bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conditional survival of patients with nonmetastatic bone osteosarcoma.
Authors: Miao Ruoyu , Wang Haotong , Choy Edwin , Cote Gregory Michael , Raskin Kevin , Schwab Joseph H. , Hornicek Francis J. , DeLaney Thomas F. , Chen Yen-Lin 
Published: May 2020

e23511 Background: Conditional survival provides a dynamic prediction of prognosis for patients surviving a defined period of time after diagnosis. This study aimed to determine the conditional survival and prognostic factors over time among patients with non-metastatic bone osteosarcoma. Methods: We reviewed 714 bone osteosarcoma patients treated from 1985 to 2016. Patients with metastatic disease at diagnosis or limited follow up were excluded, resulting in 587 cases for analysis. Clinical and pathological variables were recorded. Predictive variables included age at diagnosis, gender, previous radiation history, tumor site, tumor size, histologic subtype, histologic grade, resection margin, chemotherapy, and radiation therapy. The multivariate Cox proportional hazards regression was used to analyze prognostic factors of conditional overall survival and progression-free survival at baseline and 5 years after diagnosis. Results: The estimated 5-year conditional overall survival increased from 71.0% (95% CI: 67.5%-75.0%) at baseline to 86.9% (95% CI: 82.6%-90.5%) at 5 years, which means if a patient with non-metastatic bone osteosarcoma survived 5 years, the chance of surviving another 5 years was 86.9%. If the patient was progression-free for 5 years, the 5-year conditional overall survival was even higher, 93.2% (95% CI: 89.5%-96.4%), and the 5-year conditional progression-free survival improved from 57.1% (95% CI: 53.3%-61.0%) at baseline to 91.2% (95% CI: 87.5%-94.6%) at 5 years. Prognostic factors for mortality and disease progression change as survival time increases. At baseline, age (p < 0.001 and p = 0.003), histologic subtype (p < 0.001 and p = 0.001), grade (p < 0.001 and p < 0.001), tumor size (p = 0.002 and p = 0.002), resection margin (p < 0.001 and p < 0.001) and chemotherapy (p = 0.001 and p = 0.001) were predictive of both overall survival and progression-free survival. However, only age (p < 0.001) and histologic subtype (p = 0.015) remained significant for mortality and resection margin (p = 0.001) for disease progression at 5 years. Conclusions: The survival probability of osteosarcoma improves as survival time increases. Estimates of conditional survival can provide useful information for individualized surveillance strategies, risk evaluation, patient counseling, and making clinical decisions.
Bone turnover markers in primary and metastatic bone tumors.
Authors: Guskova Nailya K. , Vashchenko Larisa N. , Barashev Artem A. , Danilchenko Ekaterina V. , Nozdricheva Anastasia S. , Tselishcheva Irina V. , Donskaya Aliya K. , Selyutina Olesya N. , Abakumova Svetlana V. , Belgova Svetlana V. , Zakharchenko Viktoria R. , Kit Oleg I. 
Published: May 2020

e23513 Background: The purpose of the study was to reveal the levels of biochemical parameters for assessing the intensity of bone metabolism in patients with primary and metastatic bone tumors. Methods: The study included 29 patients aged 55.9±12.17 years with primary (group 1, n = 12) and metastatic (group 2, n = 17) bone tumors. Group 2 included patients with breast cancer (2a, n = 10) and renal cancer (2b, n = 7) with a history of pathological fractures. Serum levels of the bone turnover marker osteocalcin, TSH, the resorption marker β-Cross Laps (C-terminal telopeptide) (Cobas e411, Japan) and calcium (Vitros 5600, USA) were measured before and after (day 14) organ-preserving treatment. The data were compared with that in non-cancer patients of similar age (n = 15) and evaluated in the Statistika 10.0 program. Results: Osteocalcin levels in group 1 prior to surgery was 1.74 times (p < 0.05) higher than in controls (13.56±1.35 ng/mL) and decreased by 35% (p < 0.05) compared to the initial values. In group 2, changes in osteocalcin levels were multidirectional: group 2a – 24% (p < 0.05) higher than in controls both before and after surgery; group 2b – similar to control values before surgery and decreased by 19% (p < 0.05) after it. Levels of β-Cross Laps in all patients before surgery were within the control range (0.49±0.02 ng/mL). After surgery, the levels in groups 1 and 2a did not change, while group 2b showed an increase in β-Cross Laps by 1.5 times (p < 0.05) and a decrease in calcium by 20% (p < 0.05) from the initial levels (2.33±0.09 mmol/L), which, along with a decrease in osteocalcin, could be the result of specific kidney damage. TSH in groups 1 and 2b was similar to controls, but initial TSH levels in group 2a were increased by 86% (p < 0.05) and did not change after surgery, as well as osteocalcin levels, which in the absence of changes in β-Cross Laps suggested a more favorable prognosis after organ-preserving treatment. Conclusions: Bone tissue remodeling processes are determined by the nature of the initial tumor. Measuring osteocalcin and β-Cross Laps in patients with specific bone lesions may be useful in assessing the risk of fractures.
The impact of next generation sequencing on sarcoma diagnosis.
Authors: Zhao Gang , Xie Lu , Guo Wei , Xi Yanfeng , Cui Yanzhi , Yu Siying , Wan Qing , Chen Donglin , Pan Xuedong , Dong XiaoWei , Wang Kai , WANG Jian 
Published: May 2020

e23528 Background: The rarity and heterogeneity of sarcoma has been complicating the diagnosis of sarcoma for years. Even expert pathologists of sarcoma could make mistakes in the diagnosis of this disease. The availability of Next Generation Sequencing (NGS) data enabled more accurate diagnosis of sarcoma. In this study, we systematically described the application of NGS on the diagnosis of sarcoma and the contribution of NGS to the diagnostic accuracy of sarcoma. Methods: A multi-center, retrospective study included 235 sarcoma patients’ tumor and paired normal samples that were sent from 56 hospitals to a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory, at Shanghai, China for Next Generation Sequencing (NGS) was performed. Using next generation sequencing based YS panel consisting 450 genes, these 235 sarcoma patients’ sample were sequenced and the NGS data was analyzed. The initial diagnosis without NGS information was reconsidered by expert pathologists. Results: Taking into consideration both the initial diagnosis and the NGS results, the final diagnosis of these 235 sarcoma cases included 8 low grade malignant fibromyxoid tumors, 11 dermatofibrosarcoma protuberans (DFSP), 38 myxoliposarcomas, 22 alveolar rhabdomyosarcomas, 11 alveolar soft tissue sarcoma, 2 desmoplastic small round cell tumors, 37 NTRK rearrangement spindle cell tumors, 40 Ewing’s sarcoma and 66 synoviosarcomas. In total, 29% initial diagnoses were changed according to NGS identified fusions, including 13% low grade malignant fibromyxoid tumors (1 FUS- CREB3L2 fusion), 27% DFSPs (3 COL1A1- PDGFB fusions), 11% myxoliposarcomas (3 FUS- DDIT3 fusions and 1 EWSR1- DDIT3 fusion), 14% alveolar rhabdomyosarcomas (2 PAX7- FOXO1 fusions and 1 FOXO1- LINC00598 fusion), 18% alveolar soft tissue sarcomas (2 ASPSCR1- TFE3 fusions), 50% desmoplastic small round cell tumor (1 EWSR1- WT1 fusion), 95% NTRK rearrangement spindle cell tumors, 13% Ewing’s sarcomas (3 EWSR1- FLI1 fusions and 2 EWSR1- ERG fusions) and 21% synoviosarcomas (9 SS18- SSX1 fusions and 5 SS18- SSX2 fusions). Conclusions: NGS would be highly recommended for accurate diagnosis of sarcoma, especially for NTRK rearrangement spindle cell tumor, the majority of which were confirmed according to NGS identified fusions.
Comprehensive genomic profiling in malignant myoepithelioma to suggest potential alternative diagnosis.
Authors: Siontis Brittany , McHugh Jonathan B. , Schrock Alexa Betzig , Pavlick Dean , Ross Jeffrey S. , Ali Siraj Mahamed , Miller Vincent A. , Robinson Dan R. , Athanikar Jyoti , Wu Yi-Mi , Chinnaiyan Arul , Baker Laurence H. , Schuetze Scott , Chugh Rashmi 
Published: May 2020

e23530 Background: Malignant myoepithelioma of soft tissue (MM) is a rare tumor affecting patients (pts) of any age without sex predilection. MM has varied histopathologic findings, with epithelioid and spindle components and differentiation along osseous, chondroid or other lineages. Morphologic features suggest MM, however histologic overlap with other lesions exists. Diagnosis requires ancillary immunohistochemical &/or molecular studies; EWSR1 rearrangement with various fusion partners has been reported. Clinical behavior is varied and poorly understood due to disease rarity. Here, we undertook comprehensive genomic profiling (CGP) of MM to evaluate for potential targetable molecular alterations and report clinical outcomes. Methods: We identified pts with MM treated at University of Michigan (UM) from 2000-2017, obtained clinical data and reviewed pathology on 10 available samples and performed integrative sequencing through Michigan Oncology Sequencing Program (MI-ONCOSEQ) on 6. For 31 additional FFPE samples, hybrid capture-based DNA CGP (n = 16) or DNA+RNA CGP (n = 15) was performed (Foundation Medicine, FM). Results: 13 pts were treated at UM; median age at diagnosis was 52 (22-88) with male predominance (9/13). Primary tumor size was 3 cm (2-9.5) and most common location was trunk (4/13) and extremity (3/13). Four pts with metastatic disease (mets) underwent systemic chemotherapy with 0 responses. Median progression free and overall survival in mets was 20 (5-75) and 57 (12-91) months, respectively. CGP analyses of all samples (Table) revealed EWSR1 rearrangement in 8.1% (3/37) and presence of PHF1-TFE3 and CIC:DUX4 rearrangements in 16% (6/37). Independent blinded histopathology review of whole slides and tissue is underway. Conclusions: MM is a rare malignancy with variable clinical course. In our series, pts with mets derived little benefit from systemic therapy. CGP revealed CDKN2A/B alteration as the most prevalent with few harboring EWSR1 rearrangement. PHF1-TFE3 was recently described in ossifying fibromyxoid tumor (OFMT) that may represent a subset of OFMT not yet expressing bone markers. The presence of hypermutation and CIC:DUX4 fusions also suggests potential alternate diagnosis. These results indicate that CGP could complement histopathologic evaluation to aid in diagnoses and treatment of this entity. [Table: see text]
Development of urine metabolomic biomarkers for ifosfamide-induced encephalopathy (IIE) in soft tissue sarcoma patients.
Authors: Kinnebrew Garrett , Liebner David A. , Phillips Audra , Stets Colin W. , Tinoco Gabriel , Mathe Ewy , Chen James Lin 
Published: May 2020

e23534 Background: In the treatment of sarcomas, high doses of ifosfamide in combination with other chemotherapeutic agents remains a backbone of cytoreductive therapy. Unfortunately, IIE remains a prevalent treatment side effect with a reported prevalence of 10-20%. Although mild hypoalbuminemia has previously been implicated as a risk factor, its risk contribution is modest. There are no clinically significant biomarkers which may help identify IIE patents. Given the correlation with hypoalbuminemia to renal function, we hypothesized that urinary metabolites may serve as potential early biomarkers for IIE. Here we report our interim biomarker findings as part of our sarcoma metabolomic biocollection protocol. Methods: All sarcoma patients that received ifosfamide were identified (2011-2020) through a sarcoma registry (OSU-14242). Development of IIE was obtained through chart review. For consented patients undergoing adriamycin and ifosfamide treatment, urine samples were obtained over the course of 5 days and two treatment cycles (OSU IRB: 2014C0181). Urine samples were subjected to targeted metabolomic analysis for known ifosfamide metabolites and untargeted metabolomic profiling. LC-MS was performed on a Sciex TripleTOF 5600 and data preprocessing with XCMS. For each metabolite, mean abundance and slope, as determined by linear regression across all time points, was compared to development of IIE coded as a binary variable. Results: A total of 70 sarcoma patients were identified, of whom 11 developed IIE for a prevalence of 15.7%. Baseline values at the start of ifosfamide treatment were a mean albumin of 3.7 g/dL (+/- 0.38) and a mean serum creatinine of 0.79 mg/dL (+/- 0.26). Both values are within our “normal range”. For seven of these patients, of whom one developed IIE, we successfully collected additional metabolomic profiling. From these data, 6,030 features (representing metabolites or metabolite fragments) were measured. Time course plots of drug metabolites for which pure standards were run showed an increase of expected chemotherapy-related metabolites at the beginning of each cycle, with inter- and intra-patient variability. IIE was associated with 70 metabolite features (by mean abundance, FDR < 5%). Metabolite identification of putative features based on tandem mass spectrometry is in process. Conclusions: This pilot study indicates that urine metabolomic analysis is feasible and may identify IIE biomarkers. We expect to confirm these results once ongoing specimen analysis is complete.
Prognostic role of pre-treatment neutrophil-to-lymphocyte ratio in patients with soft tissue sarcoma.
Authors: Park Se Jun , Lee Jinsoo , Shin Kabsoo , Kim Hyunho , Kim In-Ho , Lee Ji Eun 
Published: May 2020

e23537 Background: Recent studies suggest that the neutrophil-to-lymphocyte ratio (NLR) may be associated with prognosis in several cancers. However, it has not been widely accepted in a clinical situation. In this study, we investigated the clinical significance of NLR as prognostic marker in patients with soft tissue sarcoma. Methods: Between January 2008 to December 2018, 168 patients with STS who had available blood counts at the time of diagnosis were retrospectively evaluated. Receiver operator characteristic (ROC) curve analysis was used to identify the optimal cut-off value for NLR in predicting overall survival. The association between NLR and overall survival (OS) and disease-free survival (DFS) was analyzed with Kaplan-meier method and multivariate Cox proportional models. Results: A total of 168 patients were analyzed, 116 (69.0%) patients were initially resectable disease. Based on the results of ROC curve analysis, patients were classified into two groups as; high-NLR ( > 1.8) and low-NLR (≤1.8). High-NLR was presented in 107 (63.7%) patients which was significantly associated initial disease status (HR 3.30; 95% CI 1.51-7.20, p= 0.002), but not with age at diagnosis ( p= 0.167). High-NLR was significantly correlated with worse OS (HR 3.14; 95% CI 1.62-6.10, p < 0.001). 3-year DFS was 26.2% for high-NLR group versus 37.3% for low-NLR group. DFS tended to be better in low-NLR group, though not statistically significant (HR 1.65; 95% CI 0.95-2.87, p= 0.078). Conclusions: Pre-treatment NLR is a useful predictive factor for prognosis in patients with soft tissue sarcoma. Further studies are needed to evaluate the association between factors representing of host inflammatory status and cancer prognosis.
Patient-reported global health predicts adverse health outcomes in a cohort of patients with advanced sarcoma.
Authors: Husain Marium , Phillips Audra , Tinoco Gabriel , Chen James Lin , Liebner David A. 
Published: May 2020

e23547 Background: Given the rare nature of sarcoma cancers and the sometimes severe treatment-related effects of chemotherapy, many patients with sarcoma face quality of life issues during treatment. Unplanned hospital admission and emergency room (ER) visits can occur from uncontrolled symptoms and ultimately delay treatment regimens and negatively impact quality of life. The PROMIS Global Health v1.2 (PROMIS-10) surveys are validated tools to assess patients’ physical and mental well-being at the time of the survey. We sought to evaluate the correlation between PROMIS-10 scores and adverse outcomes of interest, including unplanned admissions/ED visits and patient mortality. Methods: All patients currently seen in the Sarcoma Clinics at Ohio State University routinely complete the PROMIS-10 survey at each clinic visit. For this pilot study, we collected the raw and normalized t-scores for PROMIS-10 surveys for all patients consented to The Ohio State University Sarcoma Registry (OSU-14242) from 6/1/2018 to 11/20/2019. We also collected data on unplanned hospital admission/ED visits and mortality data for each patient. Results: A total of 864 surveys for 112 patients were collected for the study period. The median number of surveys answered per patient was 6. Mean global physical t-scores (43.7 ± 8.5) and mental t-scores (47.9 ± 9.2) were lower than reference scores for the general US population (p < 0.001). 109 of 112 patients experienced an unplanned admission or ED visit during the study, with a total of 270 such encounters during the study period. PROMIS-10 scores were slightly but significantly lower for patients experiencing an admission or ED visit within 30 days of taking the survey (physical: 41.9 vs 44.1, p = 0.006; mental: 46.4 vs 48.2, p = 0.035). A total of 26 patients died during the study period; surveys completed prior to death were consistent with a greater level of physical and mental distress, with the median physical t-score = 34.9 (range: 23.5 – 50.8) and mental t-score = 43.5 (range: 33.8 – 67.6). Conclusions: We showed that we are able to obtain worthwhile data to objectively evaluate patients’ physical and mental well-being through survey data during cancer treatment. We are currently performing additional confirmatory analysis of the predictive value of the PROMIS-10 survey for adverse events and for treatment-related complications.
Epitheliod sarcoma: Molecular insights into proximal versus classic variant.
Authors: Frezza Anna Maria , Sigalotti Luca , Del Savio Elisa , Baldazzi Davide , Sbaraglia Marta , Righi Alberto , Gambarotti Marco , Barisella Marta , Brich Silvia , Dei Tos Angelo Paolo , Stacchiotti Silvia , Maestro Roberta 
Published: May 2020

e23552 Background: Epithelioid sarcoma (ES) is an ultra-rare sarcoma with distinctive pathologic and clinical features, marked by the loss of the expression of the SWI/SNF chromatin remodeling complex subunit SMARCB1. The current WHO classification recognizes two ES subtypes, different by morphology, clinical behavior and outcome: the “classic-type” and “proximal-type” ES. This study is aimed to better understand the molecular grounds sustaining this difference, and to identify new potential treatment targets to personalize therapy in this rare disease. Methods: RNA sequencing profiling was conducted on FFPE samples. Functional annotation enrichment was evaluated through over representation and gene set enrichment analyses (GSEA). Inference of immune contexture was obtained through deconvolution and single sample GSEA (ssGSEA) approaches. Results: Twelve samples from 5 proximal-type ES and 7 classic-type ES were profiled, 10 naïve and 2 pre-treated with chemotherapy. Proximal variant samples featured an overepresentation of MYC activity signatures and of other signatures impacting on cell cycle, protein synthesis and chromatin metabolism. Pathways enriched in the classic variant included NOTCH/HEDGEHOG and immune system regulation (e.g. inflammatory, interferon alpha and interferon gamma). Accordingly, deconvolution and ssGSEA approaches predicted an increased immune infiltration in classic subtype samples, essentially involving T cells, as well as increased expression of HLA class I molecules. Conclusions: Different regulatory networks seem to contribute to the different biologic and clinical behavior of proximal and classic ES. These preliminary data suggest a potential greater sensitivity of proximal type ES to drugs targeting the cell cycle, whilst immune checkpoint inhibitors might have some activity in classic variant ES. Further studies are ongoing to validate these preliminary observations.
Patient and diagnostic intervals of sarcoma patients: Results from a survivorship study in the Netherlands.
Authors: Soomers Vicky L.M.N. , Husson Olga , Desar Ingrid M.E. , van de Sande Michiel , De Haan Jacco , Verhoef Cornelis , Vriens Ingeborg , van Houdt Winan J. , van de Poll-Franse Lonneke V , Van Der Graaf Winette T.A. 
Published: May 2020

e23553 Background: Sarcoma patients are hypothesised to experience long intervals to cancer diagnosis, due to the rarity of the disease, heterogeneous presentation, and complexity of histological diagnosis. Comprehensive assessment of patient interval (time between first symptom and presentation to a doctor), diagnostic interval (time between presentation to a doctor and diagnosis ), and their associated factors is needed to improve referral pathways and outcomes for sarcoma patients. We investigated patient and diagnostic intervals and identified factors associated with prolonged intervals in order to identify risk groups. Methods: We conducted a cross-sectional cohort study among adult sarcoma survivors, diagnosed between 2008-2016. After informed consent, patient-reported interval length was collected via (online) questionnaires. This data was linked to the Netherlands Cancer Registry, which collects clinical data from patients at diagnosis. Descriptive statistics were used to describe interval lengths. Logistic regression analyses were conducted to investigate associations of patient and tumour characteristics (gender, age at diagnosis, time since diagnosis, histology, presence of metastases, grade, and localisation), with patient and diagnostic interval length. Results: 1099 survivors completed questionnaires (response rate 58%); 53% had a patient interval ≥1 month. Risk factors for a patient interval ≥1 month were bone or breast sarcoma, and being young(18-39 years). An interval ≥3 months (33%) was associated with dermatofibrosarcoma protuberans, bone sarcoma, low grade, and location in skin or pelvis. Diagnostic interval length was ≥1 month in 53%; risk groups were bone sarcomas, females, and young (18-39) or middle-aged (40-69) patients. In 27% the diagnostic interval lasted ≥3 months; risk groups were synovial sarcoma, chordoma, bone sarcomas in general, females, and being young (18-39) or middle aged (40-69). Conclusions: Over half of sarcoma survivors had a patient interval ≥1 month; a third ≥3 months. More than half of them reported a diagnostic interval ≥1 month; a quarter ≥3 months. Females and young patients were more at risk for a long diagnostic interval. Although limited by its retrospective nature, this study is the largest that studied the interval in a sarcoma survivorship group. Our current QUEST study (NTR-7253) will study the diagnostic trajectory prospectively to confirm these findings and find reasons for these results.