bluuebunny/crossref_metadata_2025_split huggingface dataset:
Final results of a FNCLCC French Sarcoma Group multicenter randomized phase II study of gemcitabine (G) versus gemcitabine and docetaxel (G+D) in patients with metastatic or relapsed leiomyosarcoma (LMS)
Authors: Pautier P. , Bui Nguyen B. , Penel N. , Piperno-Neumann S. , Delcambre-Lair C. , Bompas E. , Collin F. , Rey A. , Jimenez M. , Duffaud F. 
Published: August 2020

10527 Background: An objective response rate (RR) of 8% and 17% with G and G+D were respectively reported in metastatic soft tissue sarcomas (Maki, J Clin Oncol. 2007). We previously reported a 5% RR in 41 evaluable patients (pts) with ‘non uterus‘ LMS randomized to each arm of this randomized phase II study (Duffaud, ASCO. 2008). We present here the results of G vs G+D in uterine and all LMS. Methods: Patients had histologically proven metastatic or unresectable LMS, one prior anthracycline- based regimen, age ≥18, measurable disease (RECIST), PS ≤ 2. Treatment was G 1,000 mg/m2(over 100 minutes, d1+d8+d15) q28 days (d) or G 900 mg/m2(over 90 min, d1+d8) and docetaxel 100 mg/m2 (over 60 min, d8) q21 days; in the G+D arm, pts received lenograstim d9–15, 25% dose reductions were employed for prior pelvic radiation. The primary endpoint was the objective RR (CR+PR), evaluated every 2 cycles. Stratification was by primary tumor location (uterus vs. non-uterus). The Simon method was used: for “uterus” study, 20 pts per arm for a 74% probability of selecting the arm with a real RR of 50%, expected baseline RR was 40%; for the “non-uterus” study, 20 pts per arm for a 92% probability of selecting the arm with a real RR of 40%, expected baseline RR was 20%. Results: From 02/06 to 12/08, 44 pts were enrolled in the “non-uterus” study, 40 pts in the “uterus” study. Currently 76/82 pts are evaluable for response (41/44 in the “non uterus” and 35/38 in the “uterus” study) and 80/84 for toxicity. In the uterus group the median age is 57 (range 41–80), 24 pts received prior pelvic radiotherapy, the median number of cycles was 5 (range 0–8) and dose received/dose planned (%) were 69% in G arm, 88% of G and 86% of D in G+D arm. No differences in toxicity were observed between both LMS locations: in the G arm, toxicity was moderate except for one pulmonary gr4; in the G+D arm one toxic death was related to gr5 thrombocytopenia and there were 2 non-haemathologic gr4 toxicities; 11 pts stopped for intolerable toxicity (3 in G and 8 in G+D arm) and 1 pt for hypersensitivity (G+D arm). Conclusions: Final tumor response for uterine LMS and updated toxicity and PFS data for all the LMS will be presented during the meeting. [Table: see text]
Myelodysplastic syndromes developing after imatinib therapy for GIST
Authors: Spadaro P. , Ingemi M. , Pitini V. , Arrigo C. , Soto Parra H. 
Published: August 2020

10532 Background: Imatinib mesylate 400 mg a day is the standard treatment for patients (pts.) who have advanced or metastatic gastrointestinal stromal tumor (GIST) even if different kit and PDGFRA mutations have a marked impact on the outcome of pts.; briefly, pts. with exon 9 mutations fared worse than those who had exon 11 mutations and both types of pts. did better than those with wild type genotype. Previously, we had detected clonal chromosomal abnormalities in the bone marrow of GIST pts. who developed a myelodysplastic syndrome during treatment with imatinib, so we performed a systematic study in a series of male and female GIST pts. during treatment with imatinib. Methods: Between January 2007 and December 2008, bone marrow samples for morphologic analysis, FISH and classical cytogenetics were obtained from 49 pts. (30 male; 19 female, mean age 62) with unresectable or metastatic GIST before and during treatment with 400 mg/d of imatinib. For pts. with progressive disease (15 pts.) or exon 9 mutant disease (5 pts.), imatinib 800 mg a day was scheduled. All pathologic material was reviewed to identify pts. with MDS or AML according to the WHO classification. Interphase and metaphase preparations were done according to the standard protocol. Results: At the time of analyses, all pts. were evaluable. Ten patients experienced anemia of grade 3–4 while five pts. developed granulocytopenia of grade 3–4. Eight pts. acquired cytogenetic chromosomal abnormalities in their bone marrow. A trisomy 8 was detectable in seven pts. even if, curiously, in four of these pts. this come and went on repeated sampling without any apparent clinical effect, three pts. developed an MDS (two refractory cytopenias with multilineage dysplasia, and one refractory cytopenia with multilineage dysplasia and ringed sideroblast). One patient developed a RAEB-1 with monosomy 7 which rapidly transformed into AML. Conclusions: During therapy with imatinib some pts. with GIST developed chromosomal abnormalities. Although, these occurrences are rare, the findings highlight the need for close monitoring of pts. with GIST treated with imatinib. No significant financial relationships to disclose.
Efficacy of a genetically modified Salmonella typhymurium against metastatic osteosarcoma in an orthotopic mouse model
Authors: Hoffman R. M. , Zhao M. , Hayashi K. 
Published: August 2020

10543 Background: We have previously developed a genetically-modified strain of S. typhimurium, selected for tumor targeting and therapy in vivo. Normal tissue is cleared of these bacteria even in immunodeficient athymic mice with no apparent side effects. Methods: In this study, the tumor-targeting strain of S. typhimurium, termed A1-R, was administered i.v. to nude mice which have primary bone tumor and lung metastasis. Primary bone tumor was obtained by orthotopic intratibial injection of 5 × 105143B-RFP (red fluorescent protein) human osteosarcoma cells. One group of mice was treated with A1-R and another group was used a as control. A1-R (5 × 107 colony-forming units) was injected in the tail vein three times on weekly basis. On day 28, lung samples were excised and observed with the Olympus OV100 Small Animal Imaging System. Results: The size of the primary tumor and RFP intensity of lung metastasis were measured. Primary bone tumor size (fluorescence area [mm2]) was 232 ± 70 in the untreated group and 95 ± 23 in the treated group (P<0.05). RFP intensity of the lung metastasis was 3 ± 1.5 × 106in the untreated group and 0.42 ± 0.33 × 106 in the treated group (P<0.05). No toxicity was observed in the treated mice. Conclusions: Therefore, bacterial treatment was effective for both primary bone tumor and lung metastasis. Treatment with the tumor-targeting but non-toxic mutant of S. typhimuriumis a promising approach to therapy of metastatic osteosarcoma. No significant financial relationships to disclose.
A prognostic score at diagnosis for Ewing tumor patients with metastatic disease at extrapulmonary sites
Authors: Ladenstein R. , Pötschger U. , Le Deley M. , Whelan J. , Paulussen M. , Oberlin O. , van der Berg H. , Dirksen U. , Craft A. , Jürgens H. 
Published: August 2020

10544 Background: To assess prognostic factors at diagnosis in prospectively treated patients with primary extra-pulmonary metastatic Ewing tumors (EPM-ET) of the EURO-E.W.I.N.G. 99 Study. Methods: From 1999 to 2005, 281 patients were enrolled. Median age was 16.2 years (0.4–49). Primary site was extremity in 84 patients and axial in 197 (115 pelvic sites), with a tumor volume >200ml in 171 patients. Treatment consisted of 6 VIDE cycles, one VAI/VAC cycle, local treatment (surgery and/or radiotherapy), and high-dose busulfan-melphalan followed by peripheral stem cell transplantation (HDT/SCT). Results: After a median follow up of 3.8 years, event-free survival (EFS) and overall survival (OS) at 3 years for all 281 patients were 27%±3% and 34%±4%. Six VIDE cycles were completed by 250 patients (89%); 169 (60%) received HDT/SCT. Cox regression analyses demonstrated increased risk for patients with more than two bone metastatic sites (hazard ratio: HR 2.0), a primary tumor volume >200ml (HR 1.8), bone marrow metastases (HR 1.6), age >14 years (HR 1.6), and additional lung metastases (HR 1.5). A risk score based on these HR identified three risk groups with EFS rates of 50% for scores <_3 (82 patients), 25% for scores >3 to <5 (102 patients), and 10% for scores >_5 (70 patients), p< 0.0001. Conclusions: A proportion of EPM-ET patients may survive with intensive multimodal therapy. Age, tumor volume, and extent of metastatic spread are relevant risk factors. A score based on these factors identifies EPMD-ET patients with a more favorable outlook at diagnosis and may facilitate risk adapted treatment approaches. No significant financial relationships to disclose.
High-dose chemotherapy with autologous stem cell transplantation for relapsed Ewing's sarcoma
Authors: Palmerini E. , Brach Del Prever A. , Fagioli F. , Luksch R. , Prete A. , Tamburini A. , Abate M. E. , Picci P. , Ferrari S. , Tienghi A. 
Published: August 2020

10545 Background: Nearly 30–40% of patients with newly diagnosed, non-metastatic Ewing's Sarcoma (EWS) relapse. Post-relapse survival (PRS) in EWS is very poor, with less than 15–20% alive 5-years after recurrence. The role of high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) is under investigation in metastatic and high risk localized EWS patients. In order to improve PRS, we employed HDCT with ASCT in EWS patients at 1st relapse. Methods: All non-metastatic EWS patients treated in Italian Sarcoma Group centers who relapsed between 1999 and June 2008 were offered HDCT (busulfan 4 mg/kg × 4 days orally and melphalan 140 mg/m2) with ASCT whenever possible (no previous HDCT; stable or responding disease after standard dose chemotherapy; adequate peripheral blood stem cells harvest). Results: 72 EWS patients experienced disease recurrence. Fifty (62%) were male. Twenty-eight (39%) of patients had previously received HDCT. Median relapse free interval (RFI) was 16 months (2.8–64). Pattern of relapse was: lung metastases in 20 (28%) patients, bone metastases in 12 (16%), local recurrence in 11 (15%) and multiple sites in 29 (40%). Treatment at 1st relapse was: standard dose chemotherapy in 31 (43%) patients; HDCT followed by ASCT in 24 (33%); palliative treatment in 12 (17%) and surgery only in 5 (7%). Three patients died of treatment-related toxicity. With a median follow-up of 24 months (1–64), the 3-year post-relapse survival (PRS) was 21% (95%CI 7–35). 3-year PRS was better for patients with a lung only relapse [48%, (95%CI 21–74)] and a RFI > 2 years [51%, (95%CI 27–76)]. 3-year PRS was 33% (95%CI 13–54) for patients treated with HDCT and 22% (95%CI 6–39) for those receiving standard dose chemotherapy. A significant (P 0.02) advantage was observed in the subgroup of patients with a shorter RFI treated with HDCT [3-year PRS 29% (95%CI 5–52)] compared to those treated with standard dose chemotherapy [3-years PRS 13%, (95%CI 2–29)]. Conclusions: Pattern of recurrence and RFI are the main factors influencing PRS in EWS. The use of HDCT with ASCT in recurrent EWS is investigational. Patients with shorter RFI could more likely benefit from HDCT. No significant financial relationships to disclose.
Long-term results with combined treatment in adult localized extraskeletal Ewing's sarcoma (ES): A retrospective analysis of 51 patients (pts) from a single referral center
Authors: Dileo P. , Bertulli R. , Piovesan C. , Marrari A. , Puma E. , Spreafico C. , Gronchi A. , Olmi P. , Gandola L. , Casali P. G. 
Published: August 2020

10548 Background: After the first description in 1975, only small series of adult extraskeletal ES have been reported. In general, adulthood is claimed to be an adverse prognostic factor, while the meaning of extraskeletal origin is less established. Methods: We retrospectively reviewed adult pts with extraskeletal, localized ES, undergoing medical therapy between 1988 and 2004, who were included in the dataset of the current Adult Sarcoma Medical Unit at Istituto Nazionale Tumori, Milano, Italy, which serves as a reference center for adult soft tissue sarcoma. Fifty-one pts were treated with a combined approach, including chemotherapy, surgery when appropriate, and radiation therapy. Overall, 27/51 pts were male, and age ranged from 16 to 63 years. Site of primary lesions was: thorax 14 (27%), limbs 18 (35%), paravertebral region 5 (10%), pelvis 4 (8%), head&neck 3 (6%), superficial trunk 6 (12%), other 1 (2%). Seven pts presented with locally advanced disease. Chemotherapy regimens included: vincristine (V), ifosfamide (I), epirubicin (E)/adriamycin (A), dacarbazine (D), actinomycinD (ActD), cisplatin (C), etoposide (Et). 35/51 pts (68%) underwent preoperative chemotherapy: 30 pts received IVE × 4–7 cycles; 5 pts received VAI alternating with IEt × 9 cycles. 42/51 pts underwent surgery; 38/51 pts received radiation therapy. Results: Response rate to induction chemotherapy including antracicline, ifosfamide + etoposide was 83%. Of these pts, 9 showed a complete response (CR), 17 a partial response (PR), 3 a minor response (MR), 3 stable disease (SD), and 3 progressive disease (PD). Overall, DFS at 10 years (y) was 55%. Pts with limb, head&neck, or superficial trunk lesions had a better outcome compared to those with other primary sites (DFS at 10y is 71% vs 33%). Conclusions: In this series of adult pts with extraskeletal ES, response rate and DFS were comparable to those of ES of bone in conventional series. The primary site may identify a subset of pts with worse outcome and prognosis, for whom more intensive treatments could be investigated. No significant financial relationships to disclose.
Outcome of patients with advanced GIST achieving a complete remission (CR) with imatinib (IM) before interruption: Pooled analysis of two consecutive prospective randomizations of the French Sarcoma Group BFR14 phase III trial
Authors: Chevreau C. , Ray-Coquart I. , Bui B. , Adenis A. , Rios M. , Duffaud F. , Darnis S. , Le Cesne A. , Moneron C. , Blay J. 
Published: August 2020

10549 Background: Patients (pts) experiencing a major response under IM treatment seem to have a better outcome than others (Cioffi, ASCO 08). IM interruption in responding patients after 1 and 3 yrs of treatment results in a high risk of rapid progression after a few months. The influence of pattern of response on PFS before IM discontinuation is unknown. Methods: Since June 2002, 415 pts were included in this trial. Fifty-eight, 50 and 12 (ongoing) non progressive pts at 1, 3 and 5 yrs respectively were randomly offered to continue (C arm) or interrupt (I arm) IM. Sixty-four pts were randomized in the I arm, 32, 25 and 7 after 1, 3 and 5 yrs of IM treatment respectively. Time to progression (TTP) of pts achieving a CR or a major PR (residual tumor < 10mm) before IM interruption was compared to outcome of pts experiencing others patterns of response. Results: Twenty-three pts achieving a CR or a major PR (36%) before randomization in the I arm, 9 after 1 yr, 10 after 3 yrs and 4 after 5 yrs of IM treatment. As of December 2008, 15 relapses were observed in the CR group (65%) versus 36 in the other cohort of pts (90%). The median TTP were 10.5 months (IC95%: 9–16 months) for the CR group and 6.1 months (IC95%: 4–9.2 months) for the non CR group (p=0.058). The median TTP were 9.4 months for the CR group vs 6 months for pts randomized after 1 yr of treatment, 12.3 months versus 5.7 months for pts randomized after 3 yrs of treatment respectively. One third of pts achieving a CR before randomization in the I arm was free of disease in December 2008. Conclusions: A CR achieved under IM is not a prerequisite for a prolonged disease-free survival in advanced GIST after 1 or 3 yrs of treatment. Despite a trend for a favourable outcome, prognosis of pts with a CR or a major PR is similar to those achieving a PR or a disease stabilisation. A selected group of advanced GIST pts in CR could be cured with IM alone. New radiological assessments or response critera have to be implemented in order to define a real CR. [Table: see text]
Neoadjuvant imatinib and organ preservation in locally advanced gastrointestinal stromal tumors (GIST)
Authors: Hohenberger P. , Oladeji O. , Licht T. , Dimitrakopoulou-Strauss A. , Jakob J. , Pink D. , Schwarzbach M. , Ströbel P. , Reichardt P. , Wardelmann E. 
Published: August 2020

10550 Background: We assessed the outcome of patients with locally advanced gastrointestinal stromal tumors (GIST) undergoing preoperative therapy with imatinib. Methods: 36 patients with biopsy proven GIST (23 f, 13 m, median age 58 (27–85) yrs, 31 primary tumors, 5 local recurrences) of the esophagus/EGJ (n=5), stomach (n=17), duodenum (n=2), small bowel (n=3), or rectum (n=9) were treated with imatinib 400mg/d for 6 mos. preop. Six pts had been found unresectable at exploratory lap. and no pt. had signs of metastases on CT/MRI and/or FDG-PET. Average tumor size was 10.5 cm (4–28 cm). According to Consensus two tumors were low risk, 11 intermediate, and 23 were high risk for aggressive behaviour. 33 pts were symptomatic. Extent of surgery, local outcome, morbidity and response to therapy were analyzed; median follow-up is 22 mos. Results: Median treatment duration was 11 mos. (range 2–31 mos). Successful dose adjustment for exon 9 mutation to 800 mg imatinib/d was used in two pts. 33 pts. completed the treatment schedule, two died from unrelated disease, another one had to be operated for tumor rupture. Of the remaining 33, median tumor size shrank to 55 mm. Two elderly patients refused surgery and continued with the drug; one pt. was found still unresectable. Complete tumor removal was possible in 28 pts without operative mortality, but two pts showed previously undetected peritoneal spread (R2 resection). Histologically, one pCR and 11 near CR/good PRs were found. The extent of resection found 5 of 6 inoperable pts now resectable and in 21/25 pts a less extensive procedure could be performed in comparison to recommendations by previous tumor boards (segmental gastric resection for gastrectomy, avoidance of pancreatectomy, transanal resection instead of colo-anal anastomosis). Two local recurrences were detected at 31 and 44 mos. postop. Conclusions: Locoregionally advanced GIST can be treated successfully with upfront imatinib at 400mg/ (800 mg in exon 9 mutation). Substantial tumor shrinkage facilitates radical but conservative surgery and results in organ-preservation in the overwhelming majority of patients. PET monitoring proved very helpful and added to CT/MRI evaluation. Long-term results on survival and metastatic spread have to be awaited. [Table: see text]
Neoadjuvant imatinib in patients with locally advanced GIST in the prospective BFR14 trial
Authors: Cassier P. A. , Blesius A. A. , Perol D. , Ray-Coquard I. , Adenis A. , Bui B. , Bertucci F. , Rios M. , Le Cesne A. , Blay J. 
Published: August 2020

10551 Background: The role of surgery in the management of patients with advanced gastrointestinal stromal tumors (GIST) in the era of imatinib mesylate (IM) remains unknown. We sought to assess the outcome of patients with locally advanced primary GIST tumors without metastases treated with IM in the neoadjuvant setting within the prospective BFR14 phase III trial. Methods: The data base of the BFR14 trial was searched for patients with locally advanced disease and no metastases. Patients with recurrent disease were excluded. Results: Twenty five patients (9 females, 16 males) met these criteria. Twenty patients were PS 0 or 1, primary tumor sites were: small intestine (n=7), peritoneum (n=7), rectum (n=4), stomach (n=4), esophagus (n=2), and pelvis (n=1). Nine of the 25 patients underwent surgical resection of the primary tumor after a median of 7.3 (range 3.4–12.1) months of treatment with IM. There was a significant improvement in progression-free survival (PFS) for patient who underwent surgical resection versus those who did not: median PFS: 28.7 month vs 12.9 months respectively (p=0.0463) this benefit did not however translate into a significant benefit in overall survival (OS), although the trend favoured the resected group: median OS median not reached vs 29.4 months (p=0.0677). Conclusions: Surgery may increase progression-free survival in patients with locally advanced GIST who become resectable following treatment with IM. [Table: see text]
Correlation between spiral CT and PET in patients with advanced GIST refractory to high-dose imatinib: A GEIS study
Authors: Fuster D. , Sierra A. , Ayuso J. R. , Poveda A. , Cubedo R. , Casado A. , Martínez-Trufero J. , López-Pousa A. , Garcia Del Muro X. , Maurel J. 
Published: August 2020

10553 Background: Small changes in tumor size or density on computed tomography (CT) are sensitive and specific methods to assess response of GISTs and correlates well with positron emission tomography with 18F-Fluorodeoxyglucose (FDG-PET) in untreated GIST patients (pts). Despite of it, there is inconsistent prospective data in imatinib (IM) refractory disease. Methods: This multicenter phase I-II study prospectively evaluated 26 pts with metastatic high-dose IM refractory GISTs treated with doxorubicin 15 - 20 mg/m2/weekly per 4 cycles, followed by IM maintanance (400mg p.o.qd). CT and FDG-PET were performed at baseline and after 2 months of therapy. Response rate was assessed by RECIST criteria by Principal Investigator (PI). CT and FDG-PET (EORTC criteria) were reviewed by two experts in abdominal CT (AR) and one expert on Nuclear Medicine in one Institution. Results: Tumor density measurements were not assessed on CT because some studies were not available in DICOM format and different tube currents were used. There were significant lower number of lesions identified by PI (n=73; median 2, range 1–6) than AR (n=122; median 5, range 1–10). Twenty-eight out of 122 lesions identified by CT did not demonstrate significant uptake in FDG-PET at baseline (upon 800mg/day of IM treatment) on FDG-PET. Mean baseline tumor size on CT was 5.9cm (ranging from 0.9 to 28cm), and mean baseline SUVmax on FDG-PET was 7.2 (ranging from 1.9 to 26.4). Nine patients responded on FDG-PET compared with 2 pts and 5 pts with RECIST or modified RECIST criteria (decrease in tumor size more than 10%), respectively. The sensitivity for RECIST or modified RECIST in identifying PET responders was 22% and 55%, showing a 100% of specificity by both methods. Good responders on FDG-PET at 2 months had significantly longer progression free survival (264 days) than non-responders (64 days) (P=0.01). Conclusions: FDG-PET is sensitive and specific to assess response of GISTs pts refractory to high-dose IM. If the prognostic value of FDG-PET can be confirmed should be employed in future studies of pts with refractory GIST. No significant financial relationships to disclose.