Combined loss of 1p and 19q is a statistically significant predictor of prolonged survival in patients with pure oligodendroglioma, independent of tumor grade. Given the lack of this association in patients with astrocytic neoplasms and the previously demonstrated chemosensitivity of oligodendrogliomas, a combined approach of histologic and genotypic assessment could potentially improve existing strategies for patient stratification and management.

PTEN mutation and EGFR amplification are important prognostic factors in patients with anaplastic astrocytoma and in older patients with glioblastoma multiforme, respectively.

This phase III prospective randomized trial of low- versus high-dose radiation therapy for adults with supratentorial low-grade astrocytoma, oligodendroglioma, and oligoastrocytoma found somewhat lower survival and slightly higher incidence of radiation necrosis in the high-dose RT arm. The most important prognostic factors for survival are histologic subtype, tumor size, and age. The study design of the ongoing intergroup trial in this population will be discussed.

One hundred and fifty patients with advanced cancer participated in a controlled double-blind study to evaluate the effects of high-dose vitamin C on symptoms and survival. Patients were divided randomly into a group that received vitamin C (10 g per day) and one that received a comparably flavored lactose placebo. Sixty evaluable patients received vitamin C and 63 received a placebo. Both groups were similar in age, sex, site of primary tumor, performance score, tumor grade and previous chemotherapy. The two groups showed no appreciable difference in changes in symptoms, performance status, appetite or weight. The median survival for all patients was about seven weeks, and the survival curves essentially overlapped. In this selected group of patients, we were unable to show a therapeutic benefit of high-dose vitamin C treatment.

This study determines the effectiveness and reproducibility of a previously published method of grading gliomas. The method under study is for use on "ordinary astrocytoma" cell types, i.e., fibrillary, protoplasmic, gemistocytic, anaplastic astrocytomas and glioblastomas, and is based upon the recognition of the presence or absence of four morphologic criteria: nuclear atypia, mitoses, endothelial proliferation, and necrosis. The method results in a summary score which is translated into a grade as follows: 0 criteria = grade 1, 1 criterion = grade 2, 2 criteria = grade 3, 3 or 4 criteria = grade 4. The histologic material and clinical data were derived from a previously reported series of patients with astrocytomas, radiotherapeutically treated at Mayo Clinic between the years 1960 and 1969. From this series, initially graded 1 to 4, according to the Kernohan system, 287 "ordinary astrocytomas" were entered into the study; 51 pilocytic astrocytomas and microcystic cerebellar-type astrocytomas also were included for comparison. Among ordinary astrocytomas, the grading method under study distinguished 0.7% of grade 1, 17% of grade 2, 18% of grade 3, and 65.3% of grade 4. A 15-year period of follow-up was available on all surviving patients. Statistical analysis showed that in ordinary astrocytomas, each of the four histologic criteria, as well as the resultant grade, were strongly correlated to survival (P less than 0.0001). Median survival was 4 years in grade 2, 1.6 years in grade 3, and 0.7 years in grade 4 tumors. Of the two patients with grade 1 ordinary astrocytomas, 1 had 11 years of survival, and the other was alive at 15 years. Furthermore, based upon the Cox Model, grade was found to be the major prognostic factor, superceding the effects of age, sex, and location. Among ordinary astrocytomas, the grading system under consideration clearly distinguished four distinct grades of malignancy, whereas, the Kernohan grading system accurately distinguished only two major groups of patients. Survival curve of patients with our grade 2 tumors coincided with the grade 1 and 2 Kernohan survival curves. Similarly, our grade 4 survival curve coincided with the Kernohan grade 3 and 4 survival curves. As a result, our proposed grading method generated an individualized curve corresponding to grade 3 tumors. Double-blind grading between two independent observers was concordant in 94% of ordinary astrocytomas; reproducibility was 81% in low-grade (grades 1 and 2) and 96% in high-grade (grades 3 and 4) astrocytomas of ordinary type.(ABSTRACT TRUNCATED AT 400 WORDS)

Allelic alterations of chromosomes 1 and 19 are frequent events in human di use gliomas and have recently proven to be strong predictors of chemotherapeutic response and prolonged survival in oligodendrogliomas (Cairncross et al., 1998; Smith et al., submitted). Using 115 human di use gliomas, we localized regions of common allelic loss on chromosomes 1 and 19 and assessed the association of these deletion intervals with glioma histological subtypes. Further, we evaluated the capacity of multiple modalities to detect these alterations, including loss of heterozygosity (LOH),¯uorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH). The correlation coe cients for detection of 1p and 19q alterations, respectively, between modalities were: 0.98 and 0.87 for LOH and FISH, 0.79 and 0.60 for LOH and CGH, and 0.79 and 0.53 for FISH and CGH. Minimal deletion regions were de®ned on 19q13.3 (D19S412-D19S596) and 1p (D1S468-D1S1612). Loss of the 1p36 region was found in 18% of astrocytomas (10/55) and in 73% (24/33) of oligodendrogliomas (P50.0001), and loss of the 19q13.3 region was found in 38% (21/55) of astrocytomas and 73% (24/33) of oligodendrogliomas (P=0.0017). Loss of both regions was found in 11% (6/55) of astrocytomas and in 64% (21/33) of oligodendrogliomas (P50.0001). All gliomas with LOH on either 1p or 19q demonstrated loss of the corresponding FISH probe, 1p36 or 19q13.3, suggesting not only locations of putative tumor suppressor genes, but also a simple assay for assessment of 1p and 19q alterations as diagnostic and prognostic markers.

Eighty-one patients with pure supratentorial oligodendrogliomas underwent surgery alone (19 patients) or surgery plus postoperative radiation therapy (63 patients) between the years 1960 and 1982. The median survival time and the 5-, 10-, and 15-year survival rates for these 82 patients were 7.1 years, 54%, 34%, and 24%, respectively; these values were significantly different from those for an age- and sex-matched normal reference population. Univariate and multivariate survival analyses were performed on 13 possible prognostic factors including: patient age and sex; presence of seizures; site, size, side, computerized tomography (CT) enhancement, grade, and calcification of the tumor; and treatment (extent of surgical resection, lobectomy, radiation dose, and radiation field). Of these factors, tumor grade as classified by the Kernohan and St. Anne-Mayo methods was most strongly associated with survival. Patients with Grade 1 or 2 tumors by either grading method had a median survival time and 5- and 10-year survival rates of approximately 9.8 years. 75%, and 46%, respectively, compared to 3.9 years, 41%, and 20% for those with Grade 3 or 4 tumors. The extent of surgical resection was also associated with survival. The 19 patients who underwent gross total resection of their tumor had a median survival time and 5- and 10-year survival rates of 12.6 years, 74%, and 59%, compared to 4.9 years, 46%, and 23%, respectively, for the 63 who had subtotal resection. When comparing the 19 patients who underwent surgery alone with the 63 who had surgery plus postoperative radiation therapy, there did not appear to be a survival benefit to be gained from the addition of postoperative radiation therapy. However, the patients who had surgery alone tended to have gross total resections and lower tumor grades. Analysis of the subset of 63 patients who underwent subtotal resection alone or with radiation therapy showed that the median survival time and 5- and 10-year survival rates were: 2 years, 25%, and 25% for the eight patients with subtotal resection alone; 4.5 years, 39%, and 20% for the 26 patients with surgery and low-dose (less than 5000 cGy) radiation therapy; and 7.9 years, 62%, and 31% for the 29 patients receiving surgery and high-dose radiation therapy (greater than or equal to 5000 cGy), respectively.

Fifty-one patients with intracranial chordomas who were surgically treated between 1960 and 1984 were studied. Median patient age was 46 years, and 73% presented with diplopia or headache. Nineteen tumors were classified as the "chondroid" type. The extent of surgical removal was a biopsy in 11 patients and subtotal removal or greater in 40. Thirty-nine patients received postoperative radiation therapy. At the time of analysis, 17 patients were alive, and the estimated 5- and 10-year survival rates were 51% and 35%, respectively, for the group of 51 patients. Univariate analysis showed that: 1) patients undergoing resection lived longer (the 5-year survival rate was 36% for the 11 biopsy patients compared with 55% for the 40 patients who had resection; 2) patients who underwent postoperative radiotherapy tended to have longer disease-free survival times; and 3) overall and disease-free survival data were the same for patients with chondroid tumors and those with typical chordomas. Multivariate analysis showed that: 1) age was the factor most strongly associated with longer overall and disease-free survival; 2) diplopia was associated with longer survival; and 3) tumoral mitotic activity tended to be associated with shorter disease-free survival. One tumor metastasized to the cervical cord, and two tumors underwent anaplastic transformation. These data suggest that the prognosis in patients with chordomas is unfavorable, young age is the single factor most strongly associated with longer survival, surgical resection is beneficial, and postoperative radiotherapy may prolong disease-free survival.