bluuebunny/crossref_metadata_2025_split huggingface dataset:
Staging work up in chondrosarcoma: Is a bone scan warranted for the metastatic workup of chondrosarcoma?
Authors: Gulia Ashish , Puri Ajay , Kurisunkal Vineet , Gupta Srinath 
Published: May 2020

e23508 Background: To assess the value of a bone scan in the metastatic workup of a patient diagnosed with chondrosarcoma of bone. Methods: Retrospective analysis. 480 patients of extremity chondrosarcomas were identified with the help of nuclear imaging records and pathology department data base over a period of 12 years. Their clinical, radiological and histopathological details were retrieved from case files and electronic medical records. All cases were staged with a CT scan of thorax and bone scan or a whole body PET-CT. All reported and suspicious cases of metastasis were reviewed again by an experienced radiologist for this study. 53 patients had to be excluded from the study due to incomplete staging modalities. Results: 427 patients were available for final evaluation. Grade was not available for 3 patients. No grade I chondrosarcoma (53) had evidence of metastasis. In the remaining high grade chondrosarcomas (374), isolated lung metastasis was seen in 9% (35 cases) (grade II-31, grade III-4), combined lung and bone metastasis was seen in 0.5% (2 cases) (all grade II) and isolated bone metastasis was seen in 1 % (4 cases) (all grade II). Conclusions: The present study shows that the incidence of bony metastasis in extremity chondrosarcomas is extremely low. A non-contrast CT thorax would be adequate for staging in conventional chondrosarcomas. In light of the present results we feel bone scan may be omitted from the staging work up of conventional skeletal chondrosarcomas. It may be reserved for only symptomatic patients.
Clinical characteristics, treatment modalities, and oncological outcomes in patients with gastrointestinal stromal tumors in Mexico.
Authors: Anaya Sanchez Luis Guillermo , Soberanis Piña Pamela Denisse , Meneses Medina Mónica Isabel , Cedro-Tanda Alberto , Rosas Camargo Vanessa , Huitzil Melendez Fidel David 
Published: May 2020

e23514 Background: In Mexico there is scarce information regarding treatment and outcomes of patients with gastrointestinal stromal tumors (GIST). Access to medical therapy in a country with limited resources may impact survival. We aim to report clinical characteristics, treatment modalities, and oncological outcomes in patients with GIST treated at our institution. Methods: Single-center retrospective review of patients with histologically confirmed diagnosis of GIST evaluated between Jan 2005 to Dec 2018. Overall survival (OS) was estimated by Kaplan-Meier curves and compared with log-rank rest. A p value < 0.05 was significant. Results: 90 cases were included with a median age of 57 years, 61% were women. Most common symptoms were gastrointestinal bleeding (68%), abdominal pain (58%) and anemic syndrome (54%). Primary tumor location was stomach (51%), small intestine (43%) and other locations (6%). 89% (n 80) were localized and 11% (n 10) metastatic. For localized tumors, Fletcher risk stratification was used to predict prognosis. We found 44% low, 29% intermediate and 27% high-risk. Treatment for localized patients was: initial surgery (95%, n76), neoadjuvant imatinib (5%, n4). Adjuvant imatinib was given to only 69% of patients that required it (31 of 45 patients with intermediate or high-risk), 12.5% (n12) of patients with localized disease had recurrence (2 of them did not receive adjuvant treatment). In the advanced seating (n10), most common site of metastasis was liver 70%. Initial treatment was surgery in 6 patients. Only 5 patients received imatinib (50% of those who required it). Only one patient had second line sunitinib. None had access to regorafenib, none had a molecular analysis performed. Survival outcomes are shown in table. Conclusions: Patients with localized GIST treated at our institution have good oncological outcomes and similar to those reported by other series. On the other hand, patients with advanced disease have inferior outcomes compared to those reported by other series possibly related to limited access to treatment. [Table: see text]
Modulation of YAP/ TAZ by statins to improve survival in epithelioid hemangioendothelioma (EHE).
Authors: Subramaniam Aparna , Zheng Jing , Yalamanchili Sudha , Conley Anthony Paul , Ratan Ravin , Somaiah Neeta , Livingston J Andrew , Zarzour Maria Alejandra , Araujo Dejka M. , Benjamin Robert S. , Patel Shreyaskumar , Ravi Vinod 
Published: May 2020

e23527 Background: EHE is a rare soft tissue tumor of endothelial origin. It is distinguished by the pathognomonic WWTR1-CAMTA1 fusion (WWTR1 is the gene symbol for TAZ) seen in 90% of the tumors. YAP1-TFE3 fusion is less common and seen in 10% of the tumors. YAP and TAZ are critical downstream effectors of the Hippo pathway that regulate tumor development, progression, invasion and metastasis by modulating the expression of many Hippo pathway targets. Recent studies have shown that inhibition of HMG-CoA reductase, a key enzyme of the mevalonate pathway, can regulate YAP/ TAZ by preventing their nuclear accumulation and inhibiting their transcriptional activity. This has led to interest in the role of statins, which inhibit HMG-CoA reductase, as a modulator of YAP/ TAZ that could benefit patients with sarcoma, particularly EHE. Methods: A retrospective analysis was performed on patients with a diagnosis of EHE at M D Anderson Cancer Center. Patients were identified using the electronic database system and screened for statin use using EMRs. Demographic and clinical characteristics were tabulated. KM method was used to assess overall survival and log rank test was used to test survival differences between the statin use and non- statin use groups. All statistical analysis was performed using STATA 14. Results: 226 patients with EHE were identified. 27 of them had recorded statin use during the course of their disease. The median OS for the statin use group was not reached and the mean OS was 221 months. The median OS for the non- statin use group was 123.9 months, while the mean OS was 160 months. The difference in OS was not statistically significant between the two groups. The median follow-up time for our cohort was 36.6 months. Conclusions: Our findings indicate a trend towards improved survival for patients with EHE who have received statins over the course of their disease. Our study is limited by a small number of patients who received statins. Prospective studies are required to assess the therapeutic benefit of statins in EHE. [Table: see text]
Prediction of histologic and molecular subsets of soft tissue sarcoma using deep learning.
Authors: Rosenberg Ari , Kochanny Sara , Dolezal James , Wang Cindy , Chen Heather , Kather Jakob Nikolas , Pearson Alexander T. 
Published: May 2020

e23529 Background: Soft tissue sarcomas (STS) are histologically and molecularly heterogenous with variable biologic behavior and differential therapeutic responses. Molecular analysis of STS is commonly utilized to identify targetable mutations or identify STS subtypes that have predictive and prognostic implications. To address the challenge of rapid, accurate classification of STS subtypes, we sought to develop an approach using a form of artificial intelligence called deep learning to identify meaningful hidden information directly from digital H+E slide images. We trained a deep learning model using genotype and phenotype data from The Cancer Genome Atlas (TCGA) and companion diagnostic digital H+E slide images, in order to identify therapeutic biomarkers and prognostic molecular subtypes. Methods: Digital whole slide images (WSIs) from TCGA were downloaded and regions of tumor were annotated by pathologists. WSIs were carved into 604 um by 604 um square tiles within the tumor region and saved at an image size of 598 px by 598 px for a resolution of ~1um/px. These tiles were used as input to a deep convolution neural network (Xception model pretrained on imagenet). Performance results are reported at the as the average of three-fold cross-validation, averaged at the patient level. Results: 206 sarcomas available through the TCGA were used as training set. Sarcoma histologies include 80 leiomyosarcoma (LMS) (27 uterine LMS and 53 non-uterine LMS), 50 dedifferentiated liposarcoma (DDLPS), 44 undifferentiated pleomorphic sarcoma (UPS), 72 myxofibrosarcoma (MFS), and 10 synovial sarcoma (SS). FNCLCC grade 1 (n = 14), grade 2 (n = 112), and grade 3 (n = 80). Histology could be predicted automatically with very high accuracy for LMS (Area under Receiver-operator curve (AUROC) 0.93 and 0.95 for uterine and non-uterine LMS respectively), DDLPS (AUROC 0.70), UPS (AUROC 0.76), and MFS (AUROC 0.76). FNCLCC grade could be predicted for grade 3, 2, 1 with AUROC of 0.79, 0.73, and 0.81 respectively. High vs. low mitotic rate (threshold 15) could be predicted with AUROC of 0.70. Within non-uterine LMS, prognostic molecular cluster could be predicted with AUC of 0.62 for cluster with worse recurrence-free and disease specific survival. Within DDLPS, DNA methylation cluster 2 associated with worse disease specific survival was predicted with AUC of 0.80. Conclusions: Deep learning algorithm analysis of histologic slides was able to predict clinically meaningful characteristics and molecular clusters with reasonable accuracy. Retrospective and prospective validation is needed.
Multiscale omic assessment of EWSR1-NFATc2 fusion positive sarcomas to identify conserved fusion breakpoint and activation of the mTOR pathway.
Authors: Seligson Nathan David , Maradiaga Richard D , Stets Colin W. , Katzenstein Howard , Millis Sherri Z. , Hays John L. , Chen James Lin 
Published: May 2020

e23536 Background: EWSR1-NFATc2 ( E-N) fusion positive sarcomas are rare cancers historically categorized as Ewing sarcomas. Emerging evidence suggests unique molecular characteristics and chemotherapy sensitivities in these cancers. Here we present the largest cohort of genomically profiled E-N fusion positive sarcomas and evaluate their breakpoints and putative pathway alterations. Methods: Comprehensive genomic profiling of 1,024 EWSR1 fusion positive sarcomas, including 14 E-N fusions, was obtained through the Foundation Medicine research database (FMI). Additional data from the Gene Expression Omnibus, the Genomics of Drug Sensitivity in Cancer (GDSC), and The Cancer Genome Atlas (TCGA) datasets were used. Descriptive statistics, principle component analysis, differential expression, and pathway analysis were used as appropriate. Results: E-N fusions identified in the FMI database demonstrated consistent breakpoints located between exon 2 and 3 on NFATc2; consistent with previous reports suggesting that the primary transactivation domain and regulatory domains of NFATc2 are conserved in the EWRS1-NFATc2 fusion. Cluster analysis demonstrated separate E-N fusion positive sarcoma grouping than other EWRS1 sarcomas, while identifying an enrichment of mTOR pathway variants in E-N fusion positive samples (p = 0.05). Gene expression data from E-N identified a significant activation of the mTOR pathway in E-N positive sarcomas compared to either EWSR1-ETS (p = 0.002) or CIC-DUX4 positive sarcomas (p < 0.001). In the GDSC database, NFATc2-High lines exhibited activation of the mTOR pathway (p < 0.0001) and were more sensitive to the mTOR inhibitor rapamycin (p = 0.0006). Pan-cancer analysis of 33 non-overlapping TCGA datasets, elevated NFATc2 mRNA expression was significantly associated with activated RICTOR and mTOR signaling (p < 0.0001). Elevated NFATc2 correlated with higher tumor grade and poorer progression-free survival and overall survival. Conclusions: Taken together, the data presented here suggests that E-N fusion positive sarcomas represent a distinct molecularly entity in comparison to traditional Ewing sarcomas. Conserved action of NFATc2 may correlate to mTOR over activation.
Sarcoma Treatment Efficacy Portal (STEP): A novel informatics portal providing real-time, real-world outcomes to clinicians.
Authors: Grosenbacher Nicholas , Phillips Audra , Liebner David A. , Tinoco Gabriel , Chen James Lin 
Published: May 2020

e23538 Background: There are currently no informatics tools that are capable of providing complex clinical decision support using real-world outcomes (RWO) for patients with sarcoma. Although existing nomograms can provide prognostic scores based on clinical or genomics features, they typically are static and lack the ability to compare outcomes for patients managed with alternative treatment strategies. To address this need, we present STEP, a Sarcoma Treatment Efficacy Portal, a web-based tool designed for real-time exploration and visualization of patient data with the potential to be integrated into clinical decision workflows during outpatient visits. Methods: At The Ohio State University, clinical histories and omics data for sarcoma patients are captured in our prospective Sarcoma Registry (NCT0267796). STEP is an interactive web-based tool built in R/Shiny and supported by a pipeline written Python that processes, transforms, and caches clinical data extracted from the Sarcoma Registry in near real-time. Protected health information (PHI) is stored on a secure HIPAA compliant server behind the hospital firewall and migrated to a secure, deidentified staging database. Results: The STEP system is powered by detailed treatment specific data elements that are continuously abstracted for over 400 patients with bone and soft tissue sarcoma. This consists of manually annotated clinical histories in addition to nearly 10 million discrete data points are pulled from the EHR (labs, ICD-9/10 codes, medications, omics data). Importantly, STEP includes a cohort builder which allows users to define a treatment group of interest though any number of variables including tumor histology, chemotherapy, and omic features of interest. For any predefined cohort, STEP can provide information on overall survival and response to a variety of treatments. It also provides sorting mechanisms for identifying candidate treatments. A secure web interface allows a simple integration into a busy clinic flow. Conclusions: STEP provides a first in class, convenient, clinician friendly platform for delivering access to real-time, real-world treatment outcomes (RWO) in patients with a diagnosis of bone or soft tissue sarcoma. Additional usability testing is forthcoming.
Multi-institutional collaboration in sarcoma and central nervous system tumors.
Authors: Gillingham Jacob , Siontis Brittany , Robinson Steven Ian , Okuno Scott H. 
Published: May 2020

e23544 Background: Rare diseases are defined as conditions that affect less than 200,000 people annually in the United States. Around 17000 cases of sarcoma will be diagnosed in 2020. Collaboration among institutions is needed to best understand rare diseases such as sarcoma. One measure of collaboration is publications with multiple institutions as authors. We sought to determine if collaboration in sarcoma has increased since 2011 and compared that to another rare disease, CNS tumors based on multi-institution-authored abstracts presented at ASCO. Methods: All sarcoma and CNS oral abstracts, clinical science symposia, poster presentations, poster discussions, and published-only ASCO Annual Meetings from 2011 to 2019 were reviewed. Collaboration was determined if the abstract authors were from more than one institution. Results: 2,134 abstracts were reviewed. Collaboration for sarcoma ranged from 0.603 to 0.720 and 0.582 to 0.755 for CNS. From 2011-2019 a positive linear trend in collaboration was found in CNS (P < 0.05), but not in sarcoma (P = NS). There was no significant trend in the incidence of collaboration in Sarcoma based on the type of presentation at ASCO. There was no difference in collaboration between bone or soft tissue sarcoma abstracts or median number of institutions collaborating between sarcoma and CNS. There were more international collaborations and absolute number of institutions in sarcoma vs CNS. Conclusions: Sarcoma collaboration has remained constant from 2011-2019 with greater number of institutions and more international collaborations as compared to CNS. CNS collaboration has increased from 2011-2019. Sarcoma collaboration at ASCO is robust and reflects the need for multi-institutional partnership.
Impact of upfront multidisciplinary tumor board (MTB) evaluation on breast sarcoma (BS) outcome.
Authors: Tolomeo Francesco , Chilà Giovanna , D'Ambrosio Lorenzo , Merlini Alessandra , Sgandurra Paola , Kubatzki Franziska , Sgrò Luca Giuseppe , Miano Sara , Manessi Giulia , Pisacane Alberto , Aliberti Sandra , Siatis Dimitrios , Gatti Marco , Biglia Nicoletta , Ponzone Riccardo , Aglietta Massimo , Grignani Giovanni 
Published: May 2020

e23546 Background: Although sarcomas may arise in any site of the body, the intrinsic challenge of BS is to affect the female most frequent cancer site with a completely different and rare set of heterogeneous tumors. Unfortunately, we lack BS-specific prospective trials to precisely guide the clinical decision-making and BS patients are often sent to sarcoma referral centers only after surgery without upfront BS MTB evaluation. Recent evidences reported a significant prognosis improvement with upfront MTB evaluation in retroperitoneal or extremity sarcomas, but whether this strategy might benefit also BS is still not defined. We retrospectively evaluated our prospectively collected database to test whether an upfront MTB evaluation at BS referral centers might impact prognosis and/or the need of subsequent surgeries. Methods: Detailed information on primary surgery, diagnosis, and ≥2 years of follow-up for non-recurring patients were required. We tested the following outcomes: event-free survival (EFS), local EFS (LEFS), distant metastases EFS (DMEFS), overall survival (OS), margin status, subsequent surgeries rate. We evaluated the different outcomes according to upfront MTB evaluation. Kaplan-Meier method was used for survival analyses. Comparisons used hazard ratios (HR). Results: We included 93 patients treated between 1/2000 and 10/2019 at 2 reference BS Centers, median age 53 years (IQR 41-70), ECOG (0;1;2) 67:16:10, high/low grade 60:33. Histotypes were: malignant phyllodes tumor 42 (45%), angiosarcoma 26 (28%), other STS 25 (27%). 27 (29%) cases were considered radiation-induced with a median time from RT of 105 months (IQR 70-127). 44 patients (47%) were discussed upfront in BS MTB, whereas 49 (53%) were not. With a median follow up of 43 months, 5-year EFS, LEFS, DMEFS, and OS for the whole population were 54%, 64%, 60%, and 62%, respectively. LEFS at 5 years had a strong association with margin status (R0 74%; R1 55%, R2 0%, p < 0.001). Regardless of histology, upfront MTB was associated with a significant lower rate of subsequent surgeries (OR 0.16, 0.06-0.41), and with better EFS, LEFS, DMEFS, and OS (HRs 0.57, 0.54, 0.63, and 0.43, respectively). Conclusions: Though retrospective, this series is one of the largest reported to date in BS. Our results highlight the need for early inter-tumor board sharing of BS to take into account sarcoma specificity in the overall disease planning. Given BS rarity, these data will hardly ever be verified in a prospective fashion. Therefore, validation of these results in the Italian Sarcoma Group database is planned.
Patient journey and quality of life (QOL) among diffuse-type TGCT in the U.S.
Authors: Bernthal Nicholas M. , Spierenburg Geert , van de Sande Michiel , Healey John H. , Stacchiotti Silvia , Bauer Sebastian , Gelderblom Hans , Staals Eric , López Bastida Julio , Fronk Eva-Maria , Ye Xin , Laeis Petra , Palmerini Emanuela 
Published: May 2020

e23565 Background: Diffuse Tenosynovial Giant Cell Tumor (d-TGCT) is a rare, locally aggressive neoplasm of joint and tendon sheath synovia, which may severely affect patients (pts) QOL due to pain, limited joint function and destruction of bone and local tissues. This study analyzes real-world data to describe d-TGCT pt journey and QOL in the US. Methods: The TGCT Observational Platform Project (TOPP), the first non-interventional prospective disease registry, enrolled d-TGCT pts at 10 Western European (EU) and 2 US sarcoma centers from Nov 2016 to Mar 2019, with prospective follow-up of 24 mo. Pts demographics, disease history and ongoing medical treatment and pt-reported outcomes (PROs) (pain, stiffness, PROMIS Physical Function [PF] and EQ-5D) were collected at baseline and every 6 mo during follow-up periods. Descriptive analyses from baseline compared US pts with Western EU pts (Table). Results: Of 166 d-TGCT pts, 30 were enrolled in the US. Mean age was 40.6 ± 12.82 y, with 63.3% female and 66.7% with tumor in knee. Median time from first symptom to diagnosis was 12 mo (range; 0–153). 28 pts (93.3%) had surgery, 4 pts (13.3%) had tyrosine kinase inhibitors (TKI), no pts had radiotherapy. 18 pts (60%) experienced >1 locoregional recurrence. Median Pain Severity Score (PSS) and Pain Interference Score (PIS) were 2.8 and 3.0, respectively. Median PROMIS PF Score was 39.8. Mean EQ-5D index score and visual analogue scale (VAS) were 0.73 ±0.229 and 75.5 ±13.31, respectively. Compared with Western EU pts, US pts reported similar PROs and QOL, were younger, had shorter delay in diagnosis, and lower use of systemic therapy or radiotherapy (Table). Conclusions: d-TGCT affects a relatively young population in the US, similar to Western EU, resulting in serious impairment in daily activities and QOL. Shorter diagnostic delay and less frequent use of non–surgical approach was observed in the US. [Table: see text]