Endoscopic Approach to Clival Chordomas: The Northwestern Experience

Original Article

Endoscopic Approach to Clival Chordomas: The Northwestern Experience Rudy J. Rahme1, Omar M. Arnaout1,2, Olabisi R. Sanusi1, Kartik Kesavabhotla1, James P. Chandler3

INTRODUCTION: Chordomas are rare primary bone tumors with a low-grade histology but an aggressive clinical behavior characterized by local invasion and recurrence. When occurring in the skull base, their treatment is limited by proximity to critical neurovascular structures. Open surgical approaches can carry high morbidity, making the development of alternative approaches desirable. We describe our experience with endoscopic endonasal approaches to clival chordomas over 13 years.

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METHODS: We performed a retrospective chart review of patients diagnosed with clival chordomas and treated with an endoscopic endonasal approach between 2003 and 2015 at Northwestern Memorial Hospital. We reviewed presenting symptoms, tumor location and size, extent of resection, complications, recurrence, adjuvant treatment, retreatment, and follow-up duration.

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RESULTS: A total of 23 charts were reviewed, with 17 included in our final review. Mean age was approximately 48 years. The most common presenting symptom was diplopia present in 70.6% of patients. Mean tumor volume was 20.2 cm3. Gross total resection was achieved in 52.9% of patients. With a mean follow-up period of 63.4 months, 5 patients had a recurrence. The most common complication was cerebrospinal fluid (CSF) leak, which was noted in 6 patients. Tumor volume was significantly higher in patients with CSF leak. No correlation between intradural extension and postoperative CSF leak was noted.

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CONCLUSIONS: Clival chordoma are challenging entities to treat. The best outcomes are achieved with gross

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total resection followed by adjuvant radiotherapy treatment. We show that the endonasal endoscopic corridor is a viable alternative approach to these lesions.

INTRODUCTION

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hordomas are rare primary bone tumors believed to arise extradurally from fetal notochordal remnants.1-7 They constitute around 0.1%e0.2% of all intracranial tumors. They are more common in males than in females, with a ratio of 1.6:1 and a peak incidence in the fourth and fifth decade of life.2-4,8 They can be found along the axial skeleton, most commonly in the sacrum and mobile spine as well as intracranially along the clivus and the spheno-occipital synchondrosis.2,5 Although considered histologically low-grade neoplasms, they are locally aggressive, with high rates of recurrence, and thus their natural history and progression resemble those of malignant tumors. Chordomas are locally destructive and can spread into the epidural space, the cavernous sinus, and the pituitary fossa.1,4,6 Although rare at presentation, there are reports of leptomeningeal carcinomatosis9,10 as well as distal metastasis, most commonly to the lungs, lymph nodes, liver, bone, skin, and brain.11-21 However, patient outcome and survival seem to be less affected by distant metastasis then by local progression of the tumor.11-17 The current treatment algorithm includes aggressive surgical approach with the goal of gross total resection (GTR) followed by radiation therapy. The location and proximity of clival chordomas to vital neurologic and vascular structures can make GTR challenging. In addition, because of their insidious onset, there is often a large tumor burden at the time of diagnosis, with

Key words Chordoma - Endonasal - Endoscopic - Outcome - Radiation - Surgery

From the 1Department of Neurological Surgery, Northwestern University, Feinberg School of Medicine and McGaw Medical Center, Chicago, Illinois; 2Department of Neurological Surgery, Brigham and Women’s Hospital, Harvard School of Medicine, Boston, Massachusetts; and 3Departments of Neurological Surgery, Otolaryngology, and Anesthesiology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA

Abbreviations and Acronyms CSF: Cerebrospinal fluid GTR: Gross total resection MRI: Magnetic resonance imaging

Citation: World Neurosurg. (2017). https://doi.org/10.1016/j.wneu.2017.10.146

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To whom correspondence should be addressed: James P. Chandler, M.D. [E-mail: [email protected]; [email protected]]

Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2017 Elsevier Inc. All rights reserved.

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impingement on the surrounding structures, adding to the complexity of surgical resection as well as radiation planning.1,4,6 Furthermore, open surgical access to the clival region may be complex and carry risk of significant morbidity, historically requiring transfacial, transbasal, or a combination of transcranial approaches.22,23 More recently, ventral endoscopic endonasal approaches have offered a less invasive alternative through a more natural and direct corridor.2,24,25 In this study, we present our experience over the past 15 years at Northwestern Memorial Hospital with the endoscopic approach to this potentially devastating disease.

23 charts reviewed 4 patients excluded because of inability to confirm chordoma diagnosis

19 charts remaining

METHODS We retrospectively reviewed the charts of all patients diagnosed with skull base chordomas treated through an endoscopic approach at Northwestern Memorial Hospital between 2003 and 2015. All surgical approaches were performed by the same surgeon (senior author J.C.). The exclusion criteria were patients who did not receive treatment, those who had an open surgical approach, and those in whom the diagnosis of chordoma could not be confirmed. Institutional review board approval was obtained before initiation of the review. Data that were collected included patient’s age at diagnosis, preoperative and postoperative symptoms, tumor location and size, surgery date and approach, extent of resection, complications, recurrence, adjuvant treatment, retreatment, and follow-up duration. GTR was defined as complete resection of the tumor. Extent of resection was defined based on postoperative imaging (both contrast-enhanced and fluid-attenuated inversion recovery sequences), which was reviewed by an independent radiologist. To calculate tumor volume, we performed a volumetric analysis using the Brainlab iPlan Net server (Brainlab AG, Feldkirchen, Germany). Imaging was imported into the software and precontrast and postcontrast imaging as well as fluid-attenuated inversion recovery sequences were analyzed to define the tumor margin. For patients whose imaging was performed at an outside institution and was missing from their charts, we used the formula for modified ellipsoid ABC/2 where A, B, and C are the 3 dimensions of the tumor in 3 orthogonal axes. This approach has been validated in the literature for intracranial processes volume assessment such as tumors and hemorrhages, with high interrater reliability.26-29 For our statistical analysis, we used the 2-tailed t test with the significance level set at a < 0.05 to compare means. When comparing proportions, we used the c2 test with a significance value set at P < 0.05. RESULTS A total of 23 patients were found after the initial review. Four of these 23 patients were removed from the study because of inability to confirm the diagnosis of chordoma on pathology slides: 2 were chondrosarcomas, 1 was fibrous tissue with no definitive chordoma, and 1 was osteoma. Two other patients were removed from the study because they were exclusively treated with an open transoral approach (Figure 1). Of the remaining 17 patients, 10 were male and 7 were female, with a mean age of 48.06 years. The most common presentation was visual symptoms, with 12 patients (70.6%) reporting diplopia, 3 (17.6%) of whom had

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2 patients treated with open surgical approach

17 charts included Figure 1. Flowchart of patient selection.

overt cranial nerve VI palsy on physical examination. Headaches were the second most common symptom, with 8 patients (47.1%), followed by paresthesias (2 patients; 11.8%), which included face and limb paresthesias. Two patients were asymptomatic at the time of diagnosis. Most patients had multiple symptoms on presentation. Table 1 summarizes all presenting symptoms. In terms of tumor characteristics, 3 patients had extension of their tumors to the sellar/parasellar region. In 1 case, the tumor extended into the occipital condyles and the cervical spine. Regarding tumor size, the mean volume was 20.2 cm3 (range, 1.93e107.6 cm3). We then compared the tumor volume between

Table 1. Presenting Symptoms

Diplopia

Number of Patients

% Patients

12

70.6

Headaches

8

47.1

Cranial nerve palsy

3

17.6

Paresthesia

2

11.8

Asymptomatic

2

11.8

Neck pain

1

5.9

Imbalance

1

5.9

Tinnitus

1

5.9

Dysphagia

1

5.9

Airway obstruction

1

5.9

Decreased smell

1

5.9

Coma

1

5.9

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patients who had a cerebrospinal fluid (CSF) leak and those who did not. In patients who experienced postoperative CSF leak, the mean tumor volume was 35.6 cm3 (standard deviation, 35.6; range, 3.6e107.6). Patients without a CSF leak had a mean tumor volume of 9.4 cm3 (standard deviation, 10.9; range, 1.93e35). Using a 2-tailed t test, the difference was statistically significant with a higher volume in the CSF leak group (P ¼ 0.04). In our series, 9 patients (52.9%) had intradural extension of their tumor. When further analyzing the dural extension of the tumor, 4 of 9 patients (44%) with intradural extension at presentation had a CSF leak postoperatively compared with 3 of 8 patients (37.5%) with preserved dural/tumor border. The difference was not statistically different between both groups (P ¼ 0.78). A total of 23 endoscopic endonasal procedures were performed in 17 patients. In 1 case, the initial surgery was performed through an open transfacial approach. The patient had multiple recurrences with re-resection through an endonasal endoscopic approach. GTR after the initial endoscopic surgery was achieved in 9 patients (52.9%). During a mean follow-up period of 63.4 months (range, 2e134 months), 5 patients had a recurrence (29.4%). One of these patients had only 1 recurrence at the time of last follow-up, 2 patients had 2 recurrences, 1 patient had 3 recurrences, and 1 patient had 5 recurrences, for a total of 13 recurrences. In 10 of these 13 recurrences, repeat surgical resection was undertaken, 7 through an endonasal endoscopic approach. The remaining 3 approaches were as follows: 1 far lateral, 1 transpetrosal, and 1 retrosigmoid craniotomy. When further analyzing our series, there were 14 first-time surgeries (3 of the 17 patients in our series had previous surgery at outside institutions) and 13 redo surgeries. Nine of the 14 first-time surgeries (64.3%) ended with GTR compared with only 2 of 13 (15.4%) in the redo surgeries. Using the c2 test, the difference was statistically significant with a P of 0.01. Of 13 recurrences, only 1 (7.6%) was after a GTR and 12 (92.3%) followed a subtotal resection. We then looked at the recurrence rates per degree of resection. There were 11 cases of GTR with only 1 recurrence (9.09%), whereas there were 12 recurrences (75%) of a total of 16 subtotal resections. The difference was statistically significant, with a P of < 0.001. Of the total 13 recurrences, 3 were treated nonsurgically. In 2 cases, recurrences were treated with radiation therapy (proton beam in one case and Gamma Knife [Elekta, Stockholm, Sweden] in the other). In the third case, the patient was transferred to hospice care. Mean time to first recurrence was 58.6 months (range, 8e113 months). Regarding adjuvant therapy, all patients had adjuvant radiation therapy. Of the 17 patients who underwent radiation therapy, 12 had stereotactic radiosurgery and 5 patients underwent proton beam therapy. After treatment, 10 patients (58.8%) showed improvement in their presenting symptoms. Five patients (29.4%) had stable symptoms. One of these patients had presented in a comatose state as a result of the long course of the disease with brainstem compression and multiple surgeries. Redo resection at our institution did not improve his neurologic status and he was flown back to his home country. Two patients, who were asymptomatic at presentation, remained so postoperatively. In terms of complications, the most common reported complication was CSF leak, which was noted in 6 patients (35.3%). There were 6 CSF leaks of 23 endonasal procedures (26%). Three

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of these 6 leaks were during recurrent surgeries, 2 occurred before the nasal vascularized flap, and in 1 case, there was a significant defect postoperatively that was difficult to seal even with a flap and required a return to the operating room for repair. Cranial nerve palsy was the second most common complication, in 5 patients (29.4%). Of these 5 patients, 3 had cranial nerve VI palsy, 1 had cranial nerve IIeVI neuritis, and 1 had cranial nerve V, VI, VIII, IX, X, XI, and XII palsies. Two of the 5 cranial nerve palsies were transient, with complete resolution. In 1 patient, the palsy was believed to be caused by tumor progression. One patient had corrective surgery for his strabismus and the other died of disease progression. Meningitis was noted in 3 patients (17.6%). Two patients (11.8%) had a stroke postoperatively, one of which was caused by radiation-induced vasculitis. At the time of writing of this report, there were 2 (11.8%) reported mortalities as a result of disease progression and 1 (5.8%) hospice transfer. Case Illustration A 16-year-old woman presented with a history of transient diplopia, precipitating brain magnetic resonance imaging (MRI). The study showed a large clival-based lesion with effacement of the pons and encroachment on the bilateral carotid arteries and basilar artery (Figure 2). The patient underwent an endoscopic endonasal approach for resection. The patient had an uncomplicated postoperative course and was discharged home, neurologically intact. Postoperative MRI (Figure 3) showed a possible small residual about 1 cm in size. The patient underwent stereotactic

Figure 2. Initial magnetic resonance imaging showing the tumor.

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Figure 4. Six-year follow-up magnetic resonance imaging with no residual/no recurrence.

Figure 3. Immediate postoperative magnetic resonance imaging showing a possible small residual.

radiation to the resection cavity and to the residual nodule 6 weeks after the surgery. Most recent MRI showed no residual or recurrence after 6 years of follow-up (Figure 4). DISCUSSION Chordomas are rare histologically benign tumors that behave locally in a malignant way. They originate from the embryonic notochord, which forms during gastrulation and induces the differentiation of the ectoderm into neuroectoderm. It is a transient embryonic structure that disappears after inducing vertebral column formation with remnants in the nucleus pulposus throughout the axial skeleton.30 Although Virchow was the first to describe the histology of these tumors in 1857, it was Rinnert who introduced the term chordoma in 1890 in reference to the notochord hypothesis.6 Although there has been no direct molecular proof of transformation of the notochordal cells into chordoma cells, the hypothesis of notochordal origin still holds for multiple reasons. First, examination of human fetal cells as well as cell tracking experiments in mice showed that the sites of development of chordoma closely correspond to those of notochordal cell remnants. This finding was determined through noted similarities in electron light microscopy and immunophenotype (cytokeratin and S100 protein expression).31-35 Second, a duplication of brachyury, a transcription factor protein encoded by the T

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gene (chromosomal region 6q27) found in normal embryonic undifferentiated notochord has been identified in association with familial chordoma as well as sporadic chordoma. Although it is still unclear what the exact role of brachyury in the pathogenesis of chordoma is, its overexpression in chordomas as well as its role in other carcinoma development suggests that it might be a major molecular driver in these tumors.6,32-35 Third, Sun et al.30 created a model of degeneration of the notochordal remnant cells into chordoma. These investigators hypothesized that these cells can either degenerate directly into chordoma or that there is an intermediate phase of benign notochordal cell tumor, which later develops into chordoma cells. However, most notochordal cells remain dormant because the occurrence of remnants is significantly higher than the incidence of chordoma. It is therefore presumed that further mutations, environmental factors, or other inciting events must be present to initiate the malignant transformation.36 Clinically, clival chordomas have an insidious onset and progression and therefore they are often diagnosed late in the disease progression, with infiltration of the surrounding tissue. Patients often present with cranial nerve palsies with reports in the literature of up to 80% of neurologic dysfunction as a result of cranial nerve involvement.37 Similar to our series, diplopia is the most commonly reported neurologic symptom.21,37,38 In addition, multiple other presenting symptoms in our series can be traced back to cranial nerve dysfunction, such as tinnitus, dysphagia, and decreased sense of smell. Presentation with endocrinopathies has also been reported if there is involvement of the sella, although it was absent from our series.39 To further characterize the tumor,

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MRI is the imaging modality of choice, because it can show the degree of involvement of the neural elements and clues regarding intradural extension. In addition, computed tomography can assess the bony anatomy and erosion, which could help in surgical planning. Vascular imaging such as computed tomography angiography or magnetic resonance angiography should also be performed to better define the relation of the tumor to the critical vascular structures such as the carotid and basilar arteries. Patients should also undergo spine imaging to rule out involvement elsewhere in the neuroaxis. In terms of treatment, pathology of the skull base presents some of the most challenging surgical diseases that neurosurgeons tackle. To address this spectrum of disease, a multitude of surgical approaches have been developed and refined over the years. The main objective behind these approaches is maximizing the extent of resection and reducing trauma to the surrounding soft tissue, the brain, and neurovascular structures, with the goal of optimizing the oncologic outcome and reducing approachrelated morbidity. As is the case in other surgical fields, the pendulum of aggressive approaches in skull base surgery, including clival chordomas, has undulated in recent years. As approaches were first developed and refined, there existed a trend toward extensive open resection with large craniotomies and tissue manipulation to obtain the required exposure and illumination for dissection.22,23,40 With the advent of advanced neuroimaging, radiosurgical and radiotherapeutic techniques, intraoperative neuronavigation, and hemostatic agents, the pendulum has swung back specifically with the evolving role of the endoscope2,5,40-42; surgeons are opting for simpler and less invasive approaches limiting iatrogenic injury. Multiple open surgical approaches have been devised to access the clival region depending on the direction of extension of the tumor.43-45 Historically, lesions in the upper clivus were approached through an orbitofrontal approach or its variants. For lesions in the midclivus, a transpetrosal approach is an option. As for the lower clivus, it can be approached through lateral skull base corridors or transfacial approaches. All these approaches are complex and not without associated morbidity and require extensive drilling, brain retraction, and manipulation of neurovascular structures. Although the open skull base approaches continue to play an important role in the surgical management of complex skull base lesions, the development and refinement of the endonasal approach, concurrent with advances in endoscopy and endoscopic instrumentation, provide an alternative surgical corridor. The ventral endoscopic approach uses the natural anatomic corridors through the nasopharynx to reach these midline tumors. The endonasal approach can be used to safely resect extradural, intradural, or interdural disease depending on the location and extent of the tumor.5,46 In our series, the open surgical approach was used when the extent of the tumor was prohibitive of endoscopic techniques. In the 2 patients excluded from this series, the transoral approach was used because of the cervical location of the tumor. The far lateral approach for one of the recurrences was also preferred because of the low lesion location. Current treatment algorithms for clival chordomas include GTR when feasible followed by radiation therapy. The rates of GTR decreased with redo surgeries compared with first-time approaches, which is in agreement with the findings in our

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series.29,47,48 The objective of surgery is maximal tumor resection with preservation of function and quality of life. If the tumor encroaches on critical structures such as the brainstem, the goal of the surgery becomes to safely decompress these structures and optimize the radiation target. Tumors at the brainstem interface should be particularly pursued to maximize the radiation dose and response without risking the toxic effect of radiation on the brainstem. This approach has been shown to improve local control and survival in these cases.49 In cases of intradural extension that is identified or suspected on preoperative imaging, plans should be made for dural reconstruction to avoid dural leaks, although we routinely preserve the option of harvesting a flap during the approach for all cases. In our endoscopic endonasal series, the intradural extension did not correlate statistically with the risk of postoperative CSF leak. This may be because of low power related to the sample size, or the presence of intradural extension and dural involvement identified clinically but that is radiographically occult. In terms of recurrences, the rates are significantly higher after subtotal resection than with GTR, which correlates with the findings in our series.29,47,48 Komotar et al.24 performed a literature review comparing open versus endoscopic approaches to clival chordomas. These investigators reviewed 37 studies reported between 1950 and 2010 with a total of 766 patients. In the review, they found that GTR was achieved in a significantly higher percentage of patients in the endoscopic approach (61%) compared with the open surgical group (48.8%). Our rate of GTR was 52.9%, which is within the range reported in the literature (48%e71%).7,24,40,50-52 New postoperative cranial nerve deficits were found in a higher percentage of patients with the open approach (24.2% of patients) compared with the endoscopic approach (1.3%).24,40 However, there was variability in reporting cranial nerve deficits because some articles reported only permanent deficits, whereas others reported both permanent and transient deficits. CSF leaks were similar with both approaches, occurring in 10.7% of cases in the open cohort versus 5% in the endoscopic cohort.24,40 In terms of medical complications, meningitis occurred in 5.9% of patients in the open cohort, significantly more than in the endoscopic cohort (0.9%). No difference was noted in pneumonia, sepsis, diabetes insipidus, and hydrocephalus.24,40 In terms of outcomes, the mortality was 21.6% in the open cohort with a wide variability in the reports in the literature (0%e100%). In the endoscopic cohort, the rate was 4.7%, representing a statistically significant difference.24,40 Local recurrence occurred significantly less in the endoscopic cohort (16.8%) compared with the open group (40%).24,40 However, these numbers are to be reviewed with a critical perspective because there are no randomized controlled trials and most data come from retrospective series. Another literature review performed by Graffeo et al.50 yielded different findings, further proving the paucity of high-level literature and evidence in chordoma management. In their study, Graffeo et al.50 reviewed published reports dating back to 1990 and found that the rate of GTR was similar in the open and the endoscopic approach (63.9% in the open cohort vs. 58.8% in the endoscopic approach). In addition, perioperative mortality was also similar in both groups (3.5% in the open group vs. 2.5% in the endoscopic group) and so were

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recurrence rates (9.3% in the open cohort and 6.8% in the endoscopic cohort). Although the divergence in findings can be caused by differences in the method and article selection, it can also be caused by the variability of the disease as well as that of the surgical management and expertise. In our series, the most common complication was CSF leak. The reported rate of CSF leak in the literature is again widely variable, from 0% to 50%.5,12,24,37,50 The variability is at least partly caused by the varying size and level of invasiveness of the tumor with destruction of the normal skull base anatomy. In our series, half of CSF leaks were in recurrent tumors, where the scar tissue makes it difficult to dissect tumor and find proper places without dural breach. When reviewing the tumor size of patients who had CSF leaks in our series, there was a clear statistically significant difference with a bigger tumor volume in these patients compared with those who did not have a CSF leak. In our experience, to avoid CSF leaks, our dural closure is performed with multiple layers. We start with a subdural inlay graft, followed by an extradural onlay graft, fibrin glue sealant, abdominal fat graft, pedicled nasoseptal flap, and another layer of sealant; a balloon catheter is inflated to keep the reconstruction in place until it heals. In high-risk cases, we place a lumbar drain intraoperatively and drain for at least 5 days. Closure with a pedicled nasoseptal flap is arguably the most important step to avoid CSF leak. Use of a lumbar drain can also be helpful in cases in which either the tumor cavity is large or if there was dural invasion and/or noted CSF leak intraoperatively. Multiple predictive factors have been studied with inconsistent and sometimes contradictory findings. Subtotal resection and dedifferentiated histology have been proposed as poor prognostic indicators.47,53-55 In particular, a 10-year meta-analysis of observational studies47 found that there was a 3.83 times increase in rate of recurrence and a 5.85 times increase in mortality in patient with incomplete resection at 5 years when compared with GTR. Gender and age were also analyzed with contradictory results in different studies, with male sex and older age noted to be a risk factor for poor outcome in some studies,1,7,49,54,56 and female gender and younger patients (including the pediatric population) in others.49,57-59 Further adding to the controversy, some studies did not find any effect of gender on prognosis.1 In terms of tumor size, results from different studies were again contradictory, with some investigators suggesting that large volume incurred reduced survival,56 whereas others did not find any correlation with tumor size.1 Radiation modality did not seem to affect survival in most studies.7,47,54 Other prognostic factors associated with poor outcome include tumor location in the middle and lower clivus and visual symptoms on presentation.1,7,56

REFERENCES 1. Choy W, Terterov S, Kaprealian TB, Trang A, Ung N, DeSalles A, et al. Predictors of recurrence following resection of intracranial chordomas. J Clin Neurosci. 2015;22:1792-1796.

2. Fraser JF, Nyquist GG, Moore N, Anand VK, Schwartz TH. Endoscopic endonasal transclival resection of chordomas: operative technique,

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The treatment algorithms for chordomas include adjuvant radiation therapy to improve tumor control as well as decrease rate of recurrence.1,3,55 The role of radiation therapy in skull base chordomas remains controversial, with some investigators advocating for adjuvant therapy only in case of subtotal resection.47,48 Even after GTR, the recurrence rates remain high.48,60,61 In addition, chordomas are relatively radioresistent tumors and high doses are required to achieve the desired effect, typically higher than 60 Gy.59,61 Advances in radiation technology have led to better targeting of lesions.3,6 Multiple modalities of radiation therapy are available and have been used, including high-dose proton and photon as well as stereotactic radiosurgery, fractionated or in a single dose.6,49,62,63 The closeness of these tumors to high-yield and sensitive structures in addition to their radioresistent nature make proton beam an attractive modality because of the ability to deliver high doses to the tumor bed with a spread-out Bragg peak and a sharp dose fall-off, thus spearing normal surrounding tissue.61,64 A true comparison of the different radiation modality is limited because of the rarity of the disease and the paucity of high-quality publications with a high level of evidence. However, a 10-year meta-analysis of observational studies showed no difference in 5-year progression-free survival when comparing the different radiation modalities, with the only exception being a lower performance of Gamma Knife compared with carbon ion.47 In our series, radiation therapy was recommended to and undertaken by all patients. Most patients underwent stereotactic radiosurgery and about a third of our patient population underwent proton beam radiation. CONCLUSIONS Treatment of skull base chordomas can be challenging because of their locally aggressive nature and high rate of recurrence. Endoscopic approaches have been shown to be promising with at least similar to lower morbidity and similar to higher rates of local control based on the published literature. Our rates of total resection, recurrence, and complications are similar to those previously reported and further consolidate the validity of the endoscopic endonasal approach in the treatment of patients with clival chordomas. However, patient selection remains paramount, and the surgeon who tackles clival chordomas must be facile with multiple approaches to be able to select the ideal approach. Nonetheless, improvement and innovations in surgical techniques and approaches as well as radiation therapy are needed to continue to improve local and distal control and long-term outcomes.

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technique, nuances, and pitfalls. Otolaryngol Clin North Am. 2016;49:167-182.

3. Ito E, Saito K, Okada T, Nagatani T, Nagasaka T. Long-term control of clival chordoma with initial aggressive surgical resection and gamma knife radiosurgery for recurrence. Acta Neurochir (Wien). 2010;152:57-67 [discussion: 67].

5. Stippler M, Gardner PA, Snyderman CH, Carrau RL, Prevedello DM, Kassam AB. Endoscopic endonasal approach for clival chordomas. Neurosurgery. 2009;64:268-277 [discussion: 277-278].

4. Mangussi-Gomes J, Beer-Furlan A, Balsalobre L, Vellutini EA, Stamm AC. Endoscopic endonasal management of skull base chordomas: surgical

6. Walcott BP, Nahed BV, Mohyeldin A, Coumans JV, Kahle KT, Ferreira MJ. Chordoma: current concepts, management, and future directions. Lancet Oncol. 2012;13:e69-e76.

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7. Jahangiri A, Chin AT, Wagner JR, Kunwar S, Ames C, Chou D, et al. Factors predicting recurrence after resection of clival chordoma using variable surgical approaches and radiation modalities. Neurosurgery. 2015;76:179-185 [discussion: 185-186]. 8. McMaster ML, Goldstein AM, Bromley CM, Ishibe N, Parry DM. Chordoma: incidence and survival patterns in the United States, 1973-1995. Cancer Causes Control. 2001;12:1-11. 9. Hatzoglou V, Karimi S, Diamond EL, Lis E, Krol G, Holodny AI, et al. Nonenhancing leptomeningeal metastases: imaging characteristics and potential causative factors. Neurohospitalist. 2016;6:24-28. 10. Krol G, Sze G, Arbit E, Marcove R, Sundaresan N. Intradural metastases of chordoma. AJNR Am J Neuroradiol. 1989;10:193-195. 11. Khurram SA, Biswas D, Fernando M. A parapharyngeal soft tissue chordoma presenting with synchronous cervical lymph node metastasis: an unusual presentation. Head Neck Pathol. 2016;10: 400-404. 12. Hindi N, Casali PG, Morosi C, Messina A, Palassini E, Pilotti S, et al. Imatinib in advanced chordoma: a retrospective case series analysis. Eur J Cancer. 2015;51:2609-2614. 13. Lebellec L, Aubert S, Zairi F, Ryckewaert T, Chauffert B, Penel N. Molecular targeted therapies in advanced or metastatic chordoma patients: facts and hypotheses. Crit Rev Oncol Hematol. 2015;95:125-131. 14. Stacchiotti S, Sommer J, Chordoma Global Consensus Group. Building a global consensus approach to chordoma: a position paper from the medical and patient community. Lancet Oncol. 2015;16:e71-e83. 15. Chambers PW, Schwinn CP. Chordoma. A clinicopathologic study of metastasis. Am J Clin Pathol. 1979;72:765-776. 16. von Witzleben A, Goerttler LT, Lennerz J, Weissinger S, Kornmann M, Mayer-Steinacker R, et al. In chordoma, metastasis, recurrences, Ki-67 index, and a matrix-poor phenotype are associated with patients’ shorter overall survival. Eur Spine J. 2016;25:4016-4024. 17. Boriani S, Chevalley F, Weinstein JN, Biagini R, Campanacci L, De Iure F, et al. Chordoma of the spine above the sacrum. Treatment and outcome in 21 cases. Spine (Phila Pa 1976). 1996;21:1569-1577. 18. Delank KS, Kriegsmann J, Drees P, Eckardt A, Eysel P. Metastasizing chordoma of the lumbar spine. Eur Spine J. 2002;11:167-171. 19. Erkmen CP, Barth RJ Jr, Raman V. Case report: successful treatment of recurrent chordoma and bilateral pulmonary metastases following an 11year disease-free period. Int J Surg Case Rep. 2014; 5:424-427. 20. McPherson CM, Suki D, McCutcheon IE, Gokaslan ZL, Rhines LD, Mendel E. Metastatic disease from spinal chordoma: a 10-year experience. J Neurosurg Spine. 2006;5:277-280.

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Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 21 August 2017; accepted 25 October 2017 Citation: World Neurosurg. (2017). https://doi.org/10.1016/j.wneu.2017.10.146 Journal homepage: www.WORLDNEUROSURGERY.org

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