Background: Liposarcoma (LPS) is one of the most frequent histotypes of soft tissue sarcoma (STS). Eribulin is a cytotoxic agent that has improved overall survival in patients with advanced LPS. Additionally, preclinical and clinical evidence suggests its influence on vascularization and cellular differentiation. Based on these data, we developed this study to investigate non-mitotic effects of eribulin in patients with advanced LPS. Methods: In this prospective monocentric observational study, we included patients with advanced LPS eligible to receive eribulin. An assessment with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and a biopsy were planned before treatment and after four cycles of eribulin. DCE-MRI scans were elaborated to obtain perfusion and permeability maps. Results: From September 2019 to January 2024, 11 patients were enrolled. Among them, 8/11 (73%) had successful pre- and post-treatment assessment. At the time of the analysis, 8/11 (73%) patients had disease progression and 4 (36%) had died, median progression-free survival (mPFS) was 3.3 months, and median overall survival (mOS) was 8.7 months. Among the evaluable patients, DCE-MRI perfusion decreased after eribulin treatment in patients with disease control (partial response or stable disease), while perfusion values increased in patients with progressive disease (PD). No significant change in permeability was found. Post-treatment histological changes were seen nearly in all patients, with decreased cellularity the most common change (50%), followed by vascularization modifications (20%). Conclusions: Eribulin appears to exhibit non-mitotic activity involving both vascularization and cell differentiation in LPS patients. Further studies are needed to better define these effects.

Introduction: Regorafenib is a tyrosine kinase inhibitor (TKI) approved in metastatic gastrointestinal stromal tumor (GIST), colorectal cancer, and hepatocarcinoma. Anyway, the toxicity profile of Regorafenib standard schedule is associated with poor compliance and a high rate of discontinuation. For this reason, there is a growing need for a Regorafenib personalized schedule emerging from the scientific community.Objective: The aim of this case series was to describe the experience of our sarcoma referral center with the continuous administration of Regorafenib as an alternative regimen to treat metastatic GIST patients.Methods: We retrospectively collected clinical, pathological, and radiological data of patients with metastatic GIST treated with daily personalized Regorafenib at a single tertiary referral center from May 2021 to December 2022.Results: We identified three patients fulfilling the inclusion criteria. The average follow-up since the start of Regorafenib was 19.1 months (12–25 months). All three patients had started a standard third-line Regorafenib schedule according to guidelines. The reasons for switching to a continuous schedule were as follows: exacerbation of symptoms during week-off treatment in the first patient, a serious adverse event (AE) in the second patient, and a combination of both conditions in the third. After switching, none of the patients reported severe AEs, and they improved control of tumor-related symptoms. Two of the patients experienced disease progression after 16 months (9 months of which is continuous schedule) and 12 months (8.1 months of which is continuous schedule) of Regorafenib, respectively; the third patient is still receiving continuous Regorafenib at the time of writing, with a progression-free survival of 25 months (14 months after the modified schedule start).Conclusion: With a similar efficacy and lower toxicities, a daily, personalized Regorafenib schedule seems to be a promising alternative to the standard regimen for metastatic GIST patients, including the frail ones. Further prospective analyses are needed to confirm the safety and efficacy of such regimen.