18F‑FDG PET/CT in metastatic chordoma: a retrospective analysis of imaging features and clinical impact

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This study aimed to evaluate its imaging characteristics, diagnostic consistency, and potential impact on clinical assessment and management. Methods: In this single-center retrospective analysis, 21 patients with pathologically confirmed chordoma and prior treatment underwent 18 F-FDG PET/CT for suspected recurrence or metastasis. Metastatic disease was diagnosed per a composite standard (biopsy, imaging progression, or characteristic multimodal findings). Relevant clinical and histopathological data were collected. Images were independently reviewed by two experienced nuclear medicine physicians for metabolic activity and whole-body disease assessment. They assessed metabolic activity at the primary site and performed whole-body evaluation. For each metastatic lesion, maximum standardized uptake value (SUVmax) and size were measured; CT features were also documented. Interobserver agreement for key assessments was formally evaluated. Results: Metastatic disease was identified in 11 of 21 patients (52.4%). Metastases were found in bone (7 patients), soft tissue (8 patients), and lung (5 patients). Site-specific metabolic patterns emerged: pulmonary metastases had lower FDG avidity (median SUVmax 2.3) correlated with size, whereas bone and soft-tissue avidity (SUVmax 3.8-3.9) was size-independent. A higher SUVmax was associated with poorly-differentiated histology (6.4 vs. 3.6, P =0.023). Notably, in 4 out of 21 patients (19.0%), PET/CT detected metastases outside the field of view of conventional imaging. Interobserver agreement was perfect for metastatic status and excellent for total lesion counts. A case illustrated differential treatment response linked to baseline metabolic avidity. Conclusions: 18 F-FDG PET/CT offers a reproducible whole-body assessment for chordoma, enabling the detection of occult metastases and revealing clinically relevant metabolic heterogeneity. These findings highlight its potential in surveillance and personalized management, warranting further prospective validation. Chordoma Metastasis 18F-fluorodeoxyglucose PET/CT Spine Surveillance Figures Figure 1 Figure 2 Background Chordoma is a rare malignant bone tumor arising from notochordal remnants, accounting for 1–4% of all primary bone malignancies [ 1 ]. It predominantly involves the axial skeleton, most commonly the sacrococcygeal region (50–60%) and skull base (25–35%) [ 2 ]. Despite its indolent histology, chordoma is locally aggressive with high recurrence rates post-resection. Distant metastasis, though infrequent at initial presentation, critically impacts prognosis, with reported rates varying from 3% to 48% across studies [ 3 ]. Metastases most often involve the lungs, bones, and liver [ 4 ]. Most large-scale studies on chordoma have focused on sacral chordoma [ 4 – 6 ], with considerable variability in reported metastasis rates and predominant metastatic sites: some studies identify bone as the most common metastatic site with an incidence of 31.4% [ 4 ], while others report the lung as the predominant site, with a much higher incidence as high as 82.7% [ 5 , 6 ]. Case reports also document spread to uncommon sites such as the heart, skin, and skeletal muscle, underscoring the unpredictable metastatic behavior of chordoma [ 7 – 10 ]. Such discrepancies are primarily attributed to differences in the selection of imaging modalities, the scope of scanned anatomical regions, and the technical sensitivity of detection methods, which collectively influence the identification of metastatic lesions—including metastases to rare sites, as well as small or indolent lesions. Clinically, magnetic resonance imaging (MRI) and computed tomography (CT) are the mainstays of imaging for chordoma. Standard follow-up relies on MRI for local surveillance and CT for lung assessment [ 4 ]. However, the regional focus of MRI may miss distant disease, while CT has limited sensitivity for extrapulmonary soft-tissue metastases, especially lesions that are isodense to muscle or bone. Integrated 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) is a functional metabolic imaging modality that enables whole-body evaluation in a single examination by detecting heightened glucose metabolism characteristic of many malignancies. It can theoretically address the limitations of conventional imaging by providing simultaneous metabolic and anatomical data across the entire body. Although its utility in identifying rare chordoma metastases has been reported anecdotally [ 9 , 11 , 12 ], systematic studies that define the metabolic profile of metastatic chordoma and describe the imaging patterns detected on whole-body PET/CT are lacking. Therefore, this study aimed to systematically define the 18F-FDG PET/CT imaging profile of metastatic chordoma, delineate its whole-body dissemination patterns, and evaluate its potential impact on clinical assessment and management. Methods Patient Population This single-center, retrospective study was conducted with approval from the Institutional Review Board; informed consent was waived. We reviewed records from January 2013 to December 2024 to identify patients with pathologically confirmed chordoma who underwent 18 F-FDG PET/CT. Inclusion criteria were: (1) pathological diagnosis of chordoma; (2) prior surgery and/or radiotherapy; (3) PET/CT performed for suspected recurrence/metastasis with no intervening antitumor therapy within the preceding 3 months. Patients with another malignancy were excluded. For each included patient, we extracted essential demographic and clinical data from electronic medical records. This included sex, age at the time of PET/CT, primary tumor location and histologic subtype, prior treatment history, and the indication for the PET/CT scan. All patients were followed after the index PET/CT, with subsequent imaging, biopsy results, and treatment decisions recorded to establish the diagnostic reference standard. PET/CT Imaging Protocol PET/CT Imaging Protocol All scans followed a standardized institutional 18 F-FDG PET/CT protocol. Patients fasted for at least 6 hours, and pre-scan blood glucose was confirmed less than 11.1 mmol/L. 18 F-FDG was injected intravenously at a weight-adjusted dose of 3.7–5.5 MBq/kg. After a 60-minute uptake period in a quiet room, imaging was performed on a PET/CT scanner (Biograph 64, Siemens, Germany). A low-dose non-contrast CT scan was acquired with the following parameters: tube voltage 120 kV, tube current 100 mAs, pitch 0.9, and slice thickness 3 mm. This was followed by a 3D PET emission scan from skull vertex to mid-thighs (3–6 bed positions, 2 minutes per bed). PET images were reconstructed using an ordered-subset expectation maximization algorithm (TrueX; 3 iterations, 21 subsets) with a 5.0 mm full-width at half-maximum Gaussian filter. Reference Standard for Diagnosis of Metastasis Given the clinical impracticality and potential morbidity of biopsy for every suspected metastatic lesion, a composite reference standard was applied for final diagnosis of metastasis, requiring fulfillment of at least one of the following criteria: (1) Pathological confirmation: Cytological or histological evidence of chordoma from a biopsy or resection of the suspected metastatic site. (2) Imaging progression: Definitive interval growth or development of a new lesion on serial follow-up imaging studies. (3) Highly suggestive multimodal imaging characteristics: A combination of a clear focal FDG uptake on PET (visibly higher than surrounding background activity) co-registered with a corresponding structural abnormality on CT (such as a soft tissue nodule/mass, lytic or mixed bone destruction) or with MRI features highly characteristic of chordoma (e.g., very high T2 signal intensity with T1 iso- or hypointensity and heterogeneous enhancement)[ 3 , 4 ]. Image Analysis and Interpretation PET/CT images were independently reviewed by two board-certified nuclear medicine physicians to identifying lesions meeting the predefined reference standard for metastasis. For each patient, the reviewers first assessed whether metabolic activity was present at the primary tumor site and, if present, measured its maximum standardized uptake value (SUVmax). Subsequently, a systematic whole-body evaluation was performed to detect potential metastatic disease. For any identified metastatic lesion, its SUVmax and maximum axial diameter were measured. The lesion volumes of interest were mapped on PET/CT fusion images using the three-dimensional outlining method, and the system automatically calculated the SUVmax. Lesion size was defined as the maximum axial diameter measured on the CT component of the PET/CT study. For lesions clearly defined on CT, size was measured directly; for isodense lesions, the maximum diameter was measured on axial PET/CT fusion images, based on the boundary defined by 40% of the lesion's SUVmax. The homogeneity of metabolic activity within each lesion was visually assessed on PET images. For each lesion, the anatomical location was recorded. Additional CT features such as density (relative to adjacent normal bone or skeletal muscle), morphology, and margin characteristics were documented. Interobserver Agreement and Consensus Process Interobserver agreement was formally assessed for key variables. Agreement on patient-level metastatic status (present vs. absent) was evaluated using Cohen’s kappa ( κ ). For metastatic patients, the reliability of total lesion counts was assessed with the intraclass correlation coefficient (ICC; two-way random-effects model). Agreement on CT density patterns of bone metastases (hyperdense, mixed, hypodense, isodense) was evaluated using weighted kappa. Kappa values were interpreted as: <0 (poor), 0–0.20 (slight), 0.21–0.40 (fair), 0.41–0.60 (moderate), 0.61–0.80 (substantial), and 0.81–1.00 (almost perfect). Discrepancies were resolved by joint re-review and consensus discussion. All subsequent analyses used this consensus dataset. Statistical Analysis All statistical analyses were performed using IBM SPSS Statistics (v27.0). Continuous non-normally distributed variables are presented as median with Confidence Interval (IQR) or range; categorical variables as counts and percentages. The Spearman's ρ was used to assess correlations between SUVmax and lesion size. Group comparisons employed the Mann-Whitney U test (two groups) or Kruskal-Wallis H test (≥ 3 groups). For paired comparisons, such as between the SUVmax of metastatic lesions and their corresponding local residual/recurrent lesions, the Wilcoxon signed-rank test was used. All tests were two-tailed, with P < 0.05 considered statistically significant. Results Patient Characteristics The cohort consisted of 21 patients (16 males, 5 females) with a median age of 61 years (range 18–89). Primary tumor sites were the cervical spine (n = 9), sacrum (n = 9), and lumbar spine (n = 3). Most tumors were of the conventional histological subtype (n = 18), while the remaining cases were sarcomatoid (n = 2) and poorly differentiated (n = 1) subtypes. The median interval from initial diagnosis to PET/CT was 39 months (range 4–156). PET/CT Findings PET/CT identified active tumor—either local or metastatic—in 20 of the 21 patients (95.2%). Local recurrence or residual tumor at the primary site was detected in 17 patients (81.0%), with a median SUVmax of 3.4 (IQR: 3.0–5.9; range: 2.2–13.4). Metastatic disease was detected in 11 patients (Table 1 ). This metastatic group had a median age of 61 years, was predominantly male (n = 9), and included patients with primary tumors in the cervical spine (n = 5), sacrum (n = 4), and lumbar spine (n = 2). Histologically, the metastatic cohort comprised conventional-type chordomas (n = 9), sarcomatoid (n = 1), and poorly differentiated (n = 1) subtypes. The single negative case showed a sacral insufficiency fracture without evidence of active disease on PET/CT. Table 1 Clinical characteristics and subsequent treatment of patients with metastatic chordoma. No. Primary Site Histologic Subtype Interval from Initial Diagnosis to Current PET/CT (Months) Prior Treatments SUVmax of Residual/Recurrent Lesion Metastatic Sites Subsequent Treatment Follow-up after PET/CT (Months) 1 Cervical Spine Conventional 64 Surgery, Radiotherapy 6.9 Lung, Soft Tissue None NA 2 Lumbar Spine Conventional 96 Surgery 3.7 Soft Tissue, Bone None NA 3 Sacrum Conventional 144 Surgery, Radiotherapy, Particle Therapy 2.8 Lung, Soft Tissue, Bone Radiotherapy 3 4 Lumbar Spine Conventional 14 Surgery, Radiotherapy 3 Soft Tissue Surgery, Radiotherapy, Immunotherapy 70 5 Cervical Spine Conventional 4 Radiotherapy, Surgery 3.6 Bone Radiotherapy, Systemic Therapy 79 6 Cervical Spine Poorly Differentiated 9 Surgery, Radiotherapy No Bone Radiotherapy 7 7 Cervical Spine Sarcomatous Differentiation 35 Surgery, Radiotherapy, Chemotherapy No Lung, Bone Chemotherapy, Surgery, Radiotherapy 19 8 Sacrum Conventional 91 Surgery No Lung, Soft Tissue Radiotherapy 9 9 Sacrum Conventional 144 Surgery, Radiotherapy 3.4 Soft Tissue, Bone None NA 10 Cervical Spine Conventional 40 Surgery, Radiotherapy 2.8 Lung, Soft Tissue, Bone Anlotinib, Radiotherapy 5 11 Sacrum Conventional 19 Surgery, Radiotherapy 3.1 Soft Tissue Particle Implantation NA Interobserver agreement was perfect for the dichotomous assessment of metastatic status and excellent for the total lesion count per patient among those with metastases (ICC = 0.96, 95% CI: 0.86–0.99). Agreement on the CT density classification of bone metastases was substantial (weighted κ = 0.765). Characteristics of Metastatic Lesions A total of 47 lesions were analyzed as metastases. Only three lesions in three patients were pathologically confirmed via biopsy (located in the ischium, gluteal muscle, and lung, respectively); the remainder were diagnosed based on imaging progression or highly suggestive imaging features. Bone metastases were found in 7 patients with a total of 21 lesions. Metastases were predominantly multifocal (6 of 7 patients, 85.7%) and distributed throughout the skeleton, most frequently in the spine (n = 13). Primary tumors in these patients located in the cervical spine (n = 4), lumbar spine (n = 2), and sacrum (n = 1). Lesions had a median size of 1.7 cm (IQR: 1.3–3.2) and a median SUVmax of 3.8 (IQR: 3.3–5.5). On CT, they displayed heterogeneous bone destruction patterns, categorized as hypodense (n = 7, 33.3%), hyperdense (n = 5, 23.8%), mixed (n = 7, 33.3%), or isodense (n = 2, 9.5%) lesions (Fig. 1 ). Metabolic activity was homogeneous in 15 lesions and heterogeneous in 6 lesions. SUVmax did not correlate with lesion size ( ρ = 0.105, P = 0.650) and did not differ significantly across CT density types ( H = 4.644, P = 0.200). An adjacent soft tissue mass was present in 33.3% of lesions but did not influence metabolic activity (SUVmax 4.1 vs. 3.6, P = 0.455). Additionally, when analyzed by primary tumor histology, metastases from conventional-type chordomas (n = 14 lesions) showed a median SUVmax of 3.6 (IQR: 3.2–4.1), while those from poorly differentiated/dedifferentiated subtypes (n = 7 lesions) exhibited a significantly higher median SUVmax of 6.4 (IQR: 4.2–6.8) ( Z = 2.278, P = 0.023). Soft-tissue metastases were identified in 8 patients (15 lesions). The median lesion size was 2.3 cm (IQR: 1.7–3.5) with a median SUVmax of 3.9 (IQR: 2.9–5.4), and no correlation was found between these two parameters ( ρ = 0.331, P = 0.228). On CT, most lesions were isodense to muscle (n = 11, 73.3%), while a minority were hypodense (n = 4, 26.7%); the CT density did not significantly affect SUVmax ( P = 0.556). On PET, metabolic activity was homogeneous in 12 lesions and heterogeneous in 3. Anatomically, the majority of lesions (n = 12, 80.0%) were located within the surgical bed or along its trajectory (Fig. 2 ). The remaining three distant subcutaneous lesions occurred in two patients, both of whom also had bone metastases, and one had concurrent pulmonary metastases. Pulmonary metastases were present in 5 patients, comprising a total of 11 nodules. All nodules appeared round-to-oval in shape with smooth margins and relatively homogeneous internal density on CT. Metabolic activity on PET was homogeneous in 9 nodules, while heterogeneous uptake was observed in the 2 larger lesions. The median size was 1.2 cm (IQR 0.8–1.5 cm) and the median SUVmax was 2.3 (IQR 0.9–2.5). A significant positive correlation was found between SUVmax and nodule size (Spearman's ρ = 0.839, P = 0.001). Notably, all 5 patients had concurrent bone or soft-tissue metastases; no isolated pulmonary metastasis was observed (Fig. 2 ). Primary tumors in these cases originated from the cervical spine (n = 3) and sacrum (n = 2). Among the 11 patients with metastatic disease, 8 patients had concurrent local residual or recurrent tumor. In these patients, the median SUVmax of bone and soft-tissue metastases (3.7) was comparable to that of the corresponding local lesions (3.3), with no statistically significant difference ( Z = 1.540, P = 0.123). Detection of Additional Metastases by PET/CT In 4 of 11 patients with metastatic disease, PET/CT detected more metastatic lesions that were outside the field of view of recent dedicated spine or pelvic MRI. These included pulmonary and bone metastases. Treatment Response and Illustrative Follow-up Case Over a median follow‑up of 9 months (range, 3–79 months) after the PET/CT examination, 7 patients remained under surveillance. Among these, 5 showed disease progression, 1 had stable disease, and 1 died from disease. Four patients were lost to follow‑up. Treatment approaches included systemic therapy, local radiotherapy, and radioactive seed implantation. In one patient with concurrent bone, lung, and soft‑tissue metastases, treatment with Anlotinib for 3 months resulted in regression of lesions with higher baseline FDG avidity but enlargement of those with lower metabolic activity (Fig. 2 ). Discussion This retrospective study illustrates the potential utility of 18 F-FDG PET/CT in providing a comprehensive metabolic assessment of disease status in patients with suspected recurrent or metastatic chordoma. In our cohort of 21 patients, PET/CT identified active tumor in 20 patients (95.2%), with metastatic disease identified in 11 patients (52.4%). The two readers were in complete agreement on this patient-level assessment of metastatic status. In 4 of these 11 patients, PET/CT detected metastases outside the field of view of recent dedicated spine/pelvic MRI. For the 11 patients with metastases, the initial independent counts of total metastatic lesions showed excellent inter-reader reliability (ICC = 0.96, 95% CI: 0.86–0.99). To our knowledge, our analysis offers the first systematic report of the metabolic profile of metastatic chordoma across different sites, revealing moderate FDG avidity (median SUVmax: 3.8 for bone, 3.9 for soft tissue, and 2.3 for lung metastases). Overall, metabolic activity was homogeneous in the majority of lesions across all sites (71.4% of bone, 80.0% of soft-tissue, and 81.8% of pulmonary metastases). Notably, the metabolic activity of bone and soft‑tissue metastatic lesions closely paralleled that of local recurrences, suggesting a consistent biologic phenotype. Furthermore, we observed a significant correlation between higher metabolic activity (median SUVmax 6.4) and aggressive histologic subtypes (poorly/dedifferentiated), indicating that SUVmax may reflect tumor aggressiveness. The relationship between SUVmax and lesion size varied by site: it was independent in bone and soft‑tissue metastases but showed a strong positive correlation in pulmonary nodules ( ρ = 0.839, P = 0.001). This dissociation highlights distinct tumor behaviors in different compartments. The imaging phenotype revealed by PET/CT diverges from classic radiological descriptions. Our cohort demonstrated a predilection for multifocal bone disease (85.7% of patients), with lesions having significantly smaller median size (1.7 cm) and only a minority (33.3%) associated with a soft‑tissue mass. In stark contrast, a prior CT/MRI‑based study by Chang et al. [ 3 ] described osseous metastases as predominantly solitary (60%), large (mean 6.4 cm), and lytic with extensive soft‑tissue components. This discrepancy likely reflects differences in both imaging technology and, importantly, the clinical context of detection. In the present study, bone metastases were detected incidentally during evaluation of the primary site or on routine follow-up, whereas in the prior series, 67% of lesions were discovered because of pain or pathologic fracture. This contrast highlights that the metabolic and whole-body nature of PET/CT, particularly when employed for asymptomatic surveillance, can characterize metastatic disease at a point of lower tumor burden. The observed metastatic pattern, with a high frequency of osseous involvement (7/11, 63.6%), contrasts with the lower rates of bone metastasis (9.6%–31.4%) reported in prior studies [ 4 – 6 ]. This discrepancy may be primarily attributed to differences in imaging methodology. The earlier studies relied on chest CT and bone scintigraphy [ 5 , 6 ] or CT and MRI [ 4 ], whereas our systematic whole-body PET/CT approach likely has a higher sensitivity for detecting early, multifocal bone marrow infiltration. Furthermore, the predominance of mobile-spine (cervical or lumbar) primary tumors in our cohort (6 of the 7 patients with osseous metastases) may also influence the observed pattern, as metastatic spread in this subgroup could be facilitated by the anatomical proximity to the vertebral venous plexus (Batson’s plexus). Moreover, pulmonary metastases occurred in 5/11 (45.5%) patients, with 80% of these cases presenting concurrently with bone metastases, suggesting that osseous spread may precede or coincide with pulmonary hematogenous dissemination. This temporal sequence aligns with Chang et al.’s [ 3 ] description of contiguous spinal axis involvement and supports the hypothesis that the vertebral venous network likely serves as a primary pathway for initial metastatic seeding in mobile-spine chordomas. The distribution of soft‑tissue metastases provides complementary insights. In our series, 80% (12 of 15) of soft‑tissue lesions were confined to surgical tracts or the operative field, consistent with prior literature attributing such spread to iatrogenic seeding [ 13 , 14 ]. This finding reinforces the importance of meticulous no‑touch surgical techniques and underscores the necessity of dedicated imaging surveillance of the operative region. Beyond locoregional spread, PET/CT detected hematogenous metastases to distant subcutaneous sites (20%, 3/15)—lesions typically occult on routine, anatomically limited MRI or CT—highlighting the value of whole‑body metabolic screening. Preliminary observations from treatment follow‑up in our cohort further underscore the potential clinical relevance of the metabolic heterogeneity captured by baseline PET/CT. In one illustrative case, a patient with multi‑organ metastases showed a differential response after 3 months of Anlotinib therapy: lesions with higher baseline FDG avidity regressed, whereas those with lower initial metabolic activity progressed. Although anecdotal, this observation suggests that pre‑treatment metabolic profiling by PET/CT might help identify lesions with different biological behaviors and susceptibilities to systemic therapy. This aligns with our cross‑sectional finding that SUVmax correlates with histologic aggressiveness. Together, these insights suggest that baseline metabolic characterization could inform more personalized treatment strategies. This study has limitations inherent to its retrospective, single-center design and small sample size. Not all metastatic lesions had pathological confirmation, though we applied rigorous composite diagnostic criterion. Future prospective, multi-center studies with larger cohorts are needed to validate our findings and potentially establish standardized PET/CT protocols for chordoma surveillance. Conclusion This study highlights the potential role of 18 F-FDG PET/CT in chordoma management. Its reproducible, whole-body metabolic assessment detects metastases beyond the field of view of conventional imaging and delineates site-specific metabolic profiles. The frequent detection of multifocal small bone metastases indicates an earlier pattern of spread than historically reported, underscoring the added value of metabolic imaging in routine surveillance. Furthermore, observed differential treatment responses linked to baseline metabolic heterogeneity suggest PET/CT may help characterize tumor biology and therapeutic susceptibility. Together with the correlation between high SUVmax and aggressive histology, these findings warrant further investigation into the prognostic and predictive utility of PET/CT for personalizing management in patients with high-risk chordoma. Abbreviations 18 F‑FDG 18 F‑fluorodeoxyglucose PET/CT Positron Emission Tomography/Computed Tomography SUVmax Maximum Standardized Uptake Value MRI Magnetic Resonance Imaging CT Computed Tomography ICC Intraclass Correlation Coefficient CI Confidence Interval IQR Interquartile Range Declarations Ethics approval and consent to participate This study was conducted as per the Declaration of Helsinki. The approval to the protocol was done by the Ethics Committee of Peking University Third Hospital and each regulation was followed. The requirement for informed consent was waived by the board due to the retrospective nature of the study. Consent for publication  Not applicable. Availability of data and material The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This work was supported by the Key Clinical Project of Peking University Third Hospital (BYSYDL2023003) Authors' contributions LS: conceptualization, image analysis, data-curation, writing-original draft, and editing. PLH: clinical and imaging data collection, data-curation. FW: supervision, data interpretation. WFZ: supervision, image analysis, editing. All authors reviewed and approved the final manuscript. Acknowledgements Not applicable. References Walcott BP, Nahed BV, Mohyeldin A, Coumans JV, Kahle KT, Ferreira MJ. Chordoma: current concepts, management, and future directions. 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Berlucchi S, Nasi D, Zunarelli E, Valluzzi A, Alicandri Ciufelli M, Presutti L et al. Cutaneous Metastasis from Cervical Spinal Chordoma: Case Report and Literature Review. World Neurosurg. 2020; 296–303. Figliozzi S, Stankowski K, Monti L, Francone M. Multiparametric cardiovascular magnetic resonance characterization of a rare chordoma metastasis to the heart. Eur Heart J Cardiovasc Imaging. 2025; 1075. Sekmen S, Hursoy N, Gucer H, Burakgazi G, Balik MS, Cubukcu SS. Muscle metastasis from cervical chordoma: a case report. Skeletal Radiol. 2025; 1331–6. Stefàno PL, Barletta G, Andrei V, Cerillo AG, Nesi G, Pilato G et al. Cardiac Metastasis of Sacral Chordoma. Ann Thorac Surg. 2021; e319–21. Cui F, Su M, Zhang H, Tian R. Humeral metastasis of sacrococcygeal chordoma detected by fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography: A case report. Radiol Case Rep. 2018; 449 – 52. Collins GR, Essary L, Strauss J, Hino P, Cockerell CJ. Incidentally discovered distant cutaneous metastasis of sacral chordoma: a case with variation in S100 protein expression (compared to the primary tumor) and review of the literature. J Cutan Pathol. 2012; 637 – 43. Kinoshita T, Okudera T, Shimosegawa E, Yoshida Y, Yasui N, Ogawa T et al. Chordoma with postoperative subcutaneous implantation and meningeal dissemination: MRI. Neuroradiology. 2001; 763-6. Fernandes Cabral DT, Zenonos GA, Fernandez-Miranda JC, Wang EW, Gardner PA. Iatrogenic seeding of skull base chordoma following endoscopic endonasal surgery. J Neurosurg. 2018; 947 – 53. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8715079","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":597044731,"identity":"59874cb1-e4b5-47b5-93a0-77f2d4e1caea","order_by":0,"name":"Le Song","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Le","middleName":"","lastName":"Song","suffix":""},{"id":597044732,"identity":"cdfa436e-d4f3-4ea4-990c-ee5f2881d935","order_by":1,"name":"Peilin Hua","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Peilin","middleName":"","lastName":"Hua","suffix":""},{"id":597044733,"identity":"db80f0c1-71a5-4ed1-a319-d099b00b16c3","order_by":2,"name":"Feng Wei","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Feng","middleName":"","lastName":"Wei","suffix":""},{"id":597044734,"identity":"3c69ffc3-48de-4be4-8725-4a6ae9306eee","order_by":3,"name":"Weifang ZHANG","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwklEQVRIiWNgGAWjYJCCAx8q/suxsTcfIE45DwMD48EZZ5iN+XiOJRCthfkwbxtz4jyJHAXitNjznzEAamFLb2PIYWD4UbGNCFskcgwOzjnHk9vGcPYAY8+Z28Ro4TE48KZMIreNsS+BmbGNGC1Ahx3gYTNIZ2PmMSBSCwPQYTxtCQlsbERruZFWAAzkA4ZtPGwJB4nyC3v/4c0fPlQckJef//jggx8VRGhhYOAwgDMPEKMeZM8DIhWOglEwCkbBiAUAFBY891ZtRO4AAAAASUVORK5CYII=","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":true,"prefix":"","firstName":"Weifang","middleName":"","lastName":"ZHANG","suffix":""}],"badges":[],"createdAt":"2026-01-28 01:23:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8715079/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8715079/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103590236,"identity":"0e41bdba-699d-4e43-8623-e405f4e17123","added_by":"auto","created_at":"2026-02-27 12:02:24","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":269634,"visible":true,"origin":"","legend":"\u003cp\u003ePET/CT manifestations of bone metastasis from chordoma. (A) Maximum intensity projection (MIP) image demonstrates multifocal FDG-avid lesions involving the neck, bilateral lungs, and skeleton (arrows). (B-D) Selected axial PET/CT fusion images and (E-G) corresponding non-contrast CT images illustrate three representative osseous metastases: a hyperdense lesion in the right scapula (short arrows, B and E) with an SUVmax of 3.5; a mixed-density lesion in the T5 vertebral body (dashed arrows, C and F) with an SUVmax of 2.2; and a hypodense lesion in the T12 vertebral body (long arrows, D and G) with an SUVmax of 4.2.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8715079/v1/eee14cae9d512f38656e94a9.jpeg"},{"id":103590235,"identity":"5e9cfb7d-7f57-4f00-a13b-471a0e29ac5d","added_by":"auto","created_at":"2026-02-27 12:02:24","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":457387,"visible":true,"origin":"","legend":"\u003cp\u003eImaging evaluation of metastatic chordoma and post-therapy response. Same patient as Figure 1. (A-C) Selected axial PET/CT fusion images and (D-F, I) corresponding non-contrast CT images demonstrate multiple lesions. (A and D) A soft‑tissue lesion antero-right to the C4 vertebral body is isodense on CT and shows mild FDG uptake (SUVmax 2.7, long arrows). (A and D) A right submandibular nodule is isodense on CT with minimal FDG uptake (SUVmax 1.2, short arrows). (B and E) A nasopharyngeal nodule is slightly hypodense on CT with intense FDG uptake (SUVmax 5.9, dashed arrows). (C, F, I) Bilateral pulmonary nodules are present: a larger, heterogeneous, FDG‑avid mass in the left lower lobe (3.8 cm × 2.7 cm; SUVmax 5.5; short arrows) and a smaller nodule in the right lung (1.5 cm in diameter; SUVmax 2.3; curved arrows). (G and H) Corresponding axial T2‑weighted MR images for anatomical correlation: The C4 paravertebral lesion (1.5 cm × 1.2 cm, long arrow, G) shows signal intensity similar to the spinal cord. The nasopharyngeal nodule (2.0 cm × 1.2 cm, dashed arrow, H) also shows cord-like signal intensity. The right submandibular nodule (1.1 cm × 0.9 cm, short arrow, G) appears hyperintense. (J-L) Follow‑up imaging following 3 months of Anlotinib treatment. (J and K) T2‑weighted MR and (L) CT images show the following changes: enlargement of both the C4 paravertebral lesion (now 2.7 cm × 2.1 cm; long arrow, J) and the right submandibular nodule (now 1.6 cm × 1.5 cm; short arrow, J); mild shrinkage of the nasopharyngeal nodule (now 1.8 cm × 1.0 cm; dashed arrow, K); reduction in the size of the left lung mass (now 3.0 cm × 2.4 cm; short arrow, L); and enlargement of the right lung nodule (now 1.9 cm × 1.6 cm; curved arrow, L).\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8715079/v1/a7e1ecb03a3c7fa373251196.jpeg"},{"id":104398863,"identity":"044073b8-d082-417e-8c80-a4d32ddc84a3","added_by":"auto","created_at":"2026-03-11 12:04:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1439170,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8715079/v1/3f4129d0-8674-434d-834b-f3014f2b4af0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"18F‑FDG PET/CT in metastatic chordoma: a retrospective analysis of imaging features and clinical impact","fulltext":[{"header":"Background","content":"\u003cp\u003eChordoma is a rare malignant bone tumor arising from notochordal remnants, accounting for 1\u0026ndash;4% of all primary bone malignancies [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It predominantly involves the axial skeleton, most commonly the sacrococcygeal region (50\u0026ndash;60%) and skull base (25\u0026ndash;35%) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Despite its indolent histology, chordoma is locally aggressive with high recurrence rates post-resection. Distant metastasis, though infrequent at initial presentation, critically impacts prognosis, with reported rates varying from 3% to 48% across studies [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Metastases most often involve the lungs, bones, and liver [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Most large-scale studies on chordoma have focused on sacral chordoma [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], with considerable variability in reported metastasis rates and predominant metastatic sites: some studies identify bone as the most common metastatic site with an incidence of 31.4% [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], while others report the lung as the predominant site, with a much higher incidence as high as 82.7% [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Case reports also document spread to uncommon sites such as the heart, skin, and skeletal muscle, underscoring the unpredictable metastatic behavior of chordoma [\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Such discrepancies are primarily attributed to differences in the selection of imaging modalities, the scope of scanned anatomical regions, and the technical sensitivity of detection methods, which collectively influence the identification of metastatic lesions\u0026mdash;including metastases to rare sites, as well as small or indolent lesions.\u003c/p\u003e \u003cp\u003eClinically, magnetic resonance imaging (MRI) and computed tomography (CT) are the mainstays of imaging for chordoma. Standard follow-up relies on MRI for local surveillance and CT for lung assessment [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, the regional focus of MRI may miss distant disease, while CT has limited sensitivity for extrapulmonary soft-tissue metastases, especially lesions that are isodense to muscle or bone.\u003c/p\u003e \u003cp\u003eIntegrated \u003csup\u003e18\u003c/sup\u003eF-fluorodeoxyglucose positron emission tomography/computed tomography (\u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT) is a functional metabolic imaging modality that enables whole-body evaluation in a single examination by detecting heightened glucose metabolism characteristic of many malignancies. It can theoretically address the limitations of conventional imaging by providing simultaneous metabolic and anatomical data across the entire body. Although its utility in identifying rare chordoma metastases has been reported anecdotally [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], systematic studies that define the metabolic profile of metastatic chordoma and describe the imaging patterns detected on whole-body PET/CT are lacking.\u003c/p\u003e \u003cp\u003eTherefore, this study aimed to systematically define the 18F-FDG PET/CT imaging profile of metastatic chordoma, delineate its whole-body dissemination patterns, and evaluate its potential impact on clinical assessment and management.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient Population\u003c/h2\u003e \u003cp\u003e This single-center, retrospective study was conducted with approval from the Institutional Review Board; informed consent was waived. We reviewed records from January 2013 to December 2024 to identify patients with pathologically confirmed chordoma who underwent \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT. Inclusion criteria were: (1) pathological diagnosis of chordoma; (2) prior surgery and/or radiotherapy; (3) PET/CT performed for suspected recurrence/metastasis with no intervening antitumor therapy within the preceding 3 months. Patients with another malignancy were excluded.\u003c/p\u003e \u003cp\u003eFor each included patient, we extracted essential demographic and clinical data from electronic medical records. This included sex, age at the time of PET/CT, primary tumor location and histologic subtype, prior treatment history, and the indication for the PET/CT scan. All patients were followed after the index PET/CT, with subsequent imaging, biopsy results, and treatment decisions recorded to establish the diagnostic reference standard.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePET/CT Imaging Protocol\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003ePET/CT Imaging Protocol\u003c/div\u003e \u003cp\u003eAll scans followed a standardized institutional \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT protocol. Patients fasted for at least 6 hours, and pre-scan blood glucose was confirmed less than 11.1 mmol/L. \u003csup\u003e18\u003c/sup\u003eF-FDG was injected intravenously at a weight-adjusted dose of 3.7\u0026ndash;5.5 MBq/kg. After a 60-minute uptake period in a quiet room, imaging was performed on a PET/CT scanner (Biograph 64, Siemens, Germany). A low-dose non-contrast CT scan was acquired with the following parameters: tube voltage 120 kV, tube current 100 mAs, pitch 0.9, and slice thickness 3 mm. This was followed by a 3D PET emission scan from skull vertex to mid-thighs (3\u0026ndash;6 bed positions, 2 minutes per bed). PET images were reconstructed using an ordered-subset expectation maximization algorithm (TrueX; 3 iterations, 21 subsets) with a 5.0 mm full-width at half-maximum Gaussian filter.\u003c/p\u003e \u003cp\u003e \u003cb\u003eReference Standard for Diagnosis of Metastasis\u003c/b\u003eGiven the clinical impracticality and potential morbidity of biopsy for every suspected metastatic lesion, a composite reference standard was applied for final diagnosis of metastasis, requiring fulfillment of at least one of the following criteria: (1) Pathological confirmation: Cytological or histological evidence of chordoma from a biopsy or resection of the suspected metastatic site. (2) Imaging progression: Definitive interval growth or development of a new lesion on serial follow-up imaging studies. (3) Highly suggestive multimodal imaging characteristics: A combination of a clear focal FDG uptake on PET (visibly higher than surrounding background activity) co-registered with a corresponding structural abnormality on CT (such as a soft tissue nodule/mass, lytic or mixed bone destruction) or with MRI features highly characteristic of chordoma (e.g., very high T2 signal intensity with T1 iso- or hypointensity and heterogeneous enhancement)[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cb\u003eImage Analysis and Interpretation\u003c/b\u003ePET/CT images were independently reviewed by two board-certified nuclear medicine physicians to identifying lesions meeting the predefined reference standard for metastasis. For each patient, the reviewers first assessed whether metabolic activity was present at the primary tumor site and, if present, measured its maximum standardized uptake value (SUVmax). Subsequently, a systematic whole-body evaluation was performed to detect potential metastatic disease. For any identified metastatic lesion, its SUVmax and maximum axial diameter were measured. The lesion volumes of interest were mapped on PET/CT fusion images using the three-dimensional outlining method, and the system automatically calculated the SUVmax. Lesion size was defined as the maximum axial diameter measured on the CT component of the PET/CT study. For lesions clearly defined on CT, size was measured directly; for isodense lesions, the maximum diameter was measured on axial PET/CT fusion images, based on the boundary defined by 40% of the lesion's SUVmax. The homogeneity of metabolic activity within each lesion was visually assessed on PET images. For each lesion, the anatomical location was recorded. Additional CT features such as density (relative to adjacent normal bone or skeletal muscle), morphology, and margin characteristics were documented.\u003c/p\u003e \u003cp\u003e \u003cb\u003eInterobserver Agreement and Consensus Process\u003c/b\u003eInterobserver agreement was formally assessed for key variables. Agreement on patient-level metastatic status (present vs. absent) was evaluated using Cohen\u0026rsquo;s kappa (\u003cem\u003eκ\u003c/em\u003e). For metastatic patients, the reliability of total lesion counts was assessed with the intraclass correlation coefficient (ICC; two-way random-effects model). Agreement on CT density patterns of bone metastases (hyperdense, mixed, hypodense, isodense) was evaluated using weighted kappa. Kappa values were interpreted as: \u0026lt;0 (poor), 0\u0026ndash;0.20 (slight), 0.21\u0026ndash;0.40 (fair), 0.41\u0026ndash;0.60 (moderate), 0.61\u0026ndash;0.80 (substantial), and 0.81\u0026ndash;1.00 (almost perfect). Discrepancies were resolved by joint re-review and consensus discussion. All subsequent analyses used this consensus dataset.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStatistical Analysis\u003c/b\u003eAll statistical analyses were performed using IBM SPSS Statistics (v27.0). Continuous non-normally distributed variables are presented as median with Confidence Interval (IQR) or range; categorical variables as counts and percentages. The Spearman's ρ was used to assess correlations between SUVmax and lesion size. Group comparisons employed the Mann-Whitney U test (two groups) or Kruskal-Wallis H test (\u0026ge;\u0026thinsp;3 groups). For paired comparisons, such as between the SUVmax of metastatic lesions and their corresponding local residual/recurrent lesions, the Wilcoxon signed-rank test was used. All tests were two-tailed, with \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cb\u003ePatient Characteristics\u003c/b\u003eThe cohort consisted of 21 patients (16 males, 5 females) with a median age of 61 years (range 18\u0026ndash;89). Primary tumor sites were the cervical spine (n\u0026thinsp;=\u0026thinsp;9), sacrum (n\u0026thinsp;=\u0026thinsp;9), and lumbar spine (n\u0026thinsp;=\u0026thinsp;3). Most tumors were of the conventional histological subtype (n\u0026thinsp;=\u0026thinsp;18), while the remaining cases were sarcomatoid (n\u0026thinsp;=\u0026thinsp;2) and poorly differentiated (n\u0026thinsp;=\u0026thinsp;1) subtypes. The median interval from initial diagnosis to PET/CT was 39 months (range 4\u0026ndash;156).\u003c/p\u003e \u003cp\u003e \u003cb\u003ePET/CT Findings\u003c/b\u003ePET/CT identified active tumor\u0026mdash;either local or metastatic\u0026mdash;in 20 of the 21 patients (95.2%). Local recurrence or residual tumor at the primary site was detected in 17 patients (81.0%), with a median SUVmax of 3.4 (IQR: 3.0\u0026ndash;5.9; range: 2.2\u0026ndash;13.4). Metastatic disease was detected in 11 patients (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). This metastatic group had a median age of 61 years, was predominantly male (n\u0026thinsp;=\u0026thinsp;9), and included patients with primary tumors in the cervical spine (n\u0026thinsp;=\u0026thinsp;5), sacrum (n\u0026thinsp;=\u0026thinsp;4), and lumbar spine (n\u0026thinsp;=\u0026thinsp;2). Histologically, the metastatic cohort comprised conventional-type chordomas (n\u0026thinsp;=\u0026thinsp;9), sarcomatoid (n\u0026thinsp;=\u0026thinsp;1), and poorly differentiated (n\u0026thinsp;=\u0026thinsp;1) subtypes. The single negative case showed a sacral insufficiency fracture without evidence of active disease on PET/CT.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics and subsequent treatment of patients with metastatic chordoma.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrimary Site\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHistologic Subtype\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eInterval from Initial Diagnosis to Current PET/CT (Months)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePrior Treatments\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSUVmax of Residual/Recurrent Lesion\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMetastatic Sites\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSubsequent Treatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eFollow-up after PET/CT (Months)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCervical Spine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eConventional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSurgery, Radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eLung, Soft Tissue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLumbar Spine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eConventional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSoft Tissue, Bone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSacrum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eConventional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSurgery, Radiotherapy, Particle Therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eLung, Soft Tissue, Bone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRadiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLumbar Spine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eConventional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSurgery, Radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSoft Tissue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSurgery, Radiotherapy, Immunotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCervical Spine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eConventional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRadiotherapy, Surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRadiotherapy, Systemic Therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCervical Spine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePoorly Differentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSurgery, Radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRadiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCervical Spine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSarcomatous Differentiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSurgery, Radiotherapy, Chemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eLung, Bone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eChemotherapy, Surgery, Radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSacrum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eConventional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eLung, Soft Tissue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRadiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSacrum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eConventional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSurgery, Radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSoft Tissue, Bone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCervical Spine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eConventional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSurgery, Radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eLung, Soft Tissue, Bone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eAnlotinib, Radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSacrum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eConventional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSurgery, Radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSoft Tissue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eParticle Implantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eInterobserver agreement was perfect for the dichotomous assessment of metastatic status and excellent for the total lesion count per patient among those with metastases (ICC\u0026thinsp;=\u0026thinsp;0.96, 95% CI: 0.86\u0026ndash;0.99). Agreement on the CT density classification of bone metastases was substantial (weighted \u003cem\u003eκ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.765).\u003c/p\u003e \u003cp\u003e \u003cb\u003eCharacteristics of Metastatic Lesions\u003c/b\u003eA total of 47 lesions were analyzed as metastases. Only three lesions in three patients were pathologically confirmed via biopsy (located in the ischium, gluteal muscle, and lung, respectively); the remainder were diagnosed based on imaging progression or highly suggestive imaging features.\u003c/p\u003e \u003cp\u003eBone metastases were found in 7 patients with a total of 21 lesions. Metastases were predominantly multifocal (6 of 7 patients, 85.7%) and distributed throughout the skeleton, most frequently in the spine (n\u0026thinsp;=\u0026thinsp;13). Primary tumors in these patients located in the cervical spine (n\u0026thinsp;=\u0026thinsp;4), lumbar spine (n\u0026thinsp;=\u0026thinsp;2), and sacrum (n\u0026thinsp;=\u0026thinsp;1). Lesions had a median size of 1.7 cm (IQR: 1.3\u0026ndash;3.2) and a median SUVmax of 3.8 (IQR: 3.3\u0026ndash;5.5). On CT, they displayed heterogeneous bone destruction patterns, categorized as hypodense (n\u0026thinsp;=\u0026thinsp;7, 33.3%), hyperdense (n\u0026thinsp;=\u0026thinsp;5, 23.8%), mixed (n\u0026thinsp;=\u0026thinsp;7, 33.3%), or isodense (n\u0026thinsp;=\u0026thinsp;2, 9.5%) lesions (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Metabolic activity was homogeneous in 15 lesions and heterogeneous in 6 lesions. SUVmax did not correlate with lesion size (\u003cem\u003eρ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.105, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.650) and did not differ significantly across CT density types (\u003cem\u003eH\u003c/em\u003e\u0026thinsp;=\u0026thinsp;4.644, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.200). An adjacent soft tissue mass was present in 33.3% of lesions but did not influence metabolic activity (SUVmax 4.1 vs. 3.6, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.455). Additionally, when analyzed by primary tumor histology, metastases from conventional-type chordomas (n\u0026thinsp;=\u0026thinsp;14 lesions) showed a median SUVmax of 3.6 (IQR: 3.2\u0026ndash;4.1), while those from poorly differentiated/dedifferentiated subtypes (n\u0026thinsp;=\u0026thinsp;7 lesions) exhibited a significantly higher median SUVmax of 6.4 (IQR: 4.2\u0026ndash;6.8) (\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.278, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.023).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSoft-tissue metastases were identified in 8 patients (15 lesions). The median lesion size was 2.3 cm (IQR: 1.7\u0026ndash;3.5) with a median SUVmax of 3.9 (IQR: 2.9\u0026ndash;5.4), and no correlation was found between these two parameters (\u003cem\u003eρ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.331, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.228). On CT, most lesions were isodense to muscle (n\u0026thinsp;=\u0026thinsp;11, 73.3%), while a minority were hypodense (n\u0026thinsp;=\u0026thinsp;4, 26.7%); the CT density did not significantly affect SUVmax (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.556). On PET, metabolic activity was homogeneous in 12 lesions and heterogeneous in 3. Anatomically, the majority of lesions (n\u0026thinsp;=\u0026thinsp;12, 80.0%) were located within the surgical bed or along its trajectory (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The remaining three distant subcutaneous lesions occurred in two patients, both of whom also had bone metastases, and one had concurrent pulmonary metastases.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePulmonary metastases were present in 5 patients, comprising a total of 11 nodules. All nodules appeared round-to-oval in shape with smooth margins and relatively homogeneous internal density on CT. Metabolic activity on PET was homogeneous in 9 nodules, while heterogeneous uptake was observed in the 2 larger lesions. The median size was 1.2 cm (IQR 0.8\u0026ndash;1.5 cm) and the median SUVmax was 2.3 (IQR 0.9\u0026ndash;2.5). A significant positive correlation was found between SUVmax and nodule size (Spearman's \u003cem\u003eρ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.839, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001). Notably, all 5 patients had concurrent bone or soft-tissue metastases; no isolated pulmonary metastasis was observed (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Primary tumors in these cases originated from the cervical spine (n\u0026thinsp;=\u0026thinsp;3) and sacrum (n\u0026thinsp;=\u0026thinsp;2).\u003c/p\u003e \u003cp\u003eAmong the 11 patients with metastatic disease, 8 patients had concurrent local residual or recurrent tumor. In these patients, the median SUVmax of bone and soft-tissue metastases (3.7) was comparable to that of the corresponding local lesions (3.3), with no statistically significant difference (\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.540, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.123).\u003c/p\u003e \u003cp\u003e \u003cb\u003eDetection of Additional Metastases by PET/CT\u003c/b\u003eIn 4 of 11 patients with metastatic disease, PET/CT detected more metastatic lesions that were outside the field of view of recent dedicated spine or pelvic MRI. These included pulmonary and bone metastases.\u003c/p\u003e\n\u003ch3\u003eTreatment Response and Illustrative Follow-up Case\u003c/h3\u003e\n\u003cp\u003eOver a median follow‑up of 9 months (range, 3\u0026ndash;79 months) after the PET/CT examination, 7 patients remained under surveillance. Among these, 5 showed disease progression, 1 had stable disease, and 1 died from disease. Four patients were lost to follow‑up. Treatment approaches included systemic therapy, local radiotherapy, and radioactive seed implantation. In one patient with concurrent bone, lung, and soft‑tissue metastases, treatment with Anlotinib for 3 months resulted in regression of lesions with higher baseline FDG avidity but enlargement of those with lower metabolic activity (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis retrospective study illustrates the potential utility of \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT in providing a comprehensive metabolic assessment of disease status in patients with suspected recurrent or metastatic chordoma. In our cohort of 21 patients, PET/CT identified active tumor in 20 patients (95.2%), with metastatic disease identified in 11 patients (52.4%). The two readers were in complete agreement on this patient-level assessment of metastatic status. In 4 of these 11 patients, PET/CT detected metastases outside the field of view of recent dedicated spine/pelvic MRI. For the 11 patients with metastases, the initial independent counts of total metastatic lesions showed excellent inter-reader reliability (ICC\u0026thinsp;=\u0026thinsp;0.96, 95% CI: 0.86\u0026ndash;0.99).\u003c/p\u003e \u003cp\u003eTo our knowledge, our analysis offers the first systematic report of the metabolic profile of metastatic chordoma across different sites, revealing moderate FDG avidity (median SUVmax: 3.8 for bone, 3.9 for soft tissue, and 2.3 for lung metastases). Overall, metabolic activity was homogeneous in the majority of lesions across all sites (71.4% of bone, 80.0% of soft-tissue, and 81.8% of pulmonary metastases). Notably, the metabolic activity of bone and soft‑tissue metastatic lesions closely paralleled that of local recurrences, suggesting a consistent biologic phenotype. Furthermore, we observed a significant correlation between higher metabolic activity (median SUVmax 6.4) and aggressive histologic subtypes (poorly/dedifferentiated), indicating that SUVmax may reflect tumor aggressiveness. The relationship between SUVmax and lesion size varied by site: it was independent in bone and soft‑tissue metastases but showed a strong positive correlation in pulmonary nodules (\u003cem\u003eρ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.839, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001). This dissociation highlights distinct tumor behaviors in different compartments.\u003c/p\u003e \u003cp\u003eThe imaging phenotype revealed by PET/CT diverges from classic radiological descriptions. Our cohort demonstrated a predilection for multifocal bone disease (85.7% of patients), with lesions having significantly smaller median size (1.7 cm) and only a minority (33.3%) associated with a soft‑tissue mass. In stark contrast, a prior CT/MRI‑based study by Chang et al. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] described osseous metastases as predominantly solitary (60%), large (mean 6.4 cm), and lytic with extensive soft‑tissue components. This discrepancy likely reflects differences in both imaging technology and, importantly, the clinical context of detection. In the present study, bone metastases were detected incidentally during evaluation of the primary site or on routine follow-up, whereas in the prior series, 67% of lesions were discovered because of pain or pathologic fracture. This contrast highlights that the metabolic and whole-body nature of PET/CT, particularly when employed for asymptomatic surveillance, can characterize metastatic disease at a point of lower tumor burden.\u003c/p\u003e \u003cp\u003eThe observed metastatic pattern, with a high frequency of osseous involvement (7/11, 63.6%), contrasts with the lower rates of bone metastasis (9.6%\u0026ndash;31.4%) reported in prior studies [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. This discrepancy may be primarily attributed to differences in imaging methodology. The earlier studies relied on chest CT and bone scintigraphy [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] or CT and MRI [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], whereas our systematic whole-body PET/CT approach likely has a higher sensitivity for detecting early, multifocal bone marrow infiltration. Furthermore, the predominance of mobile-spine (cervical or lumbar) primary tumors in our cohort (6 of the 7 patients with osseous metastases) may also influence the observed pattern, as metastatic spread in this subgroup could be facilitated by the anatomical proximity to the vertebral venous plexus (Batson\u0026rsquo;s plexus). Moreover, pulmonary metastases occurred in 5/11 (45.5%) patients, with 80% of these cases presenting concurrently with bone metastases, suggesting that osseous spread may precede or coincide with pulmonary hematogenous dissemination. This temporal sequence aligns with Chang et al.\u0026rsquo;s [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] description of contiguous spinal axis involvement and supports the hypothesis that the vertebral venous network likely serves as a primary pathway for initial metastatic seeding in mobile-spine chordomas.\u003c/p\u003e \u003cp\u003eThe distribution of soft‑tissue metastases provides complementary insights. In our series, 80% (12 of 15) of soft‑tissue lesions were confined to surgical tracts or the operative field, consistent with prior literature attributing such spread to iatrogenic seeding [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. This finding reinforces the importance of meticulous no‑touch surgical techniques and underscores the necessity of dedicated imaging surveillance of the operative region. Beyond locoregional spread, PET/CT detected hematogenous metastases to distant subcutaneous sites (20%, 3/15)\u0026mdash;lesions typically occult on routine, anatomically limited MRI or CT\u0026mdash;highlighting the value of whole‑body metabolic screening.\u003c/p\u003e \u003cp\u003ePreliminary observations from treatment follow‑up in our cohort further underscore the potential clinical relevance of the metabolic heterogeneity captured by baseline PET/CT. In one illustrative case, a patient with multi‑organ metastases showed a differential response after 3 months of Anlotinib therapy: lesions with higher baseline FDG avidity regressed, whereas those with lower initial metabolic activity progressed. Although anecdotal, this observation suggests that pre‑treatment metabolic profiling by PET/CT might help identify lesions with different biological behaviors and susceptibilities to systemic therapy. This aligns with our cross‑sectional finding that SUVmax correlates with histologic aggressiveness. Together, these insights suggest that baseline metabolic characterization could inform more personalized treatment strategies.\u003c/p\u003e \u003cp\u003eThis study has limitations inherent to its retrospective, single-center design and small sample size. Not all metastatic lesions had pathological confirmation, though we applied rigorous composite diagnostic criterion. Future prospective, multi-center studies with larger cohorts are needed to validate our findings and potentially establish standardized PET/CT protocols for chordoma surveillance.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study highlights the potential role of \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT in chordoma management. Its reproducible, whole-body metabolic assessment detects metastases beyond the field of view of conventional imaging and delineates site-specific metabolic profiles. The frequent detection of multifocal small bone metastases indicates an earlier pattern of spread than historically reported, underscoring the added value of metabolic imaging in routine surveillance. Furthermore, observed differential treatment responses linked to baseline metabolic heterogeneity suggest PET/CT may help characterize tumor biology and therapeutic susceptibility. Together with the correlation between high SUVmax and aggressive histology, these findings warrant further investigation into the prognostic and predictive utility of PET/CT for personalizing management in patients with high-risk chordoma.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003csup\u003e18\u003c/sup\u003eF‑FDG \u0026nbsp;\u003csup\u003e18\u003c/sup\u003eF‑fluorodeoxyglucose\u003c/p\u003e\n\u003cp\u003ePET/CT\u0026emsp;Positron Emission Tomography/Computed Tomography\u003c/p\u003e\n\u003cp\u003eSUVmax\u0026emsp;Maximum Standardized Uptake Value\u003c/p\u003e\n\u003cp\u003eMRI\u0026emsp;Magnetic Resonance Imaging\u003c/p\u003e\n\u003cp\u003eCT\u0026emsp;Computed Tomography\u003c/p\u003e\n\u003cp\u003eICC\u0026emsp;Intraclass Correlation Coefficient\u003c/p\u003e\n\u003cp\u003eCI\u0026emsp;Confidence Interval\u003c/p\u003e\n\u003cp\u003eIQR\u0026emsp;Interquartile Range\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted as per the Declaration of Helsinki. The approval to the protocol was done by the Ethics Committee of Peking University Third Hospital and each regulation was followed. The requirement for informed consent was waived by the board due to the retrospective nature of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Key Clinical Project of Peking University Third Hospital (BYSYDL2023003)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLS: conceptualization, image analysis, data-curation, writing-original draft, and editing. PLH: clinical and imaging data collection, data-curation. FW: supervision, data interpretation. WFZ: supervision, image analysis, editing. All authors reviewed and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWalcott BP, Nahed BV, Mohyeldin A, Coumans JV, Kahle KT, Ferreira MJ. Chordoma: current concepts, management, and future directions. Lancet Oncol. 2012; e69\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkiyama T, Ogura K, Gokita T, Tsukushi S, Iwata S, Nakamura T et al. Analysis of the Infiltrative Features of Chordoma: The Relationship Between Micro-Skip Metastasis and Postoperative Outcomes. Ann Surg Oncol. 2018; 912\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChang C, Chebib I, Torriani M, Bredella M. Osseous metastases of chordoma: imaging and clinical findings. Skeletal Radiol. 2017; 351\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKishimoto R, Omatsu T, Hasegawa A, Imai R, Kandatsu S, Kamada T. Imaging characteristics of metastatic chordoma. Jpn J Radiol. 2012; 509\u0026thinsp;\u0026ndash;\u0026thinsp;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShi Q, Guo W, Yu S, Xu J, Ji T, Tang X. Clinical characteristics and predisposing factors of lung metastasis in sacral chordoma: a cross-sectional cohort study of 221 cases. Front Oncol. 2024; 1416331.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStacchiotti S, Casali PG, Lo Vullo S, Mariani L, Palassini E, Mercuri M et al. Chordoma of the mobile spine and sacrum: a retrospective analysis of a series of patients surgically treated at two referral centers. Ann Surg Oncol. 2010; 211\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBerlucchi S, Nasi D, Zunarelli E, Valluzzi A, Alicandri Ciufelli M, Presutti L et al. Cutaneous Metastasis from Cervical Spinal Chordoma: Case Report and Literature Review. World Neurosurg. 2020; 296\u0026ndash;303.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFigliozzi S, Stankowski K, Monti L, Francone M. Multiparametric cardiovascular magnetic resonance characterization of a rare chordoma metastasis to the heart. Eur Heart J Cardiovasc Imaging. 2025; 1075.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSekmen S, Hursoy N, Gucer H, Burakgazi G, Balik MS, Cubukcu SS. Muscle metastasis from cervical chordoma: a case report. Skeletal Radiol. 2025; 1331\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStef\u0026agrave;no PL, Barletta G, Andrei V, Cerillo AG, Nesi G, Pilato G et al. Cardiac Metastasis of Sacral Chordoma. Ann Thorac Surg. 2021; e319\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCui F, Su M, Zhang H, Tian R. Humeral metastasis of sacrococcygeal chordoma detected by fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography: A case report. Radiol Case Rep. 2018; 449\u0026thinsp;\u0026ndash;\u0026thinsp;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCollins GR, Essary L, Strauss J, Hino P, Cockerell CJ. Incidentally discovered distant cutaneous metastasis of sacral chordoma: a case with variation in S100 protein expression (compared to the primary tumor) and review of the literature. J Cutan Pathol. 2012; 637\u0026thinsp;\u0026ndash;\u0026thinsp;43.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKinoshita T, Okudera T, Shimosegawa E, Yoshida Y, Yasui N, Ogawa T et al. Chordoma with postoperative subcutaneous implantation and meningeal dissemination: MRI. Neuroradiology. 2001; 763-6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFernandes Cabral DT, Zenonos GA, Fernandez-Miranda JC, Wang EW, Gardner PA. Iatrogenic seeding of skull base chordoma following endoscopic endonasal surgery. J Neurosurg. 2018; 947\u0026thinsp;\u0026ndash;\u0026thinsp;53.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-medical-imaging","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmim","sideBox":"Learn more about [BMC Medical Imaging](http://bmcmedimaging.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmim/default.aspx","title":"BMC Medical Imaging","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Chordoma, Metastasis, 18F-fluorodeoxyglucose, PET/CT, Spine, Surveillance","lastPublishedDoi":"10.21203/rs.3.rs-8715079/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8715079/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Systematic data on \u003csup\u003e18\u003c/sup\u003eF-fluorodeoxyglucose positron emission tomography/computed tomography (\u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT) in metastatic chordoma are scarce. This study aimed to evaluate its imaging characteristics, diagnostic consistency, and potential impact on clinical assessment and management.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e In this single-center retrospective analysis, 21 patients with pathologically confirmed chordoma and prior treatment underwent \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT for suspected recurrence or metastasis. Metastatic disease was diagnosed per a composite standard (biopsy, imaging progression, or characteristic multimodal findings). Relevant clinical and histopathological data were collected. Images were independently reviewed by two experienced nuclear medicine physicians for metabolic activity and whole-body disease assessment. They assessed metabolic activity at the primary site and performed whole-body evaluation. For each metastatic lesion, maximum standardized uptake value (SUVmax) and size were measured; CT features were also documented. Interobserver agreement for key assessments was formally evaluated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eMetastatic disease was identified in 11 of 21 patients (52.4%). Metastases were found in bone (7 patients), soft tissue (8 patients), and lung (5 patients). Site-specific metabolic patterns emerged: pulmonary metastases had lower FDG avidity (median SUVmax 2.3) correlated with size, whereas bone and soft-tissue avidity (SUVmax 3.8-3.9) was size-independent. A higher SUVmax was associated with poorly-differentiated histology (6.4 vs. 3.6, \u003cem\u003eP\u003c/em\u003e=0.023). Notably, in 4 out of 21 patients (19.0%), PET/CT detected metastases outside the field of view of conventional imaging. Interobserver agreement was perfect for metastatic status and excellent for total lesion counts. A case illustrated differential treatment response linked to baseline metabolic avidity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT offers a reproducible whole-body assessment for chordoma, enabling the detection of occult metastases and revealing clinically relevant metabolic heterogeneity. These findings highlight its potential in surveillance and personalized management, warranting further prospective validation.\u003c/p\u003e","manuscriptTitle":"18F‑FDG PET/CT in metastatic chordoma: a retrospective analysis of imaging features and clinical impact","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-27 12:02:19","doi":"10.21203/rs.3.rs-8715079/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-15T06:52:32+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-12T16:12:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"188025571443284393625839298838779371899","date":"2026-03-06T06:50:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"216271992645755200605689083040799884917","date":"2026-03-04T04:09:36+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-25T15:54:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"220887217364988722355171403317649498698","date":"2026-02-24T14:55:02+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-24T11:35:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-23T10:44:41+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-30T16:38:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-30T01:36:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Medical Imaging","date":"2026-01-30T01:30:55+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-medical-imaging","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmim","sideBox":"Learn more about [BMC Medical Imaging](http://bmcmedimaging.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmim/default.aspx","title":"BMC Medical Imaging","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6d447a91-c792-4033-b3e5-8134720b075c","owner":[],"postedDate":"February 27th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-13T07:58:00+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-27 12:02:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8715079","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8715079","identity":"rs-8715079","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}