tbuckley/cabot-search huggingface dataset:
Paclitaxel plus nedaplatin vs. paclitaxel plus carboplatin in women with epithelial ovarian cancer: A multi-center, randomized, open-label, phase III trial.
Authors: Li Li, Qingqing Zhuang, Zeyi Cao, Ru Tie Yin, Yaping Zhu, Lirong Zhu, Xing Xie, Youzhong Zhang, Li Li, Qiang Wu, Jianhua Zheng, Qi Zhou, Xiaoping Li, Lingying Wu, Youji Feng, Changyu Wang
Journal: Journal of Clinical Oncology (2018)

e17519 Background: The multi-center, randomized, open-lable, phaseⅢ trial discussed in the present study was performed to compare clinical outcomes of nedaplatin (NDP) plus paclitaxel, and carboplatin (CBP) plus paclitaxel for treatment of epithelial ovarian cancer (EOC). Methods: In the current study, 182 patients with International Federation of Gynecology and Obstetrics (FIGO) stage II–IV EOC were randomly assigned to receive NDP plus paclitaxel or CBP plus paclitaxel at 3-week intervals for a total of six courses. The primary endpoints were progression-free survival rate (PFS) and overall survival rate (OS). The secondary endpoints were toxicity profiles. Results: The median follow-up was 44.63 months [95% confidence interval (CI) 33.67-46.47 months] for the NDP group and 47.63 months (95% CI 45.13-49.07 months) for the CBP group. Overall, there was no significant difference in PFS and OS between two groups (P = 0.09 for PFS, and P = 0.65 for OS). For the patient with FIGO stage III-IV EOC, the NDP plus paclitaxel regimen significantly prolonged PFS (P = 0.02) but did not result in improved OS (P = 0.53) when compared with the CBP group. The patients in the NDP plus paclitaxel group also exhibited a lower incidence rate of grade 3 or 4 leucopenia (P = 0.03). Other hematological and non-hematological toxicity profiles were similar between the two groups. Compared with CBP plus paclitaxel regiments, NDP plus paclitaxel regiments achieved comparable survival outcomes and similar toxicity profiles. However, patients of FIGO stage III-IV EOC may experience more clinical benefits form NDP plus paclitaxel treatment, including a prolonged PFS and a lower incidence rate of leucopenia. Conclusions: Therefore, an NDP-based regimen may be an alternative choice when using platinum-based agents to treat EOC. Clinical trial information: ChiCTR-TRC-11001333.
Cytoreductive surgery (CRS) and heated intra-peritoneal chemotherapy (HIPEC) in the management of peritoneal carcinomatosis in a community setting.
Authors: Maurice Arregui, Kirpal Singh, Niraj K. Gupta, Gabriel Arevalo, Rocio Fuentes, Victor Maciel, Brandon Keith Martinez, Vinay Mathavan, Erin MaCammack, Tariq Aziz, Marius Callin, Chad Davis
Journal: Journal of Clinical Oncology (2016)

e15668 Background: CRS followed by HIPEC is an invaluable tool in the management of peritoneal carcinomatosis (PC). Our objective was to analyze the efficacy and treatment related morbidity/mortality at our cancer program. Methods: A retrospective analysis of a prospective data base was done. 66 patients with PC were treated between 1/99 and 2/2013. Perioperative morbidity/mortality data along with long-term follow-up data was collected. Eight patients had more than one procedure. Patients were treated with curative and palliative intent. Adverse events were recorded according to Dindo's classification. Median follow-up was 47 months. Results: 66 patients underwent CRS + HIPEC. M/F ratio was, 28/38. Median age was 57years. Primary diagnoses were, Appendiceal (47), Colorectal (15), Ovarian, mesothelioma, liosarcoma and PMP(1)each. Mean Peritoneal Cancer Index (PCI) was 22.8 (4-39). Mean OR time was 741 min (300-1200). Mean blood loss 689.2 ml. Grade III/IV toxicities were seen in 15% of the patients. The common toxicities were, respiratory (33%), GI (31%) and hematologic (20%). Complete/Near complete resection was achieved in 72% of the cases. 30 day mortality was 4.5% (3/66). All 3 deaths were from sepsis. Average length of stay was 15.4 days ( 6-37). Mean overall survival for all the patients was 657.6 days (14-4822). The overall survival was depended on the diagnosis and the PCI. Conclusions: CRS and HIPEC is an effective tool in the management of PC for appropriately selected patients and can be performed even at community cancer programs with required expertise. Our efficacy and safety data correlates well with the other published studies.
Multi-omic molecular profiling of pancreatic neuroendocrine tumors.
Authors: Rishi Patel, R Joseph Bender, Quanlin Li, Dana Pan, Richard Tuli, Michael J. Pishvaian, Andrew Eugene Hendifar
Journal: Journal of Clinical Oncology (2017)

e15685 Multi-omic Molecular profiling of Pancreatic Neuroendocrine Tumors Authors: Rishi R Patel, Joseph Bender, Quanlin, Dana Pan, Lynn Matrisian, David Halverson, Emanuel Petricoin, Subha Madhavan, Richard Tuli, Michael Pishvaian, Andrew Hendifar; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA Background: Pancreatic Neuroendocrine Tumors (pNETs) are a rare malignancy with an incidence of 2 per 1,000,000. In 2016, the Pancreatic Cancer Action Network and Perthera initiated the Know Your Tumor (KYT) initiative in an effort to improve coordination across clinical spectrums in regards to multi-omic molecular profiling and clinical outcomes data pertaining to pancreatic tumors. We used data collected as part of the KYT effort to describe demographic, clinical and genomic data for pNETs. Methods: From 2015 - 2016, 15 patients with pNET were enrolled in the KYT program, which helped facilitate tissue acquisition, clinical data collection, and multi-omic molecular profiling. Using the data collected, we performed Fisher’s Exact to assess for statistical significance between genetic alterations and histology. Results: 11/15 of our patients were female. 8/15 had metastatic disease at the time of diagnosis, while 5/15 had locally advanced disease at the time of diagnosis. 29 genetic alterations were pathogenic. KMT2D and MEN1 were jointly found in 6/15 of our patients. 5/15 with pathogenic alterations in p53, 2/15 with DAXX, 5/15 with alteration in RB1, and 2/15 with alterations in PTEN and TSC2. 2 patients had pathologic alterations in mismatch repair genes, MLH1 and MSH1. Two genes had a statistically significant relationship to pNET histology. Alterations in MEN1 (p = 0.0097) and SPTA1 (p = 0.0333) were associated with high grade tumors (p = 0.0097). Of note, both of the patients under the age of 35 shared an alteration in ATR, which none of the other enrollees expressed. Conclusions: In PNETS, multi-omic profiling through the KYT program identified targetable alterations in several key pathways. Outcome data will be explored.
<i>TP53</i> Outperforms Other Androgen Receptor Biomarkers to Predict Abiraterone or Enzalutamide Outcome in Metastatic Castration-Resistant Prostate Cancer
Authors: Bram De Laere, Steffi Oeyen, Markus Mayrhofer, Tom Whitington, Pieter-Jan van Dam, Peter Van Oyen, Christophe Ghysel, Jozef Ampe, Piet Ost, Wim Demey, Lucien Hoekx, Dirk Schrijvers, Barbara Brouwers, Willem Lybaert, Els G. Everaert, Daan De Maeseneer, Michiel Strijbos, Alain Bols, Karen Fransis, Nick Beije, Inge E. de Kruijff, Valerie van Dam, Anja Brouwer, Dirk Goossens, Lien Heyrman, Gert G. Van den Eynden, Annemie Rutten, Jurgen Del Favero, Mattias Rantalainen, Prabhakar Rajan, Stefan Sleijfer, Anders Ullén, Jeffrey Yachnin, Henrik Grönberg, Steven J. Van Laere, Johan Lindberg, Luc Y. Dirix
Journal: Clinical Cancer Research (2018)

Abstract Purpose: To infer the prognostic value of simultaneous androgen receptor (AR) and TP53 profiling in liquid biopsies from patients with metastatic castration-resistant prostate cancer (mCRPC) starting a new line of AR signaling inhibitors (ARSi). Experimental Design: Between March 2014 and April 2017, we recruited patients with mCRPC (n = 168) prior to ARSi in a cohort study encompassing 10 European centers. Blood samples were collected for comprehensive profiling of CellSearch-enriched circulating tumor cells (CTC) and circulating tumor DNA (ctDNA). Targeted CTC RNA sequencing (RNA-seq) allowed the detection of eight AR splice variants (ARV). Low-pass whole-genome and targeted gene-body sequencing of AR and TP53 was applied to identify amplifications, loss of heterozygosity, mutations, and structural rearrangements in ctDNA. Clinical or radiologic progression-free survival (PFS) was estimated by Kaplan–Meier analysis, and independent associations were determined using multivariable Cox regression models. Results: Overall, no single AR perturbation remained associated with adverse prognosis after multivariable analysis. Instead, tumor burden estimates (CTC counts, ctDNA fraction, and visceral metastases) were significantly associated with PFS. TP53 inactivation harbored independent prognostic value [HR 1.88; 95% confidence interval (CI), 1.18–3.00; P = 0.008], and outperformed ARV expression and detection of genomic AR alterations. Using Cox coefficient analysis of clinical parameters and TP53 status, we identified three prognostic groups with differing PFS estimates (median, 14.7 vs. 7.51 vs. 2.62 months; P &amp;lt; 0.0001), which was validated in an independent mCRPC cohort (n = 202) starting first-line ARSi (median, 14.3 vs. 6.39 vs. 2.23 months; P &amp;lt; 0.0001). Conclusions: In an all-comer cohort, tumor burden estimates and TP53 outperform any AR perturbation to infer prognosis. See related commentary by Rebello et al., p. 1699
Continuation of epidermal growth factor tyrokine kinase inhibitor with or without chemotherapy beyond gradual progression in non-small cell lung cancer patients.
Authors: Ling Peng, Qiong Zhao, Yina Wang, Haibo Mou, Yemin Tang, Danna Hu, Lei Zeng, Bo Zhao
Journal: Journal of Clinical Oncology (2016)

e20531 Background: Several studies have demonstrated that continuous administration of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) could provide addtitional survival benefit for advanced non-small cell lung cancer (NSCLC) patients who had gained benefit from prior EGFR TKI therapy. However, whether EGFR TKI combined with chemotherapy could prolong survival in patients of gradual progression is still unclear. The present study was conducted to evaluate the clinical outcome of continuation of EGFR TKI monotherapy or combination with chemotherapy in such a clinical setting. Methods: We retrospectively reviewed our single center database and analyzed all NSCLC patients treated with EGFR TKI at our institutions from Feb 2012 to Nov 2015. All eligible patients must meet the criteria of gradual progression. The main clinical endpoints were time interval between PFS1 (gradual progression or death) and PFS2 (off-EGFR TKI progression) and overall survival (OS). Results: A total of 51 patients were included in our study. Baseline characteristics were well balanced. Exon 19 deletion mutations and L858R point mutations were detected in 16 and 8 patients, respectively. Twenty one, 22 and 8 patients were treated with EGFR TKI in the 1st, 2nd and 3rd line setting. The median PFS1 for EGFR TKI monotherapy group and combination group was 366 and 249 days, respectively (P = 0.017). The median PFS2 was 532 and 395 days (monotherapy vs combination), respectively (P = 0.009). The time interval from PFS1 to PFS2 was 161 and 122 days (monotherapy vs combination), respectively (HR = 1.93, 95% CI: 0.96 - 3.89, P = 0.065). The median OS was not reached in the monotherapy group, and 799 days in the combination group (HR = 1.56, 95% CI: 0.62 - 3.91, P = 0.344). There were no statistical differences between two groups in terms of the time interval from PFS1 to PFS2 and OS. Conclusions: Our results showed that compared with EGFR TKI monotherapy, the combination of chemotherapy beyond gradual progression may not confer survival benefit to NSCLC patients, although there were no statistical significance. Further prospective studies are warranted. Clinical trial information: NCT01998061.
Mortality in young adults with Ewing sarcoma treated at specialized cancer centers in California.
Authors: Elysia Marie Alvarez, Marcio H. Malogolowkin, Brad Pollock, Qian Li, Neyssa Marina, Theodore Wun, Theresa Keegan
Journal: Journal of Clinical Oncology (2017)

10538 Background: Ewing sarcoma is a rare malignancy of the soft tissue or bone that is most frequently seen in children and adolescents. One study suggested that care at specialized cancer centers (SCC) may mitigate survival disparities associated with public insurance in patients with sarcoma, but no large population-based studies have considered how location of care affects survival outcomes. Methods: We performed a retrospective, population-based cohort analysis of patients hospitalized within one year of diagnosis with primary Ewing sarcoma between 2000–2013 using the California Cancer Registry linked with state hospitalization data. Patients were divided into two groups based on whether they received inpatient treatment at a SCC [Children’s Oncology Group (if age ≤25) and/or National Cancer Institute-designated center] or not. We excluded 12 patients whose location of cancer treatment could not be determined. Multivariable Cox proportional hazards regression identified factors associated with mortality. Results are presented as adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results: Of the 470 patients with newly diagnosed Ewing sarcoma, 40% were female, 52% were non-Hispanic white, and 53% had private health insurance. Sixty-one percent received their inpatient care at a SCC. Multivariable analysis across all ages demonstrated that higher mortality was associated with increasing age, metastatic disease, and large tumors, but mortality was not impacted by treatment at an SCC (HR 0.77, CI: 0.55-1.08; p = 0.134). However, when analyses were stratified by age, treatment at a SCC was associated with lower mortality among patients ages 19–39 years, but not among younger or older patients, and this association was only apparent within 2 years of diagnosis (HR = 0.43, CI: 0.23-0.79; p = 0.007). Conclusions: Our results suggest that treatment for Ewing sarcoma at a SCC significantly improves survival in young adults adjusted for other factors known to be associated with poor prognosis (metastatic disease, larger tumor size and older age). The lower mortality in this age group may be due to access to clinical trials and other specialized services specific to young adults available at SCCs.
Subtype‐specific inherited predisposition to pemphigus in the Chinese population
Authors: S.Y. Zhang, X.Y. Zhou, X.L. Zhou, Y. Zhang, Y. Deng, F. Liao, M. Yang, X.Y. Xia, Y.H. Zhou, D.D. Yin, P. Ojaswi, Q.Q. Hou, L. Wang, D.Y. Zhang, D.M. Xia, Y.Q. Deng, L. Ding, H.J. Liu, W. Yan, M.M. Li, W.T. Ma, J.J. Ma, Q. Yu, B. Liu, L. Yang, W. Zhang, Y. Shu, H. Xu, W. Li
Journal: British Journal of Dermatology (2018)

Pemphigus is a group of rare life-threatening mucocutaneous autoimmune diseases, presenting mainly as two subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Inherited predispositions to pemphigus have long been speculated but they remain poorly understood.To identify common and specific nongenetic and genetic factors associated with pemphigus and its subtypes in the Chinese population.A genome-wide association study (GWAS) was performed in 496 unrelated patients with pemphigus (including 365 with PV and 104 with PF) and 1105 controls without pemphigus.A sex preference was observed only in PV (57·5% female) and not in PF (47·1% female). For male patients only, the mean age at diagnosis was significantly lower for PV than for PF (P < 0·001). The strongest associated single-nucleotide polymorphisms are in the human leucocyte antigen (HLA) region: rs70993900 (PV; P = 1·5 × 10-45 ) and rs9469220 (PF; P = 1·1 × 10-8 ). HLA-DQB1*05:03 ranks at the top (P = 4·7 × 10-40 ; odds ratio 12·4) in both subtypes, with significantly different risk allele frequency (RAFPV = 34·2% vs. RAFPF = 18·8% vs. RAFcontrol = 4·4%), whereas HLA-DRB1*14:01 and HLA-DRB1*04:06 are PV specific. HLA-DQB1*03:03 and HLA-DQB1*03:02 show significant subtype specificity in opposite directions. All of these associations were validated in the replication series with 147 cases of pemphigus and 604 controls. Multiple novel non-HLA susceptibility loci were also identified in the GWAS.This study represents the largest GWAS on pemphigus in the Chinese population published to date, and has allowed us to identify HLA haplotypes significantly shared between or specific to the two main subtypes of pemphigus.
TCT-120 Long-term Outcomes in Women and Men Following Percutaneous Coronary Intervention: An individual patient data pooled analysis from 21 randomized trials
Authors: Ioanna Kosmidou, Yiran Zhang, Martin Leon, Patrick Serruys, Clemens von Birgelen, Pieter Smits, Ori Ben-Yehuda, Akiko Maehara, Roxana Mehran, Gregg Stone
Journal: Journal of the American College of Cardiology (2018)
Phase 1b/2 trial of cancer stemness inhibitor napabucasin (NAPA) + nab-paclitaxel (nPTX) and gemcitabine (Gem) in metastatic pancreatic adenocarcinoma (mPDAC).
Authors: Tanios S. Bekaii-Saab, Alexander Starodub, Bassel F. El-Rayes, Safi Shahda, Bert H. O'Neil, Anne M. Noonan, Walid Labib Shaib, Wahid Tewfik Hanna, Sameh Mikhail, Anterpreet S. Neki, Yue Chang, Xiaoshu Dai, Wei Li, Emily Brooks, Cindy Oh, Laura Borodyansky, Chiang Li
Journal: Journal of Clinical Oncology (2018)

4110 Background: NAPA is an oral investigational agent, hypothesized to inhibit cancer stemness pathways, including STAT3 pathway implicated in cancer stem-cell viability. We report updated data in a study of mPDAC patients (pts) (NCT02231723) treated with NAPA + nPTX + Gem, including a subgroup of pts eligible for enrollment in the ongoing phase 3 study (NCT02993731, CanStem111P). Methods: A phase 1b/2 multicenter study in mPDAC pts was done to assess the recommended phase 2 dose, PK profile, and signals of anticancer activity of NAPA + nPTX + Gem. Pts received NAPA 240 mg BID + weekly nPTX 125 mg/m2 + Gem 1000 mg/m2 for 3 of every 4 weeks until disease progression or other discontinuation criteria. Results: Of 59 study pts, 47 (79.7%) were treatment-naïve, and 12 (20.3%) had prior adjuvant treatment. There were no notable PK interactions or dose-limiting toxicities. The most common adverse events included grade 1 diarrhea, neuropathy, pyrexia, and grades 1/2 nausea and fatigue. Among all 59 pts, disease control rate (DCR) was observed in 46 (78.0%) with 2 complete responses (CR) (3.4%) and 26 partial responses (PR) (44.1%) with maturing median progression-free survival (mPFS) and overall survival (mOS) of 7.06 and 9.59 mo, respectively. Among the 50 evaluable pts by RECIST, DCR was 92.0%, with 2 CR (4.0%) and 26 PR (52.0%). Of 9 nonevaluable pts, treatment stopped due to disease progression (3), death (1), noncompliance (2), pt withdrawal (2), and insurance coverage loss (1). In 29 pts eligible for CanStem111P trial, mPFS and mOS is 7.10 and 12.62 mo, respectively. Clinical trial information: NCT02231723. ORR, objective response rate; N/A, not yet reached 1Evaluable: received ≥1 dose of study drug and had ≥1 on-study RECIST evaluation Conclusions: NAPA was well tolerated when combined with nPTX + Gem, with encouraging signs of activity in mPDAC, which are now being further investigated in an ongoing phase 3 study. Subset DCR % ORR % 1 yr OS rate (95% CI) 2 yr OS rate (95% CI) Evaluable1 All Evaluable All All 92.0 78.0 56.0 47.5 46 (33,58) 13 (5,25) Pts eligible for CanStem111P 88.5 79.3 53.8 48.3 54 (34,70) N/A
War metaphors in scientific publications in oncology: A bibliometric analysis.
Authors: Heidemarie Haller, Hannah Vogel, Anna Paul, Gustav Dobos, Thomas Ostermann
Journal: Journal of Clinical Oncology (2016)

10064 Background: In our cultural memory the diagnosis of cancer is conventionally been associated with martial metaphors. In the “war on cancer”, conceptual framing relate cancer to an inner enemy that have to be fought. As research has shown that such framing is not associated with improved survival or coping with cancer, we conducted a bibliometric analysis of the frequency and content of war metaphors in scientific publications in oncology. Methods: A systematic title search in PubMed was performed using the search terms war, fight or battle in combination with cancer related terms. Meta data of the publications including year, origin, type of cancer, and impact factor were extracted and analyzed descriptively and by trend tests of Cox and Steward for the time course of relative frequencies and impact factors. In addition, word count analysis of metaphoric title wordings was performed using MaxQDA. Results: Literaturesearch found a total of 848 publications. After exclusion of duplicates and not eligible records, a final set of 725 articles from 1946 to 2015 was included in the analysis. The majority of publications were on cancer in general (77.3%), followed by breast cancer (5.7%) and lung cancer (2.9%). Publications were mostly originated in the US (48.0%), France (7.0%), United Kingdom (5.8%) and Germany (5.7%). The mean impact factor was 4.32 ± 7.72. Statistical trend analyses found that the mean impact factor increased within the course of time (z = 4.28; p = 0.001), whereas the relative frequency of metaphoric publications significantly decreased (z = 3.17; p = 0.001). The most used title wordings were “fight” in 53.9%, “against” in 51.6%, “war” in 35.6%, and battle in 15.7% of the publications that might be “won” in 8.4% and were “lost” in 3.2%. Additional metaphors included “weapons” in 3.6%, “front” in 1.7%, and “forces”, “evil” and “killing” in 0.4% of the publications, respectively. Conclusions: Metaphors of war even have found their way in scientific publications and are still a rhetorical device in the field of cancer research. They might be replaced by a more rational scientific approach in order to better life with cancer.
Therapeutic Lifestyle Changes Improve HDL Function by Inhibiting Myeloperoxidase-Mediated Oxidation in Patients With Metabolic Syndrome
Authors: Anna V. Mathew, Lei Li, Jaeman Byun, Yanhong Guo, George Michailidis, Mamta Jaiswal, Y. Eugene Chen, Rodica Pop-Busui, Subramaniam Pennathur
Journal: Diabetes Care (2018)

Phagocyte-derived myeloperoxidase (MPO) and proinflammatory HDL are associated with metabolic syndrome (MetS) and increased cardiovascular disease risk. Therapeutic lifestyle changes (TLCs), such as a Mediterranean diet and exercise, decrease this risk. However, the link among TLCs, HDL, and MPO-mediated oxidative stress remains unclear.