Clivus chordomas: Heterogeneous tumor extension requires adapted surgical approaches

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Highlights

  • Patients with clivus chordomas had a 5-year PFS of 44.7 %.

  • The sixth nerve palsy could significantly be improved by surgery.

  • Vast and infiltrative tumor extension constitute major limitations of surgical resection.

  • Irradiation with carbon ions after chordoma surgery is recommended.

Abstract

Objective

Clivus chordomas are semi-malignant, but infiltratively growing tumors. Currently, a widely-accepted treatment concept encompasses maximal, but safe, surgical resection and radiotherapy. Caused by the size and the tumor extension, different surgical approaches, especially in recurrent cases, might be necessary.

Methods

Retrospective review of 50 patients on whom 70 surgeries were performed: 29 in primary and 41 in recurrent cases. Based on MRI images, all cases were asserted according to the size and the extension of the tumor. Used surgical approaches were evaluated. Postoperative complications, neurological function prior to and after the surgery, the extent of tumor resection on postoperative MR images were assessed and progression-free survival was calculated.

Results

Tumor size was estimated as small (< 5 cm3) in 8, as medium (5−20 cm3) in 21, as large (20−100 cm3) in 17, and as giant (> 100 cm3) in 4 patients. Most frequently used surgical approaches in primary cases were the transsphenoidal one and midfacial degloving (51.7 % and 17.2 %, respectively). In recurrent cases, dependent on the tumor extension, transsphenoidal (21.9 %), retrosigmoidal (29.3 %), and pterional (19.5 %) approaches, as well as midfacial degloving (17.1 %) were used. Due to the vast tumor extension and infiltration, gross total or near total resection could be achieved in 12 patients (24 %), only. There was no mortality and no major complications in primary cases. In recurrences, however, postoperative hemorrhages and strokes emerged in 4.9 % and 7.1 %. Minor complications occurred in 17.1 % and were dominated by CSF leaks (12.2 %), both in primary in recurrent cases. While most cranial nerve impairments were caused by tumor infiltration of the cavernous sinus, and hence have not improved by treatment, the sixth nerve palsy as a consequence of tumor mass compression, could significantly be improved by surgery. Following surgery, patients were subjected to radiotherapy (68.9 % for primary cases, and 36.6 % for recurrences) mainly with carbon ions. Overall, 5-year progression-free survival was 44.7 %.

Conclusion

Caused by the heterogenous pattern of growth of clivus chordomas, surgical approaches should be chosen individually. Vast and infiltrative tumor extension constitute major limitations of surgical resection, and hence result in poor progression-frees survival.

Introduction

Clivus chordomas are rare tumor entities derived from remnants of the notochord, accounting for 1–4 % of all bone malignancies [1]. While 50 % of all chordomas grow within the sacrococcygeal area, 35 % arise within the skull base, specifically within the clivus, and the remaining 15 % within the adjacent midline structures, like the cervical spine [2]. Referring to their growth pattern, chordomas are described as slow-growing, yet infiltrative low-grade malignancies. Different genetic profiles of chordomas might contribute and explain different pattern of growth, e.g. the expression of TGF β, PTEN and Ki-67, or the upregulation of cadherins, mTOR and c-MET molecules or their pathways [[3], [4], [5], [6]].

As a widely-accepted treatment strategy, maximal surgical resection preserving neurological function followed by radiation therapy is recommended, especially since medical treatment, e.g. the inhibition of the specific ATP-binding side of the thyrosin kinasis by imatinib or erlotinib, has failed to show convincing effects of tumor control [[7], [8], [9]]. As chordomas are considered being relatively radioresistant, radiation doses higher than 70 Gy Relative biological effectiveness (RBE) are required in order to achieve tumor control [10]. Conventional photon therapy, however, is unbale to deliver higher doses than 50−60 Gy without causing damage to the neighboring tissue [11]. Therefore, high conformal radiotherapy is required to achieve dose escalation in the tumor without damage of the organs at risk. Protons or carbon ions might offer advantages due to their different physical and biological effect compared to photons [[12], [13], [14], [15], [16], [17]]. Therefore, maximal surgical resection forms the basis for any adjacent therapy and therefore, for long-term tumor contro [18].

Clivus chordomas show a huge variety of tumor extension ranging from local tumor infiltration of the clivus bone, to intracranial tumor extension through the dura compressing the brain stem; and to vast and extended tumor outspread involving the entire skull base, the cavernous sinus and reaching the posterior fossa or the cervical spine (Fig. 1). Therefore, surgical resection is challenging, achieving gross total tumor resection is rare [19], and surgical approaches have to be adjusted to the size, location and extension of the tumor. Considering the location, in most cases anterior approaches are suitable. Hereby, the modified microscopical approach, or midfacial degloving, have been standard for many years [20,21]. Recently, new techniques, such as the endoscopic endonasal approach (EEA), have been implemented as less invasive approaches with better visualization [[22], [23], [24], [25], [26], [27], [28], [29]]. Only in selective cases other approaches to the lateral skull base or the cerebellopontine angle are necessary.

While most studies emphasize mainly the grade of tumor resection, the huge variety of tumor extension, and hence the use of different suitable surgical approaches, and in particular special aspects of recurrent cases are widely lacking in the literature. Therefore, we describe in this current study our series of patients with clivus chordomas treated in our university center from 2006 to 2019, emphasizing the adjustment of surgical approaches dependent on the tumor extension, changes in the surgical management by the implementation of endoscopic techniques, and outcome.

Section snippets

Material and methods

In the present study, we retrospectively assessed our series of 50 patients diagnosed with clivus chordomas treated in our university hospital from 2006 to 2019. On those 50 patients, with an average age of 39 years (range from 16 to 77 years), we performed 70 surgical procedures. 29/50 (58 %) patients were males, 21/50 (42 %) patients were females. In 29 cases it was the primary surgery, in 41 cases, however, we performed surgery on recurrences, both having been treated earlier in our own and

Results

Patients were suffering from tumor-related symptoms until diagnosis in the average for 8 ± 17 months (range 0–84 months) (Table 1). Beside headaches that 34 % of all patients were complaining about, double vision (48 %) and deterioration of the visual acuity (18 %) were also prominent. Furthermore, patients showed symptoms of the posterior fossa, such as vertigo (14 %), dysphagia (18 %) and insecure gait (12 %). In only a few cases, cranial nerves were also affected, e.g. the trigeminal- or

Discussion

In this study, we reported our results of 50 patients on whom we performed 70 surgical procedures for Clivus chordomas – 41 in recurrent cases. Due to the huge variety of tumor extension, we classified them into 4 groups according to their tumor size and extension. Especially smaller (< 5 cm3) or middle-sized (5−20 cm3) tumors showed dorsal or fronto-temporal extension, while large (20−100 cm3) or giant (> 100 cm3) ones infiltrate the entire skull base. The choice of the used surgical approach

Conclusion

Depending on the variety in tumor size and extension, as well as the infiltrative pattern of growth, we have used different surgical approaches aiming for maximal, but safe, surgical tumor resection. While in patients with circumscribed small- or middle sized clivus chordomas, surgical resection and adjuvant radiotherapy offers a solid treatment concept, in patients with widespread and vast infiltrative tumor growth, especially in recurrent cases, surgery is often limited, and hence

Ethnical standards

This retrospective study was performed in accordance with the guidelines for ethnical practices and the Declaration of Helsinki (1964). All patients gave informed consent for their retrospective analysis of their data. None of the authors have any conflict of interests. None of the authors have received any funding related to this study.

Credit author statement

Zweckberger Klaus MD PhD1*: Leading of the entire research project, main surgeon (neurosurgery), writing the manuscript, supervision of data aquisition

Henrik Giese MD1*: Co-writer of the manuscript, Figures, Video, data acquisition, statistics

Benjamin Haenig1: MD-candidate responsible for the data acquisition and statistics

Federspil Philippe A. MD PhD2: Co-writer of the manuscript (ENT parts), main-surgeon ENT; data acquisition ENT

Baumann Ingo MD PhD2: Co-writer of the manuscript (ENT parts),

Acknowledgments

We would like to thank our colleagues from the department of Neuroradiology for providing pre-and postoperative imaging, our colleagues from the department of Neuropathology for histological assessment of the tissue, and Anna Haenig supporting statistical calculations.

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    These authors contributed equally to this manuscript.

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