Chordoma represents a central nervous system tumor with an incidence of 8.4 per 10 million individuals in the U.S. Current treatment options include surgical resection and radiotherapy. Despite recent studies demonstrating significant improvement in molecular understanding of disease, treatment options remain limited. To evaluate a database of high-throughput drug screening in conjunction with a systematic literature review of potential novel target sites. A systematic review using terms "chordoma" AND "targeted therapy" OR "clinical trial" yielded 4560 articles, which were screened, and a total of 88 were included in the final analysis. Evaluation of the Chordoma Foundation high-throughput drug screening database was cross-referenced with published literature. Targeted therapies mostly involved receptor tyrosine kinase inhibitors. Cyclin-dependent kinase (CDK) inhibitors suppressed chordoma cell proliferation and brachyury expression in vitro and xenograft models. Epigenetic modulators showed therapeutic promise by altering chromatin states associated with brachyury overexpression. Genomic analyses showed recurrent alterations in TBXT, CDKN2A/B, PTEN, and chromatin remodeling genes such as SMARCB1 and PBRM1. Immunotherapeutic approaches had efficacy in preclinical models through PD-L1 blockade, NK, and CAR-T cell strategies. Vaccine-based therapies showed limited clinical benefit. RNA-based therapies represent emerging strategies that need more studies. Biomarker-guided repurposing of therapies approved in other tumors remains the fastest path to redefining the treatment model, but chordoma rarity and low mutation burden limit the impact of genomics in target discovery. This analysis indicates several potential candidate drugs that may be rapidly deployable in a clinical trial setting.

Background: Traumatic brain injury (TBI) is a leading cause of mortality and disability, particularly in patients on anticoagulation therapy. While anticoagulants are linked to higher TBI mortality, the specific impact of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) on severe TBI (sTBI) outcomes remains unclear, especially in light of newer reversal agents. Therefore, this study evaluates long-term mortality and complication risks associated with pre-injury use of DOACs and VKAs in sTBI patients from a large, real-world cohort. Methods: A retrospective cohort study was conducted using the TriNetX global research network, identifying patients with sTBI between 2016 and 2022. Patients were grouped based on pre-injury anticoagulant use: DOAC, VKA, or none. Propensity score matching was performed, adjusting for age, comorbidities, and baseline characteristics. The primary outcome was all-cause mortality at 1-, 3-, 6-, and 12-months post-injury. Secondary outcomes included hospital and surgical complications up to 30 days post-injury. Results: A total of 40,563 patients met the inclusion criteria. At all time intervals, no significant mortality differences were found between the PSM-matched groups. Conclusions: In patients with sTBI, pre-injury DOAC or VKA use was not associated with increased short- or long-term mortality. These findings suggest that, with current perioperative practices, anticoagulation can be managed without adversely affecting outcomes.

Introduction: Chordomas are rare, locally aggressive tumors of the spine and skull base typically managed with maximal surgical resection followed by adjuvant radiotherapy. Although postoperative radiotherapy improves local control, the optimal interval for initiation remains uncertain, as early delivery may exacerbate wound-related complications while delayed initiation may allow tumor progression. Methods: We performed a retrospective cohort analysis using the multi-center, national TriNetX Research Network. Adults with histologically confirmed skull base and/or spinal chordoma who underwent surgical resection followed by radiotherapy were stratified into ultraearly (≤2 weeks), standard (4–6 weeks), or delayed (≥10 weeks) radiotherapy initiation groups. Propensity score matching was used to adjust for demographic and clinical covariates. The primary outcome was all-cause mortality at 1, 3, and 5-years. Secondary outcomes included wound dehiscence, surgical site infection, and neurologic complications. Results: A total of 378 patients met the inclusion criteria. Ultraearly radiotherapy was not associated with significant differences in mortality at 1 year (RR 1.338; 95% CI 0.833–2.15; p = 0.22), 3 years (RR 1.233; 95% CI 0.858–1.772; p = 0.25), or 5 years (RR 1.196; 95% CI 0.876–1.633; p = 0.25) compared with standard timing. Delayed radiotherapy, however, demonstrated significantly reduced mortality at 1 year (RR: 0.53; 95% CI: 0.331–0.851; p = 0.01), 3 years (RR 0.641; 95% CI 0.449–0.914; p = 0.01), and 5 years (RR 0.654; 95% CI 0.473–0.905; p = 0.01) compared with standard timing. Event counts for secondary outcomes were insufficient for robust statistical comparison. Conclusions: Radiotherapy timing following surgical resection of chordoma did not impact short-term survival, but delayed radiotherapy significantly decreased 1, 3 and 5-year mortality. Rare secondary complications were seen. These findings suggest that the delayed initiation of radiotherapy may be helpful for patients with chordoma, supporting the need for prospective, long-term studies to clarify the balance between oncologic efficacy and perioperative morbidity.

Background/Objectives: The endoscopic transorbital approach (ETOA) has emerged over little more than a decade as a minimally invasive corridor to the anterior and middle cranial fossae, reaching territory lateral to the optic nerve and internal carotid artery that is difficult to access endonasally. Its flagship indication is the spheno-orbital meningioma, where the corridor aligns with the pathology and functions best as a planned, often decompressive strategy rather than a route to radical resection. This narrative review synthesizes the current evidence and defines the approach’s role, limitations, and priorities. Methods: PubMed/MEDLINE, Scopus, and Web of Science were searched for English-language anatomical studies, clinical series, systematic reviews, and meta-analyses on the transorbital approach published between January 2016 and August 2026. Results: The evidence remains dominated by small, retrospective, single-center series and a handful of recent meta-analyses. Reported short-term outcomes—favorable proptosis relief, acceptable visual and cranial-nerve results, low pooled complication rates, and short recovery—are encouraging but constrained by short follow-up, heterogeneous nomenclature, and outcome reporting that grades residual tumor globally rather than by anatomical compartment. Gross total resection rates are lower than after transcranial surgery, and oncological equivalence has not been established. Technical, reconstructive, ophthalmic, and anatomical factors define the corridor’s ceiling, and ETOA is best positioned against endonasal and transcranial alternatives as a complementary rather than competing tool. Conclusions: ETOA is an established corridor whose maturation depends on reconstructive refinement, a flatter learning curve, standardized terminology and outcome sets, and prospective comparative data—consolidation rather than anatomical expansion.