bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of immune contexture, age, and tumor stage in peripheral neuroblastic tumors (PNT).
Authors: Renne Salvatore Lorenzo , Camisaschi Chiara , Spagnuolo Rosalin Dolores , Podda Marta Giorgia , Barisella Marta , Castelli Chiara , Luksch Roberto , Collini Paola 
Published: September 2018

e22006 Background: PNTs, a family of tumors arising in the embryonal remnants of the sympathetic nervous system, account for 7-10% of all tumors in children. NMYC status, stage, and age are the most important prognostic factors. The association of patient age and prognosis could be influenced by the maturity of immune system. The aims of this study were to describe the immune contexture in PNTs and to investigate its relationships with patient age and tumor stage. Methods: A cohort of 45 consecutive children with PNT diagnosed and treated at a single centre (2008-2014) with available primary tumor specimen at disease diagnosis and no prior chemotherapy was investigated. Immunohistochemistry for CD45, CD3, CD20, CD14, CD163, CD68, PDL1(P142), and FOXP3 was performed. Presence and status of immune infiltration were scored as follow: the presence of aggregates was assessed at 2.5X scanning magnification and recorded as "high" if present or "low" if no aggregates were visible. Patient age was categorized according to London WB et al (2005) using a 460 days cut-off and INSS tumor stage was considered. Results: Patient age ranged between 8 days and 14 years. Tumor infiltrating CD45 and CD3 scores were lower in INSS tumor stage 4 compared to other INSS tumor stages (CD45: OR=12.37, 95%CI 1.38 -171.00, P=0.01; CD3: OR=9.86, 95%CI 1.52-114.13; P<0.01). Similarly, the monocytes and macrophages markers CD163 and CD14 were associated with tumor INSS stage. The expression of these markers was significantly higher in patient older than 460 days (CD163: OR=4.41, 95%CI 0.77-32.12, P=0.03; CD14: OR=6.94, 95%CI 0.79-335.33, P<0.01). Interestingly, PD-L1 was detected only on immune cells but not on neuroblastic cells. Finally, Treg(FOXP3+) score was low in all but one case. Conclusions: Immune contexture in PNT significantly varies across patient age and tumor stage suggesting a role for maturity of immune system in these patients. [Table: see text]
The rates of ABO, Rh, and Kell antigens in children with cancer.
Authors: Maslov Andrey A. , Guskova Nailya , Guskova Ekaterina , Avanesova Kristina , Belgova Svetlana V. , Gornostaeva Ekaterina , Tselishcheva Irina V. , Zakharchenko Viktoria , Torpudzhyan Izabella , Donskaya Aliya K. , Gusareva Marina A. , Abakumova Svetlana V. , Golomeeva Nadezhda , Nozdricheva Anastasia 
Published: September 2018

e22007 Background: The purpose of the study was to analyze phenotypic characteristics of red blood cells by the AVBO, Rh and Kell systems in children with cancer. Methods: ABO and Rh blood groups were determined and erythrocyte antigens (D, С, с, Сw, Е, е, К, k) were typed (AutoVue Innova, USA) in blood samples of 114 children with solid tumors. Results: ABO blood groups distribution was as follows: A(II) > O(I) > B(III) > AB(IV) with A(II) prevalence. Rh(D)-positive phenotype was observed in 82 (71.9%) patients of 114: 47 (57.3%) boys and 35 (42.6%) girls. 32 (28.1%) patients of 114 were Rh(D)-negative: 15 (46.8%) boys and 17 (53.1%) girls. Only 8 (7%) children were Kell-positive, which was similar to the antigen prevalence in European population. 4 erythrocyte phenotypes were the most frequent in Rh(D)-positive patients: СсDееK− (34.1%), ССDееK− (22.0%), ccDEeK− (13.4%) and СсDЕеK− (11.0%). I.e., more than a half of children with oncopathologies (56.1%) had Kell-negative phenotypes, СсDееK− and ССDееK−. 86.4% of Rh(D)-positive patients had homozygous combinations of Rhesus antigens causing transfusion reactions - СС, сc, ЕЕ and ее. 18 (22.0%) of Rh(D)-positive patients were homozygous for the C antigen and 64 (78.0%), i.e. every third patient, had the c antigen. Children with the C antigen may be sensitized to the c antigen through blood transfusion with subsequent development of hemolytic complications. The K (Cellano) antigen was found in all children, and 93% of them had kk phenotype and 7% - Kk. The Сw (Willis) antigen was revealed only in 5 (6.0%) Rh(D)-positive patients with rare phenotypes - CwCceeK-, CwccEeK-, CwCcEEK-, CwCcEeK-. Matching a donor for patients with one of these phenotypes could pose a problem. Conclusions: Studying phenotypic characteristics of red blood cells is necessary for providing a successful blood transfusion, especially in children Kell-positive for the K antigen, in children homozygous for the C antigen with ССDееК- phenotype and in children with the Сw antigen and СwСсееК-, СwссЕеК-, СwСсЕЕК- and СwСсЕеК- phenotypes.
Efficiency and toxicity of mifamurtid in childhood osteosarcoma.
Authors: Tacyildiz Nurdan , incesoy Ozdemir Sonay , Unal Emel Cabi , Dincaslan Handan , Yavuz Gulsan , Asarcikli Fikret , Tanyildiz Gulsah , Yildiz Yusuf 
Published: September 2018

e22010 Background: There are only few data concerning efficiency and toxicity of mifamurtide in children with osteosarcoma (OS). The aim of this study was to evaluate efficiency and side effects of mifamurtide in childhood OS. Methods: We retrospectively analyzed the data of 18 patients with OS and who received mifamurtide between January 2012 and December 2016. Four hundred seventy seven doses of 2 mg/m2intravenous mifamurtide, along with paracetamol premedication were given in 15 patients with primary non-metastatic OS after complete surgical resection and 3 patients with progressive OS. Results: There were 11 males and 7 females, and the median age was 14 years (ranged, 9-18). The median follow-up time was 20 months (ranged, 7-51). The metaphyseal plates around the knee was the most frequent disease location with 94.4%. The median necrosis percentage was 94 (range, 35-100). All patients received Euromos protocol. The most common side effects were chills and fever (17/18). These reactions were observed in 4 patients during every administration, in only one patient at last administration and in the remaining 12 patients during first or first two administration. Headache, myalgia and arthralgia were observed in 2 patients during every infusion. In another one case, headache was observed during only first two infusions and he also hearing loss was developed (could be related CisPlatin) Back pain was observed in two patient during first infusion but one them suffered with severe back pain after few doses and stoped Mifamurtid. . Grade 3-4 neutropenia, trombocytopenia, abnormal liver enzymes and abnormal BUN and creatinin levels were not observed in patients who received mifamurtide alone after completion of chemotherapy. Of the 15 patients with primary non-metastatic OS treated with the addition of mifamurtide to chemotherapy, 13 showed complet remission for median 24 months (ranged,16-36) and 2 patients are still under treatment with complet remission. Of the 3 patients with progressive disease, 2 died and 1 had progressive disease for 51 months. Conclusions: Mifamurtide therapy is safe and well tolerated in childhood OS. Chills and fever were the major side effects, These events were transient and often no longer observed in subsequent administrations.
Safety and efficacy of fosaprepitant in pediatric patients for prevention of chemotherapy induced nausea and vomiting.
Authors: Kusick Karissa N , Waldron Madeline , Zembillas Anthony , Wai Maya , Hanna Rabi , Anderson Peter Meade 
Published: September 2018

e22023 Background: Aprepitant is an antiemetic that antagonizes the substance P neurokinin-1 receptor. Fosaprepitant is an intravenous prodrug of aprepitant and is FDA-approved for the prevention of chemotherapy-induced nausea and vomiting (CINV) in adults. Although the FDA extended approval of oral aprepitant to children and adolescents for CINV, pediatric patients have challenges obtaining aprepitant due to insurance or have difficulty taking oral medications during chemotherapy. Fosaprepitant is a logical alternative but data are lacking for safe and effective dosing in children. In 2015, fosaprepitant was added to our hospital formulary for pediatric patients receiving moderate to highly emetogenic chemotherapy. The fosaprepitant dose established was 150mg for weight ≥30kg or 3mg/kg/dose for < 30kg. There is also potential for overall cost savings to our institution. Fosaprepitant is about half the cost of aprepitant using equivalent adult doses. Methods: This retrospective chart review was considered exempt from IRB.All pediatric patients who received fosaprepitant between April 2015 and October 2016 while inpatient were included.Patients undergoing bone marrow transplant were excluded from the study.The primary objective was to determine safety of fosaprepitant. To evaluate safety, incidence of infusion related reactions related to fosaprepitant administration were assessed. Secondary objectives include efficacy of fosaprepitant in pediatric patients and evaluation of cost savings. To evaluate efficacy, the use of breakthrough antiemetics, documented emesis, and Adapted Rhodes Index for Nausea and Vomiting score were collected. Descriptive statistics were used for all data analyses on a per cycle basis. Results: A preliminary safety evaluation of 20 patients ages 9 months through 16 years received 87 doses of fosaprepitant for CINV prophylaxis.Six patients < 30kg received weight-based dosing; the other 14 patients received a dose of 150mg.One patient experienced an infusion related reaction from fosaprepitant but symptoms resolved after the infusion was stopped. Conclusions: Fosaprepitant appears to be safe and cost-effective to prevent CINV in children.
Pretreatment neutrophilto lynphocyte ratio in ewing sarcoma family of tumors: An analysis of 570 patients.
Authors: Biswas Bivas , Jha Akash , Batra Atul , Sengupta Moushumi , Bakhshi Sameer 
Published: September 2018

e22504 Background: Ewing sarcoma family tumor (ESFT) is a systemic disease and inflammatory in nature. Inflammatory biomarkers have been identified as prognostic marker in various malignancies including sarcoma. Here we have evaluated the prognostic implication of pretreatment neutrophil to lymphocyte ratio (NLR) in ESFT. Methods: We have calculated baseline NLR from peripheral blood parameters in 570 patients of ESFT treated with uniform chemotherapy protocol in our institution from June’2003 to Feb’2015. Treatment protocol consists of neoadjuvant chemotherapy followed by surgery and/or radiotherapy as local treatment modality and adjuvant chemotherapy. NLR was dichotomized as high and low with high NLR defined as value over the median. Data was censored on 30th Jan’2016. Results: Median age was 15 years (range: 0.1-55) with male: female ratio of 40:17 and 41% (n = 236) patients had metastasis at presentation. Most common sites of tumor were long bones in 209 (37%), thorax in 108 (19%) and pelvis in 90 (16%) patients. Hundred-one (18%) had a soft tissue primary. Twenty-five percent (n = 144) patients had systemic symptoms at presentation. Median symptom duration was 4 months (range: 0.5-36) with median tumor size 8.8 cm (range: 1.6-26). Median NLR was 1.55 (range: 0.08-12.87). High NLR was associated with older age (p = 0.002), female sex (p = 0.02), low serum albumin (p = 0.003) and high lactate dehydrogenase level (p = 0.03). After median follow-up of 32 months (range: 0.8-152), 5-year event-free survival (EFS) was 25.3% & 35.8% and overall survival (OS) was 38% & 48.7%, respectively in whole cohort and in those with localized disease. In the whole cohort, high NLR ( > 1.55) emerged as independent prognostic factor predicting inferior EFS (Hazard ratio-1.36, p = 0.03) along with metastasis at presentation (p < 0.001) and tumor diameter > 8 cm (p = 0.005), in multivariate analysis. NLR couldn’t predict OS. Conclusions: High pretreatment NLR emerged as independent prognostic factor predicting inferior EFS in patients with ESFT. It is an easily available and cost effective biomarker. Prognostic nature of NLR should be evaluated in a prospective study and if proven, should be included in prognostic model to tailor therapy.
Systemic treatment preferences for patients with advanced desmoid-type fibromatosis (DF) in Europe.
Authors: Van Cann Thomas , Requilé Annelies , Schoffski Patrick 
Published: September 2018

e22523 Background: The treatment of DF as a rare, benign mesenchymal tumor is poorly standardized and based on physician’s choice. Only a few clinical trials have assessed the different treatment options in DF and randomized evidence is virtually non-existing. We evaluated systemic treatment preferences for patients (pts) with advanced DF among European sarcoma experts, aiming to provide a reference for a generally acceptable control treatment for potential prospective randomized trials. Methods: A 7-item structured questionnaire was sent to physicians in Europe and Israel involved in the multidisciplinary care and experimental treatment of mesenchymal tumors, to assess their systemic treatment choices for DF. Results: The questionnaire was sent to 266 experts (117 institutions, 21 countries), 54 experts (52 institutions, 14 countries) responded. Wait and see was the most common primary approach for pts with advanced DF. (Symptomatic) Disease progression and failure or non-availability of local treatment options were cited as common reasons for considering systemic therapy. Treatment preferences for pts with sporadic vs hereditary DF were similar, with a tendency of earlier use of chemotherapy in hereditary DF. At least 28 different agents or regimens are used in DF. Tamoxifen +/- nonsteroidal anti-inflammatory agents (NSAIDs) or NSAIDs alone are most commonly used in first line, followed by methotrexate- or anthracycline-containing regimen. Tyrosine kinase inhibitors are often used in further lines; other drugs are sporadically used. Clinical trial activity in DF was restricted to only one country/one multi-centric study. Conclusions: DF pts in Europe and Israel have broad off label access to systemic agents, but only to a few clinical trials. Treatment approaches are diverse, poorly standardized and based on weak evidence. There is an urgent need for practice-defining, prospective randomized trials. Such trials should ideally select a homogeneous population of pts with well documented, progressive, symptomatic disease and/or functional impairment after wait and see and/or local treatments. NSAIDs +/- tamoxifen could be considered a generally accepted standard control treatment for clinical trials.
Low-dose chemotherapy with methotrexate and vinblastine for desmoid tumors: A single institution experience.
Authors: Souza Juliana , Lourenco Henrique Monnerat , Mendes Gelcio L. Q. 
Published: September 2018

e22524 Background: Desmoid tumor (DT) is a rare and locally invasive proliferative disease. Although, the absence of metastatic potential, it has the propensity for locally invasive growth and recur. Chemotherapy may be considered in inoperable and/or recurrent disease. Methods: Patients with histological diagnosis of DT and treated with weekly low-dose chemotherapy with vinblastine and methotrexate between January 1998 and December 2015 were identified and their medical records were analyzed. Results: Of 23 patients analyzed, most of them were women (female-to-male ratio 2.8:1). The median age at presentation was 29 years (range, 18-59 years). Tumors location was: thoracoabdominal wall (n: 11, 47.8%), extremities (n: 7, 30.4%), abdominal cavity (n: 1; 4 %), and head and neck (n: 4, 17.3%). Tumor sizes were documented in 18 cases and ranged from 3 to 20 cm in largest linear dimension (median, 10 cm). Eight (34.7%) female had pregnancy history and 2 (8%) had familial adenomatous polyposis history. Eleven (47,8%) underwent surgery as first-line treatment. Five (21.7%) patients received first-line treatment with vinblastine and methotrexate, four (17.3%) patients as second-line, and 14 (60.8%) patients as third and fourth-line. Fourteen ( 60.8%) patients had stable disease, four (17.3%) had partial response, and five (21.7%) patients had progressive disease during chemotherapy treatment. After a median follow-up of 58 months, 12 patients had progression disease and 2 patients died. The median PFS was 29 months, without any progression after 32 months. Conclusions: Weekly low-dose chemotherapy with vinblastine and methotrexate appears to have significant activity. Chemotherapy could be an acceptable alternative to radical surgery in selected patients with desmoid tumors.
Multimodality treatment of synovialsarcoma: A single institution experience.
Authors: Greto Daniela , Delli Paoli Camilla , Francolini Giulio , Becherini Carlotta , Dominici Luca , Saieva Calogero , Scotti Vieri , Campanacci Domenico Andrea , Beltrami Giovanni , Scoccianti Guido , Loi Mauro , Desideri Isacco , Meattini Icro , Bonomo Pierluigi , Livi Lorenzo 
Published: September 2018

e22530 Background: Synovialsarcoma (SS) is a relatively rare cancer, accounting for 8% of all Soft-Tissue Sarcomas (STS). Identifying prognostic factors could allow to improve treatment strategy for this disease. Methods: Data of 52 patients treated at University of Florence between 1999 and 2016 were retrospectively analysed. Patients and treatment features (Table 1) were correlated with outcome. Results: At a median follow-up of 8.4 years, 9 deaths, 3 local recurrences (LR) and 19 distant metastases (DM) have occurred (17,3%, 5,8% and 36,5%, respectively). Survival Kaplan-Meier analysis showed that Overall survival (OS), Local recurrence disease free survival (DFS-LR) and Distant metastases disease free survival (DFS-DM) were 74,5%, 90% and 59,3%, respectively. Size>10 cm was the only significant predictor of OS (p=0,004). Age>40, size>10 cm and G3 significantly influenced DFS-DM (p=0,043, p=0,002 and p=0,002, respectively). Cox univariate regression analysis confirmed the impact of size on OS (HR 5.8, 95% CI 1.37-24.43, p=0,017). Size (HR 5.06, 95% CI 1.73-14.79, p=0.003) and Grade (7.19, 95% CI 1.65-31.37, p=0.009) influenced DFS-DM. G3 was the only independent prognostic factor associated with DFS-DM. Conclusions: These data confirm that age, size and grade significantly influence outcome in patients affected by SS. Further studies are needed in order to develop tailored treatment strategies in this setting. [Table: see text]
Management of liposarcoma: A single institutional analysis.
Authors: Greto Daniela , Becherini Carlotta , Saieva Calogero , Francolini Giulio , Campanacci Domenico Andrea , Beltrami Giovanni , Scoccianti Guido , Meattini Icro , Loi Mauro , Bonomo Pierluigi , Desideri Isacco , Delli Paoli Camilla , Dominici Luca , Livi Lorenzo 
Published: September 2018

e22531 Background: Liposarcoma (LPS) are classified into subtypes: well-differentiated (WDLPS), de-differentiated (DDLPS), myxoid (MLPS) and pleomorphic (PLS). We report a single institution cohort of patients with LPS, undergoing surgery and radiotherapy, to explore prognostic factors related to outcome and toxicity. Methods: This retrospective analysis included 186 LPS patients. Patient, tumor, and treatment variables were analyzed for local recurrence (LR-DFS) and distant metastasis (DM-DFS) disease free survival and overall survival (OS). Results: At a median follow-up of 8.6 years (range, 0.1-27.3 years), Kaplan-Meier (KM) survival analysis showed that LR, DM and OS were 75.5%, 76.6% and 48.1%, respectively. KM analysis showed that Age>56, DDLPS and lower limb localization were related to LR (p=0,001, p=0,0001 and p=0,0001, respectively). Association between LR, Age and DDLPS persisted both at univariate (p=0,003 and p=0,0001, respectively) and multivariate Cox regression (CR) analysis (p=0,024 and p=0,002). Age, tumor depth and grading influenced distant recurrence, both at KM (p=0,023, p = 0.026 and p = 0.016) and univariate CR (p=0,026, p=0,042 and p=0,012). Age and grading were confirmed at multivariate analysis (p=0,009 and p 0,017). Patients with WDLPS and wide excision had significantly better OS (p=0,001 and p=0,03, respectively), while histologic G3 and age>56 were related with worse OS (p= 0,008 and p=0,0001, respectively). Age, DDLPS and Grade were related to OS at univariate (p=0,0001, p=0,0001 and p=0,03, respectively) and multivariate CR analysis (p=0,031, p=0,0001 and p=0,001, respectively). Conclusions: Our analysis confirmed that Grade, tumor depth and histological subtype influenced survival. Further studies are needed in order to explore the influence of hystopathologic features on treatment outcomes. [Table: see text]
Oncometabolite succinate to promote angiogenesis by upregulating VEGF expression through GPR91-mediated STAT3 and ERK activation.
Authors: Mu Xianmin , Zhao Ting , Xu Che , Shi Wei , Geng Biao , Shen Jiajia , Zhang Chen , Pan Jinshun , Yang Jing , Hu Shi , Lv Yuanfang , Wen Hao , You Qiang 
Published: September 2018

e23000 Background: Altered cellular metabolism is now generally acknowledged as a hallmark of cancer cells, the resultant abnormal oncometabolites cause both metabolic and nonmetabolic dysregulation and potential transformation to malignancy. A subset of cancers has been found to be associated with mutations in succinate dehydrogenase genes which result in the accumulation of succinate. However, the function of succinate in tumorigenesis remains unclear. In the present study, we aim to investigate the role of oncometabolite succinate in tumor angiogenesis. Methods: Succinate levels were measured in gastric cancer and paracancerous tissues as well as cell culture supernatants from normal cells and gastric cancer cells. Chemotactic motility, capillary structure formation and proliferation of primary human umbilical vascular endothelial cells (pHUVECs) were determined in the presence of succinate in vitro. Moreover, the vessel formation in zebrafish embryo was also used to examine the effect of succinate on angiogenesis. The activation of STAT3 and ERK signaling by succinate was checked by Western Blot. Results: Our data demonstrated the accumulation of markedly elevated succinate in gastric cancer tissues compared with that in paracancerous tissues. Moreover, succinate was able to increase the chemotactic motility, tube-like structure formation and proliferation of pHUVECs in vitro, as well as promote the blood vessel formation in transgenic zebrafish. Our mechanistic studies reveal that succinate upregulates vascular endothelial growth factor (VEGF) expression by activation of signal transducer and activator of transcription 3 (STAT3) and extracellular regulated kinase (ERK)1/2 via its receptor GPR91 in a HIF-1α independent mechanism. Conclusions: These data indicate an important role of the succinate-GPR91 axis in tumor angiogenesis, which may enable development of a novel therapeutic strategy that targets cancer metabolism.