Sandro Pasquali

Description:In the original online version of this article there is an error in the funding information. FRRB-584-797, 60 should be Fondazione Regionale per la Ricerca Biomedica (Regione Lombardia), project ID 1751036.

Description:Background: Malignant peripheral nerve sheath tumor (MPNST) is a rare and aggressive sarcoma often associated with neurofibromatosis type 1, whose clinical management remains complex and challenging. Few publications exist on pediatric MPNST, and limited data are available on the best treatment approach, in particular regarding local therapy. Methods: This retrospective analysis concerned 45 patients less than 18 years old with MPNST, treated at a referral center for pediatric sarcomas from 1983 to 2023. Patients were treated using a multimodal approach, based on the protocols adopted at the time of their diagnosis. Results: For the series as a whole, the median event-free survival (EFS) and overall survival (OS) were 16 and 26 months, respectively, and 5-year EFS and OS were 28.8% and 40.1%. The first event was local failure in 18 cases, local failure plus metastases in nine cases, and metastases-only in four cases. At univariable analysis, survival was better for males and patients younger than 15 years, and was influenced by tumor invasiveness and tumor size. With regard to treatment modalities, survival rates were significantly better for patients who responded to chemotherapy; EFS, local relapse-free survival (LRFS), and OS were better for patients who had a surgical resection; EFS and LRFS were better for patients who received radiotherapy combined with surgery, while OS was better for patients who had R0 resection. Conclusions: Our study confirmed the unsatisfactory outcome of MPNST pediatric patients. Our series would suggest that a combined local treatment that included both surgical resection and radiotherapy could improve local control.

Description:Sarcomas are a large family of rare and heterogeneous mesenchymal tumors, which respond poorly to available systemic treatments. Translation of preclinical findings into clinical applications has been slow, limiting improvements in patients' outcomes and ultimately highlighting the need for a better understanding of sarcoma biology to develop more effective, subtype-specific therapies. To this end, reliable preclinical models are crucial, but the development of 3D in vitro sarcoma models has been lagging behind that of epithelial cancers. This is primarily due to the rarity and heterogeneity of sarcomas, and lack of widespread knowledge regarding the optimal growth conditions of these in vitro models. In this review, we provide an overview of currently available sarcoma tumoroid models, together with guidelines and suggestions for model development and characterization, on behalf of the FORTRESS (Forum For Translational Research in Sarcomas) international research working group on 3D sarcoma models.

Description:Objective: The Complexity Index in SARComas (CINSARC) predicts the metastatic risk in patients with soft tissue sarcoma. The aims of this study were to provide the first independent validation of CINSARC in patients with retroperitoneal sarcoma (RPS) and to evaluate whether CINSARC could enhance the performance of Sarculator. Methods: A retrospective cohort included patients with primary localized RPS resected with curative intent (2011-2015) at a single institution. The STRASS cohort comprised patients from the surgery-only arm of the EORTC-STBSG-62092 (STRASS) trial who had undergone CINSARC categorization. Patients were classified as CINSARC low-risk (C1) vs high-risk (C2). Primary study endpoints were overall survival (OS) and disease-free survival (DFS). Sarculator performance was assessed in terms of discrimination (Harrell's C-index) and calibration (calibration plots, Brier score) before and after adding CINSARC. Results: The study cohorts included 104 and 69 patients, respectively, with similar OS. In a pooled cohort, at multivariable analysis for OS considering Sarculator and CINSARC, only Sarculator was significantly associated with OS (HR 1.93, 95%CI 1.35, 2.74, p<0.001). In multivariable analysis for DFS, both Sarculator (HR 1.51, 95%CI 1.09, 2.09, p=0.013) and CINSARC (HR 2.01, 95%CI 1.26, 3.23, p=0.004) were significantly associated with DFS. However, the addition of CINSARC did not improve Sarculator's discrimination or calibration for either OS or DFS. Conclusions: This study validates CINSARC as a prognostic predictor for OS and DFS in patients with primary RPS. CINSARC did not improve the performance of Sarculator, suggesting that its addition to the Sarculator may not provide added clinical benefit.

Description:Soft tissue sarcomas (STS) represent a large group of rare and ultra-rare tumors distinguished by unique morphological, molecular and clinical features. Patients with such rare cancers are generally underrepresented in clinical trials which has limited the introduction of new treatment options and subsequent improvement of patient outcomes. Preclinical models of STS that recapitulate the human disease can aid progress in identifying new effective treatments. However, due to the rarity of these tumors there are limited STS models available. Here we review the existing preclinical models of STS, including patient-derived cell lines and organoids, patient-derived xenografts and genetically engineered mouse models. We discuss the advantages and disadvantages of the different models and describe to what extent they have aided clinical translation. Finally, we consider what can be done in the future to enhance their predictivity in the preclinical setting.