bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imatinib mesylate as a preoperative therapy in dermatofibrosarcoma: Results of a multicentric phase II study on 25 patients
Authors: Misset J. , Kerob D. , Porcher R. , Verola O. , Dalle S. , Maubec E. , Madelaine-Chambrin I. , Calvo F. , Mathieu-Boue A. , Pedeutour F. , Lebbe C. 
Published: March 2020

10032 The treatment of dermatofibrosarcoma protuberans (DFSP) relies on a wide local excision with frequent need of reconstructive surgery. A (17,22)translocation with Co1A1-PDGF fusion is present in > 90 % of the cases. Some patient's observations and a report on 9 patients suggest that Imatinib mesylate (IM), targeting PDGFRβ, has a clinical interest in DFSP. The primary aim of this phase II multicentric study was to define the percentage of clinical responders (RECIST) to a preoperative 2 months 600mg IM daily before wide local excision. The secondary goals were to determine tolerance, imaging (ultrasound and MRI), pathological responses and to analyse PDGFRβ phosphorylation status and tumour cell apoptosis in sequential tissues specimen. A flexible design with interim analysis after recruitment of 6 patients was used. 18 to 28 patients had to be enrolled to detect a 30% clinical response rate (relative decrease of tumor of at least 30%) with power 80%, using a one-sided test against 5%, at the 2.5% one-sided level. The interim analysis yielded a clinical response in 3 of 6 patients without severe adverse event. An independent committee advised to continue the trial to obtain a total number of at least 24 patients, in order to reduce the confidence interval of response rate. Twenty-five adults suffering from primary or recurrent DFSP have been included from July 2004 to May 2006, 13F and 12 M, median age 42.4 years [range 23.0–72.5]. Tumour characteristics were as follows: primary (n=20), recurrence (n=5) involving trunk(n=14), head or neck (n=3), limbs (n=6), other n=2; median size was 4.5cm [range 2.4–16]. Translocation t(17;22) was detected in 12 of 12 informative tumours following caryotype or FISH analysis. A clinical response was achieved in 9 (36%) patients(95%CI 18.9–57.5). The median relative decrease of tumor was of 20.0% [range -12.5;100]. Apart from expected grade 1 or 2 side effects, we observed 1 grade 3 neutropenia, 1 grade 3 maculopapular rash and 1 grade 4 transient transaminitis. Imatinib has been recently approved for the treatment of unresectable or metastatic dermatofibrosarcoma. Our results should prompt us to analyse the clinical benefit of a longer duration neoadjuvant treatment for patients with DFSPin order to reduce surgical margins [Table: see text]
Incidence of gastrointestinal stromal tumors (GISTs) in France: Results of the PROGIST survey conducted among pathologists
Authors: Monges G. , Coindre J. , Scoazec J. , Bouvier A. , Blay J. , Loria-Kanza Y. , Mathieu-Boue A. , Bisot-Locard S. 
Published: March 2020

10047 Background: GISTs are the most common mesenchymal tumors of the gastrointestinal tract but data on the annual incidence of this tumor is scarce due to previous lack of well-defined pathologic criteria. The aim of this study was to investigate the incidence of GISTs in France and describe the distribution according to age, sex, circumstances of discovery, localization and risk categories. Methods: This prospective epidemiologic study was performed among pathologists who were asked to declare all the cases of GIST over a one year period. All pathology centers (330 centers) in France were proposed to participate and asked to report exhaustively the cases diagnosed from 1 December 2004 to 30 November 2005. Results: 591 cases of GISTs were reported, 535 new cases and 56 cases of relapse. However, some large centers were not able to participate. So, the annual estimated incidence was 12 cases/million inhabitants in France. The main characteristics of the new cases of GIST were as follows: mean age 65 (± 13.2) (range: 16–93) years, 48.6% men and 51.4% women, circumstances of discovery: fortuitous 163 (30.5%), symptomatic 249 (46.5%), unknown 123 (23%). The primary tumor locations were: stomach 341 (63.7 %), small intestine 115 (21.5%), mesentery 35 (6.5%), colon/rectum 17 (3.2%), esophagus 4 (0.7%), unknown 23 (4.3%). 95.3% of GISTs were cKIT (CD117) + and 3.7 % were cKIT -. According to the Fletcher consensus criteria, based on tumor size and mitotic rate, among the 490 localized GISTs 14.7% were considered to be at very low prognostic risk, 25.5% at low-risk, 23.1 % at intermediate risk and 23.1 % at high-risk. For 13.6 % data were missing. Conclusions: This study is providing for the first time an estimation of the annual incidence of GISTs and a description of the characteristics of these tumors in France based on pathology registration. The true incidence may be slightly higher as some large centers were not able to reported their cases. These results are comparable to what has been reported in recent studies in other European countries. No significant financial relationships to disclose.
A population based study of the incidence, clinical course and prognostification of GIST in Scotland in the pre-imatinib era (1995–1999)
Authors: Graham J. S. , Dunbar G. , Walsh S. , Dick C. , White J. D. 
Published: March 2020

10050 Background: GIST's are rare tumours characterised by C-KIT and or CD34 positivity. Population based studies have been performed in countries including Iceland, Spain, Sweden and Holland but this is the first in the United Kingdom. Methods: Pathology records from the entire country were screened for actual or potential GIST cases and the tissues stained with CD117 for C-KIT to confirm a genuine diagnosis of GIST. The primary endpoint was to calculate the incidence of GIST in Scotland from 1995–1999. Secondary endpoints included information re stage, site, survival, sex, age and geographical distribution, and to validate the NIH (National Institute for Health) prognostic index currently used. To date 132 patients have been confirmed with GIST who were previously diagnosed as having either GIST or another similar malignancy. We await final information from 1 region. Results: Primary Endpoint. The incidence of GIST in Scotland from 1995–1999 was 5.2/million/year. Secondary endpoints. Median age at time of diagnosis was 69 with a similar male to female ratio. Original tumour site was 55.8% gastric, 38 % small bowel, 2.3 % colorectal; other sites were < 1 % each. 50.4% were originally diagnosed as GIST's. Other diagnosis included leiomyoma (21.7%) and leiomyosarcoma (14%). All others were <5% each. According to the prognostic index 10.9% were very low risk, 26.4% low risk, 23.3% intermediate, 30.2% high risk Conclusions: Although C- KIT staining was not standard practice during the study period a high percentage of patients were correctly diagnosed originally. Despite a study designed to maximise case ascertainment we report an incidence of GIST in Scotland lower than that of other studies (11 to 14.5 million/ year). This discrepancy may be due to differing study designs and/or failures in the original pathology coding; fundamental in our methodology. Ongoing work to assess the importance of original tumour site, size, prognostic index, etc is underway and this data will be available prior to the 2007 Annual Meeting. No significant financial relationships to disclose.
Tyrosine kinases as possible therapeutic targets in pulmonary artery intimal sarcoma
Authors: Dewaele B. , Floris G. , Sciot R. , Prenen H. , Wozniak A. , Guillou L. , Coindre J. , Fletcher C. , Schöffski P. , Debiec-Rychter M. 
Published: March 2020

10055 Background: Pulmonary artery intimal sarcomas (PAIS) are very rare, highly malignant and clinically aggressive tumors, with yet elusive underlying pathogenic mechanisms and histogenesis. Our aim was to gain molecular insight in the oncogenic events leading to PAIS development, and to investigate the possibility of a pharmacological approach for the treatment of PAIS, specifically targeting the receptor tyrosine kinases (RTK) activated in these tumors. Methods: Fourteen cases of advanced high grade poorly differentiated PAIS were analyzed by immunohistochemistry and selectively by a variety of cytogenetic/molecular techniques, e.g. karyotyping, FISH, mRNA in situ hybridization, array-CGH, tyrosine kinases RT-PCR assay and Western blotting analysis. The study was supplemented by sequencing of PDGFRA, PDGFRB, KIT, VEGFR-1, VEGFR-2 and EGFR genes. Ex vivo functional assays were applied to test the sensitivity of PAIS primary tumor cells to different, clinically approved RTK inhibitors. Results: We demonstrate that (1) PAIS do not have mutations within the kinase domains of PDGFRs, KIT, VEGFRs or EGFR, (2) all cases show a similar cytogenetic molecular profile, characterized by amplification of PDGFRA/KIT/VEGFR2 and MDM2/CDK4 genes, while EGFR, PDGFRB and VEGFR1 are frequently polysomic but rarely highly amplified, (3) high level of expression of PDGFRA, VEGFR1/VEGFR2 and EGFR is uniformly present in the tested tumors, (4) PAIS demonstrate activation (phosphorylation) of PDGFRA and downstream PI3K-AKT and MAP-Kinase signaling pathways, (4) in ex vivo assays, a potent effect of BMS354825 on proliferation and survival of primary cells of PAIS is proven. Conclusions: PDGFRA is amplified and activated in PAIS, thus constituting one of many possible targets for the therapy. Tested inhibitors showed differential efficacy for inhibition of PAIS cells by ex vivo assays. No significant financial relationships to disclose.
Phase I/II study of docetaxel (D), gemcitabine (G), and bevacizumab (B) in patients (pts) with advanced or recurrent soft tissue sarcoma (STS)
Authors: Verschraegen C. F. , Fekrazad H. M. , Rabinowitz I. , Quinn R. , Snyder D. , Judson P. , Purdy M. , Lee F. C. 
Published: March 2020

10056 Background: The combination of G and D has shown efficacy against refractory STS (Hensley, JCO 2002). STS have a high content of VEGF, which is associated with poor prognosis. This phase I/II study assesses the safety, tolerability, efficacy, and pharmacodynamics (PD) of B in combination with G+D, given on a two-weekly schedule to minimize adverse events (AEs). We are reporting the phase I results. Methods: Untreated pts with advanced or recurrent STS and ECOG PS =2 were eligible. Some pts were treated in a neoadjuvant setting, when surgically appropriate. Planned doses were G 1,000, 1,250, and 1,500 mg/m2, D 50 mg/m2, and B 5 mg/kg iv, every 2 wks. G doses were escalated in serial pt cohorts to determine the maximum tolerated dose (MTD) of G with fixed doses of D and B. MTD was assessed on the first 2 cycles (1 cycle = 2 wks). Treatment was continued until progression or unacceptable toxicity. For neoadjuvant therapy, B was given only for 4 cycles, followed by 4 cycles without B in anticipation of surgery and pts came off study at that point. PD and antitumor efficacy were also assessed. Results: Nine pts have been treated on the phase I escalation arm, including 3 in the neoadjuvant setting. There were no dose limiting toxicities. After 4 cycles with G at 1,500 mg/m2, there was 1 asymptomatic grade 4 bowel perforation at the site of the tumor in a pt with initially inoperable leiomyosarcoma (LMS). After emergency surgery, the pt is free of disease. Observed grade 1 and 2 AEs include alopecia, diarrhea, fatigue (5 each), rigors (4), nausea, dyspnea, headaches (3 each), chest pain, epistaxis, stomatitis, anemia (2 each), rash, hypertension, neuropathy, leukopenia (1 each). There were 1 CR (angiosarcoma), 2 PR, (myxoid sarcoma, undifferentiated sarcoma), 4 NC (2 LMS, liposarcoma, PNST), and 2 PD (myxoid sarcoma, PNST). Necrosis was observed, including in NC disease. Three pts are free of disease after surgery. Conclusions: The combination of G, D, and B given every 2 weeks is safe and has demonstrated some activity in pts with advanced or recurrent STS. The phase II arm is ongoing at G 1,500 mg/m2 with 4 pts already enrolled. Mature data including PD will be reported at the meeting. No significant financial relationships to disclose.
Impact of the smallest surgical margin on local recurrence in soft tissue sarcoma treated with surgery with or without radiotherapy: First ten year results of a prospective treatment protocol at Helsinki University Central Hospital
Authors: Tarkkanen M. , Sampo M. , Huuhtanen R. , Tukiainen E. , Bohling T. , Blomqvist C. 
Published: March 2020

10064 Background: A single-institution experience using a prospective treatment protocol for soft tissue sarcoma (STS) of the extremity and trunk wall was reviewed. Special interest of smallest surgical margin on local control was taken. Methods: Between 1987 and 1997 361 patients with STS were treated by the STS Group at Helsinki University Central Hospital. Patients with borderline malignancies or metastatic disease were excluded leaving 270 patients to the present study. All patients included underwent surgery. Postoperative radiotherapy was administered if the smallest surgical margin was less than 2.5 cm when there was no natural barrier, irrespective of tumor grade. Results: With a median follow-up of 6.6 years, the 5-year local control for the whole study population was 76 %. On multivariate analysis, the smallest surgical margin in centimeters, adequacy of treatment according to protocol and postirradiation sarcoma were prognostic for local control. A margin of at least 2,5 cm yielded recurrence-free rate of 89 % at five years. Conclusions: Our findings show that size, depth and grade of the tumor, and patient`s age at diagnosis do not have independent prognostic effect on local control, nor has recurrent disease at referral. Instead, surgical margin in centimeters and adequacy of treatment according to protocol had independent prognostic value for local control. This is encouraging since these factors can be affected by aggressive local treatment. Soft tissue sarcomas should be referred to a specialized multimodality treatment group before biopsy or any surgery. A surgical margin of 2–3 cm yield a reasonable local control in STS even without radiotherapy. No significant financial relationships to disclose.
High-dose Ifosfamide (HDIFX) as a 14-day continuous infusion (ci) in advanced adult soft tissue sarcoma (STS): A single- institution retrospective case series analysis
Authors: Coco P. , Fumagalli E. , Bertulli R. , Dileo P. , Grosso F. , Stacchiotti S. , Piovesan C. , Sanfilippo R. , Accolla M. , Casali P. G. 
Published: March 2020

10067 Background: High-dose IFX (≥12 g/sqm) is active even in STS patients pretreated with standard-dose IFX, though with substantial toxicity. Prolonged continuous infusion, through a portable pump, may be an alternative way of administration. A Phase II study thereof is ongoing in Italy, but some pts have been treated off the study, either prior to its start or for practical reasons. Such consecutive pts seen at a single institution have been retrospectively reviewed. Methods: Between July 2001 and September 2006, 45 adult patients (M:F = 25:20; mean age 47 yrs; PS 0–1) with progressing advanced/metastatic STS, all previously treated with anthracyclines and standard-dose IFX, were given ciHDIFX, at the dose of 14 g/sqm as a 14-day continuous infusion every 4 weeks, using two portable infusional devices, with equidose Mesna, lasting 7 days each. Diagnosis was leyomiosarcoma in 12 patients, synovial sarcoma in 9, liposarcoma in 5, and other histological types in 19. Disease was advanced inoperable in 6 pts, and metastatic in 39. The total number of cycles was 176 (median number per pt: 4). Results: A PR was seen in 5 pts (synovial sarcoma, 2; leyomiosarcoma, 1, liposarcoma, 1; chondrosarcoma, 1), and SD in 22 (>6 mos in 12), for a clinical benefit rate = 37%. PFS at 6 months was 35%. Median PFS was 11 mos in pts with PR and 6 in those with SD. Median PFS was 8 months in 9 patients undergoing complete tumor resection. Most common side effects were nausea (G1–2 in 14 pts) and asthenia (G1–2 in 15 pts). G2 anemia was seen in 8 pts, G2 neutropenia in 6. One pt with a single kidney had a reversible G2 hypercreatininemia. No grade 3–4 toxicity were recorded. Conclusions: In this series, ciHDIFX was associated with a PR and 6-mos PFS rate in the range of active second-line agents in advanced STS. This regimen was exceedingly well tolerated. No significant financial relationships to disclose.
Secondary sarcomas after radiation in patients with breast cancer
Authors: Mery C. M. , George S. , Raut C. P. 
Published: March 2020

10072 Background: Studies have shown that radiation (RT) predisposes patients with breast cancer (BCa) to develop a secondary sarcoma (SS). Few have analyzed recent incidence trends or have been powered to assess specific histologies. The goal of this study was to quantify the risk of developing different types of SS after RT in BCa and assess time trends using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Females with microscopically-confirmed non-metastatic BCa reported to SEER between 1973 and 2003 were included. Development of SS was analyzed with Kaplan-Meier curves and proportional hazard models, and reported as hazard ratios (HR) with 95% confidence intervals. Descriptive variables were analyzed with chi square. Results: The cohort of 482,469 BCa patients (age 60.1±13.4yrs) was divided in 2 groups: RT (37%) and no RT, based on treatment. RT patients were younger (p<0.0001) and had more partial mastectomies (p<0.0001). RT usage increased with time (from 23% in 1973–1977 to 48% in 2001–2003, p<0.0001). 874 patients developed SS 12–343 months after BCa diagnosis. RT patients had a higher incidence of all SS (30 vs 21 cases/100,000 person-years, HR: 1.57 [1.4–1.8]), angiosarcomas (HR: 7.8 [4.9–12.2]) and malignant fibrous histiocytomas (MFH) (HR: 2.5 [1.6–3.9]). Risk was increased in sites close to the RT field (chest and ipsilateral arm) (HR: 4.17 [3.2–5.5]) but not in others (HR: 1.07 [0.91–1.3]). Risk increased with age and time period at BCa diagnosis (p<0.0001). RT remained a significant predictor of SS development after adjustment for these variables (HR: 1.5 [1.3–1.7]). The hazard of developing SS after RT increased over the first several years after diagnosis of BCa, peaked at 10–14 years, and then decreased again, reaching the non-RT hazard at ∼22 years. 5-yr survival after SS diagnosis was 38%. Conclusions: Administration of RT for BCa increases the risk for development of SS, in particular angiosarcomas and MFH in sites associated with the RT field. Risk of SS has increased with time, independently of RT usage. Patients receiving RT for BCa should be followed closely for more than 20 years. No significant financial relationships to disclose.
Synovial sarcoma of the extremities and trunk: A long lasting disease
Authors: Merimsky O. , Soyfer V. , Goffman A. , Issakov J. , Bickels J. , Dadia S. , Kollender Y. , Meller I. 
Published: March 2020

10073 Background: Synovial sarcoma (SS) of an extremity or trunk is a relatively rare type of soft tissue sarcoma. SS most commonly affects adolescents and young adults. SS usually originates at an extremity, carries a t(X;18)(p11;q11) translocation, and approached by limb sparing surgery, radiation therapy, and chemotherapy. Methods: A retrospective analysis of clinical and histopathological data of 73 patients with proven SS, treated at the National Unit of Orthopedic Oncology, from January 1991 through December 2004 was performed. Results: At a median follow-up time of 6 years, a local-recurrence was observed in 17.8% of the patients, while systemic recurrence in 35.6% (local-only in 6.8 %, systemic-only in 24.6 %, and combined in 11%). Accumulation of events of local and systemic recurrence following a limb sparing approach, did not reach a plateau even after 192 months from diagnosis. The 10-year local recurrence free survival (LRFS), the 10-year systemic recurrence-free survival (SRFS), and the 10-year overall survival (OS) were 78%, 68%, and 61%, respectively. The median SRFS time was 180 months, while the median LRFS and OS have not been reached yet. LRFS was significantly better for ILP treated patients; SRFS was influenced by a shorter delay in diagnosis. Conclusions: The practical aspects of our observations are the need for long-term follow-up for diagnosis of recurrence, the fact that not all local or distant recurrences are necessarily associated with shortening of overall survival, and the important role of induction ILP with TNF in cases of extremity SS. No significant financial relationships to disclose.
Localized myxoid/round cell liposarcoma in adult patients. IL6 protein expression analysis
Authors: Gomez-Roca C. A. , Ruiz-Soto R. , Castaing M. , Marty V. , Bonvalot S. , Terrier P. , Le Pechoux C. , Domont J. , Cioffi A. , Le Cesne A. 
Published: March 2020

10075 Background: Myxoid/round cell liposarcoma (MLPS) is an uncommon soft tissue sarcoma with a relatively favorable prognosis and is considered a low grade malignancy. Methods: Retrospective analysis of 123 localized MLPS adult patients (pts) treated at our institution from 1987 to 2005 was performed. Paraffin embedded tissue was analyzed for IL6, IL6 receptor, NFkB and bcl-2 protein expression (positive (+) or negative) by tissue microarray immunostaining. Results: The median age of the 77 males and 46 females was 42 years (yr) (range 15–70). Lower extremity (LE) was the site more affected (77 pts). Median tumor size was 11 cm (range 2.5–40 cm), 87 were deep tumors and 63 were grade 1 tumors. Preoperative biopsy was carried on 38 pts. All but 2 pts underwent surgery (R0 24%, R1/R2 76%); 44 pts had a second surgery. Chemotherapy (CT) and radiation therapy were given to 30% and 52% of pts respectively. Complete remission was achieved in 98% of pts. After a median follow up of 6 yr (range 0.1–19 yr) 53 pts relapsed (43%); 37 locally, 11 distant and 5 both. Metastases occurred in 26 pts, 17 solitary and 9 multiple. The 5-yr, 10-yr and 15-yr DFS were 56%, 48% and 44% respectively. Median time to first relapse was 6.5 yr (range 0.1–16 yr). The 5-yr, 10-yr and 15-yr OS are 90%, 79% and 64% respectively. Tumor site, pre-surgical biopsy, R0 surgery and second surgery correlates with a better DFS in the multivariate analysis. So far 19 tumors have been studied for, NFkB (+) 57%, IL6 (+) 47% and Bcl2 (+) 30%, positivity. All tumors (+) for IL6 were also (+) for IL6 receptor. None of the proteins correlated to DFS and/or OS. Conclusions: Pts with localized resected MLPS require a prolonged follow-up since relapses occur after 10 yrs. PFS and OS correlate with an optimal loco-regional treatment. Half of MLPS expressed IL6, probably involving an autocrine phenomenon; whether this cytokine is involved in tumor aggressiveness, remains to be established. No significant financial relationships to disclose.