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Fifteen patients with progressive primary malignant or metastatic brain tumors were treated on a clinical and pharmacokinetic study with intracarotid cisplatin and bleomycin. Toxicity was tolerable and consisted mainly of nausea and vomiting. Neurologic toxicity included focal seizures (1), leukoencephalopathy (1), and motor weakness (1). Five patients had improvement in CT scans and four patients had stabilization of disease. Recommended dosage for future clinical trials are cisplatin 60 mg/m2 and bleomycin 100 units. Pharmacokinetics of intracarotid cisplatin revealed the jugular vein concentration was twice the peripheral vein level at the end of infusion. Cisplatin is a drug which has demonstrated in vitro activity against malignant gliomas (1). Clinical trials with intravenous administration of cisplatin has shown definite, although limited antitumor activity against primary brain tumors (2,3,4) and metastatic brain tumors (5,6). To enhance its antitumor effect, cisplatin has been administered by the intracarotid route (7,8,9). The results appear encouraging, but neurological and ophthalmological toxicity may occur (8). In our initial study with intracarotid cisplatin, 35 patients with malignant brain tumors (23 with primary brain tumors and 12 with brain metastases) progressing after cranial irradiation +/- chemotherapy were treated. Of 20 evaluable patients with primary tumors, 6 responded to therapy and 5 had stable disease. Five of 10 evaluable patients with brain metastases responded and 2 had stable disease. For responding primary brain tumor patients the median time to progression was 33 weeks. The recommended dose for intracarotid cisplatin was 60-75 mg/m2 administered every 3-4 weeks (7,8). Higher cisplatin doses produced more central neurological toxicity. There is limited data on the central nervous system pharmacology of cisplatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Between January 1982 and June 1986, 60 consecutive patients with high-grade astrocytomas [39 glioblastoma multiforme (GBM), 21 anaplastic astrocytoma (AA)] were treated with radiation therapy after biopsy (13 patients) or resection (47 patients). Fifty-three patients were treated with limited-volume irradiation, and seven patients received whole-brain irradiation. The mean tumor dose was 65.4 Gy. In 35 patients, chemotherapy was given as part of their initial treatment. The 1- and 2-year survivals for GBM patients were 40 and 14%, respectively. Survival figures for AA patients were 76 and 52% at 1 and 2 years, respectively. The progression-free rate at 1 year was 13% in GBM and 29% in AA patients. Thirty-four of 48 patients who received limited-volume irradiation had evidence of progression on postirradiation CT scans. Six patients (3 GBM, 3 AA) had evidence of a new intracranial metastatic site on CT scan. In three patients the metastasis was within the previously irradiated volume, and in the other three patients, it was outside this volume. All six had evidence of progression of their primary tumor at the original location on CT scan prior to the discovery of the metastatic site. Twenty-one patients (15 GBM, 6 AA) had at least one postirradiation reoperation for a recurrent mass. Nineteen patients had recurrent tumors in the primary site, and two patients had necrosis but no tumor. Patients who received limited-volume irradiation for high-grade astrocytomas achieved the same survival results as patients treated previously with whole brain irradiation. New intracranial metastases did not influence the outcome, since these were always antedated by tumor progression at the primary site.

Twenty-three patients with malignant melanoma metastatic to the central nervous system (CNS) were treated with intracarotid cisplatin-based chemotherapy. Twenty-two had failed prior cranial radiation therapy (one patient refused radiation therapy) and had progressive brain metastases documented by computerized tomography (CT). Intracarotid cisplatin 40-75 mg/m2 was administered alone (seven patients) with 1,3-bis(2-Chloroethyl)-1-nitrosourea (BCNU) (13 patients) or bleomycin (three patients). Courses were repeated monthly with CT scan. Seven patients (30%) had objective improvement in CT scans and three patients (13%) had stabilization of disease. The median time to tumor progression for responding patients was 20 weeks (range 8-34 weeks) while stable disease ranged from 9-12 weeks. In three patients the extracranial disease progressed while the brain metastases responded. Neurological and retinal toxicity were potential complications of therapy. Intracarotid cisplatin-based chemotherapy may be useful for palliation in selected patients with malignant melanoma and CNS metastases.

CT findings of 15 patients with histologically proven primary central nervous system (CNS) lymphoma were reviewed with pathologic correlation in order to evaluate variable CT patterns. There were a total of 32 lesions. Of the 15 patients studied, seven had acquired immunodeficiency syndrome (AIDS), all diagnosed within the past 3 years. The CT observations of eight non-AIDS patients were consistent with findings reported previously. Most of the lymphomatous lesions were either hyper- or isodense, round or oval masses with homogeneous contrast enhancement and variable surrounding edema. Pathologic examination showed tightly packed preserved lymphoma cells without necrosis. In AIDS patients, rim or ring enhancement of lymphoma, indistinguishable from brain abscess, was frequently seen. Histologic examination consistently showed extensive tumor necrosis with preservation of viable tumor cells at the periphery. A third and infrequent CT pattern was multiple infiltrative nonnodular solid enhancement with extensive edema. Pathologic correlation showed infiltrating viable tumor cells without necrosis. The rim- or ring-enhancing brain lesion seen in AIDS patients can either be an abscess or a primary lymphoma; proper tissue collection is essential for correct diagnosis and appropriate treatment.

Five cases, four histologically proved, or hamartoma of the tuber cinereum and hypothalamus in children (age range: 2--12 years) are reported. Three cases had pubertas praecox, and in all of these the hamartoma was located in the basal cistern between the chiasm and pons, and had a collar button shape and size typical of hamartoma of the tuber cinereum. In the third case, which presented with headache, a huge calcified mass in the suprasellar region was initially thought to be craniopharyngioma. The fourth case had a hamartoma within the substance of the hypothalamus and presented with hyponatremia and temporal lobe seizures.

Twenty-one cases of malignant gliomas showing multiple tumor foci on CT are described. In 11 patients multiple lesions were evident on the initial CT scan (synchronous lesions); the other 10 patients developed one or more lesions months to years after the original gliomas (metachronous lesions) were documented. Distinctions between multifocal and multicentric gliomas are discussed and CT patterns presented. A diagnosis of synchronous multicentric or multifocal glioma should be considered in patients with multiple parenchymal masses and no known primary tumor elsewhere.

The intracranial CT findings of mineralizing microangiopathy, a rare condition, are described in seven patients. The underlying pathology was posterior fossa medulloblastoma (four patients), cerebelloastrocytoma (two patients), and acute lymphatic leukemia (one patient). Each of the seven patients was less than 10 years old. Dystrophic calcification was present in the corticomedullary junction, lentiform nucleus of the basal ganglia, corticomedullary junction, and dentate nucleus of the cerebellum. Three of the patients had subtle neurologic signs related to the mineralizing microangiopathy, but none died of central nervous system disease. Although three factors--radiation therapy, chemotherapy, and increased intracranial pressure--probably have a synergistic role in the pathogenesis, radiation is believed the dominant factor. The minimum dose required to induce this damage is 2000 rad.

Three cases of intracranial perineural metastasis from adenoid cystic carcinoma of the head and neck are presented. The metastases presented more than 1 year (14 months to 5.5 years) after the primary tumor had been successfully treated without any evidence of local recurrence. Computed tomography of the intracranial metastasis demonstrated well-demarcated, hyperdense, enhancing extraaxial masses indistinguishable from meningioma. An intracranial extraaxial mass lesion with the appearance of a meningioma in a patient with known adenoid cystic carcinoma of the head and neck, regardless of the presence or absence of local recurrence, should be considered as metastasis until proved otherwise.

Five cases of rare gliosarcoma are described with pathologic correlation. Because of its sarcomatous component, gliosarcoma tends to present as a sharply defined, round or lobulated, hyperdense solid mass with relatively homogeneous contrast enhancement and peritumoral edema. Sharp demarcation of the tumor from surrounding tissue may lead to complete removal and prolonged survival despite high malignancy. However, aggressive tumor regrowth occurs often after incomplete resection. The genesis of gliosarcoma is also discussed.

Eighteen patients with progressive or recurrent intracerebral malignant neoplasms after cranial radiation therapy were entered in a phase-I trial of intracarotid bis-chloroethylnitrosourea (BCNU) and cisplatin. Thirty-six courses of varying doses of BCNU and cisplatin were infused intraarterially via a percutaneous, trasfemoral approach. Courses were repeated every 4-6 weeks upon patients' recovery from toxicity. Intraarterial cisplatin or BCNU alone was administered if the blood counts were still subnormal. CT scans and neurologic examinations were performed monthly. Major toxic effects included ipsilateral retinal (amaurosis) in 4 patients and neurologic toxicity in 2 patients (minor focal seizure, reversible obtundation in one patient, and transient hemiparesis in one patient). One patient was infused by a catheter inserted into the supraclinoid internal carotid artery and had no further visual deterioration and no major side effects. Tumor regression was observed in patients previously treated with radiation and/or systemic chemotherapy, including 4 of 9 who had recurrent malignant gliomas, and 2 of 9 who had metastatic tumors. Recommended dose for phase-II trials is BCNU 100 mg/m2 and cisplatin 60 mg/m2 every 4-6 weeks. Retinal and neurologic toxicity are possible side effects.

Thirty-seven cases of juvenile pilocytic astrocytoma were reviewed retrospectively to determine their CT and MR characteristics. All cases occurred in pediatric patients, except for one in a young adult. There was a propensity for tumors to be located around the third and fourth ventricles. On CT the tumors were all sharply demarcated and smoothly marginated and rarely had associated edema. The lesions tended to be round or oval. The tumor matrix was most often hypo- or isodense with marked enhancement. Cyst formation, either micro- or macrocystic or combined, was frequently observed, and tumor calcification occurred occasionally. On MR the tumors appeared hypo- or isointense on T1-weighted images and hyperintense on T2-weighted images. The radiologic appearances of juvenile pilocytic astrocytomas are quite characteristic. By using age of presentation, typical location, configuration, and enhancement patterns, the presurgical diagnosis of juvenile pilocytic astrocytoma can be made with a high index of confidence.

Intracarotid BCNU (100 mg/m2) and cisplatin (60 mg/m2) were administered to 36 patients with malignant brain tumors recurrent or progressive after cranial irradiation. Courses of therapy were repeated at 4-6 week intervals. Of 23 evaluable patients with recurrent glioma, 9 (39%) had tumor regression by CT scan and 3 had stable disease. The median time to tumor progression for responding patients was 37 weeks. For all patients with primary tumors it was 14 weeks. Six of 9 patients with no prior chemotherapy had a response and 1 had stable disease. Of 14 patients who had received prior chemotherapy, 3 had a response and 2 had stable disease. Survival ranged from 9 weeks to 95+ weeks (median 34 weeks) from start of therapy. Six of 23 patients with primary tumors are alive 1 year or more following therapy. Four of 11 patients with brain metastases had a response and 2 had stable disease. Major neurologic toxicity of intracarotid BCNU and cisplatin appeared cumulative and consisted of reversible hemiparesis in 3% of 118 courses, TIA in 1%, expressive aphasia in 9%, lethargy in 3%, seizures in 12%, and reversible confusion in 1%. Retinal toxicity consisted of mild blurring of vision in 4 patients and ipsilateral blindness in 5 patients. Three of 22 patients who had received supraophthalmic infusion later developed evidence of leukoencephalopathy. Intracarotid BCNU and cisplatin appears to have modest increase in activity over intracarotid cisplatin alone (Cancer 54:794, 1984), however, neurologic and retinal toxicity may also be increased.

Five cases, four histologically proven, of hamartoma of the tuber cinereum and hypothalamus in children are reported. The ages of the patients range from 2 to 12 years. Three cases had pubertas praecox, and in all of these the hamartoma was located in the basal cistern between the chiasm and pons and had a collar button shape and size typical of hamartoma of the tuber cinereum. In the third case, a huge calcified mass in the suprasellar region was initially thought to be craniopharyngioma. The fourth case had a hamartoma within the substance of the hypothalamus and presented with hyponatremia and temporal lobe seizures.

The radiographic findings in 35 cases of untreated intracranial oligodendrogliomas were reviewed. The mean age of the patients was 34.6 years, and seizure disorder and headache were the most frequent presenting symptoms. Slightly less than two-thirds of the tumors were histologically pure and almost half were low-grade. Most lesions were cerebral and peripheral in location, and the majority were in the frontal lobes. On CT the tumors were usually hypo- or isodense. Contrast enhancement of tumor occurred in nearly half the cases, and was usually mild and poorly defined. Tumor calcification often occurred, and hemorrhage or cystic formation was not infrequent. Occasionally, calvarial erosion was associated with the tumors because of their peripheral location and slow-growing nature. The lesions were usually sharply demarcated and without edema. MR most frequently revealed hypointense lesions on T1-weighted images and abnormal hyperintensity on T2-weighted scans. In regard to grading or purity of oligodendrogliomas, no significant correlations were found except for a suggestion that higher-grade and mixed tumors tend to enhance more often on CT. The radiographic features of oligodendroglioma are quite characteristic but not pathognomic. A high preoperative suspicion might lead to more appropriate tumor management. MR, although less sensitive in detecting tumor calcification, is superior to CT in defining the tumor extent, which is beneficial for surgical and postsurgical radiotherapy planning.

Of a total of 52 cases of ependymomas, 38 were intracranial, with 15 being supratentorial and 23 infratentorial. Pre- and postoperative computed tomographic scans were correlated with surgical pathologic findings in four cases of supratentorial ependymomas. Pathologic specimens were analyzed from another four cases for which only postoperative scans were available. Seven cases had no computed tomographic studies, but pathology reports were available. Common computed tomography findings for these tumors included para- or intraventricular location, one or more cystic areas within the tumor, and calcifications within the lesion or around its periphery. Proven subependymal spread of tumor was evident by computed tomography in one case. Mixing of ependymoma with oligodendroglioma was present in four cases and with both oligodendroglioma and astrocytoma in two cases. Microscopic calcifications were more frequently seen in ependymomas that were mixed with oligodendroglioma.

Twenty-eight patients with malignant brain tumors (16 with primary brain tumors and 12 with brain metastases) progressing after cranial irradiation with or without chemotherapy received varying doses of intracarotid VP-16. Courses of therapy were repeated every 4 weeks along with computerized axial tomography scan and neurologic examination. Of 15 evaluable patients with primary malignant brain tumors, 1 responded to therapy and 5 had no immediate tumor progression for 2-10 months. None of 12 evaluable patients with brain metastases responded to intracarotid VP-16 although 5 had no immediate tumor progression from 1-4 months. Side effects of treatment were uncommon. Using this route of administration, intracarotid VP-16 does not appear to increase response rates in patients with primary malignant brain tumors, compared with results reported for intravenous VP-16.