bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic algorithm for gastrointestinal stromal tumor (GIST) using patient registry data impacts pathology guidelines.
Authors: Rothschild Sara , Call Jerry , Corless Christopher L. , Gill Anthony , Miettinen Markku , Rubin Brian 
Published: May 2020

e23519 Background: The Life Raft Group (LRG) identified that succinate dehydrogenase (SDH) deficient GISTs are under-recognized. In the LRG Registry only 30% of KIT/PDGFRA wildtype patients had received the advanced mutational testing (or SDHB staining) required to identify this unique subtype of GIST with a different natural history and response to treatment, and very strong familial associations. We proposed that two changes would significantly increase the diagnosis of SDH-deficient GIST patients: 1. SDHB staining for all GIST patients with a stomach primary tumor at initial biopsy, 2. Initial pathology report should contain strong recommendations for specific mutational testing. Methods: The LRG collaborated with key medical opinion leaders on a diagnostic algorithm that illustrated the need for wider use of targeted diagnostic procedures and submitted the algorithm to the College of American Pathologists (CAP) GIST editorial board. Results: Because SDH-deficient GISTs require germline genetic analysis and, if mutation related, subsequent surveillance for paragangliomas/pheochromocytomas, and cascade genetic testing for family members, it is necessary to screen all gastric GISTs for loss of SDH by immunohistochemistry. This is best accomplished by immunohistochemical staining for SDHB, which is lost in all genetic subtypes of SDH-deficient GISTs. If SDHB is absent, additional staining for SDHA may be performed, as this protein is selectively lost in SDHA-mutant GISTs and this may help focus genetic analysis. All patients with SDH-deficient GIST should be referred to a genetic counselor. The CAP incorporated both SDHB and SDHA testing paradigms into the updated GIST protocols which were published in August 2019. Conclusions: We believe this will result in significantly better diagnosis and treatment for SDH-deficient GIST patients. We encourage other groups that advise on guidelines to develop similar recommendations. This is a great example of a patient advocacy group utilizing real world evidence derived from a patient registry to influence protocols for treatments that affect GIST patients on a large scale.
A comprehensive characterization of anatomical and molecular risk factors in gastric gastrointestinal stromal tumor.
Authors: Boye Kjetil , Wiedswang Anne Marit , Meza-Zepeda Leonardo A. , Hompland Ivar , Lobmaier Ingvild , Berner Jeanne-Marie , Stoldt Stephan , Hølmebakk Toto 
Published: May 2020

e23522 Background: Gastric gastrointestinal stromal tumors (GISTs) demonstrate a remarkable diversity in clinical behavior. Established risk criteria identify patients prone to recurrence with high sensitivity, but factors that could add specificity are needed. The aim of this study was to give a comprehensive picture of localized, gastric GIST and to investigate prognostic factors in a large population-based series. Methods: Patients with primary gastric GISTs completely resected between 2000 and 2018 were identified in the sarcoma database at Oslo University Hospital. Gastric subsite was divided into the upper, middle and lower thirds. Macroscopic growth pattern was coded as luminal, exophytic or transmural based on imaging and surgical reports. Mutation analysis was performed by Sanger sequencing of selected exons in KIT and PDGFRA and by targeted next-generation sequencing. Results: The cohort comprised 295 patients, representing 98% of patients in the region reported to the Cancer Registry of Norway. Of 292 tumors suitable for anatomical classification, 122 were located in the upper third of the stomach (41.8%), 120 in the middle (41.1%), and 50 in the lower third (17.1%). The number of luminal, exophytic and transmural tumors were 100 (34.1%), 94 (32.1%) and 99 (33.8%), and 2 tumors were not possible to classify. KIT mutations were detected in 183 of 256 tumors (71.5%), PDGFRA mutations in 62 (24.2%), whereas only 11 patients (4.3%) had KIT and PDGFRA wild-type tumors. Transmural tumors were larger, more often located in the upper third, had higher mitotic activity, and more frequently had KIT del557/558 mutations. KIT mutated tumors had a predilection for the upper two thirds and PDGFRA mutated tumors for the lower two thirds. Recurrences were rare among patients with luminal or exophytic tumors, with a 5-year RFS of 96% versus 71% with transmural tumors (HR 8.45; 95% CI 3.69-19.36; P< 0.001). RFS was inferior with transmural tumor growth also among high-risk patients, 46% versus 83% at 5 years ( P= 0.001). Excluding patients with tumor rupture, there was only one recurrence among 24 high-risk patients with luminal or exophytic primaries, of whom 11 did not receive adjuvant therapy. Conclusions: This study provides a comprehensive, population-based description of the anatomical and molecular landscape of gastric GIST, with findings of potential clinical relevance. Transmural tumor growth was a predictor of poor outcome and could supplement established risk factors in selecting patients for adjuvant imatinib treatment.
The real world outcomes of 3-year adjuvant therapy with imatinib in patients with high-risk molecular profiled gastrointestinal stromal tumors (GIST).
Authors: Rutkowski Piotr , Zietek Marcin , Cybulska-Stopa Bozena , Streb Joanna , Gluszek Stanislaw , Jankowski Michał , Lopacka-Szatan Karolina , Las-Jankowska Manuela , Hudziec Piotr , Klimczak Anna , Olesinski Tomasz , Switaj Tomasz , Kosela-Paterczyk Hanna , Bylina Elzbieta , Osuch Czeslaw 
Published: May 2020

e23524 Background: The real-world data on outcomes of adjuvant therapy in high-risk gastrointestinal stromal tumors (GIST) are very limited. Methods: We have analyzed the data of 107 consecutive patients (52 male, 56 female) with GIST after resection treated with adjuvant imatinib (for planned 3 years with initial dose 400 mg daily, started not later than 4 months after operation) in 6 oncological centers in 2013-2018. All patients were required to have high risk of recurrence (at least 50% according to NCCN/AFIP criteria), known mutational status to exclude PDGFRA D842V mutants and KIT/PDGFRA-wild type cases from therapy. Median follow-up time was 24 months. Results: The most common primary localization of GIST was small bowel (63 patients; 59%), followed by the stomach (40 patients; 37%). The majority of GIST cases harbored exon 11 KIT mutations (88 cases, 82%), 11 cases had exon 9 KIT mutations (10%), 8 had other KIT/PDGFRA mutations potentially sensitive to imatinib. Thirty three patients (31%) finished 3-year adjuvant imatinib therapy as planned, 59 (55%) still continue therapy, 4 (4%) patients had finished adjuvant therapy prematurely due to toxicity, 6 (6%) due to disease progression on treatment and 5 (4%) due to other reasons. The disease relapse was detected in 16 patients, of them in 4 cases in exon 9 KIT mutants (36%), and 10 cases in patients with exon 11 KIT mutations (11%) [p < 0.05]. Estimated 4-year relapse-free survival (RFS) rate is 78%. Conclusions: The early results of adjuvant therapy with imatinib in routine practice outside clinical trials in high-risk mutation-drive GIST patients only confirm high efficacy of this therapy with better tolerability than in clinical trials. Moreover, overrepresentation of exon 9 KIT mutants in a group of patients with disease relapse may indicate that standard 400 mg dose in adjuvant treatment is not sufficient for prevention of disease relapse.
The prognostic value of CINSARC in a randomised trial comparing histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001).
Authors: Pasquali Sandro , Braglia Luca , Chibon Frederic , Coindre Jean Michel , Italiano Antoine , Romagosa Cleofe , Bague Silvia , Dei Tos Angelo Paolo , Palmerini Emanuela , Quagliuolo Vittorio , Martin Broto Javier , Lopez-Pousa Antonio , Grignani Giovanni , Brunello Antonella , Blay Jean-Yves , Diaz Beveridge Robert , Stacchiotti Silvia , Merlo Domenico F , Casali Paolo Giovanni , Gronchi Alessandro 
Published: May 2020

e23531 Background: The Complexity INdex in SARComas (CINSARC) is a gene expression signature related to mitosis and chromosome integrity that stratifies risk for recurrence of soft tissue sarcoma (STS) patients. The aim of this study was to validate the prognostic value of CINSARC in patients enrolled in a randomised trial that compared histotype-tailored neoadjuvant chemotherapy with standard chemotherapy in patients with high-risk STS (ISG-STS 1001). Methods: CINSARC is 67-gene-expression-based signature that has been previously tested in retrospective series. The ISG-STS 1001 was a phase 3 RCT comparing histotype-tailored and anthracycline-based chemotherapy in localised, high-risk STS of the extremities or trunk wall, with one of five histological STS subtypes: high-grade myxoid liposarcoma, leiomyosarcoma, synovial sarcoma, malignant peripheral nerve sheath tumour, and undifferentiated pleomorphic sarcoma. Outcome variables were disease-free survival (DFS), overall survival (OS) and tumour response according to RECIST v1.1. Results: CINSARC was assessed in pre-treatment biopsies of 87 in 435 patients participating in the study. Thirty and 57 patients segregated in the lower (C1) and higher (C2) CINSARC risk group, respectively. Incidence of local recurrences (LR) and distant metastasis (DM) did not differ between C1 and C2 CINSARC groups [2 (6.6%) and 11 (19.3%) patients had a LR, respectively, and 10 (33.3%) and 14 (24.5%) patients had DM, respectively, P = 0.800]. Consistently, we did not observe statistically significant differences for DFS and OS between patients in the CINSARC C1 and C2 groups (log-rank test, P = 0.522 and P = 0.480, respectively). RECIST tumour response was analysed in a subset of patients (N = 39), showing that a RECIST SD was more likely in C1 (N = 12/14, 85.6%) compared to C2 (N = 18/25, 72%) group, while both RECIST PD and PR were more commonly detected in C2 [3/25 (12%) and 4/25 (16%), respectively] compared to C1 [0/14 (0%) and 1/14 (7.1%), respectively] group. Conclusions: In high-risk STS patients treated with preoperative chemotherapy within a RCT, CINSARC did not correlate with different DFS and OS. While this may well be due to a failure of this gene signature in this patient population, an alternative hypothesis is that preoperative chemotherapy may improve the prognosis of higher-risk patients. Clinical trial information: NCT01710176 .
Potential use of homologous recombination deficiency score as an indicator of therapy selection in leiomyosarcoma patients.
Authors: Zhou Yuhong , Guo Xi , Guo He , Zhuang Rongyuan , Liu Wenshuai , Zhang Yong , Tong Hanxing , Wang Zhiming , Wang Yan , Lv Chentao , Lu Weiqi , Dai Chun , Liu Jun 
Published: May 2020

e23539 Background: Leiomyosarcoma (LMS) is one of the most frequent sarcoma subtypes. While surgical resection is the standard treatment of LMS, chemotherapy and radiation have shown additional survival benefit. However, the treatment response is variable and selection of appropriate agents is difficult due to the great heterogeneity of LMS. Matching DNA damaging reagents or PARP inhibitors, to tumors with a general homologous recombination deficit (HRD), can help to deploy these reagents more precisely. We explored the correlation of HRD score with the activation of PARP signaling pathway and retrospectively tested the effect of platinum-based therapy on an LMS patient with high HRD score. Methods: Nineteen LMS samples were subjected to whole exome sequencing and their HRD scores were calculated using a published algorithm. Nine of the LMS samples were also subjected to RNA-seq analysis and undergone GSEA to profile PARP pathway expression. CIBERSORT was employed to profile infiltrating immune cells. Results: The 19 LMS samples are defined as HRD-high (11 samples) or HRD-low (8 samples) if their HRD score is above or equal to, or below the medium respectively. For the 9 samples undergone RNA-seq, 97 genes have differential expression between the two groups (p-value < 0.05, fold change≥ 2). GSEA revealed 23 enriched pathways. Interestingly, PPAR signaling pathway is the most highly enriched one (EnrichmentScore = 0.506, P.adj = 0.005). No other pathogenic germline or somatic mutation in HRD related genes, for example BRCA1/2, is enriched. Additionally, high HRD score is significantly correlated with infiltrating Tregs, monocyte, and M0 macrophages as found in CIBERSORT analysis. To retrospectively test whether HRD score can be used to predict the response to inhibitors of DNA repair pathway, we identified one patient who had received platinum-based combination therapy after failure of first-line chemotherapy. The patient is a 40-year-old female with stage IV LMS and has a high HRD score. She achieved PR with 6-month PFS and remains progression free up to the abstract date, supporting a good correlation between high HRD score and advanced chemotherapy in LMS patients. Conclusions: High HRD score is correlated with activated PPAR pathway and infiltrating Tregs, monocytes and M0 macrophages, and can potentially be used to identify LMS patients with good response to platinum-based chemotherapy even though they have no obvious germline and somatic mutation in genes involved in DNA repair.
Uterine sarcomas, insight into its risk factors: A systematic review.
Authors: Hana Caroline , D'Amato Gina Z. 
Published: May 2020

e23540 Background: Uterine sarcomas are rare and aggressive malignant tumors that arise from the smooth muscle or connective tissue cells of the uterus. They account for approximately 1% of the female tract malignancies and 3% of all malignant tumors of the uterus. The risk factors that would predispose to uterine sarcomas have always been unknown, with no clear correlation with specific etiologies. This review is to investigate the risk factors that have been looked at by prior studies to have a better understanding of the population at higher risk for uterine sarcomas. Methods: A total of 88 studies were obtained via Pubmed search. The search terms included: Uterus, sarcoma, and risk factors. We also included reviews with the following mesh terms: Uterus, Sarcoma, Etiology and factors. We reviewed studies in English (n = 75) and French (n = 4) languages, human studies and comprising adults. We included only studies with electronic copies. Retrospective, case-control studies and systematic reviews were included. Results: Of the 88 studies, 18 mentioned risk factors and demographic characteristics of the population with uterine sarcomas. Some studies have shown an association with the tumor size – especially more than or equal to 8cm-, uterine weight, patient’s age being > 45-50 years old, age at menarche, obesity, tamoxifen use, previous pelvic irradiation, as well as genetic associations. Mixed evidence has been found regarding the role of the ethnicity, age at menopause, age at first live birth and exogenous estrogen use. Breast cancer has been linked to more aggressive histologic cell types. Conclusions: Given its relatively rare incidence, uterine sarcoma has been mysterious in regards to its risk factors. The results of this review highlight the need for further studies to investigate the risk factors and exposures that may lead to development of uterine sarcomas, as well as linking them to the different histologic types.
The Epstein-Barr virus and osteosarcoma in Iranian children.
Authors: Rahbar Mahtab , Mardanpour Keykhosro 
Published: May 2020

e23543 Background: This study was conducted to describe the possible association between EBV infection and OS in Iranian children. Methods: This study carried out at Kermanshah university hospital on 48 OS tissue and ten non-cancerous bone tissue as a control group by three laboratory methods. The real-time polymerase chain reaction (RT-PCR) and Chromogenic in-situ hybridization (CISH) done to detect the Epstein Barr Encoded RNA (EBER1) expression as long as immunohistochemistry staining (IHC) to detect EBV latent membrane protein-1 (LMP-1) in tumor cells and controls. Overall-survival (O-S), prognosis free survival (PFS) and disease-free survival (DFS) provided based on the Kaplan-Meier method. Results: Specimen considered positive when EBER using PCR and CISH associated with LMP-1 using IHC stain were expressed separately in the same sample. Six out of eighty-four (12.5%) of OS cases were simultaneously EBV positive in all three methods within the tumor cells as compared to the control group. (P < 0.22) Association between EBV positivity and histologic characteristics of OS cases such as nodal involvement (P < 0.04), metastasis (P < 0.04), Ki67 reactivity (as proliferation index) (P < 0.03), and tumor stage (P < 0.05) were significant. EBV Positive patients show worse clinical symptoms in older age as well as the worse prognosis compared with negative patients. EBV positive patients presented shorter DFS, PFS, and OS. Conclusions: Our research could not find a statistical association between EBV infection and OS in Iranian children significantly. Meanwhile, we found, EBV infection could interfere in the invasive behavior of tumors. [Table: see text]
Factors of angiogenesis (VEGF and CD34) in primary and recurrent soft tissue sarcomas.
Authors: Nepomnyashchaya Evgeniya M. , Ulianova Elena P. , Sagakyants Aleksandr B. , Novikova Inna A. , Vashchenko Larisa N. , Ausheva Tatiana V. , Shulgina Oksana G. , Dashkova Irina R. , Vladimirova Liubov Yu , Kit Oleg I. 
Published: May 2020

e23545 Background: The tumor ability to induce and maintain angiogenesis is one of the main stages of its development. Studies of molecular mechanisms of angiogenesis showed that the dynamic balance that ensures the formation and development of new vessels inside the tumor depends on pro- and anti-angiogenic factors. VEGF and the CD34 endothelial cell marker are considered among the main activators of angiogenesis. Our purpose was to study characteristics of angiogenesis in primary and recurrent soft tissue sarcomas. Methods: The study included 30 patients with primary sarcomas (group 1) and 26 patients with recurrent sarcomas (group 2). Sections of tissues embedded in paraffin blocks were studied by immunohistochemistry using the Thermo Scientific 480S automated stainer. The Reveal Polyvalent HRP-DAB Detection System was used for the visualization. The density of blood vessels stained with antibodies against VEGF and CD34 was determined. The statistical analysis of results was performed in the STATISTICA 10.0 program (StatSoftInc., USA). Results: The numbers of blood vessels ranged: CD34 in group 1 – 7-16 blood vessels in one field of view; in group 2 – 2-18 vessels. VEGF in group 1 – 2-20 vessels, with up to 40 vessels in 3 cases (11.5%) only; in group 2 – 5-11 vessels, with up to 20 vessels in 2 cases (7.7%). The average numbers of microcirculatory vessels stained with antibodies against VEGF and CD34 were: CD34 –12.2±1.04 and 8.4±1.4 (p = 0.0247) in groups 1 and 2, respectively; VEGF – 12.8±4.06 and 8.4±11.6 (p = 0.3074) in groups 1 and 2, respectively. Conclusions: The IHC analysis showed the minimal numbers of microcirculatory vessels in one field of view in patients with recurrent soft tissue sarcomas. The value was 1.5 times lower for both CD34 and VEGF, compared to patients with primary tumors. However, only CD34 value was statistically significant (the Mann–Whitney U-test). Probably, a certain decrease in angiogenesis factors in recurrent tumors can be explained by adjuvant chemotherapy suppressing tumor growth.
Analysis of trends in race and gender disparities in incidence-based mortality in patients diagnosed with soft tissue sarcomas from 2000 to 2016.
Authors: Pappoppula Lakshmi Priyanka , Ajebo Germame Hailegiorgis , Yeh Justin , Hector Picon , Krutchik Allan N. , Guddati Achuta Kumar 
Published: May 2020

e23549 Background: The clinical course of soft tissue sarcomas is often dependent on the grade of the tumor. The incidence of soft tissue sarcomas have been known to be higher in males compared to females and more in African Americans compared to Caucasians (1995 to 2008 SEER data). The variability of incidence-based mortality in low grade and high grade soft tissue sarcomas with respect to gender and race over the past decade has not been well studied. This study analyzes the rates of incidence-based mortality from the years 2000 to 2016 amongst for both the grades, genders and racial groups. Methods: The Surveillance, Epidemiology, and End Results (SEER) Database was queried to conduct a nation-wide analysis for the years 2000 to 2016. Incidence-based mortality for all stages of low grade and high grade soft tissue sarcomas was queried and the results were grouped by race (Caucasian/White vs African American/Black) and gender. All stages and ages were included in the analysis and trend from 2000 to 2016 was analyzed. Results: Incidence-based mortality rates (per 10000) for low grade and high grade soft tissue sarcomas for both races and genders are shown in the table below. The incidence-based mortality rates for Caucasians are similar to African American in both grades and genders. Rates were not analyzed for American Indian and Asian/Pacific Islanders due to small sample size. Mortality rates of high grade soft tissue sarcomas were significantly higher compared to low grade tumors. A higher rate of mortality is noted in Caucasian males compared to African Americans males despite past observations of higher incidence in African Americans. There was no significant change in the rate when trended over the past decade (2007 to 2016). Conclusions: This study highlights the higher rate of incidence-based mortality in Caucasian males compared to African American males in the past 15 years despite a lower incidence reported in the 1995 to 2008 period. With no significant change in mortality rates/year noted during this time period, this study implies that soft tissue sarcomas in Caucasian males have worse outcomes. Further research is needed to understand the mechanism underlying this disparity. [Table: see text]