Leiomyosarcoma

Combined detection of ATRX expression and ALT activation status can effectively assist in the differential diagnosis of uLMS from its mimickers. In addition, the presence of ATRX loss and/or ALT activation in STUMP and uLM suggests a malignant potential and seems to warrant close clinical follow-up and individualized diagnosis and treatment decisions.

Imaging documented rapid tumor progression over a short interval, which rendered radical resection impossible and complicated efforts to improve quality of life. However, the patient attempted to receive multiple treatments-interventional therapy, chemotherapy, targeted therapy, and immunotherapy-but the response was poor, survival was under 10 months, and the patient ultimately died.

Then the patient was recommended ALK-TKIs treatment after detecting ALK rearrangement, and achieved complete response (CR) from a second-generation ALK-TKI inhibitor, iruplinalkib, after resistance to the first-generation inhibitor crizotinib. This is the first case of iruplinalkib achieved therapeutic success in uterine IMT, suggesting that a sequential ALK-TKIs with iruplinalkib could be an optimal targeted therapeutic strategy for ALK-rearranged IMTs.

These data provide a comprehensive overview on the prevalence on homozygous and heterozygous 9p21 deletions in cancer and demonstrate that different cancer types markedly differ in their ratio of homozygous/heterozygous 9p21 deletions. The strong concordance between homozygous 9p21 deletions and absent MTAP immunostaining highlights the effectiveness of immunohistochemistry in detecting MTAP deficiency.

These findings highlight recurrent alterations in TP53, RB1, and ATRX and suggest potential roles for IGF2 and AXIN1 in leiomyosrcoma metastatic disease that warrant further investigation.

P2, N=48, Suspended, M.D. Anderson Cancer Center | Recruiting --> Suspended

P2, N=17, Completed, Stanford University | Active, not recruiting --> Completed | Trial primary completion date: May 2026 --> Jan 2026

P3, N=218, Terminated, Polaris Group | Trial completion date: Dec 2027 --> May 2026 | Recruiting --> Terminated | Trial primary completion date: Dec 2027 --> May 2026; Lack of Efficacy, no safety concern.

P2, N=73, Recruiting, Northwestern University | N=29 --> 73 | Trial completion date: Jul 2029 --> Jul 2033

uSMTs exhibit a broad morphologic spectrum in LFS, and multiple molecular alterations may drive tumorigenesis, including MED12, FH, TP53, RB1, ATRX, and a novel ACTG2::BRAF fusion. Although some may be incidental, uSMT in this setting appears enriched for atypical morphology, FH deficiency, and aberrant p53 expression, suggesting an interplay between p53 and FH pathways in tumorigenesis.

These findings highlight the clinical relevance of immune infiltration in retroperitoneal DDLPS and LMS. Moreover, they support the rationale for further exploration of the immune architecture for prognostic biomarkers and development of targeted immunotherapeutic strategies to improve the clinical outcomes of the patients.

P2/3, N=140, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Dec 2026 --> Mar 2026