bluuebunny/crossref_metadata_2025_split huggingface dataset:
A challenging case of Mesenchymal Chondrosarcoma involving the thyroid and special considerations for diagnosis
Authors: Nachawi Noura , Lew Madelyn , Konopka Kristine , Sandouk Zahrae 
Published: March 2020

AbstractBackgroundThyroid ultrasound is usually used to risk-stratify incidental thyroid nodules. Nodules with high risk sonographic features for malignancy are evaluated by fine-needle aspiration. The role of core needle biopsy for thyroid nodules is limited to cases where the fine needle aspiration is inconclusive.Case presentationWe describe a rare case of mesenchymal chondrosarcoma of the thyroid gland with uncertain primary origin. Thyroid ultrasound showed right sided large, solid, hypoechoic nodule with calcifications and peripheral vascularity and unremarkable isthmus and left thyroid lobe. Fine needle aspiration of the right nodule suggested lymphocytic thyroiditis. The sonographic findings contradicted the typical bilateral clinical and sonographic picture of lymphocytic thyroiditis. A core needle biopsy showed mesenchymal chondrosarcoma.ConclusionThis case highlights the importance of correlating pathologic diagnosis with sonographic findings, the appropriate utilization of fine needle aspiration and core needle biopsy to evaluate thyroid nodules and the rare incidence of mesenchymal chondrosarcoma involving the thyroid.
Recent progress in the development of advanced biofuel 5-ethoxymethylfurfural
Authors: Chen Binglin , Yan Guihua , Chen Gaofeng , Feng Yunchao , Zeng Xianhai , Sun Yong , Tang Xing , Lei Tingzhou , Lin Lu 
Published: March 2020

AbstractBiomass-derived 5-ethoxymethylfurfural (EMF) with excellent energy density and satisfactory combustion performance holds great promise to meet the growing demands for transportation fuels and fuel additives to a certain extent. In this review, we summarized the relative merits of the EMF preparation from different feedstocks, such as platform chemicals, biomass sugars and lignocellulosic biomass. Advances for EMF synthesis over homogeneous (i.e. inorganic acids and soluble metal salts), heterogeneous catalysts (i.e. zeolites, heteropolyacid-based hybrids, sulfonic acid-functionalized catalysts, and others) or mixed-acid catalysts were performed as well. Additionally, the emerging development for the EMF production was also evaluated in terms of the different solvents system (i.e. single-phase solvents, biphasic solvents, ionic liquids, and deep eutectic solvents). It is concluded with current challenges and prospects for advanced biofuel EMF preparation in the future.
Masitinib mesylate in imatinib-resistant advanced GIST: A randomized phase II trial.
Authors: Adenis Antoine , Le Cesne Axel , Bui Nguyen Binh , Bouche Olivier , Domont Julien , Ray-Coquard Isabelle , Penel Nicolas , Blesius Aurore , Montestruc Francois , Moussy Alain , Hermine Olivier , Blay Jean-Yves 
Published: March 2020

10007 Background: Masitinib is an oral tyrosine kinase inhibitor with greater in vitro activity and selectivity than imatinib against wild-type and juxtamembrane mutations of KIT (Dubreuil, 2009, PLoSONE). This trial studied efficacy and safety of masitinib at 12 mg/kg/day and sunitinib at 50 mg/day for the treatment of imatinib-resistant GIST. Methods: Patients with inoperable, locally advanced or metastatic GIST and showing disease progression while treated with imatinib 400 mg/day received either masitinib or sunitinib until progression. Primary endpoint was PFS evaluated with RECIST with OS as a secondary endpoint. Based upon an 80% power to detect with a Fleming design a median PFS ≥3 months (alpha 10%, unilateral), a population of 44 patients (22 per arm) was required. Stratification was applied based on mutation status. Results: 44 patients (exon 11 [66%], exon 9 [11%], wild-type or other [5%], not done at baseline [18%]) were randomized into masitinib (n=23) or sunitinib (n=21) treatment-arms from 9 centers between 02/2009 and 09/2011. After a median follow-up of 14 months, median PFS was 3.9 months (95%CI [2.6;8.1]) for masitinib vs 3.8 months [1.9;11] for sunitinib. Of those patients progressing under masitinib, 88% received sunitinib in third line. Median OS was not reached (NR) (95%CI [21;NR]) for masitinib vs 15 months [9.4;22] for sunitinib. The 18-month and 24-month OS rates for masitinib vs sunitinib were 79% (95%CI [53;92]) vs 20% [1.5;55], and 53% (95%CI [9.5;84]) vs 0%, respectively. Similar results were seen in the exon 11 subpopulation with median OS for masitinib NR (95%CI [NR;NR]) vs 15 months [9.6;22] for sunitinib. The safety profile of masitinib was better than sunitinib with a lower occurrence of severe related adverse events (AEs) (17% vs 52%) and related AEs leading to discontinuation (0% vs 9.5%). In masitinib treated patients, nausea, diarrhea and asthenia were the most common related AEs. Conclusions: Although PFS curves looked similar, this study apparently showed a longer survival in the masitinib treatment-arm with a better safety profile than sunitinib. Masitinib may potentially offer patients a new active compound for advanced GIST in the second-line setting.
Is CTNNB1 mutational analysis predictive for progression in patients with sporadic desmoid tumors primarily observed?
Authors: Colombo Chiara , Miceli Rosalba , Domont Julien , Perrone Federica , Fiore Marco , Le Cesne Axel , Le Pechoux Cécile , Gronchi Alessandro , Bonvalot Sylvie 
Published: March 2020

10016 Background: Recently, a wait and see (W&S) approach has been proposed for patients affected by desmoid tumor (DT). Specific CTNNB1 mutation has been correlated with higher risk of recurrence after surgical resection. Aim of this study was to evaluate the correlation between CTNNB1 mutation type and time to progression in patients primarily observed (TTP). Methods: We included all consecutive patients:(1) primarily observed at the Fondazione IRCSS Istituto Nazionale Tumori (Milano, Italy) or Institut Gustave Roussy (Paris, France) for primary sporadic DTs (2) with available FFPE preserved tissue for CTNNB1 mutational analysis, (3) with measurable disease and adequate follow-up. TTP from date of diagnosis to date of radiological (PRO-R) or symptomatic (PRO-S) progression were conducted by Kaplan-Meier method and log-rank test to compare strata. Results: A total of 79 patients (August 2002- July 2011) were included (81% female, 19% male); median age was 34 (IQ, 10-77); sites distribution: abdominal/chest wall (75%), extremity (21%), intra-abdominal (4%). CTNNB1 mutations were observed in 76% of DT samples: 41A (48%), 45F (25%), 45P (2%); 24% were WT. Median follow-up was 19 mo (IQ, 11-28). Thirty-six patients experienced progression (86% PRO-R, 14% PRO-S): 41A (47%), 45F (55%), 45P (100%), WT (26%). An inferior TTP at 36 months was observed in mutated patients vs WT, while no difference was detected for specific subtype mutated patients (WT 68%, 45F 24%, 41/45P 35%, p= 0.045). A variety of different treatments including surgery, hormonal therapy, chemotherapy, antiCOX2 or persistent W&S approach were proposed at progression. Forty-two patients did not receive any treatment. Conclusions: A clear trend towards a lower risk of progression was observed in WT patients, but no difference between specific mutated patients (45F vs 41/45P) was observed. Prospective studies to eventually clarify the potential role of CTNNB1 as prognostic tool in tailoring desmoids treatment are presently underway.
Gemcitabine/docetaxel for metastatic or locally advanced soft tissue sarcoma: A retrospective single-center experience.
Authors: Egerer Gerlinde , Wuchter Patrick , Dietrich Sascha , Schmier Johann Wilhelm , Ho Anthony D , Schmitt Thomas 
Published: March 2020

10040 Background: Soft tissue sarcoma (STS) represent a group of rare malignant tumors. Survival for patients with disseminated disease is dismal. Gemcitabine/docetaxel (GD) is a commonly used systemic 2°-line regime in this setting. Methods: Here we report on our single center experience of GD (G 900 mg/m² or 675 mg/m² d1+8 and D 100 mg/m² d8) in STS. Patients were retrospectively analysed. Restaging according to RECIST criteria of primary tumor site and metastases was performed every 3 cycles or on clinical progression. Progression-free (PFS) and overall survival (OS) were estimated using the method of Kaplan and Meier. Results: Between 2005 and 2011, 34 STS patients (male=20, female=14, median age 59 years [range 32-75]) were treated with GD at our institution. Histological subtypes comprised leiomyo- (n=13), lipo- (n=7), pleomorphic- (n=6), rhabdomyo- (n=3), synovial sarcoma (n=2), and other subtypes (n=3) with tumor grades being G1 (n=1), G2 (n=9) and G3 (n=24). Primary tumor sites included extremities (n=19), abdomen/retroperitoneum (n=10), trunk (n=3), and others (n=2). Metastases were found in lung (n=26), soft tissue/solid organs (n=12), bone (n=8) and lymph nodes (n=5). Patients had received no (n=2), 1 (n=22), 2 (n=9) or 3 (n=1) previous lines of CTX. A total number of 158 cycles was administered with a median number of 6 cycles (range 1-6) per patient. Best response by RECIST criteria after 3 cycles of treatment was PR (n=2, 6%). Disease stabilisation (SD) was achieved in further 22 subjects, resulting in a clinical benefit rate (CBR) of 70%. Median PFS and OS for the whole population were 7.7 and 15.3 months, respectively. PFS at 6 months was 62%. Patients responding to therapy had a significantly longer median PFS with 8.6 months (p <0.0001; HR 33.1) and OS with 22.5 months (p<0.0001; HR 20.2). Major toxicities included hand-foot syndrome (n=10), febrile neutropenia (n=7), mucositis (n=7), oedema (n=5), hematological toxicity (n=4) and polyneuropathy (n=3), leading to dose reductions in 10 patients. Conclusions: GD is an active regimen in STS with tolerable side effects. CBR was 70% after 3 cycles. Patients achieving at least SD had a significantly prolonged PFS and OS.
Delay in diagnosis and treatment of soft tissue sarcomas (STS): Causes of late intervention and their role in prognosis—A prospective, multidisciplinary group study.
Authors: Comandone Alessandro , Berno Elisa , Boglione Antonella , Oliva Cristiano , Ingui' Manuela , Linari Alessandra , Giubellino Elena , Gino Giancarlo , Brach del Prever Elena Maria , Faletti Carlo , Piana Raimondo , Turbiglio Marco , Monasterolo Gabriella , Pochettino Paolo , Dal Canton Orietta , Chiado' Cutin Simona , Bergnolo Paola 
Published: March 2020

10055 Background: STS are 1% of malignant tumors in adults. Rarity, heterogeneity in presentation, low expertise in primary care physicians (PCP) or in general hospitals, organisation problems in specialized centers may cause a delay in both diagnosis and treatment. Aim of this study is to acknowledge the barriers to optimal care and the consequences of the delay on prognosis. Methods: Patients with STS of the extremities, trunk, retroperitoneum treated and followed from 1999 to 2011 by the same multidisciplinary group were included. Time and pattern of symptoms onset, anatomic site, tumor volume, patients’ age, gender and home, interval between diagnosis and surgical treatment or neoadjuvant chemotherapy; time to start adjuvant RT or CT were considered in a univariate - multivariate analysis. Results: 449 adult patient (53% F, 47% M, median age 55 years) were followed for a median time of 116.38 months. 65.7% of STS were at the extremities, 17.6% retroperitoneal, 16.7% at the trunk wall. Median volume at diagnosis was 8 cm for trunk and extremities; 15 cm for retroperitoneum. Commonest histologies: liposarcoma. 18.2%; leiomyo 16.8%; mixofibro 13.6%. Increasing mass, pain, and abdominal disconfort were the main revealing signs of diseases. Median time of delay were: from onset of symptom to first medical visit 68 days for trunk and extremities, 82 for retroperitoneum; 104 days from symptoms to histological diagnosis; 129 days from symptoms to start of therapy. Time to surgery after definitive diagnosis was 12 days in extremities and 21 in abdomen. Adjuvant CT started 22 days after surgery for extremities, 25 in trunk, 35 in retroperitoneum. RT initiated after 78 days. Longer delay in treatment lead to worse prognosis: MS 89.95 months if delay was > 3 months; 190.40 months if wait was < 3 months (p 0.007). Conclusions: Low self consciousness of the patient; misdiagnosis or inadequate approach in general hospitals; late referral to specialized centres are 75% of the cause of wasted time. Organization problems at the referral Centre concur for 25% of delay. Guidelines implementation and educational programme among general population and PCP are necessary.
Preclinical study of trabectedin (TR) and poly(ADP-ribose)polymerase 1 (PARP-1) inhibitor combination in soft tissue sarcoma (STS).
Authors: Pignochino Ymera , Capozzi Federica , Dell' Aglio Carmine , Basiricò Marco , Tarraran Loredana , D'Ambrosio Lorenzo , Galizia Danilo , Palesandro Erica , Gammaitoni Loretta , Sangiolo Dario , Benassi Maria Serena , Aglietta Massimo , Grignani Giovanni 
Published: March 2020

10066 Background: TR is an alkylating agent approved in Europe for the treatment of advanced STS as second/third line therapy. TR binds to the minor groove of DNA and interferes with gene transcription and nucleotide excision repair mechanism, inducing DNA double strand breaks (DSBs), and S/G2 cell cycle arrest. There is a strong clinical interest to increase TR activity combining it with other anti-cancer drugs. PARP-1 inhibitors disable DNA base-excision repair mechanism causing the accumulation of DSBs and look like a reasonable TR partner to be explored. We focused our in vitro studies on the effects of the combination of TR with the PARP-1 inhibitor Olaparib (OL). Methods: We explored the activity of TR-OL combination against a panel of different histotypes of STS cell lines, evaluating cell viability after 72h treatment with escalating doses of TR (0-2 nM), OL (0-20 µM), and their constant combination. Following colony formation, cell cycle, apoptosis (annexin V+/PI+) and DNA damage (phospho-histone H2AX - Ser139) were checked. Results: The TR-OL combination strongly affects STS cell viability, showing synergism (Combination Index < 1, based on Chou–Talalay method) on 8 out of 13 cell lines tested. We observed a strong synergism, as a massive reduction of colony growth (402.91, MES-SA, and DMR-SN-8.4.98 lines) induced by the combination if compared with each single agent (78% vs. ~27% : p<0.05). OL potentiates the S/G2 cell-cycle arrest caused by TR at 48h (Control= 29%, TR= 33.4%, OL= 31.5%, TR-OL= 80.9%), and induces a strong increase of the apoptotic cells at 72h (Control= 17.4%, TR= 28.3%, OL= 33.5%, TR-OL= 56.8%). Furthermore, the TR-OL synergism on DNA damage is confirmed by a significant increase of the DSBs marker (Control= 8.7%, TR= 59.5%, OL= 23.8%, TR-OL= 76.5%). Conclusions: These results validate the biological rationale to combine TR and PARP-1 inhibitors in STS and suggest assessing this drug combination in the clinical setting.
Neoadjuvant chemotherapy for adult soft tissue sarcomas: A phase II trial.
Authors: Aguiar Samuel , Ferreira Fabio Oliveira , Batista Ranyell Spencer Sobreira , Bressan Alexsander Kurowa , Mello Celso Lopes , Lopes Ademar 
Published: March 2020

10069 Background: Treatment of soft tissue sarcomas (STS) is characterized by high rates of local control, but poor overall survival because of distant relapses and high rates of wound complications, when preoperative radiation is used. The objective of this study was to test the effectiveness of a protocol with neoadjuvant chemotherapy for STS. Methods: A phase II single-arm prospective trial was carried out. Only adult patients with high grade extremity lesions and tumors deep and larger than 5 cm were included. A total of four cycles of chemotherapy was administered pre-operatively. The chemotherapeutic regimen was: ifosfamide – total of 9.0 g/m2 per cycle, infused in 2 hours from Day 1 to Day 5 (1.8 mg/m2/day). Half of the equivalent dose of mesna was infused 15 min pre-ifosfamide and 4 hours post-ifosfamide. Doxorubicin – total of 60mg/m2 per cycle, was infused in bolus on Day 1. Filgrastima 300 mcg, SC, was administered after the last dose of chemotherapy for 5 days. Radiation was given after surgery. Toxicity was classified by the NIH Toxicity Criteria and response was determined by the RECIST criteria. The others endpoints were the amputation and the wound-related complication rates. Results: Between January, 2005 and May, 2011, 42 patients were included. 21(50%) patients have completed the 4 cycles. Nineteen patients (45.2%) have grade 3 or 4 toxicity, and one (2.3%) death related to treatment had occurred. Between severe complications, febrile neutropenia was the most frequent. By using the RECIST criteria, we observed 10(24.5%) cases of progression, 24(58.5%) cases of stable disease, and 7(17%) partial responses. No complete clinical or radiological response was observed. In the pathological analysis of the surgical specimens, 4(9.7%) cases showed no residual disease (complete pathological response), and a total of 6 (14.6%) showed ≤ 5% of viable residual cells. The amputation rate was 4.8% (2 cases) and complications related to the wound were observed in 9 patients (21.9%). Conclusions: The protocol showed a good rate of objective and pathological response, low rate of complications related to the operative wound, and maintained an acceptable amputation rate. On the other hand, we observed high rate of progression, by RECIST criteria.
Pharmacokinetics of escalated dose of imatinib in patients with advanced gastrointestinal stromal tumors.
Authors: Yoo Changhoon , Ryu Min-Hee , Ryoo Baek-Yeol , Park Inkeun , Beck Mo Youl , Kang Yoon-Koo 
Published: March 2020

10085 Background: Although escalated dose (ED, 800 mg daily) of imatinib (IM) is one of important options in resistant gastrointestinal stromal tumors (GIST) on standard dose (SD, 400mg daily), there has been lack of pharmacokinetic data at ED. We therefore explore the potential relationship between IM plasma trough level (Cmin), and clinical outcomes or toxicities in patients treated with ED. Methods: Between 2008 and 2011, steady-state IM Cmin was measured in 66 patients with GIST who received ED of IM using liquid chromatography-tandem mass spectrometry. Percent change from IM Cmin at SD was calculated in 43 patients that both SD and ED IM Cmin were measured. The association with efficacy and toxicity was analyzed with grouping patients into quartiles according to IM Cmin at ED and percent change. Results: Median age was 59 years (range, 36–77) and 40 patients were male. KIT exon 11 and 9 mutation was detected in 32 and 18 patients, respectively. At ED, partial response was achieved in 4 patients (6%) and stable disease was in 32 patients (48%). The median progression-free survival was 4.2 months (95% CI, 1.8-6.6) and overall survival was 38.5 months (95% CI, 7.6-69.3). The mean (± standard deviation) IM Cmin at ED was 3552 (± 1540) ng/mL. IM Cmin was significantly increased after dose escalation (p <0.001), and mean percent change from IM Cmin at SD was 162% (± 100). Body surface area (p=0.01), hemoglobin (p=0.001), and neutrophil count (p=0.006) were significant covariates for IM Cmin at ED in multivariate analysis. The group of quartiles of IM Cmin at ED and percent change was not associated with response and survival outcomes. However, grade 3-4 hematologic or grade 2-4 non-hematologic toxicity was observed in 9% (1/11) of patients in the lowest percent change quartile (Q1, <90%) compared with 56% (18/32) in Q2 to Q4 (p=0.012), although absolute values were not associated with toxicity. Conclusions: In GIST patients treated with ED of IM, IM Cmin was not associated with response and survival. Clinically significant toxicity following dose escalation was correlated with percent change of IM Cmin, rather than absolute values. Monitoring of IM Cmin might help to predict or manage ED of IM induced toxicity.
Masitinib in imatinib-naive advanced gastrointestinal stromal tumor (GIST): Five-year follow-up of the French Sarcoma Group phase II trial.
Authors: Le Cesne Axel , Blay Jean-Yves , Bui Nguyen Binh , Bouche Olivier , Domont Julien , Cioffi Angela , Le Boulicaut Julie , Moussy Alain , Hermine Olivier , Adenis Antoine 
Published: March 2020

10089 Background: Masitinib is a tyrosine kinase inhibitor that in vitro has greater activity and selectivity than imatinib against KIT. This multicenter, open label, phase 2 study evaluated efficacy and safety of masitinib as a first-line treatment of advanced GIST. Initial results with a median follow-up of 34 months, were previously reported in EJC 2010. We present here 5-year follow-up data from the same series with updated safety and survival data. Methods: Imatinib-naïve patients (pts) with inoperable, advanced GIST received oral masitinib (7.5 mg/kg/day) until progression, refusal or toxicity. Results: Thirty pts with a median age of 58 years (60% of males) were included from 06/2005 to 04/2007 in 5 institutions. At the cut-off date of 13/09/2011, 7/30 pts (23%) were still under treatment with median follow-up of 65 months and the median overall survival (OS) had not yet been reached (NR). The 5-year OS rate was 61.5% (95% CI [41.1;76.6]) (see Table). Among patients with confirmed KIT exon 11 mutation, 8/9 pts (89%) were still alive with one pt having died from non-treatment related causes (surgical complication) following a complete response while receiving masitinib. No additional progressions have been reported giving a total of 14 events (13 progressions and 1 death). Updated median PFS was 41.3 months (95% CI [17.5;53.8]).No additional grade 3/4 adverse events have been reported. Conclusions: Long term results of masitinib confirm an interesting activity with prolonged PFS and OS. The median PFS rate in masitinib compares very favorably to that of imatinib, which is reported as 18 months (JCO 26:626, 2008). The 5-year OS rates for masitinib in the overall and exon 11 populations also compare favorably to imatinib, both of which are reported at ≤50% for imatinib (JCO 26:626, 2008; JCO 28:1247, 2010). These results support the head to head comparison with imatinib in the currently ongoing phase 3 randomized clinical trial in first line advanced GIST pts. [Table: see text]