Introduction
Cervical spine metastasis is less frequent than metastasis to other parts of the spine. 1 Unfortunately, metastatic disease in the cervical spine can result in severe pain, respiratory failure, and neurological quadriplegia due to metastatic spinal cord compression (MSCC). 2 MSCC is regarded as an oncologic emergency that occurs in up to 10% of adult patients with cancer during their disease courses and can become symptomatic, which involves intractable pain, neurological deficits, or even bladder and bowel dysfunction, adversely affecting the patient’s quality of life. 2 , 3 Treatments for MSCC in the cervical spine include radiotherapy, 4 vertebroplasty, 5 surgery, 6 corticosteroids, and symptom control, alone or in combination, which are effective for improving or maintaining neurological function, relieving pain, stabilizing the spine, and positively improving the patient’s quality of life. 7
In 2005, a phase III trial strongly suggested that direct decompressive surgery following postoperative radiotherapy was superior to treatment with radiotherapy alone for MSCC in terms of ambulatory status, regaining the ability to walk, ambulatory duration, and survival in selected patients. Notably, patients with MSCC in the cervical spine were included in this study. 8 Therefore, posterior approaches, starting with decompressive laminectomy followed by spine stabilization, have traditionally been the most common surgical procedures for MSCC.
Surgery is technically challenging in the cervical spine due to the complicated anatomy of this region, and metastatic disease in the cervical spine is considered a poorer prognosis than in the thoracic and lumbar spine. Few publications have addressed the surgical results and clinical outcomes of cervical spine metastasis, let alone MSCC in cervical spine treated with posterior decompression and spine stabilization. In this study, pain outcome and neurological recovery were used to evaluate surgical results, and factors for survival and neurological outcomes were also analyzed.
Patients and methods
Nineteen patients with MSCC in the cervical spine who had been operated with decompression and spine stabilization were retrospectively analyzed in our department between May 2013 and May 2017. The indication for surgery was neurological deficit (sensory and/or motor function impairment, sphincter dysfunction) due to MSCC which had been confirmed by spinal magnetic resonance imaging, and a life expectancy of at least 3 months. Surgery was not performed on those whose expected survivals were <3 months and in those whose health was too poor to undergo surgery. That was consistent with the Spine Oncology Study Group. 9 All patients had severe pain before surgery. The diagnosis of cancer or bone metastasis was confirmed histologically. All the patients were operated with posterior decompression and spine stabilization in our department ( Figure 1 ). Corticosteroids were routinely used before surgery. Local radiotherapy, systemic chemotherapy, and targeted therapy were performed after the wound healed, about 3–4 weeks after the surgery. Patients with missing data were not included. The Medical Research Ethics Board of the Affiliated Hospital of Academy of Military Medical Sciences approved this retrospective study and waived patient consent for review of medical images and records, as all data were anonymized. This study was conducted in accordance with the Declaration of Helsinki.
Visual analog scale (VAS), ranging from 0 to 10, was used to evaluate the worst pain, average pain, and pain interference for each patient at baseline and following surgery within 24 hours and at 1, 3, 6, and 12 months. Neurological recovery was assessed based on Japanese Orthopaedic Association Score (JOAS; Table 1 ) within 24 hours before the operation and 24 hours, 1, 3, 6, and 12 months after the operation. In addition, 10 characteristics were analyzed for postoperative neurological and survival outcome. These characteristics included age (≤57 years vs >57 years, median age: 57 years), sex (female vs male), type of primary cancer (slow growth vs rapid growth), ambulatory status (can vs cannot), extra-spinal bone metastasis (no vs yes), visceral metastasis (no vs yes), time for developing motor deficit (≤2 weeks vs >2 weeks), 125 I seed brachytherapy (no vs yes), complication (no vs yes), and JOAS (severe: score <10 vs mild: score ≥10). All the above-mentioned characteristics were commonly analyzed in previous studies.
Analysis of the VAS and JOAS in a 24-hour period was performed via repeated measures of the correlated variance model across each time point, supplemented by Wilcoxon rank-sum test. Univariate and multivariate analyses of the survival outcome were performed with the Kaplan–Meier method and the log-rank test and the multiple Cox regression model, respectively. Both univariate and multivariate analyses of the neurological prognosis were performed with the ordered-logit model. A P -value of ≤0.05 was considered statistically significant. Statistical analysis was performed using SAS 9.2 software (SAS Institute Inc, Cary, NC, USA).
Results
Patient characteristics
Patients’ demographic data are summarized in Table 2 . The median age of the patients (9 females and 10 males) was 51 years (range: 29–69 years). Cases were classified into two groups according to primary tumor’s growth rate. The slow growth group included breast cancer (four cases), thyroid cancer (three cases), and renal cancer (one case) while the rapid growth group included lung cancer (eight cases), esophagus cancer, colorectal cancer, and unknown original cancer site (one case each). The involved levels were C1 in one case (5%), C2 in three cases (16%), C3 in three cases (16%), C4 in four cases (21%), C5 in five cases (26%), C6 in seven cases (37%), and C7 in seven cases (37%), which showed low incidence in the upper cervical spine. The median length of follow-up was 10 months (range: 3–18 months).
Surgical results
The mean worst pain score in a 24-hour period was 8.6 before the operation. At 1 day, 1, 3, 6, and 12 months after the operation, the mean worst pain scores decreased to 5.6, 4.5, 3.8, 2.6, and 2.4, respectively (all P <0.001 vs baseline; Table 3 , Figure 2 ). Similar decreases in average pain and pain interference were observed. In detail, the worst pain relief (a 2-score drop in pain was defined as clinically significant relief) was observed in 78.9% of the patients, average pain relief was achieved in 89.5% of the patients, and pain interference relief occurred in 84.2% of the patients after surgery. The median JOAS in a 24-hour period was 11.0 before the operation. At 1 day, 1, 3, 6, and 12 months after the operation, the median JOAS increased to 12.0 ( P =0.469), 13.0 ( P =0.010), 14.0 ( P <0.001), 15.0 ( P <0.001), and 14.0 ( P <0.001), respectively.
Clinical outcomes
In the entire cohort of 19 patients, the overall median survival time was 11.5 months; 6-month and 12-month survival rates were 73.7% and 46.3%, respectively. According to the univariate analysis, factors that were found to be related to longer survival were slow growth cancer, ambulatory ability, 125 I seed brachytherapy, no surgery-related complication, and higher JOAS ( Table 4 ). Median survival time was 13.7 months (95% CI, 3.0–45.1 months) for patients with slow growth cancer and 6.4 months (95% CI, 1.9–11.5 months) for those with rapid growth cancer, and the difference was significant ( P <0.001). Besides, patients who were ambulatory had longer median survival time than those who were not (13.7 months; 95% CI, 6.2–31.4 months vs 5.4 months; 95% CI, 0.5–8.2 months) ( P =0.024). And patients who had undergone 125 I seed brachytherapy also had longer median survival (20.8 months; 95% CI, 6.4–35.0 months vs 6.2 months; 95% CI, 1.9–13.6 months) ( P =0.034). Furthermore, patients with postoperative complications (4.1 months; 95% CI, 0.5–11.4 months) were found to have shorter median survival than those without any postoperative complication (13.7 months; 95% CI, 6.4–31.4 months) ( P <0.001). Finally, compared with patients with lower JOAS (4.4 months; 95% CI, 1.9–11.4 months), patients with higher JOAS were observed to have longer median survival (13.7 months; 95% CI, 6.4–31.4 months) ( P =0.010). According to the multivariate analysis of survival outcome, the type of primary cancer ( P =0.033), ambulatory status ( P =0.004), extra-spinal bone metastasis ( P =0.021), 125 I seed brachytherapy ( P =0.014), and surgery-related complication ( P =0.009) maintained significance. JOAS lost significance, while extra-spinal bone metastasis became significant. As for the neurological outcome, ambulatory status ( P =0.028), surgery-related complication ( P =0.019), and JOAS ( P =0.013) had significant impact based on the univariate analysis, while only JOAS ( P =0.013) showed significance based on the multivariate analysis. Notably, patients with ambulatory ability ( P =0.028), no surgery-related complication ( P =0.019), and higher JOAS ( P =0.013) had better neurological outcome. Besides, patients with no visceral metastasis and shorter time for developing motor deficit also had a better neurological outcome, but both did not reach significance.
Complications
Surgery-related complications occurred in five patients (26.3%). Operation site infection was observed in two cases, which was successfully treated by continuous irrigation. One patient showed epidural hematoma and required surgical removal. Cerebrospinal fluid leakage was found in one case and required percutaneous lumbar drainage. Pneumonia occurred in one case and was controlled by antibiotics.
Discussion
MSCC is an oncological emergency, which initially and reversibly causes edema, venous congestion, and demyelination, and prolonged compression can lead to vascular injury, cord necrosis, and permanent damage. Importantly, patients who have no neurological function for >48 hours are unlikely to improve. 10 Current data suggest that radiation therapy, corticosteroids, and surgery, alone or in combination, can relieve pain and preserve neurologic function. 7 The commonly used surgical procedures for patients with MSCC include excisional surgery, palliative decompression, and minimally invasive surgery. Excisional surgery can remove the whole metastasis and may realize long-term survival without cancer burden, but its complication rates are very high. Generally speaking, palliative decompression is the standard surgical procedure for MSCC. Palliative decompression, posterior decompression, and spine stabilization, had lesser complication rates, lower bleeding risks, and adequate decompressions as compared with excisional surgery. Thus, rapid decompression and immediate spine stabilization for MSCC has become the standard treatment for MSCC due to its increased efficacy over conventional radiotherapy in preserving neurological function and improving survival prognosis. 8 , 11
Reduction in pain and the preservation of motor function in patients with MSCC may significantly improve the patients’ quality of life. Surgery for MSCC in the cervical spine was found to be effective in terms of pain control and neurological recovery. In the present study, the worst pain, average pain, and pain interference showed improvement when preoperative and postoperative pain scores were compared at each time point. In detail, the worst pain relief (a 2-score drop in pain was defined as clinically significant relief) was observed in 78.9% of the patients, average pain relief was achieved in 89.5%, and pain interference relief occurred in 84.2% after surgery. Regarding neurological outcome, postoperative JOAS was increased at each time point as compared with preoperative JOAS. 68.4% of the patients could walk 4 weeks after surgery, 15.8% of the non-ambulatory patients before operation regained the ability to walk, and 52.6% of the patients maintained their ambulatory status. Similar results were obtained in another prospective multicenter study. Fehlings et al 12 concluded that surgical intervention provided immediate and sustained improvement in pain, neurologic, functional, and patients’ quality of life after analyzing 142 MSCC patients. There was an improvement in ambulatory status, lower extremity, and total motor scores at 6 months after surgery. Oswestry Disability Index and pain interference also improved at 6 weeks and 3, 6, and 12 months, postoperatively. Moreover, at 3 months after surgery, the American Spinal Injury Association impairment scale grade improved. Regarding surgical procedure, surgical levels were similar with the cancer-involved levels. Generally, the fusion range was the upper and lower two vertebrae of the surgical levels.
Several prognostic factors have been identified to assess survival prognosis after surgery for spinal metastasis. Tokuhashi et al 13 , 14 presented a scoring system including six parameters, ie, general condition, number of extra-spinal bone metastases, number of spinal metastases, the incidence of metastases to a major internal organ, type of primary malignancy, and finally grade of neurological deficit. Sioutos et al 15 found that preoperative neurological status, the anatomic site of the primary carcinoma, and the number of vertebral bodies involved were significantly associated with survival. Robson 10 reported that prognostic indicators that suggest surgery would more likely be beneficial are histological findings such as multiple myeloma, lymphoma, or breast, prostate, or renal cancers, good motor function at presentation, good performance status, limited comorbidity, single-level spinal disease, absence of visceral metastasis, and long interval from primary diagnosis. Bauer and Wedin 16 showed that absence of visceral metastases, solitary skeletal metastases, and type of primary cancer (not lung, breast, and renal cancer, lymphoma or myeloma) were significantly associated with longer survival. Heidecke et al 17 concluded that histology of the primary tumor, the extent of metastasis, and baseline general condition were the most important prognostic factors for survival in patients with cervical metastasis after surgery.
Except for the factors found in the study of Heidecke et al, the above prognostic factors were not specific to cervical spine metastasis after surgery. However, participants in the Heidecke et al study were operated for spine metastasis in general, not particularly for MSCC. In our series, the type of primary cancer, ambulatory status, extra-spinal bone metastasis, 125 I seed brachytherapy, and surgery-related complication status were found to be significantly associated with postoperative survival in patients with MSCC in cervical spine after surgery. And, only JOAS had a significant impact on the postoperative neurological outcome. As for the postoperative overall survival and survival rates, the median overall survival was found to be 11.5 months and the 1-year survival rate was 46.3%, which conformed to other studies. 17 , 18 Surgery-related complications occurred in 26.3% of the entire cohort of patients and were reported in other studies to occur in 10%–30% of patients. 12 , 19 , 20
The limitation of this study includes the following aspects. First, the study was based on retrospective data, which unavoidably result in bias. Second, the statistical analyses included only 19 cases and over 10 years of data were used. The changes in diagnosis, treatment, clinical/medical knowledge, etc may remarkably influence the surgical results and postoperative outcomes. Finally, data on systemic treatment following treatment were not available in most patients, which also could bias survival outcome and surgical results. Therefore, a larger and prospective study is warranted.
In conclusion, posterior decompression and spine stabilization for painful cervical spine metastasis resulting from spinal cord compression was found to be effective for neurological recovery and pain control with a tolerable rate of complications. The type of primary cancer, ambulatory status, extra-spinal bone metastasis, 125 I seed brachytherapy, and surgery-related complications were found to be significantly associated with postoperative survival, and JOAS has a significant impact on the postoperative neurological outcome. These factors can help select the individual treatment methodology for patients with MSCC in the cervical spine.
Acknowledgments
This study was funded by the Medical and Health Science and Technology Innovation Project of Sanya (no 2018YW04), and the PLA General Hospital Science and Technology Innovation Nursery Fund Project (no.17KMM31).
Disclosure
The authors report no conflicts of interest in this work.
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