Recurrent Chordoma Research Articles

Analysis of sphenoid sinus lateral pneumatization for endonasal endoscopic surgery.

Background:The purpose of this study was to analyze sphenoid sinus lateral pneumatization (SSLP), especially in Asian populations, and to identify cautionary items when using the endoscopic endonasal approach (EEA) for parasellar/lateral lesions.Methods:We analyzed SSLP and the width of SS (SSW) in 121 patients who had undergone EEA from 2008 to 2013 at the Division of Neurosurgery, Keio University Hospital. SSLP was defined as the distance between the SS lateral edge and the medial aspect of the pterygoid process on coronal reconstruction computed tomography. SSW was defined as the distance between the midline and lateral wall. We recorded SSLP and SSW for 242 sides. Further, we present two characteristic cases.Results:The average SSLP and SSW were 7.0 mm (−10.0–25.8 mm) and 21.8 mm (6.0–40.2 mm), respectively. No correlation between pneumatization and age was observed at age 15 or more. Sphenoid pneumatization was significantly wider in male than in female patients. There was no relationship between lateral and sagittal plane pneumatization. In a patient with recurrent chordoma who had an undeveloped SSLP, the tumor was removed via the medial space in the internal carotid artery. In another patient who had a giant pituitary adenoma and average SSLP, the tumor was located in the middle cranial fossa and was removed via the lateral internal carotid space through the left SSLP.Conclusions:Wide variations were observed in SSLP and SSW. For EEA, pneumatization is an instrument corridor. Preoperative assessment of SSLP is important, especially for parasellar lesions.

Two Cases of Dedifferentiated Chordoma in the Sacrum.

Dedifferentiated chordoma (DC) is defined as a chordoma containing sarcoma components. DC is distinguished from conventional chordoma by the rapidity of tumor growth and the potential for distant metastasis. We report two cases of DC, which are developed in the sacrum. We reviewed the medical records and imaging studies of 2 patients diagnosed with DC and the literature published. In the first case, percutaneous biopsy revealed that it was conventional chordoma in the sacrum. Patient underwent radiation therapy (RT). Six years after the RT, the tumor recurred. Surgical removal was performed and the recurrent tumor was diagnosed as DC in histopathologic examination. In the second case, a patient underwent gross total resection of sacral tumor, which was diagnosed with conventional chordoma. Aggravated tumor was detected after 4 months, and patient underwent reoperation. The second operation revealed the transformation of the tumor into DC. The survival time of the patients after the diagnosis was 10 and 31 months. Dedifferentiated chordoma is a rare and highly aggressive tumor. De novo type exists, but it usually transformed from recurrent chordoma after surgical resection or radiation.

Factors predicting recurrence after resection of clival chordoma using variable surgical approaches and radiation modalities.

Clival chordomas frequently recur because of their location and invasiveness. To investigate clinical, operative, and anatomic factors associated with clival chordoma recurrence. Retrospective review of clival chordomas treated at our center from 1993 to 2013. Fifty patients (56% male) with median age of 59 years (range, 8-76) were newly diagnosed with clival chordoma of mean diameter 3.3 cm (range, 1.5-6.7). Symptoms included headaches (38%), diplopia (36%), and dysphagia (14%). Procedures included transsphenoidal (n=34), transoral (n=4), craniotomy (n=5), and staged approaches (n=7). Gross total resection (GTR) rate was 52%, with 83% mean volumetric reduction, values that improved over time. While the lower third of the clivus was the least likely superoinferior zone to contain tumor (upper third=72%/middle third=82%/lower third=42%), it most frequently contained residual tumor (upper third=33%/middle third=38%/lower third=63%; P<.05). Symptom improvement rates were 61% (diplopia) and 53% (headache). Postoperative radiation included proton beam (n=19), cyberknife (n=7), intensity-modulated radiation therapy (n=6), external beam (n=10), and none (n=4). At last follow-up of 47 patients, 23 (49%) remain disease-free or have stable residual tumor. Lower third of clivus progressed most after GTR (upper/mid/lower third=32%/41%/75%). In a multivariate Cox proportional hazards model, male gender (hazard ratio [HR]=1.2/P=.03), subtotal resection (HR=5.0/P=.02), and the preoperative presence of tumor in the middle third (HR=1.2/P=.02) and lower third (HR=1.8/P=.02) of the clivus increased further growth or regrowth, while radiation modality did not. Our findings underscore long-standing support for GTR as reducing chordoma recurrence. The lower third of the clivus frequently harbored residual or recurrent tumor, despite staged approaches providing mediolateral (transcranial+endonasal) or superoinferior (endonasal+transoral) breadth. There was no benefit of proton-based over photon-based radiation, contradicting conventional presumptions.

18F]-Fluoromisonidazole Positron Emission Tomography/Computed Tomography Visualization of Tumor Hypoxia in Patients With Chordoma of the Mobile and Sacrococcygeal Spine

To investigate [18F]-fluoromisonidazole positron emission tomography/computed tomography (FMISO-PET/CT) detection of targetable hypoxic subvolumes (HSVs) in chordoma of the mobile or sacrococcygeal spine. A prospective, pilot study of 20 patients with primary or locally recurrent chordoma of the mobile or sacrococcygeal spine treated with proton or combined proton/photon radiation therapy (RT) with or without surgery was completed. The FMISO-PET/CT was performed before RT and after 19.8-34.2 GyRBE (relative biologic effectiveness). Gross tumor volumes were delineated and HSVs defined including voxels with standardized uptake values ≥1.4 times the muscle mean. Clinical characteristics and treatments received were compared between patients with and without HSVs. The FMISO-PET/CT detected HSVs in 12 of 20 patients (60%). Baseline and interval HSV spatial concordance varied (0%-94%). Eight HSVs were sufficiently large (≥5 cm(3)) to potentially allow an intensity modulated proton therapy boost. Patients with HSVs had significantly larger gross tumor volumes (median 410.0 cm(3) vs 63.4 cm(3); P=.02) and were significantly more likely to have stage T2 tumors (5 of 12 vs 0 of 8; P=.04). After a median follow-up of 1.8 years (range, 0.2-4.4 years), a local recurrence has yet to be observed. Three patients developed metastatic disease, 2 with HSVs. Detection of targetable HSVs by FMISO-PET/CT within patients undergoing RT with or without surgery for treatment of chordoma of the mobile and sacrococcygeal spine is feasible. The study's inability to attribute interval HSV changes to treatment, rapidly changing hypoxic physiology, or imaging inconsistencies is a limitation. Further study of double-baseline FMISO-PET/CT and hypoxia-directed RT dose escalation, particularly in patients at high risk for local recurrence, is warranted.

Skull base reconstruction after endoscopic endonasal resection of skull base chordomas

Objective To describe the techniques for the reconstruction of skull base defects after minimally invasive endoscopic resection of skull base chordomas.Methods The records of 146 patients who presented with skull base chordomas between Aug.2007 and Oct.2013 were retrospectively reviewed.The skull base defects after endoscopic endonasal resection of the chordomas were classified according to the dimensions of the dural defects as the following:(Type Ⅰ) The dura of skull base was intact after the tumour resection (113 cases) ; (Type Ⅱ) The dural defect was equal or less than 1 cm (12 cases) ; (Type Ⅲ) The dural defect was greater than 1 cm (21 cases).Three different reconstruction methods were utilized according to the classification of the skull base defects.The reconstruction of the type Ⅰ defect was performed mainly using artificial material; type Ⅱ in a multilayer fashion,mainly using an array of autologous free material including fat,muscle,muscle fascia and artificial material; type Ⅲ using vascular pedicle nasoseptal flap and autologous free material.Results There was no case of postoperative cerebrospinal fluid (CSF) leakage occurred following the reconstruction of type Ⅰ.One case of postoperative CSF leak (8.3％) occurred following the reconstruction of type Ⅱ and two (9.5％) occurred following the reconstruction of type Ⅲ.The rate of postoperative CSF leakage of all the cases is 2.1％.Conclusions Different reconstruction methods should be chosen according to different types of skull base defects.Reducing the use of vascular pedicle nasoseptal flap as much as possible could minimize the trauma of nasal cavity,increase the degree of comfort of the patients and offer convenience for the next skull base reconstruction after the resection of recurrent chordomas. Key words: Chordoma; Endoscopic ; Skull base reconstruction

PD-1, PD-L1, PD-L2 expression in the chordoma microenvironment

Chordomas are rare malignant tumors that are postulated to arise from remnants of the notochord. Currently, the interaction between chordomas and the host immune system is poorly understood. The checkpoint protein, PD-1 is expressed by circulating lymphocytes and is a marker of activation and exhaustion. Its ligands, PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273), are expressed on a variety of human cancers; however this pathway has not been previously reported in chordomas. We used flow cytometric and RT-PCR analysis in three established primary and recurrent chordoma cell lines (U-CH1, U-CH2, and JHC7) as well as immunohistochemical analysis of chordoma tissues from 10 patients to identify and localize expression of PD-1 pathway proteins. PD-1 ligands are not constitutively expressed by chordoma cells, but their expression is induced in the setting of pro-inflammatory cytokines in all cell lines examined. In paraffin embedded tissues, we found that tumor infiltrating lymphocytes expressed PD-1 in 3/6 cases. We also found that, although chordoma cells did not express significant levels of PD-L1, PD-L1 expression was observed on tumor-infiltrating macrophages and tumor infiltrating lymphocytes. Our study suggests that PD-1, PD-L1, and PD-L2 are present in the microenvironment of a subset of chordomas analyzed. Future studies are needed to evaluate the contribution of the PD-1 pathway to the immunosuppressive microenvironment of chordomas.

Prognostic significance of immunohistochemical expression of VEGFR2 and iNOS in spinal chordoma.

To clarify whether vascular endothelial growth factor receptor 2 (VEGFR2) and inducible nitric oxide synthase (iNOS) are involved in the angiogenesis and recurrence of spinal chordoma tissues and influence the overall survival. All patients affected by a spinal chordoma surgically treated between 1986 and 2007 were reviewed. We examined the expression of VEGFR2 and iNOS with immunohistochemistry using a tissue microarray containing 120 chordoma samples. Local recurrence and overall survival (OS) were analyzed. A series of 40 chordoma patients who underwent surgery for a total of 120 lesions (including 80 recurrent lesions) were identified (sacrum 77.5%, lumbar spine 17.5%, cervical/thoracic spine 5%). Surgical margins were wide in 30 (75%), marginal in 8 (20%) and intralesional in 2 (5%) patients. Median follow-up was 120months. The 5- and 10-year OS of the entire series of patients was 78.6 and 30%, respectively. There were five primary chordomas (12.5%) with moderate and 35 (87.5%) with strong expression of VEGFR-2. All recurrent spinal chordomas displayed strong expression of VEGFR-2. The expression of iNOS was predominately moderate to high in primary chordomas: There were 15 tumors (37.5%) with moderate and 25 tumors (62.5%) with strong expression. All recurrent chordomas displayed strong expression of iNOS. The high expression of VEGFR-2 and iNOS affected the OS. The OS at 10years was only 30%.

Difficulty distinguishing benign notochordal cell tumor from chordoma further suggests a link between them.

BackgroundMuch discussion about benign notochordal cell tissue in vertebrae has centered on the nature of its relationship, if any, to chordoma. Often referred to as benign notochordal cell tumors (BNCTs), these lesions have unique morphological features, however, differentiating between notochordal cells in discs, BNCT, and chordoma can be difficult. They are described as radiologically distinct from chordoma, with lysis, contrast enhancement, and a soft tissue mass indicating chordoma.MethodsAll chordomas diagnosed at our institution, the Istituto Ortopedico Rizzoli (Bologna, Italy), prior to 2008 were reviewed, yielding 174 cases. Five were limited to bone; one was a recurrent chordoma without original data available. The remaining four were re-evaluated in detail.ResultsThere were three women and one man, aged 33–57 years (mean, 48 years). Two were BNCTs and two were mixed lesions containing BNCT and chordoma. On computed tomography, all were radiopaque with areas of lysis. One BNCT was heterogeneous on magnetic resonance imaging, enhancing after contrast. Microscopically, one BNCT had a well-defined cystic area with a sclerotic border. The other had a minute atypical area; it recurred as chordoma. The mixed lesions had areas of definitive BNCT, definitive chordoma, and atypical areas that did not meet the criteria for either. The atypical areas in all three cases ‘blended’ with areas of chordoma or BNCT.ConclusionThese cases illustrate the ongoing challenges in differentiating between BNCT and chordoma. All had unique imaging features; three had atypical microscopic areas blending with BNCT or chordoma, strengthening the argument for a relationship between the two entities and supporting the idea that some BNCTs may progress to chordoma. Our study dispels the notion that any single radiologic criterion used to distinguish between chordoma and BNCT is reliable, opening the discussion as to whether or how to monitor BNCTs.

Staged ‘intentional’ bridging vein ligation: a safe strategy in gaining wide access to skull base tumors

The venous drainage of the temporal lobe, through bridging veins to the middle cranial fossa, is pivotal in determining the surgical corridor for skull base lesions. In dealing with select cases, where venous drainage was an obstacle in the surgical approach, we hypothesized that staged 'intentional' ligation of the dominant pathway of venous drainage would provide a safer and wider access to skull base tumors. We study the indications and safety of this surgical strategy in the management of skull base lesions. From 1995 to 2012, 318 patients with skull base tumors were treated at our institute by the fronto-orbito-zygomatic (FOZ) or transpetrosal approaches, eight of whom we planned for staged 'intentional' bridging vein ligation. Seven patients underwent planned ligation of the bridging veins from the temporal lobe to the middle cranial fossa floor in the first stage, followed by definitive surgery through the desired skull base approach, in the second stage, while in one patient the strategy was abandoned. These patients were evaluated with respect to their clinical presentation, pre- and post-operative radiology including venogram, intra-operative findings and post-operative course. Seven patients, four males and three females, with ages ranging from 16 to 63 years, underwent staged 'intentional' bridging vein ligation. The diagnoses were recurrent craniopharyngioma in four, and petroclival meningioma, sphenopetroclival meningioma and spheno-orbital meningioma in one each. Six of these lesions were approached from the dominant (left) side, while one lesion was on the right side. Venograms done after the first-stage procedure showed obliteration of the dominant venous drainage with opening up of anastomotic venous channels in all patients. All patients tolerated the first-stage procedure well; only one patient showed asymptomatic mild temporal lobe edema on MRI, which resolved in 3 weeks. None of the patients had venous complications after definitive surgery. One patient with recurrent chordoma, who was planned for staged ligation, did not undergo ligation as, intra-operatively, the draining channel turned out to be a cortical vein, which could be mobilized without ligation. In an attempt to detether the temporal lobe, the disconnection of the bridging veins from the temporal lobe to the middle cranial fossa floor in the first stage may lead to re-direction of the venous outflow over time. This may allow skull base surgeons a better surgical corridor and ensure safety of venous structures during the definitive surgery.

Molecular profiling of chordoma

The molecular basis of chordoma is still poorly understood, particularly with respect to differentially expressed genes involved in the primary origin of chordoma. In this study, therefore, we compared the transcriptional expression profile of one sacral chordoma recurrence, two chordoma cell lines (U-CH1 and U-CH2) and one chondrosarcoma cell line (U-CS2) with vertebral disc using a high-density oligonucleotide array. The expression of 65 genes whose mRNA levels differed significantly (p<0.001; ≥6-fold change) between chordoma and control (vertebral disc) was identified. Genes with increased expression in chordoma compared to control and chondrosarcoma were most frequently located on chromosomes 2 (11%), 5 (8%), 1 and 7 (each 6%), whereas interphase cytogenetics of 33 chordomas demonstrated gains of chromosomal material most prevalent on 7q (42%), 12q (21%), 17q (21%), 20q (27%) and 22q (21%). The microarray data were confirmed for selected genes by quantitative polymerase chain reaction analysis. As in other studies, we showed the expression of brachyury. We demonstrate the expression of new potential candidates for chordoma tumorigenesis, such as CD24, ECRG4, RARRES2, IGFBP2, RAP1, HAI2, RAB38, osteopontin, GalNAc-T3, VAMP8 and others. Thus, we identified and validated a set of interesting candidate genes whose differential expression likely plays a role in chordoma.

Generation of a patient-derived chordoma xenograft and characterization of the phosphoproteome in a recurrent chordoma

The management of patients with locally recurrent or metastatic chordoma is a challenge. Preclinical disease models would greatly accelerate the development of novel therapeutic options for chordoma. The authors sought to establish and characterize a primary xenograft model for chordoma that faithfully recapitulates the molecular features of human chordoma. Chordoma tissue from a recurrent clival tumor was obtained at the time of surgery and implanted subcutaneously into NOD-SCID interleukin-2 receptor gamma (IL-2Rγ) null (NSG) mouse hosts. Successful xenografts were established and passaged in the NSG mice. The recurrent chordoma and the derived human chordoma xenograft were compared by histology, immunohistochemistry, and phospho-specific immunohistochemistry. Based on these results, mice harboring subcutaneous chordoma xenografts were treated with the mTOR inhibitor MLN0128, and tumors were subjected to phosphoproteome profiling using Luminex technology and immunohistochemistry. SF8894 is a novel chordoma xenograft established from a recurrent clival chordoma that faithfully recapitulates the histopathological, immunohistological, and phosphoproteomic features of the human tumor. The PI3K/Akt/mTOR pathway was activated, as evidenced by diffuse immunopositivity for phospho-epitopes, in the recurrent chordoma and in the established xenograft. Treatment of mice harboring chordoma xenografts with MLN0128 resulted in decreased activity of the PI3K/Akt/mTOR signaling pathway as indicated by decreased phospho-mTOR levels (p = 0.019, n = 3 tumors per group). The authors report the establishment of SF8894, a recurrent clival chordoma xenograft that mimics many of the features of the original tumor and that should be a useful preclinical model for recurrent chordoma.

Proton Therapy for Reirradiation of Progressive or Recurrent Chordoma

To report the results in patients reirradiated with proton therapy for recurrent or progressive chordoma, with or without salvage surgery. A retrospective review of 16 consecutive patients treated from 2005 to 2012 was performed. All patients had received at least 1 prior course of radiation therapy to the same area, and all but 1 patient had at least 1 surgical resection for disease before receiving reirradiation. At the time of recurrence or progression, half of the patients underwent additional salvage surgery before receiving reirradiation. The median prior dose of radiation was 75.2 Gy (range, 40-79.2 Gy). Six patients had received prior proton therapy, and the remainder had received photon radiation. The median gross tumor volume at the time of reirradiation was 71 cm(3) (range, 0-701 cm(3)). Reirradiation occurred at a median interval of 37 months after prior radiation (range, 12-129 months), and the median dose of reirradiation was 75.6 Gy (relative biological effectiveness [RBE]) (range. 71.2-79.2 Gy [RBE]), given in standard daily fractionation (n=14) or hyperfractionation (n=2). The median follow-up time was 23 months (range, 6-63 months); it was 26 months in patients alive at the last follow-up visit (range, 12-63 months). The 2-year estimate for local control was 85%, overall survival 80%, chordoma-specific survival 88%, and development of distant metastases 20%. Four patients have had local progression: 3 in-field and 1 marginal. Late toxicity included grade 3 bitemporal lobe radionecrosis in 1 patient that improved with hyperbaric oxygen, a grade 4 cerebrospinal fluid leak with meningitis in 1 patient, and a grade 4 ischemic brainstem stroke (out of radiation field) in 1 patient, with subsequent neurologic recovery. Full-dose proton reirradiation provided encouraging initial disease control and overall survival for patients with recurrent or progressive chordoma, although additional toxicities may develop with longer follow-up times.

Endoscopic endonasal approach in the management of skull base chordomas—clinical experience on a large series, technique, outcome, and pitfalls

Skull base chordomas represent very interesting neoplasms, due to their rarity, biological behavior, and resistance to treatment. Their management is very challenging. Recently, the use of a natural corridor, through the nose and the sphenoid sinus, improved morbidity and mortality allowing also for excellent removal rates. Prospective analysis of 54 patients harboring a skull base chordoma that were managed by extended endonasal endoscopic approach (EEA). Among the 54 patients treated (during a 72 months period), 21 were women and 33 men, undergoing 58 procedures. Twenty-two cases (40%) were recurrent and 32 (60%) newly diagnosed chordomas. Among the 32 newly diagnosed chordomas, a gross total resection was achieved in 28 cases (88%), a near total (>95% of tumor) in 2 cases (6%), a partial (>50% of tumor) in 2 cases (6%). Among the 22 recurrent chordomas, resection was complete in 7 cases (30%), near total in 7 (30%), and partial in 8 (40%). The global gross total resection rate was 65% (35/54 cases). Four patients (11%) recurred and 4 (11%) progressed within a mean follow-up of 34 months (range 12-84 months). Four patients (11%) were re-operated; one patient (1.8%) died due to disease progression, one patient (1.8%) died 2 weeks after surgery due to a massive bleeding from an ICA pseudo aneurysm. CSF leakage occurred in four patients (8%), and meningitis in eight cases (14%). No new permanent neurological deficit occurred. The EEA management of skull base chordomas requires a long and gradual learning curve that once acquired offers the possibility of either similar or better resection rates as compared to traditional approaches while morbidity is improved.

Recurrent Upper Cervical Chordomas After Radiotherapy

Retrospective review of a case series. To present and analyze our surgical results of recurrent chordomas in the upper cervical spine after radiotherapy and compare 2 surgical strategies. Surgical treatment of recurrent chordomas in the upper cervical spine after radiotherapy is clinically rare but extremely challenging. No reports are found in the literatures focusing on the surgical results and strategies of such recurrent chordomas. Clinical data of 8 patients with recurrent chordomas in the upper cervical spine after radiotherapy were retrospectively reviewed. Preoperative symptoms were relieved after our surgical procedures in 7 of the 8 patients. Total tumor removal was achieved in 6 of the 8 patients. Surgical complications mainly including cerebrospinal fluid leak and incision disunion were observed in 6 of the 8, and all the 3 patients after transoral operation had those complicated surgical complications, whereas the other 3 of the 5 patients after anterior retropharyngeal operation had relatively slighter complications. The disease free survival rates 1 year and 2 years after the surgery in this series were 50% and 12.5%, respectively, comparing with the general survival rates 1 year and 2 years after the surgery 87.5% and 37.5%. Revised surgery is effective for improving quality of life of patients with recurrent upper cervical chordomas after radiotherapy before further tumor recurrence. However, the prognosis of those patients is usually poor and surgical complications mainly including incision disunion and cerebrospinal fluid leak are common. To reduce the risk of surgical complications, anterior retropharyngeal approach may be superior to the transoral approach. N/A.

Multidisciplinary Management of Recurrent Chordomas

The management of recurrent chordomas are clinically challenging because of its relentless nature. Local therapy, whether surgery or radiation, are important considerations since local progression of disease results in significant morbidity and locally aggressive treatment is often required. Stereotactic radiosurgery, shown to be very effective for radioresistant histologies, may be an important radiotherapeutic approach for recurrent tumors. Ultimately, the treatment of recurrent chordoma is palliative in intent, thus, enthusiasm for improving local control must be tempered against the possible impact of treatment on quality of life. Judicious use of radiotherapy and surgery can often provide meaningful palliation and local control of recurrences. Systemic treatment options, particularly with targeted molecules have great potential for chordomas in the recurrent setting, as the risk of disseminated disease is higher. The development of tools to help assess potential targets for drug therapy will be crucial. The incorporation of locally aggressive therapy and effective systemic therapy will be critical for the successful management of recurrent chordomas. At present, there is a paucity of published data regarding salvage therapy. Nonetheless, advances in surgical, medical, and radiation oncology are providing new avenues of research and potentially may have significant impact upon successful salvage treatment.

Preliminary Results of High-Dose Single-Fraction Radiotherapy for the Management of Chordomas of the Spine and Sacrum

En bloc wide-margin excision significantly decreases the risk of chordoma recurrence. However, a wide surgical margin cannot be obtained in many chordomas because they arise primarily in the sacrum, clivus, and mobile spine. Furthermore, these tumors have shown resistance to fractionated photon radiation at conventional doses and numerous chemotherapies. To analyze the outcomes of single-fraction stereotactic radiosurgery (SRS) in the treatment of chordomas of the mobile spine and sacrum. Twenty-four patients with chordoma of the sacrum and mobile spine were treated with high-dose single-fraction SRS (median dose, 2400 cGy). Twenty-one primary and 3 metastatic tumors were treated. Seven patients were treated for postoperative tumor recurrence. In 7 patients, SRS was administered as planned adjuvant therapy, and in 13 patients, SRS was administered as neoadjuvant therapy. All patients had serial magnetic resonance imaging follow-up. The overall median follow-up was 24 months. Of the 24 patients, 23 (95%) demonstrated stable or reduced tumor burden based on serial magnetic resonance imaging. One patient had radiographic progression of tumor 11 months after SRS. Only 6 of 13 patients who underwent neoadjuvant SRS proceeded to surgery. This decision was based on the lack of radiographic progression and the patient's preference. Complications were limited to 1 patient in whom sciatic neuropathy developed and 1 with vocal cord paralysis. High-dose single-fraction SRS provides good tumor control with low treatment-related morbidity. Additional follow-up is required to determine the long-term recurrence risk.

Recurrent skeletal extra-axial chordoma confirmed with brachyury: Imaging features and review of the literature

A small number of tumors bearing histological resemblance to axial chordoma arising from the bone or soft tissue outside the axial skeleton have been reported. These lesions have historically been referred to as parachordoma, chordoma periphericum (CP), or extra-axial chordoma (EAC). With the introduction of the immunohistochemical stain brachyury, a sensitive and specific marker for notochordal origin, chordomas arising in extra-axial locations (i.e., CP, EAC), are now diagnosed with more accuracy and distinguished from parachordoma, which resembles chordoma on histology. The distinction between EAC and parachordoma is clinically important because EAC confirmed by immunoreactivity for brachyury tends to grow and recur with local bone destruction. Prior to the introduction of brachyury, the diagnosis of EAC was challenging and therefore the imaging features of EAC have not been comprehensively described. We report two cases of recurrent EAC confirmed by the expression of brachyury arising from the distal femur and distal tibia and describe the imaging findings from radiography and MRI at initial diagnosis and at recurrence.

High expression of survivin in sacral chordoma

Chordoma is a rare and invasive malignant tumor which primarily relies on surgical treatments. Anticipation of its recurrence and patient survival longevity has been a critical issue of the treatments. This retrospective study examined the survivin expression of sacral chordoma in 30 patients undergoing surgery in our hospital from January 2000 to July 2010, and compared it with chordoma recurrence. Survivin expression was 70 % positive in 30 patients. The positive expression of survivin with recurrence was significantly higher than that without recurrence (p = 0.017) and was inversely related to the continuous disease-free survival time (p < 0.001). Survivin expression was associated with recurrence. The correlation suggested that the survivin expression could be used as an independent predictor of recurrence and could be a potential bio-target gene of angiogenesis in sacral chordoma.

Understanding the Cell Cycle in the Pathophysiology of Chordomas: A Molecular Look

Chordomas are rare, slow-growing infiltrative tumors that are typically located in the skull base or sacral spine, although they can be found anywhere within the axial skeleton. Classically, these tumors show characteristic physaliferous cells filled with vacuolated cytoplasm of mucoid matrix. The 3 histologic types of chordomas are the conventional, chondroid, and dedifferentiated types, with the last 2 having the worst prognosis given an increase risk of sarcomatous degeneration. They are classically immunoreactive to S-100 and a number of cytokeratins (6, 15, 17, 19, 20). Although most chordomas are sporadic, there are cases of familial chordomas (6, 12, 13). Current treatment has changed over the last few decades, but remains focused on surgical excision followed by conventional or proton-beam radiotherapy. Recurrences are common and are seen in up to 68% of cases, and are managed with repeat surgery or radiotherapy. The 5- and 10-year survival rates for patients with chordomas are in the range of 68% and 40%, respectively (10, 14). Recent clinical research has demonstrated the effectiveness and increased overall survival in patients with chordomas via en bloc or wide margin vertebrectomies without violation of the tumor capsule, followed by radiotherapy (8, 9). Despite the groundbreaking innovation in clinical treatment and management of patients with chordomas, the molecular understanding remains far behind. Chordomas are cytogenetically quite diverse tumors. Molecular cytogenetic studies have demonstrated that a variety of chromosomal markers exist in primary and recurrent chordomas, as well as frequent quantitative changes in the tumor cell genome. For example, case studies have reported that the most common abnormality is a monosomy of chromosome 1 and gain of chromosome 7 (2, 11, 22, 23). Also, other studies have shown chromosome 1p and 3p anomalies to be associated early on in chordoma genesis. Likewise, 1q anomalies have been correlated with recurrence in

Endoscopic resection of malignant sinonasal tumours with or without chemotherapy and radiotherapy

An increasing number of transnasal endoscopic surgical procedures are being performed, and these procedures are now also utilised in the management of malignant sinonasal tumours. This study aimed to evaluate the outcome of endoscopic resection of sinonasal malignancies, with or without chemotherapy and radiotherapy. Between 2000 and 2009, six patients with sinonasal malignancies (diagnosed on pre-operative biopsy) underwent endoscopic resection at our hospital. The histopathological diagnoses varied and included squamous cell carcinoma, olfactory neuroblastoma, chordoma, extramedullary plasmacytoma and haemangiopericytoma. Surgical resection was combined with chemotherapy and/or radiotherapy in four cases. The mean follow-up period was 43 months. One patient suffered local recurrence of chordoma, 84 months after the first operation, but this was successfully treated with proton beam radiotherapy. These results suggest that endoscopic resection may be a valid alternative to conventional resection in selected cases of malignant sinonasal tumour.