No abstract

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.

A case is reported of a tumor composed of both oligodendrogliomatous and sarcomatous elements. The interpretation is offered that the sarcoma arose secondarily by neoplastic transformation of the hyperplastic blood vessels formed in response to the presence of the oligodendroglioma. This tumor may be considered analogous to the astrocytoma-sarcoma, which is much more common, and to the metastatic carcinoma with secondary sarcoma, of which one case has been reported.

Sera from 30 patients with astrocytoma were tested for antibody reacting with cell surface antigens of cultured autologous astrocytoma cells. Ten percent of the patients had antibody detectable by mixed hemacsorpt on assays, S50% by immune adherence and proteinA'assaysand 100% by anti-C3-mixed hemadsorption assays. Absorption analysis of reactive sera with autologous, allogeneic, and xenogeneic cells permitted the definition of three classes of astrocytoma cell surface antigens. Class I antigens showed an absolute restriction to autologous astrocytoma cells. Class II antigens were shared by all astrocytomas tested and could be detected also on neuroblastoma, sarcoma, and some (but not all) melanoma cell lines; these antigens were not found on cell lines derived from carcinomas or normal tissues. Class III antigens were widely distributed on cultured normal and malignant cells of human and animal origin. In this series, sera from 2 patients recognized class I antigens, 4 patients' serum recognized class II antigens, and 13 atients' sera recognized class III antigens. Absorption tests have shown that the AJ (class II) antigen of astrocytoma is serologically related to the previously described AH (class II) antigen of melanoma; in tests of nine melanoma cell lines, there was a correspondence between the AJ and AH phenotypes. This method of autologouslyping provides a way to classify the cell surface antigens of astrocytomas and to assess the clinical significance of humoral immunity to these antigens.An underlying assumption of much work in cancer immunology is that cancer cells can be distinguished from normal cells by the presence of distinctive antigens on the surface of the cancer cells. The evidence supporting this assumption comes primarily from transplantation studies in inbred mice and rats with tumors induced by chemical carcinogens, such as methylcholanthrene, or by viruses, such as polyoma. The repeated demonstration that these tumors are immunogenic in syngeneic hosts represents the cornerstone of the field of cancer immunology.Despite the enormous literature that has centered on the question of tumor-specific antigens of human cancers, the existence of such antigens must still be considered in the realm of speculation, not fact. The general impression by many in the field of tumor immunology as well as those in related fields, that tumor-specific antigens have been demonstrated in many types of human cancers, is simply not justified. The critical issue with regard to tumor-specific antigens is, of course, the question of specificity, and demonstrating the specificity of a serological or cell-mediated reaction is orders of magnitude easier in the mouse than in man. Lacking inbred mouse strains, hyperimmune antisera, and transplanted tumor cell lines with defined antigenicity, the human cancer serologist seeking evidence for tumor-specific antigens is faced with an exceedingly difficult task. Heteroimmune sera prepared against human cancer cells that at first have the appearance of tumor specifi...

We reviewed the records of 100 consecutive patients with histologically verified pituitary adenomas who underwent transsphenoidal decompression of the optic nerves and chiasm. The patients' ages ranged from 18 to 80 years, with a median of 52 years. Preoperatively, all patients had objective signs of visual acuity or field defects. Postoperatively, visual acuity was normal or improved in 79% of the eyes and the visual fields were normal or improved in 74%. The visual outcome (for both acuity and fields) was better in younger patients and those with a shorter duration of symptoms. Patients with lesser degrees of preoperative visual acuity compromise had better postoperative visual acuity outcome. However, the severity of preoperative visual field defects did not seem to predict postoperative field outcome, and even patients with severe preoperative field defects often had striking postoperative improvement. Patients who had undergone prior operation were less likely to have either visual acuity or visual field improvement after reoperation. Postoperative deterioration in visual acuity was noted in only 5 patients (6 eyes). Complications were few. There were 4 instances of cerebrospinal fluid rhinorrhea, but only 2 patients needed operative repair. There was no instance of permanent diabetes insipidus, although 17 patients developed transient diabetes insipidus. In most cases, visual improvement was sustained. The average duration of follow-up was 26 months. Three patients required a subsequent operation to correct visual loss in the immediate postoperative period, but only 1 patient has undergone late operation for recurrence of tumor. There was no operative mortality.