Showing papers by "Philippe Terrier published in 2013"
TL;DR: It is found that CD3(+) TIL were highly activated in GIST and were especially enriched in areas of the tumor that conserve class I MHC expression despite imatinib mesylate treatment, which encourages the prospective validation of immune biomarkers for optimal risk stratification of patients with GIST.
Abstract: Cancer immunosurveillance relies on effector/memory tumor-infiltrating CD8 + T cells with a T-helper cell 1 (T H 1) profile. Evidence for a natural killer (NK) cell-based control of human malignancies is still largely missing. The KIT tyrosine kinase inhibitor imatinib mesylate markedly prolongs the survival of patients with gastrointestinal stromal tumors (GIST) by direct effects on tumor cells as well as by indirect immunostimulatory effects on T and NK cells. Here, we investigated the prognostic value of tumor-infiltrating lymphocytes (TIL) expressing CD3, Foxp3, or NKp46 (NCR1) in a cohort of patients with localized GIST. We found that CD3 + TIL were highly activated in GIST and were especially enriched in areas of the tumor that conserve class I MHC expression despite imatinib mesylate treatment. High densities of CD3 + TIL predicted progression-free survival (PFS) in multivariate analyses. Moreover, GIST were infiltrated by a homogeneous subset of cytokine-secreting CD56 bright (NCAM1) NK cells that accumulated in tumor foci after imatinib mesylate treatment. The density of the NK infiltrate independently predicted PFS and added prognostic information to the Miettinen score, as well as to the KIT mutational status. NK and T lymphocytes preferentially distributed to distinct areas of tumor sections and probably contributed independently to GIST immunosurveillance. These findings encourage the prospective validation of immune biomarkers for optimal risk stratification of patients with GIST. Cancer Res; 73(12); 3499–510. ©2013 AACR .
268 citations
TL;DR: Comparing genomic profiles of adult versus pediatric SS, it is shown that metastasis is associated with genome complexity in both situations and that the adult genome is more frequently rearranged, Accordingly, pediatric patients with an even genomic profile do not develop metastasis.
Abstract: Purpose Synovial sarcoma (SS) occurs in both children and adults, although metastatic events are much more common in adults. Whereas the importance of the t(X;18) translocation in SS oncogenesis is well established, the genetic basis of SS metastasis is still poorly understood. We recently reported expression (CINSARC; Complexity Index in Sarcoma) and Genomic Index prognostic signatures related to chromosome integrity in sarcomas and GI stromal tumors. Here we investigate whether these signatures can also predict outcomes in SS. Patients and Methods One hundred patients who had primary untreated SS tumors were selected for expression and genomic profiling in a training/validation approach. Results CINSARC and Genomic Index have strong independent and validated prognostic values (P < .001). By comparing expression profiles of tumors with or without metastasis, 14 genes that are common to the CINSARC signature were identified, and the two top-ranked genes, KIF14 and CDCA2, were validated as prognostic marke...
133 citations
TL;DR: Soft-tissue leiomyosarcomas represent a heterogeneous group of tumors with at least two categories, retroperitoneal and extremities leiomers, having specific clinical outcome and molecular features, and future clinical trials should consider this heterogeneity for a better stratification of patients.
Abstract: Purpose: Data about the prognostic factors of soft-tissue leiomyosarcomas and their correlation with molecular profile are limited. Experimental Design: From 1990 to 2010, 586 adult patients with a primary soft-tissue leiomyosarcoma were included in the French Sarcoma Group (GSF) database after surgery of the primary tumor. Multivariate analyses were conducted by Cox regression model in a backward stepwise procedure. Genetic profiling was conducted for 73 cases. Results: Median age was 59 years (range, 21–98 years). The median follow-up of patients alive was 46 months. The 5-year metastasis-free survival (MFS) rate was 51% (95% location and grade > I were independent adverse prognostic factors for MFS). The 5-year overall survival (OS) rate was 63% [95% confidence interval (CI), 59–67]. On multivariate analysis, age ≥ 60 years old, tumor size > 5 cm, deep location, and grade > I were independent adverse prognostic factors for OS. Molecular profiling identified specific clusters with activation of different biologic pathways: retroperitoneal leiomyosarcomas are characterized by overexpression of genes involved in muscle differentiation and nonretroperitoneal leiomyosarcomas characterized by overexpression of genes mainly involved in extracellular matrix, wounding, and adhesion pathways. The CINSARC signature but not comparative genomic hybridization (CGH) profiling was predictive of outcome. Conclusion: Soft-tissue leiomyosarcomas represent a heterogeneous group of tumors with at least two categories, retroperitoneal and extremities leiomyosarcomas, having specific clinical outcome and molecular features. Future clinical trials should consider this heterogeneity for a better stratification of patients. Clin Cancer Res; 19(5); 1190–6. ©2013 AACR .
50 citations
TL;DR: In leiomyosarcomas compared with other specific tumor types such as undifferentiated pleomorphic sarcoma and myxofibrosarcoma, the accuracy for transgelin varied from 80 to 87% whereas it was lower for all other markers (between 51 and 80%).
37 citations
TL;DR: Pre-existing lymphoedema, tumour size and age >70 are probably the major prognostic factors in patients with localised angiosarcomas and the achievement of R0 margins is probably of major importance for improving the patient outcome.
29 citations
TL;DR: Conservative and planned en bloc surgery achieves good local control with low morbidity in aggressive angiomyxoma and Radiotherapy could enhance local control in advanced disease.
Abstract: Background The purpose of this study was to assess the value of conservative surgery in aggressive angiomyxoma (AA) in our institutional series. Method This was a retrospective review of patients with AA treated at our institution between 1999 and 2010. Results Fourteen consecutive patients were analyzed: 8 primary tumors and 6 recurrences. Female/male ratio was 13:1; median female age was 36 years. Median size of primary lesions was 12 cm (range, 7–17 cm). Median size of recurrences was 20.5 cm (range, 3–44 cm). Twelve patients were operated on. Two asymptomatic patients whose surgery would have been mutilating were placed under wait and see. Four patients had concomitant visceral resections because of massive infiltration. No tumor rupture was recorded on pathological examination. Margins were R0 (n = 2), R1 (n = 10), and R2 (n = 0). Seven patients (50%) received radiotherapy. Median postoperative follow-up was 69 months, and no patient was lost at follow-up. All patients operated on (primaries and recurrences) had no evidence of recurrence. Conclusion Conservative and planned en bloc surgery achieves good local control with low morbidity. Radiotherapy could enhance local control in advanced disease. Wait and see is an exploratory option for asymptomatic, stable, and nonprogressing AA in which surgery would be mutilating.
21 citations
TL;DR: The cumulative probabilities of local (LR) and of metastatic (MR) relapse with death as a competing event and the outcomes of interest were 3369 adult patients with localized STS from January 1990 to December 2009.
Abstract: 10575 Background: Competing risk is the risk of an event that interferes with the probability of experiencing the disease-specific outcome of interest. Indeed, the occurrence of a competing risk (f...
4 citations
TL;DR: In this paper, the authors used a micro-costing method to assess the cost of molecular biological techniques in the diagnosis of five types of sarcoma, including fluorescence in situ hybridization (FISH), reverse transcription polymerase chain reaction (RT-PCR), mean reverse transcription and CGH-array.
Abstract: Sarcomas represent a complex and heterogeneous group of rare malignant tumors and their correct diagnosis is often difficult. Recent molecular biological techniques have been of great diagnostic use and there is a need to assess the cost of these procedures in routine clinical practice. Using prospective and observational data from eight molecular biology laboratories in France, we used "microcosting" method to assess the cost of molecular biological techniques in the diagnosis of five types of sarcoma. The mean cost of fluorescence in situ hybridization (FISH) was 318 € (273-393) per sample; mean reverse transcription polymerase chain reaction (RT-PCR) cost ranged from 300 € (229-481) per formalin-fixed, paraffin-embedded specimen to 258 € (213-339) per frozen specimen; mean quantitative polymerase chain reaction (Q-PCR) cost was 184 € (112-229) and mean CGH-array cost was 332 € (329-335). The cost of these recently implemented techniques varied according to the type of sarcoma; the method of tissue collection and local organizational factors including the level of local expertise and investment. The cost of molecular diagnostic techniques needs to be balanced against their respective performance.
2 citations
TL;DR: A large number of patients with localized STS, treated with neoadjuvant anthracycline/ifosfamide-based chemotherapy and assessable for response to chemotherapy were included prospectively in the French Sarcoma Group (GSF) database from 1985 to 2011.
Abstract: 10578 Background: The role of neoadjuvant and adjuvant chemotherapy in localized synovial sarcoma (SS) is still controversial. Histologic response to neoadjuvant chemotherapy is an independent prognostic variable in bone sarcomas. Data regarding the prognostic value of response to noeadjuvant chemotherapy in STS are limited. Methods: 68 patients with localized STS, treated with neoadjuvant anthracycline/ifosfamide-based chemotherapy and assessable for response to chemotherapy were included prospectively in the French Sarcoma Group (GSF) database from 1985 to 2011. All the cases were reviewed by the pathology subcommittee of the GSF. Radiological response to chemotherapy was assessed according to RECIST criteria. Good response was defined as partial response or stable disease according to RECIST and ≤10% recognizable tumor cells in the surgical specimen. Poor response was defined as stable or progressive disease according to RECIST and ≥ 50% recognizable tumors cells in the surgical specimen. All the other...
1 citations