Response assessment in neuro-oncology (a report of the RANO group): assessment of outcome in trials of diffuse low-grade gliomas.

Although low-grade gliomas (LGG) have a less aggressive course than do high-grade gliomas, the outcome of these tumours is ultimately fatal in most patients. Both the tumour and its treatment can cause disabling morbidity, particularly of cognitive functions. Because many patients present with seizures only, with no other signs and symptoms, maintenance of quality of life and function constitutes a particular challenge in LGG. The slow growth pattern of most LGG, and the rare radiological true responses despite a favourable clinical response to treatment, interferes with the use of progression-free survival as the primary endpoint in trials. Overall survival as an endpoint brings logistical challenges, and is sensitive to other non-investigational salvage therapies. Clinical trials for LGG need to consider other measures of patient benefit such as cognition, symptom burden, and seizure activity, to establish whether improved survival is reflected in prolonged wellbeing. This Review investigates clinical and imaging endpoints in trials of LGG, and provides response assessment in neuro-oncology (RANO) criteria for non-enhancing tumours. Additionally, other measures for patients with brain tumours that assess outcome are described. Similar considerations are relevant for trials of high-grade gliomas, although for these tumours survival is shorter and survival endpoints generally have more value than they do for LGG.

Tibial nailing using a suprapatellar rather than an infrapatellar approach significantly reduces anterior knee pain postoperatively: a multicentre clinical trial.

AIMS: The aim of this study was to compare the incidence of anterior knee pain after antegrade tibial nailing using suprapatellar and infrapatellar surgical approaches. PATIENTS AND METHODS: A total of 95 patients with a tibial fracture requiring an intramedullary nail were randomized to treatment using a supra- or infrapatellar approach. Anterior knee pain was assessed at four and six months, and one year postoperatively, using the Aberdeen Weightbearing Test - Knee (AWT-K) score and a visual analogue scale (VAS) score for pain. The AWT-K is an objective patient-reported outcome measure that uses weight transmitted through the knee when kneeling as a surrogate for anterior knee pain. RESULTS: A total of 53 patients were randomized to a suprapatellar approach and 42 to an infrapatellar approach. AWT-K results showed a greater mean proportion of weight transmitted through the injured leg compared with the uninjured leg when kneeling in the suprapatellar group compared with the infrapatellar group at all timepoints at all follow-up visits. This reached significance at four months for all timepoints except 30 seconds. It also reached significance at six months at 0 seconds, and for one year at 60 seconds. CONCLUSION: The suprapatellar surgical approach for antegrade tibial nailing is associated with less anterior knee pain postoperatively compared with the infrapatellar approach Cite this article: Bone Joint J 2019;101-B:1138-1143.

Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas.

BACKGROUND/METHODS: Gliomas are common malignant neoplasms of the central nervous system. Among the major subtypes of gliomas, oligodendrogliomas are distinguished by their remarkable sensitivity to chemotherapy, with approximately two thirds of anaplastic (malignant) oligodendrogliomas responding dramatically to combination treatment with procarbazine, lomustine, and vincristine (termed PCV). Unfortunately, no clinical or pathologic feature of these tumors allows accurate prediction of their response to chemotherapy. Anaplastic oligodendrogliomas also are distinguished by a unique constellation of molecular genetic alterations, including coincident loss of chromosomal arms 1p and 19q in 50%-70% of tumors. We have hypothesized that these or other specific genetic changes might predict the response to chemotherapy and prognosis in patients with anaplastic oligodendrogliomas. Therefore, we have analyzed molecular genetic alterations involving chromosomes 1p, 10q, and 19q and the TP53 (on chromosome 17p) and CDKN2A (on chromosome 9p) genes, in addition to clinicopathologic features in 39 patients with anaplastic oligodendrogliomas for whom chemotherapeutic response and survival could be assessed. RESULTS/CONCLUSIONS: Allelic loss (or loss of heterozygosity) of chromosome 1p is a statistically significant predictor of chemosensitivity, and combined loss involving chromosomes 1p and 19q is statistically significantly associated with both chemosensitivity and longer recurrence-free survival after chemotherapy. Moreover, in both univariate and multivariate analyses, losses involving both chromosomes 1p and 19q were strongly associated with longer overall survival, whereas CDKN2A gene deletions and ring enhancement (i.e., contrast enhancement forming a rim around the tumor) on neuroimaging were associated with a significantly worse prognosis. The inverse relationship between CDKN2A gene deletions and losses of chromosomes 1p and 19q further implies that these differential clinical behaviors reflect two independent genetic subtypes of anaplastic oligodendroglioma. These results suggest that molecular genetic analysis may aid therapeutic decisions and predict outcome in patients with anaplastic oligodendrogliomas.

Corticosteroid-induced magnetic resonance imaging changes in patients with recurrent malignant glioma.

PURPOSE: We studied corticosteroid-induced magnetic resonance (MR) scan changes in patients with recurrent malignant glioma to determine if corticosteroid therapy started concurrently with investigational treatment might yield false-positive responses. PATIENTS AND METHODS: Ten symptomatic patients not on corticosteroids when malignant glioma recurred had a baseline MR scan performed before corticosteroid treatment, followed by serial scans at weekly intervals for 1 month while on dexamethasone (16 mg/d). The maximum cross-sectional areas and volumes of the gadolinium-enhancing regions (tumor) and T2-weighted abnormalities (tumor plus edema) were compared quantitatively and qualitatively for each series of scans. RESULTS: Nine of 10 patients (90%) had a measurable reduction in the size of the gadolinium-enhancing region or T2-weighted abnormality with corticosteroid treatment. The maximum cross-sectional area and volume of the gadolinium-enhancing region decreased by at least 25% in three of 10 patients (30%). The maximum cross-sectional area and volume of the T2-weighted abnormality decreased by at least 25% in five of 10 patients (50%). Maximum measurable radiologic improvement was evident within 2 weeks in most patients. MR scans were judged improved by the reporting neuroradiologist in seven of 10 (70%). These subjective visual improvements were also evident within 2 weeks, but generally described as slight or modest. CONCLUSION: Corticosteroid-induced MR scan reductions in tumor size may confound the assessment of response of recurrent malignant gliomas to investigational agents. For patients who start corticosteroids for symptom control, investigational treatment should be delayed until a new baseline MR image is established 2 weeks later. Response is then judged by comparing subsequent MR scans with the new corticosteroid-influenced baseline image.

Response criteria for phase II studies of supratentorial malignant glioma.

We suggest "new" response criteria for phase II studies of supratentorial malignant glioma and favor rigorous criteria similar to those in medical oncology, with important modifications. Four response categories are proposed: complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Response in this scheme is based on major changes in tumor size on the enhanced computed tomographic (CT) or magnetic resonance imaging (MRI) scan. Scan changes are interpreted in light of steroid use and neurologic findings. We advocate careful patient selection, emphasize pitfalls in the assessment of response, and suggest guidelines to minimize misinterpretations of response.

Phase I study of topotecan plus cranial radiation for glioblastoma multiforme: results of Radiation Therapy Oncology Group Trial 9507.

PURPOSE: A phase I trial was conducted by the Radiation Therapy Oncology Group (RTOG) to determine the maximum-tolerated dose of topotecan that could be safely combined with standard cranial radiation for glioblastoma multiforme. A secondary objective was to document the acute and late toxicities of this combination of chemotherapy and radiation. PATIENTS AND METHODS: Forty-seven patients with histologically confirmed glioblastoma multiforme were entered onto this phase I trial. Three cycles of topotecan were administered at 21-day intervals commencing at day 1 of cranial radiotherapy (60 Gy/30 fractions). Each cycle consisted of daily 30-minute intravenous (IV) infusions for 5 days. The dose of topotecan was escalated in three-dose increments from 0.5 mg/m(2)/d to 1.0 mg/m(2)/d to 1.5 mg/m(2)/d in different patient groups. RESULTS: The majority of patients were over age 50. Three dose levels of topotecan were tested. Fifteen patients accrued to level 1 (topotecan dose 0.5 mg/m(2)/d). No grade 4 toxicities were seen. Sixteen patients accrued to level 2 (topotecan dose 1.0 mg/m(2)/d), five of whom had brief episodes of grade 4 neutropenia. Seventeen patients accrued to level 3 (1.5 mg/m(2)/d). Six of these patients had brief episodes of grade 4 neutropenia and four developed grade 3 thrombocytopenia. No serious nonhematologic or late toxicities were seen. Median survival for all patients was 9.7 months. There was no apparent difference in survival by topotecan dose schedule. CONCLUSION: Toxicity was acceptable at an IV topotecan dose of 1.5 mg/m(2)/d administered daily for 5 days every 21 days for three cycles. A phase II trial has been performed using this dose of topotecan.

Randomized comparison of diaziquone and carmustine in the treatment of adults with anaplastic glioma.

PURPOSE: We conducted a phase III trial comparing intravenous (IV) diaziquone (AZQ) and carmustine (BCNU) as single agents in patients with cerebral anaplastic gliomas who had received surgery and radiotherapy. Its purpose was to compare the efficacy of AZQ with that of BCNU, the standard agent for brain tumor chemotherapy. PATIENTS AND METHODS: Randomization between the two regimens occurred 8 weeks after completion of radiotherapy. A total of 251 patients were randomized to receive either AZQ or BCNU, and there were no significant differences between the two treatment arms in any of the known prognostic variables, including age, histologic grade, and Karnofsky performance status (KPS). RESULTS: There was no significant difference in either time to tumor progression or survival between the two treatment arms. Age and histology were strong predictors of outcome, whereas KPS had relatively less effect. Three groups of patients with distinctly different outcomes could be identified: (1) older age (45+) and glioblastoma/gliosarcoma (GBM/GS) patients had a median survival of 37 weeks after randomization; (2) patients with either older age or GBM/GS had a median survival of 61 weeks; and (3) younger age (< 45) and non-GBM/GS (usually anaplastic astrocytoma) patients had a median survival of 147 weeks. Toxicity was primarily hematologic, although acute gastrointestinal toxicity and chronic pulmonary toxicity were more common with BCNU. Patients randomized to AZQ who had significant hematologic toxicity that required dose reduction after the first treatment cycle had significantly longer time to tumor progression and survival than those who did not require dose reduction (P = .011 and .016, respectively). CONCLUSION: There was no significant difference in efficacy between AZQ and BCNU in patients with anaplastic gliomas as tested in this study, although AZQ was somewhat better tolerated.

Molecular subtypes of anaplastic oligodendroglioma: implications for patient management at diagnosis.

PURPOSE: In a prior study of anaplastic oligodendrogliomas treated with chemotherapy at diagnosis or at recurrence after radiotherapy, allelic loss of chromosome 1p correlated with better chemotherapeutic response and overall survival. However, in this group of patients in whom therapeutic management was not uniform, loss of 1p did not identify all chemosensitive tumors, nor did all patients whose tumors harbor a 1p loss have long survival. EXPERIMENTAL DESIGN: To clarify the clinical relevance of molecular genetic testing at the time of diagnosis for patients with anaplastic oligodendrogliomas, we studied a larger, more homogeneous group of 50 patients with histologically defined anaplastic oligodendrogliomas treated with a chemotherapeutic regimen as the principal initial therapy. RESULTS: We demonstrate that these tumors can be divided genetically into four therapeutically and prognostically relevant subgroups. Patients whose tumors have combined but isolated losses of 1p and 19q have marked and durable responses to chemotherapy associated with long survival, with or without postoperative radiation therapy. Other tumors with chromosome 1p alterations also respond to chemotherapy, but with shorter duration of response and patient survival. Tumors lacking 1p loss can also be divided into two subgroups: those with TP53 mutations, which may also respond to chemotherapy but recur quickly, and those without TP53 mutations, which are poorly responsive, aggressive tumors that are clinically and genotypically similar to glioblastomas. CONCLUSIONS: These data raise the possibility, for the first time, that therapeutic decisions at the time of diagnosis might be tailored to particular genetic subtypes of anaplastic oligodendroglioma.

Steroid-induced CT changes in patients with recurrent malignant glioma.

The magnitude and time course of steroid-induced CT changes were analyzed in 11 patients with recurrent malignant glioma. CTs were obtained before and at regular intervals after starting dexamethasone (16 mg/d). Midline shift, ventricular compression, edema, enhancement intensity, and the size of the enhancing mass often improved with steroid treatment. Improvement occurred within 2 weeks in most instances. Changes in the volume of the enhancing tumor were assessed quantitatively in eight patients. In six, the mass was smaller after 2 weeks of steroid therapy, and in two the reduction approached 50%. Steroid-induced CT changes can mimic treatment responses. If steroids are necessary for symptom control, patients should be taking these medications for 2 weeks before a baseline CT is obtained and investigational treatment started.

Neoadjuvant procarbazine, CCNU, and vincristine for anaplastic and aggressive oligodendroglioma.

The authors reviewed the results of neoadjuvant (preradiation) procarbazine, CCNU, and vincristine chemotherapy for anaplastic oligodendrogliomas because, increasingly, chemotherapy is prescribed before radiation for oligodendroglial neoplasms. The data indicate that 70% of patients respond to neoadjuvant chemotherapy, whereas 30% require early radiation because they either have chemoresistant tumors or experience unacceptable chemotoxicity.

Metastatic anaplastic oligodendroglioma.

We report 7 patients, ages 21 to 49 years, with systemic metastasis from anaplastic oligodendroglioma. Metastases developed in the scalp, cervical lymph nodes, bone, and other organs 1 to 76 months after the most recent surgery and 18 to 86 months after diagnosis. Systemic metastases responded to focal radiotherapy or nitrosourea-based chemotherapy for 6 to 18 months. Five patients have died, 4 to 24 months after the appearance of systemic metastases, all with progressive cerebral and systemic tumor. We observed 2 distinct patterns of spread of oligodendroglioma. Pattern 1, initial scalp or regional lymph node involvement followed by distant metastasis, was associated with multiple craniotomies. Pattern 2, distant metastasis without scalp or regional lymph node spread, was associated with early radiotherapy and chemotherapy. Longer-than-expected survival was not essential to metastasis. We speculate that anaplastic oligodendrogliomas possess special characteristics favoring metastasis and that early aggressive treatment alters the biology of this disease.

Primary leptomeningeal lymphoma: report of 9 cases, diagnosis with immunocytochemical analysis, and review of the literature.

We describe 9 patients who presented with a neoplastic meningitis of lymphomatous origin. No evidence of parenchymal central nervous system or systemic tumor was identified either at the time of presentation or throughout the course of their disease. We have chosen to call this entity "primary leptomeningeal lymphoma" (PLML). This unusual form of neurologic lymphoma must be differentiated from the more common clinical situations of primary parenchymal lymphoma with meningeal involvement and systemic lymphoma complicated by lymphomatous meningitis.

Temozolomide for recurrent high-grade glioma.

Despite aggressive treatment, the high-grade malignant glioma (specifically, anaplastic astrocytoma and glioblastoma multiforme) have a poor prognosis with current methods. Relapse is nearly universal, responses in recurrent disease are not enduring, and quality of life because of tumor growth is poor. New treatment strategies that address symptom control and quality of life as well as progression-free and overall survival are urgently needed. Temozolomide (Temodar in the United States, Temodal globally; Schering Corporation, Kenilworth, NJ), a novel, oral, antineoplastic agent, has shown efficacy against high-grade glioma with a favorable safety profile, while maintaining or improving quality of life. In a pivotal randomized, international phase II trial comparing temozolomide (n = 112) with procarbazine (n = 113) in patients with glioblastoma multiforme, temozolomide significantly improved median and 6-month progression-free survival and 6-month overall survival. Additionally, patients receiving temozolomide had superior responses in all seven quality-of-life domains tested, which included the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire functions and brain-cancer-specific symptoms. A large, multicenter, single-arm trial (N = 162) showed an impressive response rate for patients with relapsed anaplastic astrocytoma receiving temozolomide, and patients maintained or improved their quality of life compared with baseline values. For patients with recurrent malignant glioma, temozolomide provides a therapeutic option with a predictable safety profile, clinical efficacy, and convenient dosing that can provide important quality-of-life benefits.

Results of a policy of surveillance alone after surgical management of pediatric low grade gliomas.

PURPOSE: To document the incidence of tumor progression in pediatric patients with low-grade gliomas (LGGs), with particular emphasis on those patients who did not receive postoperative chemotherapy or radiotherapy (RT). METHODS AND MATERIALS: A database of 128 patients with histologically confirmed LGGs (World Health Organization Grade I-II), age

Allelic loss of chromosome 1p and radiotherapy plus chemotherapy in patients with oligodendrogliomas.

INTRODUCTION: Allelic loss of the short arm of chromosome 1 predicts radiographic response to chemotherapy and long overall survival times in patients with anaplastic oligodendrogliomas. Using a database of patients with oligodendrogliomas in whom chromosome 1p status was known, we explored whether allelic loss of 1p also predicted longer duration of tumor control when radiotherapy was part of the initial treatment of these patients. MATERIALS AND METHODS: We measured progression-free survival following radiotherapy in a cohort of patients with World Health Organization (WHO) Grade II and WHO Grade III oligodendrogliomas. The effects on progression-free survival of patient age, Karnofsky performance score (KPS), tumor grade when irradiated and chromosome 1p status were examined by univariate and multivariate statistical analyses. For the subset of patients with newly diagnosed anaplastic oligodendrogliomas, relationships between use of chemotherapy, chromosome 1p status and progression-free survival were also examined. RESULTS: Fifty-five patients (29 male, 26 female; ages 18-75 years; median, 44 years; KPS 50-90, median 80) were irradiated for either a WHO Grade II (n = 19) or Grade III (n = 36) oligodendroglioma. Twenty-eight patients had chemotherapy immediately prior to radiotherapy, and 27 had chemotherapy at progression following radiotherapy. The median radiation dose was 54 Gy in 30 fractions. Loss of heterozygosity (LOH) at chromosome 1p was evident in 36 tumors and absent in 19. Overall median progression-free survival after radiotherapy was 40.4 months. Median progression-free survival was 55.0 months for patients whose tumors harbored 1p loss vs. 6.2 months for those patients whose tumors retained both copies of chromosome 1p (p < 0.001). On both univariate and multivariate analyses, chromosome lp loss was the principal independent predictor of longer progression-free survival for patients with Grade II and III oligodendrogliomas. For Grade III oligodendrogliomas, chemotherapy as an adjunct to radiotherapy prolonged tumor control for those patients whose tumors harbored allelic loss of chromosome 1p (p = 0.004). CONCLUSION: These data suggest allelic loss of chromosome 1p in patients with oligodendroglial neoplasms predicts longer progression-free survival among patients receiving radiotherapy +/- chemotherapy as part of their initial treatment. Chromosome 1p loss may be an important stratification variable in future therapeutic trials of oligodendroglioma.

A prospective study of short-course radiotherapy in poor prognosis glioblastoma multiforme.

PURPOSE: Older age and poor performance status at presentation are unfavorable prognostic factors for patients with glioblastoma multiforme. Some studies suggest a shorter, palliative course of radiotherapy may confer similar benefits as compared to a radical course in such patients. We report a prospective, single arm trial, describing the use of a short-course of radiation in patients with glioblastoma and poor prognostic features. METHODS AND MATERIALS: Twenty-nine patients with pathologically confirmed glioblastoma and age > or = 65 years or with initial KPS < or = 50 were treated with a short-course of whole brain radiotherapy (30 Gy/10 fractions/2 weeks). Computer tomography tumor volume, dexamethasone requirements, Spitzer quality of life index, and Karnofsky performance status were measured pre and 1 month postradiation. Overall survival for the study patients was compared with that of radically treated and supportive care only historical controls. RESULTS: Indices of tumor response were stable or improved in 60% of patients evaluable 1 month postradiotherapy. Median survival for all study patients was 6 months. Median survivals in similar groups of radically treated and supportive care only patients were 10 and 1 month(s), respectively. A survival advantage for the radical vs. short-course treatment was observed for the subset of patients with a pretreatment KPS > 50. CONCLUSION: Elderly patients with a low pretreatment KPS (< or = 50) may be treated adequately with a short, palliative course of radiotherapy. Elderly patients with a higher pretreatment KPS (> 50), however, may benefit from a higher dose radiotherapy regimen.

Supratentorial malignant glioma: patterns of recurrence and implications for external beam local treatment.

Pre- and postoperative computerized tomography scans, simulator films, and computerized tomography scans documenting tumor recurrence were analyzed on 70 patients with supratentorial malignant glioma treated with whole brain plus boost radiation therapy to determine sites of recurrence in relation to the boost. The boost was planned using the postoperative computerized tomography scan. Tumor recurred in 53 patients--within the boost in 38 (72%), partly outside the boost in 12 (23%), outside the boost but within the brain in one (2%), in the boost and in the spinal cord in one (2%), and in the spinal cord only in one (2%). All recurrences confined to the brain were found within 4 cm of the enhancing tumor as defined by the preoperative computerized tomography scan. Recurrences outside the boost were more common with inadequate boost margins, small boost volumes, temporal lobe tumors, and homolateral wedge pair technique. Survival was not adversely affected by recurrence outside the boost. We recommend that patients with malignant glioma be treated by parallel opposed fields with a margin that is 4 cm beyond the edge of the preoperative enhancing tumor, as seen on computerized tomography scan.

Malignant glioma--timing of response to radiation therapy.

PURPOSE: The response of malignant gliomas to radiation was examined retrospectively in 71 patients with newly diagnosed supratentorial malignant gliomas. Questions asked included frequency, timing and clinical significance of response. METHODS AND MATERIALS: After surgery, all were treated with whole brain plus boost radiotherapy followed 8 weeks later by chemotherapy. The rate, degree, and timing of response to radiation were determined by comparing postoperative, end of radiation, and prechemotherapy CT scans on each patient. RESULTS: Postoperative residual tumor was evident on 63/71 postoperative scans. Twenty-two of 63 tumors (35%) had a partial or complete response to radiation. Twenty (32%) had responded by the end of radiation; 17 maximally. Six to 8 weeks later, three responding tumors had responded further and two previously stable ones had begun to respond. Only three tumors (5%) responded completely. A greater proportion of anaplastic gliomas than glioblastomas responded to radiation (52% vs. 26%). Protracted or delayed responses were only observed in patients with anaplastic glioma. Patients who responded to radiation did not live significantly longer than non-responders. However, tumor progression prior to chemotherapy was associated with significantly shorter survival. CONCLUSION: This CT scan-based analysis demonstrates that malignant gliomas are only moderately radioresponsive tumors and also demonstrates that response to radiation, if it is going to occur, is usually evident by the end of treatment.

A phase III randomized prospective trial of external beam radiotherapy, mitomycin C, carmustine, and 6-mercaptopurine for the treatment of adults with anaplastic glioma of the brain. CNS Cancer Consortium.

PURPOSE: This study was designed to evaluate strategies to overcome the resistance of anaplastic gliomas of the brain to external beam radiotherapy (ERT) plus carmustine (BCNU). Patients were > or = 15 years of age, had a histologic diagnosis of malignant glioma, and a Karnofsky performance status (KPS) > or = 60%. METHODS AND MATERIALS: In Randomization 1, patients were assigned to receive either ERT alone (61.2 Gy) or ERT plus mitomycin C (Mito, IV 12.5 mg/m(2)) during the first and fourth week of ERT. After this treatment, patients went on to Randomization 2, where they were assigned to receive either BCNU (i.v. 200 mg/m(2)) given at 6-week intervals or 6-mercaptopurine (6- MP, 750 mg/m(2) IV daily for 3 days every six weeks), with BCNU given on the third day of the 6-MP treatment. Three hundred twenty-seven patients underwent Randomization 1. One hundred sixty-four received ERT alone, and 163 received ERT + Mito [average 52.7 years; 63% male; 69% glioblastoma multiforme (GBM); 66% had a resection; 56% KPS > or = 90%]. Step-wise analysis of survival from Randomization 1 or 2 indicates that survival was significantly diminished by: (a) age > or = 45 years (b) KPS < 90%; (c) GBM/gliosarcoma histology; (d) stereotactic biopsy as opposed to open biopsy or resection. Median survival from Randomization 1 in both arms (ERT + Mito) was 10.8 months. Median survival from Randomization 2 was 9.3 months for BCNU/6MP vs. 11.4 months for the BCNU group (p = 0.35). Carmustine/6-MP showed a possible survival benefit for histologies other than GBM/GS. Two hundred and thirty-three patients underwent Randomization 2. The proportion of patients in the ERT group who terminated study prior to Randomization 2 was significantly less in the ERT group than in the ERT + Mito group (20 vs. 37%, p < 0.001). CONCLUSIONS: (a) The addition of Mito to ERT had no impact on survival; (b) patients treated with ERT + Mito were at greater risk of terminating therapy prior to Randomization 2; (c) there was not a significant survival benefit to the addition of 6-MP to BCNU.

Aggressive oligodendroglioma: a chemosensitive tumor.

Aggressive oligodendrogliomas, tumors that are symptomatic, enlarging, enhancing, and usually but not always anaplastic, respond to chemotherapy. We have observed responses to chemotherapy in 18 of 19 consecutively treated patients with newly diagnosed or recurrent aggressive oligodendrogliomas. A regimen of procarbazine, CCNU (lomustine), and vincristine (PCV) is predictably effective, but other drugs have antioligodendroglioma activity. Cooperative group trials will be necessary to determine the most effective drug, or combination of drugs, and to explore fully the role of chemotherapy in the treatment of this uncommon glioma.