Acute peritumoral brainstem hemorrhage of a clival chondrosarcoma successfully treated via endoscopic endonasal surgery: illustrative case.

BACKGROUND: Chondrosarcoma is typically a slow-growing tumor, and intratumoral hemorrhage is rare. Acute brainstem hemorrhage due to chondrosarcoma has rarely been reported. OBSERVATIONS: A 77-year-old man presented with the sudden onset of headache and vomiting followed by a declining level of consciousness, progressive right hemiparesis, and left ophthalmoplegia. Magnetic resonance imaging showed pontine hemorrhage and a mass in the retroclival space compressing the brainstem. Emergency endoscopic endonasal surgery was performed. Intraoperative observation revealed that a hematoma was located in the pons and subdural space around the tumor mass, suggesting that the hematoma had likely been caused by the rupture of small vessels around the pons, not by intratumoral hemorrhage. The pathological diagnosis was chondrosarcoma. The patient recovered well and underwent radiotherapy. LESSONS: This report describes a case of sudden neurological deterioration due to hemorrhage in a patient with chondrosarcoma of the skull base. An emergency endoscopic endonasal approach for mass reduction and hematoma removal was effective in the acute setting. This approach revealed the suspected etiology of peritumoral hemorrhage, not intratumoral hemorrhage. https://thejns.org/doi/10.3171/CASE2460.

Comparative overall survival analysis of chordomas of the base of the skull from the Surveillance, Epidemiology, and End Results (SEER) program between 2000 and 2020.

Chordomas of the skull base are rare, slow growing, locally invasive cancers with limited long-term survival analysis reported in the literature. We seek to provide comparative survival analysis of patients on a long-term (20-year) basis using population-level data. The Surveillance, Epidemiology, and End Results (SEER) program was queried for cases of chordoma relegated to the base of the skull, diagnosed between 2000 and 2020. Demographic, disease, and treatment information were analyzed using Cox proportional hazards and log-rank comparisons. 630 patients with chordoma of the skull base were identified. Age ≤ 49 years at diagnosis was associated with increased five-, 10-, and 20-year overall survival (hazard ratio (HR) = 0.39, 0.33, and 0.30, respectively; p < 0.001 for all). Treatment with surgery and adjuvant radiotherapy was associated with increased five-, 10-, and 20-year survival (HR = 0.71, 0.79, and 0.79, respectively; p < 0.001 for all). On univariate analysis, widowed patients had decreased survival (20-year overall survival = 34.8% [15.3%-34.8%] compared to married patients (74.4% [68.1%-80.8%]. Surgery remains the primary treatment associated with increased survival among patients with chordoma of the skull base, with adjuvant radiotherapy serving a complimentary role. Demographic factors such as marital status are also associated with changes in survival.

Exceptionally giant neglected sacral chordoma in a post-poliotic residual paralysis patient - a rare case scenario.

Chordoma is a rare malignant tumour with an incidence of 0.1 case per 1 lakh population per year. The sacrococcygeal region is the most common site to be involved. Herein, we are reporting a case of sacral chordoma, who is a 32-year-old male patient, a known case of post-polio residual paralysis on the left lower limb, who presented with complaint of pain in the lower back and gluteal region for 2 years with swelling in the gluteal region for 1 year, which was gradually increasing in size for 1 year with associated weight loss. MRI revealed an ill-defined lytic expansile altered signal intensity lesion involving S3 to S5 and coccygeal vertebral bodies measuring 13.2 × 16.2 × 14 cm (ap × tr × cc) with adjacent large lobulated heterogeneous soft tissue component and showed multiple coarse calcifications. The lesion anteriorly displaced and abutted the rectum and was deriving its blood supply from branches of bilateral internal iliac arteries. The patient was planned and underwent wide-margin resection (middle sacrectomy with R0 margins with preservation of both S2 and right S3 nerve roots). Histologic Grade was reported to be G2, moderately differentiated, high grade. Pathologic stage classification was reported as pT3a. Postoperatively patient had the same neurological status and was discharged on advice to do full weight bearing walking and self-intermittent catheterisation and laxatives. He was on routine follow up and improved well symptomatically.

Muscle metastasis from cervical chordoma: a case report.

Chordomas are rare primary bone tumours that commonly occur in the sacrococcygeal and skull base region and have high rates of local recurrence. They have a locally aggressive course and the most common site of distant metastasis is the lung. The aim of this case report is to present the imaging findings of instance of muscle metastasis, a rare occurrence in cervical chordoma.

Case report of large solitary skull base metastasis from renal cell carcinoma as initial clinical presentation: Radiological findings and differentials.

A 58-year-old male with good past health presented with headache and visual disturbance for 1 month. Computed tomography (CT) and magnetic resonance imaging (MRI) were performed, showing a large aggressive midline mass with epicenter at the skull base and sellar-suprasellar region. There was marked heterogenous enhancement and intratumoral calcifications. It demonstrated clivus erosion, sphenoid sinus invasion, cavernous sinus invasion and optic chiasm compression. The imaging features were considered to be consistent with clival chordoma and the patent underwent emergent endoscopic transsphenoidal surgical excision. The difficult operation found an unexpected highly vascularized tumor and histopathology of the excision showed clear cell renal cell carcinoma metastasis. Subsequent work up of the patient with positron emission tomography-computed tomography (PET-CT) confirmed suspicion of the primary tumor, arising from left kidney. This case demonstrates an underestimated differential diagnosis of a large aggressive skull base mass as the first initial clinical presentation of metastatic disease.

Prognostic factors and overall survival in pelvic Ewing's sarcoma and chordoma: A comparative SEER database analysis.

Background: This study aimed to develop and validate nomograms to predict overall survival (OS) for pelvic Ewing's sarcoma (EWS) and chordoma, identify prognostic factors, and compare outcomes between the two conditions. Methods: We identified patients diagnosed with pelvic EWS or chordoma from the SEER database (2001-2019). Independent risk factors were identified using univariate and multivariate Cox regression analyses, and these factors were used to construct nomograms predicting 3-, 5-, and 10-year OS. Validation methods included AUC, calibration plots, C-index, and decision curve analysis (DCA). Kaplan-Meier curves and log-rank tests compared survival differences between low- and high-risk groups. Results: The study included 1175 patients (EWS: 611, chordoma: 564). Both groups were randomly divided into training (70 %) and validation (30 %) cohorts. OS was significantly higher for chordoma. Multivariate analysis showed year of diagnosis, income, stage, and surgery were significant for EWS survival, while age, time to treatment, stage, and surgery were significant for chordoma survival. Validation showed the nomograms had strong predictive performance and clinical utility. Conclusions: The nomograms reliably predict overall survival (OS) in pelvic EWS and chordoma, helping to identify high-risk patients early and guide preventive measures. The study also found that survival rates are significantly higher for chordoma, highlighting different prognostic profiles between EWS and chordoma.

Role of Proton Beam Therapy in Spinal Chordomas: A Narrative Review of The Literature.

Chordomas are rare malignant neoplasms arising from vestigial remnants of the embryonic notochord. Approximately 55-70% of chordomas develop within the vertebral column. Their affinity to develop within the bones of the axial skeleton and propensity to locally invade and recur makes them challenging candidates for complete surgical excision. Adjuvant therapies are hence necessary to improve outcomes; for which chemotherapy has been observed to be largely ineffective, owing to the tumour being resistant to it. Radiotherapy is the current adjuvant therapy of choice for chordoma management. Over the years, proton beam therapy (PBT) has been the subject of medical attention, given the dosimetric benefits it confers over traditional radiotherapy, allowing more concentrated radiation to be given to the target of interest and reducing damage to surrounding normal tissue. A review of the current literature reveals PBT offers significantly better outcomes when used as an adjuvant to maximal surgical resection rather than as a definitive therapy.

Three-dimensional virtual reality-assisted surgical planning for neuronavigated sacrectomy of a chordoma: a technical note.

PURPOSE: Sacral chordomas are slow growing but locally aggressive tumours with a high rate of local recurrence if not completely removed. Surgical resection with negative margins represents the most important survival predictor but it can be challenging to accomplish. Thanks to improvements in intraoperative imaging and surgical techniques, en bloc resection through a partial sacral resection with wide surgical margins has become feasible but it comes with a significant morbidity rate. In this technical note we detail the virtual reality-assisted surgical planning used during resection. METHODS: A 70-year-old patient underwent en bloc resection of the tumor by an antero-posterior two-stage surgery approach. Pre-operatively, based on MR- and CT-imaging, virtual objects were designed, representing the tumour, the surrounding bone and the neurovascular structures. This 3D-model was used to plan the well delimited partial sacral resection and the posterior surgical approach. Intraoperatively the instruments were registered, allowing for a real-time visualization of the tumor, of the neurovascular structures, and for an optimal margin control resection. RESULTS: Postoperatively the patient was intact in the lower extremities, without any deficit up to S1 roots. An intentional middle-low sacral amputation of S2-S5 roots was necessary to have a wide resection with free margins. At follow-up, the patient did not present any lower extremities motor deficit with an improvement of sensory function on S1 dermatome. CONCLUSION: Three-dimensional virtual reality-assisted surgical planning for neuronavigated sacrectomy in chordoma is useful, feasible and safe. This technology can increase surgeon's chances to perform a larger margin-free resection decreasing the risk of neurovascular damage.

Degenerative Atypia in Clival Chordoma: Two Case Reports.

In this study, we report surgical management combined with radiotherapy in two patients with typical chordoma. Different types of radiation have varied effects on chordomas when they are radiated. Classical cases display cellular atypia and fibrosis following irradiation, while necrosis and fibrosclerosis are observed after carbon ion therapy, implying that it is possible to control the tumor more effectively using carbon ion therapy with minimal side effects.

Clinical and Radiologic Follow-Up in Ecchordosis Physaliphora: A Case Series and Literature Review.

OBJECTIVE: This study endeavors to assess the clinical and radiologic findings of ecchordosis physaliphora (EP) in patients under long-term observation at our clinic as well as in cases reviewed from the existing literature. METHODS: In our study, we evaluated EP lesions in a total of 16 patients who underwent follow-up and treatment in the neurosurgical unit. We conducted a retrospective review using magnetic resonance imaging and computed tomography studies to confirm the diagnoses as EP. We conducted a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, encompassing a database search from inception to January 2024. We included confirmed cases of EP from both surgically and conservatively reported studies. RESULTS: Our study included a total of 16 patients, consisting of 9 (56.25%) men and 7 (43.75%) women, with an average age of 45 ± 17.3 years. Among them, 7 (43.75%) patients presented with headaches, while 3 (18.75%) reported hearing loss. Incidental EP was detected in 6 (37.5%) patients in the study during imaging performed for different indications. The key radiological features of EP comprised hypointensity on T1, hyperintensity on T2, and an absence of magnetic resonance imaging gadolinium enhancement. In 1 out of the 16 cases, we employed an endoscopic endonasal approach for resection, and there was no recurrence observed over an average postoperative follow-up period of 24 months. Among the 15 patients who underwent conservative follow-up, 12 (80%) had the classical type B EP, one (10%) patient exhibited benign notochordal tumor in the C2 vertebra, and another (10%) patient presented with a variant type EP. CONCLUSIONS: Utilizing a combination of imaging modalities, ensuring a clear radiological distinction between EP and chordoma, can offer substantial advantages in this context. Given that EP might be incidentally discovered and nonresistant symptoms may resolve on their own, considering conservative treatment before surgery may be a viable option in all cases.

Coccygeal tumours unveiled: a retrospective cohort analysis from a tertiary referral centre.

BACKGROUND: Isolated tumours affecting the coccyx are infrequent, with only a handful of documented cases in the literature. Herein, we highlight the most extensive consecutive case series involving various isolated coccyx tumours with varied clinical presentations and imaging features. METHODS: A retrospective search of our tertiary Orthopaedic oncology institute's oncology and Radiology database [Radiology Information System, Picture Archiving and Communication System, and Computerised Radiology Information System] for the keyword "Coccyx" and "Tumour" was performed over 15 years (between December 2007 and August 2022). Data collected was correlated with local histopathology and laboratory records. Patient demographics, clinical characteristics, and complementary imaging findings were recorded for analysis. RESULTS: One hundred and three lesions originating in the coccyx with a mean age of 62 years (range 25-90 years) were identified. There was a male preponderance with 59 male and 44 female patients (1.3:1.0). The most typical tumour noted was chordoma. Other lesions included a dermoid cyst, a myxopapillary ependymoma, a notochordal remnant, an osteochondroma, an Ewing sarcoma, and a teratoma. CONCLUSION: Our analysis suggests that most of the tumours involving coccyx are chordomas with a few rarely encountered benign and malignant tumours. Radiological imaging plays a vital role in characterising isolated tumours affecting the coccyx and guiding appropriate patient management. ADVANCES IN KNOWLEDGE: This is the largest reported series of coccygeal tumours. Chordoma is the commonest coccygeal tumour. Patients with unexplained coccydynia should undergo detailed investigations, preferably with cross-sectional imaging.

Interleukin-7 expression by CAR-T cells improves CAR-T cell survival and efficacy in chordoma.

Chordoma is a rare bone tumor that frequently recurs after surgery, and the prognosis is poor with current treatments. This study aimed to identify potential novel immunotherapeutic targets for chordomas by identifying target proteins in clinical samples as well as tumor microenvironmental factors to enhance efficacy. Fourteen chordoma samples were analyzed by single-cell RNA sequencing, and B7-H3 and IL-7 were identified as potential targets and potentiators, respectively. B7-H3-targeted chimeric antigen receptor T (CAR-T) cells and B7-H3 CAR-T cells expressing IL-7 were synthesized and their anti-tumor activity evaluated in vitro, including in primary chordoma organoid models. The B7-H3 CAR-T/IL-7 therapy showed enhanced cytotoxicity and prolonged duration of action against tumor cells. Additionally, IL-7 modulated favorable subpopulations of cultured CAR-T cells, diminished immune checkpoint expression on T-cell surfaces, and enhanced T-cell functionality. The incorporation of IL-7 molecules into the B7-H3 CAR structure augmented CAR-T-cell function and improved CAR-T-cell efficacy, thus providing a novel dual therapeutic strategy for chordoma treatment.

Clival chordomas and chondrosarcomas in Denmark-Outcomes in 33 patients following the national centralization of treatment in 2010.

PURPOSE: This 13-year consecutive case series aims to provide a comprehensive overview of all patients operated for clival chordomas and clival chondrosarcomas in Denmark since the centralization of treatment in 2010, comparing outcomes to international series. METHODS: This was a retrospective review of 33 patients with clival tumors, comprising 22 chordomas and 11 chondrosarcomas, who were treated at Copenhagen University Hospital between years 2010 and 2023. Data were collected from digital patient records and pathology reports. RESULTS: The symptoms leading to diagnosis primarily included double vision, headaches, and dizziness. In general, patients were in good health, with a mean Charlson Comorbidity Index score of 1.6. The complication rate of the index surgery was 51.5%. Adjuvant radiotherapy was applied in 51.5% of the cases. In patients with clival chordomas, the mean age was 51.1 years, ranging from 16 to 83 years. At the time of diagnosis, the mean tumor volume was 20.9 cm3 and the five-year overall survival rates were 79.1% (95% confidence interval (CI): 62.4-100). In patients with chondrosarcomas, the mean age was 48.2 years, ranging from 15 to 76 years. At the time of diagnosis, the mean tumor volume was 22.3 cm3 and the five-year overall survival 90% (95% CI: 73.2-100). CONCLUSION: The centralized treatment of clival tumors in Denmark demonstrates incidence, survival, and complication rates comparable to those found in other international series. Given the variations in treatment strategies, tumor localizations across series, and small sample sizes, the further analysis of larger compiled multicenter datasets for clival tumors could provide more solid evidence regarding the management of these rare tumors.

Conventional Spinal Chordomas: Investigation of SMARCB1/INI1 Protein Expression, Genetic Alterations in SMARCB1 Gene, and Clinicopathological Features in 89 Patients.

The partial loss of SMARCB1/INI1 expression has recently been reported in skull base conventional chordomas, with possible therapeutic implications. We retrospectively analyzed 89 patients with conventional spinal chordomas to investigate the differences in the immunohistochemical expression of SMARCB1/INI1 and the underlying genetic alterations in the SMARCB1 gene. Moreover, we assessed the correlation of clinicopathological features (age, gender, tumor size, tumor location, surgical margins, Ki67 labelling index, SMARCB1/INI1 pattern, previous surgery, previous treatment, type of surgery, and the Charlson Comorbidity Index) with patient survival. Our cohort included 51 males and 38 females, with a median age at diagnosis of 61 years. The median tumor size at presentation was 5.9 cm. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates were 90.8% and 54.9%, respectively. Partial SMARCB1/INI1 loss was identified in 37 (41.6%) patients with conventional spinal chordomas (27 mosaic and 10 clonal). The most frequent genetic alteration detected was the monoallelic deletion of a portion of the long arm of chromosome 22, which includes the SMARCB1 gene. Partial loss of SMARCB1/INI1 was correlated with cervical-thoracic-lumbar tumor location (p = 0.033) and inadequate surgical margins (p = 0.007), possibly due to the high degree of tumor invasiveness in this site. Among all the considered clinicopathological features related to patient survival, only tumor location in the sacrococcygeal region and adequate surgical margins positively impacted DFS. In conclusion, partial SMARCB1/INI1 loss, mostly due to 22q deletion, was detected in a significant number of patients with conventional spinal chordomas and was correlated with mobile spine location and inadequate surgical margins.

The impact of socioeconomic determinants on the access to care and survival in patients with spinal chordomas- a national cancer database analysis.

PURPOSE: Chordomas are rare malignant neoplasms primarily treated surgically. Disparities related to race and socioeconomic status, may affect patient outcomes. This study aims to identify prognostic factors for access to care and survival in patients with spinal chordomas. METHODS: The NCDB database was queried between the years 2004 and 2017. Kaplan-Meier curves were constructed to compare survival probabilities among different groups, based on race and socioeconomic determinents. RESULTS: 1769 patients were identified, with 87% being White, 5% Hispanic, 4% Black, and Asian each. The mean age was 61.3 years. Most patients received care at academic/research centers and lived in a large metropolitan area, with no difference between races. A significantly higher percentage of Black patients did not undergo surgery (p < 0.001), with no statistically significant difference in survival between races (p = 0.97). A higher survival probability was seen in patients with other government insurances (p < 0.0001), in higher income quartiles (p < 0.0001), in metropolitan areas (p = 0.023), and at an academic/research center (p < 0.0001). A lower survival probability was seen in patients who are uninsured, in rural areas, and at community cancer programs (p < 0.0001). CONCLUSION: This study highlights disparities in access to surgical intervention for patients with spinal chordomas, especially among Black individuals. It emphasizes the significant impact of insurance status and income on access to surgical care and highlights geographical and institutional variations in survival rates. Addressing socioeconomic differences is crucial for fostering equity in neurosurgical outcomes.

How to Prevent Local Recurrence of Sacral Chordoma Treated with Carbon-Ion Radiotherapy: An Analysis of the Risk Factors of Local Failure and an Adequate Disease Margin.

INTRODUCTION: Recent reports have described the usefulness of carbon ion radiotherapy (CIRT) for inoperable sacral chordomas. However, its long-term local control rate needs to be improved. The present study identified the risk factors that affect the local relapse of sacral chordomas and the appropriate margins from the tumors. METHODS: Forty-nine patients with sacral chordoma treated with CIRT between 2011 and 2022 were retrospectively analyzed. Factors predicting the risk of local recurrence were evaluated, including age, sex, tumor size, muscle invaded with tumor, and surgery before CIRT. To determine the appropriate margin, the distance between the clinical target volume (CTV) and the out-field recurrent lesions was analyzed. RESULTS: The patients included 37 males and 12 females with a mean age of 67.1 years. A multivariate analysis showed that a tumor size >8 cm and invasion into the gluteus maximus muscle were significant risk factors with hazard ratios of 5.56 and 15.20 (p = 0.02 and 0.01), respectively. Out-field recurrence occurred in 13 cases, with 6, 3, and 4 relapses occurring in the muscle, bone, and both, respectively. The tumor occurred within 20 mm from the CTV in 60% of relapses in the muscles. CONCLUSION: The current study presented novel findings on CIRT for sacral chordomas, although there were several limitations, such as a short follow-up period to investigate slow-growth tumors and a small number of tumor specimens owing to inoperative cases. A tumor size >8 cm and invasion into the gluteus maximus muscle were shown to be risk factors for recurrence in the treatment of sacral chordoma with CIRT. Our findings further suggest that an additional 2-cm margin from the CTV in the muscle fiber direction is recommended during CIRT.

Intraparenchymal Chordoma in the Brain Stem: A Review of Surgical Management and Case Highlight.

We present a rare case of an intraparenchymal chordoma in the brain stem of a 69-year-old male with a history of multiple chordoma recurrences. Chordomas are uncommon tumors that originate from notochordal remnants, with intraparenchymal presentations in the brain stem being particularly rare. A 69-year-old male with a history of clival chordoma three years after primary endoscopic resection and adjuvant proton-beam radiotherapy and a recurrence one year postoperatively for which he underwent a second surgery, presented with severe headaches, weakness, diaphoresis, and difficulty ambulating. Head CT in the ER revealed a 2.7 x 3.5 cm hyperdense lesion in the pons, indicating acute hemorrhage. Magnetic resonance imaging (MRI) suggested a hemorrhagic radiation-induced cavernoma. A right retrosigmoid craniotomy was performed, and the lesion was resected without major complications. Final pathology reported an intraparenchymal hemorrhagic chordoma. To our knowledge, this is the first case of intra-axial chordoma, particularly in the brain stem. It highlights the importance of considering intraparenchymal chordoma on the differential when evaluating for recurrence versus other treatment-induced pathologies and changes. This may prompt the neurosurgeon to reconsider treatment options and weigh the risks of watchful waiting versus biopsy or even aggressive surgical management.

Clinical characteristics and predisposing factors of lung metastasis in sacral chordoma: a cross-sectional cohort study of 221 cases.

Introduction: Limited studies are available on the topic of lung metastasis in sacral chordoma. The primary objective of this study was to investigate the prevalence, characteristics, associated factors, and prognosis of lung metastasis in sacral chordoma. Methods: A total of 221 cases with primary sacral chordoma, all of whom underwent surgical resection at our center, were included in this study. Comprehensive demographic information, imaging findings, and oncological evaluations were collected and thoroughly analyzed. The diagnosis of lung metastasis in the majority of cases was established through radiographic examinations. Results: The prevalence of lung metastasis in the cohort was 19.5%, with the lung emerging as the predominant site of distant metastasis. Recurrent chordoma cases exhibited a significantly higher lung metastasis rate in comparison to newly diagnosed chordoma cases (33.33% and 12.76%, p=0.0005). Patients with lung metastasis had a larger tumor size, a higher proportion of previous sacral chordoma surgeries and a greater likelihood of postoperative recurrence. Associated factors of lung metastasis were tumor size, postoperative recurrence and radiotherapy. Patients with lung metastasis exhibited decreased median overall survival (91 vs. 144 months for those without lung metastasis, p<0.05) and recurrence-free survival (27 vs. 68 months, p<0.001) times. Discussion: Lung is the most common site of distant metastasis in sacral chordoma with an incidence rate nearly 20%. Larger tumor size and postoperative recurrence are risk factors for lung metastasis while radiotherapy is a protective factor. Occurrence of lung metastasis in sacral chordoma is a negative prognostic factor.

Hypoxic Upregulation of IER2 Increases Paracrine GMFG Signaling of Endoplasmic Reticulum Stress-CAF to Promote Chordoma Progression via Targeting ITGB1.

Currently, the oncogenic mechanism of endoplasmic reticulum stress-CAF (ERS-CAF) subpopulation in chordoma remains unknown. Here, single-cell RNA sequencing, spatial transcriptomics, GeoMx Digital Spatial Profiler, data-independent acquisition proteomics, bulk RNA-seq, and multiplexed quantitative immunofluorescence are used to unveil the precise molecular mechanism of how ERS-CAF affected chordoma progression. Results show that hypoxic microenvironment reprograms CAFs into ERS-CAF subtype. Mechanistically, this occurrs via hypoxia-mediated transcriptional upregulation of IER2. Overexpression of IER2 in CAFs promotes chordoma progression, which can be impeded by IER2 knockdown or use of ERS inhibitors. IER2 also induces expression of ERS-CAF marker genes and results in production of a pro-tumorigenic paracrine GMFG signaling, which exert its biological function via directly binding to ITGB1 on tumor cells. ITGB1 inhibition attenuates tumor malignant progression, which can be partially reversed by exogenous GMFG intervention. Further analyses reveal a positive correlation between ITGB1high tumor cell counts and SPP1+ macrophage density, as well as the spatial proximity of these two cell types. 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.