bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term results of a randomized phase II study of trabectedin by two different dose and schedule regimens in patients with advanced liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide
Authors: Demetri G. D. , Schuetze S. , Blay J. , Chawla S. , von Mehren M. , Casali P. , Morris D. , Bayever E. , Alfaro V. , LeCesne A. 
Published: August 2020

10509 Background: This prospective, international randomized study evaluated two trabectedin dosing regimens [1.5 mg/m2 24-hour i.v. infusion once every 3 weeks (q3wk 24-h) vs. 0.58 mg/m2 3-hour i.v. infusion every week for 3 weeks of a 4-week cycle (qwk 3-h)] in adult patients (pts) with unresectable and/or metastatic liposarcoma or leiomyosarcoma following failure of at least prior anthracycline and ifosfamide chemotherapy. Methods: Pts were treated and continuously followed in this trial, and we now present final OS data with long-term follow-up (median = 41 mo). With 234 deaths, the study would have >80% power to detect a minimum 45% improvement in median overall survival (OS) (2-sided 5% significance level). Results: The primary efficacy endpoint (time to progression, TTP) was superior for the q3wk 24-h arm, as previously reported [Morgan, et al. J Clin Oncol: 25(18S June 20 Suppl.) 10060 (2007)]. At cutoff, 235 deaths had occurred (13% censored). This final OS analysis confirms the previously reported trend towards improved survival with trabectedin q3wk 24-h despite crossover of 32% of pts from qwk 3-h to the q3wk 24-h dosing regimen. Pts treated with q3wk 24-h had a 16% reduction in the relative risk of death (HR=0.843; p=0.1931). Median (95%CI) OS were 13.9 mo (12.5–18.6; q3wk 24-h) and 11.8 mo (9.9–14.9; qwk 3-h) (log-rank p=0.1920). OS rates at 12 mo were 60% (q3wk 24-h) and 50% (qwk 3-h). Sensitivity analyses censoring at crossover further highlighted this favorable trend in survival with trabectedin q3wk 24-h. With longer follow-up, updated median TTP (investigator assessment, 223 progression events) was 4.2 vs. 2.5 mo [HR: 0.658; p=0.0032], favoring the q3wk 24-h arm. With 59 additional cycles (for a total of 1,532 cycles) and longer exposure, trabectedin safety profile was consistent with that previously reported. Conclusions: Final survival data reinforce the internal consistency of all efficacy-related endpoints showing improved outcomes associated with the trabectedin q3wk 24-h regimen with an acceptable safety profile in this population of patients with advanced, previously-treated leiomyosarcomas and liposarcomas. [Table: see text]
A phase II clinical trial of neoadjuvant trabectedin in patients with nonmetastatic advanced myxoid/round cell liposarcoma (MRCL)
Authors: Gronchi A. , Le Cesne A. , Bui N. B. , Palmerini E. , Demetri G. , Hohenberger P. , Hohl R. J. , Pilotti S. , Perez I. , Lardelli P. 
Published: August 2020

10525 Background: Trabectedin (ET-743, Yondelis), a marine-derived alkaloid has demonstrated significant activity in the treatment of soft tissue sarcomas (STS) in phase III trials, and has recently received EMEA approval in this indication. A subtype that accounts for 10% of STS, MRCL, displays the fusion FUS-CHOP in 95% of all cases. Preliminary results of neoadjuvant trabectedin (T) in advanced MRCL show reduction in the radiological density of the tumor, clinical improvement, and a pathological complete response (pCR) in the resected tumor mass. A phase II study to further determine the response to T in the MRCL population is presented. Methods: In this multicenter Phase II trial, patients (pts) with locally advanced (stage III) or locally recurrent MRCL were treated for 3 - 6 cycles with T (1.5 mg/m2 q3wk) in the neoadjuvant setting. Main endpoints were: pCR rate, objective response rate by RECIST, and correlation of molecular parameters from tissue samples with clinical outcomes. Results: Twenty-five pts with locally advanced MRCL have been recruited, of whom 20 are evaluable. All had the translocation (t12q13, 16p11) which causes the chimeric FUS-CHOP. Median age was 53 (23–75) and male:female ratio was 1. Thirteen pts completed therapy and underwent curative surgery. Pathological assessment was performed in 10 pts: 2 achieved pCR, 1 as per central pathology review and 1 by local pathology assessment. In addition, 1 pt had a very good pathological response. Ten patients remain to be histologically evaluated. Response rate by RECIST from pts who completed therapy was: 6 partial responses (46%) and 7 disease stabilizations. Remarkably, pathological response does not entirely correlate with response by RECIST since the pts with pCR still had radiological disease but no malignant component was found in the excised tumor mass (only connective and reactive tissue). Two serious adverse reactions of severe rhabdomyolysis, and asthenia, nausea and transaminase elevation were reported. Most common toxicities were liver enzyme elevation, neutropenia and thrombocytopenia. Conclusions: These preliminary results in terms of objective and complete pathologic responses, strongly suggest that T may have a role in the neoadjuvant setting in pts with MRCL. [Table: see text]
Randomized phase II study of dacarbazine plus gemcitabine versus DTIC alone in patients with advanced soft tissue sarcoma: A Spanish Group for Research on Sarcomas (GEIS) study
Authors: Garcia Del Muro X. , Fra J. , Lopez Pousa A. , Maurel J. , Martín J. , Martínez Trufero J. , Casado A. , Cruz J. , Gómez España M. A. , Lavernia J. 
Published: August 2020

10529 Background: Dacarbazine (D) and gemcitabine (G) are active as single agents in the treatment of patients (pts) with advanced soft tissue sarcoma (STS) resistant to standard chemotherapy. The purpose of this study was to assess if the combination of D and G (Buesa et al. Cancer. 2004;101:2261) improved clinical outcome compared with standard D. Methods: Pts with advanced STS progressing after doxorubicin and ifosfamide, PS 0–2, no prior G or D, measurable disease and adequate organ function, were randomized to receive G 1,800 mg/m2 as a fixed dose infusion rate (10 mg/m2/min) and D 500 mg/m2 every 2 weeks, or D 1,200 mg/m2 alone every 3 weeks. Pts were stratified by PS and interval since the initial diagnosis. The primary endpoint was progression-free rate (PFR) at 3 months, based on EORTC reference values. A one-sample binomial design was used. To detect an increase in PFR at 3 months from 40% to 60% with a power of 80% and a two-sided alpha of 0.05, 49 pts had to be accrued per arm (an additional 10% was permitted, to allow for pts who could not be evaluated). Results: From November 2005 to September 2008, 113 pts from 18 centers were randomized. 3 pts were ineligible. Baseline characteristics were well-balanced between both arms. The median number of cycles administered of D+G and D were 6 (2–13) and 2 (1–10), respectively. PR and SD >12 weeks rates were 9% and 38% (D+G) vs. 4% and 19% (D) respectively (p=.01). PFR at 3 months was 59% (D+G) vs. 35% (D) (p=.001). 29 pts were free of progression at 3 months among the first 49 pts in the D+G arm (26 required to be the study positive). Median progression-free survival was 4.4 (D+G) vs. 1.9 (D) months (p=.002). Median overall survival was 17.1 (D+G) vs. 9.9 (D) months (p=.007). Asthenia, emesis and stomatitis were the most common nonhematologic effects. Severe anemia and thrombocytopenia were more frequent with D and granulocytopenia with D+G. Conclusions: The combination of D plus G is active and well-tolerated in pts with pretreated STS, yielding significant improvement in survival. No significant financial relationships to disclose.
A dose-escalating study of XRP6258 in combination with capecitabine, in patients (pts) with metastatic breast cancer (MBC) progressing after anthracycline and taxane therapy: Preliminary results
Authors: Besse-Hammer T. , Villanueva C. , Campone M. , Machiels J. , Awada A. , Magherini E. , Dubin F. , Semiond D. , Pivot X. B. 
Published: August 2020

1053 Background: Cabazitaxel (X), a new taxoid showed activity in taxane resistant MBC. Capecitabine (C) is approved in MBC pts pretreated with anthracycline and taxane. Methods: A standard 3+3 escalation scheme explored doses of combined intravenous X (Day (D)1) with oral C twice daily (D1to14), every 3 weeks (q3w). The study objectives were the identification of dose limiting toxicities (DLTs), recommended dose (RD) of the combination, assessment of safety, pharmacokinetics (PK) and activity at the RD in an expanded cohort. Results: 32 MBC pts pretreated with taxane and anthracycline were enrolled and treated (15 in the dose escalation part and 17 at the RD). Data for the first 25 pts, are available so far: median age 52 [34–74], ECOG-PS 0/1: 15/10, in first or second line chemotherapy, median of 3 (1–7) organs involved (mainly: bone, liver, lymph nodes). In the escalation part, X+C were administered at 3 dose levels (DL) (Table). DL2 was defined as the RD and the expansion cohort was initiated. PK analysis did not show any drug-drug interaction with this schedule of administration. Overall, out of the 25 pts (125cy), the main Gr3–4 toxicities (N pts) were asthenia (4), hand-foot syndrome (4), neutropenia (15), febrile neutropenia (1), neutropenic infection (1), no toxic death. Efficacy was observed at each DL with a total of 1 complete response, 4 partial responses (PR) and 16 stabilizations (including 3 unconfirmed PR). Conclusions: X was safely combined to C. X at 20 mg/m2 D1 + C at 1000 mg/m2 twice a D (D1–14), q3w is the RD. Updated results for efficacy and safety will be presented. [Table: see text] [Table: see text]
Type of progression in patients treated with imatinib for advanced gastrointestinal stromal tumor (GIST): A study based on the EORTC-ISG-AGITG trial 62005
Authors: Van Glabbeke M. M. , Verweij J. , Casali P. , Zalcberg J. , Le Cesne A. , Reichardt P. , Issels R. , Judson I. , Debiec-Rychter M. , Blay J. 
Published: August 2020

10536 Background: Development of resistance in GIST patients responding to targeted agents is heterogeneous, and different types of mutations may be observed in different lesions of the same patient. Progressive disease (PD) is defined as increase in size of initial lesions, occurrence of new lesions, or both (RECIST): mixed progression (MXPD), were new lesions develop when old lesions are still responding could represent a different type of biological event. We evaluated the impact of progression type and time to first PD (TTP) on survival after progression (SAP) in a randomized phase III trial comparing two doses of imatinib as first line treatment of GIST in 946 patients. Methods: PD was classified into 5 categories: PD in old lesion without new lesions (PD-), and new lesions associated with CR (CR+), PR (PR+), NC (NC+) and finally PD (PD+); MXPD was defined as CR+ or PR+. We investigated the correlations between type of PD, baseline patients’ characteristics, imatinib dose, TTP and SAP with univariate (UVA) and multivariate (MVA) analysis. Results: Currently, 516 patients with PD have been radiologically documented. PD-, CR+, PR+, NC+, and PD+ were observed respectively in 47%, 2%, 10%, 8%, and 33% of the cases. MXPD was more frequent in patients without prior chemotherapy (15% vs 8%), or with a long TTP (0–6 m: 1%; 6–12 m: 8%; 12–24 m: 12%; 24–60 m: 19%; 60+ m: 25%). MXPD was less frequent in KIT exon 9 mutants (7%) and wild types (4%) than in KIT exon 11 mutants (17%) (UVA), but this is entirely explained by their shorter TTP (MVA). No other correlation was found with imatinib dose or baseline factors. SAP was shown to increases with TTP (P<0.0001), and was independently (and adversely) affected by PD of old lesions and development of new lesions: when compared to PD- patients, TTP adjusted SAP hazard ratio for patients with new lesions were 0.28 (CR+), 1.07 (PR+), 1.32 (NC+) and 1.61 (PD+). SAP was longer after MXPD (UVA), but this is explained by their longer TTP (MVA). Conclusions: In GIST patients treated with imatinib, survival after first progression increases with time to progression and decreases with “severity” of progression. Mixed progressions occur later than other types of progression, and therefore lead to a longer further survival. [Table: see text]
Age as prognostic factor in osteosarcoma
Authors: Hagleitner M. , Hoogerbrugge P. , Flucke U. , Schreuder H. , van de Luijtgaarden A. , van der Graaf W. , te Loo M. 
Published: August 2020

10537 Background: Osteosarcoma may occur at all ages but has a distinct age distribution from 10 to 20 years old. Several retrospective studies of osteosarcoma suggest a favourable outcome for children compared to adults. To evaluate whether age is indeed related to outcome, we retrospectively analyzed patients with osteosarcoma under the age of forty. Furthermore, we retrospectively analyzed whether outcome of osteosarcoma in young adult patients is different when treatment took place in a pediatric or an adult oncology department. Methods: Patients with primary osteosarcoma treated in our hospital between 1978 and 2008 were included in this study. To evaluate the role of age, patients were divided in two groups: less than 20 and 20 - 40 years of age. Prognostic factors including histological response after neoadjuvant chemotherapy, were analyzed using Cox regression multivariate analysis. Results: In total, 102 patients with primary osteosarcoma were included. Overall survival (OS) of the whole population was 50.7% with a 5-years event-free survival of 47.1%. Age markedly affected survival with an OS of 61.1% in patients below 20 years of age and 38.6% in the patient group between twenty and forty years (p=0.014). There was no significant difference in prognostic factors, such as presence of metastasis at diagnosis. Pediatric patients under the age of 10 had a superior OS of 71.4% (p =0.02) compared to patients older than 10 years. Overall survival of patients aged 14–20 years was not significant different when treated in a pediatric oncology department as compared to treatment in an adult department (57.9% vs. 47.4%, p= 0.705) . Osteosarcoma patients older than 20 years, showed a worse histologic response to pre-operative chemotherapy and experienced more toxicity. Dose reduction due to toxicity was applied in 20.8% of adults vs. in 1.9% (p=0.002) of the children. Conclusions: Based on the results found in this study, we conclude that age is an independent prognostic factor for outcome of patients with primary osteosarcoma. No significant financial relationships to disclose.
Clinical outcomes of patients with breast cancer in a phase I clinic: The M. D. Anderson Cancer Center experience
Authors: Wheler J. J. , Tsimberidou A. , Moulder S. , Cristofanill M. , Hong D. , Naing A. , Pathak R. , Liu S. , Feng L. , Kurzrock R. 
Published: August 2020

1054 Background: Patients with metastatic breast cancer refractory to standard therapy are eligible for phase I trials. We assessed prognostic factors and clinical outcomes for patients with breast cancer in a phase I clinic focused on targeted agents. Methods: We reviewed the medical records of sequential patients with metastatic breast cancer who presented to our phase I clinic from September 2004 to May 2008. We assessed the relationship between overall survival and patients’ demographic and clinical characteristics using both univariate and multivariate (Cox proportional hazard model) analyses. Results: Ninety-two patients were identified with median age of 53 years (range 28 to 83 years). The median number of prior therapies was 5 (range 1 to 16). The median follow-up of surviving patients is 7.4 months. The median overall survival is 6.7 (95% CI: 5.2, 9.7) months. In univariate analysis, factors predicting shorter survival were elevated Ca-125 (p = 0.001) (Ca27.29 was not significant), albumin < 3.5 g/dL (p = 0.002), worsening ECOG performance status (p = 0.004), absolute neutrophil count < 7.3 x 109/L (p = 0.004), ≥ 10 prior treatment regimens (p = 0.008), ≥ 5 prior chemotherapy-only regimens (p = 0.008), body mass index (BMI) < 25 (p = 0.018), and elevated platelet counts (p = 0.007). In multivariate analysis, independent factors predicting shorter survival were ≥10 prior treatments (vs. <10 prior treatments) (HR = 3.27; 95% CI 1.37, 7.81; p = 0.0077), ECOG performance status 2–3 (vs. 0–1) (HR = 2.92; 95% CI 1.28, 6.66; p = 0.01), and albumin < 3.5 g/dL (vs. > 3.5g/dL) (hazard ratio [HR] = 2.88; 95% CI; 1.41, 5.89; p = 0.004). Of 78 patients treated on a first phase I trial, 14 (18%) demonstrated stable disease (SD), with a median duration of 18 weeks (range 10–25). Of those 19 patients treated on a second phase I trial, 6 (32%) had SD with a median duration of 12 weeks (range 8–17). Two of 4 (50%) patients treated on a third phase I trial had SD with a median duration of 20 weeks (range 16–24). Conclusions: Patients with metastatic breast cancer referred for our phase I studies had a median survival of 6.6 months. In this preliminary analysis, independent factors predicting shorter survival were ≥ 10 prior treatments, worsening ECOG performance status and low albumin levels. No significant financial relationships to disclose.
A retrospective study of parameters influencing survival after surgical resection of lung metastases of bone and soft tissue sarcomas
Authors: Piperno-Neumann S. , Homicsko K. , Mussot S. , Anract P. , Laurence V. , Pierga J. , Mignot L. , Chapelier A. 
Published: August 2020

10541 Background: Due to the high rate of isolated lung metastases of sarcomas, a multidisciplinary approach combining chemotherapy with pulmonary metastasectomy (PM) is helpful to achieve R0 resection and try to increase progression free survival (PFS) and overall survival (OS). The aim of this retrospective study is to describe the clinical and tumor features of 70 consecutive operated patients and to identify the factors influencing survival. Methods: 70 patients undergoing PM at Foch Hospital or CCML between 1995 and 2006 were identified, with follow-up (FU) for a minimum of 3 years after last PM. Statview program has been used to create survival curves, Cox proportional hazard model for multivariate analysis. Results: 64 patients had grade II/III sarcomas of mainly lower limb origin.15 patients had synchronous lung metastases, 35 showed bilateral lesions (mean number of 4, mean size of 12 mm). No patient had extrapulmonary disease at the time of PM. 51% were primary bone sarcomas (24 osteo, 9 Ewing, 3 chondro) and 49 % were soft tissue sarcomas (including 12 synovial, 9 leio). The primary tumor treatment consisted in conservative surgery in 58 patients (83%). 49 patients received neo and/or adjuvant chemotherapy, 22 patients had postoperative radiotherapy. All patients underwent PM: 1 pneumonectomy, 15 lobectomy and 54 wedge resection. 21 patients required bilateral PM. The resection margins were classified R0/R1/R2 in 54/16/0 patients, R0 was confirmed in 44 by CT scan in a month after PM. With a median FU from diagnosis of 7.7 years, the median OS for all patients reached 59 months, and the median survival after metastasectomy (OSPM) 31 months. The 5-year OS and OSPM rates were 77% and 59% respectively. The mean PFS was 20 months. 25 patients underwent subsequent PM for recurrent lung metastases, 30 are still alive. On univariate analysis, primary high grade, DFI>24 months, number of metastases>3 and largest diameter>25 mm were significant negative factors for OS. Multivariate analysis confirmed the importance of high grade, DFI, and size of metastases for OS. R0 was associated with prolonged PFS after PM. Conclusions: Accurate patient selection and technical aspects of PM are related to optimal R0 rate. DFI may be a surrogate marker for tumor biology. No significant financial relationships to disclose.
ACRIN 6665/RTOG 0132 phase II trial of neoadjuvant imatinib mesylate (IM) for primary and recurrent operable malignant GIST: Imaging findings and correlation with genotype and GLUT4 expression
Authors: Van den Abbeele A. D. , Gatsonis C. , de Vries D. J. , Melenevsky Y. , Szot Barnes A. , Yap J. T. , Godwin A. K. , Blevins M. , Eisenberg B. , Siegel B. A. 
Published: August 2020

10552 Background: IM has improved the treatment of GIST patients (pts), but few achieve objective response despite significant clinical benefit. Imaging of tumor metabolism may provide earlier assessment of therapeutic response. In this study, FDG-PET metabolic response (MR) was compared with RECIST, GLUT4 expression, and KIT/PDGFRA mutation status. Methods: FDG-PET was done at baseline, 1–7 days, and 4 or 8 weeks (wk) after IM initiation. Best objective response was defined by RECIST. Immunohistochemical (IHC) tumor GLUT4 expression and mutation analyses were done at baseline and/or surgery. Background-subtracted SUVmax was measured in all lesions and summed; MR based on EORTC criteria was compared to RECIST, GLUT4 expression, and KIT/PDGFRA mutation status. Results: FDG-PET showed high tumor glycolytic activity at baseline (mean SUVmax = 14.2, range: 1.3–53.2), decreasing after 1 wk of IM (5.5, range: 0.5–47.7, p < 0.001, n = 44), and again prior to surgery (3.0, range: 0.5–36.1, p < 0.001, n = 40). FDG-PET response at wk 1 was 3 complete MR (CMR), 33 partial MR (PMR), 6 stable metabolic disease (SMD), and 2 progressive metabolic disease (PMD). Prior to surgery, FDG-PET response was 3 CMR, 33 PMR, 4 SMD, and no PMD. For 39 pts, RECIST best response was 2 PR, 36 SD, and 1 PD. GLUT4 expression decreased in 19 pts with PMR, and 3 with SMD. Among 12 pts with exon 11 mutation, 11 had PMR, 1 SMD; among 5 pts with wild-type genotype, 4 had PMR, and 1 SMD. Conclusions: After IM initiation, MR by FDG-PET was documented earlier (1–7 days), and was of much greater magnitude (36/40) than that documented by RECIST (2/39). IHC data suggest that: (1) GLUT4 plays a role in FDG uptake in GIST; (2) GLUT4 decreases in most pts with PMR; and, (3) the biologic action of IM interacts with glycolysis and GLUT4 expression. No difference in PMR was seen in pts with exon 11 vs. wild type mutations. [Table: see text]
Simultaneous gastrointestinal stromal tumor (GIST) and desmoid fibromatosis (DF)
Authors: Dumont A. G. , Lev D. , Lazar A. , Joensuu H. , Trent J. 
Published: August 2020

10568 Background: Desmoid Fibromatosis (DF) is one of a group of rare fibrous tissue proliferations (2–4 cases per year per million) which tend to be locally aggressive but have no propensity for metastasis. Gastrointestinal Stromal Tumor (GIST) is the most common mesenchymal tumors of the gastrointestinal tract and also rare (15–20 cases per year per million). Anecdotal reports of individuals with both diseases led us to investigate the number of patients at our institute with both types of cancer and their clinical, and histopathologic features. Methods: We identified four cases of GIST associated with DF at the M. D. Anderson Cancer Center between 1995 and 2008 using an IRB-approved protocol. Two more cases were identified from the patient database at the University of Helsinki. Results: Our patients were three men and three women aged from 39 to 66. Two patients were African Americans and 3 were Caucasians. In 5 cases, the GIST was diagnosed prior to the DF while one case had both tumors synchronous at presentation. The primary site of the GIST was gastric in 4 cases and the others were jejunal and mesenteric. Three patients had their DF occur in the surgical incision site mimicking a recurrence of GIST. The 3 others were intra-abdominal DF. There were no cases of DF occurring outside of the GI tract. One GIST patient was metastatic at presentation and one developed metastasis before DF was diagnosed. In 5 cases, imatinib mesylate was administered to the patients with partial response. In all cases KIT expression was observed immunohistochemically for GIST and but not for DF. Additionally, all cases of DF but no cases of GIST were found to have beta-catenin expression by immunohistochemistry. Conclusions: Our findings suggest that concurrent DF may occur in patients with GIST. Additionally, DF may mimic the recurrence of GIST or imatinib resistance. The association of these two sarcomas should be further explored. No significant financial relationships to disclose.