About the Author(s)


Louisa M. Mbokazi Email symbol
Department of Radiation Oncology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

Sheynaz Bassa symbol
Department of Radiation Oncology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

Krishanthavathie Pillay symbol
Department of Radiation Oncology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

Citation


Mbokazi LM, Bassa S, Pillay K. Review of presentations and radiotherapy outcomes of patients with malignant spinal cord compression. S. Afr. j. oncol. 2025; 9(0), a305. https://doi.org/10.4102/sajo.v9i0.305

Original Research

Review of presentations and radiotherapy outcomes of patients with malignant spinal cord compression

Louisa M. Mbokazi, Sheynaz Bassa, Krishanthavathie Pillay

Received: 26 Apr. 2024; Accepted: 15 Aug. 2024; Published: 13 Jan. 2025

Copyright: © 2025. The Author(s). Licensee: AOSIS.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: Malignant spinal cord compression (MSCC) is the commonest radiotherapy emergency. A high index of suspicion, prompt diagnosis, early referral and treatment is important to restore quality of life and improve survival in patients with MSCC.

Aim: This study aimed to evaluate the clinical and treatment characteristics of patients presenting with MSCC at the Radiation Oncology department.

Setting: The study was conducted at Steve Biko Academic Hospital, Radiation Oncology.

Methods: This is a retrospective review of 110 patients who were treated for MSCC between January 2022 and November 2023. Information on patients’ characteristics, disease characteristics, imaging findings, radiotherapy dose prescription, clinical response and survival was extracted from clinical records.

Results: Breast and prostate cancer were the most frequent primary disease sites. Most patients presented in a poor Eastern Cooperative Oncology Group (ECOG) performance status (PS 4), de novo disease (63%) and multilevel vertebral involvement (70%). Eighty-four patients (76.4%) received a single fraction treatment (6 Gy – 8 Gy). The median overall survival was 145 days. Patients with a Rades score of 32–37 points had a statistically significant better overall survival at 1 year compared with those with a score of 22–31 points. There was no difference in survival between single versus multiple fraction treatment.

Conclusion: A single fraction radiotherapy schedule is acceptable in this setting where most patients present with extensive disease and non-ambulatory baseline function.

Contribution: The findings from this study could be used to establish protocols for treatment strategies in facilities with limited resources.

Keywords: radiotherapy; malignant spinal cord compression; palliative; treatment outcomes; dose fractionation.

Introduction

Malignant spinal cord compression (MSCC) is a common radiotherapy emergency. Treatment is aimed at reversing the neurological deficit, relieving pain, improving quality of life and extending survival. The cumulative incidence of MSCC in the last 5 years of life is approximately 2.5% but varies depending on the primary diagnosis.1,2 Approximately 3.4% of all skeletal-related events from bone metastases are attributed to MSCC, with prostate, breast, hepatocellular (HCC) and lung cancer being the most frequent incidences of cancer.3 Data on the incidence and outcome of MSCC in Africa are sparse. Approximately 14% – 30% of non-traumatic spinal injuries in Africa are related to malignancy superseded by tuberculosis and human immunodeficiency virus (HIV) infection.2,4 The lack of radiotherapy facilities in Africa and advanced disease stage predict a poorer outcome in patients with cancer.5,6

Imaging with whole spine magnetic resonance imaging (MRI) is the gold standard for the diagnosis of MSCC and should be performed immediately or, within 24 h of a suspected diagnosis of MSCC.7 A computed tomography scan (CT scan) with fine cuts is an acceptable alternative when MRI is not available.1

Corticosteroids should be commenced immediately or within 12 h of onset of symptoms.8 Steroids reduce cord oedema and restore vascularity.9 The delay in administration of corticosteroids is associated with six-fold risk of remaining non-ambulatory following treatment.10

Radiotherapy has been the mainstay of treatment of MSCC. Since 2005, surgery has been advocated in carefully selected patients as it has been shown to improve, prolong post treatment ambulatory status and reduce the need for steroids and analgesics.11 However, 11% of patients experience post-surgical complications and a third fail to complete planned adjuvant radiotherapy because of a decline in performance status.1 The Spinal Instability Neoplastic Score (SINS) scoring system is a useful tool to identify potential surgical candidates.12 It comprises one clinical component and five imaging defined components, and surgery is recommended for score > 7.13 The standard surgical intervention is decompressive surgery followed by conventional radiotherapy.

The updated Rades score has identified four factors (primary disease site, ambulatory status, sensory loss, sphincter preservation) that may be used to predict post-radiotherapy ambulatory status, local control and survival.1 Patients with lower scores were more likely to benefit from combined surgery and radiotherapy approach. A combination of SINS score and Rades prognostic groups may be used to identify patients who would benefit from a combined surgical and radiotherapy approach.14

The commonly used radiotherapy schedules are 20 Gy in five fractions, 30 Gy in 10 fractions and more frequently, a single fraction of 8 Gy. The SCORAD study compared two fractionation regimens for the treatment of MSCC.2,15 A single fraction 8 Gy was non-inferior to 20 Gy in five fractions.2,15 Treatment with external beam radiotherapy most often yields a partial response (60%) with fewer complete responses (10% – 25%).15

There is a lack of evidence with regard to the outcomes of MSCC in sub-Saharan Africa. A lack of resources means that patients are often misdiagnosed, untreated and often do not return for follow up.

We present the results of a single institute review of clinical characteristics and survival in a cohort of patients presenting for radiotherapy to the Department of Radiation Oncology (name redacted).

Methods

The study was approved by the MMed Committee and the Ethics Committee of the Faculty of Health Sciences, University of Pretoria. A waiver of informed consent was obtained from the university ethics committee in view of the retrospective nature of the study. The data were obtained from the clinical case records of patients treated with radiotherapy for MSCC between January 2022 and November 2023 at Steve Biko Academic Hospital. A total of 110 patient records were analysed.

The inclusion criteria were:

  • Age 18 years or older
  • A biopsy confirmed of malignancy
  • Spinal cord compression confirmed on radiological imaging, either MRI or CT scan
  • Patients who received radiotherapy for the treatment of MSCC.

The exclusion criteria were:

  • Age < 18 years
  • Bone metastases without MSCC
  • Patients with MSCC who did not receive radiotherapy as part of the treatment.
Data collection

The information was obtained from patient hospital files. This included details on clinical presentation, diagnosis, imaging findings, treatment prescription and follow up data. A large proportion of patients were lost to follow up and post-treatment ambulatory status could not be assessed, and therefore survival was the applied outcome measure. Survival status was tracked using patient identity numbers or through attempts to telephonically contact patients or family members.

Ambulatory status was recorded pre- and post-treatment, and a change in baseline scores was reported. Ambulatory status was graded using a 4-tiered scoring system, which is in accordance with the World Health Organization performance status (PS), which is based on the Medical Research Council muscle power criteria, with 4 depicting the worst status.2 The Rades score was calculated based on a 4-level scoring system that includes primary site, ambulatory status, sensory deficit and sphincter control.1 Survival was measured from the time of first consultation for MSCC to death from any cause. The date of the first consultation was selected as this was the most consistent time point. The department has an emergency consultation policy for all suspected or confirmed cases of MSCC.

Performance status was measured using the Eastern Cooperative Oncology Group (ECOG) performance score. The following information was obtained from the clinical records: age at presentation, gender, symptom duration, date of imaging, date of consultation, imaging modality and date, primary site, de novo or metachronous disease, other metastatic sites, ambulatory status, prior therapy, sites of compression, dose prescription and follow up response assessment. The survival status of patients who were lost to follow up or could not be contacted was confirmed through an online database, which is linked to the National Department of Home Affairs.

Statistical analysis

Statistical analysis was assisted by the Department of Statistics (name redacted). The sample size was determined using Equation 1:

where n = sample size, p = assumed proportion (50%), z = z-value at 95% confidence (1.96), d = desired level of absolute precision (10%), which yielded a total of 96 patients records. The minimum sample size required for this study was 96. Furthermore, a 10% increase was made to make allowance for attrition, resulting in a sample size of 106 patient records. This step was necessary so that the study can achieve reliable statistical significance. It was assumed that this sample size will reduce the type I and type II errors and the effect of known and unknown confounders. Thus, the power (1-β) (the % chance of detecting difference) of the study was set at 80%. Statistical analysis was performed using STATA® BE 18.0 software. Descriptive statistics were used to analyse patient characteristics. The Kaplan–Meier curve was used to describe survival data. Survival in days was determined from the date of first consultation to the date of death. The log rank test was used to assess factors that were significantly associated with risk of death on univariate analysis with a p-value of < 0.05 deemed significant. The Cox regression model was used to identify the effect of multiple co-variates on survival.

Ethical considerations

All patients receiving radiotherapy were required to sign an informed consent document after being counselled with regard to the need and side effects of treatment. This included permission for the use of data for research purposes. All data were anonymised, and patient identifiers were not included in the data collection forms or in the publication data. The study was conducted with the approval of the University of Pretoria Human Ethics Committee (reference no. 1/2024) and the approval of the Chief Executive Officer of Steve Biko Academic Hospital.

Results

Patient characteristics

The patient characteristics are summarised in Table 1. There was a slight female preponderance with a total of 59 (54%) females and 51 (46%) males. The mean age of presentation for the entire cohort was 54.06 years (range 24–85 years, standard deviation [s.d.]: 14.06). Women presented on average 10 years earlier, with mean 49.48 years versus 59.17 years for men, t (108) = 3.83, p = 0.0002.

TABLE 1: Summary of patient characteristics (N = 110).
Disease characteristics

Breast (43%), prostate (29%) and haematological (13%) malignancies accounted for most primary disease sites (Figure 1). Most patients were assessed to have an ECOG PS of 4 (50%), limited baseline ambulatory function (65%), absent motor function (37%) and sensory loss (79%). Most patients presented with a Rades score of 22–31 (54%) followed by 32–37 (45%) and Rades score of 17–21 (1%) (Figure 2).

FIGURE 1: Pie graph of primary aetiological sites.

FIGURE 2: Frequency table of Rades score in treatment population.

Almost two-thirds presented with metastatic disease at initial diagnosis of malignancy (63% vs. 37%) while 46 patients (51%) had disease confirmed at other sites. The thoracic vertebrae were most often involved (n = 88; 80%) followed by lumbar (n = 48; 44%), cervical (n = 26; 24%) and sacral and pelvic region (n = 14, 13%). Seventy per cent (70%) of patients had multiple levels of spinal involvement.

Referral characteristics

Most patients were referred from within the institution, Steve Biko Academic Hospital, followed by Kalafong hospital and Dr George Mukhari Academic hospital (Figure 3). The mean duration of symptoms, prior to investigation, was 2.7 months (range: 0.25–36 months, s.d.: 4.65). Magnetic resonance imaging (60%) was the most frequently used modality for diagnosis followed by CT scan (40%). The average waiting time from imaging to first consultation was 9 days following MRI imaging and 22 days after CT imaging. The difference was not statistically significant t (98) = −0.72, p = 0.46.

FIGURE 3: Hospital referral patterns in percentage.

Treatment characteristics

Thirty-two patients (29%) had two, non-continuous radiotherapy fields. An average of six vertebral levels (range 2–18 levels, s.d.: 2.56) were encompassed in the single radiotherapy field cohort and an average of five vertebral levels (range 2–10 levels, s.d.: 1.60) in those who received an additional treatment field. Most patients were treated with a single fraction of 8 Gy (38%) followed by a single fraction of 6 Gy (31%) and 20 Gy in five fractions (19%) (Figure 4).

FIGURE 4: Dose fractionation scheme.

Outcomes

Of the 110 patients, 70 were confirmed deceased. The mean overall survival rate was 165 days with a range of 3–568 days and median overall survival of 143 days (Figure 5).

FIGURE 5: Overall Kaplan–Meier survival estimates for the entire group.

On univariate analysis, we tested the effect of the following on survival: age (< 65 years, ≥ 65 years), baseline ambulatory function, ECOG score, primary site, de novo metastatic disease, multiple skeletal sites, number of fractions (single vs. multiple), pretreatment Rades score. We excluded the two cases with a Rades score of 17–21 from the final analysis. The effect of Rades score was evaluated at 1 year and again at the end of the study period (Figure 6). The Rades score was the only variable demonstrating a significant effect on overall survival on both univariate or multivariate analysis (p = 0.004, 95% confidence interval [CI]: 19.9–103.4). This effect was clinically significant at 1 year (hazard ratio [HR]: 0.44, 95% CI: 0.25–0.75) versus end of the study period (HR: 0.71, 95% CI: 0.43–1.16) (Figure 7). The total number of fractions, single fractions versus multiple fractions had no effect on the overall survival in this cohort.

FIGURE 6: Kaplan–Meier survival estimates at 1 year per Rades score.

FIGURE 7: Kaplan–Meier survival estimates at the end of the study period.

Discussion

The 2022 South African Globocan statistics reported over 100 000 newly diagnosed cases and 65 000 deaths, attributable to cancer.16 Breast, cervical, prostate and lung cancer rank among cancers with the highest incidence and mortality in South Africa.16 Breast, prostate and non-small lung cancer demonstrate a propensity for bone metastases especially in locally advanced disease.17 It is therefore not surprising that these represented the most frequent primary incidences of cancer in this study.

The large number of patients presenting with MSCC, and de novo disease is indicative of the treatment challenges in low and middle-income countries. Patients present with advanced disease and upfront metastases because of various reasons including ineffective screening protocols and difficulties in accessing the healthcare system.18 Upfront skeletal imaging to exclude metastases is imperative in patients who present with locally advanced breast, prostate and lung cancer. The lack of effective systemic therapies in the public sector increases the risk of disease progression and skeletal events including MSCC.

Early intervention in patients with MSCC is essential for better outcomes with radiotherapy. The average duration of symptoms in this study was 2.7 months and bearing in mind that most patients were referred from within the institution, this delay is of concern. This could be related to a lack of clinical suspicion or delays in confirming the diagnosis.

While the diagnosis was often made on MRI imaging (60%), a large number were treated based on CT findings. The latter was because of a breakdown of the MRI scanner in August 2023 and delays in replacement of the MRI scan. Computed tomography scan lacks the sensitivity of MRI, and the diagnosis may be missed, or the extent of disease not adequately appreciated.19 Nonetheless, delays with referral is evident from the average time between imaging to the date of first consultation (22 days). This is likely because referring clinicians may not understand the urgency in treating MSCC and the impact thereof. Malignant spinal cord compression is a prioritised referral at our radiation oncology unit and patients are seen on the day of referral or the following day depending on the proximity of the referring centre. This is an indication of the need to educate other specialities of the importance of prompt diagnosis, early referral and treatment. Patients are referred by peripheral and district hospitals, some located over 100 km from this institution, and where diagnostic radiology is often unavailable or not functional.

To achieve better outcomes, it is important that patients with known metastatic disease, especially axial bone metastases, be educated about the signs and symptoms of MSCC and the importance of early treatment. Referring healthcare professionals should also be made aware of the urgency of diagnosis of MSCC and the subsequent early intervention for reversal or preservation of neurological sequelae.

Many patients presented with a baseline ambulatory status grade 4 (65% of patients), absent motor function, high disease burden and limited systemic therapy options. It is often difficult to determine if radiotherapy is beneficial in these patients. As a result, patients presenting with a poor ECOG PS, and who were non-ambulatory were offered a single fraction of radiotherapy. Patients with favourable PS or ambulatory before starting radiotherapy were more likely to receive a course of 20 Gy in five fractions. Rades et al. have published a 3-tiered scoring system to predict life expectancy (> 2 months) in patients presenting with MSCC. Primary sites, aside from lymphoma or myeloma are allocated a score of 0, along with an acute onset of motor symptoms (< 7 days) and non-ambulatory status. A score of 2–3 was associated with a 39% treatment success rate as opposed to a score of 0 or 1. This is an objective means to limit treatment to those patients who are most likely to benefit. Although haematological malignancies, often multiple myeloma, accounted for 10% of cases, a subgroup analysis by primary malignancy did not show any difference with regard to treatment outcome in this cohort.

The Rades score was an important predictor of survival and the median survival for the 32–37-point group was 184 days versus 105 days for those with a score of 22–31 points. It is important to implement an objective assessment tool as a baseline assessment to improve decision making.

Limitations

With this study being retrospective, the data relied mainly on adequate record keeping. The main challenges were poor record keeping and it was difficult to obtain data for some variables from the notes provided. Patients’ follow up was poor as many patients rely on public transport to return for appointments either directly or via the referring hospital. This is impossible for a non-ambulant patient with a poor ECOG PS. As a result, survival and not ambulatory status was the outcome measure. We will be implementing a formal assessment tool for all newly diagnosed MSCC. This will include a chart to document all the components of the Rades scale and to systematically delay post-treatment follow-up. Patients will be followed up in person or telephonically to assess treatment outcomes. A prospective study is long overdue in this setting.

Conclusion

There is a lack of data on the management and outcome of MSCC in low- and middle-income countries, especially in Africa. This article provides evidence of the challenges associated with treatment of patients in this setting. Nonetheless, a single fraction of radiotherapy provides effective palliation for MSCC in a resource-constrained setting.

Acknowledgements

Competing interests

The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article.

Authors’ contributions

L.M.M., S.B. and K.P. contributed to this study through conceptualisation, methodology, formal analysis, investigation, data curation, writing, resources, review and editing. S.B. and K.P. were also involved in the supervision of the study.

Funding information

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Data availability

Raw data were generated at Steve Biko Academic Hospital. Derived data supporting the findings of this study are available from the corresponding author, L.M.M., on request.

Disclaimer

The views and opinions expressed in this article are those of the authors and are the product of professional research. It does not necessarily reflect the official policy or position of any affiliated institution, funder, agency, or that of the publisher. The authors are responsible for this article’s results, findings, and content.

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