Metastatic Spinal Cord Compression Secondary to Lung Cancer By Flemming Bach, Niels Agerlin, Jens B. Sorensen, Torben B. Rasmussen, Per Dombernowsky, Per S. Sorensen, and Heine H. Hansen Purpose: Metastatic spinal cord compression (MSCC) is a disabling complication to cancer, the optimal treatment for which is not settled. An analysis was performed for all patients with MSCC secondary to lung cancer in East Denmark from 1979 to 1988. Patients and Methods: The total series included 102 cases with small-cell carcinoma (SCLC; 40%), adenocarcinoma (ACL; 26%), squamous cell carcinoma (SQLC; 18%) and large-cell carcinoma (LCC; 9%). Symptoms, clinical presentations, and therapeutic results are described. Results: The outcome of treatment depended fundamentally on the patient's neurologic condition at the time of the diagnosis. All patients with SCLC who were able to walk at the time of MSCC remained ambulatory, whereas 15% of the nonambulatory SCLC patients regained walking ability. In non-SCLC, 95% of patients continued to be able to walk, whereas 22% regained the ability to walk. No major differences in the immediate outcome of treatment between the various histologic types of lung cancer
METASTATIC
SPINAL cord compression (MSCC) is a disabling complication to cancer. The initial symptoms may be sparse, but without treatment the symptoms will progress to complete loss of spinal cord function below the level of the compression. The optimal treatment of choice for MSCC (decompressive laminectomy, radiotherapy [RT], chemotherapy, or a combination of all of them) is still not settled. In a large proportion of patients, the results of treatment are poor with regard to both response and quality of life.1-7 The main determinant for the neurologic outcome after treatment is the pretreatment neurologic status, whereas the prognosis of survival is related to the origin of the primary malignant disease.1, 2 The incidence of MSCC generally reported is approximately 5%, which frequently is observed in patients with lung, breast, prostate, and renal cancer.'",8- Although the incidence of lung cancer in industrialized countries is increasing,12-14 the treatment results in patients with MSCC have been elucidated poorly secondary to this malignancy. Accordingly, we analyzed the records of all patients with lung cancer and MSCC in the eastern part of Denmark during a 10-year period to describe the occurrence, symptoms, outcome of treatment, and prognosis with regard to the different treatment modalities and
histologic subtypes. PATIENTS AND METHODS The analysis included all patients with MSCC secondary to lung cancer who were admitted to departments of oncology, neurology, and neurosurgery in the eastern part of Denmark from January
and the different treatment modalities were observed; however, 82% of the patients with non-SCLC benefited from treatment with laminectomy followed by radiotherapy (RT) compared with either laminectomy (47%) or RT (39%) alone (P = .03, ? test). The group of patients who were treated with laminectomy followed by RT had a better survival (median value, 3.5; range, 0 to 132 months) than patients who were treated with either laminectomy (median value, 1.5; range, 0 to 32 months) or RT (median value, 1; range, 0 to 59 months) alone (P = .03, log-rank test). No significant difference was observed in survival between the various histologic types of lung cancer (P = .18, log-rank test). Conclusion: Despite a short survival, early diagnosis and immediate treatment is crucial because it may preserve the gait function in 97%of lung cancer patients who develop malignant spinal cord compression. J Clin Oncol 10:1781-1787. © 1992 by American Society of Clinical Oncology. 1979 through December 1988. The departments serve a population of 2.4 million. Spinal cord compression was diagnosed in 102 patients. The clinical diagnosis of MSCC was confirmed by lumbar metrizamide or Omnipaque (iohexol; Sanofi Winthrop Pharmaceuticals, New York, NY) myelography combined with cervical or cisternal myelography or postmyelographic computed tomographic (CT) scan in case of total blockage of the contrast medium after lumbar injection. When decompressive surgery was performed, the procedure took place immediately after the myelography. The technique used in all cases was a posterior laminectomy, with a mean extension of three vertebra (range, one to six vertebrae). No stabilizing instruments were inserted. Additional RT usually began within 5 to 8 days after the operation. In patients who were treated with RT alone, the first dose was given as soon as possible after the myelography as a single posterior field directed against the involved part of the spine, and included at least one adjacent vertebra above and below the epidural block. Beam sources were photon rays, using megavoltage x-rays, 1.2 mV to 6 mV. Tumor dose was 22 to 28 Gy in 4 to 7 fractions given during a 4- to 7-day period with a single fraction of 4 to 5.5 Gy. The majority of the patients received 5.5 Gy daily for 4 consecutive days. Surgery was performed regularly if the patient's malignant
From Department of Oncology, University HospitalHerlev, Departments of Neurosurgery, University Hospitals Glostrup and Hvidovre, and Departmentsof Neurosurgery,Oncology, and Neurology, Rigshospitalet, Copenhagen, Denmark. SubmittedAugust 19, 1991; accepted July 9, 1992. Address reprint requests to Flemming Bach, MD, Department of Oncology, University Hospital Herlev, DK-2730, Copenhagen, Denmark. © 1992 by American Society of ClinicalOncology. 0732-183X/92/1011-0018$3.00/0
Journalof Clinical Oncology, Vol 10, No 11 (November), 1992: pp 1781-1787
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1782 diagnosis was not histologically verified, or if RT had been applied previously against epidural metastases at the same spinal level. Patients who were paraplegic for more than 24 hours usually were not offered a laminectomy, but received RT instead. Corticosteroids (prednisone) were administered routinely in doses of 150 mg daily from the establishment of the diagnosis of MSCC and during treatment; the dose was tapered during a 3-week period. The symptoms and signs were evaluated on the basis of hospital records concerning the patients' rating of pain, motor disturbances, sphincter control, and sensory functions. Pain was categorized as (1) no pain at all; (2) localized back pain alone; and (3) radicular or root pain. The motor function was divided into four grades: (1) no motor deficit; (2) moderate deficit, walking ability preserved; (3) paraparesis, unable to walk; and (4) paraplegia. The sphincter function was classified into three grades: (1) normal function; (2) sphincter dysfunction; and (3) incontinence, bladder catheter required. The sensory function was classified as: (1) no sensory disturbance; (2) loss of sensation below a level corresponding to the lesion; and, (3) other sensory disturbances. Because the investigation was retrospective, it was not possible to evaluate all of the parameters adopted in all patients. The outcome of treatment was classified into two categories. (1) Benefit of treatment was defined as patients without progressive neurologic deficits and preserved gait after treatment and/or patients without gait before treatment regaining walking ability. (2) No benefit of treatment was defined as patients with progressive neurologic deficits and/or patients without walking ability after treatment. The median length of clinical follow-up was 2.5 months (range, 1 to 51 months). Survival follow-up was performed in all patients, and the last status took place in January 1991. Statistical evaluation was performed using log-rank life-table 2 analysis. The X test was used in evaluating the differences in the outcome of treatment. RESULTS Patients Characteristics
During the period of investigation, the incidence of lung cancer in Denmark seemed to stabilize in men but
Fig 2. Age (10-year intervals) and sex distribution of 102 patients with spinal cord compression secondary to lung cancer. E, Male; E, female.
increase in women. 14 However, the incidence of MSCC did not increase (Fig 1), and the frequency obtained in the subgroup of patients with MSCC secondary to small-cell lung carcinoma (SCLC) at 2.8%, which was based on the number of patients who were registered in the area during the period of investigation, was similar to that from a previous study (incidence 3.5%) of the same histologic subtype of lung cancer in almost the same geographic area in Denmark.' The total series consisted of 102 patients, 18 women and 84 men, with a median age of 60 years (range, 33 to 81). The age and sex distribution is shown in Fig 2; the highest incidence was in the fifth decade. In Table 1, the distribution according to histologic subtype of lung cancer is demonstrated. In seven cases, the histologic type was not available, and these patients were excluded from the statistical evaluation when calculations included histologic subtypes. Ninety-eight percent of the patients had the malignant diagnosis established at the time of MSCC develop-
ment. The period from the primary malignant diagnosis
20 a
15
Age groups (10 years intervals)
to the MSCC varied considerably according to the different histologic types (Fig 3). It was predominantly patients with SCLC who developed MSCC initially, 75% within the first month, and 87% within the first 3 months. In contrast, patients with squamous cell carcinoma (SQLC) passed 30 months before a similar fraction of patients had developed MSCC. Patients' delay
/--
o
_
10
Table 1. Histologic Subclassification in 102 Lung Cancer Patients With Spinal Cord Compression
5
78
79
80
81
82
83 84 Years
85
86
87
88
89
Fig 1. Incidence of spinal cord compression secondary to lung cancer in the eastern part of Denmark from 1979 to 1988.
SCLC Non-SCLC Adenocarcinoma SQLC LCC Unclassified subtype
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41 54 27 18 9 7
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SPINAL CORD COMPRESSION AND LUNG CANCER .- A
Table 3. Sensory Deficits in 102 Patients With Lung Cancer and Spinal Cord Compression According to Histologic Subgroups
1
0
6
12
18
24
30
36 42 Months
48
54
60
66
72
78
Fig 3. Time interval between the primary malignant diagnosis and the development of spinal cord compression in 95 lung cancer patients. (---), SQLC; (-), SCLC; (....), adenocarcinoma; (---), LCC.
(time from first symptom indicating incipient spinal compression to consulting a doctor) and doctors' delay (time from first consultation with symptoms that indicated incipient MSCC to establishment of the diagnosis) were 18 and 3 days (median), respectively. Symptoms and ClinicalFindings The majority of patients had pain at the time of MSCC (77%), either localized back pain alone (37%) or back pain with radicular pain (40%). In 60%, the first motor complaint was unsteadiness in walking. At the time of diagnosis of MSCC, almost two thirds of the patients had severe motor deficits and were unable to walk, although one-third had moderate motor deficits with gait function still preserved. Severe sphincter dysfunction occurred in 59% of the patients (incontinence or retention that required catheterization). Twelve percent had mild dysfunction (eg, urgency of normal bladder sensation) (Table 2). Sixty-six percent of the patients had sensory loss below the level of the spinal compression and 24% had other sensory disturbances, whereas 10% had normal sensibility (Table 3). When we focused on the histologic subtypes, a distinct segmental level of sensory loss was Table 2. Neurologic Symptoms and Clinical Findings in 102 Patients With Lung Cancer and Spinal Cord Compression Pain (%) 40 Radiculor pain 37 Local back pain alone 23 No pain
Sensory (%) 66 Loss of sensation below a spinal level 24 Othersensory disturbances 10 Normalsensibility
Sphincter Motor Functions (%) Disturbances (%) 63 Paraplegic/no gait
59 Retention/ catheter
33 Mild deficit/ gait preserved
12 Moderate
4 No deficit
29 No symptoms
Sensory Deficit
SCLC (%)
Normal Sensory disturbances Loss of sensation below a spinal level
9 28 63
ACL SQLC (%) (%)
LCC Total (%) (%)
8 34 58
11 33 56
16 6 78
10 24 66
demonstrated at the time of diagnosis of MSCC mainly in patients with SQCL (78%; Table 3). The majority of the epidural metastases (74%) were located in the thoracic region, and SQCL was also the type with the highest number of metastases in the upper thoracic region (60%). In contrast, patients with SCLC and adenocarcinoma (ACL) had no obvious predominant localization of spinal cord compression (Table 4). In no case was MSCC associated with kyphosis. In Table 5, the anatomic localization of the compressions are shown. The majority of the tumors were localized circularly (51%) or in the posterior/lateral region (27%) of the spinal canal. Myelography was performed in 83% of patients, and CT scan was performed with subarachnoid contrast injection in 14%. A total blockage in the subarachnoid space was observed in 64%, a partial blockage in 14%, and multiple blockages in 4%. Treatment Among the 95 patients who were eligible for response, 30 patients had a laminectomy performed, 39 received RT, and 26 had laminectomy followed by RT. All received corticosteroids in doses of 150 mg prednisone while on treatment for MSCC. Four patients were not assessable for response to treatment (three with SCLC, one with SQLC), and three patients did not receive any treatment. No difference in age or sex was demonstrated when the various histologic types of lung cancer were compared with the different treatment modalities. Only 26% Table 4. Anatomic Level of Spinal Cord Compression in 102 Patients With Lung Cancer Level Cervical Upper thorax Lower thorax Lumbar Several Upper thoracic Lower thoracic
SCLC (%)
ACL (%)
8 43 27 14 8
46 31 23 -
SQLC (%) 60 16 24 * t
•Thoracic vertebra 1-6. tThoracic vertebra 7-12.
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LCC (%)
Total (%)
33 56 11 -
5 44 30 18 3
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Table 5. Intraspinal Anatomic Localization of Spinal Cord Compression in Patients With Lung Cancer Who Had a Posterior Laminectomy
Table 7. Treatment Effect on Bladder Function (%) in 102 Lung Cancer Patients With Spinal Cord Compression
SCLC
ACL
SQLC
LCC
Total
(%)
(%)
(%)
(%)
(%)
2 4 2 11 25
-
-
2 6 4
2 4 16 27 51
Anterior Posterior Anterior/lateral Posterior/lateral Circular
8 2 14
4 8 8
of the patients who had a laminectomy were able to walk before treatment, in contrast to 49% and 46%, respectively, of the patients who were treated with RT alone or laminectomy followed by RT (Table 6). The motor and bladder function response is listed in Tables 6 and 7. Forty-one percent were ambulatory before treatment, and 52% were ambulatory after treatment. Patients with SCLC retained the ability to walk, which differed from patients with non-SCLC, of whom 5% lost this ability. In patients with SCLC, 15% regained the ability to walk compared with 22% of the non-SCLC patients (Table 8). Accordingly, the pretreatment motor deficits seemed to be the most important determinant for the posttreatment motor function; nearly all of the patients who were able to walk before Table 6. Immediate Outcome According to Different Treatment Modalities, Histology, and Pretreatment Walking Ability (gait) Pretreatment
Laminectomy SCLC Non-SCLC ACL SQLC LCC Radiotherapy SCLC* Non-SCLC ACL SQLC* LCC Laminectomy + RT SCLCt Non-SCLC ACL SQLC LCC
Total
Gait (%)
27 10 17 7 6 4 40 16 24 13 9 2 25 14 11 6 3 2 92
26 33 24 0 50 25 49 50 46 54 22 50 46 50 45 33 67 50 40
+/-
7/20 3/7 4/13 0/7 3/3 1/3 18/22 8/8 10/14 7/6 2/7 1/1 12/13 7/7 5/6 2/4 2/1 1/1 37/55
+ Benefit
- Benefit
No.
%
No.
%
13 5 8 2 5 1 17 8 9 6 3 0 16 7 9 5 2 2 46
48 50 47 29 83 25 46 50 39 46 33 0 67 50 82 83 67 100 50
14 5 9 5 1 3 20 6 14 7 5 2 8 6 2 1 1 0 42
52 50 53 71 17 75 54 38 61 54 56 100 33 43 18 17 33 0 46
NOTE. In the seven patients with unknown histologic subtype, three had laminectomy, two had radiotherapy, and two had laminectomy followed by radiotherapy. Four patients were not assessable for response: *two patients with SCLC and one with SQLC in the group treated with radiotherapy; tone patient with SCLC treated with laminectomy plus radiotherapy.
Normal Dysfunction Catheter
Before Treatment
After Treatment
29 12 59
30 22 48
treatment retained this ability. No major changes were observed after treatment in the number of patients with normal sphincter function and in the number who needed a catheter (Table 7). Treatment outcome of the different treatment modalities among the various histologic types is shown in Table 6. In patients with SCLC, the outcome of treatment seemed to be independent of treatment modalities, whereas in patients with non-SCLC, the combined treatment with laminectomy followed by RT was superior. Approximately 82% benefited from the combined treatment (P = .03, x 2 test) compared with only 39% of patients treated with RT and 47% who were treated with laminectomy. In regard to survival, the group of patients who were treated with laminectomy plus RT, survived longer (median value, 3.5 months; range, 0 to 132 months) than patients who were treated with either laminectomy (median value, 1.5 months; range, 0 to 32 months) or RT (median value, 1 month; range, 0 to 59) (P = .03, log-rank test, laminectomy followed by RT v laminectomy or RT alone; Fig 4). Figure 5 demonstrates the probability of survival among the different histologic subtypes of lung cancer after the MSCC. Patients with SQCL apparently had poorer survival (median value, 1 month; range, 0 to 32 months) compare with patients with SCLC (median value, 2.5 months; range, 0 to 132 months), ACL (median value, 1.5 month; range, 0 to 19 months), and large-cell carcinoma (LCC; median value, 1.5 month; range, 0 to 8 months). Still, the differences were not significantly different (P = .06, log-rank test, SQCL v all others). No major difference was demonstrated in the number of long-term survivors subsequent to the diagnosis of MSCC; only 9% survive for more than 12 months. These results also reflect the conclusion that patients with SQCL seem to develop MSCC with some delay time. Table 8. Ability of Gait in 102 Lung Cancer Patients Who Were Treated for Spinal Cord Compression.
Retained walking ability Regained walking ability
All (%)
SCLC (%)
Non-SCLC (0)
97 19
100 15
95 22
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SPINAL CORD COMPRESSION AND LUNG CANCER
Months Fig 4. Probability of survival (%) from the diagnosis of spinal cord compression according to the different treatment modalities (P = .03, log-rank test, laminectomy followed by RT v laminectomy or RT alone). 0, RT; A, laminectomy; 0, RT plus laminectomy.
DISCUSSION
The observation that lung cancer, especially SCLC and ACL, often and with increasing frequency metastasizes to the CNS possibly because of prolonged survival is well known. 15 ,16 The frequency of 2.8% in the present study of patients with SCLC who developed MSCC is in accordance with a previous report that covered the same geographic area (3.5%)." Although SCLC is not the most common type of lung cancer in Denmark (SQLC 30%, ACL 25%, SCLC 20%, and LCC 5%),14 it is the
most frequent cell type that accounted for MSCC (40%). The fact that patients with non-SCLC were not cared for routinely in departments of oncology in Denmark might result in a diminished referral of patients with MSCC and, thereby, an underestimation of the real incidence in patients with non-SCLC. Spinal cord compression is usually accompanied by pain, either radicular or localized back pain, disturbance of sensation, loss of walking ability, and sphincter 100-
40 0 80
40-
0
1
2
3
4
5
6
7
8
9
10
11
12
Months Fig 5. Probability of survival (%) from the diagnosis of spinal cord compression according to histologic subtypes of lung cancer (P = .06,
log-rank test, SQLC v all others). 0, SQLC; 0, SCLC; A, adenocarcinoma; O, LCC.
dysfunctions. Nevertheless, asymptomatic intraspinal metastases were supposed to be even more common than symptomatic metastases, and pain may be the only symptom for a considerable period.17 Some investigations strongly recommend myelography in patients with the onset of back pain because spinal epidural metastases have been detected in more than 50%, despite the fact that one third of the patients had no evidence of myelopathy. Furthermore, the use of both CT scans and myelography has been recommended in a recent report."8 Consequently, changes in pain pattern, eg, from local to radicular pain, can be the first indicators of medullary compression and should lead to confirmatory diagnostic procedures, as should the occurrence of gait ataxia. In two thirds of the patients, a distinct segmental level of sensory loss was found, although this level was predominantly present in patients with SQCL (78%). It is uncertain whether this clinical manifestation is associated with the relatively late tendency to develop MSCC and concomitant slow symptom progression in SQCL patients. No difference in the number of total blockages was demonstrated in the various histologic groups. As previously mentioned, the initial symptoms may be sparse, and some studies report extensive patient and doctor delays. In this series, the patients' delay was 18 days and the doctors' delay 3 days. These in comparison with short delays from other studies may reflect that most patients developed MSCC while being treated for primary malignant disease, or during control as outpatients in relatively close connection to the hospital. Some variations were observed between the different types of lung cancer. In SCLC, 75% of the cases of MSCC was diagnosed during the first month after the primary malignant diagnosis was established, which contrasts with 12 months for ACL and 21 months for SQLC. No major differences were noted when the histologic subtypes or treatment methods were compared according to age and sex. However, some referral bias was observed in the patients' pretreatment walking abilities; Patients who received RT and offered laminectomy followed by RT were probably in a better neurologic condition than patients who had a laminectomy alone (positive gait function 49%, 46%, and 26%, respectively). The usual treatment for MSCC has been laminectomy with or without postoperative irradiation, 3,4,6,1 9-22 although a number of investigators have claimed that RT alone is as effective. 3,5,23,24 In this study, all patients who
were offered surgery had a posterior laminectomy performed because anterior laminectomy is not used rou-
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BACH ET AL
tinely in this category of patients in Denmark.25 The majority of the spinal compressions were localized circular or posterior/lateral (78%) compared with anterior or anterior/lateral (18%). It is not known if these patients would have benefited from anterior decompressive surgery; however, the poor survival prognosis in this group of patients has to be taken into consideration when the benefits or risks of complications of performing an anterior laminectomy with stabilizing material and the routinely performed laminectomy are compared. The value of chemotherapy especially in SCLC as a treatment of MSCC is not clear. Ongoing investigations are performed to explore this issue, 26 but the overall results of treatment, without regard to the different treatment modalities, were preservation of gait function in 97% of those patients who were ambulatory before treatment and restoration of walking abilities in 19% of the patients who were unable to walk before treatment. These results are identical to treatment response in previous series, 5,232, 4,27-30 and although no previous re-
ports have dealt with the different histologic subtypes in lung cancer, our findings confirm that the results in regard to walking ability depend on the patient's pretreatment ambulatory status. The significance of the primary tumor type as an indicator of treatment outcome is not derived from the present study. In a study by Greenberg et a15 no difference was demonstrated between patients with highly or less radiosensitive tumors. Additionally, the
role of the dose and schedule of corticosteroids is uncertain. Greenberg et al described very high response rates and immediate pain relief using high-dose dexamethasone during the initial RT both in groups with highly or less radiosensitive tumors. Whether the outcome was caused by primary corticosteroid tumor shrinkage or reduction of edema with secondary improved reoxygenation is unknown. No long-term follow-up concerning the outcome of treatment in regard to walking ability and bladder function was performed in the present study. It is known that recovery may be delayed, 31,32 and some of the patients without walking ability immediately after treatment may have regained this ability. Although no definite conclusions can be drawn based on the present study, the treatment results in SCLC were independent of the different treatment modalities, in contrast to non-SCLC in which the combined approach of laminectomy followed by RT seemed to be superior to either one of the two treatments. Spinal cord compression still constitutes one of the major problems in neuro-oncology, but immediate treatment is crucial to preserve neurologic functions. When the literature is reviewed, only one prospective, randomized, clinically controlled study that compares laminectomy plus RT or RT alone has been published. 28 No difference in the outcome of treatment was observed, which still leaves controversy regarding the best form of treatment.
REFERENCES 1. Bach F, Larsen BH, Rohde K, et al: Metastatic spinal cord compression. Occurrence, symptoms, clinical presentations and prognosis in 398 patients with spinal cord compression. Acta Neurochir 107:37-43, 1990 2. S0rensen PS, Bcrgesen SE, Rohde K, et al: Metastatic epidural spinal cord compression: Results of treatment and survival. Cancer 65:1502-1508, 1990 3. Dunn RC, Kelly WA, Wohns RNW, et al: Spinal epidural neoplasia. A 15-year review of the results of surgical therapy. J Neurosurg 52:47-51, 1980 4. Stark RJ, Henson RA, Evans SJW: Spinal metastases. A retrospective survey from a general hospital. Brain 105:189-213, 1982 5. Greenberg HS, Kim JH, Posner JB: Epidural cord compression from epidural tumor: Results with a new treatment protocol. Ann Neurol 8:361-366, 1980 6. Livingston KE, Perrin RG: The neurosurgical management of spinal metastases causing cord and cauda equina compression. J Neurosurg 3:839-843, 1978 7. Nather A, Base K: The results of decompression from metastatic extradural tumors. Clin Orthop 169:103-108, 1982 8. Barron KD, Hirano A, Araki S, et al: Experiences with
metastatic neoplasms involving the spinal cord. Neurology 9:91106, 1959 9. Bansal S, Brady LW, Olsen A, et al: The treatment of metastatic spinal cord tumors. JAMA 202:686-688, 1967 10. Posner J: Neurological complications of systemic cancer. Med Clin North Am 55:625-646, 1971 11. Pedersen AG, Bach F, Melgaard B: Frequency, diagnosis and prognosis of spinal cord compression in small cell lung bronchogenic carcinoma. Cancer 55:1818-1822, 1985 12. Muir C, Waterhouse J, Mack T, et al: Cancer incidence in five continents, vol 5. Lyon, France, IARC Scientific Publications, 1987 13. Silverberg E, Lubera JA: Cancer statistics 1988. Cancer 38:5-22, 1988 14. Frolund C, Krasnik M, Rosenstock, et al: Lung cancer in Denmark, 1943-1986. Cancer statistic no. 26. Danish Med Bull 152:1241-1245, 1990 15. Pedersen AG: Diagnostic procedures in the detection of CNS metastases from small cell lung cancer, in Hansen HH (ed): Lung Cancer. Basic and Clinical Aspects. Boston, MA, Martinus Nijhoff, 1986, pp 153-182 16. Sorensen JB, Hansen HH, Hansen M, et al: Brain me-
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SPINAL CORD COMPRESSION AND LUNG CANCER tastases in adenocarcinoma of the lung: Frequency, risk groups, and prognosis. J Clin Oncol 6:1474-1480, 1988 17. Rodichock LD, Ruckdeschel JC, Harper GR, et al: Early detection and treatment of spinal epidural metastases; the role of myelography. Ann Neurol 20:696-702, 1986 18. Grossman SA, Weissmann DE, Wang H, et al: Early diagnosis of spinal epidural metastases using out-patient computed tomographic myelography. Eur J Cancer 26:495-499, 1990 19. Wright RL: Malignant tumors in the spinal extradural space. Results of surgical treatment. Ann Surg 157:227-231, 1963 20. Brice J, McKissock WS: Surgical treatment of malignant extradural spinal tumours. Br Med J 1:1341-1344, 1965 21. Smith R: An evaluation of surgical treatment for spinal cord compression due to metastatic carcinoma. J Neurol Neurosurg Psychiatr 28:152-158, 1965 22. Hall AJ, Mackay NNS: The results of laminectomy for compression of cord and cauda equina by extradural malignant tumor. J Bone Joint Surg 55:497-595, 1973 23. Gilbert RW, Kim JH, Posner J: Epidural spinal cord compression from metastatic tumor: Diagnosis and treatment. Ann Neurol 3:40-51, 1978 24. Cobb CA, Leavens ME, Eckles N: Indications for nonoperative treatment of spinal cord compression due to breast cancer. J Neurosurg 47:653-658, 1977
25. Alho A: Surgical treatment of spinal metastases in the Nordic countries. Nord Med 106:289-290, 1991 26. Hansen SW, Larsen SH: The neurological outcome of spinal cord compression in patients with lung cancer. Sixth World Conference on Lung Cancer, Melbourne, Australia, November 1991 (abstr) 27. Shaw MDM, Rose JE, Paterson A: Metastatic extradural malignancy of the spine. Acta Neurochir 52:113-120, 1980 28. Young RF, Post EM, King GA: Treatment of epidural metastases. Randomized prospective comparison of laminectomy and radiotherapy. J Neurosurg 53:741-748, 1980 29. Tang SG, Byfield JE, Sharp TR, et al: Prognostic factors in the management of metastatic epidural spinal cord compression. J Neuro Oncol 1:21-28, 1983 30. Constans JP, Divitis ED, Donzelli R, et al: Spinal metastases with neurological manifestations. Review of 600 cases. J Neurosurg 59:111-118, 1983 31. Larsen SH, Rasmusson B, Sorensen PS: Recovery of gait after radiotherapy in paraplegic patients with metastatic spinal cord compression. Neurology 40:1234-1237, 1990 32. Tarlov M, Herz E: Spinal cord compression studies. IV. Outlook with complete paralysis in man. Arch Neurol Psychiatry 72:43-51, 1954
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METASTATIC
SPINAL cord compression (MSCC) is a disabling complication to cancer. The initial symptoms may be sparse, but without treatment the symptoms will progress to complete loss of spinal cord function below the level of the compression. The optimal treatment of choice for MSCC (decompressive laminectomy, radiotherapy [RT], chemotherapy, or a combination of all of them) is still not settled. In a large proportion of patients, the results of treatment are poor with regard to both response and quality of life.1-7 The main determinant for the neurologic outcome after treatment is the pretreatment neurologic status, whereas the prognosis of survival is related to the origin of the primary malignant disease.1, 2 The incidence of MSCC generally reported is approximately 5%, which frequently is observed in patients with lung, breast, prostate, and renal cancer.'",8- Although the incidence of lung cancer in industrialized countries is increasing,12-14 the treatment results in patients with MSCC have been elucidated poorly secondary to this malignancy. Accordingly, we analyzed the records of all patients with lung cancer and MSCC in the eastern part of Denmark during a 10-year period to describe the occurrence, symptoms, outcome of treatment, and prognosis with regard to the different treatment modalities and
histologic subtypes. PATIENTS AND METHODS The analysis included all patients with MSCC secondary to lung cancer who were admitted to departments of oncology, neurology, and neurosurgery in the eastern part of Denmark from January
and the different treatment modalities were observed; however, 82% of the patients with non-SCLC benefited from treatment with laminectomy followed by radiotherapy (RT) compared with either laminectomy (47%) or RT (39%) alone (P = .03, ? test). The group of patients who were treated with laminectomy followed by RT had a better survival (median value, 3.5; range, 0 to 132 months) than patients who were treated with either laminectomy (median value, 1.5; range, 0 to 32 months) or RT (median value, 1; range, 0 to 59 months) alone (P = .03, log-rank test). No significant difference was observed in survival between the various histologic types of lung cancer (P = .18, log-rank test). Conclusion: Despite a short survival, early diagnosis and immediate treatment is crucial because it may preserve the gait function in 97%of lung cancer patients who develop malignant spinal cord compression. J Clin Oncol 10:1781-1787. © 1992 by American Society of Clinical Oncology. 1979 through December 1988. The departments serve a population of 2.4 million. Spinal cord compression was diagnosed in 102 patients. The clinical diagnosis of MSCC was confirmed by lumbar metrizamide or Omnipaque (iohexol; Sanofi Winthrop Pharmaceuticals, New York, NY) myelography combined with cervical or cisternal myelography or postmyelographic computed tomographic (CT) scan in case of total blockage of the contrast medium after lumbar injection. When decompressive surgery was performed, the procedure took place immediately after the myelography. The technique used in all cases was a posterior laminectomy, with a mean extension of three vertebra (range, one to six vertebrae). No stabilizing instruments were inserted. Additional RT usually began within 5 to 8 days after the operation. In patients who were treated with RT alone, the first dose was given as soon as possible after the myelography as a single posterior field directed against the involved part of the spine, and included at least one adjacent vertebra above and below the epidural block. Beam sources were photon rays, using megavoltage x-rays, 1.2 mV to 6 mV. Tumor dose was 22 to 28 Gy in 4 to 7 fractions given during a 4- to 7-day period with a single fraction of 4 to 5.5 Gy. The majority of the patients received 5.5 Gy daily for 4 consecutive days. Surgery was performed regularly if the patient's malignant
From Department of Oncology, University HospitalHerlev, Departments of Neurosurgery, University Hospitals Glostrup and Hvidovre, and Departmentsof Neurosurgery,Oncology, and Neurology, Rigshospitalet, Copenhagen, Denmark. SubmittedAugust 19, 1991; accepted July 9, 1992. Address reprint requests to Flemming Bach, MD, Department of Oncology, University Hospital Herlev, DK-2730, Copenhagen, Denmark. © 1992 by American Society of ClinicalOncology. 0732-183X/92/1011-0018$3.00/0
Journalof Clinical Oncology, Vol 10, No 11 (November), 1992: pp 1781-1787
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1782 diagnosis was not histologically verified, or if RT had been applied previously against epidural metastases at the same spinal level. Patients who were paraplegic for more than 24 hours usually were not offered a laminectomy, but received RT instead. Corticosteroids (prednisone) were administered routinely in doses of 150 mg daily from the establishment of the diagnosis of MSCC and during treatment; the dose was tapered during a 3-week period. The symptoms and signs were evaluated on the basis of hospital records concerning the patients' rating of pain, motor disturbances, sphincter control, and sensory functions. Pain was categorized as (1) no pain at all; (2) localized back pain alone; and (3) radicular or root pain. The motor function was divided into four grades: (1) no motor deficit; (2) moderate deficit, walking ability preserved; (3) paraparesis, unable to walk; and (4) paraplegia. The sphincter function was classified into three grades: (1) normal function; (2) sphincter dysfunction; and (3) incontinence, bladder catheter required. The sensory function was classified as: (1) no sensory disturbance; (2) loss of sensation below a level corresponding to the lesion; and, (3) other sensory disturbances. Because the investigation was retrospective, it was not possible to evaluate all of the parameters adopted in all patients. The outcome of treatment was classified into two categories. (1) Benefit of treatment was defined as patients without progressive neurologic deficits and preserved gait after treatment and/or patients without gait before treatment regaining walking ability. (2) No benefit of treatment was defined as patients with progressive neurologic deficits and/or patients without walking ability after treatment. The median length of clinical follow-up was 2.5 months (range, 1 to 51 months). Survival follow-up was performed in all patients, and the last status took place in January 1991. Statistical evaluation was performed using log-rank life-table 2 analysis. The X test was used in evaluating the differences in the outcome of treatment. RESULTS Patients Characteristics
During the period of investigation, the incidence of lung cancer in Denmark seemed to stabilize in men but
Fig 2. Age (10-year intervals) and sex distribution of 102 patients with spinal cord compression secondary to lung cancer. E, Male; E, female.
increase in women. 14 However, the incidence of MSCC did not increase (Fig 1), and the frequency obtained in the subgroup of patients with MSCC secondary to small-cell lung carcinoma (SCLC) at 2.8%, which was based on the number of patients who were registered in the area during the period of investigation, was similar to that from a previous study (incidence 3.5%) of the same histologic subtype of lung cancer in almost the same geographic area in Denmark.' The total series consisted of 102 patients, 18 women and 84 men, with a median age of 60 years (range, 33 to 81). The age and sex distribution is shown in Fig 2; the highest incidence was in the fifth decade. In Table 1, the distribution according to histologic subtype of lung cancer is demonstrated. In seven cases, the histologic type was not available, and these patients were excluded from the statistical evaluation when calculations included histologic subtypes. Ninety-eight percent of the patients had the malignant diagnosis established at the time of MSCC develop-
ment. The period from the primary malignant diagnosis
20 a
15
Age groups (10 years intervals)
to the MSCC varied considerably according to the different histologic types (Fig 3). It was predominantly patients with SCLC who developed MSCC initially, 75% within the first month, and 87% within the first 3 months. In contrast, patients with squamous cell carcinoma (SQLC) passed 30 months before a similar fraction of patients had developed MSCC. Patients' delay
/--
o
_
10
Table 1. Histologic Subclassification in 102 Lung Cancer Patients With Spinal Cord Compression
5
78
79
80
81
82
83 84 Years
85
86
87
88
89
Fig 1. Incidence of spinal cord compression secondary to lung cancer in the eastern part of Denmark from 1979 to 1988.
SCLC Non-SCLC Adenocarcinoma SQLC LCC Unclassified subtype
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41 54 27 18 9 7
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SPINAL CORD COMPRESSION AND LUNG CANCER .- A
Table 3. Sensory Deficits in 102 Patients With Lung Cancer and Spinal Cord Compression According to Histologic Subgroups
1
0
6
12
18
24
30
36 42 Months
48
54
60
66
72
78
Fig 3. Time interval between the primary malignant diagnosis and the development of spinal cord compression in 95 lung cancer patients. (---), SQLC; (-), SCLC; (....), adenocarcinoma; (---), LCC.
(time from first symptom indicating incipient spinal compression to consulting a doctor) and doctors' delay (time from first consultation with symptoms that indicated incipient MSCC to establishment of the diagnosis) were 18 and 3 days (median), respectively. Symptoms and ClinicalFindings The majority of patients had pain at the time of MSCC (77%), either localized back pain alone (37%) or back pain with radicular pain (40%). In 60%, the first motor complaint was unsteadiness in walking. At the time of diagnosis of MSCC, almost two thirds of the patients had severe motor deficits and were unable to walk, although one-third had moderate motor deficits with gait function still preserved. Severe sphincter dysfunction occurred in 59% of the patients (incontinence or retention that required catheterization). Twelve percent had mild dysfunction (eg, urgency of normal bladder sensation) (Table 2). Sixty-six percent of the patients had sensory loss below the level of the spinal compression and 24% had other sensory disturbances, whereas 10% had normal sensibility (Table 3). When we focused on the histologic subtypes, a distinct segmental level of sensory loss was Table 2. Neurologic Symptoms and Clinical Findings in 102 Patients With Lung Cancer and Spinal Cord Compression Pain (%) 40 Radiculor pain 37 Local back pain alone 23 No pain
Sensory (%) 66 Loss of sensation below a spinal level 24 Othersensory disturbances 10 Normalsensibility
Sphincter Motor Functions (%) Disturbances (%) 63 Paraplegic/no gait
59 Retention/ catheter
33 Mild deficit/ gait preserved
12 Moderate
4 No deficit
29 No symptoms
Sensory Deficit
SCLC (%)
Normal Sensory disturbances Loss of sensation below a spinal level
9 28 63
ACL SQLC (%) (%)
LCC Total (%) (%)
8 34 58
11 33 56
16 6 78
10 24 66
demonstrated at the time of diagnosis of MSCC mainly in patients with SQCL (78%; Table 3). The majority of the epidural metastases (74%) were located in the thoracic region, and SQCL was also the type with the highest number of metastases in the upper thoracic region (60%). In contrast, patients with SCLC and adenocarcinoma (ACL) had no obvious predominant localization of spinal cord compression (Table 4). In no case was MSCC associated with kyphosis. In Table 5, the anatomic localization of the compressions are shown. The majority of the tumors were localized circularly (51%) or in the posterior/lateral region (27%) of the spinal canal. Myelography was performed in 83% of patients, and CT scan was performed with subarachnoid contrast injection in 14%. A total blockage in the subarachnoid space was observed in 64%, a partial blockage in 14%, and multiple blockages in 4%. Treatment Among the 95 patients who were eligible for response, 30 patients had a laminectomy performed, 39 received RT, and 26 had laminectomy followed by RT. All received corticosteroids in doses of 150 mg prednisone while on treatment for MSCC. Four patients were not assessable for response to treatment (three with SCLC, one with SQLC), and three patients did not receive any treatment. No difference in age or sex was demonstrated when the various histologic types of lung cancer were compared with the different treatment modalities. Only 26% Table 4. Anatomic Level of Spinal Cord Compression in 102 Patients With Lung Cancer Level Cervical Upper thorax Lower thorax Lumbar Several Upper thoracic Lower thoracic
SCLC (%)
ACL (%)
8 43 27 14 8
46 31 23 -
SQLC (%) 60 16 24 * t
•Thoracic vertebra 1-6. tThoracic vertebra 7-12.
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LCC (%)
Total (%)
33 56 11 -
5 44 30 18 3
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Table 5. Intraspinal Anatomic Localization of Spinal Cord Compression in Patients With Lung Cancer Who Had a Posterior Laminectomy
Table 7. Treatment Effect on Bladder Function (%) in 102 Lung Cancer Patients With Spinal Cord Compression
SCLC
ACL
SQLC
LCC
Total
(%)
(%)
(%)
(%)
(%)
2 4 2 11 25
-
-
2 6 4
2 4 16 27 51
Anterior Posterior Anterior/lateral Posterior/lateral Circular
8 2 14
4 8 8
of the patients who had a laminectomy were able to walk before treatment, in contrast to 49% and 46%, respectively, of the patients who were treated with RT alone or laminectomy followed by RT (Table 6). The motor and bladder function response is listed in Tables 6 and 7. Forty-one percent were ambulatory before treatment, and 52% were ambulatory after treatment. Patients with SCLC retained the ability to walk, which differed from patients with non-SCLC, of whom 5% lost this ability. In patients with SCLC, 15% regained the ability to walk compared with 22% of the non-SCLC patients (Table 8). Accordingly, the pretreatment motor deficits seemed to be the most important determinant for the posttreatment motor function; nearly all of the patients who were able to walk before Table 6. Immediate Outcome According to Different Treatment Modalities, Histology, and Pretreatment Walking Ability (gait) Pretreatment
Laminectomy SCLC Non-SCLC ACL SQLC LCC Radiotherapy SCLC* Non-SCLC ACL SQLC* LCC Laminectomy + RT SCLCt Non-SCLC ACL SQLC LCC
Total
Gait (%)
27 10 17 7 6 4 40 16 24 13 9 2 25 14 11 6 3 2 92
26 33 24 0 50 25 49 50 46 54 22 50 46 50 45 33 67 50 40
+/-
7/20 3/7 4/13 0/7 3/3 1/3 18/22 8/8 10/14 7/6 2/7 1/1 12/13 7/7 5/6 2/4 2/1 1/1 37/55
+ Benefit
- Benefit
No.
%
No.
%
13 5 8 2 5 1 17 8 9 6 3 0 16 7 9 5 2 2 46
48 50 47 29 83 25 46 50 39 46 33 0 67 50 82 83 67 100 50
14 5 9 5 1 3 20 6 14 7 5 2 8 6 2 1 1 0 42
52 50 53 71 17 75 54 38 61 54 56 100 33 43 18 17 33 0 46
NOTE. In the seven patients with unknown histologic subtype, three had laminectomy, two had radiotherapy, and two had laminectomy followed by radiotherapy. Four patients were not assessable for response: *two patients with SCLC and one with SQLC in the group treated with radiotherapy; tone patient with SCLC treated with laminectomy plus radiotherapy.
Normal Dysfunction Catheter
Before Treatment
After Treatment
29 12 59
30 22 48
treatment retained this ability. No major changes were observed after treatment in the number of patients with normal sphincter function and in the number who needed a catheter (Table 7). Treatment outcome of the different treatment modalities among the various histologic types is shown in Table 6. In patients with SCLC, the outcome of treatment seemed to be independent of treatment modalities, whereas in patients with non-SCLC, the combined treatment with laminectomy followed by RT was superior. Approximately 82% benefited from the combined treatment (P = .03, x 2 test) compared with only 39% of patients treated with RT and 47% who were treated with laminectomy. In regard to survival, the group of patients who were treated with laminectomy plus RT, survived longer (median value, 3.5 months; range, 0 to 132 months) than patients who were treated with either laminectomy (median value, 1.5 months; range, 0 to 32 months) or RT (median value, 1 month; range, 0 to 59) (P = .03, log-rank test, laminectomy followed by RT v laminectomy or RT alone; Fig 4). Figure 5 demonstrates the probability of survival among the different histologic subtypes of lung cancer after the MSCC. Patients with SQCL apparently had poorer survival (median value, 1 month; range, 0 to 32 months) compare with patients with SCLC (median value, 2.5 months; range, 0 to 132 months), ACL (median value, 1.5 month; range, 0 to 19 months), and large-cell carcinoma (LCC; median value, 1.5 month; range, 0 to 8 months). Still, the differences were not significantly different (P = .06, log-rank test, SQCL v all others). No major difference was demonstrated in the number of long-term survivors subsequent to the diagnosis of MSCC; only 9% survive for more than 12 months. These results also reflect the conclusion that patients with SQCL seem to develop MSCC with some delay time. Table 8. Ability of Gait in 102 Lung Cancer Patients Who Were Treated for Spinal Cord Compression.
Retained walking ability Regained walking ability
All (%)
SCLC (%)
Non-SCLC (0)
97 19
100 15
95 22
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SPINAL CORD COMPRESSION AND LUNG CANCER
Months Fig 4. Probability of survival (%) from the diagnosis of spinal cord compression according to the different treatment modalities (P = .03, log-rank test, laminectomy followed by RT v laminectomy or RT alone). 0, RT; A, laminectomy; 0, RT plus laminectomy.
DISCUSSION
The observation that lung cancer, especially SCLC and ACL, often and with increasing frequency metastasizes to the CNS possibly because of prolonged survival is well known. 15 ,16 The frequency of 2.8% in the present study of patients with SCLC who developed MSCC is in accordance with a previous report that covered the same geographic area (3.5%)." Although SCLC is not the most common type of lung cancer in Denmark (SQLC 30%, ACL 25%, SCLC 20%, and LCC 5%),14 it is the
most frequent cell type that accounted for MSCC (40%). The fact that patients with non-SCLC were not cared for routinely in departments of oncology in Denmark might result in a diminished referral of patients with MSCC and, thereby, an underestimation of the real incidence in patients with non-SCLC. Spinal cord compression is usually accompanied by pain, either radicular or localized back pain, disturbance of sensation, loss of walking ability, and sphincter 100-
40 0 80
40-
0
1
2
3
4
5
6
7
8
9
10
11
12
Months Fig 5. Probability of survival (%) from the diagnosis of spinal cord compression according to histologic subtypes of lung cancer (P = .06,
log-rank test, SQLC v all others). 0, SQLC; 0, SCLC; A, adenocarcinoma; O, LCC.
dysfunctions. Nevertheless, asymptomatic intraspinal metastases were supposed to be even more common than symptomatic metastases, and pain may be the only symptom for a considerable period.17 Some investigations strongly recommend myelography in patients with the onset of back pain because spinal epidural metastases have been detected in more than 50%, despite the fact that one third of the patients had no evidence of myelopathy. Furthermore, the use of both CT scans and myelography has been recommended in a recent report."8 Consequently, changes in pain pattern, eg, from local to radicular pain, can be the first indicators of medullary compression and should lead to confirmatory diagnostic procedures, as should the occurrence of gait ataxia. In two thirds of the patients, a distinct segmental level of sensory loss was found, although this level was predominantly present in patients with SQCL (78%). It is uncertain whether this clinical manifestation is associated with the relatively late tendency to develop MSCC and concomitant slow symptom progression in SQCL patients. No difference in the number of total blockages was demonstrated in the various histologic groups. As previously mentioned, the initial symptoms may be sparse, and some studies report extensive patient and doctor delays. In this series, the patients' delay was 18 days and the doctors' delay 3 days. These in comparison with short delays from other studies may reflect that most patients developed MSCC while being treated for primary malignant disease, or during control as outpatients in relatively close connection to the hospital. Some variations were observed between the different types of lung cancer. In SCLC, 75% of the cases of MSCC was diagnosed during the first month after the primary malignant diagnosis was established, which contrasts with 12 months for ACL and 21 months for SQLC. No major differences were noted when the histologic subtypes or treatment methods were compared according to age and sex. However, some referral bias was observed in the patients' pretreatment walking abilities; Patients who received RT and offered laminectomy followed by RT were probably in a better neurologic condition than patients who had a laminectomy alone (positive gait function 49%, 46%, and 26%, respectively). The usual treatment for MSCC has been laminectomy with or without postoperative irradiation, 3,4,6,1 9-22 although a number of investigators have claimed that RT alone is as effective. 3,5,23,24 In this study, all patients who
were offered surgery had a posterior laminectomy performed because anterior laminectomy is not used rou-
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BACH ET AL
tinely in this category of patients in Denmark.25 The majority of the spinal compressions were localized circular or posterior/lateral (78%) compared with anterior or anterior/lateral (18%). It is not known if these patients would have benefited from anterior decompressive surgery; however, the poor survival prognosis in this group of patients has to be taken into consideration when the benefits or risks of complications of performing an anterior laminectomy with stabilizing material and the routinely performed laminectomy are compared. The value of chemotherapy especially in SCLC as a treatment of MSCC is not clear. Ongoing investigations are performed to explore this issue, 26 but the overall results of treatment, without regard to the different treatment modalities, were preservation of gait function in 97% of those patients who were ambulatory before treatment and restoration of walking abilities in 19% of the patients who were unable to walk before treatment. These results are identical to treatment response in previous series, 5,232, 4,27-30 and although no previous re-
ports have dealt with the different histologic subtypes in lung cancer, our findings confirm that the results in regard to walking ability depend on the patient's pretreatment ambulatory status. The significance of the primary tumor type as an indicator of treatment outcome is not derived from the present study. In a study by Greenberg et a15 no difference was demonstrated between patients with highly or less radiosensitive tumors. Additionally, the
role of the dose and schedule of corticosteroids is uncertain. Greenberg et al described very high response rates and immediate pain relief using high-dose dexamethasone during the initial RT both in groups with highly or less radiosensitive tumors. Whether the outcome was caused by primary corticosteroid tumor shrinkage or reduction of edema with secondary improved reoxygenation is unknown. No long-term follow-up concerning the outcome of treatment in regard to walking ability and bladder function was performed in the present study. It is known that recovery may be delayed, 31,32 and some of the patients without walking ability immediately after treatment may have regained this ability. Although no definite conclusions can be drawn based on the present study, the treatment results in SCLC were independent of the different treatment modalities, in contrast to non-SCLC in which the combined approach of laminectomy followed by RT seemed to be superior to either one of the two treatments. Spinal cord compression still constitutes one of the major problems in neuro-oncology, but immediate treatment is crucial to preserve neurologic functions. When the literature is reviewed, only one prospective, randomized, clinically controlled study that compares laminectomy plus RT or RT alone has been published. 28 No difference in the outcome of treatment was observed, which still leaves controversy regarding the best form of treatment.
REFERENCES 1. Bach F, Larsen BH, Rohde K, et al: Metastatic spinal cord compression. Occurrence, symptoms, clinical presentations and prognosis in 398 patients with spinal cord compression. Acta Neurochir 107:37-43, 1990 2. S0rensen PS, Bcrgesen SE, Rohde K, et al: Metastatic epidural spinal cord compression: Results of treatment and survival. Cancer 65:1502-1508, 1990 3. Dunn RC, Kelly WA, Wohns RNW, et al: Spinal epidural neoplasia. A 15-year review of the results of surgical therapy. J Neurosurg 52:47-51, 1980 4. Stark RJ, Henson RA, Evans SJW: Spinal metastases. A retrospective survey from a general hospital. Brain 105:189-213, 1982 5. Greenberg HS, Kim JH, Posner JB: Epidural cord compression from epidural tumor: Results with a new treatment protocol. Ann Neurol 8:361-366, 1980 6. Livingston KE, Perrin RG: The neurosurgical management of spinal metastases causing cord and cauda equina compression. J Neurosurg 3:839-843, 1978 7. Nather A, Base K: The results of decompression from metastatic extradural tumors. Clin Orthop 169:103-108, 1982 8. Barron KD, Hirano A, Araki S, et al: Experiences with
metastatic neoplasms involving the spinal cord. Neurology 9:91106, 1959 9. Bansal S, Brady LW, Olsen A, et al: The treatment of metastatic spinal cord tumors. JAMA 202:686-688, 1967 10. Posner J: Neurological complications of systemic cancer. Med Clin North Am 55:625-646, 1971 11. Pedersen AG, Bach F, Melgaard B: Frequency, diagnosis and prognosis of spinal cord compression in small cell lung bronchogenic carcinoma. Cancer 55:1818-1822, 1985 12. Muir C, Waterhouse J, Mack T, et al: Cancer incidence in five continents, vol 5. Lyon, France, IARC Scientific Publications, 1987 13. Silverberg E, Lubera JA: Cancer statistics 1988. Cancer 38:5-22, 1988 14. Frolund C, Krasnik M, Rosenstock, et al: Lung cancer in Denmark, 1943-1986. Cancer statistic no. 26. Danish Med Bull 152:1241-1245, 1990 15. Pedersen AG: Diagnostic procedures in the detection of CNS metastases from small cell lung cancer, in Hansen HH (ed): Lung Cancer. Basic and Clinical Aspects. Boston, MA, Martinus Nijhoff, 1986, pp 153-182 16. Sorensen JB, Hansen HH, Hansen M, et al: Brain me-
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SPINAL CORD COMPRESSION AND LUNG CANCER tastases in adenocarcinoma of the lung: Frequency, risk groups, and prognosis. J Clin Oncol 6:1474-1480, 1988 17. Rodichock LD, Ruckdeschel JC, Harper GR, et al: Early detection and treatment of spinal epidural metastases; the role of myelography. Ann Neurol 20:696-702, 1986 18. Grossman SA, Weissmann DE, Wang H, et al: Early diagnosis of spinal epidural metastases using out-patient computed tomographic myelography. Eur J Cancer 26:495-499, 1990 19. Wright RL: Malignant tumors in the spinal extradural space. Results of surgical treatment. Ann Surg 157:227-231, 1963 20. Brice J, McKissock WS: Surgical treatment of malignant extradural spinal tumours. Br Med J 1:1341-1344, 1965 21. Smith R: An evaluation of surgical treatment for spinal cord compression due to metastatic carcinoma. J Neurol Neurosurg Psychiatr 28:152-158, 1965 22. Hall AJ, Mackay NNS: The results of laminectomy for compression of cord and cauda equina by extradural malignant tumor. J Bone Joint Surg 55:497-595, 1973 23. Gilbert RW, Kim JH, Posner J: Epidural spinal cord compression from metastatic tumor: Diagnosis and treatment. Ann Neurol 3:40-51, 1978 24. Cobb CA, Leavens ME, Eckles N: Indications for nonoperative treatment of spinal cord compression due to breast cancer. J Neurosurg 47:653-658, 1977
25. Alho A: Surgical treatment of spinal metastases in the Nordic countries. Nord Med 106:289-290, 1991 26. Hansen SW, Larsen SH: The neurological outcome of spinal cord compression in patients with lung cancer. Sixth World Conference on Lung Cancer, Melbourne, Australia, November 1991 (abstr) 27. Shaw MDM, Rose JE, Paterson A: Metastatic extradural malignancy of the spine. Acta Neurochir 52:113-120, 1980 28. Young RF, Post EM, King GA: Treatment of epidural metastases. Randomized prospective comparison of laminectomy and radiotherapy. J Neurosurg 53:741-748, 1980 29. Tang SG, Byfield JE, Sharp TR, et al: Prognostic factors in the management of metastatic epidural spinal cord compression. J Neuro Oncol 1:21-28, 1983 30. Constans JP, Divitis ED, Donzelli R, et al: Spinal metastases with neurological manifestations. Review of 600 cases. J Neurosurg 59:111-118, 1983 31. Larsen SH, Rasmusson B, Sorensen PS: Recovery of gait after radiotherapy in paraplegic patients with metastatic spinal cord compression. Neurology 40:1234-1237, 1990 32. Tarlov M, Herz E: Spinal cord compression studies. IV. Outlook with complete paralysis in man. Arch Neurol Psychiatry 72:43-51, 1954
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