Chordoma

In chordoma, we propose that in addition to conventional bone resorption by osteoclasts, chordoma cells possess bone-dissolving activity at the tumor-bone boundary. Furthermore, bone destruction and tumor expansion may occur in a positive feedback loop.

Bioinformatics analysis and the dual luciferase reporter assay confirmed that CBX3 was a direct target gene of miR-1224 and that miR-1224 induced the proliferation of chordoma cells through the inhibition of CBX3. In summary, miR-1224 reduced the proliferation of chordoma cells through inhibition of CBX3, which provides a theoretical basis for selecting a novel therapeutic target for chordoma.

P2, N=10, Completed, Jonsson Comprehensive Cancer Center | Active, not recruiting --> Completed | Trial completion date: Apr 2025 --> Sep 2023 | Trial primary completion date: Apr 2024 --> Sep 2023

This study provides a comprehensive single-cell landscape of human chordoma and highlights its heterogeneity and the role played by TGF-β in chordoma progression. Our findings substantiate the potential of VEGFR as a target for CAR-T cell therapies in chordoma which, together with modulated TGF-β signalling, may augment the efficacy of CAR-T cells.

A better understanding of the current status and prospects of immunotherapy for BM is crucial for the rationale selection of appropriate BM patients for immunotherapy. This study is expected to help clinical physicians and researchers gain comprehensive insights into the developmental trends of BM immunotherapy, providing practical guidance for the application of immunotherapy in BM patients.

P2, N=267, Active, not recruiting, Epizyme, Inc. | Trial primary completion date: Jun 2024 --> Feb 2024

Moreover, silencing SIRT5 suppressed tumor growth in mice. These findings suggested that SIRT5 promoted the malignant advancement of chordoma by regulating the desuccinylation of c-myc.

Chordomas presenting in early childhood in the sacral location have been reported as a rare manifestation of tuberous sclerosis complex. The combination of these findings led to a diagnosis of tuberous sclerosis, confirmed with the finding of a heterozygous TSC2 gene deletion; treatment with sirolimus resulted in regression of cardiac rhabdomyomas and hypopigmented macules.

P2, N=64, Active, not recruiting, Institut Curie | Trial completion date: Feb 2024 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Jun 2024

P1, N=154, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2024 --> Nov 2024 | Trial primary completion date: Jun 2024 --> Nov 2024

For normalization of RT-PCR experiments in gene profiling of chordoma, we recommend the use of the stable genes YWHAZ, TBP and PGK1.

Our findings shed light on the natural immunity against chordomas through the identification of distinct immune contextures. Understanding their immune landscape could guide the development and application of immunotherapies in a tailored manner, ultimately leading to an improved clinical outcome for patients with chordoma.

P1, N=55, Active, not recruiting, Bavarian Nordic | Recruiting --> Active, not recruiting

P2, N=40, Recruiting, Grupo Espanol de Investigacion en Sarcomas | Trial completion date: Dec 2023 --> Sep 2024 | Trial primary completion date: Dec 2023 --> Sep 2024

High HIF-1α expression may become a potential new biological indicator to predict poor prognosis in patients with spinal chordoma. HIF-1α may also represent a novel therapeutic target for the treatment of spinal chordoma.

No IDH2 mutations were found. The use of independent diagnostic methods may improve the detection of IDH-mutant specimens in chondroid tumors.

In contrast, lnc-GLYATL2-2 can directly interact with the PD-L1 protein to prevent degradation, thereby promoting high levels of PD-L1 expression simultaneously at the transcriptional and translational levels in chordoma cells. These results provide a new perspective on the diagnosis and prognosis of ICs and provide theoretical evidence for immunotherapy in patients with ICs.

P=N/A, N=40, Recruiting, Leiden University Medical Center

P2, N=818, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> May 2026 | Trial primary completion date: Oct 2024 --> May 2026

Adult patients with previously treated, progressive chordoma participated in an open-label, single-institution, single-arm, pilot clinical trial of intravenous pemetrexed 900 mg/m2 every 3 weeks and supportive medications of folic acid, vitamin B12, and dexamethasone. High-dose pemetrexed appears tolerable and shows objective antitumor activity in patients with chordoma. Phase II studies of high-dose pemetrexed are warranted.

miR-186-5p, miR-125b-5p, miR-1260a, and their target protein mRNAs including AMOT, NPTX1, RYR3, P2RX5, TNFSF14 may be the basement of chordoma research.

P2, N=30, Recruiting, Xuanwu Hospital, Beijing

Over 30 patients were enrolled with ACC, NEN, and sdGIST, allowing for clinical/genomic analyses across tumors. Longitudinal follow-up and expansion of cohorts are ongoing to advance understanding of disease course and establish external controls for interventional trials.

All patients who had metastasis or died showed the "chordoid" or "sarcomatoid" morphology. Our findings suggest that UC with myxoid stroma/chordoid features shows characteristic expression of luminal and basal markers and different prognosis according to the morphologic pattern spectrum.

Utilizing pseudo-temporal mapping, we delineated the trajectories of CD8 and CD4 T cells in chordomas, spanning from blood to tumor stroma and encompassing naïve, memory, cytotoxic, and T cell exhaustion profiles. Through an integrated TCR profiling methodology, we observed extratumoral clonal expansion of cytotoxic and memory T cells in the blood, whereas the majority of intratumoral T cells with shared motifs exhibited terminal exhaustion. Leveraging GLIPH2, we identified binding patterns exclusively enriched in exhausted T cell receptors' binding sites and uncovered shared motifs within the reactive tumor-infiltrating compartment, implying the existence of potential reservoirs for anti-tumor immunity.

Pemetrexed 900 mg/m2 was administered intravenously every 3 weeks, with supportive medications of folic acid, vitamin B12, and dexamethasone. A phase II study is in development. (NCT03955042)

Pemetrexed 900 mg/m2 was administered intravenously every 3 weeks, with supportive medications of folic acid, vitamin B12, and dexamethasone. A phase II study is in development. (NCT03955042)

The authors' machine learning algorithm identified pan-cytokeratin as the largest contributor to recurrence among other IHC markers after SBC resection. Machine learning may facilitate the prediction of outcomes in rare tumors, such as chordomas.

P2, N=19, Active, not recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=21, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Nov 2023 --> Nov 2024 | Trial primary completion date: Nov 2023 --> Nov 2024

P2, N=818, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Oct 2023 --> Oct 2024

P=N/A, N=400, Recruiting, Ohio State University | Trial primary completion date: Dec 2023 --> Dec 2025

Our comprehensive picture of the microenvironment of primary and recurrent chordomas provides deep insights into the mechanisms of chordoma recurrence. FN1 is an important target for chordoma therapy.

Magnetic resonance imaging at simulation combined with proton radiotherapy for female sexual organ sparing may provide a technically feasible route to more equitable sexual outcomes for female patients. These results will guide future studies to optimize proton treatment techniques for female sexual organ sparing for future trials.

The MR images acquired using the optimized parameters showed minimal artifacts to scan spine patients with hardware. By using the low-tesla MR images, spinal chordoma and chondrosarcoma patients could be treated to improve tumor control probabilities with minimized complications.

Five-fraction proton therapy for the treatment of clival chordomas and chondrosarcomas is dosimetrically feasible and well tolerated for selected patients. Proton therapy remains a limited resource, consequently, reducing treatment time can have significant financial and psychosocial implications. Longer follow up is needed to validate these results.

The volume of irradiated skin and Dmax are associated with the risk of developing acute RIST in patients treated with PBS PBT. Further work is being done to develop a model predictive of acute RIST in clinical setting.

Medicaid patients may be less likely to receive surgery and suffer from poorer survival. These disparities may be especially prominent among minorities.

This is the first molecularly stratified clinical trial in chordoma, an under-researched orphan malignancy with no approved drug therapy. Palbociclib monotherapy resulted in modest tumor activity with manageable toxicity. Combination therapies should be considered to improve efficacy.

These findings depict the CAF landscape for chordoma and may provide insights into the development of novel treatment approaches.