Effects of Medulloblastoma Resections on Outcome in Children: A Report from the Children's Cancer Group

Abstract

We reviewed the data of children with high-stage primitive neuroectodermal tumors (medulloblastomas) who were treated on Children's Cancer Group-921 protocol to evaluate the correlation between tumor resection and prognosis. Patients enrolled in the study had either tumors that were operatively categorized to be Chang tumor stage 3b or 4, postoperative residual tumors > 1.5 cm2, or evidence of tumor dissemination (Chang metastasis Stages [M Stages] 1-4) at diagnosis. Resections were analyzed in two ways, as follows: 1) by the extent of resection (percent of the tumor that was removed), as estimated by the treating neurosurgeon; and 2) by the extent of residual tumor (how much of the tumor was left), as estimated from postoperative scans. Two hundred and three children were enrolled in the study with institutional diagnoses of primitive neuroectodermal tumors-medulloblastomas; diagnoses were confirmed by central neuropathological review in 188 patients. Progression-free survival (PFS) at 5 years was 54% (standard error, 5%). As in previous Children's Cancer Group studies, age and M stage correlated with survival; PFS was significantly lower in children 1.5 to 3.0 years old at diagnosis and in those with any evidence of tumor dissemination (M Stage 1-4). On univariate analysis, neither extent of resection nor extent of residual tumor correlated with PFS. However, adjusting for other factors, extent of residual tumor was important; PFS was 20% (standard error, 14%) better at 5 years in children with no dissemination (M Stage 0) who had< 1.5 cm2 of residual tumor (P = 0.065) and was 24% (standard error, 14%) better at 5 years in children > 3 years old with no tumor dissemination (M Stage 0) and with < 1.5 cm2 residual tumor (P = 0.033). On the basis of our observations, we conclude that extent of tumor resection, as estimated by the neurosurgeon, does not correlate with outcome but that extent of residual tumor does correlate with prognosis in certain children (those who are > 3 years old, with no tumor dissemination). In contrast to age and M stage, the major factors associated with outcome, residual tumor is an important variable in outcome, one that neurosurgeons can control.

Pediatric Brain Tumors: Current Treatment Strategies and Future Therapeutic Approaches

“…Studies have shown that patients with less then 1.5 cm 2 residual disease had improved survival. [5][6][7] Some patients might require a ventricular shunt or third ventriculostomy prior to resection of the tumor. The majority of patients will have resolution of the hydrocephalus after tumor resection, but approximately 40% will require permanent shunt placement.…”

Accurate classification of childhood brain tumours by in vivo 1H MRS – A multi-centre study

“…However, the importance of a complete resection varies between the tumour types. A complete macroscopic resection is highly prognostic for ependymomas [1,2], whereas small amounts of residual medulloblastoma (up to 1.5cm 2 ) are not of prognostic significance if treated with radiotherapy and chemotherapy [3] and small residual masses of pilocytic astrocytoma may be observed without further treatment [4]. Histopathology is usually not available for several days after the operation and intraoperative histopathology is commonly used to inform the surgeons of the likely tumour type but the techniques available are not accurate [5] and this strategy does not allow patient-specific clinical management planning prior to surgery.…”

Accumulation of genomic aberrations during clinical progression of medulloblastoma

“…However, the predictive performance of current risk stratiWcation, which is entirely based on clinical variables, needs to be improved because of the dismal prognosis of children with tumor relapse, and because of relevant treatment-induced long-term eVects of survivors [21]. Clinical staging systems based on age, metastatic stage at diagnosis and, in some studies, extent of surgical resection have so far been the most useful methods for the stratiWcation of patients into standard and high risk therapy groups [1,26,27]. Additionally, after reWnement of the histological classiWcation of MB in the 2007 WHO classiWcation, the histological subtype is of potential prognostic relevance: large cell/anaplastic MB behaves more aggressively, while nodular/ desmoplastic variants show a more favorable clinical course as compared to the large group of classic MB [3,5,7,10,13,14,17].…”