Japanese Journal of Clinical Oncology Advance Access originally published online on May 9, 2009
Japanese Journal of Clinical Oncology 2009 39(7):431-434; doi:10.1093/jjco/hyp039
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© The Author (2009). Published by Oxford University Press. All rights reserved
Vertebral Metastases with High Risk of Symptomatic Malignant Spinal Cord Compression
Department of Radiology, Shikoku Cancer Center, Matsuyama, Ehime, Japan
For reprints and all correspondence: Yasushi Hamamoto, Department of Radiology, Shikoku Cancer Center, Kou-160, Minamiumemoto-Machi, Matsuyama 791-0280, Ehime, Japan. E-mail: yhamamot{at}shikoku-cc.go.jp
Received December 19, 2008; accepted March 26, 2009
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Abstract |
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 TOP Abstract INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONConflict of interest statementReferences |
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Objective: To find vertebral metastases with high risk of symptomatic malignant spinal cord compression (MSCC), features of vertebral metastases caused motor deficits of the lower extremities were examined.
Methods: From 2004 through 2006, 78 patients with metastases of the thoracic and/or the cervical spine were treated with radiation therapy (RT). Of these, 86 irradiated lesions in 73 patients were evaluable by magnetic resonance imaging and/or computed tomography at the initiation of RT and were reviewed retrospectively in this study. Twenty-eight patients (38%) had motor deficits at the initiation of RT. Assessed factors were age, sex, primary disease (lung, breast, digestive system and other cancer), lamina involvement, main level of tumor location and vertebral-body involvement.
Results: Incidence of motor deficits at the initiation of RT was 55% for lesions with lamina involvement and 5% for lesions without lamina involvement (P < 0.0001). Incidence of motor deficits was 15% for lesions located mainly in the cervical spine and/or the upper thoracic spine (Th1–4), 54% for lesions located mainly in the middle thoracic spine (MTS) (Th5–8) and 30% for lesions located mainly in the lower thoracic spine (Th9–12) (P = 0.0095). Age, sex, primary disease and vertebral-body involvement were not statistically significant factors for incidence of motor deficits due to MSCC (P > 0.9999, P = 0.7798, P = 0.1702 and P = 0.366, respectively).
Conclusions: Vertebral metastases with lamina involvement tended to cause symptomatic MSCC. Latent development of MSCC occurred more frequently in the MTS compared with other levels of the thoracic and the cervical spine.
Key Words: neoplasm metastasis • spinal cord compression • paraplegia • risk factors
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INTRODUCTION |
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Malignant spinal cord compression (MSCC) is one of the most dreaded complications of metastatic cancer. Its natural history is usually progressive pain, paralysis, sensory loss and sphincter dysfunction. Ninety percent of patients with MSCC have pain (local and/or radicular) and up to 50% of patients with MSCC may be unable to walk and have sensory and/or bladder/bowel dysfunction (1,2). Furthermore, patients with paralysis either at presentation or after treatment have a much shorter life time than ambulatory patients (3–6). Once paralysis of the lower extremities due to MSCC occurs, complete recovery of motor function is often difficult. It was reported that motor function improved only in 40% of patients after radiation therapy (RT) (7). Therefore, early diagnoses and early treatment are important. RT may be useful to prevent progression of motor deficits when RT is performed before occurrence of irreversible changes in the spinal cord. All vertebral metastases have possibility to cause motor deficits due to MSCC ultimately; however, majority of vertebral metastases do not cause symptomatic MSCC during the life time of cancer patients. Searching for vertebral metastases with high risk of motor deficits due to MSCC would be useful to select targets for RT or careful observation. To find vertebral metastases with high risk of symptomatic MSCC, we analyzed features of vertebral metastases cause motor deficits of the lower extremities.
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PATIENTS AND METHODS |
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Patients
From January 2004 to August 2006, 78 patients with metastases of the thoracic spine and/or the cervical spine were treated with RT for the purpose of pain control, relief of spinal cord compression and prevention of fracture in our institution. For pain relief, RT was performed when adequate pain control could not be achieved by analgesic drugs (non-steroid anti-inflammatory drugs and/or opioid). For relief of MSCC, RT was preferable in majority of patients. Surgery was performed for patients with comparatively good prognoses and without a major risk factor for surgical treatment. Most patients with MSCC were not applicable to this condition. In addition, there was no full-time orthopedist in our institution before 2006. As a result, most patients with MSCC were treated with RT in our institution.
Among 78 patients underwent RT to metastases of the thoracic spine and/or the cervical spine, 86 irradiated lesions in 73 patients could be evaluated by magnetic resonance imaging (MRI) and/or computed tomography (CT) and were reviewed retrospectively in this study. Assessment of tumor sites and extensions in the irradiated vertebrae was performed by MRI for 70 lesions and performed by CT for the remaining 16 lesions.
In all patients but two, distribution of involved vertebrae in cervical and thoracic spine was assessed by one or more imaging modalities (bone scan using Tc-99m-hydroxymethylene diphosphonate for 59 patients, MRI of whole cervical and thoracic spine for 58 patients, positron emission tomography/CT using 18F-fluoro-2-deoxy-D-glucose for 6 patients, continuous CT imaging from neck to abdomen for 2 patients and whole body scan using Tc-99m-pyridoxyl-5-methyl tryptophan for 1 patient with hepatocellular carcinoma). The responsible lesions for motor deficits were determined based on these imaging findings. Two patients without imaging evaluation of whole cervical and thoracic spine did not have motor deficits of the lower extremities.
Vertebral metastases outside radiation fields were excluded from objects of analysis in this study. Twenty-eight patients (38%) had motor deficits of the lower extremities due to MSCC at the initiation of RT. Patient characteristics are shown in Table 1 and characteristics of lesions are shown in Table 2.
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Methods of Evaluation and Statistical Analysis
Assessed factors were age (<60 vs.
60), sex, primary disease (lung cancer, breast cancer, digestive system cancer and other cancer), main levels of lesions in the spinal column, existence of lamina involvement and existence of vertebral involvement. From our clinical experience, we noticed that vertebral metastases caused motor deficits of the lower extremities often had lamina involvement, and metastases of cervical spine and upper thoracic spine often cause uncontrollable severe pain rather than motor deficits. Therefore, we selected lamina involvement and main levels of lesions in the spinal column as factors to assess. Laminae are a part of a vertebral arch. A vertebra consists of an anterior segment ‘the vertebral body’ and a posterior part ‘the vertebral arch’. The vertebral arch is formed by a pair of pedicle and a pair of laminae and supports seven processes (four articular processes, two transverse processes and one spinous process). The laminae are two broad plates, extending dorsally and medially from the pedicles, fusing to complete the roof of the vertebral arch. Levels of lesions were classified into (i) the cervical spine and/or the 1st to 4th thoracic spine (cervical and/or upper thoracic spine, CUTS), (ii) the 5th to 8th thoracic spine (middle thoracic spine, MTS) and (iii) the 9th to 12th thoracic spine (lower thoracic spine, LTS). 
2 test or Fisher's exact method was used for evaluation of inter-group differences in incidence of motor deficits. |
RESULTS |
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Incidence of motor deficits at the initiation of RT for each factor is shown in Table 3.
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Incidence of motor deficits at the initiation of RT was higher in lesions with lamina involvement (55%) compared with lesions without lamina involvement (5%) with statistic significance (P < 0.0001). In addition, 93% (26/28) of lesions caused motor deficits at the initiation of RT had lamina involvement (bilateral involvement, 18 lesions; unilateral involvement, 8 lesions). There was no statistically significant difference in incidence of motor deficits between lesions with bilateral lamina involvement (58%) and lesions with unilateral lamina involvement (50%) (P = 0.5982). Vertebral-body involvement was observed in 71 of 86 lesions. Incidence of motor deficits at the initiation of RT was 35% in lesions with vertebral-body involvement and 20% in lesions without vertebral-body involvement (P = 0.366).
Incidence of motor deficits at the initiation of RT was 15% for lesions of the CUTS, 54% for lesions of the MTS and 30% for lesions of the LTS (P = 0.0095). The most common chief complaints were pain for lesions of the CUTS, motor deficits for the MTS and pain for the LTS. Incidence of chief complaint of pain and motor deficits was 56% and 15%, respectively, for lesions of the CUTS, 42% and 54%, respectively, for lesions of the MTS and 61% and 30%, respectively, for lesions of the LTS.
Age, sex and primary disease were not significantly significant factors for incidence of motor deficits (Table 3).
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DISCUSSION |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONConflict of interest statementReferences |
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The mechanism of cord injury is not entirely understood. The early myelopathy associated with MSCC may be due to impairment of venous drainage leading to intramedullary vasogenic edema. Irreversible cord necrosis results from ischemia. The most common types of cancers causing MSCC are breast cancer, prostate cancer and lung cancer (8). Loblaw et al. reported that breast cancer, lung cancer and prostate cancer accounted for 21%, 23% and 18%, respectively, of the 3458 patients with MSCC. The proportion of cancer patients who had MSCC at the presentation of their disease was 0.23%, and 2.5% of the patients dying of cancer had at least one admission for MSCC in the 5 years preceding death (9). Approximately 70% of the patients had loss of neurologic function between the onset of symptoms and the start of treatment. The majority of delays were caused by lack of symptom recognition by the patient and diagnostic delay at the general practitioner or general hospital level (10). Early recognition of MSCC symptoms and early treatment are necessary to prevent development of symptoms of MSCC. Although close follow-up by imaging modality and early RT seem to be useful to prevent MSCC and preserve neurologic function, it may be difficult to carry out close follow-up and/or early RT for all patients with spinal metastases in clinical practice. To know what lesions should be followed up closely and what lesions need early RT is important. Among the assessed factors, vertebral metastases with lamina involvement and vertebral metastases located in the MTS seemed to be high-risk lesions for motor deficits. Incidence of motor deficits was higher in lesions with lamina involvement compared with lesions without lamina involvement with statistical significance. In addition, >90% of lesions causing motor deficits had lamina involvement. A possible explanation of high incidence of motor deficits in lesions with lamina involvement is that tumors of the lamina easily expand into the epidural space and cause MSCC comparatively early. Careful follow-up or early RT should be considered for vertebral metastases with lamina involvement. From our results, lesions without lamina involvement seemed to have comparatively low risk of imminent motor deficits.
Lesions of the MTS tended to cause motor deficits more frequently compared with lesions of the CUTS and the LTS in our series. Severe local pain and/or painful radiculopathy, which were often difficult to control with analgesics alone, were common chief complaints in patients with lesions of the cervical spine. In addition, physicians tended to be more afraid of fracture of the cervical spine compared with that of the thoracic spine. As a result, lesions of the cervical spine tended to be treated earlier. Lesions of the cervical spine are sometimes treated with RT even when they are asymptomatic. Among lesions of the thoracic spine, lesions of the upper thoracic spine and the LTS tended to cause comparatively severe pain preceding MSCC more frequently compared with lesions of the MTS. Latent development of MSCC seemed to be more frequent in lesions of the MTS compared with the CUTS and the LTS. A prospective cohort study reported that 
90% of the patients with MSCC complained of back pain (11). However, comparatively mild back pain often can be decreased to the level of bearable by analgesics. Physicians often do not pay much attention to the condition of metastases of thoracic spine when comparatively good pain control is achieved. As a result, timing of RT tended to be delayed in lesions of MTS. More attention to latent development of MSCC should be paid even for patients in whom comparatively good pain control is achieved.
Primary disease was not a significantly factor for incidence of motor deficits in our study. A population-based study reported that cumulative incidence of MSCC is disease-specific; however, the differences were comparatively small. It was reported that cumulative incidence of MSCC is highest in multiple myeloma (8%), followed by prostate cancer (7%), nasopharyngeal cancer (6.5%) and breast cancer (5.5%) (9). Comparatively small number of patients in our study and inherently small differences in disease-specific cumulative incidence of MSCC might lead to our result.
Based on our results, vertebral metastases with lamina involvement and vertebral metastases located in MTS have comparatively high risk of motor deficits due to MSCC. Concerning prognostic factors for survival, histologic type of myeloma, thyroid cancer, renal cell carcinoma, breast cancer and prostatic cancer is highly associated with good prognoses (12). Especially in patients with comparatively good survival prognoses, vertebral metastases with lamina involvement and vertebral metastases located in MTS should be followed up carefully by imaging modalities and should receive early treatment.
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CONCLUSION |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONConflict of interest statementReferences |
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In conclusion, vertebral metastases with lamina involvement tended to cause MSCC with motor deficits and need early RT or careful follow-up. Latent development of MSCC tended to occur in lesions of the MTS compared with lesions of the CUTS and the LTS. We should pay attention to this tendency.
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Conflict of interest statement |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONConflict of interest statementReferences |
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None declared.
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References |
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