Effect of low-dose ketamine on PerioperAtive depreSsive Symptoms in patients undergoing Intracranial tumOr resectioN (PASSION): study protocol for a randomized controlled trial.

BACKGROUND: Perioperative depressive symptoms (PDS) are common mental comorbidities that influence clinical outcomes and prognosis. However, there is no rapid-acting treatment to address these symptoms during a limited hospital stay. METHODS/DESIGN: This is a single-center, randomized, placebo-controlled, and double-blind trial. Randomization will be applied and stratified by the severity of PDS (moderate versus severe). Eighty patients who are scheduled for elective supratentorial brain tumor resection with PDS will be randomly allocated to the ketamine or placebo group with a ratio of 1 to 1. Patients in the ketamine group will be administered low-dose ketamine (0.5 mg/kg) intravenously for 40 min while the dural mater is being cut into, whereas patients in the placebo group will receive the same volume of normal saline at the same infusion rate at the same time points. The primary endpoint is the rate of PDS response at 3 days after surgery. Secondary outcomes include efficacy parameters such as the rate of PDS remission and safety outcomes such as the incidence of postoperative delirium, quality of recovery, and psychiatric side effects. DISCUSSION: This study aims to determine whether ketamine could improve the depressive symptoms of perioperative patients undergoing supratentorial brain tumor resection. It will also examine the safety of administering ketamine as an intraoperative anti-depressant. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03086148 . Registered on 22 March 2017.

Neurocognitive status in patients with newly-diagnosed brain tumors in good neurological condition: The impact of tumor type, volume, and location.

OBJECTIVE: Neurocognitive function is of great importance in patients with brain tumors. Even patients in good neurological condition may suffer from neurocognitive dysfunction that affects their daily living. The purpose of the present study was to identify risk factors for neurocognitive dysfunction in patients suffering from common supratentorial brain tumors with minor neurological deficits. METHODS: A prospective study evaluating neurocognitive dysfunction in patients with a newly-diagnosed brain tumor in good neurological condition was performed at a major German academic institution. Patients underwent extensive neurocognitive testing assessing perceptual speed, executive function, visual-spatial and verbal working memory, short- and long-term memory, verbal fluency, fluid intelligence, anxiety, and depression. For each patient, a healthy control was pair-matched based on age, sex, handedness, and profession. RESULTS: A total of 46 patients and 46 healthy controls underwent neurocognitive testing. Patients suffered from glioblastoma multiforme (10), cerebral metastasis (10), pituitary adenoma (13), or meningioma (13). There was neither any difference in age, educational level, fluid intelligence, neurological deficits, and anxiety nor in any depression scores between tumor subgroups. Overall, neurocognitive performance was significantly worse in patients compared to healthy controls. Larger tumor volume, frontal location, and left/dominant hemisphere were associated with worse executive functioning and verbal fluency. Additionally, larger tumors and left/dominant location correlated with impairments on perceptual speed tasks. Frontal tumor location was related to worse performance in visual-spatial and short- and long-term memory. Tumor type, clinical presentation, and patient self-awareness were not associated with specific neurocognitive impairments. CONCLUSIONS: Patients suffering from newly-diagnosed brain tumors presenting in good neurological condition display neurocognitive impairments in various domains. Larger tumor volumes, frontal location, and left/dominant hemisphere are important predictors for potential neurocognitive deficits. Tumor type, clinical presentation, or self-awareness are less significant at the time of diagnosis.

Psychiatric comorbidity in temporal DNET and improvement after surgery.

BACKGROUND: "Alien tissue" may be responsible for a higher frequency of psychiatric disorders in patients with temporal lobe epilepsy (TLE). Also, ganglioglioma and dysembryoplastic neuroepithelial tumors (DNET) could represent a risk-factor for the development of post-surgical psychoses. Classically, severe psychiatric disorders contra-indicate epilepsy surgery. OBJECTIVES: Assessment of inter-ictal psychiatric disorders in 10 consecutive patients with temporal DNET, before and after epilepsy surgery with a minimum of a 2-year follow-up evaluation. METHODS: DNETs were confirmed on histological examination. Psychiatric disorders were classified according to the DSM-IV-TR. RESULTS: Five patients presented inter-ictal psychiatric disorders with, according to the DSM-IV-TR, undifferentiated schizophrenia (one case), "borderline" personality (two cases), intermittent explosive disorder with slight mental retardation (one case), and personality disorders not otherwise specified but with some traits of dependent personality and with mythomania (one case). The condition of these five patients dramatically improved after surgery. No psychiatric behavior or "de novo" psychosis was observed after surgery in any of the patients. CONCLUSION: The prevalence of inter-ictal psychiatric disorders appears to be high in epileptic patients with a temporal lobe DNET primarily in relation to personality and behavioral problems with some degree of impulsivity and verbal aggressiveness. The improvements after surgery suggest that this therapy could be performed in these patients and severe psychiatric disorders do not contra-indicate this procedure.

Effect of cognitive rehabilitation in a case of thalamic astrocytoma.

We describe the effectiveness of rehabilitative training for a neuropsychological deficit following the removal and treatment of a fibrillary astrocytoma (Grade II) in a young man. The rehabilitative training was based on cognitive and motivational techniques and has been carried out for a period of 3 months (2 times per week). The results, even if limited to a single case, seem to support the idea that cognitive rehabilitation should facilitate the brain's reorganization of basic cognitive functions in the neuro-oncologic field.

Specificities of Awake Craniotomy and Brain Mapping in Children for Resection of Supratentorial Tumors in the Language Area.

BACKGROUND: In the pediatric population, awake craniotomy began to be used for the resection of brain tumor located close to eloquent areas. Some specificities must be taken into account to adapt this method to children. OBJECTIVE: The aim of this clinical study is to not only confirm the feasibility of awake craniotomy and language brain mapping in the pediatric population but also identify the specificities and necessary adaptations of the procedure. METHODS: Six children aged 11 to 16 were operated on while awake under local anesthesia with language brain mapping for supratentorial brain lesions (tumor and cavernoma). The preoperative planning comprised functional magnetic resonance imaging (MRI) and neuropsychologic and psychologic assessment. The specific preoperative preparation is clearly explained including hypnosis conditioning and psychiatric evaluation. The success of the procedure was based on the ability to perform the language brain mapping and the tumor removal without putting the patient to sleep. We investigated the pediatric specificities, psychological experience, and neuropsychologic follow-up. RESULTS: The children experienced little anxiety, probably in large part due to the use of hypnosis. We succeeded in doing the cortical-subcortical mapping and removing the tumor without putting the patient to sleep in all cases. The psychological experience was good, and the neuropsychologic follow-up showed a favorable evolution. CONCLUSIONS: Preoperative preparation and hypnosis in children seemed important for performing awake craniotomy and contributing language brain mapping with the best possible psychological experience. The pediatrics specificities are discussed.

Awake craniotomy for supratentorial gliomas: why, when and how?

Awake craniotomy has become an increasingly utilized procedure in the treatment of supratentorial intra-axial tumors. The popularity of this procedure is partially attributable to improvements in intraoperative technology and anesthetic techniques. The application of awake craniotomy to the field of neuro-oncology has decreased iatrogenic postoperative neurological deficits, allowed for safe maximal tumor resection and improved healthcare resource stewardship by permitting early patient discharge. In this article, we review recent evidence for the utility of awake craniotomy in the resection of gliomas and describe the senior author's experience in performing this procedure. Furthermore, we explore innovative applications of awake craniotomy to outpatient tumor resections and the conduct of neurosurgery in resource-poor settings. We conclude that awake craniotomy is an effective and versatile neurosurgical procedure with expanding applications in neuro-oncology.

Regression of recurrent malignant gliomas with convection-enhanced delivery of topotecan.

BACKGROUND: Convection-enhanced delivery of chemotherapeutics for the treatment of malignant glioma is a technique that delivers drugs directly into a tumor and the surrounding interstitium through continuous, low-grade positive-pressure infusion. This allows high local concentrations of drug while overcoming the limitations imposed by toxicity and the blood-brain barrier in systemic therapies that prevent the use of many potentially effective drugs. OBJECTIVE: To examine the safety profile of a conventional chemotherapeutic agent, topotecan, via convection-enhanced delivery in the treatment of recurrent malignant gliomas and secondarily to assess radiographic response and survival. METHODS: We performed a prospective, dose-escalation phase Ib study of the topoisomerase-I inhibitor topotecan given by convection-enhanced delivery in patients with recurrent malignant gliomas. RESULTS: Significant antitumor activity as described by radiographic changes and prolonged overall survival with minimal drug-associated toxicity was demonstrated. A maximum tolerated dose was established for future phase II studies. CONCLUSION: Topotecan by convection-enhanced delivery has significant antitumor activity at concentrations that are nontoxic to normal brain. The potential for use of this therapy as a generally effective treatment option for malignant gliomas will be tested in subsequent phase II and III trials.

Validation of EORTC prognostic factors for adults with low-grade glioma: a report using intergroup 86-72-51.

PURPOSE: A prognostic index for survival was constructed and validated from patient data from two European Organisation for Research and Treatment of Cancer (EORTC) radiation trials for low-grade glioma (LGG). We sought to independently validate this prognostic index with a separate prospectively collected data set (Intergroup 86-72-51). METHODS AND MATERIALS: Two hundred three patients were treated in a North Central Cancer Treatment Group-led trial that randomized patients with supratentorial LGG to 50.4 or 64.8 Gy. Risk factors from the EORTC prognostic index were analyzed for prognostic value: histology, tumor size, neurologic deficit, age, and tumor crossing the midline. The high-risk group was defined as patients with more than two risk factors. In addition, the Mini Mental Status Examination (MMSE) score, extent of surgical resection, and 1p19q status were also analyzed for prognostic value. RESULTS: On univariate analysis, the following were statistically significant (p<0.05) detrimental factors for both progression-free survival (PFS) and overall survival (OS): astrocytoma histology, tumor size, and less than total resection. A Mini Mental Status Examination score of more than 26 was a favorable prognostic factor. Multivariate analysis showed that tumor size and MMSE score were significant predictors of OS whereas tumor size, astrocytoma histology, and MMSE score were significant predictors of PFS. Analyzing by the EORTC risk groups, we found that the low-risk group had significantly better median OS (10.8 years vs. 3.9 years, p<0.0001) and PFS (6.2 years vs. 1.9 years, p<0.0001) than the high-risk group. The 1p19q status was available in 66 patients. Co-deletion of 1p19q was a favorable prognostic factor for OS vs. one or no deletion (median OS, 12.6 years vs. 7.2 years; p=0.03). CONCLUSIONS: Although the low-risk group as defined by EORTC criteria had a superior PFS and OS to the high-risk group, this is primarily because of the influence of histology and tumor size. Co-deletion of 1p19q is a prognostic factor. Future studies are needed to develop a more refined prognostic system that combines clinical prognostic features with more robust molecular and genetic data.

Health-related quality of life and cognitive functioning in adult patients with supratentorial WHO grade II glioma: status prior to therapy.

The present prospective study intends to evaluate health-related quality of life (HRQL) and cognitive functioning in adult patients with supratentorial World Health Organization (WHO) grade II glioma (LGG) prior to observation/therapy and to determine possible influences of tumor-related factors on these measures. Adult patients with biopsy-proven supratentorial LGG were considered eligible (study period 18 months). Besides detailed documentation of patient clinical status we evaluated HRQL using the Short Form-36 (SF-36) Health Survey and applied the Beck Depression Inventory. Furthermore, attention and verbal memory functions were tested. Data from matched healthy control populations served as reference, and T-values were compared using Mann-Whitney U tests. For correlation of scores the Pearson test was utilized. Thirty-three patients with median Karnofsky Performance Status (KPS) of 80 were evaluated. Selective and divided attention showed significant impairment (P < 0.005), while verbal memory functions were unaffected. HRQL evaluated by SF-36 Health Survey was significantly reduced predominantly in the psychological domains (P < 0.025 to P < 0.0005). Nine patients displayed mild to moderate depression. Duration of symptoms >20 weeks and presence of seizures negatively affected aspects of HRQL, while cognitive functions were not influenced. KPS <80 correlated significant only with reduced physical functioning (P < 0.002) and role functioning (P < 0.01) on the SF-36 Health Survey. While displaying good clinical status, patients with LGG showed significant impairment in aspects of attention and affections of HRQL already at time of diagnosis. These results suggest that these impairments originate from the tumor and/or potentially from confrontation with the diagnosis itself.

Factors involved in maintaining prolonged functional independence following supratentorial glioblastoma resection. Clinical article.

OBJECT: The median survival duration for patients with glioblastoma is approximately 12 months. Maximizing quality of life (QOL) for patients with glioblastoma is a priority. An important, yet understudied, QOL component is functional independence. The aims of this study were to evaluate functional outcomes over time for patients with glioblastoma, as well as identify factors associated with prolonged functional independence. METHODS: All patients who underwent first-time resection of either a primary (de novo) or secondary (prior lower grade glioma) glioblastoma at a single institution from 1996 to 2006 were retrospectively reviewed. Patients with a Karnofsky Performance Scale (KPS) score ≥ 80 were included. Kaplan-Meier, log-rank, and multivariate proportional hazards regression analyses were used to identify associations (p < 0.05) with functional independence (KPS score ≥ 60) following glioblastoma resection. RESULTS: The median follow-up duration time was 10 months (interquartile range [IQR] 5.6-17.0 months). A patient's preoperative (p = 0.02) and immediate postoperative (within 2 months) functional status was associated with prolonged survival (p < 0.0001). Of the 544 patients in this series, 302 (56%) lost their functional independence at a median of 10 months (IQR 6-16 months). Factors independently associated with prolonged functional independence were: preoperative KPS score ≥ 90 (p = 0.004), preoperative seizures (p = 0.002), primary glioblastoma (p < 0.0001), gross-total resection (p < 0.0001), and temozolomide chemotherapy (p < 0.0001). Factors independently associated with decreased functional independence were: older age (p < 0.0001), coexistent coronary artery disease (p = 0.009), and incurring a new postoperative motor deficit (p = 0.009). Furthermore, a decline in functional status was independently associated with tumor recurrence (p = 0.01). CONCLUSIONS: The identification and consideration of these factors associated with prolonged functional outcome (preoperative KPS score ≥ 90, seizures, primary glioblastoma, gross-total resection, temozolomide) and decreased functional outcome (older age, coronary artery disease, new postoperative motor deficit) may help guide treatment strategies aimed at improving QOL for patients with glioblastoma.

Neuropsychological differences between survivors of supratentorial and infratentorial brain tumours.

BACKGROUND: The purpose of this study is to evaluate the relationship between brain tumour location and core areas of cognitive and behavioural functioning for paediatric brain tumour survivors. The extant literature both supports and refutes an association between paediatric brain tumour location and neurocognitive outcomes. We examined neuropsychological test data to identify any differences in neurocognitive and behavioural profile associated with supratentorial versus infratentorial tumour location. METHODS: Following Institutional Review Board approval, the medical records and neuropsychological test data collected between 1997 and 2002 for 70 children treated for brain tumour at Children's Hospital Los Angeles were reviewed. Fifty-one per cent of the participants had tumours located in the supratentorial regions of the brain, whereas 49% had infratentorial tumours. Primary medical treatments involved tumour resection (90%), cranial radiation therapy (76%), chemotherapy (71%), and 59% all three medical procedures. The two tumour location groups did not differ significantly in the cumulative treatment dose of irradiation to the tumour bed or in the dose delivered to the whole brain. Neuropsychological test data included measures of verbal and non-verbal intellectual functioning, attention/working memory, processing speed, verbal and visual memory, fine motor skills, visual-motor integration, academic achievement, and social-emotional functioning. Differences between the two groups were evaluated using anova, t-tests and chi-squared statistical tests. RESULTS: The supratentorial and infratentorial tumour location groups did not differ on measures of intellectual functioning. However, survivors of infratentorial tumours performed more poorly on selected measures of more specific cognitive functions and on parent-report of social-emotional functioning relative to survivors of supratentorial tumours, even when age at diagnosis was held as a covariate. Higher frequency of auditory deficits was noted in the infratentorial tumour group and was associated with lowered academic achievement scores. CONCLUSIONS: The differences by location found in more specific neurocognitive and social-emotional variables, after controlling for age at diagnosis, may possibly reflect tumour location-specific effects. However, this interpretation remains tentative given the limitations in our study and inability to control for the range of medical and treatment-related factors that may have contributed towards the outcomes observed in our sample. At the same time, most of our findings appear consistent with reports from recent studies in this area.

Patient-assessed satisfaction and outcome after microsurgical resection of cavernomas causing epilepsy.

OBJECT: Microsurgical resection of supratentorial cavernomas associated with intractable epilepsy is performed frequently. Despite its common occurrence, little is known about patient perceptions of microsurgical resection for cavernomas. This survey study was performed to investigate patient perceived outcome after surgery for cavernomas associated with intractable epilepsy. METHODS: The authors' surgical database was searched for cavernoma resection performed between 1971 and July of 2006. Of the initial 173 patients identified, 102 met criteria for medically intractable seizures. These 102 patients were then mailed a survey to determine follow-up and patient satisfaction. Thirty-nine surveys were returned as undeliverable, and 30 (48%) of the remaining 63 patients responded. RESULTS: The average age at surgery for patients responding to this survey was 40 +/- 16 years compared with 35 +/- 15 years for all 102 patients. At prolonged follow-up, 87% of patients reported being seizure-free. Of those with seizures, 2 (7%) reported being nearly seizure-free (rare disabling seizures), 2 (7%) believed they had a worthwhile improvement in seizure frequency, and no patient (0%) in this series believed they did not have a worthwhile improvement in seizure frequency. Ninety percent of responders stated they definitely, and 10% probably, would have surgery again. No patient responded that they probably or definitely would not have epilepsy surgery. Mean clinical follow-up was 36 +/- 8 months and survey follow-up was 97 +/- 13 months for these 30 patients. Use of the mail-in survey increased follow-up length 2.7 times longer compared with clinical follow-up. CONCLUSIONS: It is clear from this select group of survey responders that patients undergoing surgery for cavernomas associated with medically intractable epilepsy are happy they underwent surgery (100%) and had excellent surgical outcomes (87% seizure-free) at prolonged follow-up of 97 +/- 13 months. These survey results support that microsurgical resection for cavernomas is highly effective and significantly improves these patients' quality of life.

[Apathy or depression? Do you have a nose for it? Four case reports of paramedian frontal tumors]. / Apathie ou dépression ? Une question de nez ? Illustration par quatre cas de tumeurs frontales paramédianes.

We report four cases of patients with clinically isolated apathy which was mistaken for depression even though they were suffering from voluminous brain tumors. These cases remind us that rigorous clinical analysis is essential: searching for signs of organic origin or psychiatric etiology is fundamental to avoid an incorrect diagnosis. In particular, these four patients displayed anosmia, an uncommon symptom for patients suffering from depression. In addition, brain imaging is important to correctly identify the most prudent medical and/or surgical management strategy. In this short discussion, we propose an algorithm for the clinical diagnosis of apathy.

Quality of life in neurooncology--age matters.

OBJECT: Due partly to therapeutic improvements and prolonged patient survival, the field of neurooncology is gradually undergoing a philosophical shift, progressively moving toward a more functional approach to patient welfare. This shift includes, as one of its defining objectives, the promotion of elevated levels of quality of life (QOL) and quality of health (QOH) for patients of all ages. Unfortunately, an adult life-stage perspective has never been used to study the long-lasting impact of age on well-being in neurooncology patients. METHODS: In this study, the authors assessed and compared the QOL and QOH scores of 42 younger adults (< or = 40 years of age) and 88 older adults (> 40 years of age) presenting with a primary supratentorial tumor. RESULTS: After having controlled for biomedical and treatment-related factors, the authors discovered that older adults reported lower functional well-being and poorer neurocognitive functioning than younger adults. This age difference appeared earlier than expected (developing as early as middle age), suggesting an accelerated effect of disease on the aging process. Importantly, it was also found that the variables that predict QOL and QOH differed depending on patient age. For example, support from friends was a significant predictor of QOL for younger adults, whereas the capacity to continue enjoying life was a significant predictor for older adults. Moreover, the presence of a high-grade tumor and increased physical pain had a negative impact on the QOH of younger adults, whereas increased difficulty with concentration negatively impacted the QOH of older adults. CONCLUSIONS: These age differences clearly warn against consolidating the QOL or QOH scores of younger and older adults, and instead suggest that age at diagnosis is essential when considering patient perspective, and when establishing tailored support programs.

Assessment of neuropsychological parameters and quality of life to evaluate outcome in patients with surgically treated supratentorial meningiomas.

OBJECTIVE: According to current outcomes research programs, assessment of a broad spectrum of parameters, including quality of life indices, is required to adequately reflect the results of a given treatment. We performed a comprehensive evaluation in patients after supratentorial meningioma surgery in a retrospective study. METHODS: In 91 consecutive patients, outcome was assessed in individual sessions in patients' homes an average of 15 months (standard deviation, +/- 3.6 months) after surgery. The survey included tests of cognitive performance, coping strategies, satisfaction with life, and a structured interview. RESULTS: We found a significant negative correlation between patient age and cognitive performance (P < 0.001), with a major decline beginning at the age of 55 years. Despite normal cognitive performance, 73% of younger patients (younger than 55 years) compared with 20% of older patients (P < 0.001) were not satisfied with life. As a major problem, 68% of younger patients described an inability to accept having this severe disease as a young person. Patients living as singles had a higher frequency of depressive coping (P < 0.05) and less satisfaction with life (P < 0.05). CONCLUSION: Comprehensive evaluation after meningioma surgery is required to prevent poor long-term results after apparently successful surgery. In our study, tests and structured interviews revealed different aspects, especially concerning patient age. Because demographic variables clearly influenced satisfaction with life, evaluation of quality of life must account for these factors to improve comparison of different studies. However, prospective studies with larger cohorts and control groups are required to prove our hypotheses.

Psychic stress in cranial-cerebral tumors.

From a historical point of view, medicine (in modem society) has set its mission as to cure diseases--medical-type issues--and to ignore patient's condition--illness endurance. By accepting this point of view with reference to their problem, patients have entered some sort of conspiracy of silence and started ignoring the emotional reaction to their medical problems (or to cancel these reactions), regarding them as irrelevant to the problem itself. This approach is also reinforced by the medical pattern that absolutely contests the idea that mind influences the body in a very important way. Another equally unproductive ideology is the idea that people could cure themselves alone even of the most serious illnesses by feeling happy or by thinking in a positive manner, or the idea that people are guilty of getting sick. This attitude resulted in creating a widespread confusion and in significant misunderstandings regarding the extent to which illness can be influenced by mind, at times even blaming someone for having got ill. In the world of illness, emotions have supremacy and fear is the only "thought". We can be so fragile emotionally speaking when we suffer from some illness because part of our mental good-humor is partially based on the illusion of invulnerability. Illness--especially a severe one--destroys this illusion and cancels the premise that our world is one in which existence is completely secure. All of a sudden, we feel thick with weaknesses, we feel helpless and vulnerable (Dixon, 1992). There is a problem when the medical personnel ignore the way patients react from an emotional point of view, even though they should exclusively take care of our physical state. This lack of interest in the emotional reality of an illness neglects something obvious which shows that the emotional state of people can play a significant role as to their vulnerability towards illness and during the recovery process (Ciofu et al., 1978). There is already a scientific basis according to which a limit to the medical efficiency appears not only during the prophylactic process but also during treatment. This efficiency can be enhanced by curing the emotional state of the patient at the same time with his/her medical state. Unfortunately, too often, the medical personnel is in a hurry or unsympathetic towards patients' despair and, seemingly, things get worse indeed in the midst of the medical system harsh reality, medical system that depends too much on time keeping performed by accountants (Ciurea et al., 2009).

Intelligence and adaptive function in children diagnosed with brain tumour during infancy.

BACKGROUND: Late effects of treatment in children diagnosed and treated for brain tumours in infancy is a major concern. Assessment of infants presenting with brain tumours is difficult and there is little information available regarding the development of infants prior to treatment and hence the impact of the tumour itself on developmental outcomes. AIM: To describe the development of children diagnosed with brain tumours in infancy and to document their cognitive and adaptive function at school entry. METHOD: Infants were psychologically evaluated at the time of diagnosis of a brain tumour and during their fifth or sixth year in preparation for school entry. RESULTS: Children diagnosed with brain tumours in infancy display developmental delays in a number of areas of adaptive function. By the time these children are school age they display further compromise in cognitive and academic skills and adaptive behaviour. Higher levels of deficit at follow-up were associated with tumour location in the supratentorium, younger age at diagnosis and longer time since diagnosis. The effect of radiotherapy could not be determined because of differing degrees of developmental compromise in the treatment groups at baseline. CONCLUSION: Brain tumours in infancy confer a risk of poor developmental progress at the time of diagnosis. These children display additional compromise of development by the time they reach school age. Research protocols evaluating the impact of treatment in infants diagnosed with brain tumours need to take account of the developmental status of the child at diagnosis.

Importance of baseline mini-mental state examination as a prognostic factor for patients with low-grade glioma.

PURPOSE: The outcome and cognitive performance data collected in a prospective, intergroup clinical trial were analyzed to assess the prognostic importance of the baseline (before radiotherapy) Mini-Mental State Examination (MMSE) score in patients with low-grade glioma. METHODS AND MATERIALS: The patients studied were 203 adults with a supratentorial low-grade glioma randomly assigned to low-dose (50.4 Gy in 28 fractions) or high-dose (64.8 Gy in 36 fractions) localized radiotherapy. Folstein MMSE scores and neurologic function scores at baseline in combination with multiple other baseline variables were analyzed. The median follow-up was 7.4 years for the 101 patients still alive. RESULTS: Patients (n = 36) with an abnormal baseline MMSE score (< or =26) had a worse 5-year progression-free survival rate (27% vs. 60%; p <0.001) and overall survival rate (31% vs. 76%; p <0.001) compared with those with a normal score. On multivariate analysis, the baseline MMSE score was a statistically significant predictor of survival. Other factors associated with overall survival were age, tumor size, and tumor histologic type. CONCLUSION: The presence of an abnormal baseline MMSE score was a strong predictor of poorer progression-free and overall survival for patients with a low-grade glioma. The baseline MMSE should be considered in future prognostic scoring systems.

Adult patients with supratentorial pilocytic astrocytomas: a prospective multicenter clinical trial.

PURPOSE: Supratentorial pilocytic astrocytomas in adults are uncommon. A prospective clinical trial was conducted to obtain clinical and outcome data in these patients. METHODS AND MATERIALS: Between 1986 and 1994, 20 eligible adults with supratentorial pilocytic astrocytomas were enrolled in a prospective intergroup trial of radiotherapy (RT) after biopsy (3 patients) or observation after gross (11 patients) or subtotal (6 patients) resection. RESULTS: At the time of analysis (median follow-up, 10 years), 1 patient (5%) had died and 19 patients (95%) were alive. The 5-year progression-free and overall survival rates were 95%. The cause of death in the patient who died (2.1 years after enrollment) was unknown; a radiographic examination obtained shortly before the patient's demise revealed no signs of progression. Progression in 1 patient approximately 1 month after enrollment required injection of (32)P into an enlarging cyst. The patient required RT approximately 18 months later because of further progression. This patient was alive without evidence of progression 9 years after RT. No toxic effects had been recorded at the latest follow-up examinations. CONCLUSION: With follow-up comparable or superior to that in many retrospective studies, the results of this prospective trial confirm that adults with pilocytic astrocytomas have a favorable prognosis with regard to survival and neurologic function. The vast majority of patients remained stable after gross or subtotal resection and no adjuvant therapy. RT need not be offered to adults with supratentorial pilocytic astrocytoma after gross or subtotal resection; instead, close observation is recommended. Because only 3 patients received RT after biopsy, it is difficult to comment on the effect of RT on their outcome as a group.

Acute effects on neuropsychological function and quality of life by high-dose multiple daily fractionated radiotherapy for malignant astrocytomas: assessing the tolerability of a new radiotherapy regimen.

Cognitive and other quality of life measures were assessed in 29 patients with supratentorial malignant astrocytomas before and after high-dose (8000 cGy) multiple daily fractionated radiotherapy. Assessments were done immediately before and after radiotherapy. Patients completed a neuropsychological evaluation and the Functional Living Index: Cancer (FLIC). Spouses completed the Family Environment Scale and the Profile of Mood States. Cognitive abilities generally improved over the course of radiotherapy. Occasionally, deterioration of potential clinical importance was observed on functions associated with the tumour site. Quality of life as assessed by the FLIC was stable in most cases and improved in five, but deteriorated in three patients. Families showed slightly less Conflict and slightly more Cohesion than the norm; this was especially so when patients had greater cognitive deficit. Emotional state of spouses was variable, with increased fatigue or reduced activity most commonly reported, followed by depression and anxiety. Mostly this improved with time or remained stable, but two spouses reported worsening emotional state. Results are generally encouraging for tolerance of this radiotherapy protocol, although they demonstrate that limited adverse effects may occur in some cases.