Medulloblastoma: tumorigenesis, current clinical paradigm, and efforts to improve risk stratification

@article{Polkinghorn2007MedulloblastomaTC,
  title={Medulloblastoma: tumorigenesis, current clinical paradigm, and efforts to improve risk stratification},
  author={William R. Polkinghorn and Nancy J. Tarbell},
  journal={Nature Clinical Practice Oncology},
  year={2007},
  volume={4},
  pages={295-304}
}
Medulloblastoma is the most common brain malignancy in children and tremendous advances have recently been made in understanding the pathogenesis of this tumor. The Hedgehog and Wingless signaling pathways are implicated in medulloblastoma development, and both pathways were discovered as a result of analyses of genetic syndromes associated with the tumor. Over the past 80 years, considerable progress has been made in the treatment of what was once a fatal disease. The first survival reports… 

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References

SHOWING 1-10 OF 100 REFERENCES

Anaplasia and Grading in Medulloblastomas

TLDR
It is believed anaplastic change represents a type of malignant progression common to many medulloblastoma subtypes and to other CNS embryonal lesions as well, and correlation of these histological changes with the accumulation of genetic events suggests a model for the histological and molecular progression of medullOBlastoma.

Atypical teratoid/rhabdoid tumor: the controversy behind radiation therapy

TLDR
A review of the literature reveals an association between initial radiation therapy and the ability to achieve a prolonged survival and underscores the importance or enrolling patients in multi-institutional prospective studies to further investigate the value of radiation to treat this pediatric neoplasm.

Molecular Insight into Medulloblastoma and Central Nervous System Primitive Neuroectodermal Tumor Biology from Hereditary Syndromes: A Review

TLDR
The published literature describing hereditary syndromes that have been associated with an increased incidence of medulloblastoma and/or central nervous system primitive neuroectodermal tumor is reviewed.

Current treatment approaches to early childhood medulloblastoma

TLDR
Future studies will clarify the prognostic relevance of desmoplasia, postoperative residual tumor and biological markers to improve stratification criteria by risk-adapted treatment recommendations.

Medulloblastoma: Present Concepts of Stratification into Risk Groups

TLDR
Staging studies have been used to stratify children with medulloblastoma into risk groups, but age at diagnosis and amount of residual disease after surgery or extent of resection have also been commonly incorporated into stratification schemata.

Clinical and molecular stratification of disease risk in medulloblastoma

TLDR
The hypothesis that a combination of clinical and molecular factors may afford a more reliable means of assigning disease risk in patients with medulloblastoma is supported, thereby providing a more accurate basis for targeting therapy in children with this disease.

Medulloblastomas With Systemic Metastases: Evaluation of Tumor Histopathology and Clinical Behavior in 23 Patients

TLDR
Metastasis of medulloblastomas outside the CNS can occur after long periods of clinical remission and is associated with anaplasia in some cases, consistent with tumor progression.

Histopathologic grading of medulloblastomas

TLDR
The authors evaluated the clinical effects of increasing anaplasia and nodularity in a large group of children with medulloblastomas, hypothesizing that increasing nodularity would predict better clinical outcomes and that increasing anaPlasia would presage less favorable results.

Staging, scoring and grading of medulloblastoma

TLDR
It is concluded that this new staging, scoring and grading system is a simple and recommendable prognostic system for all patients treated surgically for medulloblastoma.

The treatment and prognosis of medulloblastoma in children. A study of 82 verified cases.

TLDR
The survival rate is greater for patients in whom a "complete" surgical excision of the tumor was performed, compared with lesser procedures, and in some cases with brain-stem involvement radiotherapy can cure or control locally advanced disease for an appreciable time.
...