Next Article in Journal
Midazolam Indications and Dosing in Palliative Medicine: Results from a Multinational Survey
Previous Article in Journal
Addressing the Rising Trend in Early-Age-Onset Cancers in Canada
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Characteristics and Outcome of Surgically Treated Patients with Intradural Extra- and Intramedullary Spinal Metastasis—A Single-Center Retrospective Case Series and Review †

by
Hanna Veronika Salvotti
,
Alexander Lein
,
Martin Proescholdt
,
Nils-Ole Schmidt
and
Sebastian Siller
*
Department of Neurosurgery, University Hospital, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany
*
Author to whom correspondence should be addressed.
Parts of this paper were presented as a poster presention at the 75th Annual Meeting of the German Society of Neurosurgery in Goettingen, Germany, on 10 June 2024.
Curr. Oncol. 2024, 31(7), 4079-4092; https://doi.org/10.3390/curroncol31070304
Submission received: 27 June 2024 / Revised: 17 July 2024 / Accepted: 18 July 2024 / Published: 19 July 2024
(This article belongs to the Section Neuro-Oncology)

Abstract

:
Objective: Intradural spinal metastases are considered rare. At present, limited information is available on incidence, surgical management, and outcomes. Methods: We conducted a retrospective patient chart review from 2002 to 2024, identifying all patients surgically treated for intradural spinal metastases. Clinical, surgical and survival data were collected and compared to literature data for patients surgically treated for extradural spinal metastases. Results: A total of 172 patients with spinal metastases were identified with 13 patients meeting inclusion criteria (7.6%). The mean age at diagnosis of intradural spinal metastases was 52 ± 22 years, with diverse primaries including lung (n = 3), breast (n = 2), sarcoma (n = 2), and six unique entities. Intradural spinal metastasis was diagnosed on average of 3.3 years after primary diagnosis. In total, we observed five (38%) intradural-extramedullary and eight (62%) intramedullary metastases, located in the cervical (38.5%), thoracic (46.1%) and lumbar spine (15.4%). The most common preoperative symptoms were pain, sensory changes, and gait ataxia (each 76.9%). Gross total resection was achieved in 54%, and local tumor control in 85%. Postoperatively, 92% exhibited clinical improvement or stability. Most frequent adjuvant treatment was radio- and/or chemotherapy in 85%. The average survival after operation for spinal intradural metastases was 5 months, ranging from 1 month to 120 months. The location of the intradural metastasis in the cervical spine was associated with a significantly more favorable survival outcome (compared to thoracic/lumbar location, p = 0.02). Conclusions: Intradural location of spinal metastases is rare (7.6%). Even so, surgical resection is safe and effective for neurological improvement, and survival appears lower compared to the reported survival of extradural spinal metastases.

1. Introduction

Intradural extramedullary spinal metastasis represent a rare entity of systemic oncological diseases accounting for approximately 5–10% of all intraspinal metastatic lesions [1,2,3]. According to the literature, intradural intramedullary metastases are even more infrequent entities, accounting for 0.9–2.1% of all secondary malignancies [4,5].
Due to innovation in diagnostic tools as well as improvement of treatment options in oncological patients with longer overall survival, a slow increase in the incidence of this type of spinal metastases seems to be observed in the past years [6,7,8]. While extradural spinal metastases are frequently addressed in the literature, studies on the incidence and therapy of intradural metastases are still rare, and single case reports dominate in the literature [9]. Cancer entities most frequently mentioned in the literature for intradural metastases include lung carcinoma, mamma carcinoma, brain tumors, and prostate carcinoma [8,10], while treatment options described in historical case reports remain highly controversial, and range from surgical resection to chemotherapy, radiosurgery, and/or radiotherapy [11,12,13,14]. Limited evidence is available that surgery in patients with intradural metastases might improve survival compared to conservative treatment methods [15,16].
Per se, the prognosis of spinal metastasis in general is, even today, poor, as they usually occur in advanced cancer stages. An average survival of approximately 12 months is reported in the literature [17]. Little so far is known if this is also true for the rare type of intradural spinal metastases, or if survival differs for this subtype of spinal metastases, especially due to the fact that intradural metastases often lead to a more rapid progression of physical impairment and a consequent reduction in quality of life and fitness for oncological adjuvant treatment [12].
The aim of this study was to determine the incidence, clinical, and pathological features, as well as post-operative outcome and survival of extra- and intramedullary intradural metastases of systemic malignant tumors treated surgically at our institution.

2. Materials and Methods

2.1. Study Design, Patient Selection, and Participation

We conducted a single-center retrospective chart review at our tertiary academic reference center including all patients undergoing surgical treatment for a spinal metastasis of a systemic malignant neoplasm between April of 2002 and March of 2024 at the Department of Neurosurgery of the University Hospital Regensburg, Germany. Patients with an intradural extra- or intramedullary metastasis were identified, and data regarding demographics, primary cancer histopathology, spinal location and relation to the spinal cord, clinical course, pre- and postoperative neurological status, extent of tumor resection, oncological treatment regime, and long-term follow-up were acquired from the patients’ records available at our institution, as well as from the University Clinical Cancer Registry at the University Hospital Regensburg.
Patients who underwent surgery for an intradural CNS-inherent tumor (e.g., tumor entities listed in the 2021 WHO Classification of CNS tumors) in the spinal region were excluded.
This study was conducted according to the principles expressed in the Declaration of Helsinki. The Ethical Committee of the University of Regensburg approved the study (No. 23-3588-103).

2.2. Clinical Evaluation

Detailed neurological assessment, as well as classification of the functional status using the McCormick scale [18], was performed in all patients with intradural metastases preoperatively at admission for planned surgical treatment, at discharge after surgery, and at every follow-up timepoint. Clinical follow-up of patients was initially performed every 3 months and until the timepoint of death. Detailed neurological examination included motor function assessment, evaluation of sensory function and pain level, as well as gait and vegetative assessment.

2.3. Surgical Procedures

Decision for or against surgery was always carried out on the basis of an individual interdisciplinary discussion, with the oncological team integrating the patient’s past treatment history, current status and preferences, the available postoperative adjuvant treatment options, and the potential goals of surgery (e.g., neurological improvement, spinal stabilization, etc.). Metastasis location and spinal level, as well as distribution within the spinal cord, were evaluated based on contrast-enhanced and non-contrast enhanced MR imaging of the spine, which was carried out in all patients preoperatively. Based on intraoperative clinical as well as radiographic observations, tumors were characterized in extramedullary, intramedullary, or extra- and intramedullary location.
Anesthesia for surgery was performed with total intravenous anesthesia, and subsequently all patients were placed in the prone position. For tumor resection, a posterior midline approach was performed, and the lamina and spinous processes overlying the tumor were exposed. Subsequently, hemilaminectomy or laminectomy were performed for tumor resection. If the metastasis did not approach the spinal cord surface to serve as an entry point for intramedullary tumor resection, a midline myelotomy was performed by sharp dissection after visual identification and marking of the anatomical midline by the surgeon. Resection was performed under microscope- and ultrasound-guidance according to the state-of the-art microsurgical techniques, as well as with the continuous multimodal IONM of both somatosensory and motor evoked potentials, as well as free-running electromyography utilizing an integrated IONM system (ISIS, Inomed Co., Emmendingen, Germany) on discretion of the performing surgeon. After resection, a watertight closure of the dura was performed. Adjuvant treatment was indicated and performed on the basis of an interdisciplinary tumor conference decision.
In all cases, tumor tissue obtained intraoperatively was sent to the Department of Pathology of our institution for analysis of the tumor entity. The extent of resection was determined according to the operative records as well as the contrast-enhanced and non-contrast-enhanced MR imaging of the spine at the 3-month follow-up. Gross total tumor resection was defined as complete tumor removal according to the operative records and no residual tumor-suspect contrast-enhancement on a postoperative MRI scan, while removal of >20% (but less than the gross total resection) of the tumor was termed subtotal resection and <20% as biopsy only. Local tumor control was assumed in cases of no further radiological change in the surgical level in further MRI follow-up scans compared to the 3-month follow-up MRI scan, while any tumor-suspect change in contrast-enhancement pattern according to the radiological evaluation was classified as local tumor recurrence/progression.

2.4. Statistical Analysis

Statistical analysis was performed using Sigma Plot for Windows v.11 (Systat Software Inc., San Jose, CA, USA). For the comparison of group differences, Student’s t-test was used for numeric values, Mann–Whitney Rank Sum test for ordinal variables, and χ2-test resp. Fisher’s exact test (in case of 2 × 2-contingency tables) for nominal variables. The reference point of this study was the date of initial diagnosis of the primary cancer (reference point 1) as well as the date of surgery for diagnosis of intradural spinal metastasis (reference point 2) of the individual patient. Patients were followed until death from any cause, or were censored at the day of last follow-up in March 2024 (end point 1). End points were overall survival (reference point 1—end point) and survival after surgery for the intradural spinal metastasis (reference point 2—end point). Survival data were analyzed using the Kaplan–Meier method. Prognostic factors were obtained from proportional hazards models (Cox regression models). p-values below 0.05 were considered statistically significant.

3. Results

3.1. Patients’ and Tumor Characteristics

During our study period, a total of 172 patients with intraspinal metastases were surgically treated in our institute. Out of these 172 patients, 13 patients (13/172 = 7.6%) with intradural spinal metastases were identified, with 5 patients harboring an completely extramedullary and 8 patients an at least partly intramedullary spinal metastasis. One patient with a lumbar extramedullary metastasis also had a small extradural tumor component, suggesting a per continuitatem spread across the dura. Mean age at diagnosis of the intradural metastasis was 52 ± 22 years, and there was a predominance of the male gender (male/female: 1.6/1). Median McCormick score was 3 (range: 2–4), and median KPS was 70 (range: 50–90).
Median time period from primary cancer diagnosis to the diagnosis of the intradural spinal metastasis was 40 months (range 8–102 months); in 2 patients (15%) the clinical manifestation of the intradural spinal metastasis led to the first diagnosis of the primary cancer (lung cancer resp. prostate cancer). While 54% of the patients had evidence of multiple systemic metastases at the timepoint of primary cancer diagnosis, the rate increased to 77% at the timepoint of diagnosis of the intradural metastasis. Seven patients (54%) had evidence of additional central nervous system metastases at the timepoint of diagnosis of the intradural metastasis or during further postoperative follow-up.
Baseline patients’ and tumor characteristics are displayed in Table 1 and Table 2. There was no significant difference in these characteristics between patients harboring completely extramedullary vs. extra-/intramedullary spinal metastases.

3.2. Surgical Characteristics and Postoperative Outcome

Two patients (with extramedullary spinal metastases) underwent surgical tumor resection on an emergency basis due to rapidly developing neurological symptoms of spinal cord compression, while 11 patients underwent elective tumor resection. The gross total tumor resection rate was 54%, and the rate of local tumor control was 85%. There were no postoperative surgical complications. Postoperative radiation and/or chemotherapy were the most frequent adjuvant treatment modalities, and were applied in 85% of the patients. One long-term survivor of a systemically metastasized cutaneous adnexal carcinoma underwent three reoperations for local recurrence of an extra-/intramedullary spinal metastasis 1.5, 6, and 15 years after the index operation.
In total, 92% of the patients showed a stable or postoperative improved neurological status after surgery, while one patient suffered from a neurological deterioration. Median postoperative McCormick score was 3 (range: 1–4).
Details for surgical characteristics and postoperative outcome are displayed in Table 3, with no significant differences between patients with completely extramedullary vs. extra-/intramedullary spinal metastases.

3.3. Survival Analysis

At the time of last follow-up (March 2024), 12 patients were deceased (92%). Median OS from diagnosis of primary cancer to death was 39 months (Figure 1A). Death was tumor-related in all patients.
Median survival after surgery for the intradural spinal metastasis was 5 months, ranging from as low as one month to as high as 120 months (Figure 1B). Uni- and multivariate regression analyses for identification of preoperative risk factors affecting survival after surgery for the intradural spinal metastasis are displayed in Table 4. The location of the intradural metastasis in the cervical spine was associated with a more favorable survival outcome (compared to thoracic or lumbar location) both in uni- and multivariate analyses (p = 0.02 and p = 0.02), while a higher preoperative McCormick score was associated with a poorer survival outcome only in multivariate analyses (p = 0.04). Survival after surgery for the intradural spinal metastasis stratified by location of the intradural metastasis and by preoperative McCormick score are displayed in Figure 2. Uni- and multivariate regression analyses for the identification of preoperative risk factors affecting survival after surgery for the intradural spinal metastasis (extent of resection, postoperative McCormick score, postoperative neurological deterioration, adjuvant radio-/chemotherapy) were also performed, but did not show any significance.

4. Discussion

Due to the advancement in diagnostic modalities and oncologic treatment methods, the incidence of intraspinal metastases seems to have slowly increased in recent years, and thus might gain further importance in everyday clinical practice in the future [6,7,8]. This is especially true because spinal intradural metastases may cause clinical symptoms such as pain, paresthesia, and neurological deficits, often leading to a severely reduced quality of life [19,20]. Per se, survival prognosis of spinal metastasis in general is, even today, poor, as they usually occur in advanced cancer stages. Little so far is known if survival prognosis might even be worse in the rare type of intradural spinal metastases or not, and if surgical treatment is safe and feasible in patients with intradural spinal metastases.
In our surgical review, we decided to focus on surgically treated intradural intra- and extramedullary metastases and aim to determine the incidence, clinico-pathological features, and clinical/functional as well as survival outcome of intradural spinal metastases of systematic malignant tumors. The incidence of patients with intradural metastases in our case series was of 7.6%. This result is comparable with findings of historical autopsy studies, where intradural extra- or intramedullary metastases were found with an incidence of approximately 5%, and therefore underline the trend in increasing incidences in recent years [3,8,21]. The mean age at presentation was 52 years, comparable to previous case series, and the majority of our patients (77%) had multiple systemic metastases at the time of diagnosis of the intradural spinal metastasis that is also in line with previous publications, where intradural spinal metastases are reported to be found in advanced systemic tumor stages [9,22,23,24].
Despite the advanced stage of tumor disease at the timepoint of diagnosis of the intradural spinal metastasis in the majority of our study patients, surgical treatment was safe and feasible in every single case without surgery-related mortality or systemic morbidity. Gross total tumor resection of the intradural metastasis was achieved in 54% of cases, and in 46%, subtotal resection was achieved; there were no cases of biopsy only in our report. This finding is comparable with those of historical case series by Wostrack et al. and Manzano et al., where total tumor resection was achieved in up to 56% of cases. While in these case series, up to 67% of patients reported improvement/stability of symptoms postoperatively, in our study, over 90% of the included patients experienced a clinical improvement or stable finding postoperatively, as measured using the McCormick Scale [4,18]. These findings indicate that, with advances in microsurgical techniques and perioperative adjuncts (e.g., IONM) over the last decades, surgical treatment of intradural metastases is currently feasible with a good efficiency as well as safety. Similarly to our results, a recent case series by Kritikos et al., including five patients treated surgically for an intramedullary metastasis, found an improved or stable neurological status in all patients after surgery [23].
However, even today, survival prognosis of spinal metastasis in general remains poor. For the classic manifestation of spinal metastases as an extradural tumor, a mean survival of 7.7 to 17 months is reported in the literature [17,25,26,27,28,29,30,31]. Little so far is known if this is also true for the rare type of intradural spinal metastases, or if survival differs for this subtype of spinal metastases. A historical case series of Schick et al. over 20 years ago, comparing intra-and extradural spinal metastases, reported hints for a markedly reduced survival time in patients with intradural in comparison to those with extradural metastases [32]. However, it remains unknown if this might also be true today considering the major advances in diagnostic tools as well as surgical and oncological treatment options in recent decades. Studies reporting on survival outcome of patients with intradural spinal metastases in recent times are still very scarce. We have intensely reviewed the current literature and collected the few case series reporting on survival outcome (see Table 5). The reported mean survival time of intradural spine metastases ranged from as low as 5 to as high as 9.6 months [1,4,6,8,9,23,33,34,35]. However, the significance of those reports is severely limited, especially with regard to a high rate of loss to follow-up or a too-short follow-up time period; the rate of patients needed to be censored from survival analysis ranged as high as 50% in those reports, and therefore markedly limits the validity of those data. In our study, we followed patients’ clinical outcome until timepoint of death (92% of our patients) or for a minimum of 10 years (8% of our patients), making it possible to obtain valid statements about patients’ survival time, which was 5 months in mean. Moreover, in the case series of Sung et al. [34] (n = 8), Payer et al. [8] (n = 22), and Goyal et al. [35] (n = 8), intramedullary metastases were analyzed, including the origin of both secondary malignancies as well as primary CNS tumors (e.g., ependymomas, gliomas, medulloblastomas) which limits the validity and comparability of these case series with those with a focus on true intradural metastases of secondary malignancies. Of note, in our study, a better preoperative McCormick Score was a significant factor for a more favorable survival after intradural spinal metastasis surgery in multivariate analysis, while the location of the intradural metastasis in the cervical spine was associated with a statistically significant more favorable survival (compared to thoracic or lumbar location) both in uni- and multivariate analysis. A possible confounder of this finding could be that, due to more severe symptoms such as gait abnormalities or problems with balance due to myelopathy, cervical spine metastases may be diagnosed at an earlier cancer stage as compared to metastases in the thoracic or lumbar region, and may therefore be associated with a more favorable prognosis. Analysis of other risk factors affecting survival (like extent of tumor, postoperative McCormick score, postoperative neurological deterioration, and adjuvant radio-/chemotherapy) did not show any further significant findings.

Strengths and Limitations

This study bares several strengths and limitations. This is a study with a long observational period of 10 years and more for each individual patient, making it possible to observe the incidence of intradural spinal metastases over an overall time period of two decades and precisely analyze the survival from diagnosis of primary cancer and surgery for intradural spinal metastasis until death or long-term follow-up. A further strength of our study is represented by the regular follow-ups of patients until the timepoint of death, which makes it also possible to evaluate clinical presentation over time. However, as more than half of the patients in our series additionally had brain metastases at the timepoint of surgery of the intradural spinal metastasis (and brain metastases were progressive in part of the patients during further follow-up), determination of the proportion of neurological and functional changes associated with the lesion at the surgical site compared to other CNS metastases is challenging. Nevertheless, overall, the achieved stabilization or improvement of the neurological status after surgery was maintained in our patients during further follow-up. Moreover, due to the rarity of this tumor entity, the overall patient number is limited; even so, we here present one of the larger recent case series in the literature. Moreover, this is a study of a retrospective and non-randomized nature, limiting the level of evidence. In the future, prospective multidisciplinary studies with a larger patient population are needed to further analyze the benefit of surgery in intradural spine metastases of malignant systemic neoplasms.

5. Conclusions

Intra- and extramedullary spinal metastases represent a rare tumor manifestation. They typically occur in advanced tumor stages, and are associated with impairing neurological symptoms and reduced life expectancy. In our study, we analyzed the clinical presentation and outcome of patients with intradural spinal metastases treated at out institution. Our study showed that surgical resection in intradural spinal metastases represents a safe and efficient method for improving clinical outcome. However, overall survival still remains poor with a mean OS of 5 months after diagnosis of the intradural spinal metastasis, which seems to be short compared to the survival times for extradural spinal metastases.

Author Contributions

Conceptualization, H.V.S., A.L. and S.S.; Methodology, H.V.S., A.L., M.P. and S.S.; Software, H.V.S., A.L., M.P. and S.S.; Validation, H.V.S., A.L., M.P., N.-O.S. and S.S.; Formal Analysis, H.V.S., A.L., M.P. and S.S.; Investigation, H.V.S., A.L. and S.S.; Resources, M.P., N.-O.S. and S.S.; Data Curation, H.V.S., A.L. and S.S.; Writing—Original Draft Preparation, H.V.S. and S.S.; Writing—Review and Editing, H.V.S., A.L., M.P., N.-O.S. and S.S.; Visualization, H.V.S., A.L., M.P., N.-O.S. and S.S.; Supervision, H.V.S., A.L., M.P., N.-O.S. and S.S.; Project Administration, H.V.S., A.L., M.P., N.-O.S. and S.S.; Funding Acquisition, H.V.S., A.L., M.P., N.-O.S. and S.S. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of the University of Regensburg (23-3588-103, 30 January 2024). Informed consent was obtained from participants included in the study according to the guidelines of the local Institutional Review Board.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study according to the guidelines of the local Institutional Review Board.

Data Availability Statement

Data available on request due to restrictions because of legal and ethical reasons.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Chow, T.S.; McCutcheon, I.E. The surgical treatment of metastatic spinal tumors within the intradural extramedullary compartment. J. Neurosurg. 1996, 85, 225–230. [Google Scholar] [CrossRef] [PubMed]
  2. Kumar, N.; Tan, W.L.B.; Wei, W.; Vellayappan, B.A. An overview of the tumors affecting the spine—Inside to out. Neuro-Oncol. Pract. 2020, 7 (Suppl. S1), i10–i17. [Google Scholar] [CrossRef] [PubMed]
  3. Traul, D.E.; Shaffrey, M.E.; Schiff, D. Part I: Spinal-cord neoplasms-intradural neoplasms. Lancet Oncol. 2007, 8, 35–45. [Google Scholar] [CrossRef] [PubMed]
  4. Wostrack, M.; Pape, H.; Kreutzer, J.; Ringel, F.; Meyer, B.; Stoffel, M. Surgical treatment of spinal intradural carcinoma metastases. Acta Neurochir. 2012, 154, 349–357. [Google Scholar] [CrossRef] [PubMed]
  5. Costigan, D.A.; Winkelman, M.D. Intramedullary spinal cord metastasis. A clinicopathological study of 13 cases. J. Neurosurg. 1985, 62, 227–233. [Google Scholar] [CrossRef] [PubMed]
  6. Gazzeri, R.; Telera, S.; Galarza, M.; Callovini, G.M.; Sperduti, I.; Alfieri, A. Surgical treatment of solitary intradural extramedullary spinal cord metastases from solid cancers of non-neurogenic origin. A multicenter study. J. Neuro-Oncol. 2021, 154, 101–112. [Google Scholar] [CrossRef]
  7. Wewel, J.T.; O’Toole, J.E. Epidemiology of spinal cord and column tumors. Neurooncol. Pract. 2020, 7 (Suppl. S1), i5–i9. [Google Scholar] [CrossRef]
  8. Payer, S.; Mende, K.C.; Pract, M.; Westphal, M.; Eicker, S.O. Intramedullary spinal cord metastases: An increasingly common diagnosis. Neurosurg. Focus 2015, 39, E15. [Google Scholar] [CrossRef]
  9. Hoover, J.M.; Krauss, W.E.; Lanzino, G. Intradural spinal metastases: A surgical series of 15 patients. Acta Neurochir. 2012, 154, 871–877. [Google Scholar] [CrossRef]
  10. Lv, J.; Liu, B.; Quan, X.; Li, C.; Dong, L.; Liu, M. Intramedullary spinal cord metastasis in malignancies: An institutional analysis and review. OncoTargets Ther. 2019, 12, 4741–4753. [Google Scholar] [CrossRef]
  11. Hong, S.H.; Chang, B.S.; Kim, H.; Kang, D.H.; Chang, S.Y. An Updated Review on the Treatment Strategy for Spinal Metastasis from the Spine Surgeon’s Perspective. Asian Spine J. 2022, 16, 799–811. [Google Scholar] [CrossRef] [PubMed]
  12. Corvino, S.; Mariniello, G.; Solari, D.; Berardinelli, J.; Maiuri, F. The role of surgery in spinal intradural metastases from renal cell carcinoma: A literature review. Cancers 2022, 14, 1595. [Google Scholar] [CrossRef] [PubMed]
  13. Miura, S.; Kaira, K.; Kaira, R.; Akamatsu, H.; Ono, A.; Shukuya, T.; Tsuya, A.; Nakamura, Y.; Kenmotsu, H.; Naito, T.; et al. The efficacy of amrubicin on central nervous system metastases originating from small-cell lung cancer: A case series of eight patients. Investig. New Drugs 2015, 33, 755–760. [Google Scholar] [CrossRef] [PubMed]
  14. Lee, S.S.; Kim, M.K.; Sym, S.J.; Kim, S.W.; Kim, W.K.; Kim, S.B.; Ahn, J.H. Intramedullary spinal cord metastases: A single-institution experience. J. Neurooncol. 2007, 84, 85–89. [Google Scholar] [CrossRef] [PubMed]
  15. Dam-Hieu, P.; Seizeur, R.; Mineo, J.F.; Metges, J.P.; Meriot, P.; Simon, H. Retrospective study of 19 patients with intramedullary spinal cord metastasis. Clin. Neurol. Neurosurg. 2009, 111, 10–17. [Google Scholar] [CrossRef] [PubMed]
  16. Kalayci, M.; Cağavi, F.; Gül, S.; Yenidünya, S.; Açikgöz, B. Intramedullary spinal cord metastases: Diagnosis and treatment—An illustrated review. Acta Neurochir. 2004, 146, 1347–1354, discussion 1354. [Google Scholar] [CrossRef] [PubMed]
  17. Candido, P.B.M.; Peria, F.M.; Pinheiro, R.P.; Costa, H.R.T.; Defino, H.L.A. Outcomes and survival of spinal metastasis with epidural compression. J. Craniovertebr. Junction Spine 2021, 12, 287–293. [Google Scholar] [CrossRef]
  18. Manzano, G.; Green, B.; Vanni, S.; Levi, A. Contemporary management of adult intramedullary spinal tumors—Pathology and neurological outcomes related to surgical resection. Spinal Cord 2008, 46, 540–546. [Google Scholar] [CrossRef] [PubMed]
  19. van Tol, F.R.; Suijkerbuijk, K.P.M.; Choi, D.; Verkooijen, H.M.; Oner, F.C.; Verlaan, J.-J. The importance of timely treatment for quality of life and survival in patients with symptomatic spinal metastases. Eur. Spine J. 2020, 29, 3170–3178. [Google Scholar] [CrossRef]
  20. Liu, Y.; Cao, X.; Zhao, X.; Shi, X.; Lei, M.; Qin, H. Quality of Life and Mental Health Status Among Cancer Patients with Metastatic Spinal Disease. Front. Public Health 2022, 10, 916004. [Google Scholar] [CrossRef]
  21. Hashizume, Y.; Hirano, A. Intramedullary spinal cord metastasis. Acta Neuropathol. 1983, 61, 214–218. [Google Scholar] [CrossRef] [PubMed]
  22. Palmisciano, P.; Chen, A.L.; Sharma, M.; Bin-Alamer, O.; Ferini, G.; Umana, G.E.; Aoun, S.G.; Haider, A.S. Intradural extramedullary spinal metastases from non-neurogenic primary tumors: A systematic review. Anticancer Res. 2022, 42, 3251–3259. [Google Scholar] [CrossRef] [PubMed]
  23. Kritikos, M.; Vivanco-Suarez, J.; Teferi, N.; Lee, S.; Kato, K.; Eschbacher, K.L.; Bathla, G.; Buatti, J.M.; Hitchon, P.W. Survival and neurological outcomes following management of intramedullary spinal metastasis patients: A case series with comprehensive review of the literature. Neurosurg. Rev. 2024, 47, 75. [Google Scholar] [CrossRef]
  24. Stein, A.A.; Weinstein, G.R.; Niezgoda, C.; Chowdhary, S.; Vrionis, F.; Houten, J.K. Myelopathy from Intradural Extramedullary Metastasis as an Initial Presentation of Metastatic Melanoma. Cureus 2018, 10, e2668. [Google Scholar] [CrossRef] [PubMed]
  25. Arrigo, R.T.; Kalanithi, P.; Cheng, I.; Alamin, T.; Carragee, E.J.; Mindea, S.A.; Park, J.; Boakye, M. Predictors of survival after surgical treatment of spinal metastasis. Neurosurgery 2011, 68, 674–681, discussion 681. [Google Scholar] [CrossRef] [PubMed]
  26. Liao, J.-C.; Chen, W.-J.; Chen, L.-H. Surgery for metastatic epidural spinal cord compression in thoracic spine, anterior or posterior approach? Biomed. J. 2022, 45, 370–376. [Google Scholar] [CrossRef] [PubMed]
  27. Wang, J.C.; Boland, P.; Mitra, N.; Yamada, Y.; Lis, E.; Stubblefield, M.; Bilsky, M.H. Single-stage posterolateral transpedicular approach for resection of epidural metastatic spine tumors involving the vertebral body with circumferential reconstruction: Results in 140 patients. Invited submission from the Joint Section Meeting on Disorders of the Spine and Peripheral Nerves, March 2004. J. Neurosurg. Spine 2004, 1, 287–298. [Google Scholar] [CrossRef] [PubMed]
  28. Kocialkowski, A.; Webb, J.K. Metastatic spinal tumours: Survival after surgery. Eur. Spine J. 1992, 1, 43–48. [Google Scholar] [CrossRef] [PubMed]
  29. Heidecke, V.; Rainov, N.G.; Burkert, W. Results and outcome of neurosurgical treatment for extradural metastases in the cervical spine. Acta Neurochir. 2003, 145, 873–881, discussion 880–881. [Google Scholar] [CrossRef]
  30. Bulthuis, V.J.; Schuermans, V.N.E.; Willems, P.C.; Curfs, I.; Ramos Gonzaléz, A.A.; van Kuijk, S.M.J.; Santbrink, H.V. Predicting Survival in Patients Presenting With Spinal Epidural Metastases: The Limburg Spinal Metastasis Score. Int. J. Spine Surg. 2023, 17, 547–556. [Google Scholar] [CrossRef]
  31. Bhanot, K.; Widdifield, J.; Huang, A.; Paterson, J.M.; Shultz, D.B.; Finkelstein, J. Survival after surgery for spinal metastases: A population-based study. Can. J. Surg. 2022, 65, E512–E518. [Google Scholar] [CrossRef] [PubMed]
  32. Schick, U.; Marquardt, G.; Lorenz, R. Intradural and extradural spinal metastases. Neurosurg. Rev. 2001, 24, 1–5. [Google Scholar] [CrossRef] [PubMed]
  33. Wu, L.; Wang, L.; Yang, J.; Jia, W.; Xu, Y. Clinical Features, Treatments, and Prognosis of Intramedullary Spinal Cord Metastases From Lung Cancer: A Case Series and Systematic Review. Neurospine 2022, 19, 65–76. [Google Scholar] [CrossRef] [PubMed]
  34. Sung, W.S.; Sung, M.J.; Chan, J.H.; Manion, B.; Song, J.; Dubey, A.; Erasmus, A.; Hunn, A. Intramedullary spinal cord metastases: A 20-year institutional experience with a comprehensive literature review. World Neurosurg. 2013, 3–4, 576–584. [Google Scholar] [CrossRef]
  35. Goyal, A.; Yolcu, Y.; Kerezoudis, P.; Alvi, M.A.; Krauss, W.E.; Bydon, M. Intramedullary spinal cord metastases: An institutional review of survival and outcomes. J. Neurooncol. 2019, 142, 347–354. [Google Scholar] [CrossRef]
Figure 1. Kaplan-Meier curves for overall survival (OS) after initial diagnosis of the primary cancer (A) as well as survival after surgery for intradural spinal metastasis (postopS) (B) for 13 patients with intradural spinal metastasis.
Figure 1. Kaplan-Meier curves for overall survival (OS) after initial diagnosis of the primary cancer (A) as well as survival after surgery for intradural spinal metastasis (postopS) (B) for 13 patients with intradural spinal metastasis.
Curroncol 31 00304 g001
Figure 2. Kaplan-Meier curves survival after surgery for intradural spinal metastasis (postopS) stratified by location of the intradural spinal metastasis (A) and by preoperative McCormick score (B) for 13 patients with intradural spinal metastasis.
Figure 2. Kaplan-Meier curves survival after surgery for intradural spinal metastasis (postopS) stratified by location of the intradural spinal metastasis (A) and by preoperative McCormick score (B) for 13 patients with intradural spinal metastasis.
Curroncol 31 00304 g002
Table 1. Baseline patients’ and tumor characteristics at the timepoint of diagnosis of intradural spinal metastasis *.
Table 1. Baseline patients’ and tumor characteristics at the timepoint of diagnosis of intradural spinal metastasis *.
Characteristics(n = 13)
gender, male/female5–8 (8/5)
mean age, yrs52 ± 22
primary cancer, no. (%)
  lung2 (15.4)
  breast2 (15.4)
  sarcoma2 (15.4)
  kidney1 (7.7)
  colorectal1 (7.7)
  cutaneous adnexal1 (7.7)
  melanoma1 (7.7)
  germ cell tumor1 (7.7)
  cancer of unknown primary (CUP) syndrome2 (15.4) [lung cancer, prostate cancer]
median time between diagnosis of primary cancer and intradural spinal metastasis, months (range)40 (8–102)
multiple systemic metastases, no. (%)10 (76.9)
location of intradural metastasis, no. (%)
  cervical5 (38.5)
  thoracic6 (46.1)
  lumbar2 (15.4)
relationship to spinal cord, no. (%)
  completely extramedullary5 (38.5)
  extra-/intramedullary6 (46.1)
  completely intramedullary2 (15.4)
extent of tumor, no. (%)
  single-level9 (69.2)
  two-level3 (21.1)
  three-level or more1 (7.7)
preoperative KPS, median (range)70 (50–90)
preoperative symptoms, no. (%)
  paresis6 (53.8)
  sensory changes10 (76.9)
  gait ataxia10 (76.9)
  pain10 (76.9)
  bladder/bowel dysfunction3 (21.1)
  non-ambulatory3 (21.1)
preoperative McCormick Score, no. (%)
  I0 (0.0)
  II3 (21.1)
  III5 (38.5)
  IV5 (38.4)
* Mean values are presented ± standard deviation.
Table 2. Description of cases with intradural metastases.
Table 2. Description of cases with intradural metastases.
No.SexPrimary CancerInitial Manifestation
of Primary Cancer
Initial Therapy
of Primary
Cancer
Time Period between Primary Cancer
Diagnosis and Metastasis
Diagnosis
Age at
Operation
Adjuvant
Therapy of Metastasis
Spinal Level of MetastasisLocation of MetastasisSymptoms of
Metastasis
Systemic
Metastases
Brain
Metastases
Additional Spine
Metastases
Postoperative Neurological Outcome at
Discharge
Resection Status
1mMelanomaLentigo malign melanoma, maculaOperative resection244471Interferon therapyC2EMLeft-sided neck painAdrenal gland, abdominal wall, lung, retroperitonealYesNoPain relieved, no neurological deficitsGross-total
2mSarcomaSpinal metastasisOperative resection038Chemotherapy, radiotherapyC 7/T2EMIncomplete cross-section, left-sided leg weaknessNoNoNoImproved motor and sensory function, ambulating with aidGross-total
3fBone Marrow (AML)AMLExtern therapy, no information available149411RadiotherapyT 6–9EMParaplegia and urinary retentionBone and soft tissueNoNoImproved motor function, persisting urinary retentionSubtotal
4mLung (small cell)Lung carcinoma with dyspnea and coughRadio-chemotherapy36065Palliative radiotherapyT 9–10EMLumbar spine pain with radiation to the right leg, hypoesthesia, 4/5 paresis,
bladder dysfunction
Mediastinum, adrenal glandYesNoPain and bladder dysfunction relieved, improved motor and sensory functionGross-total
5mGerminomaHeadacheVCS,
chemotherapy
24618CP/VP 16 BlockC 3EMNeck painNoYesNoPain relievedGross-total
6mRenal (clear cell)Osseous tumor left scapulaLeft side nephrectomy34438Chemotherapy, radiotherapyL 1–5IMBreeches hypoesthesiaSoft tissueNoYesStable compared to preoperative statusSubtotal
7mLung (large cell)Spinal metastasisNo therapy4374RadiotherapyL 1IMBack pain, paresthesia in right legLymph nodesYesNoStable compared to preoperative statusSubtotal
8fBreastBreast carcinomaExtern therapy, no information available120373RadiotherapyT 9–10IMWeakness of left > right leg, paresthesia and pain in both legs, not ambulatoryLungNoYesPain relieved, improved motor function of left leg, ambulating with aidSubtotal
9fBreastBreast carcinomaOperative resection42950RadiotherapyC1IMVertigo, paresthesia in all extremitiesBone, lymph nodesYesNoDeteriorated (postoperatively new right-sided hemiparesis)Gross-total
10fSweat glandsSweat gland carcinomaOperative resection227248RadiotherapyC 6–8IMPain in left arm, paresthesia in left hand, weakness in left armBoneNoNoPain relieved, improved motor and sensory functionSubtotal
11mRectumRectum carcinomaRadio-chemotherapy99347RadiotherapyCranio-cervical junction- C2IMWeakness in right arm, paresthesiaLung, boneYesNoImproved motor and sensory function, ambulating independentlyGross-total
12mProstateParaparetic syndromeRadio-chemotherapy30368Palliative radiotherapyT 8IMReduction in strength below pelvic girdle, not ambulatoryBone, lung, lymph nodesNoYesMinor improvement in motor function, not ambulatorySubtotal
13fLung (small cell)Cerebellar metastasisNo therapy44568Palliative treatmentT 2–3IMDiscrete paresis of right leg, hypoesthesia right leg, ataxiaLung, lymph nodesYesNoImproved motor function, ataxia unchanged compared to preoperative statusGross-total
Table 3. Surgical characteristics and postoperative outcome *.
Table 3. Surgical characteristics and postoperative outcome *.
Characteristics(n = 13)
surgical approach, no. (%)
  hemilaminectomy3 (21.1)
  laminectomy/laminoplasty9 (69.2)
  staged anterior + posterior stabilization and tumor resection 1 (7.7)
mean operation time, min.181 ± 92
resection rate, no. (%)
  gross total resection7 (53.8)
  subtotal resection6 (46.2)
  biopsy only0 (0.0)
median length of in-patient stay, days (range)12 (6–71)
postoperative surgical complications, no. (%)
  CSF fistula0 (0.0)
  hematoma0 (0.0)
  wound breakdown0 (0.0)
  infection0 (0.0)
postoperative change in neurological status, no. (%)
  improved8 (61.5)
  stable4 (30.8)
  deteriorated 1 (7.7)
postoperative McCormick score, no. (%)
  I2 (15.4)
  II3 (21.1)
  III3 (21.1)
  IV5 (38.4)
postoperative change in McCormick score, no. (%)
  improved6 (46.2)
  stable6 (46.1)
  deteriorated 1 (7.7)
adjuvant treatment, no. (%)
  radiotherapy9 (69.2)
  chemotherapy/targeted therapy4 (30.8)
local recurrence rate, no. (%)2 (15.4)
median time period until local recurrence, months (range)12 (6–17)
reoperation rate for local recurrence during follow-up, no. (%)1 (7.7)
* Mean values are presented ± standard deviation.
Table 4. Preoperative risk factor analysis affecting survival after surgery for intradural spinal metastasis.
Table 4. Preoperative risk factor analysis affecting survival after surgery for intradural spinal metastasis.
UnivariateHazard Ratio (p Value/95% CI)
age at surgery
per year1.01 (0.80/0.97–1.04)
preoperative KPS
score value0.99 (0.64/0.94–1.04)
preoperative McCormick score
I vs. II vs. III vs. IV1.81 (0.17/0.77–4.22)
multiple systemic metastases (at the timepoint of surgery for intradural metastasis)
yes vs. no1.99 (0.38/0.43–9.32)
additional central nervous system metastases (at the timepoint of surgery for intradural metastasis)
yes vs. no0.99 (0.98/0.31–3.15)
relationship to spinal cord
completely extramedullary vs. at least partly intramedullary1.01 (0.98/0.32–3.48)
location
cervical vs. thoracic vs. lumbar 3.27 (0.02/1.21–8.87)
extent of tumor
per level0.93 (0.89/0.30–2.84)
MultivariateHazard Ratio (p Value/95% CI)
age at surgery
per year0.97 (0.41/0.90–1.05)
preoperative KPS
score value1.03 (0.56/0.94–1.11)
preoperative McCormick score
I vs. II vs. III vs. IV8.16 (0.04/1.09–61.31)
multiple systemic metastases (at the timepoint of surgery for intradural metastasis)
yes vs. no6.03 (0.28/0.24–152.94)
additional central nervous system metastases (at the timepoint of surgery for intradural metastasis)
yes vs. no5.47 (0.20/0.40–74.30)
relationship to spinal cord
completely extramedullary vs. at least partly intramedullary0.29 (0.29/0.03–2.84)
location
cervical vs. thoracic vs. lumbar 15.11 (0.02/1.44–158.97)
extent of tumor
per level0.36 (0.52/0.02–7.38)
OR: odds ratio, CI: 95% confidence interval.
Table 5. Case series reporting on survival outcomes of surgically treated intradural spinal metastases.
Table 5. Case series reporting on survival outcomes of surgically treated intradural spinal metastases.
StudyYear of PublicationNo. of CasesExtramedullary
/Intramedullary
Spinal Metastases
Mean Survival
(after Surgery)
Minimum Length of Follow-UpPercentage of Censored Data
Chow et al. [1]199610extramedullary10.7 months3 months40%
Wostrack et al. [4]201294 intramedullary,
5 extramedullary
7.3 months3.5 months11%
Hoover et al. [9] 2012153 intramedullary,
12 extramedullary
5 monthsn.a.33%
Sung et al. [34]20138intramedullary4.5 months1 month-
Payer et al. [8]201522intramedullary11.6 months2 months50%
Goyal et al. [35]20198intramedullary4.5 months2 months-
Gazzeri et al. [6]202143extramedullary9.6 months5 months16%
Wu et al. [33]20226intramedullary5 months<1 month50%
Kritikos et al. [23]202496 intramedullary,
3 intra/extramedullary
7 months5 months44%
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Salvotti, H.V.; Lein, A.; Proescholdt, M.; Schmidt, N.-O.; Siller, S. Characteristics and Outcome of Surgically Treated Patients with Intradural Extra- and Intramedullary Spinal Metastasis—A Single-Center Retrospective Case Series and Review. Curr. Oncol. 2024, 31, 4079-4092. https://doi.org/10.3390/curroncol31070304

AMA Style

Salvotti HV, Lein A, Proescholdt M, Schmidt N-O, Siller S. Characteristics and Outcome of Surgically Treated Patients with Intradural Extra- and Intramedullary Spinal Metastasis—A Single-Center Retrospective Case Series and Review. Current Oncology. 2024; 31(7):4079-4092. https://doi.org/10.3390/curroncol31070304

Chicago/Turabian Style

Salvotti, Hanna Veronika, Alexander Lein, Martin Proescholdt, Nils-Ole Schmidt, and Sebastian Siller. 2024. "Characteristics and Outcome of Surgically Treated Patients with Intradural Extra- and Intramedullary Spinal Metastasis—A Single-Center Retrospective Case Series and Review" Current Oncology 31, no. 7: 4079-4092. https://doi.org/10.3390/curroncol31070304

Article Metrics

Back to TopTop