tbuckley/cabot-search huggingface dataset:
Primary gastric diffuse large B-cell lymphomas: Single center experience.
Authors: Nur Soyer, Fergun Yilmaz, Nazan Ozsan, Fahri Sahin, Guray Saydam, Murat Tombuloglu, Mine Hekimgil, Filiz Vural
Journal: Journal of Clinical Oncology (2014)

e19535 Background: Primary gastric diffuse large B cell lymphomas (PG- DLBCL) are rare entities and their optimal treatment is not well documented. The combination chemotherapies consist of cyclophosphomide, doxorubicin, vincristin and prednisolone (CHOP) is mostly used for PG-DLBCL but effect of addition of rituximab (R-CHOP) to the treatment is not precise. Methods: In this study, we retrospectively analyzed the data (clinical characteristics, type of treatments, response rate, progression free survival and overall survival rates and the prognostic factors effecting survival) of 45 patients diagnosed as PG-DLBCL in 15 years. Results: 38 patients were treated with R- CHOP and 7 of them were treated with CHOP regimen. The median duration of follow up was 30 (range; 1 - 114 months) months and the complete response rate was 86.6 %. The median overall survival (OS) and disease free survival (DFS) rates were 116 (range; 5.8 – 226) and 110 (range; 0-243) months respectively. Expected five year OS and DFS were 81.3 % and 83.9 % respectively. We could not find a statistically difference between the patients treated with or without rituximab in terms of OS rates (p>0.05) but the median DFS was statistically lower in patients treated without rituximab (57.1% versus 89.5%) (p=0.04). There is statistical difference between OS (p<0.0001) and DFS (p=0.001) rates in patients with early and late stage diseases. While five year OS and DFS in patients with early stage (Lugano stage I and II 1) disease were 96.4 % and 96.7% respectively, in patients with late stage disease 50.4 % and 55.9% respectively. Conclusions: In conclusion, although combination therapies with rituximab will affect the DFS rates positively, OS rates were not affected by addition of rituximab to combination regimens. The prognosis was favorable in patients with early stage disease who were treated with R-CHOP regimens but patients with disseminated disease addition of rituximab doesn't change the less favorable prognosis. Prospective randomized large cohort studies are needed to generate guidelines for the treatment of PG-DLBCL.
Comparative Analysis between RQ-PCR, Digital-Droplet-PCR and Next-Generation-Sequencing (NGS) of Immunoglobulin/T-Cell Receptor Gene Rearrangements to Monitor Minimal Residual Disease in Adult Acute Lymphoblastic Leukemia Patients
Authors: Irene Della Starza, Lucia Anna De Novi, Alessandra Santoro, Salemi Domenico, Marzia Cavalli, Roberta Soscia, Francesca Paoloni, Lucia Menale, Valerio Apicella, Caterina Ilari, Antonella Vitale, Marco Vignetti, Renato Bassan, Sabina Chiaretti, Anna Guarini, Robin Foà
Journal: Blood (2018)
Impact of race on outcome of stage II colon cancer subjects not receiving adjuvant therapy.
Authors: Amy L. Cleveland, Eric R Siegel, Rangaswamy Govindarajan
Journal: Journal of Clinical Oncology (2014)

6574 Background: The etiology of racial disparity in colorectal cancer outcome has been controversial. Higher mortality rates (per 100,000/yr.) of 31.4 in African Americans [AA] compared to 21.4 in Caucasians [C] could be due to biology or treatment-related variables. Access to care within the Veterans Affairs [VA] health system is similar for all veterans. The outcome of subjects with stage II colon cancer treated with surgery alone in the VA system was investigated in order to evaluate the possibility of difference in tumor biology rather than patient and treatment related variables. Methods: A retrospective study of recurrence and overall survival [OS] comparing AA vs. C was conducted using data from the VA health system’s 10-institution database (VISN-16) from 10/1/1996 to 3/31/2010 adjusted for age, gender, T-stage, and number of lymph nodes (LN) resected at the time of surgery. None of the subjects received adjuvant therapy. Patient characteristics were analyzed via chi-square tests. OS was analyzed using Kaplan-Meier methods. Results: There were 226 deaths among 513 subjects during 2,645.4 total years of follow-up. Median OS was 9.9 years in AA versus 7.9 years in C (log-rank p=0.22). Age, gender, T stage, and number of lymph nodes were balanced between races (see table). Conclusions: There was no difference in OS of AA compared to C with stage II colon cancer subjects treated with surgery alone. The two groups had no statistical difference in stage, median age, gender, lymph node resection or T stage. These results indicate that the difference in the outcome of AA and C with colon cancer may not be due to tumor biology. Variable African American Caucasian p Value N=513 135 (26%) 378 (74%) Median age (range) in years 71 (40-91) 71 (44-87) 0.98 ≥12 lymph nodes excised 69 (49%) 175 (46%) 0.57 T stage T1 1 (0.7%) 5 (1.3%) 0.83 T2 3 (2.2%) 7 (1.8%) T3 60 (44%) 182 (48%) T4 69 (51%) 180 (48%) Gender 97.0% male 97.9% male 0.82 Recurrence 18/120 (15%) 37/346 (11%) 0.21 Median overall survival (years) 9.94 7.91 0.22
Abstract 16209: Causes of Troponin Elevation and Associated Mortality in Young Adults
Authors: Candace Wu, Avinainder Singh, Bradley Collins, Amber Fatima, Arman Qamar, Jon Hainer, Josh Klein, Petr Jarolim, Khurram Nasir, Marcelo F Di Carli, Deepak L Bhatt, Ron Blankstein
Journal: Circulation (2017)

Background: While increased serum troponin levels are often due to myocardial infarction (MI), increased levels may also be found in a variety of other clinical scenarios. Although these causes of ...
An Informative Prognostic Ability of New Scoring Model in Myelodysplastic Syndrome: Short Telomere Length and Somatic Mutation Integrated with IPSS-R
Authors: Hee Sue Park, Junseo Park, Kyongok Im, Sung-Min Kim, Jiwon Yun, Dajeong Jeong, Dong-Yeop Shin, Sang Mee Hwang, Sung-Soo Yoon, Dong Soon Lee
Journal: Blood (2018)
Clinical validation of a medical device for in vivo isolation of circulating tumor cells in prostate cancer patients: One-year follow-up.
Authors: Gerit Theil, Kersten Fischer, Thomas Krahn, Andre Schumann, Kathrin Haubold, Antje Stresemann, M.Raschid Hoda, Kolja Hegel, Klaus Luecke, Paolo Fornara
Journal: Journal of Clinical Oncology (2014)

e16027^ Background: The presence of circulating tumor cells (CTCs) in peripheral blood of patients indicates tumor cell extravasation and is a prerequisite for formation of metastasis. Detection and characterization of these rare cells could provide a powerful approach for early disease diagnosis as well as disease monitoring. Primary goal of this pilot study was to demonstrate isolation of CTCs in prostate cancer patients (PCa) by using an in vivomedical device. Methods: The GILUPI CellCollector, an in vivo medical wire coated with antibodies against epithelial cell adhesion molecule (EpCAM), was inserted into a cubital vein for 30 minutes. To confirm binding of CTCs to the device, immuncytochemistry staining for cytokeratins and CD45 was performed ex vivo. So far, 248 applications in 21 metastasized PCa (PCa-m), each with up to 8 wire applications, 31 localized PCa (PCa-l) with up to 3 applications, as well as 23 men with benign prostatic hyperplasia (BPH) were evaluated. 90 applications were directly compared to the CellSearch system. In addition, prostate-specific antigen (PSA) and Gleason scores were correlated with CTC counts. Results: CTCs were isolated in 65% of all applications (82% of PCa-m and 48% of PCa-l). Regarding the direct comparison with the CellSearch system, the CellCollector captured CTCs in 53% of PCa-l, the CellSearch system only in 12%. In PCa-m, the CellCollector detected CTCs in 78%, CellSearch system only in 61%. The follow up of PCa-l after radical prostatectomy demonstrates a non-significant variation in the CTC-number (Bland-Altman plot CTC-bias 1.6; SD 3.7). Comparison of ROC-curves in PCa-m indicates that CTC counts provide a higher level of prognostic accuracy as compared to PSA levels (AUC: 0.93 vs 0.81). Interestingly, Kaplan Meier demonstrates a significant difference in overall survival between patients diagnosed with <5 vs >5 CTCs (p 0.027). Conclusions: The CTC detection rate in patients with prostate cancer with GILUPI’s CellCollector demonstrates much better sensitivity compared to the CellSearch system and could provide an important tool for the detection of biomarkers and disease monitoring. Clinical trial information: ISRCTN10403616.
Oxygenated theranostic nanoplatforms with intracellular agglomeration behavior for improving the treatment efficacy of hypoxic tumors
Authors: Jun Zhou, Chencheng Xue, Yanhua Hou, Menghuan Li, Yan Hu, Qiufang Chen, Yanan Li, Ke Li, Guanbin Song, Kaiyong Cai, Zhong Luo
Journal: Biomaterials (2019)
Chromids Aid Genome Expansion and Functional Diversification in the Family <i>Burkholderiaceae</i>
Authors: George C diCenzo, Alessio Mengoni, Elena Perrin
Journal: Molecular Biology and Evolution (2018)

Multipartite genomes, containing at least two large replicons, are found in diverse bacteria; however, the advantage of this genome structure remains incompletely understood. Here, we perform comparative genomics of hundreds of finished β-proteobacterial genomes to gain insights into the role and emergence of multipartite genomes. Almost all essential secondary replicons (chromids) of the β-proteobacteria are found in the family Burkholderiaceae. These replicons arose from just two plasmid acquisition events, and they were likely stabilized early in their evolution by the presence of core genes. On average, Burkholderiaceae genera with multipartite genomes had a larger total genome size, but smaller chromosome, than genera without secondary replicons. Pangenome-level functional enrichment analyses suggested that interreplicon functional biases are partially driven by the enrichment of secondary replicons in the accessory pangenome fraction. Nevertheless, the small overlap in orthologous groups present in each replicon's pangenome indicated a clear functional separation of the replicons. Chromids appeared biased to environmental adaptation, as the functional categories enriched on chromids were also overrepresented on the chromosomes of the environmental genera (Paraburkholderia and Cupriavidus) compared with the pathogenic genera (Burkholderia and Ralstonia). Using ancestral state reconstruction, it was predicted that the rate of accumulation of modern-day genes by chromids was more rapid than the rate of gene accumulation by the chromosomes. Overall, the data are consistent with a model where the primary advantage of secondary replicons is in facilitating increased rates of gene acquisition through horizontal gene transfer, consequently resulting in replicons enriched in genes associated with adaptation to novel environments.
Thyroid peroxidase antibodies in breast cancer.
Authors: Idris Yucel, Yasemin Kemal, Guzin Gonullu, Kubilay Ekiz
Journal: Journal of Clinical Oncology (2014)

e22211 Background: Since Beatson first described the use of thyroid extracts to treat patients with metastatic breast carcinoma more than a century ago, many studies have investigated the relationship between thyroid disorders and breast cancer. Recent reports have focused attention on the possible links between autoimmune thyroid disease and breast carcinoma. The presence of thyroid peroxidase antibodies (TPOab) has been reported to be associated with improved outcome in these patients. This study aimed to evaluate the association between TPOab and clinicopathologic characteristics in breast cancer. Methods: The study included 317 cases of invasive breast cancer treated with mastectomy or breast-conserving surgery at 19 Mayis University Hospital between 2008 and 2012.Serum thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) levels in serum were measured byelectrochemiluminescence immunoassay.Statistical analysiswere performed with chi-square tests. Results: Among the 317 newly diagnosed patients with breast cancer, 253 (79.8 % ) patients with TPOab ≤ 34IU/mL were considered TPOab negative, and 64 (20.2 % ) patients with TPOab > 34 IU/mL as TPOab positive. No cases with distant metastases were found in the 64 patients of the TPOab positive group. However 20 (7.9 % ) of 253 patients without TPOab displayed distant metastases (p = 0.01). TPOab positive patients had higher TSH levels compared to TPOab negatives (2.81 vs 4.48, p=0.000). Although all the patients could not be followed up over the same time period, local recurrence or distant metastasis occured in the TPO positive group in only 1 patient, whereas in the TPO negative group, 15 patients developed metastasis or local recurrence. Conclusions: High TPOab levels have been reported to be an important factor in antibody-dependent cell cytotoxicity, so there may be an association between autoimmune thyroiditis and protective anti-tumor mechanisms. In this study, TPOab was determined to be significantly associated with a lower frequency of distant metastasis in breast cancer. In the future this antibody may be used as an independent prognostic factor but further investigations are needed to confirm this.
Phase I/II study of resiquimod as an immunologic adjuvant for NY-ESO-1 protein vaccination in patients with melanoma.
Authors: Rachel Lubong Sabado, Anna C. Pavlick, Sacha Gnjatic, Crystal M Cruz, Isabelita Vengco, Farah Hasan, Farbod Darvishian, Luis Chiriboga, Rose Marie Holman, Juliet Escalon, Caroline Muren, Crystal Escano, Ethel Yepes, Dunbar Sharpe, Sylvia Adams, Patrick Alexander Ott, Achim A Jungbluth, Linda S. Pan, Ralph Rudolph Venhaus, Nina Bhardwaj
Journal: Journal of Clinical Oncology (2012)

2589 Background: The TLR 7/8 agonist, Resiquimod has been shown to induce local activation of immune cells, production of cytokines, and antigen-presentation by dendritic cells, features desirable for cancer vaccine adjuvants. In this study, we evaluated the safety and immunogenicity of vaccination with NY-ESO-1 protein emulsified in Montanide ISA-51 VG when given with or without Resiquimod in patients with surgically resected stage IIB-IV melanoma patients. Methods: This is a two-part study design. Part I represents an open-label dose-escalation with Resiquimod using 2 cohorts treated with 100ug NY-ESO-1 protein emulsified in 1.25mL Montanide (day1) followed by topical application of 1000mg of the 0.2% Resiquimod gel on days 1 and 3 for cohort-1 (N=3) or days 1, 3, and 5 for cohort-2 (N=3). The cycles were repeated every 3 weeks, total of 4 cycles. Part II of the study is blinded. Patients were randomized to receive 100ug NY-ESO-1 protein emulsified in 1.25mL Montanide (day1) followed by topical application of placebo gel (Arm-A; N=8) or 1000mg of 0.2% Resiquimod gel (Arm-B; N=12) using the dosing regimen established in Part I. Blood samples were collected at baseline, one week after each cycle of vaccination, and at follow-up visit for the assessment of NY-ESO-1-specific humoral and cellular immune responses. Results: Enrollment has been completed. 25/26 patients received all 4 vaccinations. The treatment was generally well-tolerated, with no grade 4 adverse events or study-related deaths. The most common toxicities were mild to moderate and included local injection site reactions (granuloma, pruritus, induration) and systemic flu-like symptoms. One patient experienced a grade 3 syncopal episode that was deemed unrelated to the drug. Another patient experienced a grade 3 injection site necrosis that was possibly related to the study drug and was removed from the study prior to receiving the 4 th vaccine. Conclusions: This study demonstrates the safety of Resiquimod as an adjuvant for NY-ESO-1 protein vaccination. The study will remain blinded until all immune monitoring assays have been completed. An updated abstract will be submitted once the study is unblinded.
Association Between Reimbursement Incentives and Physician Practice in Oncology
Authors: Aaron P. Mitchell, Jason S. Rotter, Esita Patel, Daniel Richardson, Stephanie B. Wheeler, Ethan Basch, Daniel A. Goldstein
Journal: JAMA Oncology (2019)

<h3>Importance</h3> Significant controversy exists regarding whether physicians factor personal financial considerations into their clinical decision making. Within oncology, several reimbursement policies may incentivize physicians to increase health care use. <h3>Objective</h3> To evaluate whether the financial incentives presented by oncology reimbursement policies affect physician practice patterns. <h3>Evidence Review</h3> Studies evaluating an association between reimbursement incentives and changes in reimbursement policy on oncology care delivery were reviewed. Articles were identified systematically by searching PubMed/MEDLINE, Web of Science, Proquest Health Management, Econlit, and Business Source Premier. English-language articles focused on the US health care system that made empirical estimates of the association between a measurement of physician reimbursement/compensation and a measurement of delivery of cancer treatment services were included. The Risk of Bias in Non-Randomized Studies of Interventions tool was used to assess risk of bias. There were no date restrictions on the publications, and literature searches were finalized on February 14, 2018. <h3>Findings</h3> Eighteen studies were included. All were observational cohort studies, and most had a moderate risk of bias. Heterogeneity of reimbursement policies and outcomes precluded meta-analysis; therefore, a qualitative synthesis was performed. Most studies (15 of 18 [83%]) reported an association between reimbursement and care delivery consistent with physician responsiveness to financial incentives, although such an association was not identified in all studies. Findings consistently suggested that self-referral arrangements may increase use of radiotherapy and that profitability of systemic anticancer agents may affect physicians' choice of drug. Findings were less conclusive as to whether profitability of systemic anticancer therapy affects the decision of whether to use any systemic therapy. <h3>Conclusions and Relevance</h3> To date, this study is the first systematic review of reimbursement policy and clinical care delivery in oncology. The findings suggest that some oncologists may, in certain circumstances, alter treatment recommendations based on personal revenue considerations. An implication of this finding is that value-based reimbursement policies may be a useful tool to better align physician incentives with patient need and increase the value of oncology care.
A rank-based randomized phase II design when the phase III design is based on overall survival (OS).
Authors: William Leonard Mietlowski, Fei Ma, Weichao Bao, Yunro Chung, Michael Shi, Patricia Ann Wood, Maria Grazia Porro
Journal: Journal of Clinical Oncology (2014)

6597 Background: Gan (2013) reported that approximately 27% of 120 randomized phase III trials with a primary endpoint of OS had statistically significant outcomes. Ratain (2005) suggests that the low phase III success rate in Oncology may stem from a low positive predictive value (PPV) in phase II trials. There were four 2012 publications that independently reported that the components of tumor assessment were independent predictors of OS. Consequently, we proposed a rank-based (RB) (Lachin 1992) randomized phase II design that differentially weights the risk of death by the type and time of disease progression and the percentage change in tumor burden and compared this design with one based on progression-free survival (PFS). Methods: We chose CONFIRM-2, a randomized phase III trial in second-line colorectal cancer comparing chemotherapy±PTK787 as a negative OS trial (n=855, hazard ratio (HR)=1.00). In the absence of a database for a positive phase III trial based on OS, we constructed two positive-OS phase III trials by oversampling long-term survivors from the CONFIRM-2 database (P1: OS HR=0.75, PFS HR=0.85 and P2: OS HR=0.74, PFS HR=0.72). We simulated 2500 phase II trials (n=150, 80% power based on a one-sided test at the 10% significance level, after 110 events, when PFS is mature) from each of the three phase III trials. We compared the specificity, sensitivity, PPV and negative predictive value (NPV) of the RB method with PFS. Results: See Table. Conclusions: We show that the rank based method may have a substantial increase in specificity and PPV for OS compared to PFS. This may reflect the ability of the components of the tumor measurement process to predict OS since a lack of effect on OS would imply a lack of effect on the components (i.e. very good specificity and PPV). The comparison of sensitivity and NPV appears to depend on the PFS HR. Further studies with other tumor types and treatment modalities are warranted. Clinical trial information: NCT00056446. Positive OS trial Design Operating characteristic Specificity Sensitivity PPV * NPV* P1 RB 0.89 0.56 0.65 0.84 PFS 0.72 0.50 0.40 0.79 P2 RB 0.89 0.77 0.72 0.91 PFS 0.72 0.91 0.55 0.96 * Assuming a prevalence of a positive phase III trial for OS of 27%.
Preclinical assessment of MEK1/2 inhibitors for neurofibromatosis type 2–associated schwannomas reveals differences in efficacy and drug resistance development
Authors: Marisa A Fuse, Christine T Dinh, Jeremie Vitte, Joanna Kirkpatrick, Thomas Mindos, Stephani Klingeman Plati, Juan I Young, Jie Huang, Annemarie Carlstedt, Maria Clara Franco, Konstantin Brnjos, Jackson Nagamoto, Alejandra M Petrilli, Alicja J Copik, Julia N Soulakova, Olena Bracho, Denise Yan, Rahul Mittal, Rulong Shen, Fred F Telischi, Helen Morrison, Marco Giovannini, Xue-Zhong Liu, Long-Sheng Chang, Cristina Fernandez-Valle
Journal: Neuro-Oncology (2019)

Neurofibromatosis type 2 (NF2) is a genetic tumor-predisposition disorder caused by NF2/merlin tumor suppressor gene inactivation. The hallmark of NF2 is formation of bilateral vestibular schwannomas (VS). Because merlin modulates activity of the Ras/Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway, we investigated repurposing drugs targeting MEK1 and/or MEK2 as a treatment for NF2-associated schwannomas.