Inr. J. Radialion Oncology 8101. Phys.. Vol. 7, pp. 721-725 Printed in the U.S.A. All rights rcscrvcd.

036~3016/81/060721-05502.00/0 Copyright 0 1981 Pergamon Press Ltd.

??Original Contribution

MYELOGRAPHY AND CYTOLOGY IN THE TREATMENT OF MEDULLOBLASTOMA

MELVIN DEUTSCH, M.D. Professor of Radiology, University Health Center of Pittsburgh, Pittsburgh, PA 152 13

DONALD H. REIGEL, M.D. Neurosurgeon, St. Francis General Hospital, Pittsburgh, PA 15201

Eight of 22 children with newly diagnosed medulloblastoma bad asymptomatic spiaal cord involvement detected by myeiograpby. Two additional patients bad demonstrable spihal cord lesioas at tbe time of relapse in the posterior fossa. Cerebral spiaal fluid (CSF) cytology results were iaakcurate in predicting cord involvement. Sevea patients have rehpsed 9-69 moaths from completion of radiotber4py. Three had initial cord involvement and also bad suheqaeat cord involvement at the time of intracraaial relap$e or afterwards. Frontal lobe involvement as the initial site of relapse occurred in 3 patieats. Computerized tom@graplty has been vahable ia tbe early detection of intracraaiai relapse. Three children are alive and well 10, 18, aad 19 moatlts respectively from time of relapse. All were retreated with radiotherapy in conjuactioa with misoaidhzole and subsequent cbemotberapy.

Medullobhstoma, Myelograpby, CSF cytology, Spinal cord taetastases.

INTRODUCTION The proper management of malignancy requires accurate determination of the extent of the primary and the detection of the disease in regions of likely involvement. For many years, the propensity of medulloblastoma to disseminate within the central nervous system has been recognized, and current concepts in the management of medullobiastoma include “prophylactic” irradiation of the entire central nervous system. However, controversy exists as to the amount of radiation needed for the prophylactic treatment of the spinal cord. In an attempt to more effectively treat the spinal cord, pre-therapy myelograms have been performed since 1974 on all children with medulioblastoma presenting to the Radia- tion Oncology Department of the University Health Center of Pittsburgh. The subsequent dose to the spinal cord is determined by the myelographic findings. Specifi- cally, demonstrable lesions are irradiated to higher doses-approaching cord tolerance-than the usual prophylactic doses. The reasons for doing “staging” myelograms were to determine the incidence of unsus- pected, but demonstrable lesions at the time of diagnosis and to determine whether myelographic findings had prognostic importance.

METHODS AND MATERIALS Twenty-two children with newly diagnosed medullo-

blastoma have had myelograms performed after surgery on the posterior fossa tumor, but before commencing radiotherapy. In addition, myelograms were performed on two patients initially treated elsewhere who presented with recurrent tumor in the posterior fossa. In all cases, there was no clinical evidence to suggest cord involve- ment.

Sixteen children were males. Nineteen were white. Two children were black and one child was Philipino. The median age for children with normal myelograms was six years (range 10 months to 14 years, 9 months). For children with abnormal myelograms, the median age was three years, 7 months (range 5 months to 14 years, 5 months).

Eight of 22 children with newly diagnosed medullo- biastoma had evidence of cord involvement on myelogra- phy. Spinal cord involvement ranged from lesions measuring several millimeters up to extensive deposits several centimeters in size.2

The results of cerebral spinal fluid (CSF) cytology examinations are shown in Table 1 & 2. Ventricular- peritoneal shunts were performed on 20 children prior to

Reprint requests to: Melvin Deutsch, M.D., Joint Radiation Radiology Meeting, New Orleans, Louisiana, October 25, Oncology Center, 3601 Fifth Avenue, Pittsburgh, PA 15213. 1979.

Presented in part at the American Society of Therapeutic Accepted for publication 3 1 March 198 1.

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722 Radiation Oncology ??Biology 0 Physics June 198 I. Volume 7, Number 6

Table I. Patients with normal myelograms

CSF cytology CSF cytology Survivai* Patient Age Sex shunt pre-op at myelography post-op (months)

I 2 3 4 5 6 7 8 9

IO II 12 13 14

63/12 5 IO/12 6 6112

13 2 IO/12

11 4 l/l2 9 7112

14 9112 I2j12 5 7112

IO/12 9 7112 26112

F Negative M N.D. M Negative M Negative F Negative M N.D. M N.D. M Negative M Negative F N.D. M Negative F Negative M Negative M N.D.

N.D. 60liJ.E.~. N.D. 49N.E.D. Positive 47 A.R. N.D. 40 N.E.D. Positive 36 Dead Negative 42 A.R. Negative 26 N.E.D. Negative 43 A.R. Negative 71 N.E.D. Negative I8 N.E.D. N.D. I2 N.E.D. Negative I8 N.E.D. Negative <3 N.E.D. N.D. c3 N.E.D.

*Survival from diagnosis. N.D. - Not done; N.E.D. - Alive, no evidence of disease; A. R. - Alive after treatment for recurrent tumor.

surgery on the posterior fossa. Shunts were inserted in order to relieve hydrocephalus and provide rapid relief of symptoms. Among the 14 children with normal myelo- grams, fluid from the lateral ventricle (shunt) was exam- ined pre-operatively in 9 patients and all were negative for malignant cells. Two patients (Table 1. patients 4 & 9), had pneumoencephalography performed pre-opera- tively. CSF from Patient 4 was negative for malignant ceils. CSF from Patient 9 contained malignant cells. During the operative procedure on the posterior fossa, CSF from the vicinity of the tumor was examined cyto- logically in three patients (Table 1, Patients 1, 5,s). CSF from Patients 1 and 5 contained malignant cells. CSF from Patient 8 was negative for malignant cells.

Myelograms were performed one-three weeks post- operatively and before initiation of radiotherapy. Ten of 14 children whose myelograms were negative had CSF examined for malignant cells at the time of myelography and two were positive. CSF from 6 of 8 children with abnormal myelograms was examined cytologically at the time of myelography. Malignant cells were found in three patients. An additional patient (Table 2, Patient 3) had re-insertion of a ventricular-peritoneal shunt post-opera-

tively. CSF from the shunt at that time contained malig- nant cells. Three children with abnormal myelograms did not have malignant cells in CSF taken at the time of shunt placement pre-operatively or at the time of my- elography (Table 1 & 2).

All patients were treated with radiotherapy directed to the entire cranial-spinal axis using two large lateral parallel opposed fields to include the brain and upper spinal cord, and a long posterior field covering the spinal cord. The cranial-spinal junction gap was calculated as previously described.’ The entire cranial-spinal axis was usually irradiated to a minimum of 3000 rad/20 treat- ments. The posterior fossa was then boosted to a total dose of 5000-5400 rad. Demonstrable lesions in the spinal cord were usually boosted to a total dose of 3900-4500 rad.

Two children presented with clinical and radiographic evidence of recurrent tumor in the posterior fossa within 13 months of having been treated elsewhere (Table 3). Patient #l had malignant ceils in CSF from the lateral ventricle and patient #2 had malignant cells in CSF from a lumbar puncture done at the time of a myelogram. Patient #2 also had a right parietal lobe lesion demon-

Table 2. Patients with cord involvement

Patient Age

(years) Sex CSF cytology CSF cytology shunt pre-op at myelography post-op

Survival* (months)

24112 2 5112

I2 IO/l2 5112

I4 S/l2 3 II/l2 3 l/l2 4 6112

M M M F M F M M

Negative Positive Negative Negative N.D. Positive (shunt) Negative N.D. Negative Negative Negative Negative Positive Positive N.D. Positive

13 Dead 27 Dead 72 A.R. 51 N.E.D. 37 N.E.D. 27 N.E.D. 26 N.E.D.

3 N.E.D.

*Survival from diagnosis. N.D. - Not done; N.E.D. = Alive, no evidence of disease; A.R. = Alive after treatment for recurrent tumor.

Myelography for medulloblastoma 0 M. DEUTSCH AVD D. H. REIGEL 723

Table 3. Patients presenting with posterior fossa recurrence--Initial treatment elsewhere

Disease Myelogram Other Survival Age initial free at intracranial CSF from

Patient Sex diagnosis (years) interval relapse tumor cytology relapse

1 Male II 9112 13 mos. Tumor at T-6 None Positive 4 months (Lateral ventrical)

2 Female 5 9 mos. Extensive Right parietal Positive 3 months involvement tumor (Lumbar puncture)

strated on computerized tomography (CT)scan. (Figure 1) Patient #I was re-treated with radiotherapy to the posterior fossa (3000 rad/ 15 treatments) and cord (2000 rad/ 15 treatments) plus chemotherapy. He expired three months following completion of radiotherapy. At autopsy, there was extensive necrosis of the cervical spinal cord, but only microscopic amounts of tumor in the left caudate nucleus and at the foramen of Luschka. Patient #2 was treated with chemotherapy and expired 3 months from documentation of her recurrence.

RESULTS Nineteen children were followed more than one year

from diagnosis; 12 whose myelograms were initially normal and 7 who had gross tumor demonstrated on myelography. Of the seven children with abnormal myelograms, four are alive and well 30-54 months (aver- age 38 l/2) from diagnosis. Of the 12 children whose

Fig. 1. Patient 2 (Table 3). Metastatic lesion right parietal lobe apparent at time of relapse in posterior fossa.

myelograms were initially negative for all metastases. 8 are alive and well 14-63 months (average 38) from diagnosis.

Three of the four patients whose initial myelograms were negative and who had recurrent tumor, had intra- cranial recurrences with negative cytology and myelo- grams at the time of relapse (Table 4, Patients 1, 2, 3). In all three patients, CT scans indicated recurrence before the patients experienced severe neurological deficits. All had biopsy confirmation of their intra-cranial recurrence. Patient #l (Table 4) experienced mild headaches which were considered to be psychological prior to the CT Scan. Patient #2 essentially was neurologically stable at the time a CT scan demonstrated relapse in the frontal lobe. Patient #3 had unilateral hearing loss for three months; a retrospective review of a CT scan done seven months prior demonstrated posterior fossa recurrence. All have been re-irradiated in conjunction with misonidazole and have had chemotherapy. All were treated in ten fractions. Two patients received 2000 rad to the entire brain and 3000 rad to the frontal lobe region. The spinal cord was irradiated to 1000 rad. Patient f3 received 3000 rad to the entire brain and 1800 rad to the spinal cord. All are alive and clinically free of disease 19, 18 and 10 months respectively from tissue documentation of recurrent tumor. The fourth patient (Table 4, Patient #4) had rapidly progressing deterioration of her neurological status over a two week period. A CT scan demonstrated tumor in the posterior fossa and spinal fluid contained malignant cells. However, she was considered too ill for myelography, and expired 4 months from time of relapse in spite of radiotherapy and chemotherapy.

Three children (Table 4, Patients #S, 6, 7) with initial cord involvement relapsed 12, 19 and 71 months from diagnosis or 9, 16 and 69 months respectively from completion of radiotherapy. All of these children devel- oped recurrent tumor in the spinal cord. Patient #5 was noted to have spinal cord involvement at autopsy one month after diagnosis of intra-cranial recurrence. Patient #6 had spinal cord involvement demonstrated on my- elography seven months after diagnosis of recurrent tumor in the frontal lobe. Unfortunately, myelography was not performed at the time the initial cranial relapse was diagnosed. Both children expired at ten and 24 months respectively after completion of their initial course of radiotherapy. The third patient (#7) presented with signs of cranial nerve impairment and extremity

724 Radiation Oncology ??Biology 0 Physics June I98 I, Volume 7. Number 6

Table 4. Patients with relapse

Disease Survival free from

Age at Initial Initial Site of interval* Patient diagnosis Sex cytology

relapse myelogram relapse (months) (months)

I 66112 M Shunt-negative Normal Frontal lobe 27 19A&W Myelogram-positive

2 11 M Myelogram-negative Normal Frontal lobe 24 18A&W 3 97112 M Shunt-negative Normal Posterior fossa 28 (CT) lOA&W

Myelogram-negative 4 2 lo/12 F Shunt-negative

35 Biopsy Normal Posterior fossa 32 4 Dead

Myelogram-positive CSF cytology- positive

5 24112 M Shunt-negative Tumor Diffuse craniol- 9 1 Dead Myelogram-positive cervical cord spinal

&T 12 6 25/12 M Shunt-negative Extensive Frontal lobe 16 8 Dead

Myelogram-ne’gative Spinal cord 23 1 12 lo/12 M Post-op shunt positive Tumor Posterior fossa 71 IA&W

cervical cord Spinal cord

*From end of initial radiotherapy. A & W - Alive and well.

weakness at the time of relapse. Tumor was detected in the posterior fossa and spinal cord. He has just completed re-irradiation of the entire CNS axis (3000 rad/ 10) plus misonidazole and is currently on chemotherapy.

DISCUSSION The incidence of clinically unsuspected gross lesions in

the spinal cord at presentation in this series is 36.4%. Both patients who presented with recurrence in the poste- rior fossa after having been treated elsewhere also had clinically unsuspected lesions in the cord as demonstrated by myeiography. CSF cytology findings have been inac- curate in predicting the presence or absence of demon- strable spinal cord involvement. The presence of malig- nant cells in the CSF may vary according to the site from which the fluid was removed and the time in relation to the posterior fossa surgery. From the small number of patients in this series it is difficult to ascribe prognostic value to the CSF cytology results. However, the two children with initially normal myelograms, but with malignant cells in the CSF at the time of myelography, both relapsed. A third child with malignant cells at the time of pneumoencephalography (pre-operatively) is still alive and well 60 months from diagnoses.

None of the seven patients who relapsed had their recurrence just in the spinal cord. Supratentorial recur- rences are reportedly rare,’ yet three of seven patients in this series presented with recurrent tumor in the frontal lobe. In all three patients, the lesion appeared to arise from the anterior mid aspect of the anterior cranial fossa (Figure 2). It is suspected that the medial aspect of the floor of the anterior cranial fossa, which forms the roof of the nasal cavity, may be shielded by the blocks used to shield the eye from the lateral whole brain portals. For this reason, it may be important to supplement the dose to

this partially protected area with an anterior field directed to the medial portion of the floor of the anterior cranial fossa.

The presence of initial cord involvement may not indicate a poor prognosis ‘in adequately irradiated patients. Demonstrable lesions in the spinal cord should

Fig. 2. Patient 1 (Table 4). Solitary metastatic lesion left frontal lo&.

Myelography for meciulloblastoma 0 M. DEUTSCH AND D. H. REIGEL 725

receive higher doses of radiation than the usual “prophy- be re-treated with radiotherapy. Although patients in this lactic” doses. Conversly, “uninvolved” spinal cords might series had their entire central nervous system re- be adequately protected by lower doses of radiation than irradiated, it might be necessary to irradiate only the commonly employed. involved volume if CSF cytology and myelograms are

Patients with solitary intracranial recurrences should negative at the time of recurrence.

REFERENCES 1. Bukovitz. A.G., Deutsch, M., Slayton, R: Orthogonal fields: Scarff, T.B.: Myelography in patients with medulloblasto-

Variations in dose vs. gap size for treatment of the central ma. Radiology 117: 461468, 1975. nervous system. Radiology 126: 795-798, 1978. 3. McFarland, D.R., Horwitz, H., Saenger, E.L., Bahr, G.K.:

Medulloblastoma-A review of prognosis and survival. Br. 2. Deutsch, M., Scotti, L.N.. Hardman. D.R., Reigel, D.H., J. Radiology 42: 198-2 14, 1969.