M. Stephen Mahaley

The morphologic effects of radiation administered therapeutically for intracranial gliomas: a postmortem study of 25 cases.

To investigate the pathologic consequences of therapeutic radiation, this morphologic study evaluated the brains of 25 patients with intracranial gliomas treated both with and without this form of therapy. Although beneficial effects of radiation such as the retardation of tumor growth were evident in these studies, among the seventeen patients who received from 5000–6000 rads for malignant gliomas, four developed “late delayed” radiation necrosis. The strong predilection of this tissue response for the white matter adjacent to the neoplasm suggests a local sensitivity which may have been engendered or enhanced by cerebral edema. A fifth case disclosed focal demyelination in the mid‐brain suggesting “early delayed” radiation necrosis, and an additional case had distinctive foci of necrosis within the brain stem. Changes of diffuse cerebral edema were noted in many of the radiated brains. It is concluded that radiation therapy in commonly employed dosages for malignant gliomas carries a risk of injury to surrounding cerebral tissues.

Chromosomal evolution in malignant human gliomas starts with specific and usually numerical deviations

Our previous karyotypic studies of malignant human gliomas have demonstrated that their most consistent early or primary gross changes include gains of #7, losses of #10, #22, and the gonosomes, and the presence of double minutes. Karyotypes of 15 additional malignant human gliomas reported here have confirmed these observations and, by enlarging our series, we can now show that in addition to double minutes, certain other gross structural abnormalities also are clearly associated with the early evolution of this type of tumor. The most prevalent deviations are deletions and translocations involving 9p. Other chromosomes commonly involved in rearrangements are #1, #6, and #13, and less frequently #7, #11, and #16.

Superiority of PCNU over AZQ in the treatment of primary brain tumors: results of a prospective randomized trial (81-20) by the Brain Tumor Study Group.

SummaryPurposeA two-arm randomized clinical trial was performed to determine the efficacy of PCNU and AZQ in the treatment ofde novo or recurrent primary brain tumors. An additional objective was to gather information on the administration and toxicity of these compounds, supplementing that obtained previously in phase I/II studies.MethodsDuring 1982 and 1983 the Brain Tumor Study Group randomized 152 adult patients with primary brain tumors to receive PCNU 75–100 mg/m2 intravenously (IV) every 8 weeks or AZQ 15 mg/m2 IV once a week for 4 weeks, every 6–8 weeks. All patients who had not received ‘full dose’ radiotherapy before randomization received it concurrently with the first course of protocol chemotherapy. The data were analyzed for the total randomized population (RP), and for 130 patients in the valid study group (VSG) formed by excluding 22 patients for whom the histologic diagnosis was not documented by central review.ResultsMedian survival times were 11.0 months for the PCNU group and 8.4 months for the AZQ group. The difference in survival curves was statistically significant for the RP (p=0.01) and the VSG (p=0.02). Lifetable analysis of the VSG showed estimated 2-year survivals of 34% for PCNU and 11% for AZQ. The advantage of PCNU remained significant (p=0.006) after adjustment for histopathologic category, age, initial performance status, and interval from initial reported surgery. Myelosuppression was the principal toxicity in both groups.

Appearance of an independent second arteriovenous malformation 3 years after subtotal resection of a first malformation

Abstract Cerebral arteriovenous malformations are thought to be congenital lesions consisting of artery-to-vein communications without an intervening capillary bed. They have been shown both to increase and to decrease in size and even to disappear spontaneously. We present a case of angiographic appearance of an independent right Sylvian fissure arteriovenous malformation 3 years after an incomplete resection of a separate right parietal arterio-venous malformation. Both arteriovenous malformations were subsequently totally resected. We propose that alterations in blood flow after manipulation of the first arteriovenous malformation produced conditions favoring enlargement of a previously unseen cryptic arteriovenous malformation. The appearance of a second arteriovenous malformation in the same patient is unique. Theories of origin and the natural history of arteriovenous malformations are discussed.

Tumoricidal activity of an acute promyelocytic leukemia cell line (HL-60) is augmented by human interferon alpha

Normal human peripheral blood polymorphonuclear leukocytes (PMNs) and cells from a human acute promyelocytic leukemia line (HL-60) were tested for cytotoxic potential against two human glioma and one normal fibroblast line. Both the PMNs and HL-60 exhibited significant cytotoxicity against the tumor targets while sparing the normal fibroblasts. However, the two glioma cell lines were not equally susceptible to the effector cells. Addition of low levels of purified human lymphoblastoid interferon alpha (IFN) during the assay period significantly enhanced the tumoricidal effect against one of the glioma targets. HL-60 cells, partially differentiated to myelocytes and metamyelocytes by incubation with dimethylsulfoxide (DMSO), expressed reduced levels of cytotoxicity; IFN added during the assay was able to restore the cytotoxic activity against both glioma cell lines. Undifferentiated HL-60 cells were also able to lyse K562 targets in a six hour 51Cr release assay; this activity was also significantly enhanced by IFN. Separate incubation of both effectors and targets proved that the enhancement of cytotoxic activity demonstrated was due to an effect on the HL-60 effector cells. In contrast, the lysis of HSB-2, another NK sensitive target cell, was not enhanced by the addition of IFN to a mixture of HSB-2 and HL-60 cells. Pretreatment of effector and target cells separately with IFN demonstrated a dual effect: IFN both protected HSB-2 targets from lysis by the HL-60 effectors and induced significantly greater cytotoxicity by HL-60 cells.