bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of skeletal-related events (SREs) following initial diagnosis of bony metastases in breast, lung, and prostate cancer.
Authors: Lamerato Lois , Glass Andrew , Wolff Greg G. , Richert-Boe Kathryn E. , Taneja Charu , Edelsberg John , Czapski Natalie , Chung Karen , Richhariya Akshara , Oster Gerry 
Published: March 2020

e19630 Background: Bony metastases (mets) are a common source of morbidity in patients (pts) with cancer, cause spinal cord compression (SCC), pathological fracture (PF), and bone pain, and often require radiotherapy (RT) and/or surgery to bone (SB). Methods: Using the tumor registry and electronic data stores at a large U.S. Midwest healthcare system that serves approximately 800,000 persons, we retrospectively identified all pts aged ≥18 years with primary breast, lung, or prostate cancer diagnosed between 1995 and 2009. Registry and electronic medical records were then used to identify pts with diagnosis of bone mets at initial cancer diagnosis or at recurrence. Trained technicians reviewed medical records for occurrence of SCC, PF, RT and SB—outcomes that have been collectively referred to as SREs. Cumulative incidence of these events was calculated in the presence of competing risk of death. Results: We identified 378 pts with breast cancer and bone mets, 272 with lung cancer and bone mets, and 420 with prostate cancer and bone mets. SREs were present at initial diagnosis of bone mets in 23% of breast cancer pts, 24% of lung cancer pts, and 10% of prostate cancer pts (Table). At 12 months, cumulative incidence of SREs was 57.3% for breast cancer (SCC, 5.1%; PF, 37.9%; SCC and/or PF, 40.2%; SB, 5.9%; RT, 27.4%), 62.7% for lung cancer (SCC, 8.9%; PF, 37.8%; SCC and/or PF, 43.3%; SB, 3.5%; RT, 32.4%), and 38.4% for prostate cancer (SCC, 7.9%; PF, 21.3%; SCC and/or PF, 26.7%; SB, 4.0%; RT, 22.9%). Use of bisphosphonates was largely confined to pts with breast cancer. Conclusions: Though breast, lung, and prostate cancers differ considerably in presentation, clinical course, and treatment, SREs are a common and serious problem in all three cancers among patients with bone mets. [Table: see text]
The effect of continuous exposure to serotonin receptor antagonism on delayed emesis: An analysis of 1,535 patients in two randomized clinical trials with granisetron (G), APF530, and palonosetron (palo).
Authors: Raftopoulos Harry , Oboyle Erin , Gralla Richard J. , Rosenberg Martin , Barr John 
Published: March 2020

e19635 Background: Serotonin-type 3 receptor antagonists (5HT3RA) are recommended by all evidence-based guideline groups. Controversies remain over the role of 5HT3RA in delayed emesis and in dosages. This analysis was conducted to examine if: 1) serotonin antagonism helps prevent delayed emesis, 2) length of continuous exposure to a 5HT3RA impacts efficacy, and 3) higher doses of a 5HT3RA influence results. Palo, a 5HT3RA with a long half life, was superior to older 5HT3RA agents in single agent trials and to G + dexamethasone (dex) in a combination trial in untreated patients (pts) (Saito et al, Lancet Oncol 2009 – Trial 1). APF530 is an extended release formulation of 2% G (500mg = 10 mg of G) in a biodegradable polymer, which with dex showed non-inferiority with palo + dex in a mix of untreated and treated pts (Grous et al, ASCO 2009 – Trial 2). Methods: We analyzed results of only untreated pts from Trial 2 so that the population was similar to those in Trial 1 (previously untreated, highly or moderately emetic chemo and received dex + single administration of a 5HT3RA). This allows comparison, over 2 trials, of G, APF530, palo at 0.25 mg and 0.75 mg. Results: See table. All three groups treated with the long acting 5HT3RA (palo at 0.25 mg or 0.75 mg) or the extended release 5HT3RA (APF530) had similar efficacy in complete control of acute, delayed, or overall 5-day emesis. Only the short acting G was associated with poorer results, in delayed and overall 5-day control. Conclusions: This analysis indicates that 1) continuous exposure to 5HT3RA as a long acting agent or as an extended release formulation provide better emetic control than the standard 5HT3RA granisetron, even with added dex, and 2) similar results were found with palo at 0.25 mg and 0.75 mg. These results indicate a role for serotonin antagonism in delayed emesis provided the patient receives continuous exposure of a 5HT3RA agent. [Table: see text]
Superior survival in children with rhabdomyosarcoma treated as per IRSG compared to as per SIOP regimen.
Authors: Aung LeLe , Tin Aung Soe , Quah Thuan Chong ,   Pediatric Oncology Group-Singapore
Published: March 2020

e20003 Background: Rhabdomyosarcoma (RMS) constitutes nearly 4% of all children diagnosed with cancer in ethnically diverse small island city of Singapore (pop. 5 million). Methods: We compared 56 children with RMS from April 1993 to December 2010 from KK Women’s and Children’s Hospital and National University Hospital, Singapore. They were treated as per Intergroup Rhabdomyosarcoma Study Group (IRSG) regimen (n=25), Société Internationale Pediatrique D’Oncologie (SIOP) regimen (n=20), and various other regimens (n=11). Results: Median age of diagnosis was 6.3 (0.1 - 17.3 years) with a median follow-up of 2.5 (0 - 15.6 years). According to IRSG classification, there were 19 (35.1%) with low risk (LR), 21 (38.8%) with intermediate risk (IR) and 14 (25.9%) with high risk (HR) disease. Fifteen (26.8%) were alveolar subtype, 23 (41.1%) were embryonal and sub-classification was not available in 18. The primary sites of tumor were: head and neck (n=22); genitourinary (n=19); extremity (n=10); and abdomen (n=5). At the time of analysis, 80.0% (n=45) were alive with no evidence of disease, 9 were dead of disease, and two were alive with disease. The 5-year EFS and OS for the cohort was 81.8% and 80.3% respectively. By disease risk group, 5-year EFS for LR was 93.3% [95% CI, 88.9 – 98.5], IR at 94.4% [95% CI, 90 – 99.6] and HR at 42.9% [95% CI, 41.5 – 47.7] respectively (p<0.001). The 5-year EFS for risk group by chemotherapy received per SIOP vs. per IRSG revealed: LR- 100% vs. 90.0% (p=0.43); IR- 100% vs. 90.9% (p=0.40); HR- 0% vs. 57.1% (0.64) respectively. Of 16 (7= HR) relapses at median of 2 years, 4 of 4 treated as per SIOP regimen were dead of disease and 2 of 3 treated as per IRSG were alive at last follow-up. Conclusions: High risk disease treated as per IRSG regimen resulted in superior EFS and OS than per SIOP. Although relapsed disease can be salvaged after initial therapy using SIOP regimen, emotional and financial impact of disease relapse on the family is vast. It would be of interest to report whether our findings can be duplicated in a collaborative international study.
Identifying TRKA and TRKB specific pathways in neuroblastoma through phosphoproteomic analysis.
Authors: Volchenboum Samuel Louis , Kristjansdottir Kolbrun , Bergelson Ilana , Khan Saira , Brodeur Garrett M. 
Published: March 2020

e20008 Background: Neuroblastoma is the most common solid tumor found in children and is difficult to treat given its genetic and clinical heterogeneity. The tyrosine kinase receptor, TrkB, is often co-expressed with the MYCN oncogene in high-risk tumors, whereas the TrkA receptor is most often found expressed in low-risk, non-MYCN amplified samples. There are differences in the gene expression profiles of TrkB- and TrkA-over-expressing cell lines, but they do not explain the phenotypic variation. We hypothesize that differences in protein translation and post-translational modifications have profound downstream effects on cellular signaling and disease phenotype. Methods: We performed quantitative proteomics using stable isotope labeling, phosphopeptide enrichment, and tandem mass spectrometry on parental SY5Y neuroblastoma cells and cell lines stably transfected with either TrkA or TrkB. Receptors were activated with NGF or BDNF and activation was inhibited with CEP-701 (Lestaurtinib), a selective tyrosine kinase inhibitor, currently in clinical trials. Samples were separated by gel electrophoresis, digested with trypsin, and applied to the mass spectrometer for protein identification. Results: We have performed quantitative phosphoproteomic analysis and compared protein expression levels and patterns in TrkA overexpressing, TrkB overexpressing, and parental SY5Y cells. The TrkA and TrkB receptors were activated with NGF and BDNF ligands, respectively, as evidenced by increased phosphorylation of ERK and AKT, with inhibition by CEP-701. Changes in protein abundance and pathway activation following both ligand binding and inhibition are being determined by quantitative phosphoproteomic analysis, and TrkA-specific and TrkB-specific differences will be presented. Conclusions: As current genomic techniques may underestimate the differences in protein expression, proteomic profiling holds great promise for describing how post-translational modifications such as phosphorylation can affect tumor phenotype. Our work may reveal key elements of TRK signaling pathways important in neuroblastoma tumorigenesis, and may lead to the identification of novel targets for therapy development.
Efficacy and tolerability of trabectedin in heavily pretreated soft tissue sarcomas (STS).
Authors: Alonso Teresa , Gajate Pablo , Casado Antonio , Segura Gonzalez Eduardo Raul , Ortega Luis , Cebrian Juan Luis , Talavera Pablo , Zugazagoitia Jon , Acosta Daniel , Diaz-Rubio Eduardo 
Published: March 2020

e20513 Background: Advanced STS have a dismal prognosis with a median overall survival of 1 year, reported in most phase III clinical trials. Although newer targeted therapies are currently being evaluated, chemotherapy continues to be the mainstay of treatment. However, due to the limited activity of current treatments, new therapies are needed. Trabectedin, an alkylating agent to the minor groove of DNA, has demonstrated significant activity after failure of anthracyclines and ifosfamide. Methods: This is a retrospective analysis of 22 patients diagnosed with advanced, heavily pretreated STS, treated with trabectedin in a single institution. From 06/ 2000 to 06/ 2011, trabectedin was administered as a 3-hour infusion every 21 days at a dose of 1.1-1.5mg/m2 with steroid premedication. No patients were excluded from this analysis. Results: Median age was 53 years (range 21-82). The most frequent histologic subtypes were: 27% liposarcomas, 18% leiomyosarcomas, 13% malignant fibrous histiocytomas and 9% synovial sarcomas. One third of patients had received 3 or more prior therapy lines. Overall response rate was 8.33% and stable disease (more than 16 weeks) was achieved in 36.3% of patients (75% of liposarcomas and 50% of leiomiosarcomas). The median duration of response was 11 weeks (range 4-22). Dose reduction was required in two patients, but no patient discontinued treatment due to drug-related toxicity. There were no treatment-related deaths. The most relevant toxicity was grade 3/4 neutropenia in 25% of patients (one case of febrile neutropenia). Grade 3/4 transaminitis was observed in the only patient who received trabectedin with doxorubicin for one cycle, and continued with trabectedin monotherapy without further liver function test disturbances. A case of transient rhabdomyolysis was observed; the patient had mild renal dysfunction and liver metastases, but recovered completely. Grade 1/2 nausea, vomiting and asthenia were reported in 8.33%, 4.17% and 45.83% of patients, respectively. Conclusions: Trabectedin achieves significant clinical benefit in heavily pretreated advanced STS patients. Trabectedin was well tolerated with reversible and manageable toxicity, demonstrating an acceptable safety profile.
Urokinase-type plasminogen activator gene (PLAU) to predict clinical outcome in invasive lobular carcinoma.
Authors: Metzger Otto , Michiels Stefan , Singhal Sandeep K. , Bertucci François , Desmedt Christine , Fumagalli Debora , Salgado Roberto , Galant Christine , Veys Isabelle , Saini Kamal V.S. , Larsimont Denis , Winer Eric P. , Piccart-Gebhart Martine J. , Sotiriou Christos 
Published: March 2020

e21010 Background: At the molecular level invasive lobular carcinoma (ILC) is mostly composed of luminal A (LA) (≈80%) followed by luminal B (≈15%) and a small fraction of HER2-positive (≈5%) tumors (Metzger et al SABCS2011). In ILC, Genomic Grade (GG) adds prognostic information to clinico-pathological (CP) characteristics (Metzger et al ASCO 2011). In this study we sought to evaluate the prognostic value of different gene signatures/modules in patients diagnosed with LA classic ILC. Methods: Gene expression data were generated from 184 consecutive frozen tumor samples using Affymetrix U133 Plus 2.0 arrays. ILC tumors were classified into molecular subtypes using the PAM50 classifier. ILC tumors characterized as classic ILC by pahtologists and as LA by PAM50 were selected for this analysis. Invasive disease free survival (IDFS) was defined as the interval between date of surgery and date of any invasive recurrence or death. Multivariate analyses for IDFS and overall survival (OS) adjusted for age, tumor size, nodal status and chemotherapy was performed for gene signatures/modules related to proliferation, invasion, immune response and signaling pathways (IGF1, PI3K, MAPK, Src, Wnt). Results: 125 LA classic ILC tumors were identified with a median follow-up of 6.6 years (95% CI 5.6-7.6). The addition of PLAU gene expression as continous variable to CP variables yielded a significant hazard ratio (HR) for IDFS (HR= 2.1 [1.1 – 4.1], Δx2= 4.5, likelihood ratio p = 0.03) and for OS (HR = 3.6 [1.4 – 9.6], Δx2= 6.9, likelihood ratio p = 0.009). GG as a continous variable yielded a significant HR for IDFS (HR= 2.6 [1.2 – 5.7], Δx2= 6.2, likelihood ratio p = 0.01), but not for OS (HR= 2.1 [0.8 – 5.5], Δx2= 2.5, likelihood ratio p = 0.11). In contrast, IGF1, PI3K, MAPK, Src, Wnt, immune response, gene-70 and gene-76 failed failed to add signficant independent prognostic value. Conclusions: In addition to GG, PLAU adds prognostic information to CP factors in LA classic ILC and may guide future drug development in this difficult to treat BC subset. Of interest, PLAU is involved in degradation of extracellular matrix contributing to cell migration and metastasis and is a major component of a validated breast cancer biomarker (UPA/PAI1).
Prevalence of EGFR mutations in non-small cell lung cancer (NSCLC) smoker patients.
Authors: Izarzugaza Yann , Domine Manuel , Rojo Federico , Casado Victoria , Leon Ana , Fernandez-Acenero Maria Jesus , Rubio Gustavo , Cordova Sharon , Madoz Juan , Martin-Valades Jose Ignacio , Arranz Juan Luis , Serrano Gloria , Carames Cristina , Zazo Sandra , Rincon Raul , Canadas Carmen , Perez-Gonzalez Nuria , Campos Angel , Lobo Francisco , Garcia-Foncillas Jesus ,   Oncology Department Hospital Universitario Fundación Jiménez Díaz, Universidad Autónoma de Madrid
Published: March 2020

e21015 Background: Mutations in the Epidermal Growth Factor Receptor (EGFR) predict a better response to tyrosine kinase inhibitors compared to platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Previous studies in caucasian population have reported a frequency of EGFR mutation of 10-15%. The aim of this study is to analyze the prevalence of EGFR mutations in caucasian smoker patients with NSCLC. Methods: Prospective mutation testing in NSCLC patients included in our institution since October 2010 to January 2012 was performed on DNA obtained from available tumor tissue and cytologic samples, using ARMS-scorpion TheraScreen EGFR 29 Mutation Test Kit (Qiagen). Results: From 218 consecutive NSCLC diagnoses, 18 (8.25%) patients showed EGFR mutations: 6 (33.3%) exon 19 deletions, 9 (50%) exon 21 mutations (7 cases L858R and 2 cases L861Q) and 3 (16.6%) exon 20 insertions. In the EGFR-mutated patients, 13 (72.25%) were never-smoker and 5 (27.7%) were smoker (3 current-smoker and 2 former-smoker). The EGFR-mutated smoker population showed the following characteristics: 3 female, 2 male; 4 adenocarcinoma, one squamous cell carcinoma; 3 stage IV, 2 stage IA at diagnosis; 1 (20%) case EGFR deletion exon 19, 1 (20%) case insertion exon 20 and 3 patients (60%) mutation exon 21 (2, L858R and 1, L861Q). Conclusions: The EGFR mutation rate in NSCLC smoking patients in our referral area is superior (27.7%) than previously reported, reinforcing the importance of including EGFR mutation testing in NSCLC smoking population for the correct management of these patients.
Gene expression profiling for prediction of tissue of origin to direct site-specific therapy in patients with CUP: Treatment outcomes by assay predictive probability.
Authors: Rubin Mark S. , Greco Frank A. , Boccia Ralph V. , Scola Michael A. , Spigel David R. , Raby Samuel , Chirwa Thabiso W. , Quinn Raven , Hainsworth John D. 
Published: March 2020

e21023 Background: Tumor profiling as a diagnostic technique in CUP depends on the detection of similarities in gene expression between the cancer and the tissue of origin. Assay-directed site-specific therapy may be most effective in tumors with high-confidence molecular predictions, since a) the prediction may be more often correct due to greater similarity between the gene expression profile of the unknown tumor to the assay reference tumor database, and b) the tumor would more likely share biologic characteristics/treatment sensitivity with cancers of known origin. Methods: In a prospective trial performed by the Sarah Cannon Research Institute (SCRI), a 92-gene RT-PCR assay (CancerTYPE ID; bioTheranostics, Inc.) was performed on tumor biopsies from previously untreated CUP pts. Pts were then assigned standard site-specific treatment directed by the assay prediction. Treatment responses were evaluated based on the strength of the assay predictions; probabilities ≥80% were arbitrarily regarded as high confidence results. Results: Between 10/08 and 12/11, 224 pts (26 predicted tumor types) received treatment. Median overall survival (OS) was longer in 113 pts (50%) with high confidence predictions: 11.7 months (mos) vs 9.8 mos; p=.03. 120 pts (59%) had assay predictions of responsive tumor types, known to derive substantial benefit from standard site-specific therapy. Treatment responses, irrespective of predictive probability, were better in these pts vs those with less responsive tumor types (median OS 12.8 vs 7.4 mos; p=.027). Further stratification of high vs lower confidence assay predictions resulted in 4 groups with different OS (p=.03) (Table). Conclusions: Site-specific therapy for CUP pts directed by results of the 92-gene assay was more effective when the probability of the assay prediction was higher, particularly in pts with assay diagnoses of more responsive tumor types. [Table: see text]
Circulating epithelial tumor cells (CETC) during preoperative chemotherapy (CTX) of patients with gastric cancer.
Authors: Schmalenberg Harald , Pachmann Katharina , Pauligk Claudia , Hochhaus Andreas , Al-Batran Salah-Eddin 
Published: March 2020

e21063 Background: we investigated CETC in blood samples accompanying a German multicenter phase II/III trial comparing perioperative CTX with epirubicin, cisplatin, 5-FU, leucovorin (ECF) every 3 weeks or 5-FU, leucovorin, oxaliplatin, docetaxel (FLOT) every 2 weeks. Methods: 7.5ml of anti-coagulated blood was drawn before the first and before the second course of CTX and after the end of preoperative CTX before surgery. After red blood cell lysis the white blood cells including the CETC were stained with a fluorescent labelled anti-epithelial antibody, positive events counted using an automated image analysis microscope and calculated per volume blood. Results: CETC were evaluable from 98 patients (FLOT: n=41; ECF: n=57). Characteristic response pattern to treatment were observed: Most patients (n=33 (81.5 %) from the FLOT arm and n=45 (79%) from the ECF arm) showed a decrease in CETC numbers during the first treatment course. Of these patients 11/33 (33%) in the FLOT arm and 24/45 (53%) in the ECF arm had a re-increase in cell numbers after chemotherapy (chi-square test p=.079). 11/11 (100% of patients with an initial increase in CETC in the FLOT arm subsequently showed decreasing CETC numbers whereas this was true only for 8/12 (66%) of the patients from the ECF arm (chi-square test p=.035). Conclusions: this is the first report on CETC during neoadjuvant CTX of gastric cancer. We have observed a rapid decrease in the number of CETC during CTX in the majority of patients in both arms. A re-increase under ongoing CTX was seen more frequently in patients receiving ECF. Whether the initial decrease of CETC correlates with tumor size reduction and subsequent difference in behaviour of CETC numbers during CTX translates into clinical outcome needs to be investigated in the frame of the ongoing German multicenter study.
Prognostic and predictive value of hedgehog (Hh) signaling in advanced non-small cell lung cancer (NSCLC).
Authors: Berardi Rossana , Santinelli Alfredo , Onofri Azzurra , Caramanti Miriam , Savini Agnese , Chiorrini Silvia , Biscotti Tommasina , Ballatore Zelmira , De Lisa Maria Grazia , Mandolesi Alessandra , Biagetti Simona , Alfonsi Simona , Pompili Cecilia , Salati Michele , Brunelli Alessandro , Mazzanti Paola , Pierantoni Chiara , Sabbatini Armando , Bearzi Italo , Cascinu Stefano 
Published: March 2020

e21070 Background: Advanced NSCLC still represents a medical challenge in cancer therapy. The Hh pathway is critical for cell growth and differentiation. The aim of our study is to evaluate the role of the Hh signaling pathway in determining the clinical outcome of NSCLC patients. Methods: The expressions of Hh-related molecules including Ptch1 and Gli1 (nuclear and cytoplasmic) were determined by immunohistochemistry in 35 histologic samples (biopsies and surgical specimens) of advanced NSCLC patients. All the neoplastic area presents in the slides was considered and both cytoplasmic and nuclear stainings were evaluated, according to the positive neoplastic cells. The intensity of the staining was considered and scored as 0 (absent), 1+ (low), 2+ (medium) and 3+ (high). Results: 18 adenocarcinomas and 17 squamous cell carcinomas were analysed. Positivity of Gli1-cytoplasmic expression and Gli1-nuclear expression were expressed in adenocarcinoma at a significantly higher level and more frequently than compared to squamous cell carcinoma (p<0.05), while Ptch1 did not differ significantly in the two histotypes. Overall survival was higher in Gli1 and Ptch1 negative tumor samples compared to the positive group (p=0.02). The 18 patients with adenocarcinoma received erlotinib as second line therapy and those presenting a lower Gli1 and Ptch1 expression experienced a significantly better progression free survival. Conclusions: These results suggest that the Hh pathway might play a major prognostic role in NSCLC with significant differences between the histotype. Furthermore it might predict the efficacy of erlotinib as second-line treatment in patients with advanced lung adenocarcinoma.