tbuckley/cabot-search huggingface dataset:
MYC+ relapsed and refractory (R/R) diffuse large b-cell lymphoma (DLBCL): Impact of additional hits and outcomes with subsequent therapy.
Authors: Narendranath Epperla, Kami J. Maddocks, Mohamed Salhab, Julio C. Chavez, Nishitha M. Reddy, Reem Karmali, Elvira Umyarova, Veronika Bachanova, Martha Jane Glenn, Ana Carolina Xavier, Zheng Zhou, Francisco J. Hernandez-Ilizaliturri, Stefan K. Barta, Frederick Lansigan, Amitkumar N. Mehta, Christopher Flowers, Jonathon Brett Cohen, Timothy S Fenske, Mehdi Hamadani, Luciano J Costa
Journal: Journal of Clinical Oncology (2017)

7541 Background: Translocations involving MYC are a hallmark of poor prognosis among patients with newly diagnosed DLBCL. The impact of MYC translocations with or without additional “hits” involving BCL2 or BCL6 in response to salvage therapy and survival in R/R DLCBL is not well defined. Methods: We performed a multicenter retrospective study of 176 patients with R/R DLBCL failing to achieve CR or relapsing within 6 months after completion of upfront chemoimmunotherapy and for whom FISH information on MYC, BCL2 and BCL6 was available. The objectives were to examine the response to salvage therapy, utilization of hematopoietic cell transplantation (HCT) and survival outcomes in MYC- (n = 120), MYC+ single hit (SH, n = 28), and MYC+ double hit (DH, n = 36) R/R DLBCL. Results: Overall response rate to first salvage therapy and utilization of HCT was comparable between the 3 cohorts (Table). 2-year OS was 0% in MYC+ SH, 8.8% in MYC+ DH and 29.9% in MYC- cases (p = 0.001) without difference in OS between SH and DH (P = 0.8). The higher risk of death for MYC+ SH (HR 1.79, 95% C.I. 1.03-3.11, P = 0.03) and MYC+ DH (HR 1.93, 95% C.I. 1.23-3.00, P = 0.004) persisted after adjustment for covariates. For patients who underwent auto-HCT, 2-year OS was 0% in MYC+ SH, 29.3% in MYC+ DH and 55.4% in MYC- cases (p &lt; 0.001) without significant difference between SH and DH (P = 0.8). All 4 MYC+patients who underwent allo-HCT relapsed in &lt; 4 months. Conclusions: MYC+ R/R DLBCL have similar response to salvage therapy than the MYC- counterparts but dismal survival irrespective of additional “hits” and even if HCT can be performed. MYC+ R/R DLBCL represents an unmet medical need and should be prioritized for clinical trials with novel agents and innovative cellular therapies. [Table: see text]
TCT-324 A Five-year and Single-centre Experience on Ultrasound Asssisted, Catheter Directed Thrombolysis in Patients with Pulmonary Embolism at High-Risk and Intermediate-High-Risk
Authors: None Cihangir Kaymaz, Ozgur Akbal, Aykun Hakgor, Hacer Tokgoz, Seda Tanyeri, None Ibrahim Tanboga, None Ali Karagoz, Berhan Keskin, Sevim Turkday, Zubeyde Bayram, Rezzan Deniz Acar, None Cem Doğan, Nihal Ozdemir
Journal: Journal of the American College of Cardiology (2018)
Resource utilization in patients with head and neck cancer: Analysis of CCTG HN6 (NCT00820248).
Authors: Ketan Ghate, Wendy R. Parulekar, Bingshu E. Chen, Alexander Montenegro, Nader Khaouam, Joy S. McCarthy, John Walker, John Waldron, Lillian L. Siu, Ana Johnson
Journal: Journal of Clinical Oncology (2017)

6067 Background: As new treatments for head and neck cancer arise, further information is required regarding resource utilization. The Canadian Cancer Trials Group HN.6 study included collected resource utilization data prospectively on patients with locally advanced squamous cell carcinoma of the head and neck treated with cisplatin or panitumumab plus radiotherapy (RT). Methods: The HN.6 phase III trial enrolled 320 patients across Canada between 2008-2011. The economic analysis was conducted from the societal perspective. Resource utilization was collected prospectively for 3 categories: outpatient, hospitalization and institutionalization (end of life care) at baseline, 8 weeks, every 3 months(mo) for 2 years and every 4 mo until 3 years. Lost productivity questionnaires were collected in the last week of RT. Descriptive statistics were used to summarize the outcomes. Categorical variables were reported by percentage and continuous variables were reported by mean and standard deviation. Results: Of 320 pts randomized, resource utilization and lost productivity data were available for 317 (99%) and 285 (89%) pts, respectively. Eighty nine pts required 130 emergency room visits (mean 1.46±0.85). There were 696 (mean 3.74±3.22) office visits among 186 pts and 367 (mean 3.95±6.43) outpatient visits among 93 pts. Surgeons, radiation oncologists and emergency room physicians were the top three providers of outpatient care with 234 (mean 2.05±1.54), 137 (mean 1.67±1.19) and 118 (mean 1.4±0.78) visits for 114, 82 and 84 pts, respectively. CT scans (286), lab tests (418), x-rays (182) and other tests (400) were conducted in 136, 180, 120 and 194 pts, respectively. Three pts were institutionalized for end of life care (mean 28 days±26.06), and 214 pts were hospitalized (mean 14.5 days±28.8). One hundred and thirteen (41%) pts reported a change in work status at the end of RT. Conclusions: Radical treatment for locally advanced SCCHN is resource intensive. Tracking resources utilized prospectively in clinical trial settings and reporting this information consists of an efficient way to inform health resource allocation decisions. Clinical trial information: NCT00820248.
Postoperative concurrent chemoradiation (CCRT) for non-squamous cell carcinoma (NSCCA) of head and neck.
Authors: Lucksamon Thamlikitkul, Janjira Petsuksiri, Suthinee Ithimakin
Journal: Journal of Clinical Oncology (2017)

e17582 Background: Surgery is the mainstay of treatment for resectable non-metastatic NSCCA of head and neck. Postoperative radiation (RT) is delivered to patients (pt) with high risk for recurrence. Unlike the squamous cell counterpart where survival advantage from adding chemotherapy (CMT) as a radio-sensitizer is evident, the benefit of CCRT is uncertain in NSCCA pt. We hypothesized that CCRT would improve disease free survival (DFS), comparing to RT alone. Methods: NSCCA of head and neck pt who underwent curative surgery and RT at Siriraj hospital from 2006 to 2015 were included in this retrospective study. Patients with residual tumor after surgery or neuroendocrine histology were excluded. The primary outcome was DFS. The secondary outcome was overall survival (OS). Results: We included 139 pt, 99 (71.2%) had RT while 40 (28.8%) had CCRT. Baseline characteristics, including age, gender, primary site, histology and radiation dose were similar between 2 groups. Salivary gland was the most common primary site (67.6%). The most common histology was adenoid cystic carcinoma (35.3%), followed by mucoepidermoid carcinoma (25.9%). Patients who received RT alone had earlier stage (Stage I 29.3%, Stage IVa 14.1%), compared to CCRT group (Stage I 7.7%, Stage IVa 38.5%), p = 0.003. High risk features (positive margin, extranodal extension or ≥ 2 cervical lymph nodes metastasis) were found in 42% and 62% of pt with RT and CCRT, respectively (p = 0.03). In CCRT group, 92% of pt received cisplatin every 3 weeks during RT period. With the median follow-up time of 54.9 months, 3-year DFS was 79.4% and 79.5% in RT and CCRT groups, respectively (p = 0.22). There was no significant difference in 3-year OS between RT and CCRT groups (89.2% vs 89.9%, p = 0.76). Among pt with high-risk features (n = 67, 48.2%), 3-year DFS and OS were not significantly different between treatment groups. However, among pt without high-risk features, 3-year DFS in RT group was significantly higher than CCRT group (84.8% vs 79.0%, p = 0.04). Conclusions: This study demonstrates no survival benefit from adding concurrent CMT to RT following curative surgery in NSCCA of head and neck. Moreover, addition of CMT may be detrimental in pt without high-risk features.
Implementation of dietary education within a multidisciplinary team approach to improve treatment accuracy and efficiency in prostate cancer external beam radiation therapy.
Authors: Taylor L Evans, Jorge Restrepo, Alice V. Cheuk, Shan Li, Nina Bektic-Marrero, George Anthony Dawson
Journal: Journal of Clinical Oncology (2018)

6599 Background: Prostate cancer is the most common cancer in the Veterans Health Administration. Radiation is an important treatment option for prostate cancer patients. Imaging is done before each daily radiation treatment to ensure the radiation beam is aimed accurately. Imaging can be inaccurate due to excess gas or stool in the rectum, which alters the treatment field and leads to delays in the daily treatment schedule, increased radiation exposure due to re-imaging, repetitive staff treatment delivery interventions, and an unsatisfactory veteran experience. Methods: A quality improvement project utilizing A3.9 Box Process Improvement Methodology (problem solving template) was undertaken to address identified gastrointestinal concerns hindering daily treatment. A dietitian integrated services into the radiation oncology clinic by providing dietary education and counseling to avoid gas-producing foods and manage bowel regularity for prostate cancer patients. Daily images were reviewed for accuracy. For 3 months prior to intervention, we examined daily treatment images and documented any interruption in treatment delivery from gas or stool in the rectum as a nutrition-related defect. Initial data analysis revealed that 62 of 195 (31.79%) daily treatment deliveries experienced nutrition-related defects. Results: As a result of changing the radiation therapy process to include dietary education to patients, we experienced a 53% reduction rate in nutrition-related defects (from 31.79% to 14.87%). Calculated cost avoidance showed an annual savings of approximately $19,300 with implementation of a multidisciplinary approach. A total of 120 daily treatment visits and 90 patient treatment hours can be saved annually with this approach. Conclusions: This project improved overall clinic function by implementing a multidisciplinary approach to prostate cancer radiation oncology care, increased patient’s satisfaction, reduced excess radiation exposure, and improved department efficiency.
Genomic profiling of pancreas ductal adenocarcinoma (PDA), actionability, and correlation with clinical phenotype.
Authors: Emmet Jordan, Maeve Aine Lowery, Ryan Ptashkin, Ahmet Zehir, Michael F. Berger, Hannah Maynard, Danielle C. Glassman, Christina M. Covington, Nikolaus Schultz, Ghassan K. Abou-Alfa, James J. Harding, David S. Klimstra, Jaclyn Frances Hechtman, David Michael Hyman, Peter J. Allen, Kenneth H. Yu, David B. Solit, Christine Iacobuzio-Donahue, Steven D Leach, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2016)

4127 Background: Molecular profiling (MP) in cancer has enabled identification of potential actionable drug targets that has prompted attempts to discover clinically validated biomarkers and driver alterations for therapeutic clinical trials. This prospective study assessed if comprehensive genetic analysis of archival paraffin embedded PDA tissue is feasible within a clinically relevant timeframe and can provide predictive and/or prognostic information along with potential targets for therapy. Methods: Archival FFPE samples from patients (pts) who consented prospectively to study were analyzed using the MSK-IMPACT platform, a hybridization capture based next generation sequencing assay for targeted deep sequencing of all exons and selected introns of 410 key cancer genes. Tumor and matched normal libraries were sequenced on an Illumina HiSeq 2500. Sequencing output was processed using a custom analysis pipeline. Demographic and treatment data were prospectively collected. Fisher’s exact tests were performed to look for associations between clinical characteristics and genetic alterations. Results: N = 211 PDA pts were enrolled from Mar 2014-Jan 2016. We report results from the first 201 pts (table 1). N = 121 had curative surgery, 51% remain disease free at time of analysis. CDKN2B (p = 0.019), RB1 (p = 0.019), MDC1 (p = 0.042) and TGFBR2 (p = 0.042) were associated with disease recurrence (DR) post resection. 55% pts were never smokers, SMAD3 mutations (MUT) were seen only in smokers (p = 0.04). RECQL4 MUT were more common in pts < 50 yrs (p = 0.0002). TGFBR2 MUT were more common in metastatic disease (p = 0.009). For the 73 pts who received 1st line platinum, CDKN2A/2B deletions (DEL) were only observed with stable disease/partial response as compared to progressive disease (p = 0.10, 0.18). Conclusions: MP is feasible in PDA pts in a clinically relevant timeframe using FFPE tissue from both primary and metastatic sites. We identified MUT associated with DR, age at diagnosis (dx), platinum response and smoking. N/% Stage at dx: I/II 101 (50%) III 31 (15%) IV 69 (34%) Mean MUT per sample 4 Most frequent MUT KRAS 91% TP53 68% CDKN2A 21% SMAD4 16% ARID1A 12% Most frequent CNA CDKN2A/B DEL 14% SMAD4 DEL 3% ERBB2 AMP 2%
Abstract IA19: Phenotype plasticity—a novel mechanism of targeted therapy resistance
Authors: Joanna Cyrta, David Wilkes, Sung Suk Chae, Matteo Benelli, Rohan Bareja, Davide Prandi, Paola Maria Giovanna Cavaliere, Himisha Beltran, Andrea Sboner, Francesca Demichelis, Mark A. Rubin
Journal: Cancer Research (2018)

Abstract Prostate cancer (PCa) is the most commonly diagnosed cancer and the third highest cause of cancer-related death in men in Europe, where it is responsible for over 90,000 deaths a year. The mainstay of treatment for metastatic PCa is androgen-deprivation therapy (ADT). Although initially effective, the treatment ultimately fails and progression to castration-resistant prostate cancer (CRPC) occurs. Given that CRPC is still driven by hormonal signaling through aberrant activation of the androgen receptor (AR), improved, more potent AR-targeting therapies have been developed for CRPC patients. However, resistance to these therapies ultimately occurs as well. One form of resistance identified by my group results in a phenotypic switch leading to androgen receptor indifference and progression to neuroendocrine prostate cancer (NEPC), which shows a distinct histomorphology and expresses neural-like markers. Unlike more commonly recognized mechanisms of ADT resistance due to AR mutations or amplification, NEPC no longer responds to AR-targeting therapy and has a mean survival of 7 months. There is mounting evidence supporting the role of epigenetic events as a mechanism for transdifferentiation of PCa to an androgen signaling-indifferent state under specific genomic conditions, involving but not limited to TP53, RB1, and PTEN loss. However, the epigenetic regulators at work and the specific changes in the epigenetic landscape are unknown. The SWI/SNF complex is a major epigenetic player, both in regulating normal cell differentiation and in cancer biology. This presentation will focus on novel data supporting the role of alterations in this complex that could contribute to PCa phenotype plasticity. Citation Format: Joanna Cyrta, David Wilkes, Sung Suk Chae, Matteo Benelli, Rohan Bareja, Davide Prandi, Paola Maria Giovanna Cavaliere, Himisha Beltran, Andrea Sboner, Francesca Demichelis, Mark A. Rubin. Phenotype plasticity—a novel mechanism of targeted therapy resistance [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr IA19.
Identification of distinctive patterns in cell signaling pathways in glioblastoma multiforme subtypes using gene expression TCGA data sets.
Authors: Konstantin Volyanskyy, Minghao Zhong, Payal Keswarpu, John T Fallon, Michael Paul Fanucchi, Nevenka Dimitrova
Journal: Journal of Clinical Oncology (2017)

e23162 Background: Cancer is characterized by a variety of heterogeneous genomic and transcriptomic patterns involving highly complex signaling biological pathways. The problem of identification of the factors driving tumor progression becomes even more challenging due to intricate interaction mechanisms between these pathways. Using novel approaches in machine learning, we demonstrate the ability to quantitatively describe characteristic signaling patterns in cancer based on transcriptomic data Methods: We used RNASeq data from 20531 genes in 174 samples of GBM from The Cancer Genome Atlas including 5 major histological subtypes – Classical, G-CIMP, Mesenchymal, Neural, and Proneural, anddeveloped predictive computational framework for molecular subtype differentiation from normal tissue relying on variance based gene selection and random forest algorithm. Results: We obtained a few key findings – (1) genes from cell signaling pathways alone differentiate each subtype from normal tissue with 100% accuracy; (2) predictive genes are specific to each subtype; (3) inferred pathway interactions are also specific to each subtype; (4) typically most of the predictive genes involved in signaling are down-regulated in tumor compared to normal tissue (MAPT, PRKCG, PDE2A, RYR2, ATP1B1, GRN1, GNAO1), however, in each subtype we observed a smaller subset of predictive genes which are highly up-regulated in tumor (ID3, FN1, JAG1, F2R, COL4A1, EDAR, CDK2, CDK4, MFNG, BIRC5, CCNB2). We detected and quantitatively evaluated characteristic signaling pathway involvement across the GBM subtypes for MAPK, RAP1, RAS, Notch, PI3K-Akt, mTOR, FoxO, Jak-STAT, Wnt, cAMP, and Calcium Signaling, providing a unique approximation for each subtype signaling profile. Conclusions: In this study, we identified gene expression profiles and associated signaling pathways for distinguishing GBM Multiforme subtypes from normal tissue. We observed and described a dense complex picture of interacting signaling pathways. The detected interactions may provide clinical insights and could be used to identify potential therapeutic targets, however, more research is needed to confirm this.
Differences in small cell lung cancer genetic profile between disease progression (PD) and partial remission (PR) patients after the standard first-line chemotherapy.
Authors: Yalei Zhang, Yongxin Geng, Yan Hao, Hui Pan, Wenhua Liang, Jun Liu, Fei Cui, Henghui Zhang, Minghui Ge, Jianxing He
Journal: Journal of Clinical Oncology (2018)

e20565 Background: Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with high malignancy, frequent metastases and poor prognosis. SCLC patients are relatively sensitive to radiotherapy and chemotherapy, which are mainly therapies in the clinical of SCLC. However, the puzzle in the therapy was the rapid resistance of tumor cells against chemotherapy and the failure of second-line chemotherapy. The purpose of this study was to use the method of precision medical detecting the genes related to SCLC and the key molecular markers that are suitable for the curative effect of chemotherapy, resulting in realize the molecular prediction of small cell lung cancer. Methods: 24 patients with first-line treatment of SCLC receiving standard chemotherapy (EP) were included, whom were reviewed and categorized into two groups: Disease progression (PD) and Partial remission (PR). Tumor tissues DNA of the patients were detected by using specific target gene capture sequencing technology to discover the gene variation in SCLC and SCLC chemotherapy curative effect related genes were analyzed by bioinformatics methods. Results: TP53,CYP2C19,ZFHX3, BCL2 are the common gene mutations in Chinese SCLC patient population; Common Genes for Copy number variations(CNV) in small cell lung cancer in China: FDPS,SOX2,MAP2K2,PSMA8,MALAT1; The comparative analysis in patients with CNV between PD and PR groups showed EGFR gene copy number variation was detected only in the PR group, and there was a significant difference between the two groups (P < 0.05, Fisher test); The tumor tissue DNA somatic cells single nucleotide variants (SNV), genotypes associated with first-line chemotherapy(EP), Tumor Mutational Burden(TMB) and Copy number instability(CNI) of tumor tissues showed no significant difference between two groups. Conclusions: There was a significant EGFR gene copy number variation difference between the PD and PR groups. The SNV,TMB and CNI of tumor tissues showed no significant difference between two groups.
Potential challenge for second-line treatments of unresectable locally or advanced-stage non-small-cell lung carcinoma unharbored sensitive driver gene mutation: A pilot study of novel antiangiogenesis inhibitor (NCT: 0325672121).
Authors: Zongyang Yu, Jinhuo Lai, Zhiyong He, Zhengwu Xu, Xi Shi, Jing Zhang, Chunwei Xu, Zhongquan Zhao, Wenwu Wang, Xiandong Lin, Wujin Chen, Wencui Kong, Xiaolong Wu, Xiaoyan Huang, Yanhong Shi, Aiping Guo, Ying Chen, Xiangwu Lin, Siyu Chen, Cheng Huang
Journal: Journal of Clinical Oncology (2018)

e21197 Background: Systemic chemotherapy is still as the standard treatment for advanced non-small cell lung cancer (NSCLC) without driver gene mutation. However, the efficacy of second-line treatment requires further improvement. Apatinib is a novel VEGFR-2 tyrosine kinase inhibitor, with activitive anti-angiogenesis . The pilot study explored the efficacy and safety of Apatinib combined with chemotherapy as an alterative second-line treatment paradigm in the unresectable locally or advanced NSCLC patients unharbored driver genes. Methods: A double-arm, open, multicenter clinical trial enrolled patients with unresectable locally advanced or advanced NSCLC unharbored driver gene mutation, and failed first-line chemotherapy. The subjects were randomized into experimental and control groups by 2:1. The experimental group received Apatinib 500mg orally, combined with Docetaxel(75mg/m2) or Pemetrexed(500mg/m2) four cycles, then maintenance of single-agent Apatinib 500mg to disease progression, intolerable toxicity or discontinuation at the patient's request . The control group was administered four cycle chemotherapy by Docetaxel(75mg/m2) or Pemetrexed(500mg/m2) only, then followed up. The primary endpoints was progression-free survival (PFS), while the secondary endpoints were overall survival (OS), disease control rate (DCR), and safety. Results: The median PFS was 6.3 vs. 2.6 months in the experimental vs. control group. The DCR was 86.67 vs. 37.5. The OS was still under follow-up. The common adverse effects included hypertension hand-foot syndrome, fatigue, rash, diarrhea, proteinuria, and bone marrow suppression. Conclusions: Apatinib combined with chemotherapy play significantly superiority of PFS and DCR in the patients with unresectable locally or advanced NSCLC unharbored sensitive driver gene mutation, with toleratable adverse effects. It might be a potential paradigm for second-line treatment of advanced NSCLC.However,further studies are essential to further confirm the efficiency and safety. Clinical trial information: NCT0325672121.