Poorly differentiated chordoma with SMARCB1/INI1 loss: a distinct molecular entity with dismal prognosis 1).
Solitary non-chordomatous lesions of the clivus are rare pathologies, which represent a diagnostic challenge.
Imaging features, although mainly specific, are not always diagnostic.
Solitary non-chordomatous lesions of the clival bone are more prevalent than expected. They should be approached with a correct differential diagnosis, considering specific epidemiological, radiological, and histopathological characteristics, to minimise diagnostic bias and allow the planning of the best treatment strategy 3).
see Clivus meningioma.
see Clival metastases.
Degenerative Pannus 4).
The management of chordomas of the base of the skull is particularly challenging as they lie adjacent to vital anatomic structures, such as the carotid and basilar arteries and the brain stem, which limits surgical access and resectability as well as delivery of high doses of radiation 5) 6).
The transnasal and transclival approach is for many chordomas a feasible and safe surgical access 7) 8) 9)
Larger tumors, especially those with extensive intradural retrochiasmal and/or deep cervical expansion, are most often resected by open craniotomy. A large number of transcranial approaches have been described in the last decade 10) 11) 12)
Staged procedures are also commonly used in the case of expansive tumor growth.
Koechlin et al. present the first case of a single-session combined transnasal and transcranial approach to radically resect a large clival chordoma.13).
see Endoscopic transnasal transclival approach
see Lateral transcondylar approach
They show a strong tendency for local recurrence even after combined surgical and radiosurgical treatment. The possibility of spreading to distant locations of the neuraxis may further complicate the treatment and causes additional morbidity.
A Retrospective review of clival chordomas treated 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.
The 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 14).
Recurrence of clival chordoma due to seeding along the surgical pathway is an infrequent mechanism of treatment failure, with only rare cases documented in the literature. When deciding on the appropriate surgical approach, the surgeon must consider the risk of septal seeding during a transseptal approach. The emergence of transnasal endoscopic skull base approaches may reduce the likelihood of surgical pathway tumor seeding 15).
A systematic search of the literature was done by Labidi et al. in March 2016 using EMBASE and PubMed for articles published between January 2006 and March 2016 to identify surgical series of clivus chordomas. Only articles describing chordomas cases arising from the clivus of craniocervical junction were included in the analysis.
Twenty-seven articles were included in this systematic review, amounting to a total of 1050 patients. The weighted mean rate of GTR was 39.9% (range 0-78.3%) in this patient population. The surgical approaches were described in 16 papers, with 6 series reporting on surgeries done exclusively through the midline corridor (116 patients). In the remaining 10 series (495 patients), the anterior midline approach (AMA) was used in a mean of 56.8% of cases. In studies including patients operated solely through an AMA, a higher GTR rate was obtained (60.7% vs. 42.0%). Postoperative complications were also different between the two cohorts, with lower cranial nerves deficits and CNS infections but higher incidence of CSF leak in the AMA group than in mixed surgical series. In a weighted mean follow-up time of 52.1±21.9 months, recurrences were observed in 38.2% of the total population of patients. Among 423 patients, the weighted 5-year PFS was 49.9±12.1% and the 5-year OS was 73.9±11.2% (N.=391). A random effects model was performed, combining data from studies reporting recurrence rates in GTR and non-GTR (N.=610), with a total odds ratio of having a recurrence for patients who had GTR vs non-GTR of 0.289 (95CI 0.184-0.453).
In this systematic review and meta-analysis of studies published in the last decade, an estimated 5-year PFS of 49.9% and 5-year OS of 73.9% were obtained. The weighted mean GTR rate in the included study was 39.9%, with a significantly reduced occurrence of recurrence in complete resections. Although anterior midline approaches may allow for higher GTR rates and fewer neurological morbidity than traditional transcranial routes, their impact of long-term survival and disease control remains largely unknown 16).
Data for 12 consecutive patients underwent GKS for post-operative residual histologically verified clival chordoma at the Department of Neurosurgery and Gamma Knife Center, International Medical Center (IMC), 42km. Ismailia Desert Road, Cairo, Egypt from 2006 through end of 2017 were retrospectively reviewed and analyzed with mean follow-up period of 45 months (range12-120 months).
In the last follow up MR, tumor growth control was achieved in 33.3% of patients (mean treated tumors volume was 2.7cc with mean peripheral prescription dose of 16 Gy), and 66.7% of patients reported lost tumor growth control (mean treated tumor volume was 9.2 cc with mean peripheral dose was 13.5 Gy). The overall tumor free progression with mean follow up period of 45mos was 33.3%. The Actuarial 2, 3 and 5 year tumor control rates after initial GKS was 35%, 30% and 25% respectively.
Without satisfactory maximum tumor reduction and sufficient high peripheral prescription radiation tumor dose, it should not be expected that GKS could efficiently control the progression of residual clival chordoma, especially for long term 17).
14 consecutive clivus chordoma cases undergoing maximum surgical resection followed by intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB), using the institutional protocol from the Gangnam Severance Hospital, Seoul, Korea, between 2005 and 2013. Total and near-total resections were achieved in 11 patients (78.6 %), partial in 2 patients (14.3 %), and 1 patient (7.1 %) received RT for recurrent tumor after total resection. Gross residual or the high-risk area defined the planning target volume (PTV)1; PTV2 was the postoperative tumor bed plus a 3-5-mm margin, and PTV3 was PTV2 plus a 5-10 mm margin. A moderate hypofractionation schedule was used: doses to PTV1, PTV2 and PTV3 were 3.9 Gy, 3.15 Gy and 2.8 Gy through 15 fractions for the first two patients, and the rest received 2.5 Gy, 2.2 Gy and 1.8 Gy through 25 fractions. The biologically equivalent dose in 2-Gy fractions (EQD2) was 65-68 Gy for PTV1, 52-56 Gy for PTV2, and 44.3-44.8 Gy for PTV3.
Median follow-up was 41 months. Eight patients were free of disease for median 42.5 months (range 23-91 months), four patients had stable disease for median 60.5 months (range 39-113 months), and 1 patient showed partial response for 38 months after RT. Local progression was seen in one patient who received EQD2 67.8 Gy after partial resection. Estimated 5-year progression-free and overall survival rates were 92.9 %. Surgery improved the neurologic deficit in six patients, and IMRT-SIB was well tolerated without lasting toxicity.
The experience suggests that maximum resection and high-dose IMRT-SIB can achieve local control without significant morbidities 18).
Cha et al. report two cases of pediatric PD chordoma with loss of SMARCB1/INI1 expression, which is very rare among the pediatric chordoma types. Both patients presented clival masses on preoperative MRI. Histologically, both tumors had nonclassic histologic features for conventional chordoma: sheets of large epithelioid to spindle cells with vesicular nuclei and prominent nucleoli. Both cases revealed nuclear expression of brachyury, loss of SMARCB1/INI1 expression and lack of embryonal, neuroectodermal, or epithelial component. One case showed heterozygous loss of EWSR1 gene by break-apart fluorescence in situ hybridization that reflected loss of SMARCB1/INI1 gene. Based on the clival location and histologic findings along with the loss of SMARCB1/INI1 expression and positivity for nuclear brachyury staining, the final pathologic diagnosis for both cases was PD chordoma 19).
In the Department of Neurosurgery, Austin Hospital, Heidelberg, Victoria, Australia, a case of a 25 year-old male patient with chordoma in the inferior clivus which was initially debulked via a transnasal endoscopic approach. He unfortunately had a large recurrence of tumor requiring re-do resection. With the aim to achieve maximal surgical resection, we then chose the technique of a transoral approach with Le Fort 1 maxillotomy and midline palatal split. Post-operative course for the patient was uneventful and post-operative MRI confirmed significant debulking of the clival lesion. The technique employed for the surgical procedure is presented here in detail as is our experience over two decades using this technique for tumors, inflammatory lesions and congenital abnormalities at the cranio-cervical junction 20).