Liposarcoma

Furthermore, we find that MAZ controls expression of the immunity-related genes by changing the epigenetic landscape in chromatin. Our study reveals an important role for MAZ in regulating immune-related gene expression.

P3, N=240, Recruiting, Boehringer Ingelheim | Initiation date: Mar 2023 --> Dec 2023

In this large-scale cohort of GLI1 co-amplified WD/DDLPS, we elucidate uniquely recurrent features including meningothelial whorls and GLI-altered morphology in dedifferentiated areas. Assessment of tumor location (retroperitoneal or mediastinal), identification of a well-differentiated liposarcoma component, and co-amplification of other spatially discrete genomic segments (1p, 6q) might aid in distinction from tumors with true driver GLI1 alterations.

Two years and six months after surgery, the patient is asymptomatic. The present case is the first report of this entity with positive immunohistochemical testing for p16, p53, S100, vimentin and absence of MDM2 gene amplification.

PMPTF is a rare, benign, and underrecognized lesion that may mimic malignancy, particularly retroperitoneal well-differentiated liposarcoma. The imaging features of this unusual pseudosarcoma differ in native and transplanted kidneys. Improved awareness of this entity will facilitate appropriate patient management and avoid unnecessary intervention.

No abstract available

P1/2, N=337, Recruiting, Pfizer | Trial completion date: Oct 2027 --> May 2028 | Trial primary completion date: Aug 2026 --> Mar 2027

Histopathological examination and positive expression for CD34 helped to arrive at the final diagnosis. Awareness about this rare entity will prevent overdiagnosis as a malignant tumor and unnecessary radical resections for this benign tumor.

Afami-cel treatment resulted in durable responses in heavily pre-treated patients with HLA-A*02 and MAGE-A4-expressing synovial sarcoma. This study shows that T-cell receptor therapy can be used to effectively target solid tumours and provides rationale to expand this approach to other solid malignancies.

P1, N=44, Suspended, M.D. Anderson Cancer Center | Not yet recruiting --> Suspended

We detected (de novo/somatic) missense mutation variants in cis position of the NTRK1 gene in a subset of DDLPS indicating modifying mutations that may contribute to tumorigenesis in a subset of DDLPS. These variants beget resistance to TRK inhibitors indicating an interesting biomarker for other studies with TRK inhibitors.

P3, N=240, Recruiting, Boehringer Ingelheim | Initiation date: Dec 2023 --> Mar 2023

Future classification systems in BST neoplasms cannot be solely based on molecular events and ideally will balance morphologic features with molecular analysis. Herein, we provide a narrative literature review of the more common BST neoplasms with shared genetic events but differing demographics, morphology, immunophenotype, and clinical behavior, re-emphasizing the importance of the hematoxylin and eosin slide and the "eye" of the practicing pathologist.

This study highlights the potential of the CD47 molecule as a promising immunotherapeutic target in STS, particularly given its elevated expression levels in diverse sarcoma types. Our data showed a notable trend linking CD47 expression to tumor grade, while also suggesting an interesting correlation between enhanced abundance of CD47 expression and a reduced hazard risk of disease progression. Although these findings shed light on different roles of CD47 in STS, further research is crucial to assess its potential in clinical settings.

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

P=N/A, N=1400, Active, not recruiting, Boehringer Ingelheim | Not yet recruiting --> Active, not recruiting

All samples were processed for histopathological analysis (HE, IHC and DNAscope™), Western blot, and qPCR; moreover, 3D collagen-based models were treated with different doses of SAR405838, a well-known inhibitor of MDM2, and cell viability was assessed in comparison to 2D model drug response...3D collagen samples showed higher cell viability after SAR40538 treatment than 2D models, while cells sensitive to the drug died by apoptosis or necrosis. Our results prompt us to extend our investigation by applying our 3D models to further oncological relevant applications, which may help address unresolved questions about dedifferentiated liposarcoma biology.

P1, N=15, Active, not recruiting, OHSU Knight Cancer Institute | Phase classification: P1b --> P1

Several regimens have been tested with modest results regarding their efficacy. Herein we discuss the systemic treatment options for WDLPS and DDLPS and review their reported clinical efficacy results.

P2, N=10, Recruiting, Mario Negri Institute for Pharmacological Research | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Dec 2024

P1, N=74, Terminated, Sumitomo Pharma America, Inc. | Trial completion date: Oct 2024 --> Jan 2024 | Recruiting --> Terminated | Trial primary completion date: Jun 2024 --> Jan 2024; Sponsor's decision to terminate further development of the program.

The aim of this review article is to provide a comprehensive summary of previously documented case reports and studies related to MPLs. By shedding light on the intricate details of MPLs, researchers and clinicians can gain valuable insights that may pave the way for improvements in diagnosis, treatment, and patient outcomes in the future.

P1, N=180, Recruiting, Numab Therapeutics AG

From 2019 to 2022, 1387 patients with STS were registered in C-CAT. The histological types included leiomyosarcoma in 357 patients, dedifferentiated liposarcoma in 178 patients, and undifferentiated pleomorphic sarcoma in 82 patients, and the others. The most commonly altered genes included TP53, CDKN2A, Rb1, and CDKN2B.

The results demonstrate that detection of ecDNA using clinical-grade NGS assays is feasible and that key oncogene FH-amp on ecDNA (e.g., EGFR, FGFR2) are common in select tumor types. ECHO may be developed as a clinical trial device to prospectively identify patients with oncogene ecDNA+ FH-amp for clinical testing of ecDNA-directed therapies.

P1, N=14, Active, not recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2024 --> Jan 2025

These findings emphasize the importance of distinguishing between primary sDDLPS and secondary lesions due to their distinct prognoses. Metastasis or superficial extensions from deep DDLP correlate with a considerably worse prognosis than those originating in superficial tissues.

Limited clinical follow-up showed no recurrence or metastasis after 1-13 months (median 4.5 months) post-surgical excision. Altogether, our data support that ASPLT can rarely develop sarcomatous transformation and offers insights into the molecular mechanisms underlying this event.

P1, N=150, Recruiting, Boundless Bio | Phase classification: P1/2 --> P1 | N=47 --> 150 | Trial completion date: Jan 2026 --> Sep 2027 | Trial primary completion date: Jan 2025 --> Sep 2026

Based on these findings, the final diagnosis was determined to be a fat-forming solitary fibrous tumor located in the retroperitoneum. It is important to consider other potential differential diagnoses, including angiomyolipoma, dedifferentiated liposarcoma, spindle cell lipoma, and atypical lipomatous tumor/well-differentiated liposarcoma.

P2, N=148, Not yet recruiting, HRYZ Biotech Co.

The majority of cases (7/9) showed decreased expression in p53 staining, suggesting that DDIT3 amplification regulates the expression of TP53 like MDM2. From a clinicopathological perspective, we hypothesize that DDIT3-amplified sarcoma, especially with 5'-predominant amplification, can be reclassified out of the UPS category.

Immunohistochemistry showed that the tumor cells were positive for CDK4 but negative for MDM2, and FISH analysis showed no MDM2 amplification. The patient only underwent tumor excision and is currently doing well.

P2, N=72, Recruiting, Alliance for Clinical Trials in Oncology | Suspended --> Recruiting

Our findings implicate a putative role for dysregulation in glucose metabolism, TGF-β and HIF1 signaling in the pathogenesis of both WD/DDLPS suggesting a possible proinflammatory tumor environment within WDLPS and subsequent activation of the TGF-β signaling pathway. Additional studies are warranted to understand the role of these pathways in the pathogenesis of WD/DDLPS.

We aim to highlight the importance of considering myxoid neurofibroma in the differential diagnosis of hypocellular myxoid spindle cell lesions encountered on fine-needle aspiration cytology.

P2/3, N=140, Active, not recruiting, National Cancer Institute (NCI)

P1/2, N=139, Recruiting, St. Jude Children's Research Hospital | Not yet recruiting --> Recruiting

The metastatic lesions contained abundant lipoblasts rather than rhabdoid cells, and we concluded this tumor was a MPLS. The presence of rhabdoid cells could be a diagnostic pitfall, and recognizing such a variation in histology would help improve diagnostic accuracy.

P1/2, N=139, Not yet recruiting, St. Jude Children's Research Hospital

WDLPS/DDLPS with myxoid-like morphology is most commonly seen in the retroperitoneum and abdominal cavity and mostly harbors DDIT3 break-apart probe amplification, while this amplification is not specific to liposarcoma. For core biopsy specimens or very rare tumors in the limbs, when histology has mucinous stroma and MLPS-like morphology, misdiagnosis of MLPS or other non-lipomatous neoplasms with myxoid morphology should be avoided.

ASCPLTs lack MDM2 amplification, but a large subset show RB1 deletion and variable expression of CD34. Though initially thought to be the malignant form of spindle cell lipoma, ASCPLTs are benign with local recurrences (∼10-15%) and no well-documented dedifferentiation or metastasis.