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Clinical and morphological aspects of metastatic spinal cord compression
Umeå University, Faculty of Medicine, Department of Medical Biosciences. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.ORCID iD: 0000-0002-4874-6800
2022 (English)Doctoral thesis, comprehensive summary (Other academic)Alternative title
Kliniska och morfologiska aspekter av metastatisk ryggmärgskompression (Swedish)
Abstract [en]

Background: Metastatic spinal cord compression (MSCC) is a serious complication of cancer leading to demyelination and axonal damage of the spinal cord with a risk of para/tetraplegia. It is most common in patients with known cancer but may also be the initial manifestation of malignancy (IMM). Patients with MSCC as the IMM have rarely been studied as a separate group. The interaction between the tumour and bone in spinal bone metastasis interferes with regulatory mechanisms, causing the formation of less mechanically competent bone and increasing the risk of spinal instability and fracture. The Spinal Instability Neoplastic Score (SINS) has been proposed as a tool in order to help clinicians evaluate tumour-related spinal instability. The SINS has shown excellent inter- and intraobserver reliability, but its prognostic value is still controversial. Bone metastases from prostate cancer are generally classified as osteoblastic due to increased bone formation. However, this categorization is probably oversimplified since there are overlapping bone cell activities between osteoblastic and osteolytic metastases. Prostate cancer bone metastases can also have a myeloma-like radiological appearance, but little is known about this subgroup of lesions. 

Aims: The aims of this work were as follows: a) to evaluate outcomes after surgery in patients with MSCC as the IMM; b) to analyse the prognostic value of the SINS regarding survival and neurological function after surgery for MSCC in patients with prostate cancer and haematological malignancies; and c) to analyse the clinical and morphological features of prostate cancer spinal bone metastases with a myeloma-like radiological appearance. 

Patients and methods: In studies I-III, we retrospectively evaluated the outcomes after surgery for MSCC in patients with MSCC as the IMM (study I, n=69), prostate cancer (study II, n=110) and haematological malignancies (study III, n=48). In study IV, tumour tissue samples from bone metastases obtained during surgery for MSCC in 110 patients with prostate cancer were analysed by immunohistochemistry and molecular transcriptomic analyses, and the results were related to the radiological appearance and clinical outcomes. 

Results: Study I: The primary tumour was identified in 59 of 69 patients. The median postoperative survival after surgery for MSCC was 20 months. Patients with prostate cancer had the longest median survival (6 years), and patients who were defined as having cancer of unknown primary tumour had the shortest median survival (3.5 months). Surgery maintained and improved the ability to walk in these patients. Study II: A total of 106 of 110 patients met the SINS criteria for potential instability or instability. There was no statistically significant difference in the overall risk of death between the SINS potentially unstable and unstable SINS categories, or in the risk of loss of ambulation one month after surgery. Study III: The median postoperative survival was 71.5 months in patients with myeloma and 58.7 months in patients with lymphoma. The SINS was not related to postoperative survival or neurological outcomes. The ability to walk before surgery was strongly associated with the postoperative ambulatory status. On multivariate Cox regression analysis, the ability to walk and a higher blood haemoglobin level prior to surgery were associated with superior survival. Study IV: A myeloma-like radiological appearance of prostate cancer spinal bone metastases was associated with poor survival and neurological outcomes after surgery for MSCC. 

Conclusions: Patients with MSCC as the IMM resemble a heterogeneous group in which survival is highly dependent on the type of primary tumour. A diagnostic workup is essential before a prognosis can be estimated in order to select candidates for surgery. The SINS may be helpful in selecting patients for surgery for MSCC, but it cannot be used to predict postoperative survival or neurological outcomes in patients with prostate cancer or in patients with haematological malignancies. A myeloma-like radiological appearance of prostate cancer spinal bone metastases is a strong negative predictor for survival and neurological outcomes after surgery for MSCC.

Place, publisher, year, edition, pages
Umeå: Umeå University , 2022. , p. 64
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2173
Keywords [en]
Bone metastasis, metastatic spinal cord compression, surgery for spinal metastases, Spinal Instability Neoplastic Score, prostate cancer
National Category
Orthopaedics
Research subject
Orthopaedics; Orthopaedics
Identifiers
URN: urn:nbn:se:umu:diva-193549ISBN: 978-91-7855-746-2 (electronic)ISBN: 978-91-7855-745-5 (print)OAI: oai:DiVA.org:umu-193549DiVA, id: diva2:1650197
Public defence
2022-05-06, Triple Helix, Universitetsledningshuset + Zoom, Umeå universitet, 09:00 (Swedish)
Opponent
Supervisors
Note

In publication not specified versions of ISBN.

Zoom meeting id: 630 5876 1958. Pass code: 174333

Available from: 2022-04-12 Created: 2022-04-06 Last updated: 2025-01-13Bibliographically approved
List of papers
1. Metastatic spinal cord compression as the first sign of malignancy: Outcome after surgery in 69 patients
Open this publication in new window or tab >>Metastatic spinal cord compression as the first sign of malignancy: Outcome after surgery in 69 patients
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2017 (English)In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 4, p. 457-462Article in journal (Refereed) Published
Abstract [en]

Background and purpose - Metastatic spinal cord compression (MSCC) as the initial manifestation of malignancy (IMM) limits the time for diagnostic workup; most often, treatment is required before the final primary tumor diagnosis. We evaluated neurological outcome, complications, survival, and the manner of diagnosing the primary tumor in patients who were operated for MSCC as the IMM.

Patients and methods - Records of 69 consecutive patients (51 men) who underwent surgery for MSCC as the IMM were reviewed. The patients had no history of cancer when they presented with pain (n = 2) and/or neurological symptoms (n = 67).

Results - The primary tumor was identified in 59 patients. In 10 patients, no specific diagnosis could be established, and they were therefore defined as having cancer of unknown primary tumor (CUP). At the end of the study, 16 patients were still alive (median follow-up 2.5 years). The overall survival time was 20 months. Patients with CUP had the shortest survival (3.5 months) whereas patients with prostate cancer (6 years) and myeloma (5 years) had the longest survival. 20 of the 39 patients who were non-ambulatory preoperatively regained walking ability, and 29 of the 30 ambulatory patients preoperatively retained their walking ability 1 month postoperatively. 15 of the 69 patients suffered from a total of 20 complications within 1 month postoperatively.

Interpretation - Postoperative survival with MSCC as the IMM depends on the type of primary tumor. Surgery in these patients maintains and improves ambulatory function.

Place, publisher, year, edition, pages
Taylor & Francis, 2017
National Category
Orthopaedics
Identifiers
urn:nbn:se:umu:diva-137890 (URN)10.1080/17453674.2017.1319179 (DOI)000404588400017 ()28492105 (PubMedID)2-s2.0-85018719919 (Scopus ID)
Available from: 2017-08-09 Created: 2017-08-09 Last updated: 2024-07-26Bibliographically approved
2. Predictive Value of the Spinal Instability Neoplastic Score for Survival and Ambulatory Function After Surgery for Metastatic Spinal Cord Compression in 110 Patients with Prostate Cancer
Open this publication in new window or tab >>Predictive Value of the Spinal Instability Neoplastic Score for Survival and Ambulatory Function After Surgery for Metastatic Spinal Cord Compression in 110 Patients with Prostate Cancer
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2021 (English)In: Spine, ISSN 0362-2436, E-ISSN 1528-1159, Vol. 46, no 8, p. 550-558Article in journal (Refereed) Published
Abstract [en]

STUDY DESIGN: We retrospectively analyzed Spinal Instability Neoplastic Score (SINS) in 110 patients with prostate cancer operated for metastatic spinal cord compression (MSCC).

OBJECTIVE: We aimed to investigate the association between SINS and clinical outcomes after surgery for MSCC in patients with prostate cancer.

SUMMARY OF BACKGROUND DATA: The SINS is a useful tool for assessing tumor-related spinal instability, but its prognostic value regarding survival and neurological outcome is still controversial.

METHODS: We analyzed 110 consecutive patients with prostate cancer who underwent surgery for MSCC. The patients were categorized according to their SINS. Patients with castration-resistant prostate cancer (CRPC, n = 84) and those with hormone-naïve disease (n = 26) were analyzed separately.

RESULTS: In total, 106 of 110 patients met the SINS criteria for potential instability or instability (scores 7-18). The median SINS was 10 (range 6-15) for patients with CRPC and 9 (7-16) for hormone-naïve patients. In the CRPC group, the SINS was classified as stable (score 0-6) in 4 patients, as potentially unstable (score 7-12) in 70 patients, and as unstable (score 13-18) in 10 patients. In the hormone-naïve group, 22 patients met the SINS criteria for potential instability and 4 patients for instability. There was no statistically significant difference in the overall risk for death between the SINS potentially unstable and unstable categories (adjusted hazard ratio 1.3, P = 0.4), or in the risk of loss of ambulation 1 month after surgery (adjusted odds ratio 1.4, P = 0.6).

CONCLUSION: The SINS is helpful in assessing spinal instability when selecting patients for surgery, but it does not predict survival or neurological outcomes. Patients with a potential spinal instability benefit equally from surgery for MSCC as do patients with spinal instability.

Level of Evidence: 3.

Place, publisher, year, edition, pages
Wolters Kluwer, 2021
National Category
Orthopaedics
Identifiers
urn:nbn:se:umu:diva-182095 (URN)10.1097/BRS.0000000000003835 (DOI)000663724700017 ()2-s2.0-85103474525 (Scopus ID)
Funder
Cancerforskningsfonden i NorrlandRegion Västerbotten
Available from: 2021-04-15 Created: 2021-04-15 Last updated: 2025-01-13Bibliographically approved
3. Epidural spinal cord compression caused by myeloma and lymphoma: outcomes after surgery in relation to Spinal Instability Neoplastic Score
Open this publication in new window or tab >>Epidural spinal cord compression caused by myeloma and lymphoma: outcomes after surgery in relation to Spinal Instability Neoplastic Score
(English)Manuscript (preprint) (Other academic)
National Category
Orthopaedics
Identifiers
urn:nbn:se:umu:diva-193547 (URN)
Available from: 2022-04-06 Created: 2022-04-06 Last updated: 2024-07-26
4. A novel radiological pattern related to poor prognosis in patients with prostate cancer with metastatic spinal cord compression
Open this publication in new window or tab >>A novel radiological pattern related to poor prognosis in patients with prostate cancer with metastatic spinal cord compression
(English)Manuscript (preprint) (Other academic)
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-193548 (URN)
Available from: 2022-04-06 Created: 2022-04-06 Last updated: 2024-07-26

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