Showing papers by "Philippe Terrier published in 2020"
TL;DR: This nationwide registry of Sarcoma patients with histology reviewed by sarcoma experts shows that the incidence of sarcomas and TIM is higher than reported, and that tumors with an incidence<106/year have a much lower access to clinical trials.
Abstract: Background Since 2010, NETSARC and RREPS collected and reviewed prospectively all cases of sarcomas and tumors of intermediate malignancy (TIM) nationwide Methods The nationwide incidence of sarcoma or TIM (2013-2016), confirmed by expert pathologists using WHO classification are presented Yearly variations and correlation with published clinical trials was analyzed Results 139 histological subtypes are reported among the 25172 patients with sarcomas (n=18710, 64%) or TIM (n=6460, 36%), respectively n=5838, n=6153, n=6654, and n=6527 yearly from 2013 to 2016 Over these 4 years, the yearly incidence of sarcomas and TIM was therefore 797, 249 and 951/106/year, above that previously reported GIST, liposarcoma, leiomyosarcomas, undifferentiated sarcomas represented 13%, 13%, 11% and 11% of tumors Only GIST, as a single entity had a yearly incidence above 10/million/year There were respectively 30, 63 and 66 different histological subtypes of sarcomas or TIM with an incidence ranging from 10 to 1/106, 1-01/106, or Conclusions This nationwide registry of sarcoma patients with histology reviewed by sarcoma experts shows that the incidence of sarcoma and TIM is higher than reported, and that tumors with an incidence
71 citations
TL;DR: An extensive review of the literature on ISPA is performed with details on the clinical presentation, diagnosis and management strategies, to make practicing oncologists aware of this rare entity with clear idea on the initial management.
Abstract: Only a few hundred cases of intimal sarcomas of pulmonary artery (ISPA) were reported on the literature. Diagnosis of this rare entity is a challenging dilemma with the need for a high expertise in the radiological and pathological identification of ISPA. Treatment strategies rely initially on an early aggressive surgery aiming for complete surgical resection with clear margins while no clear recommendations guiding the choice for additional drug therapy or radiotherapy exist. In this article, we perform an extensive review of the literature on ISPA with details on the clinical presentation, diagnosis and management strategies. An additional goal of this paper is to make practicing oncologists aware of this rare entity with clear idea on the initial management.
21 citations
TL;DR: In this large retrospective cohort of patients with ECM, location of primary tumor and solitary lung metastases seem to be associated with better survival, and Chemotherapy did not impact survival in unselected patients.
Abstract: Background: Extraskeletal myxoid chondrosarcoma (EMC) is a rare subtype of STS, which usually arises in extremities. It carries reciprocal translocations involving the NR4A3 gene. It displays an indolent behavior, but studies with long follow-up showed a high proportion of local and distant recurrences. For patients with progressing metastatic disease anthracycline-based chemotherapy is the standard front-line regimen, though has limited activity. There is some evidence on possible activity of antiangiogenetics. Methods: This is a retrospective study conducted at Istituto Oncologico Veneto and at Institut Gustave Roussy. All patients with a confirmed diagnosis of EMC from January 1980 to December 2018 were extracted from a prospectively maintained database. Results: 59 patients were identified, 37 male (62.7%) and 22 female (37.3%) with a M/F ratio of 1.7/1. We performed molecular analysis in 23 cases, all carried a EWSR1-NR4A3. Out of 49 patients treated with curative intent, 28.6% developed local recurrence and 40.8% patients developed metastases. In patients who had been radically resected (R0) local recurrence occurred in 7.6% of cases and metastases occurred in 15.4% of cases; in patients treated with R1 surgery, rates of relapse were higher. Twenty patients received chemotherapy for metastatic disease; best response was partial response with clinical benefit in 50% of patients. Fourteen patients received a second line of chemotherapy, with 46.1% disease control rate. A drug holiday was proposed to 8 patients with a mean duration of 22.8 months. Median overall survival was 180 months for the study population and 76 months for metastatic patients. No significant prognostic role was found for all studied variables, yet a trend of better survival for complete surgery, location in extremities of primary tumor and solitary lung metastases was observed. Chemotherapy for metastatic disease was negatively associated with survival. Conclusion: In this large retrospective cohort of patients with ECM, location of primary tumor and solitary lung metastases seem to be associated with better survival. Chemotherapy did not impact survival in unselected patients. Further research is necessary in order to identify more active regimens and to provide clinical and molecular factors to select patients that could delay systemic treatment for metastatic disease.
15 citations
TL;DR: The identification of the exon 3 CTNNB1 mutation in breast spindle cell lesions is a highly specific tool for the diagnosis of DFB, in addition to extensive immunohistochemical analysis, and underlines the importance of APC in DFB tumorigenesis.
Abstract: Desmoid fibromatosis (DF) is a rare, locally aggressive, nonmetastasizing fibroblastic/myofibroblastic tumor with a tendency to recur and an unpredictable clinical course A "wait-and-see" policy is the new standard of care DF are characterized by activating alterations of the wnt/β-catenin pathway: CTNNB1 or adenomatous polyposis coli gene (APC) mutations (these mutations being mutually exclusive) Desmoid-type fibromatosis of the breast (DFB) is rare with an incidence of 02% of breast tumors The diagnosis of DFB is difficult, as it must be distinguished from metaplastic carcinoma and other spindle cell lesions Sequencing of 128 DFB identified a lower rate of CTNNB1 mutations using Sanger (656%) or Sanger+next-generation sequencing (777%) and a higher rate of APC mutations (118%) than in all-site DF By excluding patients with familial adenomatous polyposis (n=2), the rate of APC mutations in DFB was high (107%) The distribution of CTNNB1 mutations in DFB was different from all-site DF, with a higher rate of T41A (689%), a lower rate of S45F (57%), and a similar rate of S45T (126%) By combining the 2 molecular techniques in a 2-step manner (Sanger, then next-generation sequencing), we increased the detection rate of CTNNB1 mutations and lowered the rate of wild-type tumors from 344% to 98%, therefore improving the diagnosis of DFB The identification of the exon 3 CTNNB1 mutation in breast spindle cell lesions is a highly specific tool for the diagnosis of DFB, in addition to extensive immunohistochemical analysis Our study also underlines the importance of APC in DFB tumorigenesis These findings have significant implications for patient care and management
10 citations
TL;DR: Leiomyosarcomas (LMS) are currently treated as a single entity but are now identified as a transcriptionally, genomically and clinically homogeneous subgroup of LMS, whose oncogenesis is driven by the acquisition of high differentiation through MYOCD over-expression, which confers them sensitivity toMYOCD/SRF inhibitors, which could thus become a potential therapeutic target.
Abstract: Leiomyosarcoma is a very aggressive tumor with poor prognosis since half of the patients will develop metastasis. Today, neither chemotherapy nor targeted or immune therapies have demonstrated efficacy. These tumors show highly rearranged genomes and appear to form a heterogenous group. Understanding their complex oncogenesis either as a single disease or by subtypes has already been challenged but the underlying mechanisms driving leiomyosarcoma development which could lead to a patient care improvement remain to be deciphered. We identified a group of tightly clustered leiomyosarcomas due to their gene expression homogeneity, named "hLMS". We derived a transcriptional signature able to consistently stratify patients from two independent cohorts. In all cohorts, hLMS were preferentially carried by women, located in the internal trunk, highly differentiated, and similarly altered at the genomic level. Through the multi-omics integrative bioinformatic analysis, we show that hLMS originate from vascular smooth muscle cells presenting both contractile and synthetic characteristics, while the other group could derive from fibroblasts. We identified the MYOCD overexpression as a hLMS-specific driver candidate and functionally showed that the MYOCD/SRF axis is only essential for hLMS survival. Identification of hLMS could become standard clinical practice, leading to the development of specific effective treatments with MYOCD/SRF inhibitors.
4 citations