tbuckley/cabot-search huggingface dataset:
Classifying endometrioid endometrial cancer by long noncoding RNA profiling: Indication of prognosis and therapy selection.
Authors: Yunyun Jiang, Gabriel Malouf, Jianping Zhang, Erika Thompson, Jean-Philippe Spano, David Khayat, Karen H. Lu, Xiaoping Su
Journal: Journal of Clinical Oncology (2014)

11064 Background: The Cancer Genome Atlas (TCGA) has recently reported an integrative analysis of endometrioid endometrial carcinoma (EEC) . However, the landscape of long non-coding RNAs (lncRNA) and its role in defining tumor subtypes with clinical relevance have not been addressed. Methods: Using TCGA molecular RNAseq profiles related to 304 primary endometrioid endometrial tumors (serous and mixed tumors were excluded), we performed genomic analysis of GENCODE lncRNAs. Furthermore, we established lncRNA expression-based subtypes with distinct signatures, and described global correlations of lncRNA expression-based subtypes with genomic aberrations and clinico-pathological tumor features. Results: Using stringent criteria, we identified 1,931 lncRNAs and predicted those that are potential drivers through integrative analysis. Unsupervised clustering of lncRNA expression revealed three robust subtypes, one of which displayed a worse overall survival as compared to the other two (Cluster C3, p=0.029). Pathological grade 3 tumors were enriched in this cluster (p<0.0001) in which microsatellite-unstable (MSI) and POLE ultramutated/hypermutated subgroups were also enriched (p<0.0001). In Cluster C3, integrative analysis with copy-number alteration and mutation revealed significant enrichment of KRAS mutation and STK11 loss, recently shown to dictate response to metformin. The coupled overexpression of lncRNA HOTAIR with EZH2 and exclusive enrichment of the EED polycomb gene targets in the same cluster indicate the association between the polycomb repressive complex 2 (PRC2) and aggressive disease, suggesting application of histone deacetylase inhibitor related therapies. Conversely, we found significant enrichment of CTNNB1 mutations in Cluster C2, suggesting WNT pathway related therapeutic methods. Conclusions: Our results revealed the application of systematic characterization of a large cohort of clinically annotated EEC with a poor prognosis cohort clearly identified. The application of lncRNA profiling can potentially be utilized as a tool for clinical outcome prediction and targeted therapy selection.
Sequential treatment in patients with metastatic pancreatic neuroendocrine tumors after progression on first-line therapy.
Authors: Erica S Tsang, Caroline Speers, Winson Y. Cheung, Hagen F. Kennecke
Journal: Journal of Clinical Oncology (2017)

426 Background: Pancreatic neuroendocrine tumors (pNETs) are rare malignancies with an age-adjusted annual incidence of 0.32/100,000, with metastatic disease at diagnosis occurring in 64%. Patients with advanced disease are considered for surgery/ablative therapy (SG) or systemic therapy (ST), including chemo- and targeted therapy, somatostatin analogues, and peptide receptor radiotherapy (PRRT). Optimal sequence of therapy is unknown and we sought to characterize sequential treatment patterns in patients with metastatic pNETs and overall survival (OS). Methods: Patients diagnosed with metastatic pNETs referred to the BC Cancer Agency between 2000-2013 and received more than one line of therapy were reviewed. Results: Of 151 patients, 81 received one line of therapy while 45 patients received &gt;1 treatment. Median age was 55.1 years (IQR 47.4-64.8) and 23 (51%) were male. Sites of metastases included liver (n=33), lymph nodes (n=5), lung (n=1), peritoneum (n=2), and bone (n=5). Median time to start of therapy was 1.5 months (IQR 0.4-3.0). First-line SG was associated with increased OS compared to first-line ST (88.9 vs. 38.2 months; p=0.004). There was no difference in OS between patients receiving second-line SG or ST, measured from start of second-line therapy. Second-line chemotherapy was associated with decreased PFS compared to alternate treatments, both after first-line chemotherapy (0.7 vs. 5.8 months; p=0.002) and after other treatments (4.8 vs. 16.7 months; p=0.002). Median length of follow-up was 48.3 months. Conclusions: We present the sequential treatment patterns of patients with metastatic pNETs. Results confirm the primary role of SG, reserving ST for secondary therapy. Upon progression, choice of second-line therapy was not prognostic and may be chosen based on disease and patient characteristics. [Table: see text]
Brachytherapy for Patients With Prostate Cancer: American Society of Clinical Oncology/Cancer Care Ontario Joint Guideline Update
Authors: Joseph Chin, R. Bryan Rumble, Marisa Kollmeier, Elisabeth Heath, Jason Efstathiou, Tanya Dorff, Barry Berman, Andrew Feifer, Arthur Jacques, D. Andrew Loblaw
Journal: Journal of Clinical Oncology (2017)

Purpose To jointly update the Cancer Care Ontario guideline on brachytherapy for patients with prostate cancer to account for new evidence. Methods An Update Panel conducted a targeted systematic literature review and identified more recent randomized controlled trials comparing dose-escalated external beam radiation therapy (EBRT) with brachytherapy in men with prostate cancer. Results Five randomized controlled trials provided the evidence for this update. Recommendations For patients with low-risk prostate cancer who require or choose active treatment, low–dose rate brachytherapy (LDR) alone, EBRT alone, and/or radical prostatectomy (RP) should be offered to eligible patients. For patients with intermediate-risk prostate cancer choosing EBRT with or without androgen-deprivation therapy, brachytherapy boost (LDR or high–dose rate [HDR]) should be offered to eligible patients. For low-intermediate risk prostate cancer (Gleason 7, prostate-specific antigen &lt; 10 ng/mL or Gleason 6, prostate-specific antigen, 10 to 20 ng/mL), LDR brachytherapy alone may be offered as monotherapy. For patients with high-risk prostate cancer receiving EBRT and androgen-deprivation therapy, brachytherapy boost (LDR or HDR) should be offered to eligible patients. Iodine-125 and palladium-103 are each reasonable isotope options for patients receiving LDR brachytherapy; no recommendation can be made for or against using cesium-131 or HDR monotherapy. Patients should be encouraged to participate in clinical trials to test novel or targeted approaches to this disease. Additional information is available at www.asco.org/Brachytherapy-guideline and www.asco.org/guidelineswiki .
Prognostic value of immunohistochemical factors in esophageal small cell carcinoma (ESCC): Analysis of clinicopathologic features of 73 patients.
Authors: Cong Li, Yigong Zhang
Journal: Journal of Clinical Oncology (2017)

37 Background: Esophageal small cell carcinoma (ESCC) is a very rare but aggressive disease with poor prognosis. The objective of this study was to describe immunohistochemical and clinicopathological features of patients with ESCC in Chinese population, and to clarify how the utilization of different marker combinations affects prognostic outcome. Methods: We retrospectively reviewed a total of 73 patients with ESCC. The tumor samples obtained were immunohistochemically analysed of neuron specific enolase enolase (NSE), synaptophysin (Syn), chromogranin A (CgA), and Thyroid Transcriptional Factor-1 (TTF-1). The positivity of these four factors and their correlation with clinical characteristics was described. The relation between positive expression of them and survival was also analysed. Results: The median age at the time of diagnosis was 57 (ranging from 36 to 77 years). 55 patients were male (75.3%) and 18 patients (24.7%) were female. Immunological reactivity of the samples was Syn 68.5%, TTF-1 46.6%, NSE 90.4%, CgA 43.8%. There were sixteen cases with four biomarkers positive (21.9%), twenty-six cases with three biomarkers positive (35.6%), fourteen cases with two biomarkers positive (19.2%), and twelve cases with only one biomarker positive (16.4%). Five cases (6.8%) were all negative. The expression of NSE was insignificantly associated with primary tumor location (P = 0.01). The 2-year and 3-year cancer-specific survivals were 24.8% and 19.9%, respectively. The median OS was 13.5 months. Although not statistically significant, expression of any factor was tended to positively affect survival. And the median OS of patients without expression of four factors was significant worse than those with at least one factor of positive expression (6.1 months vs 15.3 months, P = 0.002). Conclusions: Chinese ESCC patients have a poor prognosis even after local or systemic treatment. Relatively high percentages of positive labeling of Syn, CgA, NSE and TTF-1 implicated their diagnostic value in ESCC. More important, these four biomarkers might be probable favourable prognostic factors for ESCC.
Prediction of pathological outcome at radical prostatectomy for MRI-ultrasound fusion prostate biopsy versus standard transrectal ultrasound guided prostate biopsy.
Authors: Hans Arora, Yaw A. Nyame, Ahmed El-Shafei, Onder Kara, Andrei Purysko, Andrew J. Stephenson, J. Stephen Jones, Eric A. Klein
Journal: Journal of Clinical Oncology (2017)

73 Background: Magnetic resonance imaging (MRI)-ultrasound (US) fusion prostate biopsy has been shown to be able to detect prostate cancer, with the goal of targeting specific lesions. Our objective was to evaluate the ability of this technique to accurately determine the final pathological outcome at the time of radical prostatectomy as compared to standard template 12-core transrectal ultrasound (TRUS) guided prostate biopsy. Methods: We performed a retrospective analysis of patients who underwent both prostate biopsy and prostatectomy at the Cleveland Clinic. Patients who underwent standard template 12-core TRUS biopsies between January 2005 through December 2013, and MRI-US fusion biopsies from January 2014 through June 2015 were included. Patients who had more than 12 cores taken during TRUS biopsy were excluded. Relevant covariates included patient demographics as well as pre-biopsy PSA and prostate size, which were collected from the electronic medical record. Continuous variables were compared using Wilcoxon rank-sum tests and categorical variables were assessed with χ2 test. Results: In total 543 patients were included. Of these, 491 underwent 12-core standard template TRUS biopsy whereas 54 underwent MRI-US fusion biopsy. Between the two groups there were no significant differences in age (median 62 years versus 63 years, p = 0.21), race (17.5% versus 12.3 % African American, p = 0.32), family history (31.5% versus 29.3% positive, p = 0.74), prostate size (47.75g, IQR 39.5-59 versus 42.7g, IQR 37-56, p = 0.08), pre-biopsy PSA (5.2 ng/mL, IQR 4.1-7.6 versus 4.97, IQR 3.24-6.95, p = 0.14). Of the fusion biopsy patients, 14 of 54 (25.9%) were upgraded from biopsy to prostatectomy, whereas 214 of 491 (43.6%) of TRUS biopsy patients were upgraded (p = 0.02). Conclusions: Of men undergoing transrectal biopsy for the diagnosis of prostate cancer, MRI-US fusion techniques have a lower rate of upgrading at final pathology at prostatectomy as compared to standard 12-core TRUS-guided biopsy.
First-line chemotherapy (CT) with pemetrexed (PEM) + cisplatin (CIS) + bevacuzimab (BEV) followed by maintenance PEM+BEV for advanced nonsquamous non-small cell lung cancer (NS-NSCLC): Final results of a single-arm phase II study.
Authors: Gunnar N Hillerdal, Jens Benn Sorensen, Gert Hoeffken, Adolfo Favaretto, Ramon Perez-Carrion, Carla Visseren-Grul, Sophie Ameryckx, Victoria Soldatenkova, Nawel Bourayou, Armando Santoro
Journal: Journal of Clinical Oncology (2013)

e19148 Background: 1st line PEM+CIS induction CT followed by PEM maintenance and 1st line BEV-based CT followed by BEV maintenance offer clinical benefit (PFS, OS) in NS-NSCLC. This study explored efficacy and safety of 1st line induction PEM+CIS+BEV followed by maintenance PEM+BEV. Methods: Pts with advanced NS-NSCLC and ECOG 0-1 were planned to receive 4 cycles PEM 500 mg/m 2 , CIS 75 mg/m 2 , BEV 7.5 mg/kg, q3w. In absence of PD and with ECOG 0-1, pts could continue on PEM+BEV until PD or unacceptable toxicity. All pts received vitamin supplementation as per PEM label. Primary endpoint was PFS; secondary were OS, response rate, toxicity. Results: 109 pts were enrolled in 5 countries. Characteristics: median age 61 yrs, males/females 59/41%, ECOG 0/1 54/46%, IIIB/IV 9/91%, adenocarcinoma 91%. 72 pts (66%) had maintenance CT. Overall median (max) no of cycles were 6 (34) for PEM+BEV and 2 (4) for CIS. Median PFS was 6.9 m (90% CI 5.7, 8.3). The table gives efficacy and G3/4 AE data. 2 pts died from study-drug related toxicity (GI hemorrhage, pneumonia aspiration; during induction). Conclusions: In this study of PEM+CIS+BEV induction followed by PEM+BEV maintenance median PFS was 6.9 m. Main G3/4 toxicities included neutropenia and fatigue, hypertension was less common. Clinical trial information: NCT01004250. [Table: see text]
Randomized trial of two schedules of palonosetron for the prevention of nausea and vomiting in patients with metastatic melanoma receiving interleukin-2–based concurrent biochemotherapy
Authors: J. Homsi, A. Y. Bedikian, K. B. Kim, N. E. Papadopoulos, W. Hwu, S. Mahoney, A. G. Vardeleon, M. Davies, P. Hwu
Journal: Journal of Clinical Oncology (2009)

e20008 Background: Interleukin-2–based biochemotherapy (BCT) is a common therapy for patients (pts) with metastatic melanoma (MM). BCT induced nausea and vomiting (N/V) remains a significant problem (26% grade 3 and 4). Palonosetron (PALO) is a 5-HT 3 receptor antagonist indicated for the prevention of N/V associated with chemotherapy. The recommended dosing schedule of PALO for patients on BCT is unknown. Methods: Chemo-naïve MM pts undergoing their first BCT cycle were randomized to receive PALO 0.25 mg as premedication intravenously on days 1 and 4, or the same dose on days 1, 3, and 5. The BCT regimen included: cisplatin (20 mg/m 2 ) and vinblastine (1.6 mg/m 2 ) on days 1–4, dacarbazine (800 mg/m 2 ) on day 1, interleukin-2 (9 MIU/m2/day) by continuous infusion on days 1–4 and interferon alpha (5 MU/m2/day) on days 1–5. A nausea episode was defined as nausea of any severity reported by the patient or documented by the nursing staff at anytime. Pts with N/V due to known central nervous system or gastrointestinal metastases were excluded. The use of additional antiemetics was recorded. Pts were followed for 21 days (days 1–7 as inpatients). The Functional Living Index-Emesis (FLIE), an emesis- and nausea-specific questionnaire, was completed starting on day 1. Results: 30 pts were enrolled. Median age was 53 years (range 23–64). Eighteen (60%) were men. The incidences of BCT related N/V and those of nausea interfering with appetite, sleep, physical activity, social life and enjoyment of life are summarized by schedule of PALO in the table below. Conclusions: PALO administered on alternate days was more effective at controlling BCT-related N/V and reduced the need for PRN antiemetics. Better control of N/V reduced the impact of N/V on patient functioning in this population. [Table: see text] No significant financial relationships to disclose.
Investigating cyclooxygenase-2 signaling in breast cancer-initiating cells.
Authors: Carolyn S. Hall, Andrew Walker, Barbara A. Laubacher, Balraj Singh, Anthony Lucci
Journal: Journal of Clinical Oncology (2012)

e21107 Investigating cyclooxygenase-2 signaling in breast cancer-initiating cells Background: Only a small fraction of breast tumor cells, breast cancer-initiating cells (CSC), have the ability to initiate tumor growth and metastasis. Some characteristics of breast CSCs have been described in vitro by employing non-adherent CSC-enriching culture conditions, however, little is known regarding prostanoid signaling or prostaglandin E 2 (PgE 2 ) production in CSCs. In this study we measured cyclooxygenase-2 (COX-2) and prostaglandin E 2 receptor expression in CSCs and assessed the effects of COX-2 and Ep4 inhibition on in vitro CSC spheroid formation and PgE 2 production. Methods: CSCs were cultured in serum-free medium using ultra low attachment plates. Cells were treated with vehicle, a COX-2 inhibitor (Celecoxib), or an EP4 inhibitor (GW627368X) at concentrations of 0.1, 1, 5, 10, 50, or 100uM for 10 days. Spheroids were quantified using a Gelcount machine. Non-linear regression was used to calculate IC 50 values. Western blots were performed using anti-COX-2, anti- EP1, 2, 3 and 4 receptor antibodies. Prostaglandin E2 production was measured using a PgE 2 immunoassay kit. Results: COX-2 protein expression was observed for MDA-MB-231 and SUM149 CSCs. EP2 and EP4 protein was detected for MCF-7, MDA-MB-231, and SUM149 CSCs. The Celecoxib IC50 values for MCF-7 and SUM149 CSC spheroid formation were 0.5 and 2.2 uM, respectively; GW627386X IC50 values for MCF-7 and SUM149 CSC spheroid formation were 1.2 and 0.3uM, respectively. No significant differences in PGE 2 production were observed for MCF-7 CSCs compared to adherent MCF-7 cells (11.5 ± 4.4 vs. 8.7 ± 2.1 pg/mL/10 6 cells; p=0.88). However, PgE 2 production in MDA-MB-231 CSCs was significantly higher than adherent MDA-MB-231 cells (1507.0 ± 329.0 vs. 13.8 ± 5.7 pg/mL/10 6 cells; p≤0.001) and SUM149 CSC PgE2 production was significantly higher than SUM149 adherent cells (4932.9 ± 501.7 vs. 194.5 ± 31.0 pg/mL/10 6 cells; p≤0.001). 10uM Celecoxib treatment inhibited PGE 2 production in MDA-MB-231 and MDA-MB-231 CSCs. Conclusions: MDA-MB-231 and SUM149 CSCs express COX-2, EP2 and Ep4 and produce high levels of PGE 2 . CSC spheroid formation is significantly decreased with COX-2 and EP4 inhibition.
The prognostic role of further positive non sentinel nodes in melanoma patients.
Authors: Roberto Patuzzo, Gianfranco Gallino, Andrea Maurichi, Roberta Ruggeri, Ilaria Mattavelli, Annabella Di Florio, Giulia Elisa Bonarini, Adele Di Fazio, Gabriella Nicolò, Mario Santinami
Journal: Journal of Clinical Oncology (2015)

e20058 Background: The aim of the study was to investigate whether the non-sentinel node (NSN) status after nodal dissection affected prognosis in melanoma patients with positive SN. Methods: We retrospectively evaluated the clinicopathological data of 1,096 consecutive patients treated from 2000 to 2014 at a single institution, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, who underwent completion lymph-node dissection (CLND) after a positivity of SN. The most frequently involved nodal basins were axilla, groin and neck; 507 positive SNs were detected in axillar basin, 477 in the inguinal-iliac one and 112 in the neck basin. Results: In the axillar nodal basin 18,7% of cases showed one or more positive further LN after the CLND. A similar rate of positive NSNs (18,5%) was found in patients who had inguinal and pelvic lymphadenectomy; of these cases, 23.2% of further positive nodes were observed in the inguinal basin while 13.8% were located in the iliac one. In the neck basin was detected a rate of 20.6% of positive further LN, an higher value respect to axillar and groin lymphatic fields. Among cases with lymphatic drainage to groin 5% of all patients (36% of patients with positive iliac LNs) had iliac LN metastasis with negative inguinal LNs. Iliac LN metastasis was independently associated with higher risk of recurrence and lower survival. 5-year disease free and overall survival was 34% and 51% for patients with iliac LN metastasis, 42% and 65% for those with axillar further LNs involvement and 29% and 46% for patients with neck further positive LNs. Older patients having thicker and ulcerated primary tumor as well as > 2 positive SNs were more likely to harbour further NSN metastases. Conclusions: The NSN status had an independent prognostic value in melanoma patients with at least two further positive LNs, suggested that SN could represent a barrier against melanoma spread. Iliac LNs were found frequently positive after ilioinguinal lymphadenectomy and should be considered for all patients.
Comparison of DNA and RNA analyte extraction and melanin removal methods from formalin-fixed, paraffin-embedded (FFPE) melanoma.
Authors: Lauren Elaine Haydu, Tiffany L Calderone, John Miller, Roland L. Bassett, Aron Joon, Jianhua Zhang, Margaret B. Morgan, Kenna Rael Shaw, Zachary A Cooper, Elizabeth M Burton, Alan Siroy, Khalida M Wani, Franceso Stingo, Veera Baladandayuthapani, Michael T. Tetzlaff, Jennifer Ann Wargo, Alexander J. F. Lazar, Michael A. Davies, Jeffrey E. Gershenwald
Journal: Journal of Clinical Oncology (2015)

e20002 Background: The increasing availability of molecular profiling techniques amenable to FFPE tissue presents a key opportunity to study the molecular basis of melanoma. In order to optimize our methodological approaches for FFPE melanoma specimens for planned integrative analyses, we compared various DNA and RNA analyte extraction and melanin removal methods on analyte yield, quality, and molecular profiles. Methods: Primary (n = 2) and metastatic (n = 6) FFPE melanoma specimens with varying degrees of melanin pigmentation (3-none/minimal, 3-moderate, 2-high) were used for systematic testing of 3 RNA and 4 DNA standard isolation protocols (SIPs). The SIPs were used in combination with four potential methods of melanin removal (Zymo column [Zymo], CTAB, both, none). RNA expression was analyzed using a Nanostring 787 custom code set, and DNA was analyzed by next-generation sequencing (n = 202 targeted genes panel [T200]). Results: Significant differences in total RNA yield/mg tumor were observed between RNA SIPs and melanin removal methods. Although all (96/96) RNA analytes passed quality control (QC) regardless of RNA SIP, melanin removal method, or melanin content, Nanostring gene counts were significantly lower for RNA using 1 SIP. Comparison of analytes from the remaining 2 SIPs and 4 melanin removal methods revealed no significant differences in gene counts, hierarchical clustering results, or variability in gene expression above a conservative multiplicity-adjusted threshold (Bonferroni, 0.05/770). For DNA isolation, only 1 SIP consistently yielded sufficient DNA from highly pigmented specimens. DNA analytes that passed QC (44 of 64) were run on the T200 NGS panel. No differences between SIPs or melanin removal methods were observed for NGS mutation calls or coverage depth. Conclusions: In these studies, melanin did not affect Nanostring-based RNA profiling. The selected SIPs for DNA (QiAmp, Zymo) and RNA (HighPure, Zymo) yielded the best analyte quality and quantity from FFPE melanoma tumors for NGS and Nanostring-based profiling, and provide a robust framework for our ongoing and planned large scale integrated molecular profiling efforts in melanoma.