- Email: [email protected]
Low grade glioma of the cerebral hemispheres in adults: a retrospective analysis of 88 cases
hr. J. Radiarmn Oncology Bml Phys., Vol. Printed in the U.S.A. All nghts reserved.
0360.3016190 $3.00 + .oO Copyright 0 1990 Pergamon Press plc
18, PP. 783-786
??Special Feature
LOW GRADE
GLIOMA OF THE CEREBRAL HEMISPHERES A RETROSPECTIVE ANALYSIS OF 88 CASES
A. C. WHITTON, H. J. G. BLOOM, M.D.,
BSc.,
M.B.,
B.S., F.R.C.R.
IN ADULTS:
AND
F.R.C.P., F.R.C.R., F.R.C.S., F.A.C.R.
Department of Radiotherapy, Royal Marsden Hospital and Institute of Cancer Research, Sutton, Surrey, England Eighty-eight adult patients with histologically verified cerebral low grade gliomas (grades 1 and 2) treated with post-operative radiotherapy at the Royal Marsden Hospital between 1960 and 1985 were reviewed. Survival of oligodendroglioma patients was greater than those with astrocytoma (64% vs 36% at 5 years) but the difference was less marked in the long term (35% vs 26% at 10 years). Previous studies have identified prognostic factors important in these tumors: age, extent of surgery, grade, performance status, and duration of symptoms. In this study of low grade astrocytomas and oligodendrogliomas, age (highly significant in the former and significant in the latter), extent of surgery (oligodendrogliomas), and performance status have been demonstrated as factors influencing outcome. The precise role of radiotherapy including the optimal radiation dose and timing of treatment remains unclear. The information, given by a retrospective analysis such as this, helps in the design of prospective, randomized studies looking at radiation dose and time of surgical and radiotherapeutic interventions, always with careful assessment needed of quality of life and treatment morbidity. Brain gliomas, Low grade astrocytoma,
Low grade oligodendroglioma,
INTRODUCTION
Radiotherapy.
formed with uniformity of radiotherapy technique under the supervision of one radiation oncologist (HJGB). Therefore, the information from this, though retrospective, may assist in designing any prospective study.
Low grade gliomas constitute about 10% of primary brain tumors ( 11, 12). They present insidiously, often with seizures that can predate any progressive neurological deficit by years. Their optimal treatment and its timing remains controversial. Whether surgical intervention should be performed at time of diagnosis or at progressive neurological deterioration and whether the addition of radiotherapy is beneficial, is still not completely elucidated. A number of retrospective studies have suggested a beneficial role for radiotherapy in low grade astrocytomas incompletely resected at surgery (3, 4, 6, 7, 13, 14). In low grade oligodendrogliomas, the role of radiotherapy is less clear (1,2, 8, 10). These studies suffer from the problems inherent in retrospective analyses and we await a prospective study to help determine the optima1 treatment. We have analyzed the results of patients treated by surgery combined with radiotherapy at the Royal Marsden Hospital from 1960 to 1985. Their treatment was per-
METHODS
AND
MATERIALS
Patient characteristics
Eighty-eight adult patients with histologically verified low grade glioma of the cerebral hemispheres treated at the Royal Marsden Hospital from 1960 to 1985 were reviewed (Table 1). Astrocytomas were 2.5 times more common than oligodendrogliomas. There were only four cases of mixed astrocytoma and oligodendroglioma. All cases were histologically verified and the pathology subsequently reviewed at the Royal Marsden Hospital. Astrocytomas were graded using the Kernohan system (5), grades 1 and 2 being “low grade.” There were 15 patients with grade 1 astrocytoma and 45 with grade 2 (7 of which were gemistocytic).
Presented at the International Neuro-Oncology Conference, Royal Marsden Hospital, London, England, September 12-14, 1988. Reprint requests to: Dr. A. C. Whitton, Ontario Cancer Treatment and Research Foundation (Hamilton Regional Cancer Centre), 7 11 Concession Street, Hamilton, Ontario, L8V 1C3, Canada.
Acknowledgements-We wish to thank Sue Ashley for computer analysis of data, Christine Gorman for help in processing data and computer input, and Suzanne Bohnet for help in preparing and typing the manuscript. Accepted for publication 12 October 1989.
783
784
1. J. Radiation Oncology 0 Biology 0 Physics Table I. Patient sex and age characteristics
Number Sex: Male Female Age: Range Median
Table 3. Functional
Astrocytoma
Oligodendroglioma
Mixed
60
24
4
29 31
12 12
4
17-70 yr. 36 yr.
17-75 yr. 41 yr.
April 1990, Volume 18, Number 4
26-44 yr. 36 yr.
Symptoms at presentation varied (Table 2) with seizures being most common and then headaches. These symptoms spread over many years but 50 cases presented with less than 2 years duration. The majority of patients (63 cases, 72%) had good functional status pre-radiotherapy with normal activity or limited partial incapacity (Table 3). Prior to 1977, tumor position was located by angiography and air studies, from 1966-1973 by isotope brain scanning, and from 1973 by CT scanning. The frontal lobes were most commonly involved for both astrocytomas and oligodendrogliomas (Table 4).
Treatment Patients were referred for radiotherapy largely from two neurosurgical centers in London-The Atkinson Morley Hospital (52 cases) and the National Hospital for Nervous Diseases (23 cases). Therefore, they were pre-selected and the low number of referrals following total tumor resection reflects this (Table 5). Additionally, it can be seen that a greater tumor resection appeared possible for oligodendrogliomas than astrocytomas with relatively less biopsies only performed. This may reflect the more localized growth of the former. Post-operative radiotherapy with megavoltage treatment (5-8 MV, apart from 4 cases with 250 KV) was used. Patients were immobilized using a mould and a three-field technique simulated with the isodose distribution computed. Wide local fields were employed. Treatments were given daily, 5 times a week with the intention of giving a dose of 50-55 Gy at 1.67 Gy per fraction in 6-6.5 weeks. In this study, minimum and maximum doses have been ascertained, and the number of fractions and overall
status pre-radiotherapy: Astrocytoma
Normal activity without signs Normal activity with signs Partial incapacity, capable of work Disabled, capable of self care Total incapacity
no. of cases
Oligodendroglioma
Mixed
10
9
1
25
9
3
3
3
19 3
3
treatment period have been recorded to give a more accurate assessment of dose. There was some variation of maximum and minimum doses per fraction with medians of 1.74 Gy and 1.57 Gy, respectively, with an overall median dose per fraction of 1.67 Gy. After recurrence of tumor, half the patients received varying combinations of surgery, further radiotherapy and chemotherapy depending on the individual situation. Statistical analysis and follow-up Results were analyzed using the Kaplan-Meier method and logrank stat test. Follow-up was from 2 years 5 months to 20 years (median 9 years) for astrocytomas and from 10 months to 18 years (median 7 years) for oligodendrogliomas.
RESULTS The survival for low grade oligodendrogliomas was better than astrocytomas though in the long term (more than 10 years) this was less marked (Fig. 1). The four cases of mixed astrocytoma and oligodendroglioma are all alive without recurrence, with one case beyond 15 years, one beyond 10 years, and the other two beyond 5 years follow-up. No difference in survival was found between grade 1 (15 cases) and grade 2 (45 cases) astrocytoma when analyzed, with the seven cases of gemistocytic type showing no worsened prognosis. There was no difference in survival according to sex, extent of surgical resection (astrocytomas), tumor dose or dose per fraction (astrocytomas), number of cerebral lobes
Table 2. Symptoms at presentation (may be multiple): no. of cases Astrocytoma Seizure Headache Cerebral motor Nausea/vomiting Cranial nerve Cerebral sensory
35 28 12 8 5 4
Oligodendroglioma 15 9 4 3 1 2
Table 4. Cerebral lobes involved (may be multiple): no. of cases
Mixed 3 2 1
1
Astrocytoma Frontal Parietal Temporal Occipital
34 18 25 2
Oligodendroglioma 16 8 4 3
Mixed 2 3
1
Lowgradegliomas0A.C.
WHITTONAND
785
H.J.G.BLooM
Table 5. Extent of surgical resection: no. of cases Astrocytoma 19 18 21 2
Biopsy Partial Subtotal Total
Oligodendroglioma
Mixed
1 10 10 3
1 2 1
involved, and duration of symptoms. However, there was a clear difference in survival by age for astrocytomas (Fig. 2) and also oligodendrogliomas (Fig. 3). The extent of surgical resection was important in oligodendrogliomas (Fig. 4) and there appeared to be a trend (though not a statistically significant one) toward improved survival for higher doses (above 55 Gy) when maximum dose was analyzed but not minimum dose or dose per fraction.
However, the radiotherapy dose range was limited and it would be difficult to show a dose-response effect. It would be necessary to perform a dose escalation study to investigate this further. Overall, for low grade gliomas, there was a significant improvement in survival for good performance status (Fig. 5). Analyzing recurrence data, there did not appear to be a plateauing of relapses and disease recurrence continued for at least 10 years. Following the relapse of astrocytomas, without further treatment (22 cases), survival was less than 6 months but with treatment (given in 18 cases), more prolonged survival was achieved with more than 30% alive at 2 years. After relapse of oligodendroglioma, without further treatment (6 cases), all were dead by 2 months but with treatment (7 cases), 20% were alive at 2 years. However, this may simply reflect patient-selection and further study is required to elucidate the most beneficial management at relapse.
i 40
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p < 0.005 0
-m 0
1
2
3
4
5
6
7
8
9
f0
YEARS SINCE SURGERY
Fig. 2. Survival curves for 60 patients with low grade astrocytoma
according to age.
DISCUSSION
This retrospective analysis can make no statement as to efficacy of post-operative radiotherapy in low grade gliomas. However, it has revealed factors important in the design of any future study. Previous studies have suggested prognostic factors in these tumors to be: age, extent of surgery, grade (in astrocytomas), performance status, and length of symptoms ( 1, 3, 6, 7, 9, 14, 15). In this study, age was shown to be a very important prognostic factor in astrocytoma and also an important factor in oligodendroglioma. Extent of surgical resection in astrocytoma, surprisingly, did not show a significant difference in outlook, possibly because the better resected cases were
5
-
-
40
-
.-___________
z $ 0 E z
o-
,,,,,,,,, Ol7345678
I
,,,I
9 IO II 12 13 14 15 YEARS SINCE SURGERY
Pig. I. Survival curves for 60 patients with low grade astrocytoma (grade 1 and 2) and 24 cases with low grade oligodendroglioma.
30 20
-
10
-
0
-
I____
p < 0.05 ,
,
(
,
0123456 Ywts
(
(
,
(
,’
,
,
7
e
9
IO
11
i2
I
I
I
13
14
is
SINCE SURGERY
Fig. 3. Survival curves for 24 patients with low grade oligodendroglioma according to age.
I. J. Radiation Oncology 0 Biology 0 Physics
786
April 1990, Volume 18, Number
4
100 90
no 70 60
so 40 30
m 10 0
0
0
I2
s
4
5
6
7
8
910
0
YEARS SINCE SURGERY
12
3
4
5
6
7
e
9
IO
fl
12
13
I4
IS
YEARS SINCE SURGERY
Fig. 4. Survival curves for 24 patients with low grade oligodendroglioma by extent of surgical resection: biopsy ( 1 case)/partial (10 cases) vs subtotal (10 cases)/total (3 cases).
Fig. 5. Survival curves for 84 patients with low grade astrocytoma and oligodendroglioma according to pre-radiotherapy functional status.
not referred for radiotherapy. In oligodendroglioma, extent of resection was important prognostically. There was an improvement in survival associated with greater performance status. There was no assessment made of post-treatment, longterm quality of life and this would clearly be important in any prospective study in a disease with relatively long survival and known treatment morbidity. Overall, the survival of these patients with low grade gliomas is comparable to other studies (1, 3, 6, 7, 8, 10,
14, 15) and, one should note, remains somewhat limited in the long term. Since the role of radiotherapy, its dose, and the optimal timing of treatment is still unclear, this needs to be resolved in prospective studies before more aggressive treatments can be considered. These studies have recently been started in Europe and North America. In a relatively rare tumor, it is important that as many patients with low grade glioma as possible be included in such studies addressing not just survival but quality of life and treatment morbidity.
REFERENCES 1. Bullard, D. E.; Rawlings, C. E.; Phillips, B.; Cox, E. B.; &hold, S. C.; Burger, P.; Halperin, E. C. Oligodendroglioma. An analysis of the value of radiation therapy. Cancer 60: 2179-2188; 1987. 2. Chin, H. W.; Hazel, J. J.; Kim, T. H.; Webster, J. H. Oligodendrogliomas. I. A clinical study of cerebral oligodendrogliomas. Cancer 45: 1458- 1466; 1980. 3. Fazekas, J. T. Treatment of grades I and II brain astrocytomas. The role of radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 2:66 l-666; 1977. 4. Gol, A. The relatively benign astrocytomas of the cerebrum. A clinical study of 194 verified cases. J. Neurosurg. 18:50 I506; 1961. 5. Kemohan, J. W.; Sayre, G. P. Tumors of the central nervous system. Atlas of tumor pathology, Fascile 35. Washington: Armed Forces Institute of Pathology; 1952. 6. Laws, E. R.; Taylor, W. F.; Chifton, M. B.; Okazaki, H. Neurosurgical management of low-grade astrocytoma of the cerebral hemispheres. J. Neurosurg. 6 1:665-673; 1984. 7. Leibel, S. A.; Sheline, G. E.; Wara, W. M.; Boldrey, E. B.; Nielsen, S. L. The role of radiation therapy in the treatment ofastrocytomas. Cancer 35:1551-1557; 1975. 8. Lindegaard, K.; Mork, S. J.; Eide, G. E.; Halvorsen, T. B.; Hatlevoll, R.; Solgaard, T.; Dahl, 0.; Ganz, J. Statistical
analysis of clinicopathological features, radiotherapy and survival in 170 cases of oligodendroglioma. J. Neurosurg. 67:224-230; 1987. 9. Piepmeier, J. M. Observations on the current treatment of low-grade astrocytic tumours of the cerebral hemispheres. J. Neurosurg. 67:177-181; 1987. 10. Reedy, D. P.; Bay, J. W.; Haln, J. F. Role of radiation therapy in the treatment ofcerebral oligodendroglioma: An analysis of 57 cases and literature review. Neurosurg. 13:499-503; 1983. L. J. Pathology of tumours of 11. Russell, D. S.; Rubinstein, nervous system, 3rd edition. London: Edward Arnold: 197 1. 12. Schoenberg, B. S. Epidemiology of primary nervous system neoplasms. In: Schoenberg, B. S., ed. Advances in neurology, Vol. 19. New York: Raven Press; 1978:475-495. 13. Sheline, G. E. The role of radiation therapy in the treatment of low-grade gliomas. Clin. Neurosurg. 33:563-574; 1986. 14. Weir, B.; Grace, M. The relative significance of factors affecting postoperative survival in astrocytomas, grades one and two. Can. J. Neurol. Sci. 3:47-50; 1976. 15. Wilkinson, I.; Anderson, J. R.; Holmes, A. E. Oligodendroglioma: an analysis of 42 cases. J. Neurol. Neurosurg. Psych. 50:304-312; 1987.
0360.3016190 $3.00 + .oO Copyright 0 1990 Pergamon Press plc
18, PP. 783-786
??Special Feature
LOW GRADE
GLIOMA OF THE CEREBRAL HEMISPHERES A RETROSPECTIVE ANALYSIS OF 88 CASES
A. C. WHITTON, H. J. G. BLOOM, M.D.,
BSc.,
M.B.,
B.S., F.R.C.R.
IN ADULTS:
AND
F.R.C.P., F.R.C.R., F.R.C.S., F.A.C.R.
Department of Radiotherapy, Royal Marsden Hospital and Institute of Cancer Research, Sutton, Surrey, England Eighty-eight adult patients with histologically verified cerebral low grade gliomas (grades 1 and 2) treated with post-operative radiotherapy at the Royal Marsden Hospital between 1960 and 1985 were reviewed. Survival of oligodendroglioma patients was greater than those with astrocytoma (64% vs 36% at 5 years) but the difference was less marked in the long term (35% vs 26% at 10 years). Previous studies have identified prognostic factors important in these tumors: age, extent of surgery, grade, performance status, and duration of symptoms. In this study of low grade astrocytomas and oligodendrogliomas, age (highly significant in the former and significant in the latter), extent of surgery (oligodendrogliomas), and performance status have been demonstrated as factors influencing outcome. The precise role of radiotherapy including the optimal radiation dose and timing of treatment remains unclear. The information, given by a retrospective analysis such as this, helps in the design of prospective, randomized studies looking at radiation dose and time of surgical and radiotherapeutic interventions, always with careful assessment needed of quality of life and treatment morbidity. Brain gliomas, Low grade astrocytoma,
Low grade oligodendroglioma,
INTRODUCTION
Radiotherapy.
formed with uniformity of radiotherapy technique under the supervision of one radiation oncologist (HJGB). Therefore, the information from this, though retrospective, may assist in designing any prospective study.
Low grade gliomas constitute about 10% of primary brain tumors ( 11, 12). They present insidiously, often with seizures that can predate any progressive neurological deficit by years. Their optimal treatment and its timing remains controversial. Whether surgical intervention should be performed at time of diagnosis or at progressive neurological deterioration and whether the addition of radiotherapy is beneficial, is still not completely elucidated. A number of retrospective studies have suggested a beneficial role for radiotherapy in low grade astrocytomas incompletely resected at surgery (3, 4, 6, 7, 13, 14). In low grade oligodendrogliomas, the role of radiotherapy is less clear (1,2, 8, 10). These studies suffer from the problems inherent in retrospective analyses and we await a prospective study to help determine the optima1 treatment. We have analyzed the results of patients treated by surgery combined with radiotherapy at the Royal Marsden Hospital from 1960 to 1985. Their treatment was per-
METHODS
AND
MATERIALS
Patient characteristics
Eighty-eight adult patients with histologically verified low grade glioma of the cerebral hemispheres treated at the Royal Marsden Hospital from 1960 to 1985 were reviewed (Table 1). Astrocytomas were 2.5 times more common than oligodendrogliomas. There were only four cases of mixed astrocytoma and oligodendroglioma. All cases were histologically verified and the pathology subsequently reviewed at the Royal Marsden Hospital. Astrocytomas were graded using the Kernohan system (5), grades 1 and 2 being “low grade.” There were 15 patients with grade 1 astrocytoma and 45 with grade 2 (7 of which were gemistocytic).
Presented at the International Neuro-Oncology Conference, Royal Marsden Hospital, London, England, September 12-14, 1988. Reprint requests to: Dr. A. C. Whitton, Ontario Cancer Treatment and Research Foundation (Hamilton Regional Cancer Centre), 7 11 Concession Street, Hamilton, Ontario, L8V 1C3, Canada.
Acknowledgements-We wish to thank Sue Ashley for computer analysis of data, Christine Gorman for help in processing data and computer input, and Suzanne Bohnet for help in preparing and typing the manuscript. Accepted for publication 12 October 1989.
783
784
1. J. Radiation Oncology 0 Biology 0 Physics Table I. Patient sex and age characteristics
Number Sex: Male Female Age: Range Median
Table 3. Functional
Astrocytoma
Oligodendroglioma
Mixed
60
24
4
29 31
12 12
4
17-70 yr. 36 yr.
17-75 yr. 41 yr.
April 1990, Volume 18, Number 4
26-44 yr. 36 yr.
Symptoms at presentation varied (Table 2) with seizures being most common and then headaches. These symptoms spread over many years but 50 cases presented with less than 2 years duration. The majority of patients (63 cases, 72%) had good functional status pre-radiotherapy with normal activity or limited partial incapacity (Table 3). Prior to 1977, tumor position was located by angiography and air studies, from 1966-1973 by isotope brain scanning, and from 1973 by CT scanning. The frontal lobes were most commonly involved for both astrocytomas and oligodendrogliomas (Table 4).
Treatment Patients were referred for radiotherapy largely from two neurosurgical centers in London-The Atkinson Morley Hospital (52 cases) and the National Hospital for Nervous Diseases (23 cases). Therefore, they were pre-selected and the low number of referrals following total tumor resection reflects this (Table 5). Additionally, it can be seen that a greater tumor resection appeared possible for oligodendrogliomas than astrocytomas with relatively less biopsies only performed. This may reflect the more localized growth of the former. Post-operative radiotherapy with megavoltage treatment (5-8 MV, apart from 4 cases with 250 KV) was used. Patients were immobilized using a mould and a three-field technique simulated with the isodose distribution computed. Wide local fields were employed. Treatments were given daily, 5 times a week with the intention of giving a dose of 50-55 Gy at 1.67 Gy per fraction in 6-6.5 weeks. In this study, minimum and maximum doses have been ascertained, and the number of fractions and overall
status pre-radiotherapy: Astrocytoma
Normal activity without signs Normal activity with signs Partial incapacity, capable of work Disabled, capable of self care Total incapacity
no. of cases
Oligodendroglioma
Mixed
10
9
1
25
9
3
3
3
19 3
3
treatment period have been recorded to give a more accurate assessment of dose. There was some variation of maximum and minimum doses per fraction with medians of 1.74 Gy and 1.57 Gy, respectively, with an overall median dose per fraction of 1.67 Gy. After recurrence of tumor, half the patients received varying combinations of surgery, further radiotherapy and chemotherapy depending on the individual situation. Statistical analysis and follow-up Results were analyzed using the Kaplan-Meier method and logrank stat test. Follow-up was from 2 years 5 months to 20 years (median 9 years) for astrocytomas and from 10 months to 18 years (median 7 years) for oligodendrogliomas.
RESULTS The survival for low grade oligodendrogliomas was better than astrocytomas though in the long term (more than 10 years) this was less marked (Fig. 1). The four cases of mixed astrocytoma and oligodendroglioma are all alive without recurrence, with one case beyond 15 years, one beyond 10 years, and the other two beyond 5 years follow-up. No difference in survival was found between grade 1 (15 cases) and grade 2 (45 cases) astrocytoma when analyzed, with the seven cases of gemistocytic type showing no worsened prognosis. There was no difference in survival according to sex, extent of surgical resection (astrocytomas), tumor dose or dose per fraction (astrocytomas), number of cerebral lobes
Table 2. Symptoms at presentation (may be multiple): no. of cases Astrocytoma Seizure Headache Cerebral motor Nausea/vomiting Cranial nerve Cerebral sensory
35 28 12 8 5 4
Oligodendroglioma 15 9 4 3 1 2
Table 4. Cerebral lobes involved (may be multiple): no. of cases
Mixed 3 2 1
1
Astrocytoma Frontal Parietal Temporal Occipital
34 18 25 2
Oligodendroglioma 16 8 4 3
Mixed 2 3
1
Lowgradegliomas0A.C.
WHITTONAND
785
H.J.G.BLooM
Table 5. Extent of surgical resection: no. of cases Astrocytoma 19 18 21 2
Biopsy Partial Subtotal Total
Oligodendroglioma
Mixed
1 10 10 3
1 2 1
involved, and duration of symptoms. However, there was a clear difference in survival by age for astrocytomas (Fig. 2) and also oligodendrogliomas (Fig. 3). The extent of surgical resection was important in oligodendrogliomas (Fig. 4) and there appeared to be a trend (though not a statistically significant one) toward improved survival for higher doses (above 55 Gy) when maximum dose was analyzed but not minimum dose or dose per fraction.
However, the radiotherapy dose range was limited and it would be difficult to show a dose-response effect. It would be necessary to perform a dose escalation study to investigate this further. Overall, for low grade gliomas, there was a significant improvement in survival for good performance status (Fig. 5). Analyzing recurrence data, there did not appear to be a plateauing of relapses and disease recurrence continued for at least 10 years. Following the relapse of astrocytomas, without further treatment (22 cases), survival was less than 6 months but with treatment (given in 18 cases), more prolonged survival was achieved with more than 30% alive at 2 years. After relapse of oligodendroglioma, without further treatment (6 cases), all were dead by 2 months but with treatment (7 cases), 20% were alive at 2 years. However, this may simply reflect patient-selection and further study is required to elucidate the most beneficial management at relapse.
i 40
i z
40
i% 0
30-
:-y;
‘,
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I_________(
7
‘L______
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E 20
:_
i-l
!_________A
i., 10
-
l-_._.__-__--__
p < 0.005 0
-m 0
1
2
3
4
5
6
7
8
9
f0
YEARS SINCE SURGERY
Fig. 2. Survival curves for 60 patients with low grade astrocytoma
according to age.
DISCUSSION
This retrospective analysis can make no statement as to efficacy of post-operative radiotherapy in low grade gliomas. However, it has revealed factors important in the design of any future study. Previous studies have suggested prognostic factors in these tumors to be: age, extent of surgery, grade (in astrocytomas), performance status, and length of symptoms ( 1, 3, 6, 7, 9, 14, 15). In this study, age was shown to be a very important prognostic factor in astrocytoma and also an important factor in oligodendroglioma. Extent of surgical resection in astrocytoma, surprisingly, did not show a significant difference in outlook, possibly because the better resected cases were
5
-
-
40
-
.-___________
z $ 0 E z
o-
,,,,,,,,, Ol7345678
I
,,,I
9 IO II 12 13 14 15 YEARS SINCE SURGERY
Pig. I. Survival curves for 60 patients with low grade astrocytoma (grade 1 and 2) and 24 cases with low grade oligodendroglioma.
30 20
-
10
-
0
-
I____
p < 0.05 ,
,
(
,
0123456 Ywts
(
(
,
(
,’
,
,
7
e
9
IO
11
i2
I
I
I
13
14
is
SINCE SURGERY
Fig. 3. Survival curves for 24 patients with low grade oligodendroglioma according to age.
I. J. Radiation Oncology 0 Biology 0 Physics
786
April 1990, Volume 18, Number
4
100 90
no 70 60
so 40 30
m 10 0
0
0
I2
s
4
5
6
7
8
910
0
YEARS SINCE SURGERY
12
3
4
5
6
7
e
9
IO
fl
12
13
I4
IS
YEARS SINCE SURGERY
Fig. 4. Survival curves for 24 patients with low grade oligodendroglioma by extent of surgical resection: biopsy ( 1 case)/partial (10 cases) vs subtotal (10 cases)/total (3 cases).
Fig. 5. Survival curves for 84 patients with low grade astrocytoma and oligodendroglioma according to pre-radiotherapy functional status.
not referred for radiotherapy. In oligodendroglioma, extent of resection was important prognostically. There was an improvement in survival associated with greater performance status. There was no assessment made of post-treatment, longterm quality of life and this would clearly be important in any prospective study in a disease with relatively long survival and known treatment morbidity. Overall, the survival of these patients with low grade gliomas is comparable to other studies (1, 3, 6, 7, 8, 10,
14, 15) and, one should note, remains somewhat limited in the long term. Since the role of radiotherapy, its dose, and the optimal timing of treatment is still unclear, this needs to be resolved in prospective studies before more aggressive treatments can be considered. These studies have recently been started in Europe and North America. In a relatively rare tumor, it is important that as many patients with low grade glioma as possible be included in such studies addressing not just survival but quality of life and treatment morbidity.
REFERENCES 1. Bullard, D. E.; Rawlings, C. E.; Phillips, B.; Cox, E. B.; &hold, S. C.; Burger, P.; Halperin, E. C. Oligodendroglioma. An analysis of the value of radiation therapy. Cancer 60: 2179-2188; 1987. 2. Chin, H. W.; Hazel, J. J.; Kim, T. H.; Webster, J. H. Oligodendrogliomas. I. A clinical study of cerebral oligodendrogliomas. Cancer 45: 1458- 1466; 1980. 3. Fazekas, J. T. Treatment of grades I and II brain astrocytomas. The role of radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 2:66 l-666; 1977. 4. Gol, A. The relatively benign astrocytomas of the cerebrum. A clinical study of 194 verified cases. J. Neurosurg. 18:50 I506; 1961. 5. Kemohan, J. W.; Sayre, G. P. Tumors of the central nervous system. Atlas of tumor pathology, Fascile 35. Washington: Armed Forces Institute of Pathology; 1952. 6. Laws, E. R.; Taylor, W. F.; Chifton, M. B.; Okazaki, H. Neurosurgical management of low-grade astrocytoma of the cerebral hemispheres. J. Neurosurg. 6 1:665-673; 1984. 7. Leibel, S. A.; Sheline, G. E.; Wara, W. M.; Boldrey, E. B.; Nielsen, S. L. The role of radiation therapy in the treatment ofastrocytomas. Cancer 35:1551-1557; 1975. 8. Lindegaard, K.; Mork, S. J.; Eide, G. E.; Halvorsen, T. B.; Hatlevoll, R.; Solgaard, T.; Dahl, 0.; Ganz, J. Statistical
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