Aloia, Jean-Nicolas Vauthey, Steven A. Curley, Milind M. Javle
Journal: Journal of Clinical Oncology (2014)

209 Background: The incidence of CCA is rising and the clinical efficacy of systemic therapy is suboptimal. Next generation sequencing (NGS) technology offers potential for targeted therapeutics against genetically heterogenous solid tumors including cholangiocarcinoma (CCA). Methods: DNA was extracted from biopsy specimens of 61 patients (pts) with CCA seen at MD Anderson Cancer Center Houston, TX. DNA sequencing was performed for 3,769 exons of 236 cancer-related genes plus 47 introns from 19 genes to an average depth of 1000X using the Illumina HiSeq 2000 platform (performed by Foundation Medicine, Cambridge, MA). Results: 174genomic alterations (GA) were identified from 61 pt samples with an average of 2.85 GAs/pt (range 0-10). GAs identified were mutations (75%), amplifications (16%), loss/deletions (7%) and others (2%). 6 (10%) tumors showed no GAs. Most frequent GAs were TP53 (34%), KRAS (30%), ARID1A (15%), PBRM1 (11%), BAP1 (8%), ERBB2 (8%), FBXW7 (8%), SMAD4 (8%) and IDH1 (8%). ERBB2 GAs included 4 mutations and 1 amplification. KRAS mutation was associated with a statistically significant reduction in overall survival (OS). Mean OS in pts with KRAS mutation was 32 weeks vs. 63 weeks in KRAS wt (t = -2.126, p = 0.039). Ingenuity Pathway Analysis indicated disruption in cell cycle, proliferation, development, death and DNA repair pathways. Targetable signaling pathways from this study are described in the Table. Targetable GAs were noted in 62% of pts. These are potentially targetable by inhibitors to ERBB2, FGF, mTOR, MEK, BRAF and PARP-1. Conclusions: These data are the single largest compilation of NGS analysis on CCA pts and demonstrate the range of GAs that are eligible for investigational targeted therapies. These results can be used as a basis to develop personalized treatments for CCA pts based on individual genetic profiles. [Table: see text]
Clinical features of young patients (below age 40) with pancreatic ductal adenocarcinoma.
Authors: Akihiro Ohmoto, Chigusa Morizane, Emi Kubo, Kazuaki Shimada, Takuji Okusaka, Shinichi Yachida
Journal: Journal of Clinical Oncology (2014)

199 Background: The median age of pancreatic ductal adenocarcinomas (PDAC) patients is approximately 70 years. We investigated clinical features of PDAC occurring in young patients (&lt; 40 years) in order to determine if any difference exists in comparison to older patients. Methods: We reviewed a single-institution database of 785 patients with pathologically proven PDAC between 2001 and 2012. We examined the clinical features in patients with PDAC below 40 years of age and compared it to those in older patients (≥ 40 years). Results: Of these 785 patients, a total of 10 patients (1.3%) under the age of 40 were identified, with a range of 28 to 37 years. Clinical features in young and older patients have been summarized (table). There are no differences between groups in terms of sex, smoking, tumor location, UICC stage, a family history of PDAC and a family history of any cancer. In the young patients group, three of them were diagnosed with localized diseases, two others with locally advanced diseases, and five others with metastatic diseases. Two of the three patients with localized diseases underwent curative operation. The five patients with metastatic diseases received chemotherapy, and only one patient achieved a partial response treated with FOLFIRINOX regimen. Two of the patients were long-term survivors, having survived over three years. Six of the patients had a family history of other cancers in first-degree relatives. Unexpectedly and most importantly, only one patient had a family history of PDAC. Conclusions: Cases of patients with PDAC below 40 years of age are rare. The clinical features in young patients were generally similar to those in older patients. Almost all young patients had no family history of PDAC, which suggests that hereditary genetic factors have a weak relationship with cases of onset of PDAC at a young age in Japan. [Table: see text]
Soluble LR11/SorLA, a Potential Circulating Marker Indicating the G-CSF-Induced Mobilization of Hematopoietic Stem Cells, Is a Modulator of G-CSF-Mediated Migration of HL-60 Cells,
Authors: Naomi Shimizu, Chiaki Nakaseko, Masahiro Takeuchi, Chikako Ohwada, Shokichi Tsukamoto, Takeharu Kawaguchi, Keigo Nishii, Meiji Jiang, Koutaro Yokote, Isamu Fukamachi, Hideaki Bujo
Journal: Blood (2011)
Microarray-based molecular diagnostics: An application to predicting prostate cancer aggressiveness
Authors: J. Moraleda, L. Buturovic, Q. Tran, A. Pattin, G. Anderson
Journal: Journal of Clinical Oncology (2005)

9646 Background: Prostate cancer is the second most common cancer in men in the US and Europe and it is the second leading cause of cancer death of men in the United States. Prostate cancer may be indolent, requiring no treatment but watchful waiting, or aggressive requiring harmful chemical or radio interventions. Currently no effective diagnostic exists to detect indolent tumors and current guidelines recommend treatment of localized prostate cancer with potentially curative therapies. Improved markers to identify those patients most likely to benefit from aggressive treatment and those who can safely avoid or delay potentially harmful clinical interventions would reduce healthcare costs, improve patient outcomes and reduce unnecessary suffering. This study was undertaken to demonstrate that when applied to microarray gene expression data, PathWok Informatics analytical models convert gene expression profiles into actionable reports that predict the aggressiveness of prostate tumors. Methods: Published data from a variety of sources was used. The data comprised output files from microarray (Affymetrix, GE Healthcare) processing of 110 frozen tumor tissue samples. Each specimen was from an aggressive or indolent lesion. All data was analyzed by the PathWork Informatics software system. Results: Cross-validation results show that the analytical system is highly accurate: 80% of samples were correctly classified, 5% were incorrectly classified, and 15% were indeterminate. Conclusions: This novel analytic system can identify the aggressiveness of a prostate lesion in a high percentage of tumors, allowing for highly predictive, laboratory independent classification of microarray data, with high potential clinical utility. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration PathWork Informatics PathWork Informatics
Analysis of long-term outcome and late toxicity in Hodgkin lymphoma survivors
Authors: I. Cedrych, A. Polakiewicz-Gilowska, E. Nowara, A. Deptala
Journal: Journal of Clinical Oncology (2008)

19537 Background: Therapy of Hodgkin lymphoma (HL) can contribute to delayed toxicity. The purpose of this retrospective study was to evaluate long-term outcome of HL survivors. Methods: The medical report data analysis of 150 patients (pts) with HL treated in an oncological center in Poland between 1992–2005 has been performed. There were 80 females and 70 males, median age 31 years (range 15–69), and 110/150 pts (73,4%) in CSI/II, 40/150 pts (26,6%) in CSIII/IV. Half of the 150 pts presented B- symptoms. The most common pathology subtypes were NS (60%) and MC (23%). Chemotherapy (MOPP, MOPP/ABV or ABVD regimen) and radiotherapy (mantle-field or involved-field) were given to 138/150 (92%) pts with average of 6 cycles/patient, and to 108/150 (72%) pts with median 45 Gy respectively. Chemoradiotherapy received 96/150 pts (64%). Results: CR achieved 122 pts (81%), PR 23 pts (15,3%), and ORR was 96,6%. With a median follow-up of 72 months, there were 24 relapses and 23 deaths (19 HL progression, 3 secondary cancer and 1 coronary heart disease). Five year DFS and OS were 78% and 92% respectively. Late toxicity/impairment of health were revealed in 62/150 pts (41,3%). There were: secondary ammenorrhea/infertility in 30 women, musculoskeletal abnormalities in 26 pts (osteoporosis, spondyloarthrosis, Perthes disease, Scheuermann disease, reumathoid arthritis), depressive syndromes ( n=10), pulmonary fibrosis (n=9), polyneuropathy (n=5), hypothyreosis (n=4,) coronary heart disease (n=3) and secondary cancer (n=7). Among these 7 malignancies there were: 1 osteosarcoma, 1 melanoma, 1 non-small cell lung cancer, 1 colon carcinoma, 1 cervical carcinoma, and 2 skin basal-cell carcinoma. A median time from the end of the treatment to development of the secondary malignancy was 8 years. The relative risk of the late toxicity/health impairment among pts treated with either initial chemotherapy alone or combined modality therapy was similar, and did not reach statistical difference (p=0.20). Conclusions: Therapy of HL provides freedom from the disease in more than 3/4 of our patients. In the group of fairly young patients, such treatment caused a substantial amount of variety health impairment, and even fatal diseases. This study indicates the need of a careful, long term medical surveillance in HL survivors. No significant financial relationships to disclose.
Policy and procedure manuals: Does existence imply standardization in practice?
Authors: Ajay Kapur, David Barbee, Yijan Cao, Abolghassem Jamshidi, Louis Potters
Journal: Journal of Clinical Oncology (2014)

275 Background: Patient safety organizations recommend the use of policy and procedure manuals (PPM) to effectuate standards and guidelines in practice. In this work we explored inter-physicist variability in the interpretation of five established physics policies amongst physicists in our department. Methods: The policies for treatment planning, 2 nd physics checks, 1 st day physics checks, weekly chart checks and final physics checks were reviewed by members of the quality management team in our department. Specific definitive statements were extracted into a spreadsheet and provided to 11 physicists and 6 dosimetrists. The intent was to obtain individual responses on adherence to the statements and thereby assess the level of standardization in perception and practice amongst the staff using free-margin kappa statistics. The responses were limited to affirmation, rejection or non-applicability. A total of 732 responses were assessed. Results: Based on the Landis-and-Koch criteria for interpretation of kappa values, the consistency amongst the respondents varied from moderate (0.40-0.60) to good (0.60-0.80). The kappa scores for the statements assessed were 0.56 for treatment planning, 0.64 for second physics check, 0.70 for the first day physics check, 0.54 for the weekly physics check and 0.73 for the final physics check. Conclusions: Validating the effectiveness of PPMs by measuring uniformity in staff interpretation is an important step in establishing their effectiveness. Mere existence of a PPM may not be sufficient. This work demonstrated reasonable uniformity of interpretation of existing policies, but underscored the need for further improvement. The review of specific policy statements with weaker consensus may lead to more effective revisions and in-servicing to enhance clarity and reduce ambiguity, re-testable using the same approach. Absence of validation will tend to retain ambiguity, thereby rendering the policy not as effective as it could be.
Nomogram for predicting overall and colostomy-free survival for patients with anal cancer.
Authors: Vassiliki Liana Tsikitis, Kim Lu, Jong Sung Kim, Kevin G. Billingsley, Charles R. Thomas, Daniel Herzig
Journal: Journal of Clinical Oncology (2014)

400 Background: The incidence of anal cancer, currently about 5,000 persons a year, is increasing in the United States. Its treatment has evolved from a radical surgical treatment including abdominoperineal resection to a combined chemoradiotherapy (CRT) (Nigro protocol) approach which allows for sphincter preservation. The specific aim of this study was to develop an accurate model and nomogram to predict overall (OS) and colostomy free survival (CFS) for patients (pts) presenting with anal cancer. Methods: Pts with de novo anal cancer were selected from the National Cancer Database (NCDB) from years 1998-2010. The database included 53,523 pts. After excluding anal margin cancer pts and pts with missing data points; 1,823 pts were included and their data analyzed. Variables included time to death, censoring indicator, age, race, sex, tumor size, surgery status, nodal status, radiation (RT) and chemotherapy (CT) separately and as a CRT. A stratified Cox proportional hazards model for OS and a logistic regression model for CFS were developed, respectively. For each primary end point, our final model was validated to ascertain whether predicted values from the model are likely to accurately predict responses on future subjects or subjects not used to develop our model. Results: Statistically significant variables in the CFS model were age, nodal status, TNM stage, RT (p ≤ 0.0001), and tumor size (p = 0.010). Similarly, for OS model statistically significant variables (all with p ≤ 0.005) fitted across the strata of TNM clinical stage included age, sex, tumor size, nodal status, and CRT. Nomograms that predict events are based on our final models with the estimated mean absolute bootstrap calibration error being only 0.011 for OS model and 0.02 for CFS model, respectively. Conclusions: A nomogram can predict OS and CFS over lifetime. Such outcome prediction tools may potentially be used as prognostic and decision support tools to guide therapy and predict pts that may need surgery in their lifetime.
Clinical pathways and quality metrics.
Authors: Peter G. Ellis, Kathleen Lokay
Journal: Journal of Clinical Oncology (2014)

273 Background: UPMC CancerCenter (UPMC) participates in a number of nationally recognized quality programs and strives to maximize quality through continuous improvement of the quality measures endorsed by these programs. Clinical pathways are potential aid in driving quality improvement through decision support and measurement. Methods: When deficiencies are identified, UPMC’s quality team develops improvement strategies including working with its pathways vendor (Via Oncology) on the placement of key decision support prompts and required data fields within its physician-facing pathways portal. Gaps in data completeness have also been identified as an opportunity to use pathways for more complete data collection during chart abstraction as well as interim reporting. Results: Due to the success above, UPMC continues to actively engage with pathways as a tool to drive adherence to and capture complete data for quality measures. If release of the UPMC data is approved by the quality measurement organization(s), UPMC will share the results of its quality measures in the full poster. Conclusions: Pathways are a tool for promoting adherence to quality measures by oncologists through the use of a point of care decision support system. Pathways are also a source of reporting quality measures across all patients in time period which allows for interim measurements and proactive identification of improvement areas. [Table: see text]
Short- and long-term outcomes of neoadjuvant-synchronus S-1+radiotherapy for locally advanced rectal cancer: Multicenter phase II study.
Authors: Takahiro Hiratsuka, Tomonori Akagi, Kentaro Nakajima, Shinichiro Empuku, Tomotaka Shibata, Yoshitake Ueda, Manabu Tojigamori, Hidefumi Shiroshita, Tsuyoshi Etoh, Shigeo Ninomiya, Kazuaki Hiroishi, Yu Takeuchi, Atsushi Sasaki, Koichiro Tahara, Kyuzo Fujii, Akio Shiromizu, Koichi Ishikawa, Toshifumi Matsumoto, Toshio Bando, Masafumi Inomata
Journal: Journal of Clinical Oncology (2016)

720 Background: Fluorouracil-based chemoradiotherapy (CRT) is regarded as a standard perioperative treatment in locally advanced rectal cancer. We investigated the efficacy and safety of substituting fluorouracil with the oral prodrug S-1. Methods: A multi-institutional (17 specialized centers), interventional phase II trial, was conducted from April 2009 to August 2011. For inclusion, patients must fulfill the following requirements before neoadjuvant CRT: (i) histologically proven rectal carcinoma; (ii) tumor located in the rectum (upper, lower); (iii) cancer classified as T3-4, N0–3 and M0; Two cycles of neoadjuvant CRT with S-1 (100 mg/m2 on days 1-5, 8-12, 22-26, and 29-33) was administered, and irradiation (total 45Gy/25fr, 1.8Gy/day, on days 1-5, 8-12, 15-19, 22-26, and 29-33) was performed. Total mesorectal excision was performed during the 4th and 8th week after the end of the neoadjuvant CRT. The primary endpoint is rate of complete treatment of neoadjuvant CRT. Secondary endpoints are response rate of neoadjuvant CRT, short-term clinical outcomes, rate of curative resection, and pathological response (grade2/3). Results: This trial included 37 patients (clinical StageIIA: 8, IIIB: 19, IIIC: 10; tumor located in the upper rectum; 4, the lower rectum; 33). A complete treatment of neoadjuvant CRT was found in 86.5% of patients (95%CI;75.5-97.5%), and an adverse event (grade 3/4) occurred in 4 patients(11.1%). Response rate (PR/CR;RECIST 1.0) was 56.8% (95%CI; 40.8-72.7%), and pathologic response rate (grade2/3) was 48.6% (95%CI; 32.5-64.8%). The median operating time was 448.5 min (IQR 340.5-505.5), and median blood loss was 422.5 mL (IQR 182.5-1125). Grade 3-4 postoperative complications occurred in 6 (16.7%) patients. The most common grade 3 or 4 postoperative complication was anastomotic leakage (2 [5.6%]). The 3-year overall survival rate was 88.5%. The 3-year disease free survival rate was 70.9%. Median length of follow-up was 42 months. Conclusions: A neoadjuvant-synchronus S-1+Radiotherapy for locally advanced rectal cancer is feasible in terms of pathological response, adverse events, accompany with favorable long-term outcome. Clinical trial information: 03396.
Improving safety culture at a large AMC.
Authors: Inga Tolin Lennes, Nie Bohlen, David P. Ryan
Journal: Journal of Clinical Oncology (2014)

105 Background: Building a culture of safety in a large, growing academic oncology practice presents several challenges including: 1) lack of basic knowledge of QI and safety processes, 2) lack of systems thinking and 3) poor cross-disciplinary relationships. In 2011, the MGH Cancer Center piloted a program where groups of cancer center employees convened to address these issues. Safety reporting by physicians was tracked as a metric for improved safety culture. Methods: Quality Rounds are held bimonthly at the main campus of the MGH Cancer Center. A comprehensive group of all members of the Cancer Center including MDs, NPs, PAs, RNs, pharmacists, medical assistants, administrators, financial coordinators, students and members of our patient and family advisory committee are invited to attend. Groups are kept small to facilitate interaction and discussion. The program consists of a didactic section which includes: 1) definitions of quality and types of variation, 2) methods of performance improvement, and 3) safety reporting systems at MGH. Case studies developed for Quality Rounds are discussed. The MGH Cancer Center data regarding safety events on our campus was reviewed. Questions, discussion and personal reflection are encouraged. Results: 188 MGH employees have participated in the Quality Rounds program. Of the participants, 94/188 (50%) were physicians. During the course of the program, physicians have been allowed to repeat attendance once. Of the participating physicians 20/94 (21%) voluntarily repeated the program. Since the implementation of Quality Rounds, physician generated safety reporting has increased 42% over 3 years. Overall reporting by physicians has increased every year since 2011. Pre and post program surveys showed that Quality Rounds shifted the perception that errors are caused by only individuals to a more comprehensive appreciation of the multi-factorial nature of errors in healthcare. Conclusions: Implementing a program designed to teach the basic tenets of healthcare quality and safety to a wide variety of cancer center employees was feasible. Physicians were a majority of participants and their involvement in the quality and safety program at MGH has increased as evidenced by increased numbers of filed safety reports after participation.
Identification and validation of an 8-gene expression signature for predicting high-Fuhrman grade renal cell carcinoma.
Authors: Fangning Wan, Yao Zhu, Chengtao Han, Qinghua Xu, Bo Dai, Hailiang Zhang, Guohai Shi, Weijie Gu, Dingwei Ye
Journal: Journal of Clinical Oncology (2016)

526 Background: Clear cell renal cell carcinoma (ccRCC) is a malignancy with heterogeneous outcomes. Currently, renal mass biopsies are commonly employed to extract disease characteristics and aid prognosis. Although the pathological diagnosis of malignant disease is accurate in contemporary reports, the classification of Fuhrman grade using biopsy specimens is still far from promising. Our aim is to generate a signature biomarker to distinguish high grade ccRCC that could be readily applied to clinical biopsy samples. Methods: Using the Cancer Genome Atlas (TCGA) database, a gene expression signature was developed to distinguish high-grade (G3/4) from low-grade (G1/2) disease. The expression profile was further validated for performance and clinical usage in 283 frozen renal cancer samples and 127 ex-vivo renal mass biopsy samples, respectively. The area under curve (AUC) was used to quantify discriminative ability and was compared using the De-long test. Results: Using the development dataset, we identified a 24-gene signature for high-grade disease with an AUC of 0.884. After applied to the replication dataset, an eight-gene profile was defined and achieved an AUC of 0.823. The accuracy of 8-gene panel was maintained in the RMB samples (AUC = 0.821). Conclusions: Using a two-stage replication design, we validated an eight-gene expression signature for predicting high Fuhrman grade of ccRCC. This tool may help to reveal the characteristics of ccRCC biopsy specimens.