scholarly journals Molecular profiling of advanced soft-tissue sarcomas: the MULTISARC randomized trial

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Antoine Italiano ◽  
Derek Dinart ◽  
Isabelle Soubeyran ◽  
Carine Bellera ◽  
Hélène Espérou ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Large Scale ◽  
Therapeutic Strategy ◽  
Alternative Hypothesis ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
Tumor Board ◽  
Driver Mutations ◽  
Reference Network ◽  
Clinical Recommendation

Abstract Background Soft-tissue sarcomas (STS) represent a heterogeneous group of rare tumors including more than 70 different histological subtypes. High throughput molecular analysis (next generation sequencing exome [NGS]) is a unique opportunity to identify driver mutations that can change the usual one-size-fits-all treatment paradigm to a patient-driven therapeutic strategy. The primary objective of the MULTISARC trial is to assess whether NGS can be conducted for a large proportion of metastatic STS participants within a reasonable time, and, secondarily to determine whether a NGS-guided therapeutic strategy improves participant’s outcome. Methods This is a randomized, multicentre, phase II/III trial inspired by the design of umbrella and biomarker-driven trials. The setting plans up to 17 investigational centres across France and the recruitment of 960 participants. Participants aged at least 18 years, with unresectable locally advanced and/or metastatic STS confirmed by the French sarcoma pathological reference network, are randomized according to 1:1 allocation ratio between the experimental arm “NGS” and the standard “No NGS”. NGS will be considered feasible if (i) NGS results are available and interpretable, and (ii) a report of exome sequencing including a clinical recommendation from a multidisciplinary tumor board is provided to investigators within 7 weeks from reception of the samples on the biopathological platform. A feasibility rate of more than 70% is expected (null hypothesis: 70% versus alternative hypothesis: 80%). In terms of care, participants randomized in “No NGS” arm and who fail treatment will be able to switch to the NGS arm at the request of the investigator. Discussion The MULTISARC trial is a prospective study designed to provide high-level evidence to support the implementation of NGS in routine clinical practice for advanced STS participants, on a large scale. Trial registration clinicaltrial.gov NCT03784014.

Adriamycin and Cis-Platinum as First-Line Treatment in Unresectable Locally Advanced or Metastatic Adult Soft-Tissue Sarcomas

2004 ◽  
Vol 27 (3) ◽  
pp. 307-311 ◽  
Author(s):  
Haralabos P. Kalofonos ◽  
Dimitrios Bafaloukos ◽  
Theodoros G. Kourelis ◽  
Michalis V. Karamouzis ◽  
Panagiotis Megas ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Rechallenge with trabectedin in patients with locally advanced or metastatic soft tissue sarcoma following drug holiday: The experience of the French Sarcoma Group (FSG).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10062-10062 ◽  
Author(s):  
Esma Saada ◽  
Chahineze Rahal ◽  
Isabelle Ray Coquard ◽  
Antoine Italiano ◽  
Christine Chevreau ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Objective Response ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
Myxoid Liposarcoma ◽  
Median Number ◽  
Drug Holiday ◽  
Who Grade ◽  
Well Differentiated ◽  
Number Of Cycles

10062 Background: Trabectedin (T) is a marine-derived alkaloid used to treat advanced soft tissue sarcomas (STS) after ifosfamide and/or anthracyclins failure. Since then, the FSG evaluated the clinical benefit in re-administrating T after an initial hold, either medically indicated or upon patient’s request. Methods: Following an online request, clinical and histopathological data were collected from six centers of the FSG who declared to have rechallenged patients. Baseline data were collected and analyze will be used. Results: From 1999 to 2011, 49 pts with T drug holiday have been identified (26 male/ 23 female), with a median age of 50 y [23-75]. Most frequent histotypes were: myxoid liposarcoma (18, 36.7%), leiomyosarcomas (13, 26.5 %) and well-differentiated/dedifferentiated liposarcoma (9, 18%). WHO grade were 1 in 14 (29%), 2 in 19 (39%) and 3 in 5 (10%) pts respectively. Patients who had a maximum of 2, 3 or 4 therapeutic sequences (TS) with T (drug-holiday and rechallenge) were 41/49 ,7/49 and 1/49 respectively. Median number of cycles for 1, 2, 3 and 4 TS were 7 [3-21], 6 [2-30], 6 [2-9] and 6. Median total number of cycles was 15 [6-43]. Median duration of drug-holiday for 1, 2 and 3 TS were 11 [3-91], 7 [2-29] and 4 months [1-5]. Grade 3-4 toxicities incidence decreased with the number of TS (occurred in 36%, 29%, 14% and 0% of pts with 1, 2, 3 and 4 TS) as well as mean T dose per cycle (1.3 mg/m², 1.2 mg/m², 1.1 mg/m² and 1.1 mg/m² for TS 1, 2, 3, 4). Efficacy decreased with number of TS (Number of CR/PR/SD/PD were 1 (2%)/15 (31%)/33 (67%)/0 for TS1; 0/4 (8%)/29 (59%)/16 (3%) for TS2; 0/1 (14%)/2 (29%)/4 (57%) for TS3 and 0/0/0/1(100%) for TS4). Median overall survival was 5.0 y [2.7-7.3] since T introduction, and 1.5 y [0.1-4.8], 0.8 y [0.5-1.3] and 0.6 y following 2nd, 3rd and 4th T reintroduction respectively. Objective response after TS2 were seen in 4 cases of grade 1 sarcomas. Conclusions: Due to the lack of cumulative toxicities over time with T, its rechallenging in responding patients to T (no progression under T) have to be considered in advanced STS.

Metronomic continuous oral cyclophosphamide as second and further line in soft-tissue sarcomas (STS) of the adult.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10572-10572
Author(s):  
Alessandro Comandone ◽  
Antonella Boglione ◽  
Elena Giubellino ◽  
Paola Bergnolo ◽  
Giancarlo Gino ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
Progression Free Survival ◽  
Oral Cyclophosphamide ◽  
Second Line ◽  
Good Tolerability ◽  
Free Survival ◽  
Heavily Pretreated ◽  
Third Line

10572 Background: In STS third line treatment is poorly defined. However many patients (pts), after aggressive therapy as first and second line progress in their disease ask to be treated. Oral cyclophosphamide (CPM) was already used in breast cancer, prostate cancer and in elderly pts with STS with favourable results. Aim of our study was to define the feasibility, tolerability and activity of oral CPM as third line and further line chemotherapy Methods: 45 pts (19 M; 26 F) with advanced or metastatic STS heavily pretreated were included. Oral CPM was given daily at total dose of 50 mg/day without interruption excepted for toxicity or progressive disease Results: Median age was 60 (32-81), histological subtypes were: leiomyosarcoma 12, liposarcoma 10, condrosarcoma 5, sinovialsarcoma 4, sarcoma NOS 4, other 10. Primary sites were: extremities 21, retroperitoneum 19, trunk 5. 41 pts were metastatic, 4 locally advanced. 41 pts were pretreated with chemotheraphy (15 were in II line, 17 in III line, 7 in IV line, 2 in V line). Median PS (ECOG) was 2 . Median duration of theraphy was 4 months (1-38). Progression free survival (PFS) ranged from 0 to 42+ months (median 4 months). Treatment was well tolerated, we registred only one episode of leucopenia G2 and one of asthenia G2. No complete responses were seen. Only 3 minimal responses and 18 stable disease were seen. Conclusions: Oral CPM showed a mild activity and good tolerability in advanced soft tissue and metastatic STS. It could be an appropriate solution as second line and further therapy and in unfit or elderly pts.

Complex surgery for locally advanced bone and soft tissue sarcomas of the shoulder girdle

2017 ◽  
Vol 27 (6) ◽  
pp. 777-786 ◽  
Author(s):  
Jan Lesenský ◽  
Andreas F. Mavrogenis ◽  
Vasilios G. Igoumenou ◽  
Zdenek Matejovsky ◽  
Karel Nemec ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
Shoulder Girdle ◽  
Complex Surgery

scholarly journals Histamine combined with melphalan in isolated limb perfusion for the treatment of locally advanced soft tissue sarcomas: preclinical studies in rats

2005 ◽  
Vol 20 (4) ◽  
pp. 275-279 ◽  
Author(s):  
Flavia Brunstein ◽  
Ivan Dunshee de Abranches Oliveira Santos ◽  
Lydia Masako Ferreira ◽  
Sandra T. van Tiel ◽  
Alexander M. M. Eggermont ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
Isolated Limb Perfusion ◽  
Brown Norway ◽  
Response Curves ◽  
Limb Perfusion ◽  
Collateral Effects ◽  
Median Diameter ◽  
The Right

PURPOSE: To evaluate the potential benefit of histamine combined with melphalan in the isolated limb perfusion (ILP) as an alternative to TNF-alfa and melphalan combination, for the treatment of irressectable soft tissue sarcomas of the limbs in Brown Norway (BN) rats. METHODS: 20 BN rats had small fragments of syngeneic BN-175 fibosarcoma inserted on the right hind limb. In 7-10 days the tumor reached a median diameter of 12-15 mm and they were randomly divided in four groups (sham, melphalan, histamine and escalating doses of histamine combined to melphalan) being submitted to experimental ILP for 30 minutes. Tumors were measured daily with a caliper and the volume was calculated. RESULTS: Response curves showed a significant effect of the combination of histamine 200 mg/mL with melphalan, with 66% overall response, including 33% complete responses (p< 0.01). There were no systemic collateral effects and locally only mild temporary edema was observed for some animals treated with histamine. CONCLUSION: Histamine combined with melphalan had a promising effect in the ILP warranting future studies to better explore the mechanism of action as well as its potential use in organ perfusion.

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