tbuckley/cabot-search huggingface dataset:
Results of interim analysis of the multicenter randomized phase III SENORITA trial of laparoscopic sentinel node oriented, stomach-preserving surgery versus laparoscopic standard gastrectomy with lymph node dissection in early gastric cancer.
Authors: Keun Won Ryu, Young Woo Kim, Jae Seok Min, Hong Man Yoon, Ji Yeong An, Bang Wool Eom, Hoon Hur, Young-Joon Lee, Gyu Seok Cho, Youngkyu Park, Mi Ran Jung, Ji-Ho Park, Woo Jin Hyung, Sang-Ho Jeong, Byung-Ho Nam
Journal: Journal of Clinical Oncology (2017)

4028 Background: The benefits and hazards of laparoscopic sentinel node oriented stomach-preserving surgery, compared to those of laparoscopic standard gastrectomy with lymph node dissection in early gastric cancer (EGC), are unknown. The SENORITA trial investigated the clinical impact of laparoscopic sentinel node oriented stomach-preserving surgery in EGC. Methods: Other than those with absolute indication for endoscopic resection, eligible patients had EGC confined to the mucosa and submucosa, with diameter ≤ 3cm, regardless of histology on preoperative evaluation. Patients were randomized for laparoscopic standard gastrectomy or laparoscopic stomach-preserving surgery. Patients were stratified based on depth (mucosa vs. submucosa) and size (≤ 2cm vs. 2 &lt; ≤ 3cm) of the EGC and by participating institution. The primary endpoint was 3-year disease-free survival (3yDFS). The expected 3yDFS was 97% and non-inferior margin was 5%. 580 patients and 24 events were needed to show non-inferiority with 80% power. One interim analysis was planned after 12 events (50%) occurred. Using the O’Brien-Fleming error spending function, the two-sided nominal significance level for the interim analysis would be 0.0054. Results: From March 2013 to May 2016 462 patients were randomized; analysis was performed in 421 after a dropout of 41 patients. Laparoscopic stomach-preserving surgery was possible in 75.6% by study protocol. Interim analysis was conducted based on 12 events (median follow-up: 15.89 months). The 3yDFS in the laparoscopic standard gastrectomy arm was 96%; the 3yDFS in the laparoscopic stomach-preserving surgery arm was 93%, (99.46% CI: -3.18%, 9.18%). The postoperative complication rates were 15.0% and 12.9%, respectively (p = 0.542). Conclusions: In this interim analysis, laparoscopic sentinel node oriented stomach-preserving surgery did not show non-inferiority for 3yDFS. The follow-up time was not mature enough to evaluate non-inferiority. Further follow-up will elucidate the role of laparoscopic sentinel node oriented stomach-preserving surgery. Clinical trial information: NCT01804998.
Diagnosing squamous cell lung carcinoma on small biopsies: Is less ultimately more?
Authors: Isabel Ruth Preeshagul, Oana Rafael, Kevin M. Sullivan, Doru Paul, Nina Kohn, Nagashree Seetharamu
Journal: Journal of Clinical Oncology (2016)

e18181 Background: Histologic subtyping of lung cancer has significant implications for treatment planning. Accurate diagnosis based on cytology/small biopsy specimens is challenging and frequently determined by morphology, as material is often not sufficient for immunohistochemical studies (IHC). We investigated the concordance between small biopsies and surgical specimens in patients with squamous cell lung cancer (SCC) and the utility of IHC for diagnostic precision in lung cancer subtyping. Methods: We conducted a 5-year retrospective analysis identifying cases of SCC diagnosed on cytology/small biopsies ± IHC with subsequent surgical specimens when available. The number of patients with SCC on surgical biopsy and the concordance between cytology ± IHC was determined. Results: 231 cases were identified. Surgery was performed on 66 cases 28.5% of which 87.9% concurred with cytological diagnosis (95% exact binomial confidence interval (CI):77.5% - 94.6%). 36 subjects with surgical biopsy had IHC data. Of those cytology cases with IHC (n=12), SCC was confirmed by surgery in 91.7% (95% CI: 61.5% - 99.8%). Of those without IHC (n=24), 95.8% were confirmed SCC by surgery, (95% CI: 78.9% - 99.9%). These rates were not different (Fisher’s exact test). All cases with IHC were morphologically squamous. Conclusions: Our data demonstrate that diagnostic precision of identifying SCC by cytology/small biopsy is comparable with or without additional IHC studies. We recommend judicious use of IHC on cytology specimens, reserving it for cases where cytomorphology is equivocal. Tissue should be preserved for molecular analysis, which may have therapeutic implications. SCC on cytology/ small biopsies n Follow-up surgical biopsy n (%) SCC confirmed on surgical biopsy n (%) Surgical diagnosis other than SCC Adenocarcinoma n (%) Large cell carcinoma n (%) Neuroendocine carcinoma n (%) Small cell carcinoma n (%) 231 66 (28.5) 58 (87.9) 5 (2) 1 (0.04) 1 (0.04) 1 (0.04)
Expression of NY-ESO-1 cancer testis antigen in prostate cancer.
Authors: Rohit K. Jain, Bo Xu, Rutika Jitesh Mehta, Elena Pop, James Mohler, Kunle Odunsi, Gurkamal S. Chatta
Journal: Journal of Clinical Oncology (2017)

e16544 Background: Poor outcomes in castrate resistant prostate cancer (CRPC) patients is a growing concern urging the need for innovative treatments. Cancer testis antigens (CTAs) like NY-ESO-1 are aberrantly expressed in several cancers including prostate cancer (PC). Given its tumor-restricted expression and ability to elicit spontaneous cytotoxic &amp; antibody-mediated immune responses, NY-ESO-1 shows promise as an immunotherapy target. With the expertise of RPCI in NY-ESO-1 targeted therapeutics and limited information on NY-ESO-1 expression in CRPC, we sought this study. Methods: Immunohistochemical expression of NY-ESO-1 was analyzed in a series of PC samples from 2 different institutions. Two TMAs consisted of triplicate cores from 37 patients with localized PC (with cores from cancerous areas &amp; the normal tissue adjacent to it), and 36 mCRPC patients. We also included 17 mCRPC whole sections for analyses. Intensity and percentage of NY-ESO-1 staining were recorded. The intensity was characterized as low (0-1+) and high (2-3+). Results: The median age in this cohort was 62 years. NY-ESO-1 IHC was positive for cytoplasmic staining in 33 of 111 (26.4%) evaluable cases including 41% in localized PC, 22.6% in benign areas adjacent to tumor, and 35.5% in CRPC. 23 (18.4%) had 1+, 7 (5.6%) had 2+ and 3 (2.4%) had 3+ cytoplasmic staining intensity. No statistical difference was noted in cytoplasmic staining with tumor grade. Gleason grade 8 -10 tumors (33 of 103 [35.4%]) correlated with lower intensity staining (0-1+) pattern (p = 0.028). NY-ESO-1 expression did not correlate with age, race, disease free or overall survival in this cohort. Conclusions: Heterogeneous NY-ESO-1 expression in PC and other tumors is linked to DNA methylation status of its promoter and tumor cells. We noted NY-ESO-1 expression in a third of the patients with CRPC, making it a credible immunotherapeutic target. NY-ESO-1 expression has been shown to be induced and upregulated in cancer by treatment with demethylating agent. Thus targeting NY-ESO-1 in concert with epigenetic modulation maybe therapeutically meaningful in patients with CRPC. Additional efforts at validating NY-ESO-1 expression in CRPC with CLIA approved IHC and qPCR assays (Omniseq) are ongoing and will be reported.
Management of Intraprocedural Anticoagulation in Patients on Non-Vitamin K Antagonist Oral Anticoagulants Undergoing Catheter Ablation for Atrial Fibrillation
Authors: Anne-Céline Martin, Anne Godier, Kumar Narayanan, David M. Smadja, Eloi Marijon
Journal: Circulation (2018)

Catheter ablation has gained a prominent role in the management of atrial fibrillation (AF), with recent data providing positive evidence on hard outcomes, including hospitalization and mortality. Ablation, however, exposes the patient to a rather unique situation, combining risks for both major bleeding and thromboembolic events. In this setting, the critical importance of rigorous anticoagulation during the procedure has been underlined, and the latest international guidelines now recommend performing AF catheter ablation with uninterrupted non-vitamin K antagonist oral anticoagulants (NOACs) and concomitant administration of unfractionated heparin adjusted to achieve and maintain a target activated clotting time of ≥300 seconds. Whereas observational studies and randomized controlled trials support the safety and efficacy of uninterrupted NOAC strategy for AF catheter ablation, recent experiences have questioned this point, showing a greater unfractionated heparin requirement in NOAC-treated patients compared with vitamin K antagonists-treated patients to achieve the target activated clotting time. Important gaps in evidence regarding optimal intraprocedural anticoagulation management need to be acknowledged. A thorough appreciation of the physiology of anticoagulation during AF catheter ablation and the relevant differences between vitamin K antagonists and NOACs is required, while also understanding the limitations of activated clotting time measurement with regard to accurate intraprocedural anticogulation monitoring. This review aims to provide a critical look at this relatively ignored aspect of AF catheter ablation, especially pitfalls in NOAC monitoring, and to identify gaps in knowledge that need to be addressed in the near future.
Re: Riccardo Bertolo, Riccardo Autorino, Giuseppe Simone, et al. Outcomes of Robot-assisted Partial Nephrectomy for Clinical T2 Renal Tumors: A Multicenter Analysis (ROSULA Collaborative Group). Eur Urol 2018;74:226–32
Authors: Zhenjie Wu, Linhui Wang
Journal: European Urology (2018)
Progression-free(PFS) and overall survival (OS) in treatment of BRAF mutation-positive metastatic melanoma: Bayesian network meta-analysis.
Authors: Mok Oh, Abdulaali Almutairi, Nimer Alsaid, Hani M. Babiker, Ali McBride, Ivo Abraham
Journal: Journal of Clinical Oncology (2018)

e21532 Background: First-line treatment options for patients with BRAF-mutated metastatic melanoma include dacarbazine (DTIC), dabrafenib (DAB), dabrafenib + trametinib (DAB+TRA), vemurafenib (VEM), and vemurafenib + cobimetinib (VEM+COB). The optimal treatment option is uncertain given the lack of direct head to head trial evidence. We aimed to indirectly estimate the comparative PFS and OS benefits of these treatment options. Methods: Following a search of PubMed, EMBASE, and Cochrane Library, a Bayesian network meta-analysis using a fixed effect model was performed to estimate hazard ratios (HRs) and 95% credible intervals (CrI) for PFS and OS for pairwise combinations of DTIC, DAB, DAB+TRA, VEM, and VEM+COB. Due to differences in length of follow up, HRs for PFS at month (m) 7 were calculated and utilized in sensitivity analyses. Results: Five randomized controlled trials (RCTs) involving 2,547 patients were included. For PFS, VEM+COB prevailed statistically (HR, 95%CrI) over DTIC (0.20, 0.14–0.28), DAB (0.61, 0.42–0.90), VEM (0.51, 0.39–0.68), but not DAB+TRA (0.89, 0.63–1.25); and DAB+TRA prevailed over DTIC (0.23, 0.18–0.29), DAB (0.69, 0.56–0.85), and VEM (0.57, 0.48–0.69). For OS, VEM+COB prevailed statistically over DTIC (0.49, 0.31–0.80) but not DAB (0.67, 0.40–1.14), VEM (0.65, 0.42–1.01), and DAB+TRA (0.92, 0.56–1.51); DAB+TRA prevailed over DTIC (0.54, 0.41–0.71), DAB (0.73, 0.58–0.92), and VEM (0.71, 0.56–0.89). In sensitivity analyses for calculated 7m PFS, VEM+COB prevailed statistically over DTIC (0.15, 0.28–0.73), DAB (0.45, 0.28–0.73), VEM (0.48, 0.34–0.69), but not DAB+TRA (0.77, 0.50–1.20); DAB+TRA prevailed over DTIC (0.19, 0.14–0.26), DAB (0.58, 0.44–0.77), and VEM (0.62, 0.48–0.80). Conclusions: This indirect treatment comparison demonstrates comparable PFS and OS benefits for VEM+COB and DAB+TRA. In addition, DAB+TRA but not VEM+COB may offer a modest OS benefit over VEM and DAB.
Health-related quality of life throughout the breast reconstruction process.
Authors: Ricardo J. Bello, Chris Devulapalli, Rika Ohkuma, Pablo Baltodano-Fallas, Nelson A. Rodriguez-Unda, Mohamad E. Sebai, Michele A. Manahan, Justin Sacks, Carisa M. Cooney, Gedge D. Rosson
Journal: Journal of Clinical Oncology (2016)

10106 Background: With rising breast reconstruction rates, questions remain on the impact of shifting modalities of reconstruction on quality-of-life (QoL) and their interaction with concurrent treatments, particularly post-mastectomy radiotherapy (PMRT). This study aimed to track QoL in breast reconstruction patients according to reconstructive modality and PMRT. Methods: We prospectively tracked patients undergoing breast reconstruction at our institution from 2010 to 2013 using Breast-Q© and RAND-36 preoperatively, after tissue expander placement, and 6 and 12 months after final reconstruction. We used Wilcoxon signed-rank test, ANOVA, and multiple linear regression to estimate associations between QoL, reconstruction type and timing, and PMRT. Results: Of 200 patients followed, 75 (37.5%) underwent implant-based, 118 (59%) autologous, and 7 (3.5%) pure fat grafting reconstructions. Thirty-three (16.5%) reconstructions were immediate, 146 (73%) staged, and 21 (10.5%) delayed. Fifty-one patients (25.5%) received PMRT. QoL increased after reconstruction for Satisfaction with Breasts, Psychosocial Wellbeing, and RAND-36 Summary Mental Health (p < 0.001), whereas Physical Wellbeing of Abdomen decreased in autologous reconstruction (p < 0.001). Autologous reconstruction was associated with higher Satisfaction with Breasts (p = 0.001) and trended toward higher Physical Wellbeing of Chest (p = 0.073). Delayed reconstruction was associated with higher Satisfaction with Breasts (p = 0.005), Psychosocial Wellbeing (p = 0.033), and Sexual Wellbeing (p = 0.014). After adjusting for confounding, PMRT was associated with lower Psychosocial Wellbeing (p = 0.040) and Sexual Wellbeing (p = 0.036). PMRT showed interaction with type of reconstruction, wherein autologous reconstruction mitigated the negative impact of PMRT on Satisfaction with Breasts (p = 0.032) and Physical Wellbeing of Chest (p = 0.034). Conclusions: Autologous and delayed reconstruction are associated with higher QoL. Importantly, autologous reconstruction may mitigate negative effects associated with PMRT. These findings are important in an economic environment driving trends towards implant-based and immediate breast reconstruction.
Evaluation of exosomal miRNAs from plasma as potential biomarkers for non-small-cell lung cancer.
Authors: Congying Xie, Xiance Jin, Zhenghua Fei, Huafang Su, Lihao Zhao
Journal: Journal of Clinical Oncology (2016)

e20004 Background: Increasing evidence illustrates that exosomal microRNAs in circulating fluids provide a promising way as biomarkers for noninvasive cancer diagnosis. The aim of this study was to evaluate the feasibility of exosomal miRNAs as a diagnostic and prognostic biomarkers in non-small-cell lung cancer (NSCLC). Methods: Blood samples from 40 NSCLC patients and 24 healthy volunteers were collected and matched with age, gender and blood collection time. Plasma exosomes were accessed by 110,000×g ultracentrifugation and visualized by NS300 equipment. The raw data of exosomal miRNA profiles of NSCLC patients and healthy individuals were generated by NGS around 400× read depth and its expression were measured by Taqman probe quantitive PCR. . Results: Exosome numbers were robust in differentiating NSCLC patients from controls [area under the curve (AUC) = 0.800; 95% confidence interval (CI) = 0.685–0.915 P < 0.01]. RNA sequencing data showed 31 miRNAs were up-regulated and 55 miRNAs down-regulated in plasma of NSCLC. TaqMan quantitative RT-PCR analyses indicated that miR-99a, miR-124 and miR-214 were significantly lower in NSCLC patients than in controls. However, miR-21 and miR-126 had significantly higher expression in NSCLC patients. Mir-214 showed high accuracy in discriminating NSCLC patients from healthy controls with a sensitivity of 0.70 and specify of 0.92 (AUC = 0.858, 95% CI = 0.765–0.950 P < 0.001). Furthermore, decreased miR-99a expression was positively correlated with TNM stage (P = 0.007), lymph node metastasis (P = 0.012), and distant metastasis (P < 0.001). Increased miR-21 expression was significantly associated with poorer pathological differentiation (P = 0.015), tumor size (P = 0.033), and lymph node metastasis (P = 0.028). Kaplan–Meier analysis demonstrated that decreased miR-99a expression contributed to poor progression-free survival (PFS) (P < 0.01) of patients. Multivariate analysis indicated that miR-99a was a independent prognostic marker of survival. Conclusions: Exosomal miRNAs in plasma could indicate the progress of NSCLC and a combination of the explored miRNA could serve as a promising biomarker for NSCLS diagnosis and prognosis.
Effect of death receptor 6 (DR6) targeted molecular ultrasound imaging on detection of ovarian tumors at early stage.
Authors: Animesh Barua, Janice M Bahr, Pincas Bitterman, Lauren E Rosen, Michael J Bradaric, Sameer Sharma, Sanjib Basu, Jacques S Abramowicz
Journal: Journal of Clinical Oncology (2016)

e17063 Background: Lack of an early detection test makes ovarian cancer (OVCA) a lethal malignancy. Although transvaginal ultrasound (TVUS) imaging is the currently used method its resolution cannot detect early stage OVCA. This study examined the suitability of a newly developed TVUS imaging agent targeting DR6 expressed by ovarian tumors. The goal was to examine whether DR6-targeted TVUS imaging agents bind with target and whether it improves early OVCA detection by enhancing TVUS signal intensity. Methods: DR6-targeted imaging agents were developed by conjugating anti-chicken DR6 antibodies with microbubbles. Four year old 140 White Leghorn hens (~20% hens of this age group develop spontaneous OVCA) were examined for OVCA by TVUS imaging before (pre-targeted, control) and after (targeted) IV injection of imaging agents. Enhancement in TVUS signal intensities was determined by subtracting gray scale pre-targeted intensities from targeted intensities. Hens were euthanized following imaging and TVUS prediction of OVCA was confirmed. Immunohistochemical (IHC) staining for DR6 and its association with TVUS intensities was examined. Differences in imaging intensity, IHC expression of DR6 and frequency of DR6-expressing microvessels among normal, early stage and late stage OVCA were analyzed by ANOVA and Mann-Whitney test. Results: DR6-targeted microbubbles bound with targets in the ovary and enhanced TVUS signal intensities remarkably. Of 140 hens, 24 had ovarian tumors associated with little or profuse ascites. Compared with pre-targeted, targeted imaging enhanced TVUS signal intensity significantly (P< 0.01) in hens with tumor at early (n = 10) or late stage (n = 14) OVCA. Gross examination confirmed TVUS prediction of tumors. IHC intensity of DR6-expresssion and frequency of DR6-expressing microvessels were significantly higher (P< 0.01) in hens with OVCA and confirmed the higher TVUS signal intensities (normal vs OVCA = 74X105 vs 88X105 in 20,000μm2area) in these hens. Conclusions: The results of this study suggest that DR6-targeted imaging agents enhance the resolution of TVUS imaging for early OVCA detection and will be a foundation for clinical studies. Support: DOD #W81XWH-14-1-0315
Distinct HLA-DPB1 Matching of Unrelated Donors for Malignant and Non-Malignant Indications Is Critical in Pediatric Hematopoietic Stem Cell Transplantation
Authors: Kremena Todorova, Verena Wiegering, Gabriele Strauss, Matthias K. Eyrich, Maximilian Gorelashvili, Viktoria Buck, Sebstian Voigt, Joern-Sven Kuehl, Wolfram Ebell, Harald Schulze
Journal: Blood (2017)
PREvalence of BRCA mutations and correlations with Demographic and clinical characteristICs in paTients with ovarian, fallopian tube or primary peritoneal cancer in Romania (PREDICT)
Authors: C.L. Cebotaru, D.L. Stanculeanu, D.M. Median
Journal: Annals of Oncology (2018)

Background: The epidemiology of ovarian cancer in Romania is not well characterized and only few limited regional data are available. Moreover, the BRCA status in patients with homologous recombination-deficient tumorsis not known and no data about dominant founder mutations exist. BRCA1/2 are tumor suppression genes critical to DNA repair through homologous recombination in response to DNA damage. Around 13% of high-grade serous ovarian cancers is attributable to germline BRCA mutations. Trial design: This is an observational, retrospective, national, multicentre study aiming to describe the prevalence of BRCA mutations in patients with platinum-sensitive high-grade serous ovarian, fallopian tube or primary peritoneal cancer. As the link between BRCA1/2 mutation and ovarian cancer is well known, the primary objective of this study is to describe the prevalence of germline BRCA mutations in Romania. Secondary objectives will explore the correlations between mutational status and demographic and clinical characteristics and identify any dominant founder mutations. Data from 234 patients tested between April 2016 –April 2017 in 47 oncology centers, will be analyzed. Data collection was made from the patient's files, by investigators, as no databases exists in Romania. It is estimated that clinical study report will be finalized by September 2018. Variables explored: BRCA status, age, weight and/or BS, parity,personal history of breast cancer, family history of cancer, stage at diagnosis, ECOG performance status, number of platinum-based chemotherapy lines, progression free interval, smoking. Clinical trial identification: D133FR00135 Observational Study. Legal entity responsible for the study: AstraZeneca. Funding: AstraZeneca. Disclosure: C.L. Cebotaru: Advisory board: Boehringer Ingelheim, Novartis, Pfizer; Lecture fees: AstraZeneca, BMS, Bayer, Ipsen, Astellas; Travel grants: Alvogen, Merck Serono, Boehringer Ingelheim; Educational grants: AstraZeneca. D.L. Stanculeanu: Grant/Research Support: Sandoz, Roche; Speaker's Bureau: AstraZeneca, Astellas, Roche, BMS, Jonson and Jonson, Pfizer, Boehringer Ingelheim, Sandoz; consultant: AstraZeneca, Astellas, Roche, BMS, Pfizer, Boehringer Ingelheim, Sandoz. D.M. Median: Advisory role: Roche, Pfizer; Lecture fees: AstraZeneca, Teva, Roche, Sandoz; Travel grants: Alvogene, A&D Pharma; Educational grants: Pfizer, AstraZeneca, Roche; Institutional grants: Novartis, Lilly, Samsung Bioepis, Tesaro, Roche, Boehringer Ingelheim.