Chordoma

In summary, our findings support the differential diagnosis between paediatric PDC and CC. Further, our findings suggest that besides distinct methylome profiles, paediatric PDC and CC are likely driven by distinct pathogenic pathways.

Furthermore, comparison with over 2,000 sarcomas highlighted CN patterns more common in chordoma (i.e. chr1q, chr2, chr7 gains and chr1p, chr3, chr9, chr10, chr13, chr14, chr18 losses) but also revealed shared aberrations, e.g. chr22 loss shared with Gastrointestinal Stromal Tumours (GISTs). This study provides a unifying classification for skull base chordoma, linking distinct genomic architectures to specific transcriptional programs and potential therapeutic vulnerabilities.

P2/3, N=60, Suspended, Centre Leon Berard | Recruiting --> Suspended

P2, N=798, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: May 2027 --> May 2026

D (30 mg/kg) + T (1 mg/kg) had limited antitumor activity in this pediatric population; however, the safety profile was manageable and consistent with the known safety profile in adult patients, with no new safety concerns identified. ClinicalTrials.gov, identifier NCT03837899; EudraCT, identifier 2018-003118-42.

P=N/A, N=400, Active, not recruiting, Ohio State University | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

Combination of camrelizumab and apatinib offered encouraging efficacy with manageable toxicity in chordoma treatment. CDKN2A alterations are associated with worse prognosis and may prove to be a potential biomarker for treatment selection.

A total of 108 studies encompassing 6349 individuals were included. Across six domains, four cross-cutting themes with prognostic and potential theranostic value emerged: copy number alterations, particularly CDKN2A/B loss; SWI/SNF complex dysfunction; stroma-tumor ratio; and immune microenvironment heterogeneity.

P2, N=818, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2026 --> May 2027 | Trial primary completion date: May 2026 --> May 2027

However, interferon-γ treatment did not induce TBXT (brachyury) expression in chordoma cells. Together, these data reveal strong associations between transcriptional states, metabolic profiles, and immune infiltration in chordomas.

This study establishes a spinal chordoma PDO platform for functional precision oncology. Our findings identify a TP53-dependent DNA-damage vulnerability engaged by gemcitabine in patient-derived three-dimensional models, supporting biomarker-informed hypothesis generation rather than routine chemotherapy in unselected patients. This PDO-based approach provides a translational framework for exploring pathway-defined therapeutic susceptibilities in rare tumors such as chordoma.

It also emphasizes the critical role of histopathological examination in distinguishing chordomas from other clival lesions, such as ecchordosis physaliphora (EP). Gross total resection (GTR) should be performed when feasible, and histologic evidence of bone invasion can be an important diagnostic clue for chordomas.