Characterization of sacral chordoma and differential diagnosis from other sacral malignancy using [18F]FDG PET/CT.

2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET)/computed tomography (CT) is known to be a helpful imaging modality for sacral chordoma, but its detailed characteristics have not been fully described. The purpose of our study was to identify the [18F]FDG PET/CT imaging characteristics of sacral chordoma and compare them with other sacral malignancy. This retrospective study included patients who underwent [18F]FDG PET/CT because of a mass involving the sacrum. Investigated visual findings included visual score and distribution, and semiquantitative parameters measured included standardized uptake values (SUVmax, SUVpeak, SUVmean), tumor-to-liver ratio (TLR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor size. Comparison studies and receiver operating characteristics (ROC) curve analysis were performed to differentiate between sacral chordoma and other sacral malignancy. Ten patients with sacral chordoma were finally included (M:F = 6:4, median age = 67 yr). On [18F]FDG PET/CT, sacral chordomas presented as a mass with minimal-moderate uptake with a usually heterogenous distribution. Compared with 12 patients with other sacral malignancies (M:F = 4:8, median age 42 yr), sacral chordoma showed a significantly lower TLR (median value 2.1 vs 6.3, P = .021). In ROC curve analysis, TLR showed the largest area under the curve (AUC) of 0.79 (cutoff ≤ 4.0; sensitivity 100.0%, specificity 58.3%; P = .004), and SUVmax showed the second largest AUC of 0.73 (cutoff ≤ 6.9; sensitivity 80.0%, specificity 66.7%; P = .034). [18F]FDG PET/CT of sacral chordoma showed minimal-moderate uptake. The TLR of [18F]FDG PET/CT was significantly lower than that of other sacral malignancy and was the most useful parameter for differentiating sacral chordoma, with the largest AUC. SUVmax could be another helpful semiquantitative parameter.

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.

Chordoma of the Oropharynx.

Background: Chordoma is a rare malignant neoplasm that predominantly arises from the axial skeleton, but can also develop in unusual locations. However, there are also rare cases of "NOS" chordoma involving the oropharyx and epithelial-myoepithelial carcinoma of the parotid gland in the same patient. According to contemporary research, chordoma is a rare malignant neoplasm that arises from the embryonic remnants of the notochord. and typically involves the clivus, sacrococcygeal bones or vertebrae. Studies have shown that the incidence of chordoma has been estimated to be one per one million people per year. Chordoma can occur at any age, but most commonly it is diagnosed in the 40-60 year old age group with the male predominance. Objective: The aim of this article was to review the case of a 74-year-old female patient with epithelial-myoepithelial carcinoma of the parotid gland and a case of "NOS" chordoma involving the oropharyx. Methods: Diagnostic methods were used to examine a female patient with two primary malignant tumors: CT neck scan, CT of paranasal sinuses, ultrasound examination, scintigraphy and operative finding. Case presentzation: Due to the anatomy complexity, complete resection of the tumor through a transoral-transpharyngeal approach was not possible. Intraoperative palpation of the mass revealed well defined submucosal lesion 20x43x46mm beginning at the level of the oro- and hypopharynx and extending superiorly to the nasopharynx, and posteriorly into the spinal canal and intervertebral foramen causing near complete occlusion of the oro and hypopharynx. The patient also underwent extracapsular dissection of the parotid tumor. Postoperative palliative radiotherapy was performed. Conclusion: Surgical treatment remains the mainstay of treatment for EMC and radiation is imperative for patients who refuse surgery and for those with advanced or inoperable diseases.

SIRT5 promote malignant advancement of chordoma by regulating the desuccinylation of c-myc.

Chordoma is a relatively rare and locally aggressive malignant tumor. Sirtuin (SIRT)5 plays pivotal roles in various tumors, but the role of SIRT5 in chordoma has not been found. This study was performed to investigate the regulatory effects of SIRT5 on cell proliferation, migration, and invasion and the underlying mechanism in chordoma. A xenograft tumor mouse model was established to assess tumor growth. Reverse transcription-quantitative polymerase chain reaction was used to analyze the mRNA levels of SIRT5 and c-myc. The effects of SIRT5 and c-myc on cell proliferation, migration, and invasion of chordoma cells were detected by cell counting kit-8, colony formation, and Transwell assays. The interaction between SIRT5 and c-myc was evaluated by co-immunoprecipitation (IP) assay. The succinylation of c-myc was analyzed by IP and Western blot. The results showed that SIRT5 expression was upregulated in chordoma tissues and cells. SIRT5 interacted with c-myc to inhibit the succinylation of c-myc at K369 site in human embryonic kidney (HEK)-293T cells. Silencing of SIRT5 suppressed the cell proliferation, migration, and invasion of chordoma cells, while the results were reversed after c-myc overexpression. Moreover, silencing SIRT5 suppressed tumor growth in mice. These findings suggested that SIRT5 promoted the malignant advancement of chordoma by regulating the desuccinylation of c-myc.

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.

Effectiveness of Carbon Ion Radiotherapy for Bone and Soft Tissue Sarcoma in Older Patients.

BACKGROUND/AIM: The aging population is expected to increase the occurrences of bone sarcoma (BS) and soft tissue sarcoma (STS). Carbon ion radiotherapy (CIRT) is reported to be effective for BS and several STSs. However, the effect of CIRT on clinical outcomes, functional prognoses, and quality of life (QOL) in older patients who underwent CIRT has not been reported. Therefore, we aimed to evaluate the effect of CIRT on clinical outcomes, functional prognoses and QOL in older patients with BS or STS. PATIENTS AND METHODS: This retrospective cohort study included 235 patients aged >70 years with BS or STS who underwent CIRT. Overall survival (OS), cancer-specific survival (CSS), and local control (LC) were evaluated in chordoma and non-chordoma patients. Furthermore, factors associated with post-CIRT Toronto Extremity Salvage Score (TESS) and EuroQoL 5-dimension 5-level (EQ-5D-5L) index were assessed. RESULTS: The overall 5-year LC, OS, and CSS rates were 81%, 62%, and 76%, respectively. In the chordoma and non-chordoma groups, the 5-year LC, OS, and CSS rates were 84%, 72%, and 87%; and 77%, 47%, and 60%, respectively. The mean post-CIRT TESS and EQ-5D-5L index were 75% and 0.71, respectively. The TESSs and EQ-5D-5L indices tended to be better among males, younger patients (<76 years old), patients with small tumor volumes, and patients with chordoma. CONCLUSION: CIRT is effective for older patients with BS, especially with chordoma, and STS with good LC and survival rates. Furthermore, post-treatment limb function and QOL were comparable with those of the other treatments and age groups.

Organelle resolved proteomics uncovers PLA2R1 as a novel cell surface marker required for chordoma growth.

Chordomas are clinically aggressive tumors with a high rate of disease progression despite maximal therapy. Given the limited therapeutic options available, there remains an urgent need for the development of novel therapies to improve clinical outcomes. Cell surface proteins are attractive therapeutic targets yet are challenging to profile with common methods. Four chordoma cell lines were analyzed by quantitative proteomics using a differential ultracentrifugation organellar fractionation approach. A subtractive proteomics strategy was applied to select proteins that are plasma membrane enriched. Systematic data integration prioritized PLA2R1 (secretory phospholipase A2 receptor-PLA2R1) as a chordoma-enriched surface protein. The expression profile of PLA2R1 was validated across chordoma cell lines, patient surgical tissue samples, and normal tissue lysates via immunoblotting. PLA2R1 expression was further validated by immunohistochemical analysis in a richly annotated cohort of 25-patient tissues. Immunohistochemistry analysis revealed that elevated expression of PLA2R1 is correlated with poor prognosis. Using siRNA- and CRISPR/Cas9-mediated knockdown of PLA2R1, we demonstrated significant inhibition of 2D, 3D and in vivo chordoma growth. PLA2R1 depletion resulted in cell cycle defects and metabolic rewiring via the MAPK signaling pathway, suggesting that PLA2R1 plays an essential role in chordoma biology. We have characterized the proteome of four chordoma cell lines and uncovered PLA2R1 as a novel cell-surface protein required for chordoma cell survival and association with patient outcome.

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.

Soft-tissue reconstruction with pedicled vertical rectus abdominis myocutaneous flap after total or high sacrectomy for giant sacral tumor.

BACKGROUND: The large soft-tissue defect after total or high sacrectomy for giant sacral tumor induces high incidence of wound complications. It remains a huge challenge to reconstruct the soft-tissue defect and achieve the preferred clinical outcome. METHODS: A total of 27 patients undergoing one-stage total or high sacrectomy for giant sacral tumors between 2016 and 2021 in a tertiary university hospital were retrospectively reviewed. Participants were divided into two groups. Thirteen patients underwent a pedicled vertical rectus abdominis myocutaneous (VRAM) flap reconstruction, whereas 14 patients underwent a conventional wound closure. Patient's clinical characteristics, surgical duration, postoperative complications, and outcomes were compared between the two groups. RESULTS: Patients in VRAM and non-VRAM groups were similar in baseline characteristics. The mean tumor size was 12.85 cm (range: 10-17 cm) in VRAM group and 11.79 cm (range: 10-14.5 cm) in non-VRAM group (P = 0.139). The most common giant sacral tumor is chordoma. Patients in VRAM group had a shorter length of drainage (9.85 vs 17.14 days), postoperative time in bed (5.54 vs 17.14 days), and total length of stay (19.46 vs 33.36 days) compared with patients in non-VRAM group. Patients in the VRAM group had less wound infection and debridement than patients in non-VRAM group (15.4% vs 57.1%, P < 0.001). CONCLUSIONS: This study demonstrates the advantages of pedicled VRAM flap reconstruction of large soft-tissue defects after high or total sacrectomy using the anterior-posterior approach. This choice of reconstruction is better than direct wound closure in terms of wound infection, length of drainage, and total length of stay.

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.

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.

Chordoma: demographics and survival analysis with a focus on racial disparities and the role of surgery, a U.S. population-based study

Background Chordoma is a rare malignant tumor of notochordal origin that may appear anywhere in the axial skeleton from the skull base to the sacrum. This study presents findings from a large database query to highlight the demographic, clinical, and pathological factors, prognosis, and survival of chordomas. Methods The Surveillance, Epidemiology, and End Results (SEER) data based was used to identify patients with a “chordoma” diagnosis from 200 to 2018. Results In a total of 1600 cases, the mean age at diagnosis was 54.47 years (standard deviation, SD ± 19.62 years). Most cases were male (57.1%) and white (84.5%). Tumor size was found to be > 4 cm in 26% of cases. Histologically, 33% with known features had well-differentiated Grade I tumors, and 50.2% of the tumors were localized. Metastasis at the time of to the bone, liver, and lung was observed at a rate of 0.5%, 0.1%, and 0.7%, respectively. The most common treatment received was surgical resection (41.3%). The overall 5-year overall survival observed was 39% (confidence interval, CI 95% 37–41; p = 0.05) with patients who received surgery having a 5-year survival rate of 43% (CI 95% 40–46; p = 0.05). Multivariate analysis showed independent factors that contributed to worse prognosis chemotherapy only as a treatment modality and no surgery as a treatment modality. Conclusion Chordomas are more common in white males and appear between the 5th and 6th decades of life. Factors that contributed to a worse prognosis were Asian, Pacific Islander, American Indian, or Alaska Native races (AU)

Dysregulation of noncoding RNA in chordoma; implications in identifying potential targets for novel therapeutic approaches.

Chordoma is a rare form of bone cancer develops in the spinal cord and skull. Instead of conventional (radio/chemotherapies) and targeted therapies, the disease is associated with high rate of recurrence and poor patient survival. Thus, for better disease management, the molecular pathogenesis of chordoma should be studied in detail to identify dysregulated biomolecules that can be targeted by novel therapeutics. Recent research showed frequent dysregulation of long noncoding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA) in association with aggressive tumor phenotypes like cell proliferation, migration, invasion, and metastasis in a variety of cancers, including chordoma. Apart from diagnostic and prognostic importance, noncoding RNAs may serve as promising targets for novel therapeutics in cancer. In this review, we summarized a list of miRNAs, lncRNAs, and circRNA found to be dysregulated in chordoma from available data published in relevant databases (PubMed), as such an approach seems to be rare to date. The dysregulated noncoding RNAs were also associated with adverse tumor phenotypes to assess the impact on disease pathogenesis and, associated downstream molecular pathways were focused. Synthetic compounds and natural products that were reported to target the noncoding RNAs in other malignancies were also listed from published literature and proposed as potential therapeutic agents in chordoma. This review will provide information for further research on chordoma focusing on detailed characterization of dysregulated lncRNAs, miRNAs, and circRNA to understand the disease pathogenesis and, exploration of suitable natural and synthetic products targeting dysregulated non-coding RNAs to develop effective therapeutic measures.

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.

Clinical indications for carbon-ion radiotherapy in the UK: A critical review.

INTRODUCTION: Carbon-ion radiotherapy (CIRT) has unique radiobiological properties that cause increased radiobiological effect and tumour control, especially with hypoxic tissues. This critical review aimed to evaluate clinical response to CIRT across all published tumour sites to establish if there is a clinical need for a CIRT centre in the UK. METHODS: A critical review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Literature searching was undertaken in November 2022 within the PubMed, Science Direct, SCOPUS and Web of Science databases using the term 'carbon ion radiotherapy' in the title, abstract or author keywords. RESULTS: After critical appraisal, data was extracted from 78 primary study papers. Strong evidence supported use of CIRT for chondrosarcoma, chordoma, nasopharyngeal, non-small cell lung cancer (NSCLC), oral cavity, prostate, rectal and salivary gland tumours. Further research is needed to strengthen the evidence base for some other tumour types. CONCLUSION: The UK's incidence and mortality rates suggest a clinical need for CIRT for chondrosarcoma, chordoma, NSCLC, oral cavity, prostate, and rectal tumours. There is a need to improve survivorship amongst pancreatic, liver, and oesophageal cancer patients. Data published relating to CIRT for these tumours is promising but of lower quality and more research is needed in these areas. IMPLICATIONS FOR PRACTICE: The clinical response to CIRT for certain tumours suggests the need for a carbon-ion centre in the UK. Demand for further research [phase III trials] has been identified, giving the UK opportunity to establish a research centre, with opportunity to treat, contributing to world-renowned research whilst improving patient outcomes.

Identification of Reference Genes in Chordoma Cells Allows Cross-Comparison of Expression Studies Across Subtypes.

AIM: To present the best housekeeping genes including clival/sacral based chordoma, and the nucleus pulposus cells. MATERIAL AND METHODS: We investigated 13 candidate reference genes in public chordoma array transcriptome datasets, validated these genes by using RT-PCR, and evaluated their stability with NormFinder, geNorm, and Bestkeeper. RESULTS: YWHAZ, TBP and PGK1 genes were identified as the most stable reference genes as confirmed with three different approaches. Conversely, KRT8, KRT19 and GAPDH genes are less stable and not appropriate for use in chordoma research. CONCLUSION: For normalization of RT-PCR experiments in gene profiling of chordoma, we recommend the use of the stable genes YWHAZ, TBP and PGK1.

Hypoxia-Inducible Factor-1α (HIF-1α) as a Factor to Predict the Prognosis of Spinal Chordoma.

STUDY DESIGN: Retrospective study. OBJECTIVE: In this study, the authors explore the potential relationship between hypoxia inducible factor-1α (HIF-1α) and the prognosis of patients with spinal chordoma. SUMMARY OF BACKGROUND DATA: Currently, prognostic factors related to the clinical course in the setting of spinal chordoma are poorly understood. Although the close relationship between HIF-1α and tumor angiogenesis, metastasis, and recurrence have been widely reported, it has not been investigated in the context of spinal chordoma. MATERIALS AND METHODS: In this study, 32 samples of chordoma patients were compared with 14 nucleus pulposus tissues as controls. The specific expression of HIF-1α was detected by immunohistochemistry. Continuous disease-free survival (CDFS) was defined as the interval from tumor resection to confirmation of the first local recurrence or distant metastasis. Overall survival (OS) was defined as the interval from the date of surgery to death related to any cause. The relationship between HIF-1α expression and the clinicopathologic characteristics of patients with chordoma was analyzed using the Pearson χ 2 test. Multivariate Cox analysis was used to evaluate whether HIF-1α expression was associated with the prognosis of patients after controlling for confounders. RESULTS: HIF-1α was mainly expressed in the cytoplasm or nucleus in all of the chordoma samples, which showed significantly higher than that in the normal nucleus pulposus tissue ( P =0.004). Multivariate Cox regression analyses showed that high HIF-1α expression and location of HIF-1α expression were significantly associated with poor CDFS (hazard ratio (HR)=3.374; P =0.021) and OS (HR=4.511; P =0.012). In addition, we further found that high HIF-1α expression both in the cytoplasm and nucleus indicated a stronger prognostic factor for poor CDFS (HR=3.885; P =0.011) and OS (HR=4.014; P =0.011) in spinal chordoma patients. CONCLUSION: High HIF-1α expression may become a potential new biological indicator to predict a poor prognosis in patients with spinal chordoma. HIF-1α may also represent a novel therapeutic target for the treatment of spinal chordoma.

Chordoma: demographics and survival analysis with a focus on racial disparities and the role of surgery, a U.S. population-based study.

BACKGROUND: Chordoma is a rare malignant tumor of notochordal origin that may appear anywhere in the axial skeleton from the skull base to the sacrum. This study presents findings from a large database query to highlight the demographic, clinical, and pathological factors, prognosis, and survival of chordomas. METHODS: The Surveillance, Epidemiology, and End Results (SEER) data based was used to identify patients with a "chordoma" diagnosis from 200 to 2018. RESULTS: In a total of 1600 cases, the mean age at diagnosis was 54.47 years (standard deviation, SD ± 19.62 years). Most cases were male (57.1%) and white (84.5%). Tumor size was found to be > 4 cm in 26% of cases. Histologically, 33% with known features had well-differentiated Grade I tumors, and 50.2% of the tumors were localized. Metastasis at the time of to the bone, liver, and lung was observed at a rate of 0.5%, 0.1%, and 0.7%, respectively. The most common treatment received was surgical resection (41.3%). The overall 5-year overall survival observed was 39% (confidence interval, CI 95% 37-41; p = 0.05) with patients who received surgery having a 5-year survival rate of 43% (CI 95% 40-46; p = 0.05). Multivariate analysis showed independent factors that contributed to worse prognosis chemotherapy only as a treatment modality and no surgery as a treatment modality. CONCLUSION: Chordomas are more common in white males and appear between the 5th and 6th decades of life. Factors that contributed to a worse prognosis were Asian, Pacific Islander, American Indian, or Alaska Native races.