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Metastatic Brain Tumors
i
METASTATIC BRAIN TUMORS KENNETH
E.
LIVINGSTON, GILBERT HORRAX AND ERNEST SACHS, JR.
IN any neurosurgical clinic the problem of management of metastatic intracranial lesions will be repeatedly encountered. The ultimate prognosis for these cases is, of course, hopeless. The immediate result in terms of useful survival is so often disappointing that the neurosurgeon accepts these cases with considerable reluctance. Yet in spite of the marked pessimism with which this group of intracranial tumors is regarded, there are occasional striking exceptions-patients who have had gratifying and worthwhile survivals following craniotomy for verified metastatic lesions. If criteria were available for identifying the cases in which useful survival is probable, the management of this problem would be less difficult. INCIDENCE
The relative incidence of intracranial metastatic tumor will vary with the type of hospital service from which material is studied. The incidence in a neurosurgical clinic will be relatively low (4.2 per cent in the Cushing series 3,6,7; 4.1 per cent in the present study). The neurosurgeon sees only a selected group of patients with intracranial metastases since many cases are never presented for surgical consideration. Actually, metastatic lesions have represented 13.5. per cent,- 17 per cent,2 and 17.9 per cent! of all intracranial tumors in autopsy series from general hospitals. PRIMARY SITES
The commonest primary source of intracranial metastasis is the lung. In a series studied by Globus, 55 per cent of all intracranial metastases were secondary to lung tumor. Other primary sources are the breast, gastrointestinal tract, kidney, thyroid, prostate, and so forth. The common pathway for metastasis to reach the cranial cavity is from the lung "Via the blood stream, and either primary or secondary pulmonary lesions will be found in at least 80 per cent of cases that come to autopsy with metastatic intracranial tumor. 6,S The importance of preoperative roentgenologic examination of the chest is thus quite apparent. In spite of the fact that the lung is so frequently involved, however, demonstration of the pulmonary lesion may be difficult or impossible. In a group. of cases with verified pulmonary lesions 35 per cent were reported as negative from roentgenologic study.4 CORRELATION OF CLINICAL FACTORS WITH DURATION OF SURVIVAL
We have reviewed the experience· of the neurosurgical department of the Lahey Clinic in dealing with surgically verified metastatic 805
806
KENNETH E. LIVINGSTON, ERNEST SACHS, JR.
brain tumors during the period from 1934 through 1945. We have been interested particularly to find criteria that might aid in identifying those cases in which useful survival is probable. During this period 1256 brain tumors have been surgically verified and of these 51 proved to be metastatic, an incidence of 4.1 per cent. This series of surgically verified metastatic brain tumors has been separated into three major groups for study: Group A: Patients with no signs or symptoms suggesting metastatic malignancy. This will include patients in whom the differentiation from primary brain tumor can be made only at operation. Group B: Patients with previously known malignant lesions. Many of these patients will have had remote surgical treatment for their primary lesion. Group C: Patients with general debilitation suggestive of systemic malignant disease. Significant weight loss was the common clinical finding in this group. In classifying survivals we have considered that all patients who failed to survive longer than one month following operation have "zero" survival. Thirty-six per cent of the patients in this series failed to survive longer than one month following craniotomy. Survival of less than six months is classified as not significant for the purposes of this study, although in particular instances survival of three, four, or five months may be very worth while. Of the entire series 30 per cent survived longer than six months, and approximately half of these (16 per cent) survived longer than two years. Table 1 compares the survival of patients on the basis of the three mlljor groupings described above. It is quite apparent that the patients if). Group C showing evidence of systematic debilitation had uniformly poor survival. No patient in this group lived six months following operation. These poor results are not explained by mortality during the first postoperative month since survivals through this period are comparable for all three groups. It is of interest that survivals in Group B proved higher than in Group A. Although both groups are small in number, the fact that patients with known primary malignant lesions had as satisfactory survival as patients with no clinical evidence to suggest malignant disease is of considerable significance. It is surprising to find that even in the presence of other demonstrable secondary lesions by roentgenologic examination of the chest, these patients all survived longer than six months and in one case longer than two years. Reference to Table 2 helps to explain these unexpected survivals in the presence of known primary malignant lesions. This table compares
i
807
METASTATIC BRAIN TUMORS
TABLE 1 SURVIVALS
I No. of CaRes
Clinical Classification
Longer than 1 month
Longer than 6 months
Longer than 24 months
13 (60%) 2 2 9 8 (67%)
7 (31.8%) 1 1 5 6 (50%) 2 3 1 0 (0%) 0 0 0 13 (30%)
4 (18%) 0 0 11 3 (25%) 2 1 0 0 (0%) 0 0 0 7 (16%)
Longer than 1 month
Longer than 6 months
Longer than 24 months
1 (6%) 10 (43.5%)
---Group I: No clinical symptoms or signs of malignant disease. Neg. chest x-ray ................ Pos. chest x-ray ................ No chest x-ray ................. Group II: Known primary malignant lesion (remote). Neg. chest x-ray ................ Pos. chest x-ray ................ No chest x-ray ................. Group III: Debilitation suggesting systemic malignant disease. Neg. chest x-ray ................ Pos. chest x-ray ................ No chest x-ray ...... , .......... Totals .......................
22
4 4,
14 12
,t
8 3 1 10
3 1 7 (70%) 2 4 1 28 (64%)
3 6 1
44*
\
* Follow-up data not available for 7 patients. TABLE 2 SURVIVALS
Duration of Intracranial Symptoms
No. of Cases
6 weeks or less ...................
15
11
23
(73%) 16 (70%)
3 months or more .................
I
0 6 (26%)
survivals in terms of the duration of intracranial symptoms prior to surgery. Of the 15 cases with symptoms of six weeks' duration or less, only one patient was alive six months following craniotomy. Of the 23 cases with symptoms of three months' duration or longer, 10 were alive after six months, and 6 of these lived longer than two years. Again, the difference between these groups is not explained by higher mortality in the first postoperative month since survivals to that point are almost identical. It is of interest that the presence of either primary or other secondary malignant lesions was established in 57.7 per cent of the patients in
¢
808
KENNETH E. LIVINGSTON, ERNEST SACHS, JR.
this series prior to surgery. In 4 additional patients a metastatic intracranial lesion was strongly suspected because of marked general debilitation, although the primary or other secondary lesions could not be identified preoperatively. Thus in approximately two-thirds of this series there was strong evidence that the intracranial symptoms were due to metastatic tumor. In approximately one-third there was no objective clinical evidence or symptomatology to suggest a metastatic lesion, although not all patients in this latter group were screened by chest roentgenologic examination. Routine roentgenologic study of the chest would undoubtedly have added to the group in which metastatic tumor could be considered clinically established. The site of the primary tumor in the cases in which it could be definitely established was not unusual, except that the relative number of lesions primary in the lung was less than would be anticipated from other studies. 4 Survival in relation to site of primary lesion is tabulated for 30 cases in Table 3. In this small group, patients with metastasis TABLE 3 SURVIVALS
Site of Primary Malignancy Kidney .... .... . .... . Breast .......... . . ... Gastrointestinal tract. ..... . Lung ... Total. . '"
Number of Cases
.....
. ... · . ·. ..... ·.
5 9 7 9 30
I
Longer than 1 month
Longer Longer than than 6 months 24 months
4 7 4 6 21
4 (80%) 3 (33%) 2 (28%) o ( 0%) 9 (30%)
(80%) (78%) (55%) (67%) (70%)
3 (60%) 2 (22%) 2 (28%) o ( 0%) 7 (23%)
from primary renal tumor had relatively much longer survival than any other group. From these data it is suggested that, of the four primary sites studied, the kidney is relatively most favorable and the lung relatively least favorable for significant survival. Of the 37 cases in which the metastatic tumor was apparently solitary and its location could be accurately defined, 73 per cent were above the tentorium, and of the supratentorial lesions, two-thirds were in the left hemisphere. This suggests that the left carotid circulation is the more frequent route for metastatic seeding to the brain. In the series of metastatic intracranial tumors studied by Globus and Meltzer,5 only 10 per cent had significant papilledema. In contrast, in the present series 60 per cent of the patients had definite choked disks. In our experience survivals have been significantly longer in the group of patients without papilledema, as shown in Table 4 which summarizes survival from this standpoint. On the basis of our experience three clinical factors will prove of considerable value in anticipating survival in cases of metastatic brain
METASTATIC BRAIN TUMORS
809
TABLE 4 SURVIVALS
--
Longer than Longer than Longer than 2 years 1 month 6 months
Optic Disk 'Choked" .. _. _._ .... . , ... "Not choked". __
....
.
17 (60%) 16 (73%)
4 (14%) 10 (4.5%)
2 (7%) 5 (31%)
tumor. These are, in order of relative importance, the presence or absence of general debilitation; the duration of intracranial symptoms, and the presence or absence of papilledema. When these criteria are applied in segregating patients in whom significant survival is unlikely, it is found that no patient with general debilitation lived six months following operation, and that only one patient with intracranial symptoms of less than six weeks' duration was alive six months after operation. The ability to anticipate survival on the basis of the presence or absence of papilledema is less striking but significant, since patients without papilledema had three times as many significant survivals as the group with choking. When these criteria are applied in selecting patients in whom significant survival is probable, it is found that 10 patients satisfied all three factors-absence of debilitation, symptoms of three months' duration or longer, and absence of papilledema. Three of these patients died during the immediate postoperative period but the remaining 7 patients all lived longer than six months, and 5 of them lived longer than two years. SUMMARY
We have reviewed the experience of the neurosurgical department of the Lahey Clinic in dealing with surgically verified metastatic brain tumors. We have found three clinical factors, the presence or absence of general debilitation, the duration of intracranial symptoms and the presence or absence of papilledema to have correlation with duration of survival in these patients. The utilization of these factors in the evaluation and estimation of survival in patients with metastatic brain tumors may prove clinically useful. REFERENCES 1. Baker, A. B.: Metastatic tumors of the nervous system. Arch. Path., 34:495-537
(Sept.) 1942. 2. Courville, C. B.: Pathology of the central nervous system. Mountain View, Calif., Pacific Press Pub. Assoc., 1945, 344 pp. 3. Cushing, H.: Intracranial tumours. Springfield, Ill., C. C. Thomas, 1932, 150 pp. 4. Globus, J. H.: Metastatic brain tumors with bronchogenic carcinoma as a primary source. J. Mt. Sinai Hosp., 10:533-564 (Jan.-Feb.) 1944.
810
KENNETH E. LIVINGSTON, ERNEST SACHS, JR.
5. Globus, J. H. and Meltzer, T.: Metastatic tumors of the brain. Arch. Neurol. & Psychiat., 48:163-226 (Aug.) 1942. 6. Grant, F. C.: Intracranial malignant metastases; their frequency and value of surgery in their treatment. Ann. Surg., 84:635-646 (Nov.) 1926. 7. Meagher, R. and Eisenhardt, L.: Intracranial carcinomatous metastasell. AnJl. Surg., 93:132-140 (Jan.) 1931. 8. Tom, M. I.: Metastatic tumours of the brain. Canad. M.A.J., .'}4:265-268 (Mar.) 1946.
METASTATIC BRAIN TUMORS KENNETH
E.
LIVINGSTON, GILBERT HORRAX AND ERNEST SACHS, JR.
IN any neurosurgical clinic the problem of management of metastatic intracranial lesions will be repeatedly encountered. The ultimate prognosis for these cases is, of course, hopeless. The immediate result in terms of useful survival is so often disappointing that the neurosurgeon accepts these cases with considerable reluctance. Yet in spite of the marked pessimism with which this group of intracranial tumors is regarded, there are occasional striking exceptions-patients who have had gratifying and worthwhile survivals following craniotomy for verified metastatic lesions. If criteria were available for identifying the cases in which useful survival is probable, the management of this problem would be less difficult. INCIDENCE
The relative incidence of intracranial metastatic tumor will vary with the type of hospital service from which material is studied. The incidence in a neurosurgical clinic will be relatively low (4.2 per cent in the Cushing series 3,6,7; 4.1 per cent in the present study). The neurosurgeon sees only a selected group of patients with intracranial metastases since many cases are never presented for surgical consideration. Actually, metastatic lesions have represented 13.5. per cent,- 17 per cent,2 and 17.9 per cent! of all intracranial tumors in autopsy series from general hospitals. PRIMARY SITES
The commonest primary source of intracranial metastasis is the lung. In a series studied by Globus, 55 per cent of all intracranial metastases were secondary to lung tumor. Other primary sources are the breast, gastrointestinal tract, kidney, thyroid, prostate, and so forth. The common pathway for metastasis to reach the cranial cavity is from the lung "Via the blood stream, and either primary or secondary pulmonary lesions will be found in at least 80 per cent of cases that come to autopsy with metastatic intracranial tumor. 6,S The importance of preoperative roentgenologic examination of the chest is thus quite apparent. In spite of the fact that the lung is so frequently involved, however, demonstration of the pulmonary lesion may be difficult or impossible. In a group. of cases with verified pulmonary lesions 35 per cent were reported as negative from roentgenologic study.4 CORRELATION OF CLINICAL FACTORS WITH DURATION OF SURVIVAL
We have reviewed the experience· of the neurosurgical department of the Lahey Clinic in dealing with surgically verified metastatic 805
806
KENNETH E. LIVINGSTON, ERNEST SACHS, JR.
brain tumors during the period from 1934 through 1945. We have been interested particularly to find criteria that might aid in identifying those cases in which useful survival is probable. During this period 1256 brain tumors have been surgically verified and of these 51 proved to be metastatic, an incidence of 4.1 per cent. This series of surgically verified metastatic brain tumors has been separated into three major groups for study: Group A: Patients with no signs or symptoms suggesting metastatic malignancy. This will include patients in whom the differentiation from primary brain tumor can be made only at operation. Group B: Patients with previously known malignant lesions. Many of these patients will have had remote surgical treatment for their primary lesion. Group C: Patients with general debilitation suggestive of systemic malignant disease. Significant weight loss was the common clinical finding in this group. In classifying survivals we have considered that all patients who failed to survive longer than one month following operation have "zero" survival. Thirty-six per cent of the patients in this series failed to survive longer than one month following craniotomy. Survival of less than six months is classified as not significant for the purposes of this study, although in particular instances survival of three, four, or five months may be very worth while. Of the entire series 30 per cent survived longer than six months, and approximately half of these (16 per cent) survived longer than two years. Table 1 compares the survival of patients on the basis of the three mlljor groupings described above. It is quite apparent that the patients if). Group C showing evidence of systematic debilitation had uniformly poor survival. No patient in this group lived six months following operation. These poor results are not explained by mortality during the first postoperative month since survivals through this period are comparable for all three groups. It is of interest that survivals in Group B proved higher than in Group A. Although both groups are small in number, the fact that patients with known primary malignant lesions had as satisfactory survival as patients with no clinical evidence to suggest malignant disease is of considerable significance. It is surprising to find that even in the presence of other demonstrable secondary lesions by roentgenologic examination of the chest, these patients all survived longer than six months and in one case longer than two years. Reference to Table 2 helps to explain these unexpected survivals in the presence of known primary malignant lesions. This table compares
i
807
METASTATIC BRAIN TUMORS
TABLE 1 SURVIVALS
I No. of CaRes
Clinical Classification
Longer than 1 month
Longer than 6 months
Longer than 24 months
13 (60%) 2 2 9 8 (67%)
7 (31.8%) 1 1 5 6 (50%) 2 3 1 0 (0%) 0 0 0 13 (30%)
4 (18%) 0 0 11 3 (25%) 2 1 0 0 (0%) 0 0 0 7 (16%)
Longer than 1 month
Longer than 6 months
Longer than 24 months
1 (6%) 10 (43.5%)
---Group I: No clinical symptoms or signs of malignant disease. Neg. chest x-ray ................ Pos. chest x-ray ................ No chest x-ray ................. Group II: Known primary malignant lesion (remote). Neg. chest x-ray ................ Pos. chest x-ray ................ No chest x-ray ................. Group III: Debilitation suggesting systemic malignant disease. Neg. chest x-ray ................ Pos. chest x-ray ................ No chest x-ray ...... , .......... Totals .......................
22
4 4,
14 12
,t
8 3 1 10
3 1 7 (70%) 2 4 1 28 (64%)
3 6 1
44*
\
* Follow-up data not available for 7 patients. TABLE 2 SURVIVALS
Duration of Intracranial Symptoms
No. of Cases
6 weeks or less ...................
15
11
23
(73%) 16 (70%)
3 months or more .................
I
0 6 (26%)
survivals in terms of the duration of intracranial symptoms prior to surgery. Of the 15 cases with symptoms of six weeks' duration or less, only one patient was alive six months following craniotomy. Of the 23 cases with symptoms of three months' duration or longer, 10 were alive after six months, and 6 of these lived longer than two years. Again, the difference between these groups is not explained by higher mortality in the first postoperative month since survivals to that point are almost identical. It is of interest that the presence of either primary or other secondary malignant lesions was established in 57.7 per cent of the patients in
¢
808
KENNETH E. LIVINGSTON, ERNEST SACHS, JR.
this series prior to surgery. In 4 additional patients a metastatic intracranial lesion was strongly suspected because of marked general debilitation, although the primary or other secondary lesions could not be identified preoperatively. Thus in approximately two-thirds of this series there was strong evidence that the intracranial symptoms were due to metastatic tumor. In approximately one-third there was no objective clinical evidence or symptomatology to suggest a metastatic lesion, although not all patients in this latter group were screened by chest roentgenologic examination. Routine roentgenologic study of the chest would undoubtedly have added to the group in which metastatic tumor could be considered clinically established. The site of the primary tumor in the cases in which it could be definitely established was not unusual, except that the relative number of lesions primary in the lung was less than would be anticipated from other studies. 4 Survival in relation to site of primary lesion is tabulated for 30 cases in Table 3. In this small group, patients with metastasis TABLE 3 SURVIVALS
Site of Primary Malignancy Kidney .... .... . .... . Breast .......... . . ... Gastrointestinal tract. ..... . Lung ... Total. . '"
Number of Cases
.....
. ... · . ·. ..... ·.
5 9 7 9 30
I
Longer than 1 month
Longer Longer than than 6 months 24 months
4 7 4 6 21
4 (80%) 3 (33%) 2 (28%) o ( 0%) 9 (30%)
(80%) (78%) (55%) (67%) (70%)
3 (60%) 2 (22%) 2 (28%) o ( 0%) 7 (23%)
from primary renal tumor had relatively much longer survival than any other group. From these data it is suggested that, of the four primary sites studied, the kidney is relatively most favorable and the lung relatively least favorable for significant survival. Of the 37 cases in which the metastatic tumor was apparently solitary and its location could be accurately defined, 73 per cent were above the tentorium, and of the supratentorial lesions, two-thirds were in the left hemisphere. This suggests that the left carotid circulation is the more frequent route for metastatic seeding to the brain. In the series of metastatic intracranial tumors studied by Globus and Meltzer,5 only 10 per cent had significant papilledema. In contrast, in the present series 60 per cent of the patients had definite choked disks. In our experience survivals have been significantly longer in the group of patients without papilledema, as shown in Table 4 which summarizes survival from this standpoint. On the basis of our experience three clinical factors will prove of considerable value in anticipating survival in cases of metastatic brain
METASTATIC BRAIN TUMORS
809
TABLE 4 SURVIVALS
--
Longer than Longer than Longer than 2 years 1 month 6 months
Optic Disk 'Choked" .. _. _._ .... . , ... "Not choked". __
....
.
17 (60%) 16 (73%)
4 (14%) 10 (4.5%)
2 (7%) 5 (31%)
tumor. These are, in order of relative importance, the presence or absence of general debilitation; the duration of intracranial symptoms, and the presence or absence of papilledema. When these criteria are applied in segregating patients in whom significant survival is unlikely, it is found that no patient with general debilitation lived six months following operation, and that only one patient with intracranial symptoms of less than six weeks' duration was alive six months after operation. The ability to anticipate survival on the basis of the presence or absence of papilledema is less striking but significant, since patients without papilledema had three times as many significant survivals as the group with choking. When these criteria are applied in selecting patients in whom significant survival is probable, it is found that 10 patients satisfied all three factors-absence of debilitation, symptoms of three months' duration or longer, and absence of papilledema. Three of these patients died during the immediate postoperative period but the remaining 7 patients all lived longer than six months, and 5 of them lived longer than two years. SUMMARY
We have reviewed the experience of the neurosurgical department of the Lahey Clinic in dealing with surgically verified metastatic brain tumors. We have found three clinical factors, the presence or absence of general debilitation, the duration of intracranial symptoms and the presence or absence of papilledema to have correlation with duration of survival in these patients. The utilization of these factors in the evaluation and estimation of survival in patients with metastatic brain tumors may prove clinically useful. REFERENCES 1. Baker, A. B.: Metastatic tumors of the nervous system. Arch. Path., 34:495-537
(Sept.) 1942. 2. Courville, C. B.: Pathology of the central nervous system. Mountain View, Calif., Pacific Press Pub. Assoc., 1945, 344 pp. 3. Cushing, H.: Intracranial tumours. Springfield, Ill., C. C. Thomas, 1932, 150 pp. 4. Globus, J. H.: Metastatic brain tumors with bronchogenic carcinoma as a primary source. J. Mt. Sinai Hosp., 10:533-564 (Jan.-Feb.) 1944.
810
KENNETH E. LIVINGSTON, ERNEST SACHS, JR.
5. Globus, J. H. and Meltzer, T.: Metastatic tumors of the brain. Arch. Neurol. & Psychiat., 48:163-226 (Aug.) 1942. 6. Grant, F. C.: Intracranial malignant metastases; their frequency and value of surgery in their treatment. Ann. Surg., 84:635-646 (Nov.) 1926. 7. Meagher, R. and Eisenhardt, L.: Intracranial carcinomatous metastasell. AnJl. Surg., 93:132-140 (Jan.) 1931. 8. Tom, M. I.: Metastatic tumours of the brain. Canad. M.A.J., .'}4:265-268 (Mar.) 1946.