SMART syndrome: a late reversible complication after radiation therapy for brain tumours

With intensified treatment leading to longer survival, complications of therapy for brain tumours are more frequently observed. Regarding radiation therapy, progressive and irreversible white matter disease with cognitive decline is most feared. We report on four patients with reversible clinical and radiological features occurring years after radiation for brain tumours, suggestive for the so called SMART syndrome (stroke-like migraine attacks after radiation therapy). All four patients (males, age 36–60 years) had been treated with focal brain radiation for a primary brain tumour or with whole-brain radiation therapy for brain metastases. Ranging from 2 to 10 years following radiation therapy patients presented with headache and focal neurological deficits, suggestive for tumour recurrence. Two patients also presented with focal seizures. MRI demonstrated typical cortical swelling and contrast enhancement, primarily in the parieto-occipital region. On follow-up both clinical and MRI features improved spontaneously. Three patients eventually proved to have tumour recurrence. The clinical and radiological picture of these patients is compatible with the SMART syndrome, a rare complication of radiation therapy which is probably under recognized in brain tumour patients. The pathophysiology of the SMART syndrome is poorly understood but bears similarities with the posterior reversible encephalopathy syndrome (PRES). These four cases underline that the SMART syndrome should be considered in patients formerly treated with radiation therapy for brain tumours, who present with new neurologic deficits. Before the diagnosis of SMART syndrome can be established other causes, such as local tumour recurrence, leptomeningeal disease or ischemic disease should be ruled out.     

Review on Quality of Life Issues in Patients with Primary Brain Tumors

Health‐related quality of life (HRQOL) has become an important outcome measure in clinical trials in primary brain tumor (i.e., glioma) patients, because they have an incurable disease. HRQOL is assessed using self‐reported, validated questionnaires, addressing physical, psychological, emotional, and social issues. In addition to generic HRQOL instruments, disease‐specific questionnaires have been developed, including for brain tumor patients. For the analysis and interpretation of HRQOL measurements, low compliance and missing data are methodological challenges. HRQOL in glioma patients may be negatively affected by the disease itself as well as by side effects of treatment. But treatment with surgery, radiotherapy, and chemotherapy may improve patient functioning and HRQOL, in addition to extending survival. Although HRQOL has prognostic significance in brain tumor patients, it is not superior to well‐known clinical parameters, such as age and performance status. In clinical practice, assessing HRQOL may be helpful in the communication between doctor and patient and may facilitate treatment decisions.     

EORTC topics in neurooncology: The long path from a focus on neurological complications of cancer towards molecularly defined trials and therapies in neurooncology

Over the past decade a series of trials of the EORTC Brain Tumor Group (BTG) has substantially influenced and shaped the standard-of-care of primary brain tumors. All these trials were coupled with biological research that has allowed for better understanding of the biology of these tumors. In glioblastoma, EORTC trial 26981/22981 conducted jointly with the National Cancer Institute of Canada Clinical Trials Group showed superiority of concomitant radiochemotherapy with temozolomide over radiotherapy alone. It also identified the first predictive marker for benefit from alkylating agent chemotherapy in glioblastoma, the methylation of the O6-methyl-guanyl-methly-transferase (MGMT) gene promoter. In another large randomized trial, EORTC 26951, adjuvant chemotherapy in anaplastic oligodendroglial tumors was investigated. Despite an improvement in progression-free survival this did not translate into a survival benefit. The third example of a landmark trial is the EORTC 22845 trial. This trial led by the EORTC Radiation Oncology Group forms the basis for an expectative approach to patients with low-grade glioma, as early radiotherapy indeed prolongs time to tumor progression but with no benefit in overall survival. This trial is the key reference in deciding at what time in their disease adult patients with low-grade glioma should be irradiated.Future initiatives will continue to focus on the conduct of controlled trials, rational academic drug development as well as systematic evaluation of tumor tissue including biomarker development for personalized therapy. Important lessons learned in neurooncology are to dare to ask real questions rather than merely rapidly testing new compounds, and the value of well designed trials, including the presence of controls, central pathology review, strict radiology protocols and biobanking. Structurally, the EORTC BTG has evolved into a multidisciplinary group with strong transatlantic alliances. It has contributed to the maturation of neurooncology within the oncological sciences.     

Assessment of quality of life in patients treated for low-grade glioma: a preliminary report.

In this pilot study quality of life was assessed in fourteen adult patients who were treated for a low-grade glioma with surgery and radiotherapy at least one year previously. Apart from widely used parameters, such as the neurological and functional status, the patients' cognitive functioning and actual affective status were determined. In addition the patients were interviewed to evaluate various aspects of quality of life. Generally no serious focal neurological deficits were found, although psychological examination showed serious cognitive and affective disturbances in most cases. Self report measures concerning cognitive functioning were not in all cases in accordance with objective test results. When the results of treatment in glioma patients are evaluated assessment of quality of life, including neuropsychological functioning, should be performed, especially as new therapeutic strategies are being developed.     

Cognitive functions and quality of life in patients with low-grade gliomas: The impact of radiotherapy

The role of early radiotherapy in the treatment of low-grade gliomas is controversial. For this reason the impact of radiotherapy on quality of life was studied in long-term survivors of biopsy-proved low-grade gliomas without signs of tumor recurrence. Twenty patients (age range, 18–66 years) had been treated with early radiotherapy; the other 21 patients (age range, 19–65 years) had undergone surgery or biopsy only. The interval from diagnosis to testing ranged from 1 to 12 years (mean, 3.5 years). Nineteen patients with low-grade hematological malignancies, surviving 1 to 15 years without central nervous system involvement, served as control subjects. Apart from the neurological and functional status, the patients' cognitive, affective, and psychological status was determined. None of the survivors had significant neurological impairment and the Karnofsky index for them was at least 70. However, more specific examinations of cognitive functions and the affective status (Profile of Mood States) indicated that, compared to the control subjects, the patients with low-grade gliomas had significantly more cognitive disturbances and suffered more frequently from fatigue and depressed moods. The two groups with low-grade gliomas, on the other hand, did not differ significantly on any of these measures. It is concluded that radiotherapy did not cause these disturbances and had no negative impact on quality of life in these patients.     

Pseudo-progression after stereotactic radiotherapy of brain metastases: lesion analysis using MRI cine-loops

Stereotactic radiotherapy (SRT) of brain metastasis can lead to lesion growth caused by radiation toxicity. The pathophysiology of this so-called pseudo-progression is poorly understood. The purpose of this study was to evaluate the use of MRI cine-loops for describing the consecutive events in this radiation induced lesion growth. Ten patients were selected from our department’s database that had received SRT of brain metastases and had lesion growth caused by pseudo-progression as well as at least five follow-up MRI scans. Pre- and post SRT MRI scans were co-registered and cine-loops were made using post-gadolinium 3D T1 axial slices. The ten cine loops were discussed in a joint meeting of the authors. The use of cine-loops was superior to evaluation of separate MRI scans for interpretation of events after SRT. There was a typical lesion evolution pattern in all patients with varying time course. Initially regression of the metastases was observed, followed by an enlarging area of new contrast enhancement in the surrounding brain tissue. Analysis of consecutive MRI’s using cine-loops may improve understanding of pseudo-progression. It probably represents a radiation effect in brain tissue surrounding the irradiated metastasis and not enlargement of the metastasis itself.