Primary Osseous Tumors Research Articles

Racial disparities in the management and outcomes of primary osseous neoplasms of the spine: a SEER analysis.

Primary osseous neoplasms of the spine, including Ewing's sarcoma, osteosarcoma, chondrosarcoma, and chordoma, are rare tumors with significant morbidity and mortality. The present study aims to identify the prevalence and impact of racial disparities on management and outcomes of patients with these malignancies. The 2000 to 2020 Surveillance, Epidemiology, and End Results (SEER) Registry, a cancer registry, was retrospectively reviewed to identify patients with Ewing's sarcoma, osteosarcoma, chondrosarcoma, or chordoma of the vertebral column or sacrum/pelvis. Study patients were divided into race-based cohorts: White, Black, Hispanic, and Other. Demographics, tumor characteristics, treatment variables, and mortality were assessed. 2,415 patients were identified, of which 69.8% were White, 5.8% Black, 16.1% Hispanic, and 8.4% classified as "Other". Tumor type varied significantly between cohorts, with osteosarcoma affecting a greater proportion of Black patients compared to the others (p < 0.001). A lower proportion of Black and Other race patients received surgery compared to White and Hispanic patients (p < 0.001). Utilization of chemotherapy was highest in the Hispanic cohort (p < 0.001), though use of radiotherapy was similar across cohorts (p = 0.123). Five-year survival (p < 0.001) and median survival were greatest in White patients (p < 0.001). Compared to non-Hispanic Whites, Hispanic (p < 0.001) and "Other" patients (p < 0.001) were associated with reduced survival. Race may be associated with tumor characteristics at diagnosis (including subtype, size, and site), treatment utilization, and mortality, with non-White patients having lower survival compared to White patients. Further studies are necessary to identify underlying causes of these disparities and solutions for eliminating them.

Efficacy and safety of COVID-19 vaccines for patients with spinal tumors receiving denosumab treatment: An initial real-clinical experience study.

Even if COVID-19 vaccine has gradually been adopted in the world, information of side effects and crosstalk in patients with spinal tumors is absent due to the exclusion from clinical research. In this research, we aimed to investigate the efficacy and safety for the patients with spinal tumors treated by denosumab. In this retrospective research, 400 patients under treatment of denosumab against spinal tumors in real-clinical experience were grouped into two cohorts according to the treatment of COVID-19 vaccine. And linked hospital data, serum samples and unsolicited related adverse events had been collected from January 22nd 2021 to June 1st 2021 respectively. 233 patients of all participants who received regular treatment of denosumab were vaccinated by mRNA or inactivated vaccine. Patients of metastatic disease and primary osseous spinal tumor showed similar distribution in both two groups. Over the study period, within 176 patients tested the status of serologic response of vaccine, 88(81.48%) and 41(87.23%) individuals injected one or two inactivated vaccines had effective antibody against SARS-CoV-2 infections. As 21 patients (85.71%) treated by mRNA vaccine did. Considering of the safety of vaccine, most common systemic adverse events were nausea or vomiting (45 events vs 23events). Interestingly, fewer participants in the vaccine group were statistically recorded in local adverse events than in the placebo group (16 events vs 33 events). Our initial real-clinical experience suggests that COVID-19 vaccines are likely safe and effective in in patients with spinal tumors receiving denosumab treatment.

Tumors of the Posterior Elements of the Spine in Children-an Overview.

In this narrative review, we aim to describe the clinical features, diagnosis, and management of common primary osseous tumors affecting the posterior elements of the spine in children. We searched PubMed, Mendeley, and Google Scholar using the terms primary osseous tumors of the spine in children, tumors of the posterior elements of the spine, and names of individual tumors. The clinical features, investigations, and treatment modalities were analyzed, and a narrative review of the topic was prepared. We have included 54 studies published in the last 20years. The majority are isolated reports or case series. Tumors of the posterior elements of the spine are rare. They are common in children and the majority of them are benign. Pain and deformity are common presentations. It is better to perform thorough investigations of children complaining of back pain to rule out primary tumors of the posterior elements of the spine.

LncSNHG14 promotes nutlin3a resistance by inhibiting ferroptosis via the miR-206 /SLC7A11 axis in osteosarcoma cells.

The most prevalent form of primary osseous malignant tumor in adolescents and children is osteosarcoma (OS). A combination of surgery and neoadjuvant/post-surgery chemotherapy is currently the standard therapy. While the chemoresistance associated with OS generally leads to poor efficacy of therapeutic agents, the relevant molecular interaction is still elusive. Here, the lncRNA (long non-coding RNA) SNHG14 was found to be significantly upregulated in the nutlin3a-resistant OS cell line NR-SJSA1 and contributes to treatment resistance by suppressing ferroptosis. In NR-SJSA1 cells, knockdown of LncRNA SNHG14 resulted in a reversal of drug resistance and activation of ferroptosis, which disappeared when ferrostatin-1, a ferroptosis inhibitor, was added. Mechanistically, lncRNA SNHG14 targeted and down-regulated the expression of miR-206, further affecting the common ferroptosis inhibitor SLC7A11, and preventing NR-SJSA1 cells from undergoing ferroptosis. In conclusion, our findings highlight the involvement of lncRNA SNHG14 in ferroptosis and chemotherapy resistance of nutlin3a-resistant NR-SJSA1 cells, thus shedding new insight on how to overcome drug resistance in osteosarcoma cells and improve treatment efficacy.

Minimally Invasive Resection of Benign Osseous Tumors of the Spinal Column: 10 Years' Experience and Long-Term Outcomes of a Specialized Center.

Background and Objectives: Benign osseous tumors of the spinal column comprise about 10% of all spinal tumors and are rare cause for surgery. However, these tumors pose various management challenges and conventional surgery may be associated with significant morbidity. Previous reports on minimally invasive resection of these lesions are rare. We report a series of patients managed by total resection of benign osseous spine tumors using MIS techniques. Surgical decisions and technical considerations are discussed. Materials and Methods: A retrospective evaluation of prospectively collected data of patients who underwent minimally invasive surgery for removal of benign osseous vertebral tumors. Demographic, clinical and radiographic features, operative details and final pathological reports were summarized. Primary outcomes were completeness of tumor resection and pain relief assessed by VAS for back and leg pain. Secondary outcome measures were recurrence of tumor on repeat post-operative MRI and postoperative unstable deformity on standing scoliosis X-rays. Results: This series included 32 cases of primary osseous spine tumors resected by minimally invasive techniques. There were 17 males and 15 females aged 5-68 years (mean 23.3). The follow-up period was 8-90 months (mean 32 months) and the preoperative symptoms duration was 9-96 months. Axial spinal pain was the presenting symptom in all the patients. Five patients also complained about radicular pain and four patients had antalgic scoliosis. The tumor involved the thoracic spine in 12 cases, the lumbar segment in 11, the cervical in 5 and the sacral area in 4 cases. Complete tumor removal was performed in all patients. No procedure-related complications were encountered. Histopathology showed osteoid osteoma in 24 patients, osteoblastoma in 5 patients, and fibrous dysplasia, fibroadenoma and eosinophilic granuloma in one case each. All patients experienced significant pain relief after surgery, and had stopped pain medications by 12 months postoperatively. No patient suffered from tumor recurrence or spinal deformity. Conclusions: Minimally invasive surgery is feasible for total removal of selected benign vertebral tumors and may have some advantages over conventional surgical techniques.

Chondrosarcoma of the Chest Wall: A Single Institution Review of 50 Cases.

Chondrosarcoma (CS) is most common primary osseous tumor of the chest wall. The aim of this study was to report results from surgical procedures and evaluate clinical factors predicting survival of patients with chest wall CSs treated in a single tertiary sarcoma center. Fifty patients with primary CS located in the ribs and sternum were included. Details of the clinical data and oncological outcomes, including local recurrence (LR) and disease-specific survival (DSS), were collected. The tumor was primarily originated in the sternum in 6 patients (12.5%) and in ribs 2 to 11 in the remaining patients. Specimens were histologically graded 1 in 13 patients (26%), 2 in 28 (56%), 3 in 8 (16%), and 1 (2%) as mesenchymal grade 3 CS. R0 margins were obtained in all cases. Reconstruction was warranted in 47 (94%) cases. Local recurrence developed in 3 (6%) patients, and the median time to LR was 17 (range, 16-68) months. Eight (16%) patients developed metastasis. Increasing tumor volume was a statistically significant factor for reduction of DSS. Chondrosarcoma of the chest wall can be treated effectively with clear margins, resulting in lower LR rate and higher DSS than CS of the extremities and pelvis. Metastasis of the chest wall mostly occurs in high-grade tumors, and the locations of the metastases differ greatly from those observed in CS of the extremities and pelvis. Metastases are commonly extrapulmonary, indicating the need for postoperative follow-up with multiple imaging modalities to monitor recurrence and metastases.

Benign primary bone tumors, long-term management into adulthood

Identifying a benign primary osseous tumor is critically important, and adults and pediatric patients manifest with different symptoms.Incorrect treatment may allow a curable neoplasm to progress into a lethal one, resulting in patient morbidity and mortality. Once confirmed as a primary bone tumor, it is important to understand the subtype of tumor and whether it is a malignant or benign neoplasm. In adults, about 80% of PBTS’s are malignant while only 40% of these tumors are malignant in children. The goal of this study is to review the special considerations for pediatric and adult benign tumors.

Chondrosarcoma patient characteristics, management, and outcomes based on over 5,000 cases from the National Cancer Database (NCDB).

IntroductionChondrosarcoma, although relatively uncommon, represents a significant percentage of primary osseous tumors. Nonetheless, there are few large-cohort, longitudinal studies of long-term survival and treatment outcomes of chondrosarcoma patients and none using the National Cancer Database (NCDB).MethodsChondrosarcoma patients were identified from the 2004–2015 NCDB datasets and divided on three primary tumor sites: appendicular, axial, and other. Demographic, treatment, and long-term survival data were determined for each group. Multivariate Cox analysis and Kaplan-Meier survival curves were generated to assess long-term survival over time for each.ResultsIn total, 5,329 chondrosarcoma patients were identified, of which 2,686 were appendicular and 1,616 were axial. Survival was higher among the appendicular cohort than axial at 1-year, 5-year, and 10-year (89.52%, 75.76%, and 65.24%, respectively). Multivariate Cox analysis identified patients in the appendicular cohort to have significantly greater likelihood of death with increasing age category, distant metastases at presentation, and male sex (p<0.001 for each). Best outcomes for seen for those undergoing surgical treatment (p<0.001). Patients in the axial cohort were with increased likelihood of death with increasing age category and distant metastases (p<0.001), while surgical treatment with or without radiation were associated with a significant decrease (p<0.001). Kaplan-Meier survival analysis showed worst survival for the axial cohort (p<0.001) and patients with distant metastases at presentation (p<0.001). Survival was not significantly different between older (2004–2007) and more recent years (2012–2016) (p = 0.742).ConclusionsFor both appendicular and axial chondrosarcomas, surgical treatment remains the mainstay of treatment due to its continued superiority for the long-term survival of patients, although advancements in survival over the last decade have been insignificant. Presence of distant metastases and axial involvement are significant, poor prognostic factors perhaps because of difficulty in surgical excision or extent of disease.

Atypical presentation of the World Health Organization Grade 1 meningioma: A case report

Meningiomas are the most common benign neoplasm of the brain whereas ectopic presentation, although reported, is rare. Among these ectopic tumors, there are a group of purely intraosseous meningiomas, which usually are diagnosed differentially from common primary osseous tumor such as fibrous dysplasia and osteoid osteoma. The World Health Organization (WHO) Grade 1 meningioma with an involvement of scalp, calvarial bone, dura, and brain seen rarely. This type of atypical presentation of the WHO Grade 1 meningioma rarely documented. The main theories to justify the unusual topography appear to be embryological remains of neuroectodermal tissue or cellular dedifferentiation. Surgical treatment seems the best curative option. Meningioma with bony involvement could be very aggressive tumor, need to prepare accordingly for surgery.

Primary Malignant Osseous Neoplasms in the Hand.

Primary malignant osseous neoplasms of the hand are rare malignancies. Comprehensive demographic and survival data regarding primary malignant osseous neoplasms of the hand are lacking in the literature. Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified all patients with primary malignant osseous neoplasms of the hand diagnosed between 1983 and 2015. Demographic data were searched for primary osseous neoplasms in the hand and higher incidence of histological subtype. A total of 197 patients were analyzed: 103 patients were diagnosed with histologically low-grade tumor, and 31 were diagnosed with high-grade tumor. Five-year cancer-specific and overall survival rates for the entire cohort were 91.4% and 81.9%, respectively. Histological high tumor grade and regional stage from SEER historic stage data were associated with unfavorable cancer-specific survival. Special caution is required if patients have histologically high-grade tumor or tumor extending beyond the periosteum into surrounding joints, as these features worsen cancer-specific mortality.

Primary Osseous Spine Tumors in Adults: A Review and Update on Diagnosis and Treatment

Objective: This article aims to provide a convenient and comprehensive review describing unique features of the most common primary osseous spine tumors, as well as current diagnostic and therapeutic modalities for each tumor. Background: Primary osseous spine tumors are a rare and diverse group of neoplasms with varying biologic behavior. Clinical, radiographic, and pathologic correlation is critical in making a correct diagnosis. Prompt treatment is necessary to optimize clinical outcomes, and is based on tumor type, location, and disease stage. Most patients with spinal tumors present with a history of pain often similar in quality and intensity as non-tumoral etiologies of back pain. Spinal neoplasms, especially malignant tumors, require a multidisciplinary approach and are best treated in dedicated cancer centers to mitigate incorrect diagnoses and inappropriate treatment. Methods: A literature review was conducted using PubMed and EBSCO. Multiple search queries for relevant articles between 2014 to present were included. Preference was given to recent articles with clinical evidence, current treatment, diagnostic modalities and/or future potential therapies and diagnostic strategies. Results: Numerous modalities including surgery, chemotherapy, evolving immunologic and targeted therapies as well as stereotactic external beam radiation therapy are utilized to optimize care. Still, current therapeutic strategies result in significant morbidity and mortality and local disease recurrence and systemic relapse are common despite chemotherapy and advanced surgical techniques. Conclusion: Because primary spinal tumors are uncommon, level I and II data are scarce though novel treatment strategies are emerging. Medical and orthopaedic oncologists and spine surgeons therefore should have a fundamental knowledge of the current state of literature pertaining to this topic.

Nomograms to predict lung metastasis probability and lung metastasis subgroup survival in malignant bone tumors.

The aim of this study was to construct and validate nomograms for predicting lung metastasis and lung metastasis subgroup overall survival in malignant primary osseous neoplasms. Least absolute shrinkage and selection operator, logistic and Cox analyses were used to identify risk factors for lung metastasis in malignant primary osseous neoplasms and prognostic factors for overall survival in the lung metastasis subgroup. Further, nomograms were established and validated. A total of 3184 patients were collected. Variables including age, histology type, American Joint Committee on Cancer T and N stage, other site metastasis, tumor extension and surgery were extracted for the nomograms. The authors found that nomograms could provide an effective approach for clinicians to identify patients with a high risk of lung metastasis in malignant primary osseous neoplasms and perform a personalized overall survival evaluation for the lung metastasis subgroup.

Role of Trans-Arterial Embolization in Management of Bone Tumors

Abstract Background: Trans-arterial embolization (TAE) is a prom-ising less aggressive modality in either primary treatment or adjuvant to surgical management of bone tumors. The main aim is to induce necrosis and decrease bleeding and therefore facilitate resection. Palliation of compression manifestation of inoperable bone neoplasm is another indication of TAE. Frequent tumors selected to this modality include vascular tumors (particularly metastases), aneurysmal bone cysts (ABC), giant cell tumor (GCT), and osteosarcoma. Aim of Study: Our aim is to assess the role of embolization in management of bone tumors. Patients and Methods: The current study prospectively evaluated 33 patients (23 males and 10 females). Their age ranged from 9 to 69 years (mean age of 43.246±19.65). Extremities, hip, vertebrae, and skull were involved by variety of bony tumors. Sixteen patients were affected by primary osseous tumors, while 17 patients had metastases. A transar-terial embolization was done in all patients as a preoperative procedure in 15 patients, definite treatmentof primary benign inaccessible tumors in 6 patients, prebiopsy embolization in 6 patients, and as a palliative treatment in 6 patients. Results: Technical success was obtained in 30 out of 33 cases with percentage of 90.9%. All benign and primary malignant bony tumors showed technical success while, 82.4% of metastatic lesions did. Clinical success was achieved in 73.3% cases of first group, 83.3% of second group, 100% of third group and 66.7% of fourth group. Four patients (12.1%) showed no clinical improvement with 9% lost follow-up. Five out of 6 benign tumors showed clinical success (83.3%) as the sixth case lost follow-up (16.7%). Embolization of 9 of primary malignant lesions was clinically successful (90%), whereas 12 out of 17 metastatic lesions were improved clinically (70.6 %), 3 cases showed no clinical success (17.6%), and 2 cases were lost at follow-up (11.8%).Conclusion: A high consideration should be given totran-sarterialembolization in the algorithmic treatment strategy of bone tumors as it is much safer and effective tool when diminution of bleeding and compression manifestations is to be specifically aimed.

Despite Advances in Tumor Management Modalities, Surgery Prevails as Best Predictor of Survival for Osteosarcoma: An Analysis of Primary Osseous Tumor Characteristics, Management, and Outcomes from the National Cancer Database

Ottesen, Taylor D. BS; Shultz, Blake S. BS; Munger, Alana M. MD; Sibindi, Cosmas BS; Yurter, Alp BS; Varthi, Arya D. MD; Grauer, Jonathan D. MD, FACS Author Information

Chondroblastoma Expresses RANKL by RNA In Situ Hybridization and May Respond to Denosumab Therapy.

Lesions of bone featuring osteoclast-like giant cells comprise a diverse group of entities, including giant cell tumor (GCT) of bone, chondroblastoma, and aneurysmal bone cyst, among others. The receptor activator of nuclear factor-κB ligand (RANKL) has been implicated in the pathogenesis of GCT of bone and may play a role in the pathogenesis of other giant cell-rich lesions as well. In addition, RANKL inhibitors (denosumab) have also been shown to have some efficacy in treating some giant cell-rich lesions. Herein, we examine RANKL expression by RNA in situ hybridization in a total of 84 osseous lesions with a focus on chondroblastoma, GCT, fibrous dysplasia, and aneurysmal bone cyst. The lesions were tested for RANKL expression using a chromogenic RNA in situ hybridization assay. RANKL expression was identified in 24/25 (96%) GCT, 24/26 (92%) chondroblastomas, 6/7 (86%) aneurysmal bone cysts, and 3/16 (19%) patients with fibrous dysplasia. RANKL expression was statistically lower in chondroblastoma and aneurysmal bone cyst compared with GCT. RANKL reactivity in fibrous dysplasia was exclusively seen in the 3 cases with osteoclast-type giant cells. Our results indicate a high proportion of chondroblastomas, GCTs, and aneurysmal bone cysts express RANKL while reactivity in fibrous dysplasia is dependent on the presence of osteoclast-type giant cells. On the basis of the success of denosumab therapy for GCTs, our results indicate that it may be a potential therapeutic option in other primary osseous tumors.

Unusual Histological Variant of a Primary Osseous Tumor of the Jaw in a 27-Year-Old Female: Review of the Literature and Case Presentation

Unusual Histological Variant of a Primary Osseous Tumor of the Jaw in a 27-Year-Old Female: Review of the Literature and Case Presentation

Laminopedicular Osteotomy for En-bloc Resection of Posterolateral Thoracic Osteoblastoma: Technical Note

Osteoblastomas are a type of primary osseous neoplasm that exhibit a proclivity for the spine, primarily the posterior elements. While generally considered benign, some variants of osteoblastoma exhibit aggressive growth with lytic osseous destruction and soft tissue invasion, with some recurring after initial treatment. Given their proximity to vital structures and potential for rapid growth, these tumors are often managed with aggressive surgery, with en-bloc resection preferred. Here we describe our osteotomy technique for resecting en bloc a posterolateral thoracic osteoblastoma causing rapidly progressive myelopathy in a 17-year-old male. Successful treatment of osteoblastoma in a 17-year-old male demonstrates the efficacy of our laminopedicular osteotomy technique in treating 1 instance of a rapidly presenting spinal tumor. This case bolsters the growing body of literature that favors the outcomes of a more conservative approach to en-bloc resection of spinal tumors.

Risk factors for lung metastasis at presentation with malignant primary osseous neoplasms: a population-based study

BackgroundLarge population-based studies of risk factor for lung metastases at the presentation with primary osseous neoplasms are lacking and necessary. We aim to examine potential risk factors of lung metastases at presentation with primary osseous neoplasms using Surveillance, Epidemiology, and End Results (SEER) database tool.MethodsWe collected patients diagnosed with primary osseous neoplasms between 2010 and 2015 from the SEER database. Patients were divided into two groups: patients with lung metastases or patients without lung metastases. Patient characteristics such as age, sex, race, tumor size, histologic types, histologic grade, and lung metastasis were collected. Univariate and multivariate logistic regression analyses were applied to determine which characteristics were risk factors for lung metastasis at diagnosis.ResultsA total of 4459 patients were collected, and 507 patients had lung metastases at presentation. Data on age, race, gender, primary site, grade, tumor size, and histology types were enrolled into the multivariate logistic analysis. Higher grade (OR = 5.197, 95% CI 3.328 to 8.117), histology type (Ewing sarcoma: OR = 1.432, 95% CI 1.020 to 2.009; osteosarcoma: OR = 1.597, 95% CI, 1.073 to 2.377), and larger tumor size (≥ 5 cm: OR = 3.528, 95% CI 2.370 to 5.251) were associated with an increased risk of lung metastasis at presentation.ConclusionHistology types (osteosarcoma and Ewing sarcoma) were related to a higher risk of lung metastases in primary osseous neoplasms patients. Patients with osteosarcoma and lager tumors or higher tumor grade were associated with higher possibility of lung metastases. Patients with Ewing sarcoma and larger tumors have more tendency of lung metastases. These patients are supposed to receive chest CT scans at the presentation with primary osseous neoplasms.

Lymph node metastasis in extremity chondrosarcomas: A series of four cases.

Background:Primary bone sarcomas mainly metastasize through haematogenous route and rarely through lymph nodes due to paucity of lymphatic channels in the bone (1). Nodal spread in chondrosarcoma is extremely rare and there are two reported cases in literature including one previously published by our institute (3, 5).Aims and Objectives:We present a series of chondrosarcoma cases (primary tumour located in the scapula, proximal femur, proximal humerus and pelvis), presenting with lymph node metastasis, treated at our institute. We assessed the oncological outcome of these cases and the impact of nodal metastasis on survival.Materials and Methods:Between January 2006 and December 2015, 243 patients of extremity and pelvic chondrosarcoma were operated at our institute. These cases were retrieved from a prospectively maintained database. Four (1.6%) of these patients developed lymph node metastasis. Clinical and radiological details of these cases were retrieved from electronic medical records and case files. Histopathology of the primary chondrosarcoma lesion and nodal metastasis was reconfirmed by a pathologist specializing in sarcomas.Conclusion:Lymph node metastasis though extremely rare in primary osseous chondrosarcoma, definitely affects their survival adversely. The rarity of the occurrence of lymph node metastasis in primary osseous tumors, especially chondrosarcoma highlights the need for multi institutional studies to pool knowledge and evaluate the prognostic significance and etiopathogenesis of lymph node metastasis in primary bone chondrosarcoma.

Knockdown of cytokeratin 8 overcomes chemoresistance of chordoma cells by aggravating endoplasmic reticulum stress through PERK/eIF2\u03b1 arm of unfolded protein response and blocking autophagy

Chordoma is a malignant primary osseous spinal tumor with pronounced chemoresistance. However, the mechanisms of how chordoma cells develop chemoresistance are still not fully understood. Cytokeratin 8 (KRT8) is a molecular marker of notochordal cells, from which chordoma cells were believed to be originated. In this study, we showed that either doxorubicin or irinotecan promoted KRT8 expression in both CM319 and UCH1 cell lines, accompanied by an increased unfolded protein response and autophagy activity. Then, siRNA-mediated knockdown of KRT8 chemosensitized chordoma cells in vitro. Mechanistic studies showed that knockdown of KRT8 followed by chemotherapy aggravated endoplasmic reticulum stress through PERK/eIF2α arm of unfolded protein response and blocked late-stage autophagy. Moreover, suppression of the PERK/eIF2α arm of unfolded protein response using PERK inhibitor GSK2606414 partially rescued the apoptotic chordoma cells but did not reverse the blockage of the autophagy flux. Finally, tumor xenograft model further confirmed the chemosensitizing effects of siKRT8. This study represents the first systematic investigation into the role of KRT8 in chemoresistance of chordoma and our results highlight a possible strategy of targeting KRT8 to overcome chordoma chemoresistance.