Arlynn F. Mulne

Study of the MIB-1 Labeling Index as a Predictor of Tumor Progression in Pilocytic Astrocytomas in Children and Adolescents

PURPOSE The pilocytic astrocytoma (PA) is the most common childhood brain tumor. This report examines the MIB-1 labeling index (LI) as a predictor of progression-free survival (PFS) among childhood PAs. PATIENTS AND METHODS Consecutive PAs were examined to determine whether the MIB-1 LI was associated with tumor progression. Other variables evaluated included tumor location, use of adjuvant therapy, extent of resection, and age at diagnosis. RESULTS One hundred forty-one children were identified (mean +/- SD age, 7.6 +/- 4.7 years; range, 0.43 to 18.56 years); 118 children had adequate tissue for MIB-1 immunohistochemistry. The 5-year PFS was 61.25%. By log-rank analysis, an MIB-1 LI of more than 2.0 was associated with shortened PFS (P =.035). Patients with PAs who underwent complete surgical resection, had tumors located in the cerebellum, and were treated with surgery only also had more prolonged PFS (P =.001 for all). Tumors in the optic pathways were associated with a shorter PFS (P =.001). Restricting the evaluation of MIB-1 LI to only incompletely resected tumors revealed an insignificant trend of MIB-1 LI of more than 2.0 having a shortened PFS. Multivariate analysis demonstrated completely resected tumors and tumors located in the cerebellum as less likely to progress (P =.001 and.019, respectively). CONCLUSION Children with PAs with an MIB-1 LI of more than 2.0 have a shortened PFS. PAs that are completely resected and are located in the cerebellum have a prolonged PFS. This initial study suggests that the MIB-1 LI identifies a more aggressive subset of PAs. Further work should focus on elucidating features of pilocytic astocytomas that will identify prospectively children at risk for progression.

Preradiation chemotherapy in advanced medulloblastoma a pediatric oncology group pilot study

Background. Children diagnosed with medulloblastoma whose tumor involves the brain stem or has spread through the cerebrospinal fluid pathways to other areas of the brain or spinal cord have a poor prognosis despite therapy with surgery, craniospinal irradiation (CSI), and chemotherapy. Preradiation chemotherapy may improve the outlook for these patients.

Robotically guided radiosurgery for children

A robotically guided linear accelerator has recently been developed which provides frameless radiosurgery with high precision. Potential advantages for the pediatric population include the avoidance of the cognitive decline associated with whole brain radiotherapy, the ability to treat young children with thin skulls unsuitable for frame‐based methods, and the possible avoidance of general anesthesia. We report our experience with this system (the “Cyberknife”) in the treatment of 21 children.

Oral methotrexate for recurrent brain tumors in children: a Pediatric Oncology Group study.

PURPOSE Children with recurrent or progressive central nervous system (CNS) tumors have an unfavorable prognosis. Based on Pediatric Oncology Group (POG) institutional pilot data, low-dose oral methotrexate (MTX) was studied. METHODS Eight dosages of MTX 7.5 mg/m2 every 6 hours were administered on a weekly schedule for as long as 18 months. Patients in six different brain tumor strata were accrued. RESULTS The response rates (complete or partial responses) were as follows: astrocytoma 2 of 10, malignant glioma 1 of 19, medulloblastoma 0 of 18, brainstem tumor 0 of 12, ependymoma 1 of 7, and miscellaneous histologic types 0 of 12. The main toxicities, mucositis, myelosuppression, and hepatic transaminase elevation were considered tolerable. CONCLUSION Low-dose oral MTX showed no significant activity against malignant glioma, medulloblastoma, brainstem tumors, and miscellaneous histologic types. Indeterminate but low response rates were observed in children with astrocytoma and ependymoma. This regimen will not be recommended for front-line therapy.

Prognostic factors in children and adolescents with low-grade oligodendrogliomas.

Few reports exist describing the progression-free and overall survival of children with low-grade (WHO grade II) oligodendrogliomas treated uniformly with aggressive surgery but without adjuvant chemotherapy or radiation therapy. Furthermore, significant prognostic features, including the MIB-1 labeling index (LI), have not been reported for children with oligodendrogliomas. The medical records of 20 consecutive patients with low-grade oligodendrogliomas were reviewed. All patients had been treated with aggressive surgical resection. Adjuvant chemotherapy and radiation therapy were reserved for radiographic or clinical progression. These patients have been followed for a median of 5.5 years (range 0.5–11.5 years) after diagnosis. To date, there have been no patient deaths. Six of the 20 patients experienced tumor progression at a median of 2.2 years (range 0.4–4.8 years) following the initial surgery. The MIB-1 LI was infrequently greater than 5. Of several prognostic factors for subsequent tumor progression that were examined, only tumors located within the parietal lobes were associated with a worse progression-free survival. Other risk factors, including presenting symptoms, age at diagnosis, MIB-1 LI and the extent of tumor resection, were not associated with an increased frequency of tumor progression.