Trends in survival for patients with metastatic soft-tissue sarcoma.

Background: The objective of this study was to determine whether the overall survival of patients with metastatic soft tissue sarcoma (STS) has improved over the last 20 years.

Methods: In total, 1024 patients who had synchronous metastatic (SM) STS or metachronous metastatic (MM) STS diagnosed between 1987 and 2006 were included prospectively in the French Sarcoma Group database after central histologic review. Four periods of diagnosis of metastatic disease were defined: P1, from 1987 to 1991 (n = 208); P2, from 1992 to 1996 (n = 287); P3, from 1997 to 2001 (n = 285); and P4, from 2002 to 2006 (n = 244).

Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial.

Background: The effect of imatinib discontinuation on progression-free survival and overall survival in long-lasting responders with advanced gastrointestinal stromal tumours (GIST) is unknown. We assessed treatment interruption in patients with non-progressive disease according to the Response Evaluation Criteria In Solid Tumors criteria after 3 years of imatinib in a randomised trial.

Methods: In this open-label national multicentre phase 3 study in France, patients with GIST free of progression after 3 years of imatinib 400 mg/day were randomly assigned to continue or interrupt imatinib.

Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity.

Sarcomas are heterogeneous and aggressive mesenchymal tumors. Histological grading has so far been the best predictor for metastasis-free survival, but it has several limitations, such as moderate reproducibility and poor prognostic value for some histological types. To improve patient grading, we performed genomic and expression profiling in a training set of 183 sarcomas and established a prognostic gene expression signature, complexity index in sarcomas (CINSARC), composed of 67 genes related to mitosis and chromosome management.

Aggressive surgery in retroperitoneal soft tissue sarcoma carried out at high-volume centers is safe and is associated with improved local control.

Background: We sought to assess morbidity and mortality in primary retroperitoneal soft tissue sarcomas (RSTS) treated by a frontline aggressive surgical approach.

Methods: A total of 249 consecutive patients with primary RSTS were treated by a frontline aggressive surgical approach at two major European institutions. Multivariable models were used for exploring the relationship between postsurgical morbidity and the number of organs resected, with adjustment for clinical variables.

Phase II study of oral masitinib mesilate in imatinib-naïve patients with locally advanced or metastatic gastro-intestinal stromal tumour (GIST).

Background: Masitinib is a tyrosine kinase inhibitor with greater in vitro activity and selectivity for the wild-type c-Kit receptor and its juxtamembrane mutation than imatinib, without inhibiting kinases of known toxicities. This phase II study evaluated masitinib as a first-line treatment of advanced GIST.

Patients And Methods: Imatinib-naïve patients with advanced GIST received oral masitinib at 7.

Prognostic and predictive factors for outcome to first-line ifosfamide-containing chemotherapy for adult patients with advanced soft tissue sarcomas: an exploratory, retrospective analysis on large series from the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG).

Background: Adult patients with advanced soft tissue sarcomas (STS) are generally treated similarly, regardless of great differences between STS subtypes, disease presentation and patients' characteristics. As ifosfamide is frequently applied in first line systemic therapy, we aimed to establish prognostic and predictive factors for outcome to ifosfamide-based therapy.

Methods: A retrospective, exploratory analysis was performed on data from 1337 advanced STS patients who received first-line ifosfamide-containing chemotherapy.

Hyperthermic isolated limb perfusion in locally advanced soft tissue sarcoma and progressive desmoid-type fibromatosis with TNF 1 mg and melphalan (T1-M HILP) is safe and efficient.

Background: In a prior randomized phase II trial comparing hyperthermic isolated limb perfusion (HILP) with four different doses of tumor necrosis factor alpha (TNF-alpha), no dose effect was detected for response, but systemic toxicity was far lower with low-dose TNF-alpha. The objective of the present study was to confirm these data on a larger sample size of locally advanced or recurrent extremity soft tissue sarcomas with low-dose TNF-alpha.

Methods: We assessed a prospective database comprising 100 HILP (38-40 degrees C) with melphalan (10 mg/L) and TNF-alpha (1 mg).

Adjuvant chemotherapy in localized soft tissue sarcomas: still not proven.

Soft tissue sarcoma is a rare and heterogeneous group of tumors in terms of histological subtypes, molecular alterations, clinical presentation, and prognosis. Yet, these tumors are most often treated similarly in the localized phase. The standard treatment of these patients requires multidisciplinary management, in particular, careful diagnostic procedures and surgery by an expert physician, preceded or followed by external radiotherapy.

Gastrointestinal stromal tumors II: medical oncology and tumor response assessment.

The finding of mutations of KIT in gastrointestinal stromal tumors (GISTs) and subsequent development of kinase-directed therapy in metastatic GIST serve as a touchstone for the translation of laboratory research into clinical therapeutics. A variety of novel developments have followed the discovery of clinical activity of kinase-directed therapy against GIST. Radiological assessment of GIST challenges the standard of care for assessing tumor responses, ie, Response Evaluation Criteria in Solid Tumors (RECIST).

Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules.

Purpose: To evaluate the safety and efficacy of trabectedin in a phase II, open-label, multicenter, randomized study in adult patients with unresectable/metastatic liposarcoma or leiomyosarcoma after failure of prior conventional chemotherapy including anthracyclines and ifosfamide.

Patients And Methods: Patients were randomly assigned to one of two trabectedin regimens (via central venous access): 1.5 mg/m(2) 24-hour intravenous infusion once every 3 weeks (q3 weeks 24-hour) versus 0.

Absence of progression as assessed by response evaluation criteria in solid tumors predicts survival in advanced GI stromal tumors treated with imatinib mesylate: the intergroup EORTC-ISG-AGITG phase III trial.

Purpose: From February 2001 to February 2002, 946 patients with advanced GI stromal tumors (GISTs) treated with imatinib were included in a controlled EORTC/ISG/AGITG (European Organisation for Research and Treatment of Cancer/Italian Sarcoma Group/Australasian Gastro-Intestinal Trials Group) trial. This analysis investigates whether the response classification assessed by RECIST (Response Evaluation Criteria in Solid Tumors), predicts for time to progression (TTP) and overall survival (OS).

Patients And Methods: Per protocol, the first three disease assessments were done at 2, 4, and 6 months.

Desmoid-type fibromatosis: a front-line conservative approach to select patients for surgical treatment.

Purpose: Surgery is still the standard treatment for desmoid-type fibromatosis (DF). Recently, the Institut Gustave Roussy (IGR), Villejuif, France, reported a series of patients treated with a front-line conservative approach (no surgery and no radiotherapy). The disease remained stable in more than half of patients.

Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas.

Lymphopenia is frequent in advanced cancers and predicts the toxicity of chemotherapy. Its effect on relapse and survival is uncertain. Its prognostic value for survival was analyzed in three databases of previously reported prospective multicenter studies: (a) FEC chemotherapy in metastatic breast carcinoma; (b) CYVADIC in advanced soft tissue sarcoma (European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group 62791); and (c) prospective, consecutive phase III studies of aggressive diffuse large-cell non-Hodgkin's lymphomas conducted at Centre Léon Bérard between 1987 and 1993.

Is there a role for discontinuing imatinib in patients with advanced gastrointestinal stromal tumour?

Purpose Of Review: Imatinib is the standard first-line treatment of patients with gastrointestinal stromal tumour in advanced phase. In this setting, the optimal duration of treatment is not known, and it is generally considered that treatment should be given until progression or intolerance.

Recent Findings: The BFR14 randomized trial tested the discontinuation of imatinib at 1 and 3 years and demonstrated that treatment discontinuation at these time points is associated with a median progression-free survival of 6 months.

Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043).

PURPOSE Given the importance of angiogenesis in soft tissue sarcoma (STS), pazopanib, an oral angiogenesis inhibitor that targets vascular endothelial growth factor receptor and platelet-derived growth factor receptor, was explored in patients with advanced STS. PATIENTS AND METHODS Patients with intermediate- or high-grade advanced STS who were ineligible for chemotherapy or who had received no more than two prior cytotoxic agents for advanced disease, who had documented progression, who had adequate performance status, and who had good organ function were eligible. Pazopanib 800 mg was given daily.

Natural killer cell IFN-gamma levels predict long-term survival with imatinib mesylate therapy in gastrointestinal stromal tumor-bearing patients.

Clinical outcomes of gastrointestinal stromal tumor (GIST)-bearing patients treated with imatinib mesylate (IM) are variable. Other than the site of mutation within the c-kit gene, prognostic features of GIST remain undefined. IM can exhibit off-target effects such as triggering natural killer (NK) cell activity.

Imatinib in the treatment of solid tumours.

The extraordinary success of imatinib in gastrointestinal stromal tumors (GIST) represents a model for molecularly targeted therapy for other solid tumors. Research is currently going to identify the molecular basis of mechanisms of action and drug resistance. In this article, we review recent advances in the clinical management of patients with GISTs treated with imatinib, but also of patients with dermatofibrosarcoma protuberans, chordoma, aggressive fibromatosis, and some other common solid tumors treated with this drug.

Resection of pulmonary metastases from sarcoma: can some patients benefit from a less invasive approach?

Background: Although video-assisted metastasectomy has been proposed for some solitary metastases, its value has not been investigated in patients with pulmonary metastases from sarcoma for which open resection remains the usual approach.

Methods: In all, 113 consecutive patients underwent curatively intended lung resection for metastases from sarcomas. Of these 113 patients, 31 were selected for a thoracoscopic wedge resection (group TS).

Primary retroperitoneal sarcomas: a multivariate analysis of surgical factors associated with local control.

Purpose: To define the optimal initial management and the best extent of surgery that would optimize margins on primary retroperitoneal sarcomas (RPS).

Patients And Methods: A total of 382 patients with primary RPS were analyzed. Sixty-five patients had a simple resection of the tumor, 120 patients had a complete compartmental resection (systematic resection of noninvolved contiguous organs), 130 patients had a contiguously involved organ resection, 21 patients had a systematic re-excision, 38 patients had an incomplete gross resection, and eight patients had a biopsy alone.

Follow-up of hepatic and peritoneal metastases of gastrointestinal tumors (GIST) under Imatinib therapy requires different criteria of radiological evaluation (size is not everything!!!).

Purpose: To define computed tomography (CT) criteria for evaluating the response of patients with gastrointestinal stromal tumors (GIST) who are receiving Imatinib (tyrosine-kinase inhibitor therapy).

Materials And Methods: This prospective CT study evaluated 107 consecutive patients with advanced metastatic GIST treated with Imatinib.

Results: Seventy patients had total or partial cystic-like transformation of hepatic and/or peritoneal metastases.

Population pharmacokinetics and pharmacogenetics of imatinib in children and adults.

Purpose: The aim of this study was to explore the effect of several demographic, biological, and pharmacogenetic covariates on the disposition of imatinib and its main metabolite (CGP74588) in both adults and children.

Experimental Design: Thirty-three children with solid malignancies included in a phase II exploratory study and 34 adults with gastrointestinal stromal tumors received 340 mg/m(2) and 400 mg imatinib, respectively. Plasma imatinib and CGP74588 concentrations observed on day 1 and at steady-state were analyzed by a population pharmacokinetic method (NONMEM) to evaluate the effect of age, body weight, age, sex, albuminemia, plasma alpha1-acid glycoprotein (AGP), and eight polymorphisms corresponding to ABCB1, ABCG2, CYP3A4, CYP3A5, and AGP (pharmacogenetic data available for 46 of 67 patients).

Phase I combination study of trabectedin and doxorubicin in patients with soft-tissue sarcoma.

Purpose: To determine the dose of trabectedin plus doxorubicin with granulocyte colony-stimulating factor support associated with manageable neutropenia and acceptable dose-limiting toxicities (DLT) in patients with recurrent or persistent soft-tissue sarcoma.

Methods: In this phase I, open-label, multicenter trial, patients previously treated with 0-1 prior chemotherapy regimens excluding doxorubicin, an Eastern Cooperative Oncology Group performance status 0-1, and adequate organ function received a 10- to 15-min i.v.