Germline findings in cancer predisposing genes from a small cohort of chordoma patients.

INTRODUCTION: Chordoma is a rare slow-growing tumor that occurs along the length of the spinal axis and arises from primitive notochordal remnants (Stepanek et al., Am J Med Genet 75:335-336, 1998). Most chordomas are sporadic, but a small percentage of cases are due to hereditary cancer syndromes (HCS) such as tuberous sclerosis 1 and 2 (TSC1/2), or constitutional variants in the gene encoding brachyury T (TBXT) (Pillay et al., Nat Genet 44:1185-1187, 2012; Yang et al., Nat Genet 41:1176-1178, 2009). PURPOSE: The genetic susceptibility of these tumors is not well understood; there are only a small number of studies that have performed germline genetic testing in this population. METHODS: We performed germline genetic in chordoma patients using genomic DNA extracted by blood or saliva. CONCLUSION: We report here a chordoma cohort of 24 families with newly found germline genetic mutations in cancer predisposing genes. We discuss implications for genetic counseling, clinical management, and universal germline genetic testing for cancer patients with solid tumors.

Multidisciplinary surgical considerations for en bloc resection of sacral chordoma: review of recent advances and a contemporary single-center series.

OBJECTIVE: Contemporary management of sacral chordomas requires maximizing the potential for recurrence-free and overall survival while minimizing treatment morbidity. En bloc resection can be performed at various levels of the sacrum, with tumor location and volume ultimately dictating the necessary extent of resection and subsequent tissue reconstruction. Because tumor resection involving the upper sacrum may be quite destabilizing, other pertinent considerations relate to instrumentation and subsequent tissue reconstruction. The primary aim of this study was to survey the surgical approaches used for managing primary sacral chordoma according to location of lumbosacral spine involvement, including a narrative review of the literature and examination of the authors' institutional case series. METHODS: The authors performed a narrative review of pertinent literature regarding reconstruction and complication avoidance techniques following en bloc resection of primary sacral tumors, supplemented by a contemporary series of 11 cases from their cohort. Relevant surgical anatomy, advances in instrumentation and reconstruction techniques, intraoperative imaging and navigation, soft-tissue reconstruction, and wound complication avoidance are also discussed. RESULTS: The review of the literature identified several surgical approaches used for management of primary sacral chordoma localized to low sacral levels (mid-S2 and below), high sacral levels (involving upper S2 and above), and high sacral levels with lumbar involvement. In the contemporary case series, the majority of cases (8/11) presented as low sacral tumors that did not require instrumentation. A minority required more extensive instrumentation and reconstruction, with 2 tumors involving upper S2 and/or S1 levels and 1 tumor extending into the lower lumbar spine. En bloc resection was successfully achieved in 10 of 11 cases, with a colostomy required in 2 cases due to rectal involvement. All 11 cases underwent musculocutaneous flap wound closure by plastic surgery, with none experiencing wound complications requiring revision. CONCLUSIONS: The modern management of sacral chordoma involves a multidisciplinary team of surgeons and intraoperative technologies to minimize surgical morbidity while optimizing oncological outcomes through en bloc resection. Most cases present with lower sacral tumors not requiring instrumentation, but stabilizing instrumentation and lumbosacral reconstruction are often required in upper sacral and lumbosacral cases. Among efforts to minimize wound-related complications, musculocutaneous flap closure stands out as an evidence-based measure that may mitigate risk.

Prognostic nomogram in middle-aged and elderly patients with chordoma: A SEER-based study.

BACKGROUND: Chordoma is a bone tumor that tends to occur in middle-aged and elderly people. It grows relatively slowly but is aggressive. The prognosis of middle-aged and elderly patients with chordoma is quite different from that of young patients with chordoma. OBJECTIVES: The purpose of the research was to construct a nomogram to predict the Individualized prognosis of middle-aged and elderly (age greater than or equal to 40 years) patients with chordoma. METHODS: In this study, we screened 658 patients diagnosed with chordoma from 1983 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. We determined the independently prognostic factors that affect the survival of patients by univariate and multivariate Cox proportional hazards model. Based on the independent prognostic factors, we constructed a nomogram to predict the overall survival (OS) rates of middle-aged and elderly patients with chordoma at 3 and 5 years. The validation of this nomogram was completed by evaluating the calibration curve and the C-index. RESULTS: We screened a total of 658 patients and divided them into two cohort. Training cohort had 462 samples and validation cohort had 196 samples. The multivariate Cox proportional hazards model of the training group showed an association of age, tumor size, histology, primary site, surgery, and extent of disease with OS rates. Based on these results, we constructed the corresponding nomogram. The calibration curve and C-index showed the satisfactory ability of the nomogram in terms of predictive ability. CONCLUSION: Nomogram can be an effective prognostic tool to assess the prognosis of middle-aged and elderly patients with chordoma and can help clinicians in medical decision-making and enable patients to receive more accurate and reasonable treatment.

Single-cell sequencing reveals VEGFR as a potential target for CAR-T cell therapy in chordoma.

BACKGROUND: Chordomas are rare osseous neoplasms with a dismal prognosis when they recur. Here we identified cell surface proteins that could potentially serve as novel immunotherapeutic targets in patients with chordoma. METHODS: Fourteen chordoma samples from patients attending Xuanwu Hospital Capital Medical University were subjected to single-cell RNA sequencing. Target molecules were identified on chordoma cells and cancer metastasis-related signalling pathways characterised. VEGFR-targeting CAR-T cells and VEGFR CAR-T cells with an additional TGF-ß scFv were synthesised and their in vitro antitumor activities were evaluated, including in a primary chordoma organoid model. RESULTS: Single-cell transcriptome sequencing identified the chordoma-specific antigen VEGFR and TGF-ß as therapeutic targets. VRGFR CAR-T cells and VEGFR/TGF-ß scFv CAR-T cells recognised antigen-positive cells and exhibited significant antitumor effects through CAR-T cell activation and cytokine secretion. Furthermore, VEGFR/TGF-ß scFv CAR-T cells showed enhanced and sustained cytotoxicity of chordoma cell lines in vitro compared with VRGFR CAR-T cells. CONCLUSIONS: This study provides a comprehensive single-cell landscape of human chordoma and highlights its heterogeneity and the role played by TGF-ß 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-ß signalling, may augment the efficacy of CAR-T cells.

N6-methyladenosine-modified circTEAD1 stabilizes Yap1 mRNA to promote chordoma tumorigenesis.

BACKGROUND: Chordoma, a rare bone tumour with aggressive local invasion and high recurrence rate with limited understanding of its molecular mechanisms. Circular RNAs (circRNAs) have been extensively implicated in tumorigenesis, yet their involvement in chordoma remains largely unexplored. N6-methyladenosine (m6A) modification holds a crucial function in regulating protein translation, RNA degradation and transcription. METHODS: Initially, screening and validation of circTEAD1 in chordoma were conducted by high-throughput sequencing. Subsequently, sh-circTEAD1 and an overexpression plasmid were constructed. Colony formation assays, cell counting kit-8, Transwell and wound healing assays were utilized to validate the function of circTEAD1 in vitro. RNA pull-down assays identified the binding proteins of circTEAD1, which underwent verification through RNA immunoprecipitation (RIP). Methylated RIP assays were conducted to detect the m6A binding sites. Following this, luciferase assay, RT-qPCR, RIP and Western blotting analyses were conducted, revealing that Yap1 was the direct target of circTEAD1. Afterwards, the same methods were utilized for the validation of the function of Yap1 in chordoma in vitro. Finally, the regulatory relationship between circTEAD1 and Yap1 in chordoma was verified by an in vivo tumour formation assay. RESULTS: CircTEAD1 was identified as an upregulated circRNA in chordoma specimens, with heightened circTEAD1 expression emerging as a prognostic indicator. In vitro experiments convincingly demonstrated that circTEAD1 significantly promoted chordoma cell invasion, migration and aggressiveness. Furthermore, the analysis revealed that methyltransferase-like 3-mediated m6A modification facilitated the cytoplasmic export of circTEAD1. The circTEAD1/IGF2BP3/Yap1 mRNA RNA-protein ternary complex not only bolstered the stability of Yap1 mRNA but also exerted a pivotal role in driving chordoma tumorigenesis. CONCLUSIONS: In this study, the role of m6A-modified circTEAD1 in chordoma was identified. The findings offer novel insights into the potential molecular targets for chordoma therapy, shedding light on the intricate interplay between circRNAs, m6A modification and Yap1 mRNA in chordoma pathogenesis.

Complications and local recurrence of chondrosarcoma and chordoma treated by total tumor resection in thoracic and lumbar spine.

BACKGROUND: En bloc resection of spinal tumors is challenging and associated with a high incidence of complications; however, it offers the potential to reduce the risk of recurrence when a wide margin is achieved. This research aims to investigate the safety and efficacy of en bloc resection in treating thoracic and lumbar chondrosarcoma/chordoma. METHODS: Data from patients diagnosed with chondrosarcoma and chordoma in the thoracic or lumbar region, who underwent total en bloc or piecemeal resection at our institution over a 7-year period, were collected and regularly followed up. The study analyzed overall perioperative complications and compared differences in complications and local tumor recurrence between the two surgical methods. RESULTS: Seventeen patients were included, comprising 12 with chondrosarcoma and 5 with chordoma. Among them, 5 cases underwent intralesional piecemeal resection, while the remaining 12 underwent planned en bloc resection. The average surgical time was 684 min (sd = 287), and the mean estimated blood loss was 2300 ml (sd = 1599). Thirty-five complications were recorded, with an average of 2.06 perioperative complications per patient. 82% of patients (14/17) experienced at least one perioperative complication, and major complications occurred in 64.7% (11/17). Five patients had local recurrence during the follow-up, with a mean recurrence time of 16.2 months (sd = 7.2) and a median recurrence time of 20 months (IQR = 12.5). Hospital stays, operation time, blood loss, and complication rates did not significantly differ between the two surgical methods. The local recurrence rate after en bloc resection was lower than piecemeal resection, although not statistically significant (P = 0.067). CONCLUSIONS: The complication rates between the two surgical procedures were similar. Considering safety and local tumor control, en bloc resection is recommended as the primary choice for patients with chondrosarcoma/chordoma in the thoracic and lumbar regions who are eligible for this treatment.

Unfolding the Art of Methodical Approach for Total Sacrectomy.

BACKGROUND: Total sacrectomy is a technically demanding surgery with substantial risks, including high morbidity and mortality due to the likelihood of exsanguination.1-3 Despite the evolution of surgical techniques,4,5 the incidence of postoperative complications remains significant.1 This study presents a systematic approach to total sacrectomy, with a particular focus on a modified technique for isolating the iliac vessels, aimed at effective management of complex sacrococcygeal masses and the reduction of operative complications. PATIENTS AND METHODS: Employing our approach, a 45-year-old male patient presenting with a sacrococcygeal mass involving the lower S1 bone and sacroiliac joint underwent total sacrectomy. A meticulous preoperative workup, including magnetic resonance imaging (MRI), was followed by precise surgical steps: sigmoid colon and rectal mobilization, isolation of the iliac vessels,2,6 lumbosacral nerve trunk preservation, and strategic anterior and posterior osteotomies. The procedure concluded with reconstruction using mesorectal fat and bilateral gluteus maximus flaps.5-7 RESULTS: The patient's operation was conducted successfully without any perioperative complications, culminating in a chordoma resection with clear margins. Postoperative recovery was swift, allowing for discharge on the seventh day. CONCLUSIONS: The application of our systematic sacrectomy method, with particular emphasis on the isolation of the external iliac veins, significantly minimized intraoperative bleeding risks and other perioperative complications. Our technique offers a reproducible and effective strategy for the surgical management of sacrococcygeal masses.

Proton beam therapy for clival chordoma: Optimising rare cancer treatments in Australia.

With the anticipated launch of the Australian Bragg Centre for Proton Therapy and Research (ABCPTR) in Adelaide, Australia, proton therapy will become a significant addition to existing cancer treatment options for Australians. The anticipated benefits will be particularly evident in rare cancers such as clival chordomas, a challenging tumour entity due to the anatomical relationship with critical structures, and proven radio-resistance to conventional radiation therapy. The article synthesises key findings from major studies and evaluates the current evidence supporting various management strategies for clival chordomas. It also considers the influence of institutional volume and multidisciplinary team management on patient outcomes and outlines how high-quality care can be effectively delivered within the Australian healthcare system, emphasising the potential impact of proton therapy on the treatment paradigm of clival chordomas in Australia.

Evaluation of cranial nerve involvement in chordomas and chondrosarcomas: a retrospective imaging study.

PURPOSE: Cranial nerve involvement (CNI) influences the treatment strategies and prognosis of head and neck tumors. However, its incidence in skull base chordomas and chondrosarcomas remains to be investigated. This study evaluated the imaging features of chordoma and chondrosarcoma, with a focus on the differences in CNI. METHODS: Forty-two patients (26 and 16 patients with chordomas and chondrosarcomas, respectively) treated at our institution between January 2007 and January 2023 were included in this retrospective study. Imaging features, such as the maximum diameter, tumor location (midline or off-midline), calcification, signal intensity on T2-weighted image, mean apparent diffusion coefficient (ADC) values, contrast enhancement, and CNI, were evaluated and compared using Fisher's exact test or the Mann-Whitney U-test. The odds ratio (OR) was calculated to evaluate the association between the histological type and imaging features. RESULTS: The incidence of CNI in chondrosarcomas was significantly higher than that in chordomas (63% vs. 8%, P < 0.001). An off-midline location was more common in chondrosarcomas than in chordomas (86% vs. 13%; P < 0.001). The mean ADC values of chondrosarcomas were significantly higher than those of chordomas (P < 0.001). Significant associations were identified between chondrosarcomas and CNI (OR = 20.00; P < 0.001), location (OR = 53.70; P < 0.001), and mean ADC values (OR = 1.01; P = 0.002). CONCLUSION: The incidence of CNI and off-midline location in chondrosarcomas was significantly higher than that in chordomas. CNI, tumor location, and the mean ADC can help distinguish between these entities.

A retrospective study on the mechanism underlying quick transfer from response to resistance in a repeated recurrent chordoma patient with molecular alterations treated with Palbociclib.

PURPOSE: There is no approved targeted therapy for chordoma at present. Although several preclinical studies have implied the potential applicability of CDK4/6 inhibitor for this rare tumor, no clinical evidence has been documented so far. The purpose of this study was to elucidate the therapeutic efficacy of CDK4/6 inhibitor for chordoma. METHODS: The next generation sequencing (as for whole-exome sequencing, WES assay) and immunohistochemical (IHC) staining of the chordoma tissue from a patient with an advanced lesion were performed before treatment. Then, the patient was treated with Palbociclib for 4 months until progression occurred in the 5th month. Surgical resection was implemented and the tumor tissue was obtained postoperatively for assessment of molecular alterations. RESULTS: Molecular features of the tumor before medical treatment suggested applicability of CDK4/6 inhibitor and the patient showed partial response (PR) according to Choi Criteria after 4 months treating with Palbociclib until progression occurred. Then, a drastic molecular alteration of the tumor as represented by emergence of dramatic E2F amplification, which is known to induce CDK4/6 independent cell-cycle entry and progression after treatment, was detected. The findings in this patient demonstrated tumor evolution under drug pressure. CONCLUSION: The findings of the present study suggest the feasibility of Palbociclib for the clinical treatment of chordoma, and imply the necessity of combination therapies rather single drug administration due to the quick resistance of the tumor to Palbociclib treatment.

Development of a Small Molecule Downmodulator for the Transcription Factor Brachyury.

Brachyury is an oncogenic transcription factor whose overexpression drives chordoma growth. The downmodulation of brachyury in chordoma cells has demonstrated therapeutic potential, however, as a transcription factor it is classically deemed "undruggable". Given that direct pharmacological intervention against brachyury has proven difficult, attempts at intervention have instead targeted upstream kinases. Recently, afatinib, an FDA-approved kinase inhibitor, has been shown to modulate brachyury levels in multiple chordoma cell lines. Herein, we use afatinib as a lead to undertake a structure-based drug design approach, aided by mass-spectrometry and X-ray crystallography, to develop DHC-156, a small molecule that more selectively binds brachyury and downmodulates it as potently as afatinib. We eliminated kinase-inhibition from this novel scaffold while demonstrating that DHC-156 induces the post-translational downmodulation of brachyury that results in an irreversible impairment of chordoma tumor cell growth. In doing so, we demonstrate the feasibility of direct brachyury modulation, which may further be developed into more potent tool compounds and therapies.

Incidence and centralization of chordoma in the Netherlands: A nationwide study between 1991 and 2020.

INTRODUCTION: Chordomas are rare malignant bone tumors arising in the axial skeleton, with an incidence of 0.3-0.88 per million inhabitants. We studied the annual incidence rate and centralization of treatment for chordoma in the Netherlands. METHODS: We retrieved pathology excerpts from the PALGA nationwide Dutch Pathology Registry between 1991 and 2019 for patients with a chordoma to calculate incidence rates. From pathology reports we extracted patient age at diagnosis, sex, year of diagnosis, localization of primary tumor, histologic chordoma subtype (conventional including chondroid, poorly differentiated or dedifferentiated), center of diagnosis (bone tumor referral center (BTC) or other hospital), and partial identification of the BTCs. RESULTS: A total of 420 individual chordoma patients were identified in the given time period. The incidence of chordoma increased from 0.593 per million inhabitants between 1991-1995 to 1.111 from 2015-2019 (P = 0.001). Median age at diagnosis was 63 years (range 1-95), 252 patients (60%) were male. The proportion of samples analyzed in a BTC either primarily or secondary, as a consultation, revision or referral, increased significantly from 29.3% to 84.4% (P < 0.001). Most primary and secondary samples were analyzed at the Leiden University Medical Center (LUMC, 54.4% and 57% respectively). CONCLUSIONS: This study shows an increase in the standardized incidence of pathology proven chordoma in the Netherlands. We observed an increase in samples being analysed in the specialized BTCs as well, which is in line with current guidelines and will hopefully lead to more accurate diagnoses and optimal treatment plans for chordoma patients in specialized treatment centers.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Multimodal profiling of chordoma immunity reveals distinct immune contextures.

BACKGROUND: Chordomas are rare cancers from the axial skeleton which present a challenging clinical management with limited treatment options due to their anatomical location. In recent years, a few clinical trials demonstrated that chordomas can respond to immunotherapy. However, an in-depth portrayal of chordoma immunity and its association with clinical parameters is still lacking. METHODS: We present a comprehensive characterization of immunological features of 76 chordomas through application of a multimodal approach. Transcriptomic profiling of 20 chordomas was performed to inform on the activity of immune-related genes through the immunologic constant of rejection (ICR) signature. Multidimensional immunophenotyping through imaging mass cytometry was applied to provide insights in the different immune contextures of 32 chordomas. T cell infiltration was further evaluated in all 76 patients by means of multispectral immunofluorescence and then associated with clinical parameters through univariate and multivariate Cox proportional hazard models as well as Kaplan-Meier estimates. Moreover, distinct expression patterns of human leukocyte antigen (HLA) class I were assessed by immunohistochemical staining in all 76 patients. Finally, clonal enrichment of the T cell receptor (TCR) was sought through profiling of the variable region of TCRB locus of 24 patients. RESULTS: Chordomas generally presented an immune "hot" microenvironment in comparison to other sarcomas, as indicated by the ICR transcriptional signature. We identified two distinct groups of chordomas based on T cell infiltration which were independent from clinical parameters. The highly infiltrated group was further characterized by high dendritic cell infiltration and the presence of multicellular immune aggregates in tumors, whereas low T cell infiltration was associated with lower overall cell densities of immune and stromal cells. Interestingly, patients with higher T cell infiltration displayed a more pronounced clonal enrichment of the TCR repertoire compared with those with low T cell counts. Furthermore, we observed that the majority of chordomas maintained HLA class I expression. CONCLUSION: 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.

Pilot Study of High-Dose Pemetrexed in Patients with Progressive Chordoma.

PURPOSE: Chordomas are ultrarare tumors of the axial spine and skull-base without approved systemic therapy. Most chordomas have negative expression of thymidylate synthase (TS), suggesting a potential for responding to the antifolate agent pemetrexed, which inhibits TS and other enzymes involved in nucleotide biosynthesis. We evaluated the therapeutic activity and safety of high-dose pemetrexed in progressive chordoma. PATIENTS AND METHODS: 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. The primary endpoint was objective response rate according to RECIST v1.1. Secondary endpoints included adverse events, progression-free survival (PFS), tumor molecular profiles, and alterations in tissue and blood-based biomarkers. RESULTS: Fifteen patients were enrolled and the median number of doses administered was 15 (range, 4-31). One patient discontinued treatment due to psychosocial issues after four cycles and one contracted COVID-19 after 13 cycles. Of the 14 response-evaluable patients, 2 (14%) achieved a partial response and 10 (71%) demonstrated stable disease. Median PFS was 10.5 months (95% confidence interval: 9 months-undetermined) and 6-month PFS was 67%. Adverse events were expected and relatively mild, with one grade 3 creatinine increased, and one each of grade 3 and 4 lymphopenia. No grade 5 adverse events, unexpected toxicities, or dose-limiting toxicities were observed. Several patients reported clinical improvement in disease-related symptoms. CONCLUSIONS: High-dose pemetrexed appears tolerable and shows objective antitumor activity in patients with chordoma. Phase II studies of high-dose pemetrexed are warranted.

Extent of Surgical Resection as a Predictor of Tumor Progression in Skull Base Chordomas: A Multicenter Volumetric Analysis.

INTRODUCTION: Skull-base chordomas are aggressive tumors with a propensity for recurrence/progression. Even with standard of care (SoC), 5-year recurrence rates are variable (19%-54%). This high recurrence/progression rate correlates with increased morbidity and mortality. We sought to analyze a multicenter cohort of skull base chordomas to identify predictors of progression in patients receiving SoC. METHODS: The [Blinded]-Neurosurgery data registry was queried for skull base chordomas treated from 2008-2020. Patients with the histopathologic diagnosis of chordoma were included. The cohort was composed of patients with preoperative and postoperative magnetic resonance imaging. Tumor volume and radiologic characteristics were obtained from axial T2 sequences using a Digital Imaging and Communications in Medicine viewer. Survival analysis was performed using Kaplan-Meier method, and time-to-event multivariate regression was performed to identify independent predictors of progression. RESULTS: The cohort included 195 patients, of which 66 patients met inclusion criteria; median age was 44, and 28 (42%) were females. Fifty-four (82%) received SoC, 7 (11%) resection only, and 5 (8%) radiotherapy only. Median preoperative and postoperative tumor volumes were 11.55 cm3 (0.33-54.89) and 0.34 cm3 (0-42.52), respectively. Recurrence rate with SoC was 37%. Postoperative tumor volume (P = 0.010) correlated with progression. A postoperative volume of >4.9 cm3 (P = 0.044), ≤81.3% of tumor resection (P = 0.02), and lower-clivus location (P < 0.005) correlated with decreased time to progression. CONCLUSIONS: Skull base chordomas can be challenging to resect. Even though maximal resection and radiotherapy improve rate of tumor progression, many of these lesions eventually recur. We have identified a postoperative tumor volume of ≥4.9 cm3 and extent of resection of ≤81.3% in this cohort as predictors of progression in patients receiving SoC.

Role of Apparent Diffusion Coefficient Map-Based First- and High-Order Radiomic Features for the Discrimination of Sacral Chordomas and Chondrosarcomas With Overlapping Conventional Imaging Features.

PURPOSE: Chondrosarcomas arise from the lateral pelvis; however, midline chondrosarcomas (10%) display similar imaging features to chordoma, causing a diagnostic challenge. This study aims to determine the diagnostic accuracy of apparent diffusion coefficient (ADC)-based radiomic features and two novel diffusion indices for differentiating sacral chordomas and chondrosarcomas. METHODS: A retrospective, multireader review was performed of 82 pelvic MRIs (42 chordomas and 40 chondrosarcomas) between December 2014 and September 2021, split into training (n = 69) and validation (n = 13) data sets. Lesions were segmented on a single slice from ADC maps. Eight first-order features (minimum, mean, median, and maximum ADC, standard deviation, skewness, kurtosis, and entropy) and two novel indices: restriction index (RI, proportion of lesions with restricted diffusion) and facilitation index (FI, proportion of lesions with facilitated diffusion) were estimated. One hundred seven radiomic features comparing patients with chondrosarcoma versus chordoma were sorted based on mean group differences. RESULTS: There was good to excellent interobserver reliability for eight of the 10 ADC metrics on the training data set. Significant differences were observed (P < .005) for RI, FI, median, mean, and skewness using the training data set. Optimal cutpoints for diagnosis of chordoma were RI > 0.015; FI < 0.25; mean ADC < 1.7 × 10-3 mm2/s; and skewness >0.177. The optimal decision tree relied on FI. In a secondary analysis, significant differences (P < .00047) in chondrosarcoma versus chordoma were found in 18 of 107 radiomic features, including six first-order and 12 high-order features. CONCLUSION: The novel ADC index, FI, in addition to ADC mean, skewness, and 12 high-order radiomic features, could help differentiate sacral chordomas from chondrosarcomas.

Antibiotic-loaded bone cement combined with negative pressure wound therapy for treating sacrococcygeal wound following sacral chordoma resection: a case report.

BACKGROUND: Sacral chordoma is a rare, malignant primary bone tumor with subtle clinical manifestations. The extensive cavity and soft tissue defect after radical resection of the tumor can lead to complications such as sacrococcygeal skin necrosis, infection, cerebrospinal fluid (CSF) leakage, and delayed healing or nonhealing. PURPOSE: To describe the treatment effect of the combination use of antibiotic-loaded bone cement (ALBC), a gluteus maximus muscle flap, and negative pressure wound therapy (NPWT) on the nonhealing sacrococcygeal wound after sacral chordoma resection. CASE REPORT: A 67-year-old woman with a sacrococcygeal wound following sacral chordoma resection was admitted to the hospital. In the 2-stage surgery, the internal fixation and synthetic dura substitute were exposed and CSF leakage was found after debridement, a gluteus maximus muscle flap was used to cover the synthetic dura substitute to address the CSF leakage, ALBC was used to cover the internal fixation, and a modified NPWT system was fixed to the wound for improved flushing and drainage. RESULTS: The previously nonhealing wound healed 3 weeks postoperatively, and satisfactory recovery was achieved by 6-month follow-up. CONCLUSION: This case report suggests that the combination use of ALBC, gluteus maximus muscle flap, and NPWT can effectively promote sacrococcygeal wound healing after chordoma resection.