bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I study of neoadjuvant chemoradiation (CRT) plus sorafenib (S) for high-risk extremity soft tissue sarcomas (STS).
Authors: Meyer Janelle Marie , Perlewitz Kelly Shea , Hayden James B. , Hung Arthur , Doung Yee-Cheen , Mansoor Atiya , Beckett Brooke , Holtorf Megan L. , Woodward William J. , Rodler Eve T. , Jones Robin Lewis , Huang Wei , Ryan Christopher W. 
Published: March 2020

10011^ Background: We previously reported a regimen of epirubicin/ifosfamide (E/I) and hypofractionated radiation (RT) followed by surgery and postoperative E/I. We hypothesize that S + CRT is safe and augments activity through anti-angiogenic mechanisms. We performed dynamic contrast-enhanced MRI using shutter speed pharmacokinetic analysis (SSM DCE-MRI) to assess preoperative therapy effect. Methods: Subjects with >5 cm, grade 2-3 extremity STS were treated in cohorts of escalating S dose using a 3+3 design based on dose-limiting toxicity (DLT) during the first 8 weeks. Daily S was initiated 14 days prior to E/I (E 30 mg/m2/day days 1-3 and I 2.5 g/m2/day days 1-3 every 21 days for 3 pre- and 3 postoperative cycles). 28 Gy preoperative RT was administered in 8 fractions during cycle 2 (E omitted). Primary objective was to determine maximum tolerated dose (MTD). DCE-MRI was performed at baseline, after 2 weeks S, and prior to surgery. Results: 16 subjects were enrolled. Histologies included pleomorphic (5), synovial (5), liposarcoma (3), other (3). All were extremity (12 lower, 4 upper) tumors. Median tumor size was 11.7 cm. The MTD of S was 400 mg daily (see table). Most common grade 3/4 adverse events among all dose levels were neutropenia (94%), anemia (75%), hypophosphatemia (69%), thrombocytopenia (56%), neutropenic fever/infection (50%), and hypokalemia (31%). 38% developed wound complications requiring surgical intervention including amputation in 1 subject. 44% had >95% histologic necrosis at surgery. No subjects have recurred with median follow-up of 15 (6-27) months. 8 subjects underwent DCE-MRI. Changes in SSM DCE-MRI biomarkers after 2 weeks S correlated with histologic response (R2=0.71). Conclusions: The addition of S to CRT is feasible with promising activity that warrants further investigation. Rate of wound complications is similar to other reports of preoperative radiation. SSM DCE-MRI detected changes in tumor perfusion after only 2 weeks of S and may prove useful to assess early drug effect in STS. [Table: see text]
Desmoid fibromatosis and pregnancy: A multi-institutional analysis of recurrence and obstetric risk.
Authors: Fiore Marco , Coppola Sara , Colombo Chiara , Bertagnolli Monica M. , George Suzanne , Le Cesne Axel , Casali Paolo Giovanni , Gronchi Alessandro , Bonvalot Sylvie , Raut Chandrajit P. 
Published: March 2020

10017 Background: Desmoid fibromatosis (DF) may be diagnosed during or after pregnancy (P). However, the risk of progression during P, or in women of child-bearing age with DF prior to P, is unknown. Furthermore, obstetric risks have not been well described. Methods: Institutional databases were reviewed at 3 sarcoma referral centers in Europe and US for women with sporadic DF from 1985 to 2011. Pregnancy and treatment data, outcomes, and obstetric complications were recorded. Results: Overall 75 women were identified. DF was diagnosed during P in 17 women (Group A) or within 6 mo after P in 10 (Group B), was in situ at the time of P in 29 women (Group C), or had been resected prior to P in 19 (Group D). Anatomic site, outcomes, and treatment for each group are in the Table. Among patients operated at diagnosis, 2/11 (18%) recurred (Group A+B). Among the entire cohort, 15 women (20%) recurred after definitive treatment and only 6 (8%) needed multiple treatments after P. Ten spontaneous regressions occurred after P (13%). Twelve women had further P following the DF-related one, and 3 (25%) needed treatment after the subsequent P. At a median follow up of 35 mo from P, 17 women did not receive any treatment (23%), and 39 remain disease-free (52%). Caesarean section was needed in 14 cases (19%), but only in 1 expressly due to DF. DF-related P was associated with abortion in 6 cases (4 spontaneous, 2 voluntary); in no case was it caused by the presence of DF. Conclusions: DF developing prior to or during P may progress during the course of P or thereafter. Spontaneous regression after P was also observed. When resected, P-related DF rarely recurs. Wait & see is an option as well. DF history is not an indication for therapeutic abortion nor a contraindication against subsequent P. [Table: see text]
Optimizing the therapy of desmoplastic small round cell tumor: Combined experience from the two major cancer centers.
Authors: Subbiah Vivek , Viny Aaron D , Anderson Peter Meade , Hayes-Jordan Andrea Anita , Qiao Wei , Benjamin Robert S. , Maki Robert G. , Ludwig Joseph A. 
Published: March 2020

10021 Background: Desmoplastic small round cell tumor (DSRCT) is a rare translocation-positive (EWS-WT1)sarcoma subtype that often presents as diffuse peritoneal sarcomatosis in male adolescents and young adults. The objective of this study was to assess the survival of patients with DSRCT from the two major cancer centers. Methods: A multi-center retrospective review was performed of patients diagnosed with DSRCT treated at The University of Texas MD Anderson Cancer Center (MDACC) and Memorial Sloan-Kettering Cancer Center (MSKCC). Results: Of the 197 pts evaluated at both cancer centers (109 from MSKCC and 88 from MDACC) 87 % were male. The mean age was 25 ± 11 years; 139 (70.6%) underwent surgery; 38 ( 19.6%) had debulking surgery, 30 received radiation therapy, and 27 underwent hyperthermic chemotherapy after debulking (CHPP), 11 had a stem cell transplant. 112 patients were seen after 2003 in both the centers vs 85 before 2003. Neoadjuvant chemotherapy included Ewing’s-like chemotherapy with MSKCC’s P6 regimen (<18 yrs of age) and VAI in adults. We further analyzed the MDACC cohort. In univariate analysis radiotherapy, surgery, CHPP, removal of primary mass + metastases, age < 30 and patients treated after 2003 were associated with significantly improved overall survival. Multi-variate analysis showed that patients treated after 2003 had 59% lesser hazard (HR=0.41) than those treated earlier (p=0.04). Comparing 1990-2003 vs. 2004-2010 survival >3 yr with DSRCT was <25 % and is now >50 %, a significant improvement. Conclusions: We present long-term outcomes for the largest series of patients diagnosed with DSRCT. A multidisciplinary approach to DSRCT treatment is required to prolong 3- and 5-yr overall survival. Our recent improved outcomes required not only aggressive chemotherapy but also regional local control measures. Best adjuvant therapy remains to be determined. A treatment algorithm will be proposed.
Immunohistochemical identification of SDHA-mutant gastrointestinal stromal tumors (GISTs).
Authors: Wagner Andrew J. , Remillard Stephen P. , Zhang Yixiang , Hornick Jason L. 
Published: March 2020

10029 Background: GISTs are most commonly driven by activating mutations in KIT or PDGFRA. However, 15% of GISTs in adults and >90% in children lack such mutations. A subset of KIT/PDGFRA wild-type GISTs shows distinctive morphologic and clinical features and loss of expression of succinate dehydrogenase (SDH) B. Only a fraction of SDHB-deficient GISTs carry loss-of-function mutations in SDHB or SDHC. Due to the complexity of its locus and the presence of several pseudogenes, SDHA is rarely analyzed. Recently, mutations in SDHA were shown to lead to loss of expression of SDHA and SDHB in paraganglionomas. We sought to determine whether SDHA IHC could identify GISTs with SDHA mutations. Methods: Tumors (n=11) with features of SDH-deficient GIST (gastric origin, epithelioid morphology, multinodular/plexiform architecture) were selected from pathology archives under an IRB-approved protocol. Expression of SDHA and SDHB was determined on tumor sections by IHC. Genomic DNA was isolated from SDHA-negative tumors and amplified using primers specific to introns flanking each of the 15 SDHA exons. Amplicons were bidirectionally sequenced and compared to genomic repository data. Exons with somatic mutations were also examined in DNA from corresponding normal tissue to determine germline status. Results: All tumors (100%) were deficient for SDHB expression by IHC. Four of 11 (36%) SDHB-deficient GISTs also lacked expression of SDHA. SDHA expression was intact in the 7 remaining tumors, including 3 with known SDHB (n=2) or SDHC (n=1) mutations. Nonsense mutations in SDHA were identified in all 4 SDHA-deficient tumors, caused by a single base pair (bp) substitution (n=3) or a single bp deletion (n=1), and heterozygous mutations were also found in DNA from normal tissue of all 4 patients. Somatic loss of the 2nd allele has thus far been found in 3 of 4 tumors; 2 by loss of heterozygosity and 1 by a 13-bp deletion. Further analysis of the 4th specimen is ongoing. Conclusions: SDHA mutations are a common cause of SDH-deficient GISTs and result in combined loss of expression of both SDHA and SDHB. Loss of SDHA expression by IHC reliably predicts SDHA mutations and can be used to select cases for SDHA genetic testing.
Dasatinib first-line treatment in gastrointestinal stromal tumors: A multicenter phase II trial of the SAKK (SAKK 56/07).
Authors: Montemurro Michael , Domont Julien , Blesius Aurore , Rutkowski Piotr , Roth Arnaud , Von Moos Roger , Inauen Roman Ignaz , Bui Nguyen Binh , Burkhard Roger , Knusli Claudio , Bauer Sebastian , Cassier Philippe A , Schwarb Heike , Le Cesne Axel , Koeberle Dieter , Dunet Vincent , Dietrich Daniel , Biaggi Christine , Prior John , Leyvraz Serge 
Published: March 2020

10033 Background: First line imatinib has improved the outcome of patients (pts) with gastrointestinal stromal tumor (GIST), but primary and secondary resistance remain a problem. Dasatinib is a second generation tyrosine kinase inhibitor (TKI) and inhibits the activity of bcr-abl, src-family kinases along with a number of other oncogenic kinases including kit. In vitro, dasatinib has shown activity against imatinib-resistant cell lines. Routinely, pts diagnosed with GIST and treated with TKIs are monitored by computed tomography (CT). 18F-fluorodeoxyglucose positron-emission-tomography (FDG-PET) measures tumor metabolic activity for early response assessment, which might be of particular use in the clinical trial setting. Methods: This two-stage phase II trial investigated dasatinib in pts with TKI-naïve GIST. Dasatinib starting dose was 2x70mg/day in pts with histologically proven, FDG-PET positive GIST. Response evaluation was done by serial CT and FDG-PET using EORTC PET response criteria (Young et al. 1999). Elective surgery was allowed after 6 months of trial treatment. Primary endpoint was response (CR+PR) by FDG-PET after one month of dasatinib. Results: 47 of planned 52 pts have been enrolled from December 2007 to November 2011, when the trial was terminated due to slow accrual. 43 pts were eligible. Median age was 61 years, 24 pts were male, 19 female and 41 had a performance status of 0 or 1. At a median follow-up of 11.9 months, 20 pts were still on treatment. Pts went off trial for elective surgery (n=6), progression (n=11), toxicity (n=3), and three patients died (one on-drug). 5% of pts experienced G4, and 38% of pts G3 toxicity, which were most often gastrointestinal or pulmonary. 28% had their dose reduced or interrupted. The primary endpoint, FDG-PET response rate (CR+PR) at 4 weeks was 67% (13 CR, 16 PR, 7 SD, 3 PD, 4 not evaluable). Median progression-free survival is 11.1 months and median overall survival not yet reached. Conclusions: Dasatinib shows promising efficacy in TKI-naïve pts with FDG-PET positive GIST. Mutational data will be presented at the meeting.
A retrospective study from the Royal Marsden Hospital (RMH) of patients with malignant perivascular epithelioid cell tumors (PEComa) receiving treatment with sirolimus (SI) or temsirolimus (TSI).
Authors: Pedersen Joanna Vitfell , Benson Charlotte , Tunariu Nina , Mitchell Scott , Fisher Cyril , Thway Khin , Larkin James M. G. , Scurr Michelle , Judson Ian Robert 
Published: March 2020

10038 Background: Perivascular epithelioid cell tumors (PEComas) are rare tumors driven by tuberous sclerosis complex gene mutations causing upregulation of mTOR. Two studies reporting a total of five patients (pts) have described the treatment of PEComa by mTOR inhibition. We report the outcome of 7 pts with PEComa treated with SI or TSI at RMH. Methods: A retrospective analysis was performed on all pts with PEComa referred to the Sarcoma unit at RMH between 2000 and 2011. Data collected included gender, performance status, site of primary tumour, tumour size, surgery, SI/TSI and SI/TSI dose, toxicity according to common toxicity criteria (CTC) version 2.0 and response by RECIST. Results: Five (71%) pts were female, median age was 46 years. Two (29%) had metastatic disease at baseline. Most common primary site was the gastrointestinal tract (29%). Six pts received SI, one TSI. Median treatment duration was 131 days (7-1135). TSI was given at 25 mg IV weekly. Median starting dose of SI was 3 mg daily (1-4), median highest dose was 4 mg daily (1-5). Best responses by computed tomography (CT) scan by RECIST criteria were partial response: 3 (43%), stable disease: 2 (29%) and progressive disease (PD): 1 (14%). One pt only received 7 days of SI and was therefore not evaluable. Two pts continue on treatment, 3 stopped due to PD, one stopped due to grade (gr) 3 thrombocytopenia and one due to gr 3 cough, but two weeks later had confirmed PD on CT. Other toxicities reported were generally mild (gr 1/2) and included mucositis (n:3), rash (n:2), fatigue (n:1), anaemia (n:1), tooth pain (n:1) and oedema (n:1). One pt experienced a grade 3 trigeminal nerve pain leading to dose reduction in SI. Therapeutic drug monitoring was not performed. Conclusions: Our study confirms that SI and TSI are well tolerated with good clinical response and supports the continuous administration of SI or TSI for PEComas. A median treatment time of only 131 days indicates that most pts have a good response to treatment, but responses are sometimes short-lived and further treatment options are needed, justifying further research into inhibitors of this signalling pathway.
Sarcoligo: Impact of local ablative treatment of oligometastatic sarcomas on overall survival.
Authors: Thariat Juliette , Moureau-Zabotto Laurence , Penel Nicolas , Italiano Antoine , Bay Jacques-Olivier , Sunyach Marie-Pierre , Boudou-Rouquette Pascaline , Salas Sébastien , Le Maignan Christine , Ducassou Marie , Aldabbagh Kais , Isambert Nicolas , Kalbacher Elsa , Pan Qiong , Pautier Patricia , Hijazi Hussam , Bertucci François , Thyss Antoine ,   Groupe Sarcome Francais-Groupe d'Etude des Tumeurs Osseuses
Published: March 2020

10042 Background: 40-50% of sarcomas become metastatic. Median survival of metastatic patients has improved over time. The probably multifactorial reasons for such improvement are not fully clear. Noteworthy, for patients with a controlled primary and a limited number of lung metastases, complete resection of their metastases yields survival rates of up to 40% at three years. Advances in surgery, radiotherapy and radiofrequency have fostered the use of local treatments for various metastatic sites (lung, liver, spine...). Methods: A multicentric retrospective study of the Groupe Sarcome Francais (GSF-GETO); approved by the nationally-review board and ethical committee, was conducted to assess the impact of local ablative treatment on overall survival. Patients who had had oligometastases (any site, 1-5 synchronous metastases) at diagnostic or during the course of disease between 2000 and 2010 were included. Results: Median age of the 243 oligometastatic sarcoma patients was 53 years-old (11-86). Patients had grade I, II and III in 7.5%, 29.6% and 63.3% of cases, respectively with various histologies. 69% of patients underwent local ablative treatment of metastases. Median follow-up was 59 months (4-212) for living patients. Median overall survival was 51 months (1-348). On univariate analysis, grade, histology, absence of chemotherapy, local ablative treatment (surgery, irradiation, radiofrequency or chemoembolisation) correlated with survival but not age or site of oligometastasis. On multivariate analyses, grade (hazard ratio HR 0.12 [CI95 0.3-0.6]) and local ablative treatment (HR 3.8 [CI95 2.1-7.1]) remained significant. Conclusions: Local ablative treatment of metastases is associated with better survival in sarcoma patients with oligometastatic disease. The role of the locoregional treatment of metastases and its impact on quality of life should be assessed prospectively.
Association between body weight and efficacy outcomes during trabectedin therapy for recurrent advanced soft tissue sarcoma (STS).
Authors: D'Incalci Maurizio , Galmarini Carlos , de la Riba Alvarez Ines , Badri Nadia , Schöffski Patrick 
Published: March 2020

10047 Background: Trabectedin is the first marine-derived antineoplastic drug approved in Europe for the treatment of patients with recurrent advanced STS. Different studies have implicated tumor-derived cytokines as mediators of cachexia in cancer patients. Preclinical studies have demonstrated that trabectedin acts on tumor microenvironment particularly reducing IL-6, which is involved in cancer-induced cachexia (Germano et al. 2011, Ligouri et al. 2011). Methods: This exploratory retrospective analysis evaluated the association between body weight increase during treatment with respect to baseline and efficacy outcomes in 319 adult patients with recurrent STS. Patients were treated in four phase II trials with trabectedin at the approved dose of 1.5 mg/m2, given as a 24-hour infusion every 3 weeks. An analysis of the concordance between weight increase and objective response (OR) rate, tumor control (TC) rate (OR+stable disease lasting ≥3 months), progression-free survival (PFS) and overall survival (OS) was performed. Results: Correlation between weight increase and responses was observed: 68% of patients who achieved OR and 70% of patients with TC increased their weight for a median of 1.2 kg. Remarkably, PFS (5.1 vs. 1.9 months; p<0.0001, log rank) and OS (21.0 vs. 8.2 months; p<0.0001, log rank) were significantly prolonged in patients who gained weight during treatment. Six and 12-months Kaplan-Meier PFS estimates and survival rates at 12, 24 and 36 months were also better in those patients. Additionally, in Cycle 1-2, a significant relationship between weight increase and improved median PFS (4.2 vs. 2.2 months; p<0.0001) and OS (19.4 vs. 9.3 months; p=0.0002) was observed. This is in concordance with the tendency to gain weight starting from the first cycle of treatment. Conclusions: This analysis suggests that weight gain is associated with favorable efficacy outcomes when patients are treated with trabectedin. Further research is needed to assess the prognostic value of weight changes as a complementary source of evaluation on the long-term clinical outcomes and impact of trabectedin on tumor microenvironment.
Interest of tumor to liver ratio 18F-FDG uptake in positron emission tomography for detection of neurofibrosarcoma in neurofibromatosis 1 patients.
Authors: Combemale Patrick , Mognetti Thomas , Allanore Laurence , Bensaid Benoit , Giammarile Fransesco , Pinson Stephane , Drouet Alain , Wolkeinstein Pierre , Blay Jean-Yves ,   French Network on Neurofibromatosis
Published: March 2020

10049 Background: Malignant peripheral nerve sheath tumors (MPNSTs) are difficult to detect in neurofibromatosis 1 (NF1) individuals. The 18F FDG positron emission tomoscintigraphy (FDG PET) is a useful tool. The Standard Uptake Value (SUV) is the gold standard but it is subject to individual variation among patients and medical centers. So we assessed the interest of FDG PET based on a specific tumor to liver uptake ratio (T/L) instead of SUV to find a reproducible and constant cut-off for detecting malignant tumors. Methods: From 2000 to 2010, we conduct a multi centric study: all patients with NF1 and presenting clinical signs of MPNST suspicion (increased tumor size, induration or pain) underwent a FDG PET. Preliminary study estimated a T/L ratio of 1.5 as cut-off for malignity. Based on semi-quantitative analysis of FDG PET images, patients were compared with this cut-off value. Results: 98 patients with 125 tumors were included. FDG PET evaluation identified 42/125 suspected lesions with T/L > 1.5; among these 30 MPNST and 12 benign lesions were found. 83/125 tumors were classified as non-suspicious and 82 were actually benign according to histology or long term follow up. The 1.5 T/L cut off corresponds to 99 % Negative Predictive Value (NPV) and 71% Positive (PPV). The positive likelihood ratio (LR) was thus equal to 7, 69 and the Negative LR to 0, with 97% sensitivity and 87% specificity. When T/L ratio is < 1.5, MPNST is eliminated with 99% NPV, thus avoiding useless surgery. When T/L ratio is above 1.5, there is a strong suspicion of malignancy. But there is a risk of false positivity, which requires discussion before any therapeutic decision. On the over hand we found no significant correlation between SUVmax and malignancy. Conclusions: This study confirms the FDG PET in the detection of NF1-associated MPNST. The tumor/liver ratio with a cut off 1.5 has a very sensitive and specific value to sort out malignant from benign tumors and thus provides adequate surgery. More this semi-quantitative analysis method is just as easy as SUV, more sensitive and more reproducible.
Head and neck sarcomas: A comprehensive cancer center experience.
Authors: Tejani Mohamedtaki Abdulaziz , Ridge John A. , Galloway Thomas J , von Mehren Margaret 
Published: March 2020

10064 Background: Head/neck sarcomas are rare, accounting for 1% of head/neck malignancies and 5% of sarcomas. There are about 1000 cases/year in the U.S. comprising of many histologic subtypes making rigorous study of these tumors difficult. Outcomes have historically been worse in this anatomic group due to unique obstacles encountered during their treatment. Methods: We retrospectively analyzed cases of head/neck soft tissue sarcomas treated at Fox Chase Cancer Center (1999–2009). Study objectives were to describe clinicopathologic characteristics, treatment and outcomes of adult head/neck sarcoma patients and identify prognostic factors for disease control and survival. Cox proportional hazards regression analysis was performed to identify predictors of DFS and OS. The HR and 95% CI for Cox model and median DFS/OS from Kaplan-Meier curves were calculated. Results: 31 patients were identified. Median age was 50 (range 15–91). 23 patients were male. Most tumors were high grade (25) and almost all were localized at presentation (29). Common histologies were synovial cell (6), rhabdomyosarcoma (5), angiosarcoma (4), lipsarcoma (4) and leiomyosarcoma (3). 25 patients with localized stage underwent excision: 9 had surgical resection only, 10 had surgical resection with neo/adjuvant radiation and 6 had surgical resection as well as neo/adjuvant chemotherapy and radiation. 7 patients required re-excision to achieve negative margins. Median DFS was 1.1 years (95% CI: 0.7–12.1) and median OS was 3.3 years (95% CI: 2.1-5.4). Of 16 patients with recurrent disease, 12 were local. Patients with positive margins had worse DFS (p=0.04) and OS (p=0.03). Tumors greater than 5cm were associated with worse DFS (p=0.07). Age and grade did not correlate with outcome. Conclusions: Head/neck sarcomas are difficult to completely excise due to anatomic constraints and local recurrence rates are high. Achieving a negative margin is critical in improving outcome. Median DFS and OS are worse than those achieved with other subsites. Head/neck sarcomas are best managed in a multi-disciplinary setting. [Table: see text]