Memory in low-grade glioma patients treated with radiotherapy or temozolomide: a correlative analysis of EORTC study 22033-26033.

BACKGROUND: EORTC study 22033-26033 showed no difference in progression-free survival between high-risk low-grade glioma receiving either radiotherapy (RT) or temozolomide (TMZ) chemotherapy alone as primary treatment. Considering the potential long-term deleterious impact of RT on memory functioning, this study aims to determine whether TMZ is associated with less impaired memory functioning. METHODS: Using the Visual Verbal Learning Test (VVLT), memory functioning was evaluated at baseline and subsequently every 6 months. Minimal compliance for statistical analyses was set at 60%. Conventional indices of memory performance (VVLT Immediate Recall, Total Recall, Learning Capacity, and Delayed Recall) were used as outcome measures. Using a mixed linear model, memory functioning was compared between treatment arms and over time. RESULTS: Neuropsychological assessment was performed in 98 patients (53 RT, 46 TMZ). At 12 months, compliance had dropped to 66%, restricting analyses to baseline, 6 months, and 12 months. At baseline, patients in either treatment arm did not differ in memory functioning, sex, age, or educational level. Over time, patients in both arms showed improvement in Immediate Recall (P = 0.017) and total number of words recalled (Total Recall; P < 0.001, albeit with delayed improvement in RT patients (group by time; P = 0.011). Memory functioning was not associated with RT gross, clinical, or planned target volumes. CONCLUSION: In patients with high-risk low-grade glioma there is no indication that in the first year after treatment, RT has a deleterious effect on memory function compared with TMZ chemotherapy.

A European Organisation for Research and Treatment of Cancer phase III trial of adjuvant whole-brain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: quality-of-life results.

PURPOSE: This phase III trial compared adjuvant whole-brain radiotherapy (WBRT) with observation after either surgery or radiosurgery of a limited number of brain metastases in patients with stable solid tumors. Here, we report the health-related quality-of-life (HRQOL) results. PATIENTS AND METHODS: HRQOL was a secondary end point in the trial. HRQOL was assessed at baseline, at 8 weeks, and then every 3 months for 3 years with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and Brain Cancer Module. The following six primary HRQOL scales were considered: global health status; physical, cognitive, role, and emotional functioning; and fatigue. Statistical significance required P ≤ .05, and clinical relevance required a ≥ 10-point difference. RESULTS: Compliance was 88.3% at baseline and dropped to 45.0% at 1 year; thus, only the first year was analyzed. Overall, patients in the observation only arm reported better HRQOL scores than did patients who received WBRT. The differences were statistically significant and clinically relevant mostly during the early follow-up period (for global health status at 9 months, physical functioning at 8 weeks, cognitive functioning at 12 months, and fatigue at 8 weeks). Exploratory analysis of all other HRQOL scales suggested worse scores for the WBRT group, but none was clinically relevant. CONCLUSION: This study shows that adjuvant WBRT after surgery or radiosurgery of a limited number of brain metastases from solid tumors may negatively impact some aspects of HRQOL, even if these effects are transitory. Consequently, observation with close monitoring with magnetic resonance imaging (as done in the EORTC trial) is not detrimental for HRQOL.

Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study.

PURPOSE: This European Organisation for Research and Treatment of Cancer phase III trial assesses whether adjuvant whole-brain radiotherapy (WBRT) increases the duration of functional independence after surgery or radiosurgery of brain metastases. PATIENTS AND METHODS: Patients with one to three brain metastases of solid tumors (small-cell lung cancer excluded) with stable systemic disease or asymptomatic primary tumors and WHO performance status (PS) of 0 to 2 were treated with complete surgery or radiosurgery and randomly assigned to adjuvant WBRT (30 Gy in 10 fractions) or observation (OBS). The primary end point was time to WHO PS deterioration to more than 2. RESULTS: Of 359 patients, 199 underwent radiosurgery, and 160 underwent surgery. In the radiosurgery group, 100 patients were allocated to OBS, and 99 were allocated to WBRT. After surgery, 79 patients were allocated to OBS, and 81 were allocated to adjuvant WBRT. The median time to WHO PS more than 2 was 10.0 months (95% CI, 8.1 to 11.7 months) after OBS and 9.5 months (95% CI, 7.8 to 11.9 months) after WBRT (P = .71). Overall survival was similar in the WBRT and OBS arms (median, 10.9 v 10.7 months, respectively; P = .89). WBRT reduced the 2-year relapse rate both at initial sites (surgery: 59% to 27%, P < .001; radiosurgery: 31% to 19%, P = .040) and at new sites (surgery: 42% to 23%, P = .008; radiosurgery: 48% to 33%, P = .023). Salvage therapies were used more frequently after OBS than after WBRT. Intracranial progression caused death in 78 (44%) of 179 patients in the OBS arm and in 50 (28%) of 180 patients in the WBRT arm. CONCLUSION: After radiosurgery or surgery of a limited number of brain metastases, adjuvant WBRT reduces intracranial relapses and neurologic deaths but fails to improve the duration of functional independence and overall survival.

Topotecan in combination with radiotherapy in unresectable glioblastoma: a phase 2 study.

Improving glioblastoma multiforme (GBM) treatment with radio-chemotherapy remains a challenge. Topotecan is an attractive option as it exhibits growth inhibition of human glioma as well as brain penetration. The present study assessed the combination of radiotherapy (60 Gy/30 fractions/40 days) and topotecan (0.9 mg/m(2)/day on days 1-5 on weeks 1, 3 and 5) in 50 adults with histologically proven and untreated GBM. The incidence of non-hematological toxicities was low and grade 3-4 hematological toxicities were reported in 20 patients (mainly lymphopenia and neutropenia). Partial response and stabilization rates were 2% and 32%, respectively, with an overall time to progression of 12 weeks. One-year overall survival (OS) rate was 42%, with a median OS of 40 weeks. Topotecan in combination with radiotherapy was well tolerated. However, while response and stabilization concerned one-third of the patients, the study did not show increased benefits in terms of survival in patients with unresectable GBM.

Cerebellar pleomorphic xanthoastrocytoma: case report and literature review.

BACKGROUND: PXA generally has histologic features characteristic of benign biological behavior, although malignant forms have been reported. This neoplasm has also been observed in atypical locations. METHODS: The authors report a case of cerebellar PXA with rapid malignant transformation in a 58-year-old woman and review the rare presentations and atypical features of this tumor. RESULTS: Among the "unusual" locations, the most frequent is the cerebellum with 15 cases having been described, 9 in adults, with an average age of 33 years. In contrast, supratentorial forms had a younger age profile (26 years). The time from onset of symptoms to diagnosis was approximately 5.3 months. PXA in the posterior fossa had a higher rate of solid enhancing tumor (9/14). Regarding histologic appearance, two thirds were composite lesions. CONCLUSIONS: The clinicopathologic features of cerebellar PXA show some differences from PXA located in the cerebral hemispheres. Recognizing the potential for PXA to present with unusual manifestations, regardless of location, has an obvious impact on the accuracy of diagnosis.

Proposal of a scoring scale as a survival predictor in intracranial oligodendrogliomas.

INTRODUCTION: Histological, clinical and radiological features, and molecular genetic analysis are among the factors that have been considered in defining the prognosis of oligodendrogliomas (OD), but they have yielded conflicting results. The purpose of this study was to test out a scoring scale based on clinical, radiological, pathological and molecular features. MATERIAL AND METHOD: To identify factors with prognostic significance, we analyzed 87 treated patients with a histological diagnosis of OD. Of the parameters analyzed, age, onset, clinical status, radiological enhancement, histological necrosis, mitosis and chromosomal anomalies emerged as significant prognosis factors using univariate analysis. Multivariate analysis revealed age and chromosomal anomalies as independent factors of survival. RESULTS: The factors with a significant prognostic value were combined to determine which grouping factors best predict outcome. The proposed score is a pure number resulting from a combination of: 2 major factors: age and chromosomal anomalies (scored 3-0); 5 minor factors: onset, clinical examination, necrosis, mitoses (scored 1-0), and radiological enhancement (scored 2-0). According to our scale, 10 survival curves were produced for overall survival. Recursive partitioning of patients with the nearest score and outcome produced four groups with a significant difference in survival (p=10(-5)). The power of both the scale and the partitioned groups for predicting outcome was more accurate than the WHO and St Anne grading systems, and the molecular sub-classification. CONCLUSIONS: Our scale is a plausible way of classifying patients harboring intracranial OD according to expected survival.

Malignant transformation of intra-cranial epithelial cysts: systematic article review.

INTRODUCTION: Epidermoid and dermoid cysts are among the most benign intra cranial tumors. Their malignant transformation into squamous cell carcinoma is rare. The authors reviewed the literature. MATERIALS AND METHODS: MEDLINE and SCIENCE DIRECT searches, and examination of the references in the selected articles yielded 74 patients, 52 of whom fulfilled Garcia's criteria and were selected for the study. Survival analyses were performed to determine whether survival differences were of statistical significance, and P < 0.05 was considered as significant. RESULTS: Malignant transformation is characterized by a rapid onset of symptoms, recurrence, leptomeningeal carcinomatosis (LC), and tumor enhancement at Computed Tomography Scan or Magnetic Resonance Imaging (87.8 showed this radiological feature). In this review, the SCCs were classified in five groups: (1) Initial malignant transformation of a benign cyst; (2) malignant transformation from a remnant cyst; (3) malignant transformation of a dermoid and epithelial cyst; (4) malignant transformation with leptomeningeal carcinomatosis; (5) other malignancies arising from benign cysts. The median survival was 9 months. Statistics show that LC was of poor prognosis and radiotherapy, although not statistically significant, seems effective against such lesions, with a median survival of 26 months as opposed to 3 months (P=0.077). CONCLUSION: Although rare, malignant transformation of intracranial epithelial cysts has a poor prognosis and surgery followed by radiotherapy seems to be the best therapeutic modality.

Oligodendroglioma: clinical study and survival analysis correlated with chromosomal anomalies.

OBJECT: Demonstration of the loss of chromosomes 1p and 19q in the presence of a brain neoplasm marks the emergence of genotype as a prognostic indicator. The authors report gene expression data for oligodendroglioma and correlate genotype with response to therapy. Gene expression subgroups may represent distinct types of disease. METHODS: Eighty-seven cases of supratentorial oligodendroglioma were selected from 145 cases treated in a single center between January 1990 and December 2001. Fluorescence in situ hybridization was used to determine the status of chromosomes 1p and 19q. Parameters evaluated included clinical data and radiological and histological features. Univariate and multivariate analyses were performed and a probability value less than 0.05 was considered significant. The patients included 48 women and 39 men. The overall mean age at presentation was 45 years for women and 36 years for men (p = 0.006). The univariate analysis identified the following as favorable prognostic factors: younger patient age (p = 10(-5)), female sex (p = 0.0025), seizure as a presenting symptom (p = 10(-5)), normal clinical examination (p = 10(-5)), absence of lesion enhancement on neuroimaging studies (p = 0.0231), lack of histological necrosis (p = 0.0003), absence of mitoses (p = 0.0014), 1p and 19q deletions (p = 0.0001), absence of recurrence (p = 0.0021), and adjuvant radiotherapy and/or chemotherapy (p = 10(-5)). The multivariate analysis identified patient age (p = 10(-5)) and chromosomal anomalies (p = 0.002) as independently linked to survival. Three molecular subtypes emerged: oligodendroglioma with 1p and 19q deletions, oligodendroglioma demonstrating polysomia and a lack of meaningful response to radiotherapy or chemotherapy, and oligodendroglioma with no 1p-9q deletion in which partial response was seen. CONCLUSIONS: According to our data, oligodendrogliomas could be divided into three molecular subtypes. Although chemotherapy seems efficient for managing this tumor, additional studies should be conducted to compare the efficacy of radiotherapy and chemotherapy.

[Standards, Options and Recommendations 2002 for the management of adult patients with intracranial gliomas (summary report)]. / Standards, options et recommandations 2002 pour la prise en charge des patients atteints de gliomes intracrâniens de l'adulte (rapport abrégé).

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVE: To define clinical practice guidelines for the management of adult patients with intracranial glioma in collaboration with the Association of French-speaking Neuro-oncologists (Anocef) and the French society of neurosurgeons (SNCLF). These recommendations cover diagnosis, classification, treatment and follow-up of patients with these tumors. METHOD: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines has been defined, the document is submitted for review by independent reviewers. RESULTS: This article is a summary version of the full document presenting the clinical practice guidelines with algorithms. The main recommendations concern the place of the surgery, radiotherapy, chemiotherapy, imagery and concomitant medical treatments in the specific treatment strategy of grade III and IV glioma, grade II glioma, gliomatosis cerebri, pilocytic astrocytoma, subependymoma, xanthoastrocytoma, intracranial ependymoma and brain stem glioma.