Sequencing of Chemotherapy and Radiotherapy for Newly Diagnosed Anaplastic Oligodendroglioma and Oligoastrocytoma.

INTRODUCTION: Adjuvant management of anaplastic oligodendrogliomas (AOs) and anaplastic oligoastrocytomas (AOAs) is guided by 2 seminal phase III trials, one of which utilized radiotherapy (RT) followed by chemotherapy (CT) (RT-CT), and the other in which CT was followed by RT (CT-RT). Both paradigms are endorsed by the National Comprehensive Cancer Network because no direct comparison in the first-line (nonprogressive) setting has been performed to date. This study of a contemporary national database sought to evaluate practice patterns and outcomes between both approaches. MATERIALS AND METHODS: The National Cancer Database (NCDB) was queried for newly diagnosed AO/AOA treated with postoperative sequential CT-RT or RT-CT. Multivariable logistic regression ascertained factors independently associated with delivery of a particular paradigm. Overall survival (OS) between cohorts was compared using Kaplan-Meier methodology. Univariate and multivariate Cox proportional hazards modeling evaluated factors associated with OS. RESULTS: Of 225 patients, 19 (8.4%) received CT-RT and 206 (91.6%) underwent RT-CT. Groups were well-balanced, although CT-RT was more often administered to men (P=0.009) and AOs (P=0.037). Median follow-up was 58 months. Median OS in the CT-RT cohort was 93 months (95% confidence interval, 37-150 mo), and 107 months (95% confidence interval, 72-142 mo) in the RT-CT group (P=0.709). Therapy sequence was not associated with OS on univariate (P=0.709) or multivariate (P=0.257) assessment. CONCLUSIONS: In the United States, most AO/AOA patients receiving sequential therapy undergo RT followed by CT. No differences in survival were observed with either approach; this addresses a knowledge gap and confirms that both paradigms are appropriate in the first-line setting.

[Usefulness of quantitative H-MR spectroscopy for the differentiation between radiation necrosis and recurrence of anaplastic oligodendroglioma].

We report a case, in which quantitative 1H-MR spectroscopy (MRS) was useful for the differentiation between radiation necrosis and a recurrent tumor. The present case is a 44-year-old man who underwent the subtotal removal of a mass lesion in the left frontal lobe. The histological diagnosis was anaplastic oligodendroglioma (WHO grade III). Postoperatively, a fractionated radiotherapy (total 64Gy) and chemotherapy were performed. MRI after the radiotherapy showed no contrast enhancing lesion. MRI, 5 years after the radiotherapy, showed a growing enhancing lesion and a T1 hypointensity lesion without enhancement, both of which indicated a recurrent tumor. MR spectroscopy was performed for the differential diagnosis of these lesions. The spectrum was acquired by the point resolved spectroscopy (PRESS) method by TR/TE=2,000 ms/68 ms, 136 ms, and 272 ms and evaluated with peak pattern and quantification value of metabolite. MRS of the enhancing lesion demonstrated a decrease of the Choline-containing compounds (Cho) concentration, disappearance of N-acetylaspartate (NAA), decrease of Creatine/ Phosphocreatine (t-Cr) and presence of Lipids (Lip) and Lactate (Lac), all of which are characteristic finding of a radiation necrosis. The histological diagnosis of this lesion showed evidence also of radiation necrosis. On the other hand, MRS of the T1 hypointensity lesion without enhancement showed, a marked high peak of the Cho concentration, which is characteristic for a recurrent tumor. The histological findings of this lesion showed a diffuse proliferation of recurrent tumor cells. Quantitative 1H-MRS is a useful tool for the differentiation between radiation necrosis and recurrent tumors.

[Application of (1)H MR spectroscopic imaging in radiation oncology: choline as a marker for determining the relative probability of tumor progression after radiation of glial brain tumors]. / Einsatz der (1)H-MR-spektroskopischen Bildgebung in der Strahlentherapie: Cholin als Marker für die Bestimmung der relativen Wahrscheinlichkeit eines Tumorprogresses nach Bestrahlung glialer Hirntumoren.

PURPOSE: To determine the relative signal intensity ratios of choline (Cho), phosphocreatine (CR) and N-acetyl-aspartate (NAA) in MR spectroscopic imaging (proton-MRSI) for differentiating progressive tumors (PT) from non-progressive tumors (nPT) in follow-up and treatment planning of gliomas. Threshold values to indicate the probability of a progressive tumor were also calculated. MATERIAL AND METHODS: Thirty-four patients with histologically proven gliomas showing a suspicious brain lesion in MRI after stereotactic radiotherapy were evaluated on a 1.5 Tesla unit (Magnetom Vision, Siemens, Erlangen, Germany) using 2D proton MRSI (repetition time/echo time = 1500/135 msec, PRESS; voxel size 9 x 9 x 15 mm (3)). A total of 274 spectra were analyzed (92 voxel were localized within the suspicious brain lesion). Relative signal intensities Cho, Cr and NAA were measured and their ability to discern between PT and nPT was assessed using the linear discrimination method, logistic regression, and the cross-validation method. PT and nPT were differentiated between on the basis of clinical course and follow-up by MRI, CT and positron emission tomography. RESULTS: The Cho parameter and the relative signal intensity ratios of Cr and NAA were most effective in differentiating between PT and nPT. The logistic regression method using the parameter ln(Cho/Cr) and ln(Cho/NAA) had the best predictive results in cross-validation. A sensitivity of 93.8 % and specificity of 85.7 % were achieved in the differentiation of PT from nPT by proton-MRSI. CONCLUSION: (1)H-MRSI has a high sensitivity and specificity for differentiating between therapy-related effects and the relapse of irradiated gliomas. This method allows for assessment of the probability of radiotherapy response or failure.

[Metabolic imaging for supratentorial oligodendrogliomas]. / Les oligodendrogliomes supra-tentoriels: imagerie métabolique.

Metabolic imaging with positron emission tomography (PET) provides, in neuro-oncology, information complementary to that provided by anatomic imaging obtained with CT-scanner or MRI. Only a few publications have yet reported its use in oligodendroglial tumors. These findings and partial results obtained in ongoing work, suggest some preliminary conclusions: 11C-MET (L-methyl-methionine) is a more appropriate tracer than 18F-FDG (fluoro-deoxy-glucose), in terms of both specificity and sensitivity, for the assessment of patients with this category of tumor. PET/MET allows differentiation between grade II and grade III oligodendrogliomas; better targeting for stereotactic biopsy; more accurate assessment of the post-operative residual tumor; identification of progression from low-grade to anaplastic grade during the disease course; differentiation between recurrence and a post-radiation processes. PET/MET allows, to some extent, prediction of response to radiotherapy; and, probably, to chemotherapy.

[Pediatric supratentorial oligodendrogliomas: Marseilles and Lyons experiences]. / Les oligodendrogliomes supratentoriels de l'enfant. A propos des séries arseillaises et lyonnaises.

BACKGROUND AND PURPOSE: The goal of this study was to analyze the main aspects of oligodendrogliomas observed in children. METHOD: The records of 35 children aged 15 years or younger (23 from Marseilles and 12 from Lyons) were reviewed. Clinical signs and symptoms, imaging findings (CT scan and pre- and post-operative MRI), extent of surgical resection, histology according to the WHO and Ste-Anne grading and survival were analysed. Considering all these factors, a statistical analyzis was undertaken in order to identify prognostic factors. DISCUSSION AND CONCLUSION: Oligodendrogliomas are rare tumors in children. The most important differential diagnosis to discuss is dysembryoplastic neuroepithelial tumor. Our study allowed us to distinguish several subgroups of patients with a different prognosis: thalamic tumors with a dismal prognosis versus hemispheric tumors. A group of cortical tumors we called "DNT-like" (hemispheric cortical tumor, isolated epilepsy, without neurological deficit and reased ICP, without edema and mass effect on MRI) with an excellent prognosis like the group with epilepsy. Histological grading (grade A/grade B and grade II/grade III) is also a prognostic factor.

Utilidad de las altas dosis de quimioterapia en tumores del SNC en niños / Usefulness of high-dose chemotherapy in children with CNS tumors

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Congenital oligodendroglioma with initial manifestation of jaundice.

Neonatal brain tumor is a rare clinical entity. The initial presentation in affected newborn infants is often subtle, nonspecific, and rarely includes focal neurologic signs. We report a 2-day-old male infant with congenital oligodendroglioma with initial manifestations of hyperbilirubinemia. Phototherapy was started immediately after admission. Because of a tense anterior fontanel and irritable crying, head ultrasonography, computed tomography, and magnetic resonance imaging were performed and revealed a heterogenous brain tumor in the left temporoparietal lobe. Craniotomy and tumor evacuation was performed, and WHO grade III anaplastic oligodendroglioma was confirmed by the pathologic studies. The patient was discharged 3 weeks later, and outpatient follow-up examination revealed a normally developed infant at 6 months of age. The cause of jaundice was thought to be secondary to tumor hemorrhage, which was not infrequent in neonatal brain tumor.

Magnetic source imaging of late evoked field responses to vowels: toward an assessment of hemispheric dominance for language.

OBJECT: The goal of this study was to determine whether the late neuromagnetic field elicited by simple speech sounds, which is detected by magnetoencephalography, may be used to estimate hemispheric dominance for language and to guide or constrain the intraoperative search for essential language sites. If sufficiently robust, a noninvasive method for assessing hemispheric dominance for language could reduce the necessity for amobarbital testing and the extent of intraoperative cortical stimulation-based mapping, both of which carry the risk of morbidity. METHODS: Fifteen patients undergoing surgery for tumors during which intraoperative language mapping would be performed and two additional patients in whom intracarotid amobarbital testing confirmed right-hemisphere language dominance participated. Following a primary auditory response sources of late neuromagnetic fields elicited by vowel stimuli were modeled and coregistered using magnetic resonance images to form magnetic source (MS) images. A laterality index (LI) was calculated by summing the number of equivalent current dipolar sources in the late fields detected from each hemisphere. In 14 right-handed patients, 10 displayed left asymmetric LIs (0.37 +/- 0.16. mean +/- standard error of the mean in 14 patients). For both right-hemisphere dominant patients in whom an LI was obtainable, the LI was rightward. Stimulation-mapped essential language sites were found in 7 of 15 patients. For six of these seven patients, the MS image-derived LI was leftward. CONCLUSIONS: Asymmetry in single equivalent dipole modeling of the late neuromagnetic field evoked by simple speech sounds correlates with hemispheric language dominance, although not to the degree necessary for individual clinical predictions. With further development, MS imaging of simple language tasks may be used preoperatively to predict language dominance and even to identify or constrain the intraoperative search for likely sites of essential language cortex.

Hemihyperaesthesia and hyperresponsiveness resembling central pain syndrome in a dog with a forebrain oligodendroglioma.

A 4-year-old male Boxer was presented with neurological signs referable to a right forebrain lesion that was confirmed with computed tomography. Whilst characteristic signs of a unilateral forebrain lesion were observed, the dominant and striking finding was a right-sided hemisensory disturbance characterised by hyperaesthesia and hyperresponsiveness. Necropsy revealed a gelatinous mass confined to the right forebrain that was identified histologically as an oligodendroglioma. The lesion was centred on the internal capsule and involved ventral frontal and temporal lobes and the ventrolateral thalamus, including lateral and medial parts of the ventrocaudal nuclear region (ventrobasilar complex) of the thalamus. On clinical and neuroanatomical grounds, the case exhibited features in common with central pain syndrome in human patients with thalamic lesions. These included a somatosensory disorder of hyperaesthesia affecting an entire side of the head and body, behavioural manifestations consistent with spontaneous pain and a lesion involving the ventrobasilar complex. Of interest, the hemisensory abnormality was ipsilateral to the lesion, contrasting with central pain in humans, in which clinical signs are contralateral to analogous lesions. It is suggested that species-specific differences in spinal cord organisation of pain pathways, particularly the greater bilateral projection of nociceptive afferents to thalamic relay nuclei in carnivores, may account for this disparity. Notably, central pain is rare in human patients with brain tumours, even those affecting the thalamus, and this may also be the case in dogs.

Patología molecular de los gliomas / Molecular biology of gliomas

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Combined 1H-MR imaging and localized 31P-spectroscopy of intracranial tumors in 43 patients.

Combined imaging and volume-selective spectroscopy of normal human brain tissue and tumors located anywhere in the brain could be obtained routinely in a clinical setting. Image-guided localized phosphorus MR spectra of healthy brain tissue have been reproducible, but further examinations seem necessary to determine individual physiologic variations. Compared with healthy brain tissue, spectra from meningiomas demonstrated the most obvious differences: the phosphocreatine peak decreased below the level of adenosine triphosphate, and the phosphodiester signal was reduced, whereas the phosphomonoester peak increased in some cases. Malignant gliomas showed less distinct changes: in particular, the phosphodiester peak was reduced and, in several cases, seemed to split. Often the phosphocreatine signal was diminished. In tumors with cystic components a poor signal-to-noise ratio was found. Four nonmalignant astrocytomas could not be differentiated from normal brain tissue spectroscopically. It has to be proved by an increased number of cases and quantification whether the observed spectral patterns can be correlated to histology. In three patients, follow-up studies during and after radiotherapy were performed. Metabolic changes were observed in one patient in a time frame in which imaging methods did not detect any change. Phosphorous spectroscopy has the potential to emerge as a useful tool in this field.