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Reducing Toxicity of Tumor Treatment

Tom Waddell and Michael Taylor

Tom Waddell and Michael Taylor with a November moustache for Cancer Research

Michael Taylor won the George Armstrong Peters Prize for 2011. His studies advance our understanding of cancer through genetic analysis of cancer transcriptomes. These are genetic markers derived from the genome of particular cancers that will allow prognostication at a level that has not been achieved using operative findings of the extent of disease, clinical or pathological staging or microscopic analysis.

In his Peters Prize Lecture at Surgical Grand Rounds, Michael described the microarray analysis of over 400 ependymomas of gene products, collected in Heidelberg and Toronto. Immunohistochemical analysis of gene products identified two classes of ependymomas that are otherwise indistinguishable. Tumours in group A had a far worse prognosis (Figure 1). Those in group B have a far better prognosis and tend to be easier to resect. They less frequently wrap around cranial nerves in the posterior fosae or invade vessels to the brain stem. It may be that eventually we will be able to spare the young developing residual brain from the debililating effects of postoperative radiation in patients with group B tumors.

Ependymoma Survival Curves

Fig. 1. Ependymoma Survival Curves

Medulloblastoma, the second major category of pediatric brain tumors, sort into four completely different groups, despite their histologic similarity. The sorting can be accomplished similarly with immunohistochemistry based on their genetic makeup (Figure 2). These genetic characteristics also show distinct differences between primary and metastatic tumours from the same patient or between primary and recurrent tumours. We are not yet at a point where the immunohistochemistry of the transcriptome can be used to guide surgery in the operating room, but the information can be used to determine whether adjuvant therapy is appropriate. Those with the WNT mutation have sufficiently favorable prognosis that a randomized trial will soon be undertaken in which the innovative arm will be the omission of postoperative radiation. This multi-centre program of de-escalation of toxic treatment will be financed by a grant from CIHR and support from the Garon Family Pediatric Cancer Centre at the Hospital for Sick Children. The Children’s Oncology Group in the United States is exploring retrospective validation of the prognostic groups based on their immunohistochemistry. This will allow future therapeutic trials using these genetic markers to stratify treatment.

Medulloblastoma Curves

Fig. 2. Medulloblastoma

Michael’s wife of 16 years, Susan, is a technical writer who edits his grants with a detectable level of impact on his excellent record of funding. His children are Alexandra, 12, Robert 9 and Andrew, 5. On the night before his Peters Prize presentation he was up working with Robert on a challenging math homework assignment. He is currently reading Michael Shermer’s “The Believing Brain”. His principal mentors have been Jim Rutka and Richard Gilbertson at the St. Jude Hospital in Memphis, Tennessee.


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