A retrospective review of the records of the Division of Neuropathology at the New York University Medical Center between 1977 and 1988 revealed 53 cases of adult supratentorial astrocytomas. Fifty were fibrillary, and three were gemistocytic. Two additional patients had pilocytic tumors and were not included in the study. The majority of patients had either a subtotal (64%) or gross total resection (19%). Biopsy (17%) was performed for deep-seated lesions and for those lesions confined to eloquent cortex. Forty-eight patients (91%) received postoperative radiation therapy. The median survival was 7 1/4 years with a 5-year survival of 64%. Multivariate regression analysis demonstrated that the most important prognosticators for improved survival were young age, absence of contrast enhancement of the original tumor on computed tomography (CT) and the performance status of the patient. Patients with hemispheric tumors died from dedifferentiation into an anaplastic astrocytoma or a glioblastoma multiforme, with a median time to recurrence of 4.5 years from the original surgery. Survival from the time of recurrence was 12 months. Subsequent operations confirmed progression towards malignancy in six of seven (86%) recurrent tumors. CT contrast enhancement of the original tumor was associated with a 6.8-fold increase in risk for later recurrence. Patients with thalamic tumors (six patients) had a poor prognosis with a median survival of less than 2 years. A review of their CT scans suggest that four died of progressive low-grade disease; however, confirmatory autopsy data were available for only one patient. This study supports others that have shown improved survival for adult patients with astrocytomas treated in the CT era.
Background. The median survival for adults with glioblastoma multiforme (GBM) is 12 months, despite surgery, radiation, and chemotherapy. Regimens using interleukin‐2(IL‐2) plus lymphokine‐activated killer (LAK) cells have been beneficial against systemic cancers, albeit with significant toxicity. Methods. Nineteen adults with recurrent malignant glioma (5 GBMs, and 4 anaplastic astrocytomas (AA)), Karnofsky performance status 60 or greater, were treated with intracavitary autologous LAK cells plus IL‐2 after reoperation. Lymphokine‐activated killer cells and IL‐2 were given on day 1, and IL‐2 alone was given 5 times during a 2‐week cycle. This cycle was repeated at 2 weeks to constitute one 6‐week course of therapy. Each two‐cycle course of treatment was repeated at 3‐month intervals for patients with stable disease or response to therapy. At the conclusion of immunotherapy, all patients were offered chemotherapy, generally carmustine or procarbazine, including responders. Corticosteroids were strictly limited during immunotherapy. Sequential reservoir aspirates were obtained for microbiologic and cytologic analyses. Results. The maximal tolerated dose for a 12‐dose course of therapy was 1.2 million international units (MIU) per dose. Dose‐limiting, cumulative IL‐2‐related central nervous system (CNS) toxicity was observed at 2.4 MIU per dose. Three responses were confirmed by computed tomography scan during therapy: one complete response (CR) (1 AA), and two partial responses (PR) (2 GBM); as well as a significant increase in GBM survival. One additional CR (GBM) was observed at 17 months. The median survival for immunotherapy patients with GBM was 53 weeks after reoperation (N = 15) (mean, 87.9 → 21.4 weeks, standard error for the mean), with 8 of 15 surviving more than 1 year (53%). The median survival for 18 contemporary patients with GBM reoperated and treated with chemotherapy was 25.5 weeks (mean, 27.4 ± 3.7 weeks), with 1/18 alive at 1 year (>6%). Six of the 15 patients with GBM had additional surgery or biopsy, and chemotherapy after immunotherapy. The contribution of subsequent chemotherapy to survival cannot be discounted. Conclusions. Lymphokine‐activated killer cells and IL‐2 can be administered safely within the CNS resulting in improved long term survival in patients with recurrent glioblastoma. Increased survival was associated with significant biologic changes characterized by a regional eosinophilia, and extensive lymphocytic infiltration. A prospective randomized clinical trial is warranted. Cancer 1995; 76:840–52.
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