Axel Le Cesne

Fast track — ArticlesEfficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study

BACKGROUNDnPrevious studies have suggested that trabectedin (ecteinascidin-743) could have antitumour activity in soft-tissue sarcoma. We aimed to study the usefulness of trabectedin in the treatment of patients with myxoid liposarcomas, a subtype of liposarcoma that is associated with specific chromosomal translocations t(12;16)(q13;p11) or t(12;22)(q13;q12) that result in the formation of DDIT3-FUS or DDIT3-EWSR1 fusion proteins.nnnMETHODSn51 patients with advanced pretreated myxoid liposarcoma who started treatment with trabectedin between April 4, 2001, and Sept 18, 2006 at five institutions in a compassionate-use programme were analysed retrospectively. Centralised radiological and pathological reviews were done for most patients. Trabectedin was given either as a 24-h continuous infusion or as a 3-h infusion, every 21 days, at 1.1-1.5 mg(2). 558 courses of trabectedin were given in total, with a median of ten courses for each patient (range 1-23). The primary endpoints were response rate and progression-free survival, and the secondary endpoint was overall survival.nnnFINDINGSnAccording to Response Evaluation Criteria in Solid Tumors (RECIST), after a median follow-up of 14.0 months (IQR 8.7-20.0), two patients had complete responses (CR) and 24 patients had partial responses (PR); the overall response was 51% (95% CI 36-65). Five patients had early progressive disease. In 17 of the 23 patients who achieved PR or CR as defined by RECIST and who had centralised radiological review, tissue-density changes, consisting of a decrease in tumour density on CT scan or a decrease in contrast enhancement on MRI (or both), preceded tumour shrinkage. Median progression-free survival was 14.0 months (13.1-21.0), and progression-free survival at 6 months was 88% (79-95).nnnINTERPRETATIONnTrabectedin was associated with antitumour activity in this series of patients with myxoid liposarcoma. The noted patterns of tumour response were such that tissue density changes occurred before tumour shrinkage in several patients. In some patients, tissue-density changes only were seen. Long-lasting tumour control was noted in responsive patients. The compassionate-use programme is still ongoing. This analysis has resulted in the initiation of two prospective studies to assess the role of trabectedin in the treatment of patients with myxoid liposarcoma in preoperative and metastatic settings. Furthermore, the selective mechanism of action for trabectedin in this translocation-related sarcoma is being studied.

Ten-Year Progression-Free and Overall Survival in Patients With Unresectable or Metastatic GI Stromal Tumors: Long-Term Analysis of the European Organisation for Research and Treatment of Cancer, Italian Sarcoma Group, and Australasian Gastrointestinal Trials Group Intergroup Phase III Randomized Trial on Imatinib at Two Dose Levels

Purpose To report on the long-term results of a randomized trial comparing a standard dose (400 mg/d) versus a higher dose (800 mg/d) of imatinib in patients with metastatic or locally advanced GI stromal tumors (GISTs). Patients and Methods Eligible patients with advanced CD117-positive GIST from 56 institutions in 13 countries were randomly assigned to receive either imatinib 400 mg or 800 mg daily. Patients on the 400-mg arm were allowed to cross over to 800 mg upon progression. Results Between February 2001 and February 2002, 946 patients were accrued. Median age was 60 years (range, 18 to 91 years). Median follow-up time was 10.9 years. Median progression-free survival times were 1.7 and 2.0 years in the 400- and 800-mg arms, respectively (hazard ratio, 0.91; P = .18), and median overall survival time was 3.9 years in both treatment arms. The estimated 10-year progression-free survival rates were 9.5% and 9.2% for the 400- and 800-mg arms, respectively, and the estimated 10-year overall survival rates were 19.4% and 21.5%, respectively. At multivariable analysis, age (< 60 years), performance status (0 v ≥ 1), size of the largest lesion (smaller), and KIT mutation (exon 11) were significant prognostic factors for the probability of surviving beyond 10 years. Conclusion This trial was carried out on a worldwide intergroup basis, at the beginning of the learning curve of the use of imatinib, in a large population of patients with advanced GIST. With a long follow-up, 6% of patients are long-term progression free and 13% are survivors. Among clinical prognostic factors, only performance status, KIT mutation, and size of largest lesion predicted long-term outcome, likely pointing to a lower burden of disease. Genomic and/or immune profiling could help understand long-term survivorship. Addressing secondary resistance remains a therapeutic challenge.

Primary Extremity Soft Tissue Sarcomas: Does Local Control Impact Survival?

BackgroundThe objective of this study was to evaluate the adequate margin in the local treatment of extremity soft tissue sarcomas (ESTS) and understand the relationship between local control and overall survival (OS).MethodsAll consecutive patients treated for a primary ESTS at a single center from 1993 to 2012 were reviewed.ResultsIn all, 531 patients were included. Twelve (2xa0%) underwent a first-line amputation. The resections were R0/R1/not available in 434 (82xa0%), 92 (17xa0%), and 5 patients (1xa0%). The median tumor size was 8xa0cm, and the tumor grades were 1 (nxa0=xa0132), 2 (nxa0=xa0201), and 3 (nxa0=xa0195). The median size of the minimal margin was 2xa0mm on fixed specimen. Preop or postop chemotherapy was administered to 222 patients, and 414 received radiotherapy. With a median follow-up period of 7 years, the 5-year actuarial local recurrence (LR) rate and OS were 8xa0% (95xa0% CI, 6–11xa0%) and 80xa0% (95xa0% CI, 76–83xa0%). Predictors of worse OS were grade 3, leiomyosarcoma, male gender, and age >60 years, whereas tumor size, margin status, and LR were not. Among patients requiring re-excision (nxa0=xa0252), the presence of residual cells correlated with OS but not LR. After preoperative treatment, a percentage of residual cells ≥10xa0% correlated with OS but not LR. In the multivariate analysis, specific subtypes (epithelioid sarcoma and myxofibrosarcoma) and margin size <1xa0mm correlated with LR, whereas grade and the tissue constituting the surgical margins did not.ConclusionsSpecific subtypes and surgical margin size <1xa0mm were correlated with a higher LR. Neither the margin status nor LR affect OS.

Presentation and outcome of frequent and rare sarcoma histologic subtypes: A study of 10,262 patients with localized visceral/soft tissue sarcoma managed in reference centers: Outcome of 29 Sarcoma Subtypes

The objective of this study was to describe characteristics at diagnosis and outcomes of adults with soft tissue sarcoma.

La progression sous traitement dans les GIST métastatiques : l’anticiper, l’évaluer, la prendre en charge

Le traitement des GIST (tumeurs stromales gastro-intestinales) metastatiques repose sur les inhibiteurs de tyrosine kinase (ITK). Le pronostic de cette maladie reste sombre et, ne disposant que de trois lignes de traitement actuellement disponibles dans le cadre de l’AMM, chacune d’entre elles doit etre optimisee avant d’envisager un changement de traitement.Quatre types de progression sont a distinguer en fonction de la presence ou non de symptomes cliniques et de l’aspect radiologique. Le clinicien doit objectiver toute progression en s’appuyant sur des criteres robustes prenant en compte a la fois la taille et la densite des lesions. Bien qu’encore trop peu utilisee, l’echographie de contraste est actuellement la technique la plus sensible pour evaluer la progression des GIST.L’analyse des cinetiques de progression est essentielle car elle conditionne l’attitude therapeutique. Face a une progression, le clinicien doit egalement ecarter tout probleme d’observance ou d’interaction medicamenteuse. Les dosages medicamenteux s’averent tres utiles dans ce contexte. Enfin, les questions de la modification du schema de traitement et du traitement local doivent etre posees en cas de progression.