Leiomyosarcoma

MutPTEN vs wtPTEN was associated with worse OS in advanced STS. If confirmed, our findings could be helpful for prognostic stratification in clinical practice and for further understanding the molecular mechanisms of STS.

P2, N=40, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P=N/A, N=19, Completed, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

P2, N=29, Recruiting, Northwestern University | Not yet recruiting --> Recruiting

The patient described herein had a TFE-positive uterine malignant PEComa with lung metastasis and responded well to the mTOR inhibitor, everolimus. Close follow-up in the last 3 years showed remission without recurrence or progression.

We report a rare case presentation of a 45-year-old man with scrotal leiomyoma that is confirmed by histology. It is important to differentiate leiomyoma from malignant course.

Across cohorts, only SDH-mutant GIST patients experienced prolonged disease control. Despite evidence of target engagement, patients enrolled to all other cohorts had short PFS, suggesting rapid adaptation to ATR inhibitor monotherapy. Among these patients, those with tumors expressing SLFN11 during berzosertib exposure derived the most clinical benefit.

We identified three unique sarcoma cell cycle phenotypes that have prognostic significance. This performs similarly to the AJCC staging system.

P2, N=10, Active, not recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Recruiting --> Active, not recruiting | Trial completion date: Jul 2024 --> Jan 2025

Surgeons should consider diverting colostomy creation for patients with risk factors such as age 70 or older, ASA-PS III/IV, and hypertension.

Our analysis of the largest number of cLMS cases to-date highlights the importance of large cohort sizes and the exploration beyond small targeted gene panels when performing molecular analyses, as it allowed a comprehensive exploration of the mutational landscape of these tumours and identification of novel candidate driver events. It also uniquely afforded the opportunity to compare the molecular phenotype of cLMS with LMS of other tissue types, such as uterine and soft tissue LMS. Given that molecular profiling has resulted in the development of novel targeted treatment approaches for uterine and soft tissue LMS, our study now allows the same opportunities to become available for patients with cLMS.

P2, N=66, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

As the cases are rare in nature, screening is impractical. Hence, the diagnosis of uterine leiomyosarcoma is done by histopathologic examination after surgery.

These findings deepen our understanding of disease etiology and offer promising avenues for drug repurposing. Experimental validation is needed to translate these insights into clinical applications and innovative treatments.

This scheme of doxorubicin, dacarbazine, and nivolumab is feasible and well tolerated. Clinical activity is encouraging and the prognostic impact of HMGB1 supports the relevance of ICD activation. Further clinical research is already underway with this concept in leiomyosarcoma.

P2, N=72, Active, not recruiting, City of Hope Medical Center | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2024 --> Dec 2024

To our knowledge, congenital periocular leiomyosarcoma has not been reported in cattle previously. This rare tumor could be included as a differential diagnosis in newborn calves with periocular masses.

The consequences of NNMT overexpression, such as the activation and inactivation of oncoproteins and tumor suppressor proteins, respectively, as well as the enrichment of the cancer stem cell population, overlap with the major mechanisms responsible for poor prognosis in mesenchymal tumors. NNMT may be investigated further in the context of antitumor treatment in patients with mesenchymal malignancies.

P1/2, N=130, Active, not recruiting, Viracta Therapeutics, Inc. | Recruiting --> Active, not recruiting

P1, N=92, Recruiting, City of Hope Medical Center | Active, not recruiting --> Recruiting | Trial completion date: Sep 2024 --> Jan 2026 | Trial primary completion date: Sep 2024 --> Jan 2026

Furthermore, inhibiting BET proteins with their small, potent inhibitors (JQ1 and I-BET 762) significantly inhibited the uLMS proliferation dose-dependently via cell cycle arrest. The connections between BET proteins and crucial biological pathways provide a fundamental structure to better understand uterine diseases, particularly uLMS pathogenesis. Accordingly, targeting the vulnerable epigenome may provide an additional regulatory mechanism for uterine cancer treatment.

Sarcomas exhibit a high degree of defects in APM components, with differences among histotypes and tumoral areas. The most commonly altered APM components were HLA Class I subunit β2-microglobulin, HLA Class I subunit α (HC10), and MHC I transporting unit TAP2. The loss of APM components was prognostic of DM and OS and clinically relevant for LMS and DDLPS. This study explores sarcoma molecular mechanisms, enriching personalized therapeutic approaches.

It is about a 79-year-old female patient, who presented with a progressive enlarged right paraaortic retroperitoneal mass, thought first to be leiomyosarcoma of vena cava on imaging. Subsequently, high alpha-fetoprotein (AFP) level and biopsy allowed the diagnosis of primary extrahepatic hepatocellular carcinoma.

P2, N=29, Not yet recruiting, Northwestern University

This is a rare case of leiomyosarcoma associated with HLRCC, and our patient remains under surveillance with interval abdominal imaging and skin examination. Leiomyosarcomas are difficult to distinguish clinically from their benign counterpart; therefore, histopathological examination is paramount with a low threshold for excision.

Transcriptional co-analysis of TCGA patient samples to YAP1 and KRAS model tumors support that these sarcoma subtypes lie along a spectrum of disease and adds guidance for further transcriptome-based refinement of sarcoma subtyping. This approach can be used to begin to understand pathways and mechanisms driving human sarcoma development, the relationship between sarcoma subtypes and to identify and validate new therapeutic vulnerabilities for this aggressive and heterogeneous disease.

An overlap remains between characteristics of PEComas and smooth-muscle tumors. At present, there are no known pathognomonic findings or specific diagnostic markers.

While ULMS patients had a relatively low proportion of PGV, a high percentage of STLMS patients with PGV had tumor biallelic status, indicating that PGV drive tumorigenesis in these individuals. These findings have significant implications for genetic testing recommendations.

P1, N=12, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

Our data emphasize the diagnostic utility of multiple epithelial markers as a first screening tool in the detection and workup of malignant cutaneous sarcomatoid neoplasms. Awareness of SMA expression in these tumors can complicate its diagnosis, and it is important to recognize this aberrant immunophenotype to facilitate definitive diagnosis and avoid misdiagnosis.

LMS is a rare neoplasm of colon. For the time being, there is no guidelines for treatment, but surgery still plays a fundamental role.

P=N/A, N=150, Recruiting, Federation Francophone de Cancerologie Digestive

We also found that H3K27ac levels are increased in the LTR12 subfamilies, which could be regulatory elements controlling the expression of proapoptotic genes such as TNFRSF10B. In summary, we provide a detailed characterization of TEs modulation in response to HDACIs and suggest the use of HDACIs in combination with ADAR inhibitors to induce cell death and support immunotherapy in cancer.

LMP2/β1i, cyclin E1, and Ki-67/MIB1 may be candidate factors for biomarkers of human uterine leiomyosarcoma. Further large-cohort clinical trials should be conducted to establish treatments and diagnostics for uterine mesenchymal tumors.

The Hippo pathway is implicated in uLMS oncogenesis, since nuclear expression of YAP1 was detected in 17 (53.1%) of the 32 patients with immunohistochemistry and YAP1 amplification was found in 8 (25%) patients.

This case is the first reported case of ILMS involving the oral cavity. Even though this lesion is very rare, this neoplasm should be included in the differential diagnosis of a spindle cell lesion with marked lymphohistiocytic infiltration.

P2, N=198, Not yet recruiting, UNICANCER

However, no significant difference was found compared to SSCCs, suggesting limited discriminatory power of TRPS1 in this context. This study sheds light on TRPS1 expression patterns in a subset of CMNTUDs, extending beyond prior studies primarily focused on epithelial tumors, while underscoring potential pitfalls associated with TRPS1 immunohistochemistry.

Despite numerous treatment strategies designed to overcome primary resistance to PD1/PD-L1 therapy, response to ICI remains limited in LMS. Neither MSI nor TMB status appear to be strong predictive markers for response to ICI in LMS.

The tumor was diagnosed as an epithelioid leiomyosarcoma. This case considered to have occurred in the ocular region, although the ocular structure was destroyed.

In summary, among the soft tissue tumors tested, ISL1 is a highly sensitive but moderately specific marker for DSRCT and may be useful to distinguish from round cell mimics including EWS and CIC::DUX4 sarcomas. The oncogenic role of ISL1 in these tumors warrants further investigation.

P2, N=48, Active, not recruiting, Fox Chase Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Dec 2024