Central nervous system lesions and advanced ovarian cancer

Central nervous system lesions and advanced ovarian cancer

GYNECOLOGIC ONCOLOGY 30, 87-97 (1988) Central Nervous System Lesions and Advanced Ovarian Cancer JAMES S. HOFFMAN, M.D.,*.’ AND YOLANDA M. PENA, M...

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GYNECOLOGIC

ONCOLOGY

30, 87-97 (1988)

Central Nervous System Lesions and Advanced Ovarian Cancer JAMES S. HOFFMAN,

M.D.,*.’ AND YOLANDA M. PENA, M.D.?

*Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, Connecticut 06032; and fDepartment of Neurology, University of Connecticut Health Center, Farmington, Connecticut 06032 Received May 14, 1987 Over the past 5 years we have seen seven cases of central nervous system tumors in patients with advanced or recurrent ovarian carcinoma. These have ranged in location from the conus medullaris to the brain and have varied in time of occurrence from the time of cancer diagnosis to 63 months following surgery. A diagnosis of metastatic ovarian carcinoma was established in six of the cases, while one patient had a second primary malignancy. All cases had prodromal and localizing neurologic symptoms which led to the suspicion of central nervous system involvement. The critical diagnostic studies were myelography and computed tomography of the brain and spine. We have reviewed our approach to diagnosis and therapy. 0 1988 Academic press. h.

INTRODUCTION

The most common mechanism of metastasis from epithelial ovarian cancer is transcoelomic, intraperitoneal spread [l]. Nonetheless, clinicians must remain alert to other mechanisms and sites of spread. The purpose of this report is to highlight the susceptibility of the central nervous system to involvement by ovarian carcinoma and to suggest the importance of early and appropriate diagnostic studies of ovarian carcinoma patients who have neurological symptoms. CASE 1

B.C. is a 44-year-old, gravida 0, female who presented with lethargy, weight loss, and increased abdominal girth. Two weeks prior to admission she developed low back pain and slurred speech. Examination revealed a 17-cm solid mass originating in the left pelvis. She was also noted to have a left foot drop and a decreased ability to concentrate. A blood urea nitrogen determination was 78 mg/dl. A retrograde pyelogram revealed bilateral ureteral obstruction. Ureteral stents were placed on each side, leading to resolution of her azotemia and her confusion. Computed tomography of the head as well as chemical and cytologic studies of her cerebrospinal fluid were normal. Exploratory laparotomy revealed extensive Stage III poorly differentiated serous cystadenocarcinoma of the ovaries. Total abdominal hysterectomy, bilateral sal’ To whom requests for reprints should be addressed. 87

009O-8258/88$1.50 Copyright 0 1988 by Academic Press, Inc. All rights of reproduction in any form reserved.

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pingo-oophorectomy, omentectomy, and extensive cancer debulking were performed. The patient recovered well postoperatively with improvement of the foot drop. She began to walk with the aid of a cane but complained of recurrent sacral discomfort. Chemotherapy was started with cis-platinum, Adriamycin, and cyclophosphamide. The following week, the patient noted progressive proximal muscle weakness in the lower extremities. She then experienced sudden loss of control of the urinary and anal sphincters. She was admitted for an emergency myelogram which showed an extradural spinal cord compression at the level of the conus medullaris. External beam radiation was begun on an emergency basis. Her strength and sphincter control improved dramatically. Subsequently, she completed her chemotherapy and remains without evidence of recurrence after 44 months. Case 2

C.D. is a 65year-old female with Stage III poorly differentiated adenocarcinoma of left ovary diagnosed in May 1986, when a pelvic mass was palpated during treatment for low back pain. At exploratory laparotomy, extension of cancer to sigmoid colon, left pelvic sidewall, and omentum were noted. A hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. Three to four weeks after surgery, the low back pain increased in intensity. A bone scan revealed increased uptake at the lumbar spine. Computerized tomography of the lumbar spine revealed a large retroperitoneal mass eroding the L3 and L4 vertebral bodies. She received her first course of c&platinum, Adriamycin, and cytoxan in June 1986. Persistence of the back pain, soreness of thigh muscles, and burning sensation of the medial aspect of the thighs prompted a neurology consult. She also complained of intractable constipation and progressive urinary retention. Neurologic examination revealed moderate muscle weakness of the thigh muscles and weakness of the right great toe. Also noted were generalized hyperreflexia with a right Babinski and decreased vibratory sensation in stocking distribution. A lumbar myelogram revealed a left ventral filling defect compressing the area of the conus medullaris and cauda equina. It encompassed a totally collapsed L3 vertebral body (Fig. 1A). Post-myelography computerized tomography confirmed the extensive L3 vertebral body destruction as well as an associated paraspinal mass at the level of the conus (Fig. 1B). A second cycle of chemotherapy was begun as well as a course of external beam radiation to the lumbar region. The patient became more ambulatory with some resolution of the pain, constipation, and urinary retention. Case 3 G.L. was a 58-year-old, gravida 3, para 3, female who presented in September 1982for anemia and abdominal mass. At surgery, right colectomy, omentectomy, and bilateral salpingo-oophorectomy were performed for advanced Stage III serous adenocarcinoma of the ovaries. This was followed by treatment with cisplatinum, Adriamycin, and cytoxan. Her condition improved dramatically, but a pelvic mass recurred and she was again explored in June 1983. The uterus was removed and further cancer debulking was done. Hexamethylmelamine was given

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FIG. 1. (A) Lumbar myelogram reveals left compressive lesion in the area of conus medullaris. L3 vertebral body is collapsed. (B) Post-myelography computed tomogram demonstrating destruction of L3 vertebral body and left paraspinal mass.

as secondary chemotherapy. In August 1983 she developed severe lower back pain radiating to the left leg. Myelography showed a herniated L5-Sl disc which was surgically repaired. She was readmitted the following month for progressive lower extremity weakness and urinary retention. Myelography showed a complete block from TIO to Ll . She had a laminectomy and excision of an epidural tumor. Histology was identical to her ovarian primary. Postoperatively, she received radiation therapy. However, her neurologic deficits did not improve and she died 3 months later of progressive abdominal carcinomatosis. Case 4

M.W. was a 68-year-old, gravida 0, female. She was transferred from a nursing home to our hospital with advanced untreated carcinoma. A large mass filled the abdomen and several nodular lesions were present in the vagina. Biopsy confirmed the diagnosis of poorly differentiated serous adenocarcinoma, suggestive of ovarian origin. By history, the patient had been weak, unable to walk, and incontinent of urine and feces for 4 months. Examination revealed quadriplegia and a sensory level of T2. An intravenous pyelogram showed bilateral partial obstruction of the ureters. Bone scan confirmed numerous bony metastases to the spine, skull, and long bones. Computed tomography of her spine showed destruction of the C4 and C5 vertebral bodies with extradural compression of the cord. External beam radiation was given to the cervical spine region. Her symptoms failed to resolve and she died later that month. Case 5 K.W. is a 53-year-old, gravida 2, para 2, female who presented in June 1981 for an enlarging pelvic mass. She had a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy for Stage III, poorly differentiated

FIG. 2. (A) Contrast-enhanced computed tomogram shows left parietal lesion with extension edema. (B) Repeat study 3 months later shows significant regression of the left parietal lesion.

serous adenocarcinoma of the ovaries. Adjuvant chemotherapy was given, including &-platinum, Adriamaycin, and cytoxan. A second-look laparotomy, including 29 biopsies, showed no evidence of residual cancer. She was well until January 1986 when she noted numbness of the medial left thigh and weakness of the right toes. Examination showed only an absent left ankle jerk and decreased pin-prick in the left L-l distribution. Ultrasound exam showed large paraaortic and iliac nodal masses. Fine-needle aspirate confirmed recurrent carcinoma. It was felt that her retroperitoneal masses explained her neurologic signs and symptoms. She was again given chemotherapy with cis-platinum which led to complete resolution of her neurologic complaints. In July 1986 ultrasound examination showed regrowth of her retroperitoneal tumor and chemotherapy was changed to hexamethylmelamine. In September 1986 she complained of progressive right hemiparesis. Examination revealed weakness of the right extremities, leg greater than arm. This was associated with right hyperreflexia and a right Babinski, and normal cranial nerve examination. Computed tomography of the brain showed a 9-mm left parietal enhancing lesion with marked peritumoral edema (Fig. 2A). She was given whole-brain radiation therapy and systemic steroids. Her hemiparesis resolved completely and a repeat tomography showed regression of her brain tumor (Fig. 2B). Case 6 A.G. was a 61-year-old, gravida 2, para 2, female. She had a total abdominal hysterectomy and bilateral salpingo-oophorectomy performed in March 1983 because of cystic ovarian tumors. These were found to be bilateral endometroid adenocarcinomas of the ovaries. No other lesions were noted within the abdomen. A chest radiograph showed a solitary lesion in the left lung which was removed, and found to have the same histology as the primary ovarian tumor. She was given adjuvant and cis-platinum, Adriamycin, chemotherapy with cyclophosphamide. She had no further evidence of illness until July 1985when she had a generalized tonic-clonic seizure. Neurologic examination was normal but computed tomographic

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study of the brain revealed an enhancing lesion in the right frontal lobe with moderate peritumoral edema. Stereotaxic biopsy revealed a Grade 3 astrocytoma. In August 1985 the tumor was partially resected, showing areas of even worse differentiation consistent with a Grade 4 astrocytoma. She received adjuvant treatment with radiation and chemotherapy. Case 7 C.G. was a 74-year-old, nulligravid female who presented in April 1982 for rapid onset of ascites and dyspnea. An exploratory laparotomy was done revealing widespread carcinomatosis. A left salpingo-oophorectomy was done, but the bulk of the cancer was felt to be unresectable. The patient was treated with cisplatinum, Adriamycin, and cyclophosphamide, which sufficed to reverse all of her symptoms. A second-look laparotomy was done which showed microscopic residual cancer in only one of 19 specimens. She was given further treatment with cyclophosphamide for the following year. She remained well until July 1986 when she presented for progressive confusion and an unsteady gait. A nodular mass was noted in her neck and chest radiograph showed numerous enlarged mediastinal lymph nodes. Computed tomography of the brain showed a large, hyperdense mass attached to the falx cerebri, causing compression of the lateral ventricles. There was marked obstructive hydrocephalus which required placement of a ventriculoperitoneal shunt. Ventricular cerebrospinal fluid cytology showed adenocarcinoma consistent with her ovarian primary. Despite whole-brain radiation therapy, her strength and concentration remained poor. She died September 1986. RESULTS

Central nervous system lesions were located throughout the neuroaxis (Table 1). There were two cases of involvement of the conus medullaris (Cases 1 and 2). Both of these occurred near the time of presentation with ovarian cancer. Another patient developed thoracic cord compression 11 months after ovarian cancer surgery (Case 3). Cervical cord compression was the initial manifestation of widespread metastatic ovarian carcinoma in one case (Case 4). Back pain was a prodromal symptom in two of the four patients with cord compression. All four developed weakness of the lower extremities and loss of sphincter control prior to their diagnosis of central nervous system involvement. Three patients developed brain tumors between 28 and 63 months after the diagnosis of advanced ovarian carcinoma. Case 5 had been diagnosed for multiple pelvic and paraaortic sites of progressive recurrent ovarian carcinoma. The diagnosis of her brain tumor was clinically related to advancing metastatic cancer. Computed tomography showed a large mass at the gray-white matter junction. There was extensive edema. These findings were highly suggestive of metastatic cancer (Fig. 2A). She was thus given whole-brain radiation therapy with excellent resolution of her neurologic syptoms. Secondary chemotherapy has failed to control her progressive disease in the abdomen. Conversely, Case 6 developed a frontal lobe tumor despite a seemingly durable remission from Stage IV carcinoma of the ovary. Stereotaxic biopsy of the lesion proved that it was a grade 4 astrocytoma

Treatment of neurologic lesion

3 III/2 Two-month history of low back Serous adenocarpain and urinary retention cinema of ovary Exam: weakness of lower extremities

11 months

44 months

remission of

Alive-NED,

Alive-partial symptoms

Outcome

Died-3 months after Lumbar myelogram: 1. Spinal decomextradural neurosurgery (abdominal pression and excision carcinomatosis) compression TlO- of Ll tumor 2. Radiation therapy

Lumbar myelogram: 1. Radiation therapy collapsed I. 2 2. Chemotherapy vertebral body and ventral extradural compression at Ll-L3

Diagnostic procedures

2 III/3 One month history of low back 1 month pain and progressive gait Serous adenocarcinema of ovary difficulty Exam: weakness of lower extremities, hyperreflexia, and urinary retention

Interval diagnosis to CNS lesion Lumbar myelogram: 1. Radiation therapy extradural 2. Chemotherapy compression of conus moduliaris

Stage/Grade

1

1 III/3 Six month history of left foot 2 weeks Serous adenocardrop, progressive weakness cinema of ovary of lower extremities, and loss of sphincter control

Case

Neurologic symtoms and signs

TABLE CASE SUMMARIES

28 months

6 IV/3 New onset generalized tonicEndometrioid clonic seizure adenocarcinoma of ovary

I III/2 Two-month history of progessive 51 months Serous adenocarcofusion cinema of ovary

63 months

tion

At presenta-

5 III/3 One week history of Serous adenocarprogressive right hemiparesis cinema of ovary

4 IV/3 Four-month history of leg Serous adenocarweakness and urinary cinema of ovary incontinence Exam: quadriplegia with a sensory level at T2

Alive-symptoms

resolved

Died-l month after radiation therapy (abdominal carcinomatosis)

CT scan of the brain: metastatic adenocarcinoma near falx cerebri

Whole-brain radiation therapy

Died-l month after wholebrain radiation

CT scan of brain: 1. Surgery partial Died-17 months after right frontal lobe resection of GBM neurosurgery (GBM) (second primary) tumor, 2. Whole-brain radiation glioblastoma therapy multiforme (GBM) proven by stereotoxic biopsy

Whole-brain radiation CT scan of the brain: left parietal therapy tumor

CT scan of cervical Radiation therapy region: bony destruction of C4 and C5 veriebral bodies with extradural cord compression

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(glioblastoma multiforme). Case 7 had also been previously diagnosed for multiple sites of recurrent metastatic ovarian carcinoma. Cytologic confirmation of metastatic cancer to the brain was obtained at the time of placement of a ventriculoperitoneal shunt. Overall, only two patients experienced complete resolution of their neurologic symptoms. In both cases, radiation therapy was used to the affected portion of the neuroaxis. This was then followed by chemotherapy. One of these cases continues to have no evidence of disease after 44 months. The other case has developed progressive cancer in the abdomen. Two other patients had partial relief of their neurologic symptoms. Both cases also developed progression of their cancers outside of the neuroaxis. In three cases the treatments failed to remedy the neurologic complaints and the systemic symptoms. Overall, only three patients from this series remain alive. Two of them have evidence of progressive cancer. DISCUSSION

Weakness of the lower extremities and loss of sphincter control are the classic signs of cord compression. These signs should alert clinicians to perform emergency myelography. Early and accurate diagnosis is very critical since recovery varies with the extent of motor weakness in the lower extremities [2,3]. Other candidates for myelography include patients with radiographic or bone scan evidence of bony metastasis to the spine. The spine is a common site of metastatic disease, accounting for up to 39% of all bony metastases [4]. O’Rourke er al. [5] have found that the use of computed tomographic metrizamide myelography demonstrates epidural cord compression in 47% of patients with bony metastasis in the spine. We utilized this technique to delineate the extent of involvement in our most recent patient (Case 2) (Fig. 1B). Computer-assisted tomography of the symptomatic portion of the cord assists both in making a diagnosis of metastatic cancer to the cord and in delineating the extent of involvement. Treatment of these patients has generally included high-dose steroids followed by decompressive laminectomy or radiation therapy [2,6-91. Various series in the literature have not demonstrated a clear difference in outcome with either modality [6-91. We have therefore reserved laminectomy for patients who need a tissue diagnosis or patients whose symptoms worsened during or after radiation therapy [2]. The efficacy of therapy is also dependent on the existence of a modality which will control the patient’s systemic disease. Cerebral neoplasms can frequently present with symptoms similar to those of an acute cerebrovascular event, such as progressive confusion, a generalized or focal seizure, or progressive hemiparesis. In patients with a known history of carcinoma, these symptoms should raise a high level of suspicion for cerebral metastasis. Brain metastases occur in 3.3-6.3% of patients with fatal cancers. This may occur as a sign of progressive disease or as the initial presenting sign of coexisting cancer [ 10-121. Brain metastases spread hematogenously and extend along the perivascular spaces of Virchow-Robin, involving meninges, parenchyma, or both. Meningeal involvement occurs most commonly in reticular and breast cancer, whereas parenchymal involvement occurs most commonly in lung, colon,

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kidney, and skin cancer [13]. Ovarian cancer is rarely associated with cerebral metastases, but most reported cases have had parenchymal rather than meningeal involvement [ 14-201. With the advent of a noninvasive procedure such as computerized tomography (CT) of the brain, lesions as small as 1 cm may be encountered. Some perform CT scans of the brain as part of staging in those patients with cancers that frequently metastasize to the brain (lung, breast, colon, kidney). Common CT findings of cerebral metastases are of well-circumscribed, spherical lesions which enhance with contrast and are usually associated with variable amounts of edema. The development of yet another noninvasive neuroradiologic procedure, the magnetic resonance imaging scan (MRI), has further increased the sensitivity for these diagnoses although the specificity is yet to be determined [21]. The magnetic resonance imager may locate additional metastases which have been missed by the CT scan. This may change the goals of therapy. In patients with progressive cancer outside of the neuroaxis and characteristic radiologic findings of cerebral metastasis, prompt treatment with steroids and whole-brain radiation therapy (WBRT) may proceed without an obligatory histologic confirmation. However, some cases with solitary brain lesions may benefit from surgical recection along with pre- or postoperative WBRT [22-241. The decision frequently depends on the histology of the cerebral neoplasm or the systemic cancer. Biopsy should be considered in cases with surgically accessible solitary cerebral lesions or in lesions presenting in unusual locations. This is especially vital when the underlying cancer appears to be in remission. The cerebral mass may have radiologic features mimicking an abscess, a benign tumor, or a primary malignant tumor. Our Case 6 is the second patient in the literature to have a glioblastoma multiforme following treatment for a gynecologic malignancy [25]. This case illustrates the importance of histology in planning therapy in these cases. Computer-assisted stereotaxic biopsy is currently available as a relatively simple way of arriving at a rapid histological diagnosis without the risk of a more complicated craniotomy [26-291. This is particularly important in deep-seated lesions where the histological margins of neoplasms are otherwise indistinguishable from cerebral edema [30]. Batson’s human cadaveric injections and animal experiments clearly demonstrated reversal of blood flow both up and down the vertebral venous system [31]. This flow is independent of the heart and lungs and probably explains the proclivity of the spine to be involved by locally advanced ovarian carcinoma. One of our cases (Case 7) of cerebral metastasis had previously developed widespread pulmonary metastases. Her brain metastasis may have traversed through the heart and lungs. In our other case (Case 5) of brain metastasis, the mechanism of spread was obscure. Her lesions developed 63 months after original diagnosis, and only after widespread abdominal and pelvic recurrence. The pattern of her involvement is consistent with metastasis via the vertebral venous system [32]. It is however, difficult to exclude the possibility of previous widespread cancer having traversed the heart and lungs. Perhaps the central nervous system had provided sanctuary for her malignancy and allowed it to eventually develop there.

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It is noteworthy, that all four cases of spinal cord metastasis occurred much sooner than the two cases of brain metastasis. Spread of cancer cells through Batson’s venous plexus is a likely cause of all of our cases of cord metastasis. REFERENCES 1. Julian, C. G., Goss, J., Blanchard, K., and Woodruff, J. D. Biologic behavior of primary ovarian malignancy, Obstet. Gynecol. 44, 873-884 (1974). 2. Martenson, J. A., Evans, R. G., Lie, M. R., et al. Treatment outcome and complications in patients treated for malignant epidural spinal cord compression @CC), J. Neurol. Oncol. 3, 77-84 (1985). 3. Rome, R. M., and Nelson, J. H. Compression of the spinal cord or cauda equina complicating gynecological malignancy: Reports of five cases and a review of the literature, Gynecol. Oncol. 5, 273-290 (1977). 4. McNeil, B. J. Value of bone scanning in neoplastic disease, Semin. Nucl. Med. 4, 277 (1984). 5. O’Rourke, T., George, C. B., Redmond, J., et al. Spinal computed tomography and computed tomographic metrizamide myelography in the early diagnosis of metastatic disease, J. Clin. Oncol. 4, 576-583 (1986). 6. Gilbert, R. W., Kim, J. H., and Posner, J. B. Epidural spinal cord compression from metastatic tumor: Diagnosis and treatment, Ann. Neurol. 3, 40-51 (1978). 7. Posner, J. Spinal cord compression: A neurological emergency, Clin. Bull. 1, 65-71 (1971). 8. Tang, S. G., Byfield, J. E., Sharp, T. R., Utley, J. F., Quinal, L., and Seagren, S. Prognostic factors in the management of metastatic epidural spinal cord compression, J. Neurol. Oncol. 1, 21-28 (1983). 9. Young, R. F., Post, E. M., and King, G. A. Randomized prospective comparison of laminectomy vs radiotherapy, J. Neurosurg. 53, 741-748 (1980). 10. Kurland, L. T. The frequency of intracranial and intraspinal neoplasm in the resident population of Rochester, Minnesota, J. Neurosurg. 15, 627-641 (1958). 11. Percy, A. K., Elveback, L. R., Okazaki, H., ef al. Neoplasms of the central nervous system: Epidemiologic considerations, Neurology 22, 40-48 (1972). 12. Brewis, M., Poskanzer, D. C., Rolland, C., et al. Neurological disease in an English city, Acta Neurologica Stand. 42, (Suppl), 24 (1966). 13. Weisberg, L. A. Cerebral computed tomography: A text-atlas. Saunders, Philadelphia, pp. 147161 (1977). 14. Larson, D. M., Copeland, L. J., Moser, R. P., Malone, J. M., Gershenson, D. M., and Wharton, J. T. Central nervous system metastases in epithelial ovarian carcinoma, Obstet. Gynecol. 68, 746-750 (1986). 15. Mayer, R. J., Berkowitz, R. S., and Griffiths, C. T. Central nervous system involvement by ovarian carcinoma: A complication of prolonged survival with metastatic disease, Cancer 41, 776-783 (1978). 16. Budd, G. T., Webster, K. D., Reimer, R. R., Martinbeau, P., and Livingston, R. B. Treatment of advanced ovarian cancer with cisplatin, Adriamycin and cyclophosphamide: Effect of treatment and incidence of intracranial metastases, J. Surg. Oncol. 24, 192-195 (1983). 17. Barker, G. H., Orledges, J., and Wiltshaw, E. Involvement of the central nervous system in patients with ovarian carcinoma, Brit. .T. Obstet. Gynecol. 88, 690-694 (1981). 18. Stein, M., Steiner, M., Klein, B., et al. Involvement of the central nervous system by ovarian carcinoma, Cancer 58, 2066-2069 (1986). 19. Sulker, A., Siegal, T., and Gez, E. Spontaneous intracranial hemorrhage in a patient with ovarian carcinoma. Gynecol. Oncol. 20, 204-208 (1985). 20. Bakri, Y. N., Lee, J. H., Lewis, G. C., Lublin, F. D., and Danoff, B. Meningeal carcinomatosis complicating gynecologic malignancies: A literature review and report of a case, Obstet. Gynecol. Surv. 38, 1-5 (1983). 21. Ramsey, R. G. Neuroradiology, Saunders, Philadelphia, 2nd ed., pp. 443-444 (1986). 22. Cairncross, J. C., Chernik, N. L., Kim, J. H., and Posner, J. B. Sterilization of cerebral metastses by radiation therapy, Neurology 29, 1195-1202 (1979).

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23. Suit, H. D., and Todoroki, T. Rationale for combining surgery and radiation therapy, Cancer 55, 2246-2249 (1985). 24. Bergonie, J., and Triboneauy, L. Interpretation of some results of radiotherapy and an attempt at determining a logical technique of treatment, Radiat. Res. 11, 587-588 (1959).

25. Barnes, A. E., Liwniecz, B. H., Schellhas, H. F., Altshuler, G., Aron, B. S., and Lippert, W. Successful treatment of placental choriocarcinoma metastatic brain followed by primary brain glioblastoma, Gynecol. Oncol. 13, 108-l 14 (1982). 26. Apuzzo, J. L. J., and Sabshin, J. K. Computed tomographic guidance stereotaxis in the management of intracranial mass lesions. Neurosurgery 12, 277-285 (1983). 27. Boethius, J., Bergstrom, M., Greitz, T., and Ribbe, T. CT localization in stereotactic surgery, Appl. Neurophysiol. 43, 164-169 (1980). 28. Kelly, P. J., Alker, G. J., Jr., Kall, B. A., and Goerss, S. Method of computed tomographybased stereotactic biopsy with arteriographic control, Neurosurgery 14, 172-177 (1984). 29. Ostertag, C. B., Mennel, H. D., and Kiessling, M. Stereotactic biopsy of brain tumors, Surg. Nemo/.

14, 275-283 (1980).

30. Kelly, P. J. Computer-assisted stereotaxis: New approaches for the management of intracranial intra-axial tumors, Neurology 36, 535-541 (1986). 31. Batson, 0. V. The function of the vertebral veins and their role in the spread of metastases, Ann. Surg. 112, 138-149 (1940). 32. Kapp, D. S., LiVolsi, V. A., and Kohorn, E. I. Cauda equina compression secondary to

metastatic carcinoma of the uterine corpus: Preservation of neurologic function and long-term survival following surgical decompression and radiation therapy, Gynecol. Oncol. 20, 209-218 (1985).