Bone Cancer

 As chordoma patients demonstrate a worse prognosis compared to chondrosarcoma patients, the differential expression of chordin, HOXA5 and ACAN and CD24 could be relevant for the pathophysiology of chordomas and may have diagnostic and treatment value. Further study on role of these genes in tumorigenesis is therefore warranted.

Pathological morphology and immunohistochemical analyses deepen our understanding of the pathological features of TSC and provide a diagnostic reference for clinicians who will encounter such cases in the future.

All the characteristics typically associated with chordomas as cancers-migration and invasion, therapeutic resistance, metastatic potential-can be driven by tumor EVs. Overall, ARF-8 EVs promoted predicted tumorigenic phenotypes in recipient cells and suggested novel therapeutic targets for chordomas.

However, doxorubicin, foretinib, and ceritinib were identified as promising therapeutic candidates due to their low IC50 values in NCC-GCTB10-C1. The establishment of NCC-GCTB10-C1 offers a critical resource for further research into GCTB, especially in the context of recurrent disease, and holds potential for the development of more effective treatment strategies.

The analysis by CellChat indicated that CTLA4 or TIGIT might act as important immune checkpoint genes to attenuate the inhibitory effect of aneuploid osteoclasts on NK/T cells, thereby enhancing the activity of NK/T cells. Our study found that both osteoblasts and osteoclasts might be involved in the development of GCTB, which may provide a new direction for the treatment of GCTB.

Denosumab has potential role for giant cell tumour of bone, it makes a less morbid surgery technically feasible. However, recurrence needs to be probed in long term follow up studies.

Treatment has been reported to range from a conservative parathyroidectomy to resection and reconstruction. We present a case of a female who presented with a facial disfigurement for four months that was hidden under the effect of a parathyroid adenoma. Our aim is to guide the surgeon in the proper detailed management of osteolytic lesions of jaws that are related to parathyroid hyperfunction.

We found that they were compatible with chemosensitivity assays, and drug screening using these cell lines led to the identification of potential therapeutic candidates for GCTB. Therefore, NCC-GCTB14-C1 and NCC-GCTB15-C1 may be useful for elucidating the pathogenesis of and developing novel treatments for GCTB.

Two patients were alive with metastatic disease (at 7 and 13 months), one dead of disease (20 months) and three disease-free (1- 26 months). We conclude that extra-axial poorly differentiated chordoma are aggressive malignancies with an unusual predilection for the knee joint and unknown pathogenesis.

No abstract available

Treatment with bisphosphonates (P = 0.17) or denosumab (P = 0.75) had no significant effect on ROR2 expression. Patients with GCT exhibit more than twofold upregulation of ROR2 expression, confirming its role in causing osteoclast-mediated bone destruction. Therefore, ROR2 may be a target for drug development in the treatment of GCT.

Recent studies demonstrated a recurrent HMGA2::NCOR2 fusion in many cases. We herein describe a case of XGET/KP-GCT arising in the right femoral head of a 19-year-old male harboring a rare novel HMGA2::COL14A1 fusion.

P1, N=55, Active, not recruiting, Bavarian Nordic | Trial completion date: Jun 2026 --> Jan 2025 | Trial primary completion date: Jun 2024 --> Feb 2024

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.