Management Of Chordomas Research Articles

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

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

Impact of proton versus photon adjuvant radiotherapy on overall survival in the management of skull base and spinal chordomas: a National Cancer Database analysis.

Chordomas are rare tumors that originate from undifferentiated remnants of the notochord. Currently, there are no established guidelines regarding the choice of adjuvant radiation modality for patients surgically treated for chordomas. Using a nationwide, multicenter database, the authors aimed to compare long-term survival outcomes associated with the use of proton or photon adjuvant therapy for the management of chordomas of skull base and spine. The National Cancer Database (NCDB) was queried for chordoma cases from 2004 to 2017. Patient, tumor, and treatment characteristics were extracted from the database. The primary outcome was overall survival (OS). Kaplan-Meier survival analyses were conducted to investigate differences in outcome on propensity score-matched cohorts of patients treated with proton or photon adjuvant radiotherapy. Of the 3490 patients available, 424 met the inclusion criteria for this study. In the prematching analysis, patients receiving adjuvant photon therapy were significantly older (median age 57.0 vs 45.0 years, p < 0.001) and were more commonly male (61% vs 43%, p < 0.001) compared with those receiving proton therapy. Races were equally distributed among radiotherapy modalities (p = 0.64). Patients with chordomas of the mobile spine or sacrum were less likely to receive proton compared with photon therapy (37% vs 58%). Patients receiving proton therapy were more often represented among private insurance holders (69% vs 52%, p < 0.001) as well as in the highest income quartile (52% vs 40%, p = 0.008). Patients traveled farther to receive proton, as opposed to photon, therapy (median 59.0 vs 34.9 miles, p < 0.001). On postmatching Kaplan-Meier analysis encompassing all chordoma cases, no difference in OS between photon and proton therapy was revealed (HR 0.75, 95% CI 0.39-1.44; p = 0.39). A Kaplan-Meier analysis only including patients with skull base chordomas reached similar results (HR 0.83, 95% CI 0.31-2.22; p = 0.71). In patients with spine chordomas, however, a significant difference was found, as proton therapy exhibited a superior OS over photon therapy (HR 0.28, 95% CI 0.09-0.81; p = 0.012). Based on this nationwide analysis, patients with private insurance and higher income were more likely to receive proton adjuvant radiotherapy, while those with spinal or sacral chordomas were less likely to receive this modality. Despite this disparity, an OS benefit was observed in patients with chordomas of the spine and sacrum who received adjuvant proton therapy, in comparison with a matched cohort of patients treated with photon therapy. Conversely, this advantageous outcome was not evident in cases of chordomas located at the skull base.

P.081 Chordoma management with artificial intelligence: a scoping review of current applications and future prospects

Background: Chordomas are rare, malignant bone tumors that present significant challenges in management and treatment due to their complex anatomical locations and propensity for recurrence. Advancements in artificial intelligence (AI) and machine learning (ML) show promise in improving chordoma management. Methods: A comprehensive literature search was conducted following PRISMA guidelines across multiple databases, including MEDLINE, Cochrane, Embase, Scopus, and Web of Science. The search targeted articles related to AI and ML applications in clinical tasks associated with chordoma management. The selection process involved systematic screening, data extraction, and assessment of inter-rater variability. Results: The search yielded 1,006 records, with 18 included for analysis. Convolutional neural networks (CNNs) excelled in tumor volume estimation, with the state-of-the-art model achieving a Dice similarity score of 74.2%, sensitivity of 79.4%, and positive predictive value of 74.3%. Clustering algorithms were effective in prognostic evaluations. Bayesian models and logistic regression demonstrated robustness in diagnostics. Support vector machines (SVMs) were noted for their diagnostic precision. Conclusions: AI and ML algorithms, particularly CNNs, clustering algorithms, Bayesian models, logistic regression, and SVMs, show promise in improving chordoma management through enhanced imaging, diagnostics, and prognostics. Future research should focus on larger, externally validated datasets and explore underutilized techniques like multi-modal data integration.

Predicting the Need for Occipitocervical Fusion for Patients with Lower Clival Chordoma: A Single-Center Retrospective Study

To assess the impact of tumor extension into the occipital condyle (OC) in lower clival chordoma management and the need for occipito-cervical fusion (OCF). A retrospective analysis was conducted on 35 patients with lower clival chordoma. The preoperative area of the intact OCs, Hounsfield units, and the integrity of the apical ligament and the tectorial membrane were assessed using preoperative imaging. Seven (20%) patients were in the OCF group. The OCF group exhibited a higher prevalence of preoperative pain in the neck or head (p = 0.006), ligament absence (p = 0.022), and increased propensity for postoperative wound issues (p = 0.022) than the non-OCF group. The OCF group had less intact OCs (p < 0.001) and higher spinal instability neoplastic score (p = 0.002) than the non-OCF group. All patients with intact OCs<60% underwent OCF, and those with OCs≥70% were treated without OCF. Those with OCs between 60% and 69% underwent OCF if the ligaments were eroded, and did not undergo OCF if the ligaments were intact. Treatment strategies varied, with endoscopic endonasal approach (EEA) alone being common. Radiation therapy was administered to 89% of patients. All three patients treated with OCF after tumor resection had wound issues; none treated with OCF before resection had wound issues. None developed atlanto-occipital instability. Survival rates did not significantly differ between groups. In the absence of mobility-related neck pain, patients with lower clival chordoma and intact OC≥60%, intact apical ligament, and intact tectorial membrane, may not require OCF.

Artificial intelligence – an aid for physicians in chordoma management? A systematic review of current applications

Artificial intelligence – an aid for physicians in chordoma management? A systematic review of current applications

Chordoma: A Comprehensive Systematic Review of Clinical Trials.

This systematic review aims to characterize ongoing clinical trials and therapeutic treatment options for chordoma, a rare notochordal remnant tumor that primarily affects the cranial base, mobile spine, and sacrum. While radical surgical resection remains the cornerstone for chordoma management, unique technical challenges posed by its proximity to critical neurovascular structures confer a tendency towards disease recurrence which often requires additional treatment modalities. In an attempt to better understand the current treatment landscape, a systematic review was designed to identify clinical trials directed at chordoma. A total of 108 chordoma trials were identified from four clinical trial databases; fifty-one trials were included in the final analysis, of which only 14 were designated as completed (27.5%). Aggregate data suggests most chordoma interventions are repurposed from other neoplasms that share common molecular pathways, with a recent emphasis on combination therapeutics within and across drug classes. Naturally, the publication and dissemination of clinical trial results remain a concern (n = 4, 28.6%), highlighting the need for enhanced reporting and transparency measures. Active clinical trial efforts are quite promising, with a renewed focus on novel biotherapeutic targets and deciphering the natural history, as well as survivorship of this complex disease.

Management of chordoma and chondrosarcoma with definitive dose-escalated single-fraction spine stereotactic radiosurgery.

The management of chordoma or chondrosarcoma involving the spine is often challenging due to adjacent critical structures and tumor radioresistance. Spine stereotactic radiosurgery (SSRS) has radiobiologic advantages compared with conventional radiotherapy, though there is limited evidence on SSRS in this population. We sought to characterize the long-term local control (LC) of patients treated with SSRS. We retrospectively reviewed patients with chordoma or chondrosarcoma treated with dose-escalated SSRS, defined as 24Gy in 1 fraction to the gross tumor volume. Overall survival (OS) was calculated by Kaplan-Meier functions. Competing risk analysis using the cause-specific hazard function estimated LC time. Fifteen patients, including 12 with chordoma and 3 with chondrosarcoma, with 22 lesions were included. SSRS intent was definitive, single-modality in 95% of cases (N = 21) and post-operative in 1 case (5%). After a median censored follow-up time of 5 years (IQR 4 to 8 years), median LC time was not reached (IQR 8 years to not reached), with LC rates of 100%, 100%, and 90% at 1 year, 2 years, and 5 years. The median OS was 8 years (IQR 3 years to not reached). Late grade 3 toxicity occurred after 23% of treatments (N = 5, fracture), all of which were managed successfully with stabilization. Definitive dose-escalated SSRS to 24Gy in 1 fraction appears to be a safe and effective treatment for achieving durable local control in chordoma or chondrosarcoma involving the spine, and may hold particular importance as a low-morbidity alternative to surgery in selected cases.

Letter: Chordoma and Ecchordosis Physaliphora: 2 Sides of the Same Coin.

To the Editor: Chordoma and ecchordosis physaliphora (EP) are tumors arising from the notochord's remains along the axial skeleton from the dorsum sella to the sacrococcygeal region. Each year, 1 person in a million is diagnosed with chordoma, but only 45 cases of EP have been reported.1-12 In 1857, Virchow invented the acronym EP for the newly discovered dorsum sella lesion, believing it was cartilage related. A year later, Muller discovered notochord rests in the synchondrosis sphenooccipitalis and hypothesized that these were the source of the EP dorsum sella masses. Ribbert then endorsed this theory.13 Over a century later, Congdon and Wolfe coined the terms benign chordoma and intradural chordoma.14,15 Cha et al justified distinguishing EP from chordoma because they are treated differently and have a different prognosis because one is more aggressive than the other. So far, approximately 45 cases of EP have been diagnosed, with 10 patients displaying symptoms. In 1 of these cases, the patient died as a result.13 Two chief aspects spring to mind when pondering this subject. The first is the manner in which these instances were diagnosed and distinguished from chordoma cases. The second issue stems from the first, namely how to determine the ideal modality of treatment when there is no objective way to distinguish between those pathologies. The articles concur that it is impossible to distinguish between them based on histology or immunohistochemistry staining results because they are derived from the same embryonic notochord. Although certain histopathologic characteristics such as hypocellularity, sparse pleomorphism, and the lack of mitosis may aid in the differentiation of EP from chordoma, they are not considered diagnostic criteria.5,6,16 In addition, it has been stated that an intradural location favors EP over chordoma, yet there are instances of chordoma being an intradural.17 From an imaging point of view, chordoma frequently presents a contrast-enhanced lesion. However, it may occasionally exhibit a mild or nonenhanced lesion similar to EP.18 A study of 28 patients found that 65% of magnetic resonance images of chordoma showed mild or no enhancement.19 Moreover, all reported spinal EPs demonstrated enhanced extradural mass, similar to chordoma lesions.3-6,13 In conclusion, differentiation based on histology, immunohistochemistry staining, radiologic results, or the presence of symptoms is inaccurate. Based on the foregoing, it is impossible, or at least impractical, to distinguish between the 2 terms because they refer to the same ailment. Additional environmental or genetic factors may influence the severity and progression of the disease.20 It would be prudent to consolidate these 2 disorders as part of the spectrum of the same disease, chordoma, and classify it based on severity according to the radiologic findings for size, location, and bone involvement. We hope this paradigm shift will lay the groundwork for novel approaches to chordoma management.

Management of Chordoma of the Sacrum and Mobile Spine.

Chordomas account for 1% to 4% of primary tumors of the spine and sacrum. En bloc resection is the preferred surgical treatment for the management of chordomas. Proton beam radiation is increasingly being used as a postoperative radiation modality for the treatment of chordomas.

Circulating tumor DNA - A potential aid in the management of chordomas.

Chordomas are a locally invasive, low-grade, CNS malignancy that are primarily found in the skull base, spine, and sacrum. They are thought to be derived from notochordal remnants and remain a significant clinical challenge due to their local invasiveness, resistance to chemoradiation, and difficulty in achieving a complete resection. Adjuvant therapy such as proton beam therapy is critical in preventing recurrence in patients who are at high risk, however this treatment is associated with increased risk of complication. Currently, intraoperative observation and imaging findings are used to determine recurrence and success of gross total resection. These methods can be unreliable due to limited operative view, bony and soft tissue involvement, and complex post-operative changes on MRI. Earlier detection of incomplete resection or recurrence will allow for earlier ability to intervene and potentially improve patient outcomes. Circulating-tumor DNA (ctDNA) is cell-free DNA that is released by tumor cells as they undergo cellular turn-over. Monitoring ctDNA has been shown to be more sensitive at predicting residual tumor than imaging in numerous solid malignancies. Furthermore, ctDNA could be detected earlier in peripheral blood as opposed to imaging changes, allowing for earlier intervention. In this review, we intend to give a brief overview of the current state of molecular diagnosis for skull base chordomas. We will then discuss current advances in the utilization of ctDNA for the management of CNS pathologies such as glioblastoma (GBM) and brain metastases. We will also discuss the role ctDNA has in the management of non-CNS pathologies such as osteosarcoma and Ewing sarcoma (EWS). Finally, we will discuss potential implications of ctDNA monitoring for chordoma management.

The impact of radiotherapy on survival after surgical resection of chordoma with minimum five-year follow-up

BACKGROUND CONTEXTLocal control remains a vexing problem in the management of chordoma despite advances in operative techniques and radiotherapy (RT) protocols. Existing studies show satisfactory local control rates with different treatment modalities. However, those studies with minimum follow-up more than 4 years demonstrate increasing rates of local failure. Therefore, mid-term local survival rates may be inadvertently elevated by studies with less than 4 years follow-up. PURPOSEThe purpose of this study is to report the mid-term results of primary spinal chordoma treated with en bloc resection and proton-based RT with minimum 5 years of follow-up. STUDY DESIGN/SETTINGRetrospective, single-center, cohort study. PATIENT SAMPLEPatients undergoing primary surgical excision of a spine or sacral chordoma tumor between 1990 and 2016 at a single-institution were included. Patients were included if they had a local failure at any time, or they had a minimum of 5 years of follow up with no local failure. Patients were excluded if a prior surgical excision was performed or metastases were present at the time of referral. OUTCOME MEASURESThe outcome measures were local recurrence-free interval (LRFI) and overall survival (OS). METHODSDemographic, clinical, oncologic and surgical variables, including margin status, as well as radiation doses and schedule (neoadjuvant, adjuvant, or both) were compared using Wilcoxon rank-sum or chi-squared testing. The goal RT dose was 70 Gray (total) and patients were stratified based on completing (C70) or receiving incomplete (I70) dosing. Overall survival (OS) and local-recurrence free interval (LRFI) were calculated using the Kaplan-Meier method. FUNDING STATEMENTNo funding was obtained for this work. RESULTSSeventy-six patients were included in the final analysis. All patients had a minimum of 5-year follow-up (median 9.3 years, range 5.1–24.7 years). There were no significant clinical differences between the C70 and I70 RT groups. OS was greater for the C70 RT group (5-year OS 82% vs. 63%, p=.001). There was similar OS for the positive margin group (5-year OS 70% vs. 61%, p=.266). LRFI was greater for the C70 RT group (5-year OS 93% vs. 78%, p=.017). There was similar LRFI for the positive margin group (5-year OS 90% versus 87%, p=.810). CONCLUSIONChordoma outcomes trend towards diminishing LRFI rates in the literature. Here we report the results of the operative management of primary spinal chordoma with minimum five year follow-up, the addition of C70 RT to surgical excision conferred a benefit to OS and local recurrence.

High dose image-guided, intensity modulated radiation therapy (IG-IMRT) for chordomas of the sacrum, mobile spine and skull base: preliminary outcomes.

To report preliminary outcomes of high dose image-guided intensity modulated radiotherapy (IG-IMRT) in the treatment of chordomas of the sacrum, mobile spine and skull base. Retrospective analysis of chordoma patients treated with surgery and/or radiotherapy (RT) in a single tertiary cancer center. Initial treatment was categorized as (A) Adjuvant or definitive high-dose RT (78Gy/39fx or 24Gy/1fx) vs (B) surgery-only or low dose RT. The primary endpoint was the cumulative incidence of local failure. A total of 31 patients were treated from 2010 through 2020. Median age was 55years, tumor location was 64% sacrum, 13% lumbar, 16% cervical and 6% clivus. Median tumor volume was 148cc (8.3cm in largest diameter), 42% of patients received curative-intent surgery and 65% received primary RT (adjuvant or definitive). 5-year cumulative incidence of local failure was 48% in group A vs 83% in group B (p = 0.041). Tumor size > 330cc was associated with local failure (SHR 2.2, 95% CI 1.12 to 7.45; p = 0.028). Eight patients developed distant metastases, with a median metastases-free survival of 56.1months. 5-year survival for patients that received high dose RT was 72% vs 76% in patients that received no or low dose RT (p = 0.63). Our study suggests high-dose photon IG-IMRT improves local control in the initial management of chordomas. Health systems should promote reference centers with clinical expertise and technical capabilities to improve outcomes for this complex disease.

Management of Chordoma With Spinal Stereotactic Radiosurgery (SSRS)

Chordomas are rare tumors of notochordal origin affecting the skull base, spine, and sacrum. Given their high propensity for local recurrence and chemo/radioresistant biology, current treatment paradigms involve maximally safe en-bloc resection with or without adjuvant radiation therapy (RT). SSRS describes a modern approach to dose escalated RT, most commonly used for spine metastases. We analyzed our large single-institution database to test the hypothesis that SSRS provides comparable oncologic and safety outcomes relative to historical controls.We identified 21 patients with mobile spine or sacral chordoma (25 lesions) treated with SSRS at our institution from 2006 to 2020. We reviewed records to obtain patient, disease, and treatment characteristics, as well as outcome data including survival, local control, and toxicity attributable to SSRS. We performed a Kaplan-Meier analysis to estimate overall survival and local control rates, and a Cox proportional hazard model was used for univariate and multivariate analysis. We also performed a logistic regression to examine risk factors for insufficiency fractures. Significance was defined at a P < 0.05 level.Patients were treated with IMRT in 1,3, or 5 fractions with a simultaneous integrated boost. The median BED2 was 312 Gy (24 Gy/1 fraction to the GTV, 16 Gy to CTV) (Range 120-312 Gy). 44% of lesions were treated in the salvage setting, and 36% were treatments for metastases. All patients had gross disease at the time of SSRS. With median follow-up of 30 months, overall survival (OS) was 95.0%, 89.1%, 48.2% and local control (LC) was 91.5%, 86.9%, and 55.3% at 1, 2, and 5 years respectively. Covariates significantly associated with OS included: performance status, prescribed BED, mobile spine location, non-metastatic site treated, disease limited to 1 site, and GTV Dmin BED2 > 119.28), and the multivariate analysis did not converge. Covariates significantly associated with LC on univariate analysis included: conventional histology, and prescribed BED, while chondroid histology was associated with decreased LC. Only prescribed BED was significant on multivariate analysis. Seven patients were treated with definitive SSRS to their primary site, and there was 1 death (not attributable to RT) and 1 local failure in this group. No radiation myelopathy events were identified. Six patients (29%) required stabilization for sacral or spinal insufficiency after SSRS (median 13 months). No features were identified that significantly predicted for fracture.To the best of our knowledge, this series represents over a quarter of all reported spine and sacrum chordoma cases treated with stereotactic radiation in the literature. Our data are comparable to published population-based and single-institution case series, particularly given the prevalence of salvage and metastatic cases in this cohort, and they support the use of SSRS throughout the disease course of spine and sacral chordoma.S. Maroongroge: None. D. Boyce-Fappiano: None. K. Diao: None. B. Amini: None. A.P. Conley: None. J. Li: Research Grant; BMS, Medtronic. Honoraria; Monteris. Travel Expenses; Elekta. D.N. Yeboa: Research Grant; Brockman Foundation, MD Anderson Shirley Stein Award, MD Anderson Cancer Center. member for reviewing abstracts; ASTRO.M. McAleer: Honoraria; PREX S. p. A., AOSpine, Osler Institute. Speaker's Bureau; Osler Institute. Travel Expenses; Osler Institute. C. Tatsui: None. L.D. Rhines: None. A.J. Ghia: None.

Surgical Management of Spinal Chordoma: A Systematic Review and Single-Center Experience

Chordoma is a rare neoplasm of the neuraxis derived from remnants of the primitive notochord. The importance of wide margins and use of adjuvant therapy in spinal chordomas are still contentious points in the management of spinal chordomas. We conducted a systematic review of the surgical management of spinal chordomas alongside our 10-year institutional experience. A systematic search of the literature was performed in November 2020 using Embase and MEDLINE for articles regarding the surgical management of chordomas arising from the mobile spine and sacrum. We also searched for all adult patients who were surgically managed for spinal chordomas at our institute between 2010 and 2020. In both the systematic review and our institutional case series, data on adequacy of resection, use of adjuvant therapy, complications, recurrence (local or metastatic), and survival outcomes were collected. We identified and analyzed 42 articles, yielding 1531 patients, from which the overall gross total or wide resection rate was 54.9%. Among the 8 cases in our institutional experience (4 sacral, 3 cervical, and 1 lumbar), we achieved gross total resection in 50% of initial operations. The recurrence rate was 25% in our gross total resection group and 50% where initial resection was subtotal. Of patients, 75% had no evidence of recurrence at most recent follow-up. Albeit difficult at times because of the proximity to neurovascular tissue, achieving a wide resection followed by adjuvant therapy for spinal chordomas is of great importance. Multidisciplinary discussion is valuable to ensure the best outcome for the patient.

Molecular features and vulnerabilities of recurrent chordomas

BackgroundTumor recurrence is one of the major challenges in clinical management of chordoma. Despite R0-resection, approximately 50% of chordomas recur within ten years after initial surgery. The underlying molecular processes are poorly understood resulting in the lack of associated therapeutic options. This is not least due to the absence of appropriate cell culture models of this orphan disease.MethodsThe intra-personal progression model cell lines U-CH11 and U-CH11R were compared using array comparative genomic hybridization, expression arrays, RNA-seq, and immunocytochemistry. Cell line origin was confirmed by short tandem repeat analysis. Inter-personal cell culture models (n = 6) were examined to validate whether the new model is representative. Cell viability after HOX/PBX complex inhibition with small peptides was determined by MTS assays.ResultsUsing whole genome microarray analyses, striking differences in gene expression between primary and recurrent chordomas were identified. These expression differences were confirmed in the world’s first intra-personal model of chordoma relapse consisting of cell lines established from a primary (U-CH11) and the corresponding recurrent tumor (U-CH11R). Array comparative genomic hybridization and RNA-sequencing analyses revealed profound genetic similarities between both cell lines pointing to transcriptomic reprogramming as a key mechanism of chordoma progression. Network analysis of the recurrence specific genes highlighted HOX/PBX signaling as a common dysregulated event. Hence, HOX/PBX complexes were used as so far unknown therapeutic targets in recurrent chordomas. Treating chordoma cell lines with the complex formation inhibiting peptide HXR9 induced cFOS mediated apoptosis in all chordoma cell lines tested. This effect was significantly stronger in cell lines established from chordoma relapses.ConclusionClearly differing gene expression patterns and vulnerabilities to HOX/PBX complex inhibition in highly therapy resistant chordoma relapses were identified using the first intra-personal loco-regional and further inter-personal chordoma progression models. For the first time, HOX/PBX interference was used to induce cell death in chordoma and might serve as the basic concept of an upcoming targeted therapy for chordomas of all progression stages.

A Review of Particle Therapy for Skull Base Tumors: Modern Considerations and Future Directions.

Skull base tumors constitute one of the established indications for particle therapy, specifically proton therapy. However, a number of prognostic factors, practical clinical management issues, and the emerging role of carbon ion therapy remain subjects of active clinical investigation. This review summarizes these topics, assesses the present status, and reflects on future research directions focusing on the management of chordomas, one of the most aggressive skull base tumors. In addition, the role of particle therapy for benign tumors of the skull base, including pituitary adenoma and acoustic neuroma, is reviewed.

Surgical Management of Skull Base and Spine Chordomas

Management of chordoma along the cranial-spinal axis is a major challenge for both skull base and spinal surgeons. Although chordoma remains a rare tumor, occurring in approximately 1 per 1 million individuals, its treatment poses several challenges. These tumors are generally poorly responsive to radiation and chemotherapy, leading to surgical resection as the mainstay of treatment. Due to anatomic constraints and unique challenges associated with each primary site of disease, gross total resection is often not feasible and is associated with high rates of morbidity. Additionally, chordoma is associated with high rates of recurrence due to the tumor's aggressive biologic features, and postoperative radiation is increasingly incorporated as a treatment option for these patients. Despite these challenges, modern-day surgical techniques in both skull base and spinal surgery have facilitated improved patient outcomes. For example, endoscopic endonasal techniques have become the mainstay in resection of skull base chordomas, improving the ability to achieve gross total resection, while reducing associated morbidity of open transfacial techniques. Resection of spinal chordomas has been facilitated by emerging techniques in preoperative imaging, intraoperative navigation, spinal reconstruction, and radiotherapy. Taken collectively, the treatment of chordoma affecting the skull base and spinal requires a multidisciplinary team of surgeons, radiation oncologists, and medical oncologists who specialize in the treatment of this challenging disease.

Systematic Review Comparing Open versus Endoscopic Surgery in Clival Chordomas and a 10-Year Single-Center Experience.

Objectives Chordomas are rare, slow-growing, and osteo-destructive tumors of the primitive notochord. There is still contention in the literature as to the optimal management of chordoma. We conducted a systematic review of the surgical management of chordoma along with our 10-year institutional experience. Design A systematic search of the literature was performed in October 2020 by using MEDLINE and EMBASE for articles relating to the surgical management of clival chordomas. We also searched for all adult patients surgically treated for primary clival chordomas at our institute between 2009 and 2019. Participants Only articles describing chordomas arising from the clivus were included in the analysis. For our institution experience, only adult primary clival chordoma cases were included. Main Outcome Measures Patients were divided into endoscopic or open surgery. Rate of gross total resection (GTR), recurrence, and complications were measured. Results Our literature search yielded 24 articles to include in the study. Mean GTR rate among endoscopic cases was 51.9% versus 41.7% for open surgery. Among the eight cases in our institutional experience, we found similar GTR rates between endoscopic and open surgery. Conclusion Although there is clear evidence in the literature that endoscopic approaches provide better rates of GTR with fewer overall complications compared to open surgery. However, there are still situations where endoscopy is not viable, and thus, open surgery should still be considered if required.

Letter: Emerging Therapeutic Targets in Chordomas: A Review of the Literature in the Genomic Era

Letter: Emerging Therapeutic Targets in Chordomas: A Review of the Literature in the Genomic Era

Combination of PARP inhibitor and temozolomide to suppress chordoma progression

Chordoma, a malignant bone cancer, is highly resistant to conventional therapeutic approaches; this greatly limits radio- and chemotherapeutic options and disease management. In the present study, we investigated three patient-derived chordoma cell lines to elucidate the molecular mechanism of resistance to therapeutics. An in vitro high-throughput chemical screening assay and an in vivo xenograft model were used to identify novel chemosensitizers for chordoma. We found that patient-derived chordoma cell lines recapitulated disease phenotypes, which were highlighted by robust resistance to medical therapy manifested as lack of DNA damage accumulation. Mechanistically, the PARP DNA repair pathway was found to play a central role in this resistance. Chemical screening confirmed that PARP inhibitors could strikingly enhance temozolomide (TMZ) therapy in chordoma cells. Combining the FDA-approved PARP inhibitor, olaparib, with chemotherapeutics not only potentiated DNA damage accumulation, cell cycle arrest, and apoptosis in vitro but also suppressed chordoma xenograft expansion in vivo. We conclude that combining PARP inhibition with TMZ could be an effective therapeutic approach for the clinical management of chordoma. KEY MESSAGES: The PARP DNA repair pathway enhances chemoresistance in chordoma cells. Combining PARP inhibitors with genotoxic agents induces chordoma cell cytotoxicity. PARP inhibitor combining with temozolomide suppresses growth of chordoma in vivo.