Medulloblastoma, the most commonly occurring malignant brain tumor in children, can be classified into four subgroups--each with a different risk profile requiring subgroup-specific therapy. Currently, subgroup determination is done after surgical removal of the tumor. Investigators at Children's Hospital Los Angeles have now discovered that these subgroups can be determined non-invasively, using magnetic resonance spectroscopy (MRS). The paper will be published online by the journal Neuro-Oncology (Oxford Press) on August 7.
"By identification of the tumor subgroup at the time of diagnosis, we will be able to begin specific therapy earlier," said Shahab Asgharzadeh, MD, of The Saban Research Institute of Children's Hospital Los Angeles, principal investigator on the study. Asgharzadeh is also an associate professor of Pediatrics and Pathology at the Keck School of Medicine of the University of Southern California (USC).
Treatment for medulloblastoma includes surgery, chemotherapy and radiation, with 5-year survival rates ranging from 30 to 90 percent depending upon risk profile. A recent discovery identified four subtypes of medulloblastoma (SHH, WNT, Group 3 and Group 4) with level of risk and clinical outcomes for each subtype varying significantly. Currently, classification requires surgical removal of the tumor followed by laboratory analysis of the tumor tissue. Given the clinical importance of subgroup determinations, a fast, reliable and easily accessible method could have a significant effect on the outcomes of children with this disease.
"MR spectroscopy is widely available, noninvasive and provides information on cellular metabolism, which is different in healthy and diseased tissue," said Stefan Bluml, PhD, investigator at The Saban Research Institute of CHLA and first author of the study. Bluml is also an associate professor of Research, Radiology and Biomedical Engineering at the Viterbi School of Engineering at USC.
Using frozen tumor tissue from 30 patients diagnosed with medulloblastoma, investigators performed subgroup analysis using standard techniques. These patients also had MRS performed at the time of diagnosis. With a screening panel composed of five metabolites, investigators found that the spectra for subgroups revealed distinct metabolic features, allowing them to differentiate subgroups SHH, WNT from Groups 3 and 4.
Clinical trials are being developed to incorporate molecular subgroups into risk and treatment stratifications. The ease of obtaining MRS at the time of diagnosis should allow its incorporation into future clinical trials aimed at validating this technique to improve diagnostic classification and, ultimately, improve outcomes in children with medulloblastoma.
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Additional contributors include co-first author Ashley S. Margol, Richard Sposto, Rebekah J. Kennedy, Nathan J. Robison, Marzieh Vali, Long T. Hung, Sakunthala Muthugounder, Anat Erdreich-Epstain, Floyd H. Gilles, Alexander R. Judkins, Mark D. Krieger, Girish Dhall and Marvin D. Nelson, of Children's Hospital Los Angeles and the Keck School of Medicine of USC; and Jonathan L. Finlay, Nationwide Children's Hospital, Columbus, OH. Funding was provided in part by the National Institutes of Health (grant CA009659-18), the American Cancer Society, Alex's Lemonade Stand Foundation and the Rudi Schulte Research Institute.
About Children's Hospital Los Angeles
Children's Hospital Los Angeles has been named the best children's hospital in California and among the top 10 in the nation for clinical excellence with its selection to the prestigious U.S. News & World Report Honor Roll. Children's Hospital is home to The Saban Research Institute, one of the largest and most productive pediatric research facilities in the United States. Children's Hospital is also one of America's premier teaching hospitals through its affiliation since 1932 with the Keck School of Medicine of the University of Southern California. For more information, visit CHLA.org. Follow us on Twitter, Facebook, YouTube and LinkedIn, or visit our blog at http://researchlablog.org/.
Journal
Neuro-Oncology