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Controversies in the management of metastatic spinal cord compression
Clinical Oncology (1995) 7:77-81 © 1995 The Royal College of Radiologists
Clinical Oncology
Review Article Controversies in the Management of Metastatic Spinal Cord Compression A . M a k r i s 1 a n d I. H . K u n k l e r 2 tRoyal Marsden Hospital, Sutton and 2Western General Hospital, Edinburgh, UK
INTRODUCTION Spinal cord compression (SCC) due to epidural metastases is an oncological emergency, complicating malignant disease in about 5% of patients [1,2]. The optimal management remains controversial [3], but many studies suggest that early treatment is an important factor [4--11]. Although the syndrome of back pain, paraparesis, paraesthesia, and bladder and bowel dysfunction is characteristic of SCC, it may remain undiagnosed in patients already debilitated with metastatic cancer until it is too late for effective treatment. A high index of clinical suspicion is therefore needed.
DIAGNOSIS The diagnosis of SCC needs to be established rapidly. For many years, myelography was the investigation of choice, especially when a combined lumbar and cisternal approach was used. Myelography can provide additional information to clinical examination and radiographs of the spine, helping to avoid geographical misses [12-14]. Myelography is, however, an invasive procedure and is generally thought to carry a risk of further neurological deterioration. This has not been proven and there are no large studies to substantiate this. The neurological deterioration may be a feature of the natural history of rapidly progressive SCC in some patients. Increasingly, magnetic resonance imaging (MRI) is replacing myelography as the investigation of choice in suspected SCC [15]. MRI is non-invasive, has high intrinsic soft tissue contrast, and has the ability to image in non-axial planes. Compared with myelopathy, it can provide additional information about the presence of bone marrow involvement and paravertebral soft tissue masses [16]. A number of studies have shown that it is either superior or equivalent to myelography when SCC is suspected [15-20]. Two studies have, however, suggested better imaging by myelography alone [21], or myeCorrespondence and offprint requests to: Dr I. H. Kunkler, Consultant Clinical Oncologist, Department of Clinical Oncology, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
lography combined with postmyelographical spinal CT [22]. For most patients it would appear that, where available, MRI will be the investigation of choice.
MANAGEMENT The optimal treatment of cpidural SCC remains to be established. New methods of treatment are evolving, while the role of the conventional ones, decompressive laminectomy and radiotherapy (RT), is not fully defined. There is a lack of randomized studies [23] in the management of SCC on which to base treatment decisions. Most studies have been retrospective reviews of the experience of single institutions. Treatments are compared with previously reported series, making the results unreliable. Furthermore, the differences in the patient characteristics between the compared groups may be greater than the observed differences in outcome as a result of treatment. Assessment of response to treatment and outcome are not standardized, thus increasing the inaccuracies in comparing different series.
Surgery Until the 1960s, decompressive laminectomy, with or without excision of turnout, was the main treatment of malignant SCC [1,24-29] The outcome after laminectomy was disappointing, which led to suggestions that there may be a role for postoperative radiotherapy in selected patients [25,26]. A number of restrospective studies failed to show any significant difference between primary radiotherapy and surgery, with or without postoperative RT, in response to treatment and survival [4,30,31]. In a large retrospective analysis of 31 series reported in the literature prior to 1984, comprising over 2300 patients with spinal metastases [32], it was concluded that RT is as effective as surgery plus RT. The authors do, however, comment that many large series were not included in the analysis 'because of imprecise definition of either the materials and methods or the results'. Findlay [3] reviewed all papers dealing with malig-
78 nant SCC between 1960 and 1983. He included in the final analysis, which totalled 1816 patients, only those papers in which sufficiently precise data were presented to allow patients to be categorized into one of three easily defined neurological groups both prior to and following therapy. Success or failure of therapy was judged solely by transference of patients between categories. He showed that only 32% and 38% respectively of those treated by laminectomy alone or laminectomy with RT were able to walk at the end of treatment, compared wtih 51% of those treated by RT alone. Furthermore, 26% of the patients treated by laminectomy alone and 20% of those treated by laminectomy and RT deteriorated by a full grade following treatment, compared with 17% by RT alone. Sorensen et al. [7] reviewed all medical records of patients treated for metastatic SCC in the eastern part of Denmark between 1979 and 1985. A total of 345 were evaluated. Although patients treated with laminectomy followed by RT seemed to respond better than those treated by RT or laminectomy alone, when their pretreatment motor function was taken into account no significant difference was found between the three groups. In the subgroup of non-ambulatory patients, however, a significantly better restoration of gait was observed in patients treated with a combination of laminectomy and RT than RT alone. A longer survival in the group treated with the combination of laminectomy and RT may reflect that these patients had less advanced disease and were in better medical condition and therefore had a better potential of regaining function. This study also failed to confirm Findlay's finding that more patients deteriorated after laminectomy than after RT. Eighteen per cent of their patients were neurologically worse after RT, compared with 10% after laminectomy and 11% with combined treatment. Landmann et al. [33], in a retrospective review of 140 patients with 153 episodes of SCC, found a better outcome following decompressive laminectomy and RT (126 patients) than following RT alone (27 patients). The validity of this study is to be questioned on two counts. First, patients may have been treated by RT only because of poor prognostic factors; secondly, there is a large imbalance in the numbers in the two groups. Details of surgical mortality or morbidity are often not reported. Where they are reported, mortality is 6%-8% [24,34,35]. Morbidity, mainly in the form of wound infection, dehiscence and delayed healing, is of the order of 10%-15% [36,37]. In a study of 80 consecutive patients with a single thoracic metastasis causing SCC, all treated by standard decompressive laminectomy with no attempt at stabilization of the spine, Findlay [38] has shown that, in the presence of vertebral collapse, there is a much reduced chance of regaining the ability to walk, a much greater possibility of further neurological deterioration, and a major increase in the incidence of postoperative spinal instability. Two approaches to overcome this problem are available: the use of posterior spinal stabilization [39-41], and the more technically aggressive anterior surgical approaches to the spine, either by trans-
A. Makris and I. H. Kunkler thoracic or thoraco-abominal approach. This is a logical approach in anteriorly situated tumours, where a posterior approach would leave the spine unstable. Several groups have reported their experience with anterior decompression and stabilization for anteriorly situated tumours causing SCC, and the results appear encouraging in selected patients [35,37,42-47]. Postoperative mortality for this aggressive approach varies from 7% to 30% [35,47]. In the only reported randomized prospective study [23] comparing laminectomy and RT with RT alone, no difference in response to treatment or survival was seen. This study was, however, too small (29 patients only) for the results to be of statistical significance, but it demonstrates that such a study is possible. A role for primary surgery may exist in paediatric tumours that invade the spinal canal via the neural foramen, compressing the spinal cord in a circumferential manner, allowing decompressive laminectomy to be an effective surgical approach [2]. Superior results were demonstrated in retrospective series for decompressive laminectomy alone or before medical therapy, compared with those who received RT and/ or chemotherapy without posterior decompression [2,48]. Surgery has a role in situations where there is no obvious primary, and histological diagnosis is required.
Radiotherapy Dose and Fractionation
Radiation was not used as a sole treatment of SCC prior to the 1960s, largely due to concern over radiation oedema [13,49], particularly if there was complete myelographic block [13]. Animal Studies. The concept of radiation oedema has been addressed in two studies using experimental animal models [50,51]. Neither of these was able to find any oedema of the tumour or nervous tissue occurring after radiation. Rubin [51], using a Murphy-Sturm lymphoma in a rat model, and Ushio et al. [50], using a less radiosensitive Walker 256 carcinoma in a rat model, went on to study the effects of fractionation and dose on the outcome of radiation therapy after SCC. Ushio [50] observed the best initial improvement with a 1000 rad (cGy) single dose, but relapse occurred rapidly. Poor initial improvement was observed with 200 rads (cGy) daily for eight doses, although the few animals who did regain the ability to walk maintained it for the longest period of time. Overall, the best fractionation schedule was 500 rads (cGy) every other day for three doses, which gave improvement almost as good as the 1000 fads (cGy) in a single dose, albeit somewhat delayed, and a duration of improvement considerably longer than the single dose. Rubin [51] studied two doses: 500 rads (cGy) daily for 3 days and 100 rads (cGy) daily for 10 days. The tumour was exceedingly radiosensitive and he was able to cure most animals using either dose schedule. The higher dose was, however, more effective.
Controversies in the Management of Metastatic Spinal Cord Compression
Animal studies allow the study of SCC in a defined setting, thus eliminating the great variability seen in clinical practice due to factors such as patient variation, different primary sites, and multiple or single metastases. However, extrapolation from dose and fractionation studies in animals to man is difficult.
Human studies. In a retrospective analysis of 73 patients [52] with SCC due to lymphoma, it was found that patients receiving a total dose less than 2500 rads (cGy) had a considerably worse outcome than those treated by doses above 2500 rads, suggesting a dose-response relationship. This result should be observed with a degree of caution, as the intention in the study was for all patients to receive the higher dose,~ However, this was not achieved in all patients because of clinical deterioration or previous RT. In another retrospective study of 70 patients with SCC [10], there was no difference in outcome from two different fractionation schedules: 3000 cGy in ten daily fractions over 2 weeks, and 3000-4500 cGy over 2.0-4.5 weeks, administered as high dose fractions of 400-500 cGy for the first 3 days, with subsequent daily fractions of 200-300 cGy. Podd et al. [9], in a retrospective study of 158 patients, found no significant differences in terms of survival, pain relief, or change in neurological status when comparing treatment given over two to five fractions with that given over six or more fractions. However, the doses prescribed are not reported. Khan et al. [53] reported successful treatment of SCC with doses between 1500 and 2500 fads (cGy) over a period of 10-20 days, Responses tended to be seen at the lower end of this dose range in the lymphomas compared with other malignancies. Doses above 3000 rads (cGy) did not improve the chances of success. He concluded that, if patients are not going to respond to moderate doses, they do not respond at all. Makin [54] reported 87 patients, the majority of whom were treated by single fraction RT; 70 patients were treated by RT alone and 17 given RT after laminectomy. Twenty-seven per cent (17/63) treated by RT alone ultimately walked, despite the group having 47% of patients already with severe paraparesis on referral and only 38% receiving RT within 48 hours of established weakness. The result of 27% ambulatory patients post-treatment is comparable with other series treated with more protracted RT schedules. If the aim of treatment is merely palliation of pain, then single fraction therapy may be adequate [55].
Impact of Bony~Soft Tissue Compression In a retrospective evaluation of the pattern of disease on the MRI scans of 62 patients with SCC [56], two main patterns were identified: 73% had predominantly soft tissue epidural disease and 24% had bone collapse. A positive response to radiotherapy was observed in 64% of those with soft tissue epidural disease and only 27% of those with bone collapse.
Steroids The role of dexamethasone, the most commonly used corticosteroid, remains unclear. The use of high dose
79
steroids is supported by animal studies [50,57]. Delattre et al. [57], using a rat model, demonstrated that dexamethasone has a dose related beneficial effect associated with a reduction in the water content of the compressed spinal cord. Ushio [50] showed a definite but short lived improvement of cord compression with high dose steroids. Sorensen et al. [58] found high dose steroid therapy (a bolus of 96 mg intravenously followed by 96 mg orally for 3 days), given as an adjunct to radiotherapy in 57 patients in a single-blind trial, to results in 18% more patients improving in gait function after treatment; this improvement was longer lasting. However, significant side effects were seen in three (11%) patients, of which two were psychiatric and one a perforated gastric ulcer requiring surgery. A positive benefit of steroids has not been reported in any other randomized trial. In a randomized trial of 37 patients [591 assigned to an initial bolus of 10 mg or 100 mg of dexamethasone intravenously, followed by 16 mg daily orally, no differences were shown between the conventional and high dose group in terms of pain, ambulation, or bladder function. Heimdal et al. [60] treated 28 consecutive patients with high dose dexamethasone (96 mg intravenous loading dose, tailed off over 14 days). They observed eight events considered as serious and so abandoned the regimen in favour of a standard dexamethasone dose of 16 mg daily. They found no significant difference in the number of ambulant paients in the group that received the high dose.
Chemotherapy Cytotoxic chemotherapy has a role to play in the management of selected cases of metastatic SCC, usually as an adjunct to local therapy by surgery and/ or radiotherapy [2]. Primary chemotherapy for SCC has been advocated for lymphoma [61,62], germ cell tumours [46,63] and myeloma [64]. Currently, however, most of these patients will be treated by initial palliative RT as long as the extent of irradiation does not compromise the bone marrow reserve necessary for chemotherapy. In breast and prostate cancer there is a place for hormone therapy as an adjunct.to surgery and/or RT. Edelman [65] described a patient with paraplegia secondary to metastatic prostate cancer dramatically responding to stilboestrol. However the response to hormonal therapy is generally too slow for it to play a significant role in the acute management of SCC.
CONCLUSION Controversies persist in the management of SCC, largely because of the lack of large randomized prospective studies with long follow-up, and uniform methods of assessment of response to treatment. Such studies would help in assessing the optimum use of surgery and radiotherapy, the different surgical
80
approaches, and the various RT dose/fractionation schedules. In the absence of such studies, the following recommendations for management of SCC due to epidural metastases can be made: 1. Early diagnosis is important. 2. A multidisciplinary team, including clinical oncologists, neurosurgeons, radiologists, nurses, physiotherapists and occupational therapists, should be involved in the management of patients with SCC. 3. If available, MRI is the investigation of choice for most patients. 4. Treatment should be insitituted as soon as possible. 5. Whether surgery or radiotherapy is the primary treatment modality will depend on the patient's general condition, tumour type, time since the onset of symptoms and the locally available expertise. 6. If surgery is used, decompressive laminectomy is appropriate for posteriorly placed tumours, while anterior decompression with cord stabilization is the operation of choice for anteriorly placed tumours. 7. For radiotherapy, a short fractionated course of treatment, in the range of 20-30 Gy in four to ten fractions would be appropriate. 8. Unless otherwise contraindicated, a short course of steroids, such as dexamethasone 10 mg intravenously initially and then 16 mg daily for 5 days, should be used.
A. Makris and I. H. Kunkler
14. 15. 16. 17. 18. 19. 20. 21. 22.
23. 24. 25. 26. 27. 28.
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Controversies in the Management of Metastatic Spinal Cord Compression
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Clinical Oncology
Review Article Controversies in the Management of Metastatic Spinal Cord Compression A . M a k r i s 1 a n d I. H . K u n k l e r 2 tRoyal Marsden Hospital, Sutton and 2Western General Hospital, Edinburgh, UK
INTRODUCTION Spinal cord compression (SCC) due to epidural metastases is an oncological emergency, complicating malignant disease in about 5% of patients [1,2]. The optimal management remains controversial [3], but many studies suggest that early treatment is an important factor [4--11]. Although the syndrome of back pain, paraparesis, paraesthesia, and bladder and bowel dysfunction is characteristic of SCC, it may remain undiagnosed in patients already debilitated with metastatic cancer until it is too late for effective treatment. A high index of clinical suspicion is therefore needed.
DIAGNOSIS The diagnosis of SCC needs to be established rapidly. For many years, myelography was the investigation of choice, especially when a combined lumbar and cisternal approach was used. Myelography can provide additional information to clinical examination and radiographs of the spine, helping to avoid geographical misses [12-14]. Myelography is, however, an invasive procedure and is generally thought to carry a risk of further neurological deterioration. This has not been proven and there are no large studies to substantiate this. The neurological deterioration may be a feature of the natural history of rapidly progressive SCC in some patients. Increasingly, magnetic resonance imaging (MRI) is replacing myelography as the investigation of choice in suspected SCC [15]. MRI is non-invasive, has high intrinsic soft tissue contrast, and has the ability to image in non-axial planes. Compared with myelopathy, it can provide additional information about the presence of bone marrow involvement and paravertebral soft tissue masses [16]. A number of studies have shown that it is either superior or equivalent to myelography when SCC is suspected [15-20]. Two studies have, however, suggested better imaging by myelography alone [21], or myeCorrespondence and offprint requests to: Dr I. H. Kunkler, Consultant Clinical Oncologist, Department of Clinical Oncology, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
lography combined with postmyelographical spinal CT [22]. For most patients it would appear that, where available, MRI will be the investigation of choice.
MANAGEMENT The optimal treatment of cpidural SCC remains to be established. New methods of treatment are evolving, while the role of the conventional ones, decompressive laminectomy and radiotherapy (RT), is not fully defined. There is a lack of randomized studies [23] in the management of SCC on which to base treatment decisions. Most studies have been retrospective reviews of the experience of single institutions. Treatments are compared with previously reported series, making the results unreliable. Furthermore, the differences in the patient characteristics between the compared groups may be greater than the observed differences in outcome as a result of treatment. Assessment of response to treatment and outcome are not standardized, thus increasing the inaccuracies in comparing different series.
Surgery Until the 1960s, decompressive laminectomy, with or without excision of turnout, was the main treatment of malignant SCC [1,24-29] The outcome after laminectomy was disappointing, which led to suggestions that there may be a role for postoperative radiotherapy in selected patients [25,26]. A number of restrospective studies failed to show any significant difference between primary radiotherapy and surgery, with or without postoperative RT, in response to treatment and survival [4,30,31]. In a large retrospective analysis of 31 series reported in the literature prior to 1984, comprising over 2300 patients with spinal metastases [32], it was concluded that RT is as effective as surgery plus RT. The authors do, however, comment that many large series were not included in the analysis 'because of imprecise definition of either the materials and methods or the results'. Findlay [3] reviewed all papers dealing with malig-
78 nant SCC between 1960 and 1983. He included in the final analysis, which totalled 1816 patients, only those papers in which sufficiently precise data were presented to allow patients to be categorized into one of three easily defined neurological groups both prior to and following therapy. Success or failure of therapy was judged solely by transference of patients between categories. He showed that only 32% and 38% respectively of those treated by laminectomy alone or laminectomy with RT were able to walk at the end of treatment, compared wtih 51% of those treated by RT alone. Furthermore, 26% of the patients treated by laminectomy alone and 20% of those treated by laminectomy and RT deteriorated by a full grade following treatment, compared with 17% by RT alone. Sorensen et al. [7] reviewed all medical records of patients treated for metastatic SCC in the eastern part of Denmark between 1979 and 1985. A total of 345 were evaluated. Although patients treated with laminectomy followed by RT seemed to respond better than those treated by RT or laminectomy alone, when their pretreatment motor function was taken into account no significant difference was found between the three groups. In the subgroup of non-ambulatory patients, however, a significantly better restoration of gait was observed in patients treated with a combination of laminectomy and RT than RT alone. A longer survival in the group treated with the combination of laminectomy and RT may reflect that these patients had less advanced disease and were in better medical condition and therefore had a better potential of regaining function. This study also failed to confirm Findlay's finding that more patients deteriorated after laminectomy than after RT. Eighteen per cent of their patients were neurologically worse after RT, compared with 10% after laminectomy and 11% with combined treatment. Landmann et al. [33], in a retrospective review of 140 patients with 153 episodes of SCC, found a better outcome following decompressive laminectomy and RT (126 patients) than following RT alone (27 patients). The validity of this study is to be questioned on two counts. First, patients may have been treated by RT only because of poor prognostic factors; secondly, there is a large imbalance in the numbers in the two groups. Details of surgical mortality or morbidity are often not reported. Where they are reported, mortality is 6%-8% [24,34,35]. Morbidity, mainly in the form of wound infection, dehiscence and delayed healing, is of the order of 10%-15% [36,37]. In a study of 80 consecutive patients with a single thoracic metastasis causing SCC, all treated by standard decompressive laminectomy with no attempt at stabilization of the spine, Findlay [38] has shown that, in the presence of vertebral collapse, there is a much reduced chance of regaining the ability to walk, a much greater possibility of further neurological deterioration, and a major increase in the incidence of postoperative spinal instability. Two approaches to overcome this problem are available: the use of posterior spinal stabilization [39-41], and the more technically aggressive anterior surgical approaches to the spine, either by trans-
A. Makris and I. H. Kunkler thoracic or thoraco-abominal approach. This is a logical approach in anteriorly situated tumours, where a posterior approach would leave the spine unstable. Several groups have reported their experience with anterior decompression and stabilization for anteriorly situated tumours causing SCC, and the results appear encouraging in selected patients [35,37,42-47]. Postoperative mortality for this aggressive approach varies from 7% to 30% [35,47]. In the only reported randomized prospective study [23] comparing laminectomy and RT with RT alone, no difference in response to treatment or survival was seen. This study was, however, too small (29 patients only) for the results to be of statistical significance, but it demonstrates that such a study is possible. A role for primary surgery may exist in paediatric tumours that invade the spinal canal via the neural foramen, compressing the spinal cord in a circumferential manner, allowing decompressive laminectomy to be an effective surgical approach [2]. Superior results were demonstrated in retrospective series for decompressive laminectomy alone or before medical therapy, compared with those who received RT and/ or chemotherapy without posterior decompression [2,48]. Surgery has a role in situations where there is no obvious primary, and histological diagnosis is required.
Radiotherapy Dose and Fractionation
Radiation was not used as a sole treatment of SCC prior to the 1960s, largely due to concern over radiation oedema [13,49], particularly if there was complete myelographic block [13]. Animal Studies. The concept of radiation oedema has been addressed in two studies using experimental animal models [50,51]. Neither of these was able to find any oedema of the tumour or nervous tissue occurring after radiation. Rubin [51], using a Murphy-Sturm lymphoma in a rat model, and Ushio et al. [50], using a less radiosensitive Walker 256 carcinoma in a rat model, went on to study the effects of fractionation and dose on the outcome of radiation therapy after SCC. Ushio [50] observed the best initial improvement with a 1000 rad (cGy) single dose, but relapse occurred rapidly. Poor initial improvement was observed with 200 rads (cGy) daily for eight doses, although the few animals who did regain the ability to walk maintained it for the longest period of time. Overall, the best fractionation schedule was 500 rads (cGy) every other day for three doses, which gave improvement almost as good as the 1000 fads (cGy) in a single dose, albeit somewhat delayed, and a duration of improvement considerably longer than the single dose. Rubin [51] studied two doses: 500 rads (cGy) daily for 3 days and 100 rads (cGy) daily for 10 days. The tumour was exceedingly radiosensitive and he was able to cure most animals using either dose schedule. The higher dose was, however, more effective.
Controversies in the Management of Metastatic Spinal Cord Compression
Animal studies allow the study of SCC in a defined setting, thus eliminating the great variability seen in clinical practice due to factors such as patient variation, different primary sites, and multiple or single metastases. However, extrapolation from dose and fractionation studies in animals to man is difficult.
Human studies. In a retrospective analysis of 73 patients [52] with SCC due to lymphoma, it was found that patients receiving a total dose less than 2500 rads (cGy) had a considerably worse outcome than those treated by doses above 2500 rads, suggesting a dose-response relationship. This result should be observed with a degree of caution, as the intention in the study was for all patients to receive the higher dose,~ However, this was not achieved in all patients because of clinical deterioration or previous RT. In another retrospective study of 70 patients with SCC [10], there was no difference in outcome from two different fractionation schedules: 3000 cGy in ten daily fractions over 2 weeks, and 3000-4500 cGy over 2.0-4.5 weeks, administered as high dose fractions of 400-500 cGy for the first 3 days, with subsequent daily fractions of 200-300 cGy. Podd et al. [9], in a retrospective study of 158 patients, found no significant differences in terms of survival, pain relief, or change in neurological status when comparing treatment given over two to five fractions with that given over six or more fractions. However, the doses prescribed are not reported. Khan et al. [53] reported successful treatment of SCC with doses between 1500 and 2500 fads (cGy) over a period of 10-20 days, Responses tended to be seen at the lower end of this dose range in the lymphomas compared with other malignancies. Doses above 3000 rads (cGy) did not improve the chances of success. He concluded that, if patients are not going to respond to moderate doses, they do not respond at all. Makin [54] reported 87 patients, the majority of whom were treated by single fraction RT; 70 patients were treated by RT alone and 17 given RT after laminectomy. Twenty-seven per cent (17/63) treated by RT alone ultimately walked, despite the group having 47% of patients already with severe paraparesis on referral and only 38% receiving RT within 48 hours of established weakness. The result of 27% ambulatory patients post-treatment is comparable with other series treated with more protracted RT schedules. If the aim of treatment is merely palliation of pain, then single fraction therapy may be adequate [55].
Impact of Bony~Soft Tissue Compression In a retrospective evaluation of the pattern of disease on the MRI scans of 62 patients with SCC [56], two main patterns were identified: 73% had predominantly soft tissue epidural disease and 24% had bone collapse. A positive response to radiotherapy was observed in 64% of those with soft tissue epidural disease and only 27% of those with bone collapse.
Steroids The role of dexamethasone, the most commonly used corticosteroid, remains unclear. The use of high dose
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steroids is supported by animal studies [50,57]. Delattre et al. [57], using a rat model, demonstrated that dexamethasone has a dose related beneficial effect associated with a reduction in the water content of the compressed spinal cord. Ushio [50] showed a definite but short lived improvement of cord compression with high dose steroids. Sorensen et al. [58] found high dose steroid therapy (a bolus of 96 mg intravenously followed by 96 mg orally for 3 days), given as an adjunct to radiotherapy in 57 patients in a single-blind trial, to results in 18% more patients improving in gait function after treatment; this improvement was longer lasting. However, significant side effects were seen in three (11%) patients, of which two were psychiatric and one a perforated gastric ulcer requiring surgery. A positive benefit of steroids has not been reported in any other randomized trial. In a randomized trial of 37 patients [591 assigned to an initial bolus of 10 mg or 100 mg of dexamethasone intravenously, followed by 16 mg daily orally, no differences were shown between the conventional and high dose group in terms of pain, ambulation, or bladder function. Heimdal et al. [60] treated 28 consecutive patients with high dose dexamethasone (96 mg intravenous loading dose, tailed off over 14 days). They observed eight events considered as serious and so abandoned the regimen in favour of a standard dexamethasone dose of 16 mg daily. They found no significant difference in the number of ambulant paients in the group that received the high dose.
Chemotherapy Cytotoxic chemotherapy has a role to play in the management of selected cases of metastatic SCC, usually as an adjunct to local therapy by surgery and/ or radiotherapy [2]. Primary chemotherapy for SCC has been advocated for lymphoma [61,62], germ cell tumours [46,63] and myeloma [64]. Currently, however, most of these patients will be treated by initial palliative RT as long as the extent of irradiation does not compromise the bone marrow reserve necessary for chemotherapy. In breast and prostate cancer there is a place for hormone therapy as an adjunct.to surgery and/or RT. Edelman [65] described a patient with paraplegia secondary to metastatic prostate cancer dramatically responding to stilboestrol. However the response to hormonal therapy is generally too slow for it to play a significant role in the acute management of SCC.
CONCLUSION Controversies persist in the management of SCC, largely because of the lack of large randomized prospective studies with long follow-up, and uniform methods of assessment of response to treatment. Such studies would help in assessing the optimum use of surgery and radiotherapy, the different surgical
80
approaches, and the various RT dose/fractionation schedules. In the absence of such studies, the following recommendations for management of SCC due to epidural metastases can be made: 1. Early diagnosis is important. 2. A multidisciplinary team, including clinical oncologists, neurosurgeons, radiologists, nurses, physiotherapists and occupational therapists, should be involved in the management of patients with SCC. 3. If available, MRI is the investigation of choice for most patients. 4. Treatment should be insitituted as soon as possible. 5. Whether surgery or radiotherapy is the primary treatment modality will depend on the patient's general condition, tumour type, time since the onset of symptoms and the locally available expertise. 6. If surgery is used, decompressive laminectomy is appropriate for posteriorly placed tumours, while anterior decompression with cord stabilization is the operation of choice for anteriorly placed tumours. 7. For radiotherapy, a short fractionated course of treatment, in the range of 20-30 Gy in four to ten fractions would be appropriate. 8. Unless otherwise contraindicated, a short course of steroids, such as dexamethasone 10 mg intravenously initially and then 16 mg daily for 5 days, should be used.
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