Sylvan B. Green

Glioblastoma multiforme and anaplastic astrocytoma: Pathologic criteria and prognostic implications

A total of 1440 malignant astrocytic gliomas from three Phase III trials of the National Brain Tumor Study Group were studied to document the clinical usefulness of subclassifying these lesions as either an anaplastic astrocytoma or a glioblastoma multiforme. As defined by a previous “blind” pathology review, the two groups of patients were compared as to mean age, mean duration of preoperative symptoms, and postrandomization survival. In addition, 10 histologic variables were studied in 150 patients with the anaplastic astrocytoma to establish internal correlations, and to relate specific histologic variables to patient age and postrandomization survival. There were highly significant differences in the age, duration of preoperative symptoms, and post randomization survival between the two groups. Internal correlations between histologic variables in the anaplastic astrocytoma disclosed statistically significant associations between the presence of lymphocytes and gemistocytic astrocytes. It is concluded that the subclassification of malignant gliomas into the anaplastic astrocytoma and the glioblastoma multiforme defines groups of patients that are significantly different in regard to age, duration of symptoms, and length of survival. The problems of tissue sampling are recognized, however, the assignment, by a blind pathology review, to two such different groups indicates that the classification has utility for large randomized clinical trials. The analysis of histologic variables in the anaplastic astrocytomas confirms previous suggestions that lymphocytes and gemistocytes frequently coexist in malignant gliomas, but in this study these inflammatory cells did not appear to influence survival. The study reemphasizes the association between advancing age and shorter survivals in patients with malignant gliomas.

Patient age, histologic features, and length of survival in patients with glioblastoma multiforme.

Histologic sections from 71 patients with glioblastoma multiforme were reviewed to identify histologic prognostic factors and to explain the significantly shorter survival in older patients. Slides were studied for 14 histologic variables from a group of 35 patients aged less 45 years and from 36 patients aged 65 years or more. The relation of these histologic factors to the length of survival and age group was then investigated. The results document the marked histologic and cytologic heterogeneity of the glioblastoma and reaffirm the importance of necrosis as a prognostic factor. The results further suggest that patients whose glioblastomas contained microcysts, pseudopalisading, cells with astrocytic differentiation, and large areas of better differentiated glioma, did better than those patients whose lesions were homogeneously composed of small cells or whose lesion had a small median nuclear size. The study reaffirmed the strong (P < 0.0001) negative relationship between advancing age and duration of postoperative survival. The presence of necrosis, a smaller standard deviation of nuclear size, the extent of vascular proliferation, the absence of well differentiated neoplastic fibrillary astrocytes, and neoplasms composed homogeneously of small cells were related to patient age and offered a possible explanation for at least part of the observed age effect. However, the strong relation between age and survival remained significant when adjusted for other variables, and the effect of age must rest largely on factors other than those detected in this morphologic study.

Prospective study of alcohol consumption and cancer.

The relation between alcohol consumption and the subsequent occurrence of the five most frequent cancers in Japanese men in Hawaii (cancer of the stomach, colon, rectum, lung, and prostate) was analyzed in a prospective study of 8006 subjects. Information on alcohol consumption was obtained through interviews in the mid-1960s, and the cohort has been followed since then. The analysis, which was adjusted for the effects of age and cigarette smoking, revealed a positive association between consumption of alcohol and rectal cancer, accounted for primarily by an increased risk in men whose usual monthly consumption of beer was 500 oz (15 liters) or more (relative risk, 3.05; P less than 0.01, as compared with those who did not drink beer). A significant positive relation between alcohol consumption and lung-cancer incidence was also found, accounted for primarily by an increased risk among subjects who consumed larger amounts of wine or whiskey, as compared with the risks among nonconsumers of these beverages (relative risk, 2.19, [P = 0.03] and 2.62 [P less than 0.01], respectively). No significant relation between alcohol consumption and the incidence of the other three cancers was found.

Trends in survival rates of patients with cancer.

Reports on survival of patients with cancer issued by the National Cancer Institute indicate marked improvement for almost all forms of cancer from the 1940s to 1950s. Subsequently, prognosis for patients with forms of cancer accounting for approximately 42 per cent of all cancers continued to improve, although at a slower rate. For cancers of the lung, colon, rectum, stomach and pancreas, little improvement in patient survival during the 1960s was observed, and for women with invasive cervical cancer, survival rates decreased slightly. One-year survival results for patients with diagnoses made during 1970-71 suggest that improvement in five-year survival observed during the 1960s for many forms of cancer will be sustained. Continued reporting of survival of patients treated in the 1970s would ultimately demonstrate the degree of effectiveness of recently introduced therapeutic procedures.

Critical Values for the One-Sided Two-Sample Kolmogorov-Smirnov Statistic

Abstract We present a new recursion for counting the number of paths which ever attain a given height. Using this recursion, we calculate exact critical values for the one-sided two-sample Kolmogorov-Smirnov statistic for n and m = 3(1)30 and for significance levels α = 0.10, 0.05 and 0.01.

Reproducibility study on the scheimpflug cataract video camera

The Zeiss Scheimpflug Cataract Video Camera was designed to photograph, store and analyze cataracts in a semi-automated fashion for cross-sectional and longitudinal studies. We conducted a reproducibility study of this system. Twenty-four normal and 61 cataractous eyes were photographed twice by each of two of the authors in the 90 degree meridian and microdensitometry was performed on each of the stored images. Reproducibility was then determined using the intraclass correlation coefficient to determine whether or not the differences encountered were due to variability in the system or due to actual differences among the images. The intraclass correlation in the lens nucleus was 0.995 with 95% confidence limits of .992-.996. Therefore, reproducibility was 99.5%. In the anterior cortex, intraclass correlation was .941 with 95% confidence limits of .919-.959. In the posterior cortex intraclass correlation was .905 with 95% confidence limits of .870-.932. Reproducibility with this instrument was therefore excellent and with certain limitations, this may be a useful instrument in monitoring lens changes in certain diseases and the effects of anti-cataract agents.

Autologous serologic responses in glioma patients correlation with tumor grade and survival

The serologic responses of 42 patients with gliomas have been evaluated in a quantitative microcytotoxicity assay utilizing autologous cultured glioma cells. Forty‐five percent of patients had detectable cytotoxic antibody apparently directed to their own cultured cells. When tumor grade was correlated with immune response, 15/20 patients with Grade I, II and III astrocytomas had antigens detectable in autologous sera whereas only 5/22 patients with Grade IV astrocytomas had such responses. None of the autologous fibroblasts from the 15 patients with paired gliomas and fibroblast lines had membrane antigens detectable using autologous sera and fibroblast absorption did not reduce antiglioma activity. Thus, the cytotoxicity observed in this assay appears to be restricted to tumor cells, suggesting reactivity against tumorassociated antigen. In addition, it appears that these immune responses are highly correlated with survival in primary malignant brain tumor patients. Cancer 52:2230‐2235, 1983.

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.