Bone Cancer

Statistical analysis using Fisher's exact test revealed significant P-values for LC3A/B (P=0.048), AMBRA-1 (P=0.033), Ki-67 (P=0.048) and surgical treatment (P=0.048). Consequently, a negative prognostic role for these two ATGs may be hypothesized in the development of CHs.

We revised 2 initial AT/RT diagnoses as poorly differentiated chordoma based on the morphology, brachyury expression, topographical features, and methylation profile. Differentiating poorly differentiated chordoma from AT/RT could be challenging; brachyury expression can be useful in diagnosing poorly differentiated chordoma over AT/RT in suitable clinical and radiological settings.

Given the rarity of this diagnosis, molecular testing was performed which revealed a unique SMARCB1 molecular profile with a single-nucleotide variant in addition to the commonly reported loss of chromosome 22q. This report of an ultra-rare sarcoma in an uncommon anatomic site highlights multiple potential pitfalls in the diagnosis of poorly differentiated chordoma, emphasizes the importance of brachyury immunohistochemistry in rendering a correct interpretation, and underscores an opportunity for further molecular analysis to better define the molecular profile of this entity.

P=N/A, N=45, Recruiting, Musculoskeletal tumor center, Peking University People's Hospital; Peking University People's Hospital

Seven cases with denosumab treatment demonstrated degrees of giant cell disappearance, increased fibrous tissue and reactive bone proliferation in the stroma... Pediatric GCTB predominantly affects females and occurs primarily in long bones, mainly around the knee joint, the majority of tumors predominantly arise in the epiphysis and extend into the metaphysis; however, in cases where the epiphyseal plates are still unclosed, the tumors may be restricted to the metaphysis. Detection of H3F3A gene mutation is crucial for the diagnosis and differential diagnosis of pediatric GCTB.

Although no immunopositivity for keratin was observed in the present giant cell granulomas cohort, we cannot completely exclude the possibility of keratin-positive giant cell-rich tumors occurring in the jaws. Therefore, oral pathologists should be aware about this condition and further studies using cohorts from different laboratories are necessary.

We regarded ABL1, EGFR, and LCK as on-target kinases; among the two corresponding on-target kinase inhibitors, osimertinib and ponatinib emerged as on-target drugs whose target kinases were significantly activated. The remaining 26 kinases and seven kinase inhibitors were excluded as off-targets. Our pharmacoproteomic approach enabled the identification of on-target kinase inhibitors that are useful for drug repositioning.

P3, N=128, Recruiting, SynOx Therapeutics Limited | Trial primary completion date: Sep 2027 --> Apr 2026

P2, N=19, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

The aim of this review is to summarize novel chordoma treatments in immune-targeted therapies. The current merits, trial outcomes, and toxicities of these novel immune and targeted therapies, including those targeting vascular endothelial growth factor receptor (VEGFR) targets and the epidermal growth factor receptor (EGFR), will be discussed.

Thorough clinical and radiological follow-up is mandatory as local recurrences are to be expected due to the infiltrative behavior. In case of a loco regional recurrence the fusion with FGFR2 may represent a therapeutic option for a targeted therapy on molecular level.

This study illustrates the dynamics between chordoma cells and TAMs in promoting chordoma invasion and suggests that IL-6/STAT3 pathway is a potential therapeutic target to reduce TAM-induced chordoma invasion.

The patient was treated with pegylated interferon and imatinib, which resulted in stable disease after three months...Analysis of ligand-receptor interactions showed significant communication between neoplastic cells and macrophages mediated by CSF1 and CSF1R. Our findings emphasize the importance of comprehensive molecular analysis in diagnosing and treating rare malignancies like TGCT.

P3, N=120, Recruiting, St. Louis University | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2025 --> Jan 2026

The present case study helps in creating an awareness and attempts to expand our knowledge in relation to the spectrum of chordoma (clinico-histological) and its immunohistochemical profile.

P1/2, N=27, Not yet recruiting, University of Florida

P=N/A, N=60, Recruiting, Mayo Clinic | N=180 --> 60

P1/2, N=86, Recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2025 --> Jun 2026 | Trial primary completion date: Sep 2025 --> Jun 2026

P4, N=35, Recruiting, Amgen | Trial completion date: Oct 2027 --> May 2028 | Trial primary completion date: Oct 2027 --> May 2028

The case underscores the importance of considering MTB infection in the differential diagnosis of chronic unilateral knee arthritis, especially given the atypical clinical manifestations and imaging findings that can mimic other conditions like PVNS.

P2, N=45, Recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Oct 2024 --> Jun 2025

P2, N=21, Active, not recruiting, Daiichi Sankyo Co., Ltd. | Recruiting --> Active, not recruiting | Trial completion date: Nov 2026 --> May 2026

Imaging examination combined with immunohistochemical H3.3 G34W positivity was used to diagnose the patient with GCTB. Understanding the unique histological morphology of this patient will help doctors correctly diagnose giant cell tumors of bone and avoid misdiagnosis.

No abstract available

Although the above described radiological findings are not specific for GCTB in head and neck region, a well-defined osteolytic lesion in the bones of head and neck region with "soap bubble" appearance on CT and hypointensity on T2WI with very low signal in the peripheral region of the tumor on MRI highly suggest GCTB for patient ages 20 to 40.

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.

Our initial findings distinguish recurrent chordomas from their primary counterparts based on cancer gene expression changes that encourage growth and proliferation, remodel the bone matrix environment, and evade the immune system. Continued investigation is needed to assemble a broader patient sample. Examining the pathways and genetic mutations across the chordoma disease progression may reveal novel therapeutic avenues for recurrent chordomas.

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