Phase II study of first-line chemotherapy with temozolomide in recurrent oligodendroglial tumors: the European Organization for Research and Treatment of Cancer Brain Tumor Group Study 26971.

PURPOSE: Oligodendroglial tumors are chemotherapy-sensitive tumors, with two thirds of patients responding to combination chemotherapy with procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ), a new alkylating and methylating agent, has demonstrated high response rates in patients with recurrent anaplastic astrocytoma. We investigated TMZ as first-line chemotherapy in recurrent oligodendroglial tumors (OD) and mixed oligoastrocytomas (OA) after surgery and radiation therapy. PATIENTS AND METHODS: In a prospective, nonrandomized, multicenter, phase II trial, patients were treated with 200 mg/m2 of TMZ on days 1 through 5 in 28-day cycles for 12 cycles. Patients with a recurrence after prior surgery and radiotherapy, and with measurable and enhancing disease on magnetic resonance imaging (MRI) were eligible for this study. Patients with large lesions and mass effect or with new clinical deficits were not eligible. Pathology and the MRI scans of all responding patients were centrally reviewed. RESULTS: Thirty-eight eligible patients were included. In three patients, pathology review did not confirm the presence of an OD or OA. TMZ was generally well tolerated. The most frequent side effects were hematologic; only one patient discontinued treatment for toxicity. In 20 (52.6%) of 38 patients (95% exact confidence interval, 35.8% to 69.0%), a complete (n = 10) or partial response to TMZ was observed. The median time to progression was 10.4 months for all patients and 13.2 months for responding patients. At 12 months from the start of treatment, 40% of patients were still free from progression. CONCLUSION: TMZ provides an excellent response rate with good tolerability in chemotherapy-naive patients with recurrent OD. A randomized phase III study comparing PCV with TMZ is warranted.     

Tumour and surgery effects on cognitive functioning in high-grade glioma patients

Background

Many high-grade glioma (HGG) patients have cognitive impairments, which impact daily functioning. Cognitive impairments can be caused by tumour-, treatment-, and patient-related factors. The effect of the tumour and of surgical resection on cognition is, however, not well known. We investigated tumour and surgical effects on cognitive functioning in patients with HGG.

Methods

At baseline, preceding surgery, 62 patients with HGG underwent neuropsychological testing concerning seven cognitive domains: verbal and working memory, attention, executive functioning, psychomotor function, information processing speed, and visuoconstructive abilities. Thirty-nine patients were included in follow-up testing after surgery, but before subsequent treatment. Tumour size and site, use of anti-epileptic drugs and corticosteroids, and extent of resection were recorded.

Results

Compared to healthy controls, cognitive functioning of patients was significantly impaired in all domains. Prior to surgery 79 % (49 of 62) of patients had cognitive impairment in at least one domain. At median follow-up of 5 weeks after surgery, 59 % (23 of 39) of patients were cognitively impaired in at least one domain. At follow-up, 49 % showed improvement, while 23 % declined. Left hemisphere tumour localization was associated with worse verbal memory (P=0.004), and larger tumours in this hemisphere with poorer executive functioning (P?<?0.001). Changes in cognitive performance at follow-up relative to baseline were not related to tumour characteristics or extent of resection.

Conclusions

Tumour-related cognitive deficits are present in a majority of HGG patients preceding surgery. Surgery does not result in cognitive deterioration in the short term in most patients.     

The impact of current treatment modalities on the outcomes of patients with melanoma brain metastases: A systematic review

Patients with melanoma brain metastases (MBM) still have a very poor prognosis. Several treatment modalities have been investigated in an attempt to improve the management of MBM. This review aimed to evaluate the impact of current treatments for MBM on patient- and tumor-related outcomes, and to provide treatment recommendations for this patient population. A literature search in the databases PubMed, Embase, Web of Science and Cochrane was conducted up to January 8, 2019. Original articles published since 2010 describing patient- and tumor-related outcomes of adult MBM patients treated with clearly defined systemic therapy were included. Information on basic trial demographics, treatment under investigation and outcomes (overall and progression-free survival, local and distant control and toxicity) were extracted. We identified 96 eligible articles, comprising 95 studies. A large variety of treatment options for MBM were investigated, either used alone or as combined modality therapy. Combined modality therapy was investigated in 71% of the studies and resulted in increased survival and better distant/local control than monotherapy, especially with targeted therapy or immunotherapy. However, neurotoxic side-effects also occurred more frequently. Timing appeared to be an important determinant, with the best results when radiotherapy was given before or during systemic therapy. Improved tumor control and prolonged survival can be achieved by combining radiotherapy with immunotherapy or targeted therapy. However, more randomized controlled trials or prospective studies are warranted to generate proper evidence that can be used to change the standard of care for patients with MBM.     

Impact of brain tumour treatment on quality of life

Measurement of Health Related Quality of Life (HRQL) in brain tumour patients is important because brain tumours and brain tumour treatment usually affect physical, cognitive as well as emotional functioning. Measurement of HRQL is important for the understanding of disease burden and for the impact of specific tumour treatment. Quality of Life is a multidimensional concept consisting of physical, psychological and social phenomena. A large number of Quality of Life instruments have been developed. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the MOS Short-Form Health Survey are two frequently used general HRQL instruments. A specific brain tumour scale is the Brain Cancer Module, which is designed to be used in combination with general questionnaires. HRQL measurement and neuropsychological examination were used to investigate the impact of radiotherapy and surgery in low-grade glioma patients and the influence of tumour volume, tumour localization, performance status and age in both low-grade and high-grade glioma patients. Received: 10 April 2002 Accepted: 16 April 2002     

Is a "vanishing tumor" always a lymphoma?

The authors report clinical and radiologic characteristics and ultimate diagnosis in 12 patients with a regressing cerebral mass lesion. Primary CNS lymphoma (PCNL) was found in only half of the patients with such a lesion. In patients showing a complete resolution of the enhancing lesion the probability of finding a PCNL is smaller and survival is longer.     

The effect of 4-aminopyridine on clinical signs in multiple sclerosis: a randomized, placebo-controlled, double-blind, cross-over study.

To find out whether treatment with 4-aminopyridine is beneficial in multiple sclerosis (MS), 70 patients with definite MS entered into a randomized, double-blind, placebo-controlled, cross-over trial in which they were treated with 4-aminopyridine and placebo for 12 weeks each (maximum dose, 0.5 mg/kg of body weight). The estimated effect of the treatment as measured with the Kurtzke expanded disability status scale, which was the main evaluation parameter, was 0.28 point (p = 0.001). A significant decrease in the scale score (1.0 point or more) was encountered in 10 patients (16.4%) during oral treatment with 4-aminopyridine whereas it was not seen during placebo treatment (p less than 0.05). A significant subjective improvement (defined as an improvement that significantly affected the activities of normal daily life) was indicated by 18 patients (29.5%) during 4-aminopyridine treatment and by 1 patient (1.6%) during placebo treatment (p less than 0.05). Significant improvements related to 4-aminopyridine occurred in a number of neurophysiological parameters. No serious side effects were encountered. However, subjective side effects such as paresthesias, dizziness, and light-headedness were frequently reported during 4-aminopyridine treatment. Analysis of subgroups revealed that there was no difference in efficacy between those patients randomized to receive 4-aminopyridine and then placebo and those randomized to receive placebo and then 4-aminopyridine or between patients with and those without subjective side effects. Especially patients with temperature-sensitive symptoms and patients characterized by having a longer duration of the disease and being in a progressive phase of the disease were likely to show clear clinical benefit.     

Proton MRS imaging in the follow-up of patients with suspected low-grade gliomas

We compared the value of changes in proton magnetic resonance spectroscopic imaging (¹H-MRSI) with changes in clinical status and/or contrast-enhanced magnetic resonance imaging (MRI) in the monitoring of patients with suspected low-grade glioma (LGG). From June 1, 1999 till May 31, 2002, we included consecutive, neurologically intact adult patients suspected of having an LGG, demonstrating non-enhancing supratentorial lesions without edema or mass effect on MRI, and in whom all treatment (including a diagnostic biopsy) was deferred. Till January 1, 2003, patients were surveyed clinically and radiologically (contrast-enhanced MRI and ¹H-MRSI). Patients who showed progression on clinical examination and/or MRI were denoted as progressive disease. Other patients were denoted as stable disease. A decrease in NAA/CHO ratio of 20% compared to the baseline value was considered as indicative for progression on ¹H-MRSI. We included 14 patients with suspected LGG. Seven patients demonstrated progressive disease during the follow-up period, preceded or accompanied by concomitant ¹H-MRSI changes in five patients. Four of these five patients were operated on within the follow-up interval. The histological diagnosis demonstrated high-grade glioma in three and LGG in one patient. In the other two patients with progressive disease, no progression was found on ¹H-MRSI. The other seven patients demonstrated stable disease, but four of them showed progression on ¹H-MRSI. Our data do not show convincing evidence that ¹H-MRSI contributes to adequate monitoring and follow-up of patients with suspected LGG. Future research should preferably include pathological data at the time of ¹H-MRSI changes.     

Impaired cognitive functioning in low-grade glioma patients: relationship to tumor localisation, radiotherapy and the use of anticonvulsants

OBJECTIVE: To determine the effects of radiotherapy and other medical interventions on cognitive functioning in patients with a low-grade glioma (LGG). DESIGN: Cross-sectional study. METHOD: A total of 195 LGG patients, of whom 104 had received radiotherapy 1-22 years previously, were compared to 100 patients with a low-grade haematological malignancy and 195 healthy controls. The analysis was aimed at differentiating between the effects of the tumour (disease duration, lateralisation) and treatment effects (neurosurgery, radiotherapy, use of anticonvulsants) on cognitive function and the relative risk of cognitive disability. RESULTS: LGG patients had lower performance levels in all cognitive domains than haematological patients and performed even worse when they were compared to healthy controls. Radiotherapy was associated with poorer cognitive functioning; however, cognitive disability was found only in patients receiving fractional doses exceeding 2 Gy. The use of anticonvulsants was strongly associated with disorders in the area of attention and planning functions. CONCLUSION: In this study, the tumour itself was the most damaging factor with respect to cognitive function and radiotherapy was associated with cognitive disability only if elevated fractional doses were used. Epilepsy or the use of anticonvulsants was also associated with diminished cognitive functioning.     

Clinical evaluation of stereotactic brain biopsies with an MKM-mounted instrument holder

Summary ¶Object. The aim of this study was to assess the clinical usefulness and accuracy of robot-assisted frameless stereotactic brain biopsies with a recently introduced MKM-mounted instrument holder. Methods. Twenty-three patients with intracranial lesions participated in this study. Depending on the size of the intracranial lesion, fiducials for image-to-patient co-ordinate transformation consisted either of bone screws or adhesive markers. Shortly after surgery, postoperative MRI-imaging was performed to demonstrate the location of the biopsy site. These images were compared with the preoperative images to assess the biopsy localisation error. Results. Postoperative biopsy sites could be demonstrated in six patients with bone screws and in 14 with adhesive markers. These two subgroups yielded average biopsy localisation errors of 3.3mm (SD 1.7mm) and 4.5mm (SD 2.0mm) respectively. This difference was not statistically significant. One biopsy was located in a liquefied haematoma. All others yielded pathological tissue. There were two postoperative haemorrhages, of which only one was temporarily symptomatic. There was no mortality in the first 30 days after surgery. Conclusions. Robot-assisted frameless point-stereotactic techniques represent an alternative to frame-based techniques for the performance of stereotactic biopsies.Published online September 18, 2003