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Background: After a huge efficacy of imatinib in treating patients with gastrointestinal stromal tumors (GISTs) was proven, a maximum effort was made to make a differential diagnosis between GISTs and gastrointestinal leiomyosarcomas (GI‐LMS), showing the latter to be an extremely rare tumor entity. Limited data on GI‐LMS biology, clinical behavior and drug‐sensibility are available, and the clinical decision‐making in this subgroup of patients is usually challenging. Methods: We conducted a multicenter, retrospective observational study on patients with diagnosed GI‐LMS from 2004 to 2020 within six high‐volume referral centers in Italy. Results: Thirty‐three patients had diagnosis of KIT‐negative GI‐LMS confirmed by sarcoma‐expert pathologist. The most common site of origin was the intestine. Twenty‐two patients had localized disease and underwent surgery: with a median follow‐up of 72 months, median disease‐free survival was 42 months. Overall survival (OS)‐rate at 5 years was 73% and median OS was 193 months. Five out of 10 patients with local relapse received a salvage surgery, and 2/5 remained with no evidence of disease. Thirteen patients received neoadjuvant (6) or adjuvant (7) chemotherapy, and 2/13 patients remained free from relapse. The median OS for patients with metastatic LMS was 16.4 months. Conclusion: GI‐LMS is very rare and extremely aggressive subgroup of sarcomas with a high tendency to systemic spread. Localized GI‐LMS at diagnosis may be cured if treated with adequate surgery with or without (neo) adjuvant chemotherapy, while de‐novo metastatic disease appeared to have a poor prognosis. Clinical effort to understand GI‐LMS biology and clinical behavior and to develop active treatment strategy, especially for metastatic‐disease, is warranted. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate changes in volume and MRI T2‐weighted intensity in desmoid‐type fibromatosis (DF) receiving methotrexate plus vinca‐alkaloids (MTX‐VA) at Istituto Nazionale dei Tumori, Milan. Methods: All cases of sporadic DF treated with MTX‐VA from 1999 to 2019 were reviewed. MRIs at baseline, 6 and 12 months of chemotherapy and at treatment withdrawal were retrospectively reviewed, contouring the tumor lesion and measuring diameters, volume, and mean T2‐signal intensity (normalized to muscle) changes. These parameters were also evaluated according to clinical variables. Results: Thirty‐two DF patients were identified. Best RECIST response was: 25% partial response, 69% stable disease, 6% progression. A ≥65% tumor volume reduction was observed in 38%, <65% reduction in 53%, an increase in 9%. 22% had RECIST stable disease with a ≥65% tumor volume reduction. T2‐signal intensity decreased by ≥50% in 47%, <50% in 41% and increased in 12%. In patients with symptomatic improvement while on therapy and in patients maintaining symptomatic improvement during follow‐up, median T2‐signal intensity showed a reduction along the time points (3.0, 1.9, 1.2, 1.1; 2.9, 2.0, 1.2, 1.2, respectively); in patients without symptomatic improvement and in those clinically progressing during follow‐up, a reduction was not observed. High T2‐signal intensity at baseline was observed in patients showing RECIST progression during follow‐up. Conclusions: In this series, RECIST detected a lower proportion of responses as compared to volumetric and T2‐signal changes. T2‐signal reduction seemed to better reflect symptomatic improvement. High T2‐signal intensity at baseline was related to a higher proportion of further progression. [ABSTRACT FROM AUTHOR]

Background: Although elderly patients (≥70 years) represent 30% of new diagnoses of soft tissue sarcoma (STS), they are underrepresented in clinical trials and are often unfit to receive standard anthracycline-based chemotherapy. Trabectedin is registered as a second-line treatment for advanced STS and is characterized by a favorable safety profile.Methods: The aim of this single-arm, phase 2 study was to investigate trabectedin (scheduled dose, 1.3-1.5 mg/m2 ) as a first-line treatment in elderly patients with advanced stage STS who are inoperable and are unfit to receive standard anthracycline-based chemotherapy. The coprimary endpoints were progression-free survival at 3 months (PFS3) and the rate of clinically limiting toxicities (CLTs). We also conducted an ancillary study on pharmacokinetics.Results: Twenty-four patients (12 men and 12 women) with a median age of 79 years (interquartile range [IQR], 74-83 years) were enrolled. The histological subtype was leiomyosarcoma in 46%, liposarcoma in 33%, and other histotypes in 21%. The median number of trabectedin courses was 4 (IQR, 3-6), with 7 patients (29%) receiving ≥6 cycles. Eight patients (33%) required dose reductions. The most frequent grade 3/4 adverse events were neutropenia in 9 patients (38%), fatigue in 5 patients (21%), and aminotransferase elevation in 5 patients (21%). PFS3, median PFS, and overall survival were 71% (80% CI, 57%-81%), 4 months, and 12 months, respectively. Ten patients (42% [80% CI, 28%-57%]) experienced CLTs. Trabectedin Cmax , half-life, clearance, and distribution volume were 1.28 ng/mL (standard deviation [SD], 0.58 ng/mL), 26.70 hours (SD, 9.09 hours), 39.98 L/h/m2 (SD, 14.08 L/h/m2 ), and 1460 L/m2 (SD, 561 L/m2 ), respectively.Conclusion: Trabectedin can be administered safely to elderly patients with STS who are unfit to receive anthracyclines. Pharmacokinetics in the elderly population was superimposable to historical data. [ABSTRACT FROM AUTHOR]