bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of imatinib plasma trough concentrations with adverse reaction in Chinese gastrointestinal stromal tumors patients.
Authors: Xia Yanzhe , Chen Sile , Cai Shirong , He Yulong , Zhang Xinhua 
Published: March 2020

11034 Background: Imatinib is the standard treatment for patients of Gastrointestinal Stromal Tumors (GISTs), but the intra- and inter-variability of imatinib plasma trough concentration (Cmin) are significant. Few studies investigated the association between Cmin and adverse reaction in Chinese GIST patients. The distribution of imatinib Cmin in different doses and the correlation of imatinib Cmin with adverse reaction in Chinese GIST patients from a high-volume center were evaluated. Methods: From 1 Jul 2017 to 31 Dec 2018, a total of 400 patients who were under imatinib treatment were prospectively studied. All patients’ informed consents were obtained. Steady state plasma samples were obtained from patients at least administrating 1 month treatment who were taking imatinib 100 to 800 mg/d, with continuous similar timing of daily dosage for more than 14 days. The adverse reaction was recorded during regular follow-up at out-patient clinic, and blood sample was collected 22±2 hours to the next dosage of imatinib. Liquid chromatography tandem mass spectrometry was applied to determine the concentration. Adverse reaction grades were referred to CTCAE v4.0. Results: A total of 368 patients who followed the same dose of imatinib with good compliance, and having at least 2 times of tests were investigated. The imatinib Cmin was 384±53 ng/mL, 776±337 ng/mL, 986±327 ng/mL, 1078±498 ng/mL, 1309±712 ng/mL, 1620±469 ng/mL, 2117±597 ng/mL and 3844±987 ng/mL in patients who were administrated with 100 mg/d (n = 3), 200 mg/d (n = 15), 250 mg/d (n = 5), 300 mg/d (n = 80), 400 mg/d (n = 235), 500 mg/d (n = 3), 600 mg/d (n = 22) and 800 mg/d (n = 5), respectively. In correlation analysis, imatinib Cmin was significantly correlated with periorbital and limbs edema (p < 0.01), anemia (p < 0.01) and rush (p < 0.01), correlated with diarrhea and conjunctival hemorrhage but not significant. Much higher Cmin was observed in severe adverse reaction (≥ grade 3) of periorbital and limbs edema and rash. There was no correlation between Cmin with leukopenia, nausea, vomiting, muscle cramp or hepatobiliary disorders. Conclusions: In Chinese GIST patients, imatinib Cmin at steady state was seems higher than Western populations previous reported, especially in higher doses (≥600 mg/d). Imatinib Cmin was correlated with anemia, periorbital and limbs edema, diarrhea and conjunctival hemorrhage, suggesting that imatinib Cmin monitor might be considered when patients were subjected to severe adverse reactions which were caused by excessive imatinib plasma concentration.
Multicenter phase II trial of pazopanib (P) in patients with angiosarcoma (AS).
Authors: von Mehren Margaret , Litwin Samuel , Ravi Vinod , Schuetze Scott , Movva Sujana , Agulnik Mark , Kraft Andrew S. , Tetzlaff Eric Daniel , Somaiah Neeta 
Published: March 2020

11039 Background: AS is a rare aggressive soft tissue sarcoma derived from endothelial cells. It can occur as cutaneous or visceral disease, be associated with chronic lymphedema, or arise after radiation therapy. Non-metastatic AS has a poor overall 5-year survival rate of 27-35%; improved treatments are needed. We hypothesized that P would have therapeutic activity in AS because of the agent’s anti-angiogenic activity. Methods: This was an open label, multi-institutional trial of P using a Simon two-stage design. The primary endpoint was to determine the PFS at 3 months and response rate defined as CR and PR in AS treated with P. Eligibility criteria included incurable AS, age≥18, adequate blood counts, cardiac, hepatic and renal function, RECIST measurable disease, ability to swallow pills and provide informed consent. P was given as 400 mg orally twice daily, with ongoing disease assessment every 8 weeks. Results: From 11/2011 - 12/2018, Twenty-nine patients were treated on study (Table; data available for 28 patients). 50% were female and 55% had cutaneous disease. Eight patients were inevaluable for response: 3 never started P (lab abnormalities day 1, n=1; consent withdrawal, n=2); 4 due to toxicity, 1 for non-compliance. As of 12/15/18, best response was SD seen in 12 patients. The 3-month PFS rate determined by Kaplan-Meyer estimate was 54.6% (95%CI 36.0, 82.9%). SD was seen in 25% (4/16) with cutaneous disease and 8.3% (1/12) with visceral disease. Toxicities were manageable and similar to prior reports. Grade 3/4 toxicities included hypokalemia, increased U/P ration, lymphocytopenia, hypertension and abnormal LFTs; there was one death due to cardiac arrest considered possibly related to P. Conclusions: Accrual rate was slower than expected possibly because P was available off-study. Treatment was feasible and did not reveal any previously unreported toxicities. Efficacy outcomes were limited by early withdrawal of patients. No RECIST responses were observed; however P has a clinically meaningful 3-month PFS, primarily in cutaneous AS. Clinical trial information: NCT01462630. [Table: see text]
Retroperitoneal soft tissue sarcoma (RPS): Recent outcome improvement and refinement of treatment strategies at a single institution.
Authors: Fiore Marco , Almond Max , Barretta Francesco , Callegaro Dario , Colombo Chiara , Radaelli Stefano , Pasquali Sandro , Barisella Marta , Morosi Carlo , Sanfilippo Roberta , Sangalli Claudia , Stacchiotti Silvia , Miceli Rosalba , Casali Paolo Giovanni , Gronchi Alessandro 
Published: March 2020

11041 Background: Extended surgery in retroperitoneal sarcoma (RPS) has resulted in less recurrences and better survival. We investigated whether outcome further improved, after the recent understanding of behavior of different RPS subtypes and introduction of multimodal therapies. Methods: Consecutive primary RPS operated at a single center were analyzed comparing 3 periods (2002-2006; 2007-2011; 2012-2016). Primary endpoints were overall survival (OS), crude cumulative incidence (CCI) of local recurrence and distant metastasis (LR, DM) for each subgroup: well differentiated (WDLPS), dedifferentiated G2 (G2DDLPS), G3 (G3DDLPS) liposarcoma, and leiomyosarcoma (LMS). Secondary endpoints: morbidity and post-relapse OS. Fisher/Chi-squared and Cochran–Armitage trends test were used. Survival was analysed by Kaplan-Meier/Cox PH or CCI/Fine Gray models in the competitive risk framework and compared with log-rank/Wald Gray tests. Multivariable analyses were performed. Results: Overall 437 RPS were operated: 82, 128 and 227 in the 1st, 2nd and 3rd period. Median follow-up was 125, 86 and 39 months. Complete resection (R0/R1) improved from 93.9% to 98.2% (p=0.059), median number of resected organs increased from 2 to 4 (p<.0001). Postoperative morbidity did not change (18.3%, 16.4%, 22.5%; p=0.269). Administration of radiotherapy and chemotherapy (CT) differed over time according to different subtypes. 5-yr OS improved (63.2% to 74.7%, p=0.005), along with a non-significant reduction in LR CCI (18.2% to 16.4%, p=0.379) and no change in DM CCI. At multivariable analysis, study period remained an independent prognostic factor for OS among the other known risk factors (3rd vs 1st period HR: 0.33, p<0.001). Subgroup analysis showed the following associations with better prognosis: 1. Improvement in 5-yr OS (from 55.0% to 70.7%, p=0.024) and LR (from 45.0% to 19.8%, p=0.060) in G2DDLPS, associated with more organs resected 2. Improvement in 5-yr OS (from 18.2% to 49.7%, p=0.035) and DM (from 70.0% to 19.8%; p=0.015) in G3DDLPS, associated with more anthracycline-based CT 3. A better 2-yr post-relapse OS (from 46.3% to 65.2%, p=0.122). Conclusions: OS of patients with DDLPS improved over time: in G2 this was associated with a refinement in the surgical approach, while in G3 with a more liberal use of anthracycline-based CT. New available therapies for recurring RPS may also have extended post-relapse OS. Prospective studies on perioperative CT for high risk RPS subtypes are eagerly awaited.
Complete remission of patients with heavily pretreated uterine sarcomas by weekly bevacizumab and temozolomide.
Authors: Takasaki Kazuki , Ikeda Sayaka , Matsuura Hiroko , Kudoh Kazuya , Yoshikawa Tomoyuki , Kouta Hiroko , Takano Masashi , Kikuchi Ryoko , Horikoshi Miyuki , Kikuchi Yoshihiro 
Published: March 2020

11051 Background: Uterine sarcomas are associated with poor prognosis snce the complete remission is extreme rare. Therefore, treatment with chemotherapy including eribulin or trabectedin, hormone therapy or molecular-targeted therapy including pazopanib or olaratumab was expectd, but the effect is not satisfactory. Thus, we evaluated the effects of temozoromide (T), derivateives of dacarbazine, and bevacizumab (B) (TB) containing or not cabozantinib (C), a multikinase inhibitor of MET, AXL, RET and VEGFR2 (TBC) in heavily pretreated cases of uterine sarcomas. Methods: From 2009 to 2018, 29 patients (pts) with heavily pretreated uterine sarcomas were enrolled. Fifteen of 29 patients were treated with T (80mg/body/day) and B (2mg/kg; days1, 8 and 15, q 4 weeks) (TB). Since 2013, C (140mg/body/week) was added to TB (TBC, n = 14). Treatment was continued until disease progression and/or unmanageable toxicities. Response was evaluated with the response evaluation criteria in solid tumors (RECIST) v1.1, and adverse events were assessed by common terminology criteria for adverse events (CTCAE) v4.0. Results: Seven pts (24 %) had carcinosarcoma, fifteen (52 %) had leiomyosarcoma, five (17 %) had undifferentiated uterine sarcoma, one (3 %) had adenosarcoma, and one (3 %) had uterine sarcoma-not other specified. Twenty-three of 29 pts were subjected to response evaluation. Five pts (22 %) had complete response (CR), three (13 %) had partial response, six (26 %) had stable disease (SD). The response rate (RR: CR+PR) and disease-control rate (DCR: CR+PR+SD) were 35 % and 70 %, respectively. The median progression-free survival was 6.5 (2-89) months. When adding C to T and B, DCR was improved from 64 % (TB) to 75% (TBC). Median administration of cycles is 7 (TB) and 5 (TBC). There were 2 dead cases from perforation, but toxicity was almost mild and manageable. Conclusions: We have experienced 5 cases of CR by TB or TBC. Moreover, addition of C to T and B resulted in better disease-control rate. Compared to other reported treatment, TB combined with C could be substantially effective in cases with heavily pretreated uterine sarcomas. These results warrant further prospective and randomized studies.
Histone H3 modifying genes may serve as a predictive marker for metastasis in synovial sarcoma.
Authors: Awasthi Achal , Seligson Nathan David , Millis Sherri Z. , Hays John L. , Chen James Lin 
Published: March 2020

11058 Background: Synovial sarcomas (SS) are rare, mesenchymal tumors that exhibit heterogeneous clinical behavior. SS is characterized molecularly by a fusion of the SS18 and one of three SSX genes. While fusion type has been shown to play a role in prognosis, little is known regarding the role of secondary genomic variants in SS. We hypothesized that frequently mutated secondary mutations corresponded to altered molecular pathways associated with accelerated disease progression. Here we present further analysis of the largest study of secondary SS genomic alterations and their potential clinical implications particularly in regard to Histone H3 modifying genes. Methods: Comprehensive Genomic Profiling (CGP) from 203 SS18-SSX fusion positive SS subjects were obtained from Foundation Medicine (FMI). Correlation between gene expression and survival endpoints were assessed in two independent datasets (GSE40018, n = 34; GSE40021, n = 58). A histone H3 score (HH3Score) was calculated through summation of expression values of MLL2, MLL3, SETD2. Altered expression was assessed for genes mutated in > 5% of SS in the FMI dataset. Datasets were also combined with appropriate adjustments for multivariate analysis. Cox proportional hazard, and Chi-squared test were used as appropriate. Results: In CGP profiling of SS, only 4 genes were seen in > 5% of subjects ( MLL3 9%, SETD2 7%, MYO18A 6%, MLL2 6%). 3 of these variants are known to regulate histone H3 activity and are collectively altered in 22% (44 of 203) of the FMI SS subjects. Notably, these H3 targeted gene alterations were found to be mutually exclusive of one another (p < 0.001). In 2 independent SS datasets, subjects with high histone H3 modifying gene RNA expression levels (HH3Score) demonstrated worsened outcomes with earlier tumor metastasis (GSE40018: HR = 0.41, 95%CI 0.15-1.07, p = 0.07; GSE40021: HR = 0.22, 95%CI 0.09-0.52, p < 0.001). Multivariate analysis demonstrated that HH3Score remained significantly correlated to metastasis-free survival (HR = 0.41, 95%CI 0.22-0.77, p < 0.01) when subjects’ age (p < 0.001) and fusion type (p = 0.60) were taken into consideration. Conclusions: Altered expression of histone H3 modifying genes may serve as a key driver for SS progression. Further prospective research is necessary to confirm its prognostic importance.
Pathologic response rates after neoadjuvant therapy for sarcoma.
Authors: Shrivastava Gautam A. , Jarboe John Stewart , Ahmed Awad , Conway Sheila Ann , Pretell Juan , Freedman Laura M. , Wolfson Aaron Howard , Rosenberg Andrew , Trent Jonathan C. , Yechieli Raphael 
Published: March 2020

11060 Background: Treatment approaches for soft-tissue sarcomas (STS) vary across sarcoma centers of excellence. A multi-institutional study showed neoadjuvant doxorubicin and ifosfamide (AI) surpassed other agents in recurrence-free survival of several sarcoma subtypes. Our institution manages high-grade STS of the extremity and trunk with neoadjuvant chemotherapy (NA-CTX), neoadjuvant radiation (NA-XRT), or neoadjuvant sequential chemoradiation (NA-CRT) followed by oncologic resection and adjuvant chemotherapy. We report the pathologic (%) necrosis in 48 patients comparing NA-XRT, NA-CTX, and NA-CRT. We also investigated initial clinical outcomes correlated with % necrosis. Methods: We reviewed records of patients who received neoadjuvant therapy for sarcoma over the last four years at our center. We required a pathology report that detailed % necrosis in the specimen. We excluded the same histologies according to RTOG 9514 and RTOG 0630 protocols. There were 48 patients evaluable. The primary regimens compared were NA-CTX, NA-XRT, and NA-CRT before oncologic resection. After determining the mean % necrosis and SE for each group, we determined statistical significance through one-way ANOVA with post-hoc Tukey HSD Test. Kaplan-Meier Analysis was used to compare rates of % necrosis with OS, LC, and DF. Radiation therapy was 50Gy in 25 fractions over 5 weeks. The most common preoperative chemotherapy regimen was 3-4 cycles of AI. Results: Whole cohort evaluation found significant improvement in % necrosis with sequential NA-CRT (78%) compared to NA-CTX (51%, p = 0.049), but a trend when compared to NA-XRT (45%, p = 0.075). Evaluation of patients only receiving neoadjuvant AI revealed significantly improved % necrosis with NA-CRT (83%) compared to either NA-CTX (44%, p = 0.011) or NA-XRT (45%, p = 0.031). At a MFU of 1.6 years we found a non-significant trend toward improved outcomes with higher % necrosis [at 70%, OS (HR = 0.11), LC (HR = 0.34), and DF (HR = 0.61)]. Conclusions: In patients diagnosed with high-grade STS of the extremity or trunk, sequential NA-CRT followed by surgery yields greater % necrosis in tumors when compared to NA-CTX or NA-XRT alone. Longer follow up is required to determine if pathologic response correlates with improved outcomes.
A single-center retrospective study of patients treated with trabectedin (TRB) with long-term follow up.
Authors: Schroeder Brett A. , He Chad , Zhang Yuzheng , Wagner Michael , Jones Robin Lewis , Cranmer Lee D. , Pollack Seth 
Published: March 2020

11061 Background: TRB is FDA approved drug for the treatment of liposarcoma (Lipo) and leiomyosarcoma (LMS). The aim of this study was to evaluate potential biomarkers associated with prolonged benefit in patients treated with TRB at our center prior to 2016. Methods: We performed a retrospective search of UW/FHCRC CASIS database to identify patients treated with TRB prior to 2016. Demographic variables and clinical variables (such as histology and treatment) were retrieved. Statistics were performed with R 3.4.1 software. Pairwise Pearson’s correlation was calculated for the # of prior chemotherapy regimens with # of TRB cycles. The Kaplan-Meir method was used to evaluate overall survival (OS). Log-rank test was conducted to compare groups in terms of OS. Results: 145 sarcoma patients treated with TRB were identified with a mean follow up of 5 years (generally on NCT01427582 or NCT01343277). Patients averaged 1.9 prior chemotherapy regimens prior to TRB (range 0-7 regimens) and received an average of 5.6 TRB doses (range 1-25 doses). Subtypes are listed on table. The # of prior regimens was negatively correlated with the # of TRB cycles that patients received (pairwise correlation coefficient = -1.77; p=0.034), suggesting that multiple prior treatment lines either made TRB less tolerable or made sarcoma less sensitive to TRB. The median OS for this heavily treated metastatic population was 0.5 years. However, patients who were able to stay on TRB for more than 5 cycles had a significantly higher OS (p=0.001). While only 23% of patients who received less than 5 cycles of TRB were alive at 5 years (95% CI: 0.15, 0.32), 53% of those who received 5 or more cycles of (95% CI: 0.39, 0.65) were alive at 5 years. Conclusions: TRB may be more effective when administered as an earlier line of therapy. Patients who are able to stay on TRB for a longer duration had a significant improvement in OS. Detailed subset analysis will be presented as will initial findings of our biomarker work. These retrospective data warrant further evaluation. Clinical trial information: NCT01427582 or NCT01343277. [Table: see text]
Prognostic factors and therapeutic options for epithelioid hemangioendothelioma (EHE): A multicenter analysis of a series of fifty-seven cases.
Authors: Vozy Aurore , Simonaggio Audrey , Terrier Philippe , Paradis Valerie , Penel Nicolas , Mir Olivier , Honoré Charles , Dumont Sarah Naomie , Spano Jean-Philippe , Le Cesne Axel 
Published: March 2020

11062 Background: EHE is a rare vascular mesenchymal tumor for which there is currently no standard for treatment particularly for metastatic disease. EHE often present metastatic evolution but metastases are not a poor prognostic factor. The aim of this study was to improve knowledge of outcome of EHE patients and see the impact of active surveillance on outcome for metastatic EHE patients. Methods: Patients with EHE treated at three centers in France were included in this retrospective cohort. Univariate analysis of prognostic factors was performed using the Cox model. Survival was estimated using the Kaplan-Meier method and long rank analysis. Results: Fifty-seven patients with EHE were collected in this analysis: 27 (47%) women and 30 (53%) men, with a median age at diagnosis of 39 years (range, 12-83). At diagnosis, 17 (29.8%) patients had a localized tumor, while 40 (70.2%) patients had synchronous metastases. The most commonly affected organs were liver (29.8%), bones (14.0%), skin, lungs and soft tissues (10.5% each). For the 17 patients with localized EHE, the median distant recurrence-free survival after resection of primary was 64.6 months, 95% CI [29.4, NA], (median follow-up of 62.7 months, range, 12.5-234.8). For the 40 patients with metastatic EHE, the median progression-free survival (PFS) was 59.0 months, 95% CI [21.3, NA], (median follow-up of 121.1 months, range, 1.0-202.0). No prognostic factor was identified for localized EHE. For metastatic EHE, age was associated with progression (p = 0.019), and presence of pleural/ascites/pericarditis effusion adversely affected overall survival (OS) (p = 0.002). An initial “wait and see” attitude was proposed to 23 patients (57.5%) while 17 patients (42.5%) were treated at diagnosis with local or systemic treatment (monotherapy or combination of chemotherapy with anthracyclin, taxane, cyclophosphamide). OS were similar in both groups of patients, 174months and 121months for chemotherapy treated patients and active surveillance patients respectively (p = 0.56). Conclusions: Presence of effusion was a significant poor prognostic factor in metastatic EHE patients. Active surveillance could be proposed for asymptomatic patients without effusion but this strategy need to be confirmed in largest or prospective randomized trials.
Activity of sirolimus in advanced epithelioid hemangioendothelioma (EHE): A retrospective analysis within the Italian Rare Tumor Network (RTR).
Authors: Simeone Noemi , Baldi Giacomo Giulio , Frezza Anna Maria , Palassini Elena , David Bruna Bianca Lopes , Vincenzi Bruno , Brunello Antonella , Dagrada Gianpaolo , Collini Paola , Morosi Carlo , Dei Tos Angelo Paolo , Casali Paolo Giovanni , Stacchiotti Silvia 
Published: March 2020

11065 Background: EHE is an exceedingly rare soft tissue sarcoma (STS) with no active standard treatment available in advanced patients (pts). We already reported on the activity of sirolimus in a retrospective series of 18 EHE treated within the RTR. We herein update this series on a longer follow-up in a larger number of pts. Methods: Adult pts affected by an advanced, progressive and centrally confirmed EHE treated with sirolimus within the RTR from 2006 to 2018 were retrospectively reviewed. Sirolimus was administered at the starting dose of 5 mg/day, until toxicity or progression. Sirolimus dose was adjusted according to plasma levels (target: 15–20 ng/dL). Response was assessed by RECIST 1.1. Survival was estimated by Kaplan-Meier method. Results: 33 patients were retrospectively identified (median age = 47 years, female = 20 (60%), male = 13 (40%); pretreated = 8, naïve = 25; presence of pleural effusion at baseline = 6). All patients had metastatic disease and evidence of disease progression before starting sirolimus. Mean sirolimus daily dose was 5 mg (range 2-10). 9 pts are still on therapy, 24 stopped sirolimus (13 progression, 5 toxicity, 6 other). 31 pts were evaluable for response (2 pts too early). Best RECIST response was: 1 (3.2%), PR, 26 (83.8%) SD, 4 (12.9%) progression. At a 14-mo median FU, median PFS (m-PFS) was 12.3 mos (range 8–15) and median OS (m-OS) was 19 mos (range 1–40). Pleural effusion correlated with a short m-PFS (3.4 vs 14.3 mos in patients without pleural effusion, p = 0.006) and m-OS (10.6 vs 40 mos in patients without pleural effusion, p <0.0001). Amongst those without pleural effusion, the proportion of pts being progression free at > 24 mos was 23%, with 54 % being alive. Conclusions: We selected pts with advanced EHE with clear evidence of disease progression. This singles out a subgroup of EHE pts with a bad prognosis. Prognosis was shown to be exceedingly bad when there was evidence of serosal effusion, and sirolimus was not effective. Though in an uncontrolled setting, apparently sirolimus is able to slightly prolong PFS and, above all, to allow mid-term freedom of progression in roughly 25% of pts.