bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toxicity and efficacy of busulfan-melphalan (BuMel) compared to treosulfan-melphalan (TreoMel) high dose chemotherapy (HDCT) consolidation in high-risk Ewing sarcoma (ES): A 12-year monoinstitutional experience.
Authors: Abate Massimo Eraldo , Paioli Anna , Cesari Marilena , Longhi Alessandra , Palmerini Emanuela , Setola Elisabetta , Carretta Elisa , Cammelli Silvia , Ronchi Letizia , Rocca Michele , Manfrini Marco , Scotlandi Katia , Donati Davide Maria 
Published: March 2020

e22507 Background: We compared toxicity and outcomes of BuMel and TreoMel HDCT consolidation with stem cell rescue in high-risk ES pts prospectively treated in 5 consecutive trials at the Istituto Ortopedico Rizzoli, Bologna, Italy. Methods: Eligible pts had histologically proven diagnosis of ES, high-risk disease defined as localized disease with poor histological/radiological response to standard chemotherapy or lung/pleural metastases or extra-pulmonary metastases or relapsed disease, were aged < 40. All pts received previous standard chemotherapy (vincristine, ifosfamide, doxorubicin, etoposide, cyclophosphamide actinomycin-D) and surgery and/or radiation therapy (RT) as local treatment. From June 1, 2011, TreoMel was used instead of BuMel to avoid potential severe complications related to busulfan, as in case of previous RT on axial skeleton/pelvis. Pts with lung metastases received lung irradiation 12-15 Gy at least 2 months after HDCT. Results: Between January 1, 2007, and September 30, 2018, 98 pts received BuMel or TreoMel: 52 pts with localized disease (7 TreoMel), 26 pts with lung/pleural metastases (5 TreoMel), 10 pts with extra-pulmonary metastases (4 TreoMel) and 10 pts with relapsed disease (1 TreoMel). Median age was 18 yrs (range 3-39 yrs). 14 out of 17 TreoMel pts received previous RT on axial skeleton/pelvis. Median follow up is 4.2 yrs (range 10 mo. - 12 yrs). Pts treated with TreoMel showed a significant lower incidence of grade 3-4 stomatitis (p = < 0.001) and of all grade ≥ 3 non-hematological toxicities (p = < 0.001). One pt died of BuMel-related toxicity (sinusoidal obstruction syndrome/veno-occlusive disease) and none after TreoMel. For localized ES, the 5yr-EFS was 66.7% (95%CI, 47.9-78) for BuMel pts and 66.7% (95CI%, 19.5-90.4) for TreoMel pts. Conclusions: In high-risk ES, TreoMel is significantly less toxic then BuMel. Combining RT on central/axial sites and TreoMel is feasible. In localized ES, results show similar 5yr-EFS between BuMel and TreoMel. TreoMel could be used instead of BuMel when busulfan is contraindicated.
Creation and characterization of a novel human PDGFRA D842V-mutant GIST cell line.
Authors: Klug Lillian Rose , Abalakov Gleb , Griffith Diana , Town Ajia , McKinley Arin , Grunewald Susanne , Bauer Sebastian , Rink Lori , Heinrich Michael C. 
Published: March 2020

e22512 Background: Activating PDGFRA mutations are seen in about 10% of gastrointestinal stromal tumors (GIST). Of these, the majority are one specific PDGFRA mutation, D842V, which confers resistance to all clinically approved tyrosine kinase inhibitors (TKI). Much has been learned about the mechanism by which TKIs work in GIST using cell lines derived from human GIST that bear activating KIT mutations. However, despite enormous effort to develop cell lines derived from human tumors over the past 15 years, there are currently no human cell models of PDGFRA D842V GIST. With the development of potent PDGFRA D842V TKI, such as crenolanib, avapritinib, and DCC2618 it is of interest to understand how these drugs affect PDGFRA-mutant GIST biology. Methods: We sought to convert the KIT-driven GIST-T1 cell line to be PDGFRA-driven by transduction with PDGFRA D842V. Endogenous KIT expression was knocked-out using CRISPR Cas9. Knockout was verified at protein and DNA levels. Clonal KIT knockout cell lines were tested for sensitivity to KIT and PDGFRA TKI both in vitro and in vivo models. Kinase dependence was determined by measuring the effect on viability after KIT and/or PDGFRA knockdown by siRNA. Results: GIST-T1 cells transduced with PDGFRA D842V display highly phosphorylated PDGFRA, imatinib resistance, and PDGFRA dependence. Cell lines that express both endogenous mutant KIT and exogenous PDGFRA D842V maintain some dependence on KIT, but less so than the parental KIT-driven GIST-T1 cell line. Complete knockout of KIT protein expression was achieved in GIST-T1 D842V cells using CRISPR-Cas9. GIST-T1 D842V KITko cell lines demonstrate sensitivity to TKI avapritinib, crenolanib, and DCC2618. Xenografts were established using GIST-T1 D842V KITko cell lines and are sensitive to avapritinib in vivo. Conclusions: The GIST-T1 D842V KITko cell line demonstrates ability to switch kinase allegiance resulting in PDGFRA-dependence and KIT-independence. This GIST-T1 D842V KITko cell line represents a novel model of PDGFRA-mutant GIST and can be used to understand the unique biological aspects of these tumors, particularly the response to new potent PDGFRA kinase inhibitors such as avapritinib which will have immense clinical relevance.
Clinical presentation, natural history and therapeutic approach in patients with solitary fibrous tumor: A retrospective analysis.
Authors: Schoffski Patrick , Timmermans Iris , Hompes Daphne , Stas Marguerite , Boecxstaens Veerle , De Leyn Paul , Coosemans Willy , Van Raemdonck Dirk , Hauben Esther , Sciot Raf , Clement Paul M. , Bechter Oliver Edgar , Beuselinck Benoit , Woei-A-Jin Feng Jung Sherida Harriette , Dumez Herlinde , Wessels Tim 
Published: March 2020

e22522 Background: Solitary fibrous tumor (SFT), a rare variant of soft tissue sarcoma (STS), is characterized by the presence of a NAB2-STAT6 fusion. Given the orphan character of SFT we performed a retrospective analysis. Methods: We retrospectively reviewed all patients (pts) with SFT treated in our institution between 12/1990 - 09/2017. Results: We identified 94 SFT pts (incl. hemangiopericytoma) with a med. follow-up for 4.7 yrs. Common anatomic sites were chest (33%), abdomen (21.3%), brain (12.8%) and extremities (9.6%). The symptomatology at diagnosis was variable. Only 6.4% presented with synchronous metastasis. Hypoglycemia (Doege-Potter syndrome) was seen in 2.1% of cases. A resection of the primary SFT was done in 86 pts (91.5%), their disease-free survival was 35.5 mo and 43% stayed SFT-free during follow-up. Local recurrence occurred in 26.7% of cases, associated with a med. overall survival (OS) of 45.1 mo. Metachronous metastasis was seen in 30.2% of pts, occurring after a med. follow-up of 36 mo. Med. OS after diagnosis of metastasis was 19.0 mo. Systemic therapy was given to 92.9% of pts with inoperable/metastatic disease. The most common 1st line therapy was doxorubicin single agent (57.7% of pts), achieving responses in 13.3% of pts. 2nd line therapies included ifosfamide and pazopanib (31.3% of pts each), 3rd line treatment was very heterogeneous. Conclusions: SFT is an orphan malignancy with a variable clinical course, low incidence of distant spread at first diagnosis but considerable risk of local failure and metachronous metastasis. Surgery is the only curative option at diagnosis, time of relapse and in case of resectable metastasis. Palliative systemic therapy is considered in pts with inoperable/metastatic disease but achieves low response rates. The natural course and survival outcomes of SFT cases treated with palliative intent tend to be better than in non-selected STS pts.
Systemic therapy in advanced dermatofibrosarcoma protuberans: Imatinib and beyond.
Authors: Gupta Anshul , Rastogi Sameer , Kumar C Santosh , Barwad Adarsh , Dhamija Ekta , Panday Rambha , Deo S. V. S. , Shishak Sorun , Aggarwal Aditi , Dutta Rimlee , Manasa Parisa , Kumar Pankaj 
Published: March 2020

e22523 Background: Imatinib is the standard treatment of advanced Dermatofibrosarcoma (DFSP). However ideal treatment of advanced DFSP patients, who have progressive disease (PD) on imatinib, remains an unanswered question. Methods: We retrospectively analysed consecutive advanced DFSP patients who presented to AIIMS Sarcoma Medical Oncology clinic between January 2016 and January 2019. Results: There were eleven patients, with median age of 35 years, seven (63.6%) of which were males. Fibrosarcomatous transformation was present in six (54.5%) patients. Four (36.4%) had locally advanced disease, while seven (63.6%) had metastatic disease. Primary site was trunk in eight (63.7%) patients. Three (75%) of the four patients who received neoadjuvant imatinib, underwent complete surgical resection. Initial dose of imatinib was 400mg OD in eight (72.7%) patients, 600 mg OD in two (18.2%) and 800 mg OD in one (9.1%) patient. The best response to imatinib was Partial response (PR) in nine (81.8%) patients, stable disease (SD) in one (9.1%) and primary PD in one (9.1%) patient. Median progression free survival (PFS) was 16 months, after a median follow up of 14 months. Five (45.4%) patients had PD on imatinib. As mentioned in table, strategies used in these patients were pazopanib (n = 3), doxorubicin (n = 2), other chemotherapy (n = 2), dose escalation of imatinib (n = 2) and reintroduction of imatinib (n = 1). One patient had prolonged stable disease on pazopanib, while remaining had PD. Conclusions: Imatinib remains prominent first line therapy in advancved DFSP. Though pazopanib has shown some promise, the treatment outcomes in second line therapy and beyond have largely been dismal and need to be studied prospectively.[Table: see text]
Is PAX3-FOXO1 associated with worse outcome in adults with rhabdomyosarcoma (RMS)?
Authors: Guram Sheena , Dirks Julia , Barot Shivali , Griffin Anthony , Weinreb Ilan , Demicco Elizabeth , Shultz David Benjamin , Abdul Razak Albiruni Ryan , Gladdy Rebecca Anne , Gupta Abha A. 
Published: March 2020

e22525 Background: Rhabdomyosarcoma (RMS) is a rare soft tissue sarcoma in adults. The PAX3-FOXO1 fusion gene is associated with alveolar rhabdomyosarcoma. PAX3-FOXO1 results from a stable reciprocal translocation of chromosomes 2 and 13, which fuses in-frame the DNA binding domain of PAX3 with the transactivation domain of FOXO1. Occasionally, PAX7-FOXO1 is expressed. In children, the PAX3-FOXO1 fusion gene is associated with worse outcome. We evaluated the prognostic role of FOXO1 fusion status in adults with RMS treated in a single, large volume sarcoma centre. Methods: A retrospective review of adult RMS patients (pts) diagnosed from 1984 to 2018 was done. Information on demographics, treatment, fusion status and survival was collected. Primary favourable site was defined as tumour arising in orbit, non-bladder/prostate genitourinary system and non-parameningeal head and neck. Factors were compared using Fisher’s Exact test. Event-free survival (EFS) was estimated by the Kaplan-Meier method and compared with log rank test. FOXO1 fusion status was coded as FP (fusion positive) or FN (fusion negative). Results: Of 134 pts identified in our database, fusion testing was performed in 55 (41%). Of these, PAX3 fusion was detected in 22 (40%). PAX7 was not detected. The median age of FP and FN pts was 25 yrs (range 18, 90) and 27 yrs (range 18, 65), respectively. Gender distribution was similar between FP and FN. Favourable site was seen in 13 (60%) FP and 21 (64%) FN. Nodal disease was present in 21 (95%) FP and 21 (64%) FN (p = 0.02). Distant metastases were present in 10 (45%) FP and 9 (27%) FN (n.s.). Treatment received was as follows for FP and FN, respectively: chemotherapy (21(95%), 33(100%)), radiation (14(64%), 22(67%)) and surgery (4(18%), 17(52%)). 5-yr EFS for pts without distant metastases was 27% (CI 22.6-76.6) and 46% (CI 21.5 – 70.5) for FP and FN respectively (n.s.). Conclusions: FP and FN RMS occurs in adults of all ages. Similar to children, adults with FP are more likely to present with nodal disease. Our study did not show that fusion status was associated with poorer EFS in adult RMS, however, larger series are needed to confirm this preliminary data.
Incidence and prevalence of synovial sarcoma in the US: An analysis using SEER*Stat.
Authors: Joseph Nedra , St. Laurent Samantha , Nelson Jeanenne Joy , Zheng Shan , Stirnadel-Farrant Heide 
Published: March 2020

e22535 Background: Synovial sarcoma (SS) is a rare and aggressive soft tissue sarcoma which primarily affects the extremities of the arms and legs, and can also occur in the head and neck, lungs and pleura, and the trunk. The disease burden of SS is generally extrapolated from overall soft tissue sarcoma (STS) with SS accounting for 4.5% of all STS (587 cases estimated in 2018 in the US) (Noone, 2018; Siegel, 2018). The objective of this study was to provide disease burden estimates specific to SS in the US. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) 18 Registries, Nov. 2017 (2000-2015) were analyzed using SEER*Stat software (v8.3.5). The incidence and prevalence of SS was estimated by utilizing SS-specific International Classification of Diseases for Oncology, V.3 (ICD-O-3) and histology codes. Data from 2011-2015 were used to project incidence rates (age-specific and age-adjusted), 5-year limited duration prevalence, number of incidence and prevalent cases, and the age distribution of synovial sarcoma for 2018. Results: In the US, the age-adjusted incidence rate of SS was 0.177 per 100,000 (estimated 580 incident cases) in 2018. SS is more frequently manifested in patients aged 20-49 years, with the highest occurrence of new cases in patients between 45-49 years (incidence rate 0.26 per 100,000). The prevalence rate of SS across all ages was 0.65 per 100,000 (estimated 2129 prevalent cases) as of January 1, 2018. Conclusions: We described incidence and prevalence rates of SS, including age-specific and age-standardized rates, and characterized the age distribution of SS. This approach provided more precise estimates that are specific to SS without extrapolation from STS, and which are not available in the literature. References: Noone AM, et al. (ed). SEER CSR, 1975-2015, https://seer.cancer.gov/csr/1975_2015/ . Siegel RL, et al. Cancer statistics, 2018. CA Cancer J Clin 2018;68:7–30.
Successful generation of patient-derived xenografts and cell lines as preclinical models for sarcomas.
Authors: Kondo Tadashi , Oyama Rieko , Kito Fusako , Noguchi Rei , Hattori Emi , Takahashi Mami , Ichikawa Hitoshi , Yoshida Akihiko , Kawai Akira 
Published: March 2020

e22549 Background: The establishment of patient-derived preclinical models has been a challenge issue in sarcomas, because of the rarity of diseases. We report our successful experience in establishing patient-derived sarcoma xenografts and cell lines. Methods: Tumor tissue samples from sarcoma patients undergoing surgery were collected by a team of orthopedicians and pathologists. Small tumor fragments were subcutaneously transplanted to immunodeficient NOG mice. The other part was used to establish a cell line using serum-containing media. The omics profiling was performed to examine the preservation of molecular backgrounds during the model establishment. Effects of FDA-approved drugs were examined in the established models. Results: Since April 2014, tumor samples from 246 sarcoma cases have been processed. The sample characteristics are summarized in the table. Currently we have established PDXs and cell lines from 39 and 27 cases, respectively. Xenografts and cell lines were established from unique sarcomas such as CIC-DUX4 fusion positive sarcoma, extraskeletal osteosarcoma, primary leiomyosarcoma of bone, and alveolar soft part sarcoma. A take rate of xenografts and cell lines varied among the sarcoma types. Omics profiles considerably changed during the process of model establishment. Anti-cancer drugs with significant tumor suppressive effects were detected. Conclusions: Our patient-derived cancer models will facilitate translational sarcoma research. The original biological features preserved in the xenografts and cell lines should be clarified to optimize the utility of sarcoma models. Currently, our cell lines are available for the academic researchers upon a request.
Apatinib for epithelioid sarcoma: analysis on eight advanced stage cases in a single institute.
Authors: Chen Yong , Sun Wei , Wang Bing , Qu Xing-Long , Zheng Bi-Qiang , Huang Wen-Ding , Sun Zheng-Wang , Wang Chun-Meng 
Published: March 2020

e22551 Background: Epithelioid sarcoma (ES) is a rare high grade soft tissue sarcoma with high incidence of lymph node involvement and distant metastasis. It is widely recognized that ES is not sensitive to chemotherapy and radiation, surgical treatment is the only curative option for localized diseases. Tyrosine kinase inhibitors (TKIs) has been proven to be effective in sarcomas, here we report the experience of Apatinib in 8 advanced ES cases. Methods: ES patients treated in Fudan University Shanghai Cancer Center from Dec, 2016 to Aug, 2018 were accrued retrospectively. Those with locally advanced diseases or distant metastasis were treated with orally Apatinib 500mg, daily use for at least 2 months. Assessment of efficacy and side effects were recorded every 2 months and patients were then treated according to reponses to Apatinib. Results: There were 8 patients with locally advanced or late stage ES in a total 20 ES patients during the study period. There were 6 males and 2 females with median age of 55 years (20-73). 3 of the 8 were classical type and 5 were proximal type. 7 of the 8 patients were locally advanced and 1 was with lung metastasis at diagnosis. 4 of the 8 had a partial response to Apatinib and one patient has a downstaged ES which was surgically removed. The other 4 had a stable disease to Apatinib but 2 were not able to tolerate side effects and stopped at first evaluation, the other 2 remains progression free. Main side effects included skin rash, hypertension and diarrhea. Hypertension was the only Grade 3-4 side effect. With median follow-up of 12 months, 6 remains progression free, the 2 patients who didn’t tolerate side effects and stopped Apatinib developed lung metastasis. Conclusions: Apatinib has unproven but promising effect in ES, TKI is an option especially for those not sensitive to cytotoxic agents and radiation.
No relevant activity of olaratumab in patient-derived soft tissue sarcoma xenografts selected for expression of platelet-derived growth factor receptor a.
Authors: Cornillie Jasmien , Van Renterghem Britt , Van Winkel Nathalie , Wellens Jasmien , Gebreyohannes Yemarshet , Debiec-Rychter Maria , Sciot Raf , Hompes Daphne , Wozniak Agnieszka , Schoffski Patrick 
Published: March 2020

e22556 Background: Soft tissue sarcoma (STS) comprises a heterogeneous family of rare tumors of mesenchymal origin. Single-agent doxorubicin (DOX) remains the standard-of-care for advanced and inoperable STS, but response rates are < 15% and survival is generally poor. In 2016, Tap et al. reported impressive results of a phase Ib/II trial combining DOX and the platelet-derived growth factor receptor a (PDGFRA)-directed antibody olaratumab (OLA), suggesting an unprecedented survival advantage of the combination over DOX alone, without providing a mechanistic rationale for the observed activity (Lancet 2016;388:488-97). We decided to evaluate the efficacy of OLA in a panel of patient-derived STS xenografts (PDX). Methods: NMRI nu/nu mice were transplanted bilaterally with tumor tissue of models expressing PDGFRA, including PDX of leiomyosarcoma (UZLX-STS22), malignant peripheral nerve sheath tumor (STS39), myxofibrosarcoma (STS59) and undifferentiated pleomorphic sarcoma (STS84). Mice were randomly divided into 4 treatment groups: (1) control, (2) DOX (3 mg/kg once weekly), (3) anti-PDGFRA [OLA (60 mg/kg twice weekly) + mouse anti-PDGFRA antibody 1E10 (20 mg/kg twice weekly)] and (4) the combination of DOX and anti-PDGFRA (same dose/schedule as single treatment arms). Tumor volume, histopathology and Western blotting were used to assess treatment efficacy. Results: Anti-PDGFRA treatment as single agent did not reduce tumor growth and did not result in significant anti-proliferative or pro-apoptotic activity. Combining DOX and anti-PDGFRA did not reduce tumor burden, though a mild inhibition of proliferation was observed in models STS39 and STS59 and a pro-apoptotic effect was seen in all models except STS22. Antitumor effects on histology were not significantly different comparing DOX and the combination treatment. Anti-PDGFRA treatment, both as a single agent as well as with DOX, did not inhibit downstream MAPK and PI3K/AKT signaling pathways. Conclusions: In vivo findings in PDX models selected for PDGFRA expression support negative findings of the phase III trial NCT02451943 with OLA reported at this meeting.
The ideal amount of physical activity to improve quality of life and symptoms in lung cancer patients: A systematic review.
Authors: Castro Gilberto , Codima Alberto , das Neves Willian , Borges Ana Paula Souza 
Published: March 2020

e23158 Background: The symptoms which burden lung cancer patients contribute to a vicious cycle of physical inactivity as the disease progresses. Some studies have shown that exercise is feasible and safe for this population, and it improves their symptoms and quality of life. However, the current recommendations are non-specific, and little is known about the optimal amount and type of exercise in this scenario. Here we aimed to identify a specific recommendation of physical activity that could work more efficiently, benefiting lung cancer patients, in terms of diminishing their symptom burden and improving quality of life. Methods: A systematic review was undertaken through structured searches on PubMed, Medline, Embase, Scopus, Web of Science and SciELO. The search protocol was registered on the Prospero platform. Rayyan QCRI was used for data extraction and determining eligible studies after a blind screening of titles and abstracts by the three authors. The Physiotherapy Evidence Database (PEDro) scale was used for quality assessment of each eligible trial in regards of risk of bias. Trials which had clear eligibility criteria and a summary score equal or superior than 6 were considered to have low risk of bias, and accepted for full text review. Results: From September/1998 to January/2019, a total amount of 1998 studies were returned from the aforementioned databases, and 17 studies were established to be eligible for quality assessment. All the 17 quality-assessed studies were randomized clinical trials. However, two of them did not clearly report the eligibility criteria and were immediately excluded. Five other studies were considered to have high risk of bias. Therefore, we considered only 10 trials to be fully reviewed, including 843 patients. Only 3 trials found significant improvement in the quality of life after their interventions, and included 243 patients. Two studies associated aerobic exercise and resistance training from 10 to 20 weeks post surgery, while the other studied intervention was Tai Chi for 10 days after each chemotherapy cycle. Conclusions: Evidence from this review suggests that exercise may improve quality of life of lung cancer patients. However, we could not identify an ideal amount nor type of physical activity given the limited available data and the heterogeneity of methods. Further studies are warranted.