Bone Cancer

The current data support the assessment of TBL structures as a reliable prognostic tool in GCTB, potentially aiding in the development of personalized treatment strategies for patients.

Clinically, a significant correlation of high IER2/ITGB1 expression with tumor aggressive phenotype and poor patient survival is observed. Collectively, the findings suggest that ERS-CAF regulates SPP1+ macrophage to aggravate chordoma progression via the IER2/GMFG/ITGB1 axis, which may be targeted therapeutically in future.

Among all the considered clinicopathological features related to patient survival, only tumor location in the sacrococcygeal region and adequate surgical margins positively impacted DFS. In conclusion, partial SMARCB1/INI1 loss, mostly due to 22q deletion, was detected in a significant number of patients with conventional spinal chordomas and was correlated with mobile spine location and inadequate surgical margins.

We conclude that these unusual tumors represent a distinct category of synoviocytic neoplasia, which we term "chondroid synoviocytic neoplasm", rather than simply ordinary TGCT with cartilage. Despite potentially worrisome morphologic features, they appear to behave in at most a locally aggressive fashion.

These findings suggest that LIS is a reliable predictive tool for clinically relevant outcomes and response to denosumab therapy in patients with GCTB. These parameters may prove to be useful in guiding prognostic risk stratification and therapeutic optimization for patients.

Follow-up examinations revealed spontaneous secondary fusion of both hemimandibles and no signs of tumor recurrence. Nearly 1 year after surgery, the owners reported no signs of tumor regrowth.

P=N/A, N=35, Recruiting, CNAO National Center of Oncological Hadrontherapy | Trial primary completion date: Feb 2024 --> Aug 2025 | Trial completion date: Apr 2025 --> Aug 2025

P2, N=15, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Sep 2024 --> Sep 2026 | Trial primary completion date: Sep 2024 --> Sep 2026

After adjusting for age, sex, tumor site, and additional treatment, patients with somatic deletions of 14q (OR = 13.73, 95% CI 1.96-96.02, P = 0.008) and 18p (OR = 13.68, 95% CI 1.77-105.89, P = 0.012) were more likely to have persistent chordoma. The study highlights genomic heterogeneity in chordoma, potentially linked to location and clinical progression.

P1, N=85, Recruiting, Abbisko Therapeutics Co, Ltd | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025

TFE3-rearranged PEComa has unique histomorphological, immunohistochemical and molecular characteristics. The biological behavior is aggressive, which could lead to recurrence and metastasis, and warrants close clinical follow-up.

Additionally, IL-7 modulated favorable subpopulations of cultured CAR-T cells, diminished immune checkpoint expression on T-cell surfaces, and enhanced T-cell functionality. The incorporation of IL-7 molecules into the B7-H3 CAR structure augmented CAR-T-cell function and improved CAR-T-cell efficacy, thus providing a novel dual therapeutic strategy for chordoma treatment.

P=N/A, N=35, Not yet recruiting, Hospices Civils de Lyon

P2, N=17, Active, not recruiting, Andrew J. Wagner, MD, PhD | Trial completion date: Jan 2025 --> Jul 2025

P=N/A, N=40, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Recruiting

The patient was discharged with oral crizotinib targeted therapy, and his condition remained stable postoperatively...Pulmonary sarcomatoid carcinoma can exhibit rapid tumor growth on imaging, and PSC should be considered in the differential diagnosis for lesions that present with a fast growth rate. Timely and appropriate treatment for PSC may lead to a good prognosis.

Using the 22C3 assay, the expression of PD-L1 was found to be variable in two cases, and beta-HCG was negative. In conclusion, giant cell carcinoma is a subtype of urothelial carcinoma associated with advanced clinical stage and a trend to lower survival rates.

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.

Our study confirms the high prevalence of FN1 fusions in CCMN. In addition, through transcriptome and methylome analyses, we have identified a novel subgroup of tumors located at the TMJ, exhibiting TGCT-like features and FN1::TEK fusions.

The results of this study provide evidence supporting the use of TSR as a reliable prognostic tool in GCTB and as a predictor of denosumab treatment responsiveness. These findings may aid in developing individualized treatment strategies for GCTB patients in the future.

The final diagnosis for the knee nodule was pigmented villonodular synovitis. This case highlights the potential for pigmented villonodular synovitis to mimic MM, requiring additional pathologic analysis to yield an accurate diagnosis.

Vimseltinib demonstrated long-term tolerability, manageable safety, dose-dependent exposure, and robust antitumor activity in patients with TGCT whose disease is not amenable to surgery.

P2, N=818, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2033 --> May 2026 | Trial primary completion date: May 2033 --> May 2026

Three patients presented with metastases as the initial manifestation of disease; 8 patients died of their tumors from 6 months to 8 years (mean: 2.7 y); 3 patients were alive and well from 4 to 6 years; and 2 patients had metastases when last seen but were lost to follow-up thereafter. The importance of recognizing this distinctive and aggressive variant of non-small cell lung carcinoma lies in avoiding confusion with a sarcoma or other types of malignancy.

P2, N=818, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2026 --> May 2033 | Trial primary completion date: May 2026 --> May 2033

This study provides overall protein and gene profiles of PVNS and identifies the crucial role of TGF-β in synovial invasion pathology. Exploring the related molecular mechanism may also reveal a new strategy or target for PVNS therapy.

P2, N=20, Completed, AmMax Bio, Inc. | Recruiting --> Completed | N=48 --> 20 | Trial completion date: Jan 2026 --> Jun 2024 | Trial primary completion date: Nov 2025 --> Jun 2024

In patients with a history of testicular mixed germ cell tumors, comparison of histomorphology using HE and Brachyury staining of lung and testicular tumors, and analyzing isochromosome 12p and 12p amplification in lung tumors using FISH is pivotal for the diagnosis of rare lung chordomas.

HMGA2::NCOR2 keratin-positive giant cell tumors in children with response to imatinib in an infant.

P2, N=11, Completed, AmMax Bio, Inc. | Active, not recruiting --> Completed

Due to histopathologic resemblance with other giant cell-rich lesions (giant cell granuloma of the jaws, brown tumor of hyperparathyroidism, and non-ossifying fibroma) for which signature mutations are known, mutational analysis of KRAS, FGFR1, and TRPV4 genes was conducted. The results revealed wild-type sequences for all the mutations tested, thereby supporting the diagnosis of tenosynovial giant cell tumor.

PPARγ and P53 have a significant role in LTGCT growth, while P53 plays a role in tumor multiplicity. They can be possible targets in LTGCTs unfit for excision.

Most patients received immunotherapy targeting the PD-1/PD-L1 interaction, and two patients received therapy targeting this interaction along with the tyrosine kinase inhibitor pazopanib...Despite challenges in patient accrual, future directions in chordoma immunotherapy may lie in vaccine-based therapies and immune checkpoint inhibitors. Understanding chordoma heterogeneity and microenvironment will likely elucidate important chordoma features that will inform future clinical trial design.

P=N/A, N=40, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

To our knowledge, this is the first report of a chordoma with RICTOR amplification, which was co-amplified with FGF10 on chromosome 5p13. RICTOR amplification may represent a clinically significant alteration in chordoma and predict response to targeted therapy with RICTOR/mTORC2 inhibitors.

Currently, there are several CDK9 inhibitors in preclinical and clinical investigations. This review aims to highlight the recent discovery and results on the transcriptional role and therapeutic potential of CDK9 in sarcoma.

Skin specimens with an exophytic mass histologically resembling cGCT but with malignant cytology should be meticulously evaluated for elements of SCC. Molecular analysis, detecting mutations like H3F3 or HMGA2-NCOR2 fusion, can aid in distinguishing cutaneous sarcomatoid squamous cell carcinoma from GCT bone or GCT soft tissue.

P1, N=21, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Nov 2024 --> Nov 2026 | Trial primary completion date: Nov 2024 --> Apr 2024

This review provides an updated overview of the clinicoradiological features, pathogenesis, histopathology, and treatment for GCTST. In addition, we will discuss the differential diagnosis of this peculiar neoplasm.

This review provides an overview of the current knowledge on the clinical presentation, pathogenesis, histopathology, and treatment of KPGCT. In addition, we will discuss the differential diagnosis of this emerging entity.

CDK7 and CDK9 inhibition was lately identified as being effective in reducing viability in four chordoma cell lines, most likely due to a reduction in brachyury levels. In this study, we determined the capability of the CDK7 inhibitor THZ1 and the CDK1/2/5/9 inhibitor dinaciclib to reduce TBXT expression at mRNA and protein levels in a broad range of nine cell lines that are models of primary, recurrent, and metastasised chordoma of the clivus and the sacrum.

P2, N=4, Terminated, AmMax Bio, Inc. | Active, not recruiting --> Terminated; Further enrollment was halted in November 2021, enrolled subjects completed the study. Sponsor stopped further recruitment in this intravenous study to focus on intra-articular route of administration in subjects with tenosynovial giant cell tumor.