medulloblastoma in adults. improved survival with supervoltage radiation therapy

4
Medulloblastoma in Adults: Improved Survival With Supervoltage Radiation Therapy GENE KOPELSON, MD.’ RITA M. LINGGOOD, MD.’ AND GEORGE M. KLEINMAN, M D t During the period from January 1962-June 1979, 17 adults (216 years of age) received postoperative supervoltage neuraxis radiation therapy for medulloblastoma. An actuarial five- and ten-year survival rate of 46% was achieved, and the major site of recurrence postirradiation was in the posterior fossa. Compared to previous pediatric series, adults may demonstrate more visceral metastases and fare less well after tumor recurrence. Compared to prior series of adult patients, the demonstrated improved survival is attributed to increased doses delivered to the posterior fossa. Cancer 491334-1337, 1982. LTHOUGH THE GREAT MAJORITY Of medulloblas- A tomas occur in childhood, pooled data from nine series reveals that approximately one-quarter to-one third of these lesions occur in adults (Table I). The oldest reported patient with biopsy-proven medullo- blastoma was age 83 years.’ Most large series give de- tailed radiotherapeutic technique and results for chil- dre~~,~-~and although most series document better short- term survival for adults, opinion differs as to whether long-term survival is better for children’-’ or ad~lts,~.’ or whether long-term survival is unaffected by age.* Since most of the previously reported series of adult patients relate experience from the 1930s-1950s when technique and equipment were more limited, we have reviewed our experience with 17 adults seen since 1962. Materials and Methods During the period from Janurary 1962-June 1979, 17 adults (216 years of age) received radiation therapy as part of initial management for medulloblastoma. There were 11 men and 6 women; ranging in age from 16-41 years (median 24 years). Pathology slides were reviewed by one of us (G.M.K.) without knowledge of the clinical course of the patient; in three cases the original slides could not be obtained and the original report was used. One patient with a mixed medullo- -- * From the Department of Radiation Medicine and + Neuropath- ology Laboratory of the Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts. Address for reprints: Gene Kopelson, MD, 31 Country Club Road, Peabcdy. MA 01960. The authors thank Mindy and Barry Printz-Kopelson and Joan Horgan for their help in the preparation of this manuscript. Accepted for publication January 27. 1981. blastoma and ependymoma is also included. The initial disease extent was staged retrospectively according to the operative staging system of Chang er al.9 as mod- ified by Harisiadis and Chang4 In two patients, a T- stage could not be assigned because the initial surgical procedures were performed only on the spinal compo- nents of the disease (Table 2). In one patient the op erative report could not be obtained. Initial posterior fossa surgery in the remaining 14 patients consisted of gross complete tumor resection in two patients, subtotal resection in 11, or biopsy in one. The time interval from surgery to initiation of ra- diation therapy ranged from 2-41 days (median 14). All patients received super-voltage radiation therapy via 6oCo y-rays or 2- or 10-MV x-rays. All roentgen doses were converted into rad with appropriate correction fac- tors. One patient died of uncontrolled primary disease TABLE I. Reported Series with Adult Medulloblastoma Patients Total No. Adults Authors Patients No. (percent) Aron’ Berger and Elvidge” Bloom er a\.’ Chatty and Earle6 C~shing*~ Quest er al.‘ Rubenstein and Northfield” Spitz et Kopelson er al. (current series) Total 24 I28 I08 105 61 118 42 97 43 721 7 (29%) 30 (23%) 16 (15%) 38 (36%) 13 (21%) 28 (24%) 15 (36%) 30 (31%) 22* (51%) 199 (28%) At the Massachusetts General Hospital from 1962-1980, 43 medulloblastoma patients were seen. Only those 17 adults who re- ceived postoperative irradiation at this institution are included in this report. A clinicopathologic review of all 43 cases is reported else- where.” OOO8-543)</82/040l/ I334 50.70 0 American Cancer Society I334

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Medulloblastoma in Adults:

Improved Survival With Supervoltage Radiation Therapy

GENE KOPELSON, MD.’ RITA M. LINGGOOD, MD.’ AND GEORGE M. KLEINMAN, MDt

During the period from January 1962-June 1979, 17 adults (216 years of age) received postoperative supervoltage neuraxis radiation therapy for medulloblastoma. An actuarial five- and ten-year survival rate of 46% was achieved, and the major site of recurrence postirradiation was in the posterior fossa. Compared to previous pediatric series, adults may demonstrate more visceral metastases and fare less well after tumor recurrence. Compared to prior series of adult patients, the demonstrated improved survival is attributed to increased doses delivered to the posterior fossa.

Cancer 491334-1337, 1982.

LTHOUGH T H E GREAT MAJORITY O f medulloblas- A tomas occur in childhood, pooled data from nine series reveals that approximately one-quarter to-one third of these lesions occur in adults (Table I ) . The oldest reported patient with biopsy-proven medullo- blastoma was age 83 years.’ Most large series give de- tailed radiotherapeutic technique and results for chil- d r e ~ ~ , ~ - ~ a n d although most series document better short- term survival for adults, opinion differs as to whether long-term survival is better for children’-’ or ad~ l t s ,~ . ’ or whether long-term survival is unaffected by age.*

Since most of the previously reported series of adult patients relate experience from the 1930s-1950s when technique and equipment were more limited, we have reviewed our experience with 17 adults seen since 1962.

Materials and Methods

During the period from Janurary 1962-June 1979, 17 adults (216 years of age) received radiation therapy as part of initial management for medulloblastoma. There were 11 men and 6 women; ranging i n age from 16-41 years (median 24 years). Pathology slides were reviewed by one of us (G.M.K.) without knowledge of the clinical course of the patient; in three cases the original slides could not be obtained and the original report was used. One patient with a mixed medullo-

-- * From the Department of Radiation Medicine and + Neuropath-

ology Laboratory of the Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.

Address for reprints: Gene Kopelson, MD, 31 Country Club Road, Peabcdy. MA 01960.

The authors thank Mindy and Barry Printz-Kopelson and Joan Horgan for their help in the preparation of this manuscript.

Accepted for publication January 27. 1981.

blastoma and ependymoma is also included. The initial disease extent was staged retrospectively according to the operative staging system of Chang er al.9 as mod- ified by Harisiadis and Chang4 I n two patients, a T- stage could not be assigned because the initial surgical procedures were performed only on the spinal compo- nents of the disease (Table 2). In one patient the o p erative report could not be obtained. Initial posterior fossa surgery in the remaining 14 patients consisted of gross complete tumor resection in two patients, subtotal resection in 11, or biopsy in one.

The time interval from surgery to initiation of ra- diation therapy ranged from 2-41 days (median 14). All patients received super-voltage radiation therapy via 6oCo y-rays or 2- or 10-MV x-rays. All roentgen doses were converted into rad with appropriate correction fac- tors. One patient died of uncontrolled primary disease

TABLE I . Reported Series with Adult Medulloblastoma Patients

Total No. Adults Authors Patients No. (percent)

Aron’ Berger and Elvidge” Bloom er a\.’ Chatty and Earle6 C ~ s h i n g * ~ Quest er al.‘ Rubenstein and Northfield” Spitz et Kopelson er al. (current series)

Total

24 I28 I08 105 61

1 1 8 42 97 43

721

7 (29%) 30 (23%) 16 (15%) 38 (36%) 13 (21%) 28 (24%) 15 (36%) 30 (31%) 22* (51%)

199 (28%)

At the Massachusetts General Hospital from 1962-1980, 43 medulloblastoma patients were seen. Only those 17 adults who re- ceived postoperative irradiation at this institution are included in this report. A clinicopathologic review of all 43 cases i s reported else- where.”

OOO8-543)</82/040l/ I334 50.70 0 American Cancer Society

I334

No. 7 MEDULLOBLASTOMA I N ADULTS - Kopelson et al. 1335

TABLE 2. Stage Distribution of Patients

M-stage

T-stage Mo M, M2 M, M. Total

T , 0 0 0 0 0 0 T2 2 0 0 0 I 3 T, 3 0 1 1 4 9 T4 0 0 0 I 1 2 T. 0 I 0 1 1 3

Total 5 I 1 3 7 17

after receiving 2800 rad to the whole brain. Of the remaining 15 patients, whole brain doses ranged from 1886-5005 rad; 12/ 16 patients received r3000 rad. The primary site (posterior fossa) doses ranged from 3772- 6000 rad; 1 1 / 16 patients received 24500 rad and 8/ 16 received r 5 0 0 0 rad. The spinal cord doses ranged from 2829-4025 rad; 10/16 received 23000 rad.

Parallel-opposed whole brain fields were used in con- junction with orthogonal spinal fields. Overlap was avoided with the use of gaps and moving junctions. Five patients received adjuvant chemotherapy as part of ini- tial management, with various combinations of cytoxan, vincristine, procarbazine and nitrosoureas.

Six patients (discussed later) were reirradiated for tumor recurrence (4/6 also received chemotherapy). Survival curves via the life-table actuarial method" were calculated from date of diagnosis.

Results

A five- and ten-year actuarial survival rate of 46% was achieved (Fig. 1). Local control in the posterior fossa was a function of dose even though there were small numbers of patients (Table 3). Most failures were at the primary site (Table 4). Results of retreatment appear in Table 5.

Discussion

I n previously reported series of adults with medul- loblastoma, ten-year survival rates have ranged between 0-24% (Table 6). However, most of these series are from the older literature in which modern equipment was not used, and details of the radiotherapeutic treat- ment (if given) of the adults was not described.

Our five- and ten-year actuarial survival rates (Fig. 1 ) of 46% (although only two patients are alive at ten years) we attribute in part to the increased dose to the posterior fossa delivered in recent years, with subse- quent increased local control (Table 3). Similar data is available only in the childhood literature.'-'"' We chose three years as a minimal time to estimate local control because approximately 75% of recurrences in

OVERALL SURVIVAL FOR i 7 ADULTS WITH MEDULLOBLASTOMA

k! 401 2o t 01 I I I I I

0 2 4 6 8 10 Y€ARS AFTER D/AGNOS/S

FIG. 1 . Life-table actuarial survival rate for adult medulloblastoma patients given postoperative radiation therapy. Numbers above line indicate patients at risk.

children develop in the first three years postirradia- t i ~ n , ' * ~ although late recurrences can develop in adults.'*

Sites of failure for adult medulloblastoma have not been described in much detail before; the data in Table 4 demonstrates that, as in childhood tumors, the major

TABLE 3. Posterior Fossa Local Control Related 10 Dose (Minimum 3-year Follow-up)

Initial posterior No. local Local fossa dose No. subsequent control followed control

(rad) local failure 2 3 years* rate

<4000 I 0 o/ I 4000-5000 4 t 3 317

25000 1 2$ 213

Six other patients have local control at t 3 years (116 with 4000-5000 rad,

t Two of these patients received adjuvant chemotherapy. $One of these patients received adjuvant chemotherapy.

and 5/6 with 25000 rad).

TABLE 4. Sites of Failure in Nine Patients ~~ ~

Site No. patients

Posterior fossa h* Spinal cord 3 Viscera 2 Cerebrospinal fluid & 7

Brain (other than posterior fossa) It In 4/6 the posterior fossa alone. In olfactory groove (see text).

1336 CANCER April I 1982 Vol. 49

TABLE 5. Management o f Recurrences in Six Patients

Initial doses Retreatment doses

Whole Posterior Recurrence Whole Posterior Status and

months brain fOSSd Spinal (months) brain fOSSd Spinal post-retrcatment

- DOD, 5 1886 3712 2829 7 1886 - 2263 4149 2829 16 1791 2168 2263 DOD, 33 3000 4500 3000 27 - 2000 - A E D . 3 4000 4982 2930 57 - 1980 -

5000 5000 3106 I5 - - 900 DOD, 4 4000 5000 3000 15 - - 1000 DOD. 6

ANED, 14

All doses in rads. Recurrent tumor at olfactory groove. DOD = dead of disease; A 13 D = alive with disease; ANED = alive

no evidence of disease.

site of treatment failure is in the posterior fossa. To our knowledge, there have been only ten previously reported adults with medulloblastoma who developed biopsy- and/or autopsy-proven extraneuroaxial distant metas- tases. I 3 - l 9 In our series, visceral metastases developed in two of nine (22%) of the patients who failed treat- ment (Table 4), a higher ratio than the 9% (3/32) re- ported in children by Harisiadis and Chang.4 Our two patients each had advanced disease at presentation (T3MI and T,M3), and their only initial surgical pro- cedure was performed on the spinal component of the disease without any shunts being placed. However, bi- opsy- and autopsy-proven distant metastases developed in each patient in bones and lymph nodes, and in one patient also in the liver and The possible increased risk of visceral metastases in adults compared to children has been described briefly in another series.*'

The one patient developing recurrence within the brain at a site other than the posterior fossa developed tumor at the olfactory groove (Table 4). This patient received only 1886 rad whole brain irradition, and since port films are unavailable, this failure could be related

both to underdosage and/or possible geographic miss to this subfrontal area.9*21*22

Of the six adults retreated for tumor recurrence (Table 5), the median survival after completion of sal- vage irradiation was only 5.5 months, compared to a mean survival of 1 1.5 months" and 14 months4 reported in two pediatric reirradiation series. One of the patients in Table 5 , whose failure occurred 57 months after di- agnosis, demonstrates that late recurrences can occur in adults.'2

In our series, of six women, two have survived 2 4 years and are at risk for long-term side effects of treat- ment upon the ovaries. Neither patient has become pregnant yet, although normal pregnancy and offspring after craniospinal irradiation in medulloblastoma pa- tients has been No patient in this series has developed a new primary cancer postirradiation, and there has been no evidence seen of radiation damage after the increased dose levels given.

In conclusion, increased survival has been demon- strated for adult medulloblastoma patients compared to series reported in the past, which we attribute to

TABLE 6. Survival in Adult Medulloblastoma Series

Authors

Years of presentation Survival rates of patients Year of (inclusive) report 5-years 10-years

Spitz et a/.26 Ringertz and Tola2* Borghi and Chiorinom Bloom er ul.' Miles and Bhandari' Chatty and Earle6 Bloom and Walsh2' Quest el al.' Bouchard* Kopelson el al. (current series)

? = information unavailable in report.

?-? 1947 1926- 1946 1950 1946-1961 1964 1950- 1964 1969 1954-1968 1970

?-? 1971 ?-? 1975

1952-? I978 1939-1963 1980 1962-1979 1982

24% 8% ?

38% 22% 26% 42% 38% 40% 46%

? 0% ?

OW 1 1 % 16% 20% 19% 24% 46%

No. 7 MEDULLOBLASTOMA IN ADULTS 0 Kopelson et al. 1337

increased doses delivered to the posterior fossa. Com- pared to children reported in the literature, adults at our institution may demonstrate more visceral metas- tases and fare less well after tumor recurrence.

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