FIGURE 3 - uploaded by Thibault Passeri
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Axial T2-weighted MRI showing a clival chordoma characterized by a high preoperative TGR (15.18%/m), 4 mo before surgery A, the day before surgery B, 48 h after surgery showing PR with a tumor remnant behind the left internal carotid artery (red arrow) C, and 5 mo after surgery (PBT was done after surgery) showing recurrence D.
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BACKGROUND
Currently, different postoperative predictors of chordoma recurrence have been identified. Tumor growth rate (TGR) is an image-based calculation that provides quantitative information of tumor's volume changing over time and has been shown to predict progression-free survival (PFS) in other tumor types.
OBJECTIVE
To explore the usefulne...
Context in source publication
Context 1
... from https://academic.oup.com/neurosurgery/advance-article/doi/10.1093/neuros/nyab164/6275957 by Assistance Publique -Hopitaux De Paris user on 19 May 2021 symptoms are not considered eligible for TGR evaluation and are directly addressed for treatment. Examples of aggressive and more indolent chordomas are shown in Figures 3 and 4. ...
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Citations
... 4,5 Despite technical advances in surgery and radiotherapy (RT), the long-term prognosis of these tumors remains poor, with progression-free survival (PFS) estimated at 65% and 32% at 5 and 10 years, respectively. 6 However, clinical outcomes in patients with chordoma are variable, and disease progression is likely determined by preoperative radiological features, 7,8 clinical characteristics, [9][10][11] surgical results, 9,12 and few biomarkers. 13 Nowadays, there are no validated molecular prognostic or therapeutic biomarkers. ...
... Moreover, considering the potential surgical and RT mor- bidities, practitioners have no means to balance treatment morbidity with quality of life. Although many clinical, radiological, or immunohistological prognostic factors have been described, 8,9,11,13 there is no clear clinical guidance on patient stratification in terms of treatment. Biomolecular prognostic markers are therefore essential to adjust the aggressiveness of treatment for each specific tumor. ...
OBJECTIVE
Chordomas are rare bone neoplasms characterized by a high recurrence rate and no benefit from any approved medical treatment to date. However, the investigation of molecular alterations in chordomas could be essential to prognosticate, guide clinical decision-making, and identify theranostic biomarkers. The aim of this study was to provide a detailed genomic landscape of a homogeneous series of 64 chordoma samples, revealing driver events, theranostic markers, and outcome-related genomic features.
METHODS
The authors conducted whole-exome sequencing (WES), targeted next-generation sequencing, and RNA sequencing of 64 skull base and spinal chordoma samples collected between December 2006 and September 2020. Clinical, histological, and radiological data were retrospectively analyzed and correlated to genetic findings.
RESULTS
The authors identified homozygous deletions of CDKN2A/2B, PIK3CA mutations, and alterations affecting genes of SWI/SNF chromatin remodeling complexes ( PBRM1 and ARID1A ) as potential theranostic biomarkers. Using matched germline WES, they observed a higher frequency of a common genetic variant (rs2305089; p.(Gly177Asp)) in TBXT (97.8%, p < 0.001) compared to its distribution in the general population. PIK3CA mutation was identified as an independent biomarker of short progression-free survival (HR 10.68, p = 0.0008). Loss of CDKN2A/2B was more frequently observed in spinal tumors and recurrent tumors.
CONCLUSIONS
In the current study, the authors identified driver events such as PBRM1 and PIK3CA mutations, TBXT alterations, or homozygous deletions of CDKN2A/2B, which could, for some, be considered potential theranostic markers and could allow for identifying novel therapeutic approaches. With the aim of a future biomolecular prognostication classification, alterations affecting PIK3CA and CDKN2A/2B could be considered as poor prognostic biomarkers.
... This heterogeneity emphasizes the importance of identifying strong prognostic clinical, radiological and biological markers assessing chordoma aggressiveness, before and after surgery, which could guide patient stratification regarding treatment strategy. In the preoperative period, the tumor growth rate has been shown to correlate with the PFS and the postoperative Ki-67 LI. 39 Recently, Zuccato et al. 40 first identified prognostic epigenetic chordoma subtypes by using plasma methylomebased biomarkers. In the postoperative period, immunohistochemical grading 41 or biomolecular markers such as PBRM1 mutation, homozygous deletion of CDKN2A/2B, and 1p36 deletion, described as poor prognostic markers, 42,43 could provide a prognostication outline to predict behaviors of SBCs and to adjust adjuvant treatment to their aggressiveness. ...
... 4,5 Despite technical advances in surgery and radiotherapy (RT), the long-term prognosis of these tumors remains poor, with progression-free survival (PFS) estimated at 65% and 32% at 5 and 10 years, respectively. 6 However, clinical outcomes in patients with chordoma are variable, and disease progression is likely determined by preoperative radiological features, 7,8 clinical characteristics, [9][10][11] surgical results, 9,12 and few biomarkers. 13 Nowadays, there are no validated molecular prognostic or therapeutic biomarkers. ...
... Moreover, considering the potential surgical and RT mor- bidities, practitioners have no means to balance treatment morbidity with quality of life. Although many clinical, radiological, or immunohistological prognostic factors have been described, 8,9,11,13 there is no clear clinical guidance on patient stratification in terms of treatment. Biomolecular prognostic markers are therefore essential to adjust the aggressiveness of treatment for each specific tumor. ...
... KEYWORDS craniovertebral junction (CVJ), cervical pedicle screw (CPS), chordoma, spine tumor, 3D-printed guides, case report Introduction For spine surgeons, dealing with unstable cervical spine has been usually challenging, especially when facing a primary craniovertebral junction (CVJ) tumor. Although the best management of CVJ chordomas is still a matter of debate, the majority of studies showed that the extent of a resection was associated with the best progression-free survival and overall survival rate (1,2). Moreover, because of the neurovascular structure crowding and the consequent frequent impossibility of performing an en-bloc removal of these tumors, the surgery goal should aim at maximal safe removal providing a safe target for subsequent proton-beam radiation therapy (3)(4)(5)(6). ...
Introduction
For spine surgeons, dealing with unstable cervical spine has been usually challenging, and this becomes more difficult when facing a primary craniovertebral junction tumor. Primary spine tumor surgery should always include column reconstruction in order to guarantee biomechanical stability of the spine, but surgeons should always be aware that instrumentations could create interferences with postoperative radiations. However, although carbon fiber instrumentations have started to be used in thoracolumbar oncology for few years, these options are still not available for cervical spine. In the reported case, the adopted strategy to obtain adequate column reconstruction was based on the idea of reducing the amount of titanium needed for posterior fixation and maximizing the distance between the radiation target and titanium rods.
Case report and aim
We present the case of a 53-year-old woman harboring a craniovertebral junction chordoma. A short occipito-C3 construct was selected. Specifically, titanium cervical pedicle screws were placed by using a new technology consisting in patient-tailored and customized 3D-printed guides. The aim of this case report is to determine the feasibility and safety of 3D-printed guides for cervical pedicle screw (CPS) positioning, even in the case of cervical spine tumor.
Conclusion
CPS could represent a good solution by providing strong biomechanical purchase and tailored 3D-printed guides could increase the safety and the accuracy of this challenging screw placement, even in oncological patients.
... 14 Then, these parameters were analyzed for their associations with patient outcomes 15 (progression-free survival [PFS] and overall survival [OS]), clinicopathological 16 features, and denosumab treatment responsiveness. 17 Results: High TGR predicted both poor PFS and OS (both P < 0.001). In addition, 18 TGR was associated with postoperative neurological dysfunction (P < 0.001), 19 Enneking staging (P = 0.016), denosumab treatment responsiveness (P = 0.035), and 20 the number of CD3 + (P < 0.001), PD-1 + (P = 0.009), PD-L1 + (P < 0.001), and FoxP3 + 21 TIL (P = 0.02). ...
... 14 15 Currently, there are no reliable indicators to predict prognosis and treatment response 16 in patients with GCTB. The Campanacci and Enneking staging systems are widely 17 used to guide clinical treatment and prognostic risk stratification, but there are still 18 large differences in the prognosis of patients with the same staging [10,11] . The recently 19 updated 8th edition of the American Joint Committee on Cancer (AJCC) staging 20 manual redefines the staging of spinal tumors; although more comprehensive in 21 guiding staging, its prognostic stratification ability remains to be demonstrated [12] . ...
... 22 Some studies have reported molecular markers associated with GCTB prognosis as 23 well [13] , but the study of these markers is limited to the small sample size, which may 24 offer inaccurate prognostic information. Tumor growth rate (TGR), as a new 25 radiological parameter in the field of oncology [14][15][16][17] , is an image-based measure of 26 tumor size over time that provides a useful complement to the Response Evaluation 27 Criteria in Solid Tumors (RECIST) in the dynamic and quantitative assessment of 28 tumor progression [14,18] . Currently, TGR has been reported to be able to predict 29 progression-free survival (PFS) in a wide range of tumors, especially slower-growing 30 3 tumors [17] . ...
Background: Currently, little is known about the prognostic value of tumor growth rate (TGR) in spinal giant cell tumors of bone (GCTB).
Objective: To investigate the correlation of TGR with clinicopathologic features, the immune microenvironment, prognosis and response to denosumab treatment of spinal GCTB.
Methods: A total of 128 patients with spinal GCTB treated at five centers from 2011 to 2021 were included. TGR was assessed by two independent neuroradiologists using at least 2 preoperative thin-section magnetic resonance imaging scans at a minimum interval of 2 months. Immunohistochemistry was used to assess tumor-infiltrating lymphocyte (TIL) subtypes for CD3, CD4, CD8, CD20, PD-1, PD-L1 and Foxp3. Then, these parameters were analyzed for their associations with patient outcomes (progression-free survival [PFS] and overall survival [OS]), clinicopathological features, and denosumab treatment responsiveness.
Results: High TGR predicted both poor PFS and OS (both P < 0.001). In addition, TGR was associated with postoperative neurological dysfunction (P < 0.001), Enneking staging (P = 0.016), denosumab treatment responsiveness (P = 0.035), and the number of CD3+ (P < 0.001), PD-1+ (P = 0.009), PD-L1+ (P < 0.001), and FoxP3+ TIL (P = 0.02). Importantly, TGR outperformed the traditional Enneking, Campanacci and American Joint Committee on Cancer staging systems in predicting the clinical outcomes of spinal GCTB.
Conclusion: These data support the use of TGR as a reliable predictive tool for clinically relevant outcomes and response to denosumab therapy of spinal GCTB, which may be helpful in guiding prognostic risk stratification and therapeutic optimization of patients.
... This heterogeneity emphasizes the importance of identifying strong prognostic clinical, radiological and biological markers assessing chordoma aggressiveness, before and after surgery, which could guide patient stratification regarding treatment strategy. In the preoperative period, the tumor growth rate has been shown to correlate with the PFS and the postoperative Ki-67 LI. 39 Recently, Zuccato et al. 40 first identified prognostic epigenetic chordoma subtypes by using plasma methylomebased biomarkers. In the postoperative period, immunohistochemical grading 41 or biomolecular markers such as PBRM1 mutation, homozygous deletion of CDKN2A/2B, and 1p36 deletion, described as poor prognostic markers, 42,43 could provide a prognostication outline to predict behaviors of SBCs and to adjust adjuvant treatment to their aggressiveness. ...
OBJECTIVE
Chordomas represent one of the most challenging subsets of skull base and craniovertebral junction (CVJ) tumors to treat. Despite extensive resection followed by proton-beam radiation therapy, the recurrence rate remains high, highlighting the importance of developing efficient treatment strategies. In this study, the authors present their experience in treating clival and CVJ chordomas over a 29-year period.
METHODS
The authors conducted a retrospective study of clival and CVJ chordomas that were surgically treated at their institution from 1991 to 2020. This study focuses on three aspects of the management of these tumors: the factors influencing the extent of resection (EOR), the predictors of survival, and the outcomes of the endoscopic endonasal approaches (EEAs) compared with open approaches (OAs).
RESULTS
A total of 265 surgical procedures were performed in 210 patients, including 123 OAs (46.4%) and 142 EEAs (53.6%). Tumors that had an intradural extension (p = 0.03), brainstem contact (p = 0.005), cavernous sinus extension (p = 0.004), major artery encasement (p = 0.01), petrous apex extension (p = 0.003), or high volume (p = 0.0003) were significantly associated with a lower EOR. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 52.1% and 75.1%, respectively. Gross-total resection and Ki-67 labeling index < 6% were considered to be independent prognostic factors of longer PFS (p = 0.0005 and p = 0.003, respectively) and OS (p = 0.02 and p = 0.03, respectively). Postoperative radiation therapy correlated independently with a longer PFS (p = 0.006). Previous surgical treatment was associated with a lower EOR (p = 0.01) and a higher rate of CSF leakage after EEAs (p = 0.02) but did not have significantly lower PFS and OS compared with primary surgery. Previously radiation therapy correlated with a worse outcome, with lower PFS and OS (p = 0.001 and p = 0.007, respectively). EEAs were more frequently used in patients with upper and middle clival tumors (p = 0.002 and p < 0.0001, respectively), had a better rate of EOR (p = 0.003), and had a lower risk of de novo neurological deficit (p < 0.0001) compared with OAs. The overall rate of postoperative CSF leakage after EEAs was 14.8%.
CONCLUSIONS
This large study showed that gross-total resection should be attempted in a multidisciplinary skull base center before providing radiation therapy. EEAs should be considered as the gold-standard approach for upper/middle clival lesions based on the satisfactory surgical outcome, but OAs remain important tools for large complex chordomas.
... It is widely accepted that whenever possible, total resection should be pursued (7,8). Chordoma in the sacrococcygeal region and other areas have a relatively high rate of total resection. ...
Objective
To investigate the imaging and clinical risk factors related to the postoperative recurrence of sacrococcygeal chordoma.
Methods
63 patients of sacrococcygeal chordoma proved by operation and pathology in our hospital from January 2009 to December 2019 were retrospectively analyzed in the related factors of imaging manifestations, pathological type, and extent of surgical resection. The recurrence of sacrococcygeal chordoma was followed up. Univariate Kaplan-Meier survival analysis and multivariate Cox regression analysis were used to analyze the related factors of recurrence.
Results
On plain radiographs and CT scans, chordoma primarily manifested as osteolytic bone loss and uneven soft tissue mass, with typical calcification or ossification (56.1 percent). Numerous chunk nodules with clearly high signal levels and short signal intervals were seen as the “pebble” in MRI characteristics on T2WI. The follow-up period ranged from 20 to 130 months, with a median time of 47.5 months. There were 14 recurrences (22. 2%) during the follow-up period. 13 patients with recurrence underwent surgery again, and 5 of them recurred after surgery (recurrence time range 3 to 97 months, median 38. 5 months). 6 (42.8%), 8 (57. 1%), and 13 (92. 9%) of the 14 patients with recurrence recurred within 2, 3, and 5 years after surgery, respectively. Univariate Kaplan-Meier survival analysis showed that occurred with local infiltration, Low differentiated chordoma, partial resection had a high postoperative recurrence rate, and all differences were statistically significant (P<0.05). Multi-factor Cox regression analysis showed whether local infiltration occurred and the degree of tumor resection were independent risk factors for tumor recurrence.
Conclusion
Sacrococcygeal chordoma has a high tendency of recurrence, and the likelihood of recurrence is higher in tumor occurred with local infiltration, non-complete tumor resection and low differentiated chordoma, which can be considered to shorten the review cycle and complete tumor resection as much as possible during surgery.
... For the intraspinal seeding metastasis in the C1-C2 region, surgical resection was the first choice and the patient still required intensive followup. Recently, Passeri et al. (7) suggested tumor growth rate (TGR), showing the percentage change in tumor size over 1 month, may be considered as a preoperative radiological indicator of tumor proliferation and seems to preoperatively identify more aggressive tumors with a higher tendency to recurrence. ...
Background:
Clival chordoma is a locally aggressive tumor originating from remnants of the embryologic notochord. Although clival chordomas account for only 0.2% of all central nervous system tumors, they are characterized by local invasion and destruction, dural invasion, bone erosion, and cranial nerve palsy, and even metastasis.
Case description:
We report a case of a 49-year-old female with an intradural spinal seeding metastasis 16 months after the initial endoscopic endonasal surgery (EES) for a clival chordoma. Gross total resection of tumor in upper clival region was achieved after initial EES and pathology revealed a classic chordoma. After 10 months, follow-up magnetic resonance (MR) showed a recurrence in situ and gamma knife was applied. After 16 months, the patient complained of neck pain and MR showed a new lesion in the spinal canal at C1 to C2 level. After craniotomy, the lesion in the spinal canal was totally removed, and pathology confirmed a chordoma with increased proliferative potential. The spinal chordoma might have occurred as a result of intradural spinal seeding metastasis through cerebral spinal fluid the during the initial operation.
Conclusions:
Chordomas are not only locally aggressive but also unpredictable and may metastasize through cerebral spinal fluid. Intensive follow-up is of great importance in the long term postoperatively time for clival chordoma patients.
Objective
The study aimed to identify if clinical features and survival outcomes of insular glioma patients are associated with our classification based on the tumor spread.
Methods
Our study included 283 consecutive patients diagnosed with histological grade 2 and 3 insular gliomas. A new classification was proposed, and tumors restricted to the paralimbic system were defined as type 1. When tumors invaded the limbic system (referred to as the hippocampus and its surrounding structures in this study) simultaneously, they were defined as type 2. Tumors with additional internal capsule involvement were defined as type 3.
Results
Tumors defined as type 3 had a higher age at diagnosis (p = 0.002) and a higher preoperative volume (p < 0.001). Furthermore, type 3 was more likely to be diagnosed as IDH wild type (p < 0.001), with a higher rate of Ki‐67 index (p = 0.015) and a lower rate of gross total resection (p < 0.001). Type 1 had a slower tumor growth rate than type 2 (mean 3.3%/month vs. 19.8%/month; p < 0.001). Multivariate Cox regression analysis revealed the extent of resection (HR 0.259, p = 0.004), IDH status (HR 3.694, p = 0.012), and tumor spread type (HR = 1.874, p = 0.012) as independent predictors of overall survival (OS). Tumor grade (HR 2.609, p = 0.008), the extent of resection (HR 0.488, p = 0.038), IDH status (HR 2.225, p = 0.025), and tumor spread type (HR 1.531, p = 0.038) were significant in predicting progression‐free survival (PFS).
Conclusion
The current study proposes a classification of the insular glioma according to the tumor spread. It indicates that the tumors defined as type 1 have a relatively better nature and biological characteristics, and those defined as type 3 can be more aggressive and refractory. Besides its predictive value for prognosis, the classification has potential value in formulating surgical strategies for patients with insular gliomas.
Skull base chordomas and chondrosarcomas are rare bone neoplasms that develop around the clivus and the petroclival region. Although they are quite similar in terms of clinical and radiological features, chordomas and chondrosarcomas differ with regard to their origin and prognosis.
The optimal treatment for skull base chordomas and high-grade chondrosarcomas includes radical surgical resection followed by high-dose radiotherapy. Because of chordomas and chondrosarcomas rarity and complex location, the surgical management of these lesions should be carried out exclusively by expert skull base teams. Providing a unique trajectory to the clivus, the endoscopic endonasal approach has considerably changed the surgical management of posterior fossa chordomas and chondrosarcomas in the last two decades. However, limitations remain, and transcranial approaches remain the best adjunct for complex lesions extending beyond the limits of what can be safely achieved with endoscopic techniques. Endoscopically assisted transcranial approaches have also made possible to widen the exposure of classic transcranial approach and to reduce the aggressiveness of the approach. For chordomas, radical resection, including infiltrated bone, remains the goal, as it is the most important prognostic factor. Skull base chondrosarcomas carry a more favorable outcome than chordomas with a better long-term control. Conversely, despite aggressive treatment, chordomas have a high rate of recurrence. The development of medical targeted therapies is strongly needed to improve the outcome of patients with advanced disease.
