Object. The majority of intramedullary spinal cord tumors (IMSCT) in children and young adults are low-grade gliomas. Radical resection of similar tumors in the cerebral hemisphere or cerebellum is usually curative; however, the conventional management for IMSCTs remains partial resection followed by radiotherapy because of the concern for surgical morbidity. Nevertheless, radical resection of IMSCTs without routine adjuvant treatment has been the rule at our institution since 1980. In an attempt to resolve this controversy, the long-term morbidity and survival in a large series of children have been retrospectively reviewed. Methods. The database records and current status of 164 patients 21 years of age and younger in whom an IMSCT was resected were reviewed. A gross-total resection (> 95%) was achieved in 76.8% of the surgical procedures. Subtotal resections (80–95%) were performed in 20.1%. The majority of patients (79.3%) had histologically low-grade lesions. There were no deaths due to surgery. When...

Radical excision of intramedullary spinal cord tumors: surgical morbidity and long-term follow-up evaluation in 164 children and young adults

PURPOSE: The aim of this study was to avoid radiotherapy and to induce an objective response in children with low-grade glioma (LGG) using a simple chemotherapy regimen based on cisplatin and etoposide. PATIENTS AND METHODS: Thirty-four children (median age, 45 months) with unresectable LGG were treated with 10 monthly cycles of cisplatin (30 mg/m2/d on days 1 to 3) and etoposide (150 mg/m2/d on days 1 to 3). Tumor originated in the visual pathway in 29 patients, in the temporal lobe in two, in the frontal lobe in two, and in the spine in one. Eight children were affected by neurofibromatosis type 1. Objective tumor response and toxicity were evaluated by magnetic resonance imaging and neurologic and functional tests at 3-month intervals. RESULTS: An objective response was obtained in 24 (70%) of 34 patients, whereas the others had stable disease. None of the children were electively irradiated. In 31 previously untreated children, overall survival was 100% and progression-free survival was 78% at 3 years...

High Response Rate to Cisplatin/Etoposide Regimen in Childhood Low-Grade Glioma

Object With the introduction of electrophysiological spinal cord monitoring, surgeons have been able to perform radical resection of intramedullary spinal cord tumors (IMSCTs). However, factors associated with tumor resectability, tumor recurrence, and long-term neurological outcome are poorly understood. Methods The authors retrospectively reviewed 101 consecutive cases of IMSCT resection in adults and children at a single institution. Neurological function and MR images were evaluated preoperatively, at discharge, 1 month after surgery, and every 6 months thereafter. Factors associated with gross-total resection (GTR), progression-free survival (PFS), and long-term neurological improvement were assessed using multivariate regression analysis. Results The mean age of the patients was 41 ± 18 years and 17 (17%) of the patients were pediatric. Pathological type included ependymoma in 51 cases, hemangioblastoma in 15, pilocytic astrocytoma in 16, WHO Grade II astrocytoma in 10, and malignant astrocytoma in ...

Factors associated with progression-free survival and long-term neurological outcome after resection of intramedullary spinal cord tumors: analysis of 101 consecutive cases: Clinical article

Object Most intrinsic infiltrative brainstem lesions diagnosed in children are gliomas, and these carry a very bad prognosis. Although the utility and risk of stereotactically guided biopsy procedures in intrinsic infiltrative brainstem lesions have been widely questioned, the neuroimaging diagnosis may be inaccurate in approximately 25% of cases, and the consequences of empirical therapy should not be underestimated. Stereotactic biopsy sampling is still performed in many centers, but the reported diagnostic yield ranges from 83 to 96%. The authors integrated positron emission tomography (PET) images into the planning for stereotactic biopsy procedures to direct the biopsy needle's trajectory to hypermetabolic foci of intrinsic infiltrative brainstem lesions. Their aim was to assess the benefit of the technique in terms of target selection and diagnostic yield. Methods Twenty children with newly diagnosed intrinsic infiltrative brainstem lesions underwent a PET-guided stereotactic biopsy procedure. The P...

Results of positron emission tomography guidance and reassessment of the utility of and indications for stereotactic biopsy in children with infiltrative brainstem tumors

Human gliomas, especially of low-grade type, have been shown to express high-affinity somatostatin receptor type 2 (J-C. Reubi et al., Am. J. Pathol, 134: 337-344, 1989). We enrolled seven low-grade and four anaplastic glioma patients in a pilot study using the diffusible peptidic vector 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) for receptor targeting. The radiopharmakon was locoregionally injected into a stereotactically inserted Port-a-cath. DOTATOC competes specifically with somatostatin binding to somatostatin receptor type 2 in the low nanomolar range as shown by a displacement curve of 125I-[Tyr3]-octreotide in tumor tissue sections. Diagnostic (111)In-labeled DOTATOC-scintigraphy following local injection displayed homogeneous to nodular intratumoral vector distribution. The cumulative activity of regionally injected peptide-bound 90Y amounted to 370-3300 MBq, which is equivalent to an effective dose range between 60 +/- 15 and 550 +/- 110 Gy. Activity was injected in one to four fractions according to tumor volumes; 1110 MBq of 90Y-labeled DOTATOC was the maximum activity per single injection. We obtained six disease stabilizations and shrinking of a cystic low-grade astrocytoma component. The only toxicity observed was secondary perifocal edema. The activity:dose ratio (MBq:Gy) represents a measure for the stability of peptide retention in receptor-positive tissue and might predict the clinical course. We conclude that SR-positive human gliomas, especially of low-grade type, can be successfully targeted by intratumoral injection of the metabolically stable small regulatory peptide DOTATOC.

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Locoregional regulatory peptide receptor targeting with the diffusible somatostatin analogue 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC): a pilot study in human gliomas.

Object. The authors conducted a retrospective review to examine and document the frequency, degree, and timing of the radiologically confirmed response to radiotherapy of low-grade gliomas in children. Methods. Between 1963 and 1995, 80 patients 17 years of age or younger were referred to the London Regional Cancer Centre in London, Ontario after diagnosis of a low-grade glioma. All patients underwent surgical resection or biopsy procedures and 47 underwent radiotherapy (40 postoperatively and seven at the time of tumor progression). Nineteen patients with residual measurable lesions who received radiation therapy were selected for volumetric analysis of tumor response to this treatment. The extent and timing of response to radiation were determined by the process of comparing postoperative, preirradiation computerized tomography (CT) scans with postirradiation, follow-up CT scans. For one patient the comparison was made by using serial magnetic resonance images. Residual tumor was found on postoperative CT scans in all cases. The mean preradiotherapy tumor volume was 17.1 cm 3 , and the postradiotherapy volume was reduced to a mean of 11.5 cm 3 . A reduction in tumor volume was demonstrated in eight patients by the time of their first postirradiation follow-up CT scan and in two patients a slower reduction in volume over time was shown, bringing the total number of responders to 10. In five of these 10 patients the tumor had shown a maximum response by the time of the first postirradiation CT scan; the median time to response was 3.3 months. A 25% or greater reduction in tumor volume was seen in eight (42%) of the 19 patients. A 50% or greater reduction was noted in five (26%) of the patients. A complete response was demonstrated at 7, 12, and 15 months, and 5 years, respectively, in four patients (21%). One responder's tumor eventually increased in size after radiotherapy and he died of his disease. The magnitude of the radiographically demonstrated response to radiation did not correlate significantly with clinical outcome (that is, survival or symptom improvement). Conclusions. On the basis of this CT scan analysis of the response of low-grade gliomas in children to radiotherapy, the authors suggest that these lesions respond to radiation, as demonstrated by tumor shrinkage on serial imaging. Major or complete responses occur occasionally. However, low-grade gliomas in children mimic other benign brain tumors such as pituitary adenomas and meningiomas in that, although growth is frequently arrested after radiotherapy, residual tumor can persist for many years, illustrating that tumor shrinkage may not be a good measure of treatment efficacy. Nevertheless, radiation therapy can result in improvement of clinical symptomatology in association with or independent of visible tumor reduction. As radiation treatment techniques become increasingly conformal and because studies indicate that lower doses of radiation may be equally effective, improvement of symptoms may be an important consideration when weighing treatment options, particularly in patients with residual or unresectable disease.

Leighton Ce

Papers

Low-grade gliomas in children: tumor volume response to radiation