The impact of radiotherapy on survival after surgical resection of chordoma with minimum five-year follow-up

Tobert, Daniel G.; Kelly, Sean P.; Xiong, Grace; Chen, Yen‐Lin; MacDonald, Shannon M.; Bongers, Michiel E R; Calderón, Santiago A. Lozano; Newman, Erik T.; Raskin, Kevin A.; Schwab, Joseph H.

doi:10.1016/j.spinee.2022.04.009

Cited by 5 publications

(5 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These patients underwent surgical resection with RT. The demographic, clinical, and surgical information of these patients has been reported elsewhere 3 …”

Section: Resultsmentioning

confidence: 99%

“…The demographic, clinical, and surgical information of these patients has been reported elsewhere. 3 There were 13 patients that developed LR. There were 19 patients that developed distant metastases in the lungs (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…However, advanced RT techniques deliver higher radiation doses with improved safety profiles to surrounding tissues. More recent data suggest that RT doses above 70 Gray, in addition to surgical resection, improve overall and LR-free survival 3 …”

Section: Discussionmentioning

confidence: 99%

“…More recent data suggest that RT doses above 70 Gray, in addition to surgical resection, improve overall and LR-free survival. 3 The rarity of this pathology creates a reliance on retrospective data, which is subject to bias even in multicenter formats. In particular, chordoma outcomes research is prone to temporal bias due to its slow growth rate.…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Local and Distant Recurrence After Surgical Resection of Chordoma

Tobert

Kelly

Xiong

et al. 2023

Spine

View full text Add to dashboard Cite

he treatment of chordoma is largely predicated on retrospective clinical research due to the rarity of the disease. En bloc resection (EBR) with negative margins and contemporary radiotherapy (RT) techniques improve overall survival. 1 However, local recurrence (LR) rates increase over time, even with negative margin resections. 2 Therefore, the length of follow-up is an important variable in retrospective clinical research efforts. The purpose of this research is to analyze the timing of LR after surgical resection of chordoma.

show abstract

“…These patients underwent surgical resection with RT. The demographic, clinical, and surgical information of these patients has been reported elsewhere 3 …”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Local and Distant Recurrence After Surgical Resection of Chordoma

Tobert

Kelly

Xiong

et al. 2023

Spine

View full text Add to dashboard Cite

show abstract

“…It often grows slowly but invasively. Surgical resection is the current standard of care, although the role of radiotherapy as a primary or adjuvant treatment continues to be explored [1]. After initial treatment, 50% of patients have local recurrence [2] and up to 40% develop distant metastases [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Virus-like particle-based delivery of Cas9/guide RNA ribonucleoprotein efficiently edits the brachyury gene and inhibits chordoma growth in vivo

Lü

Deng

et al. 2023

Discov Onc

View full text Add to dashboard Cite

Purpose Chordoma is a rare and aggressive bone cancer driven by the developmental transcription factor brachyury. Efforts to target brachyury are hampered by the absence of ligand-accessible small-molecule binding pockets. Genome editing with CRISPR systems provides an unprecedented opportunity to modulate undruggable transcription factor targets. However, delivery of CRISPR remains a bottleneck for in vivo therapy development. The aim was to investigate the in vivo therapeutic efficiency of Cas9/guide RNA (gRNA) ribonucleoprotein (RNP) delivery through a novel virus-like particle (VLP) by fusing an aptamer-binding protein to the lentiviral nucleocapsid protein. Methods The p24 based ELISA and transmission electron microscopy were used to determine the characterization of engineered VLP-packaged Cas9/gRNA RNP. The deletion efficiency of brachyury gene in chordoma cells and tissues was measured by genome cleavage detection assay. RT-PCR, Western blot, immunofluorescence staining, and IHC were employed to test the function of brachyury deletion. Cell growth and tumor volume were measured to evaluate the therapeutic efficiency of brachyury deletion by VLP-packaged Cas9/gRNA RNP. Results Our “all-in-one” VLP-based Cas9/gRNA RNP system allows for transient expression of Cas9 in chordoma cells, but maintains efficient editing capacity leading to approximately 85% knockdown of brachyury with subsequent inhibition of chordoma cell proliferation and tumor progression. In addition, this VLP-packaged brachyury-targeting Cas9 RNP avoids systemic toxicities in vivo. Conclusion Our preclinical studies demonstrate the potential of VLP-based Cas9/gRNA RNP gene therapy for the treatment of brachyury-dependent chordoma.

show abstract