To Biopsy or Not to Biopsy- How Did We Get Here?
Dr Foreman gave the dismal background on DIPG treatments. The only treatment known to help prolong life in these children is radiation; however, attempts to intensify radiation treatments have not improved outcome. In addition, chemotherapy has been tried both before and after radiation without success. In fact, the UKCCSG stated, “This approach should be abandoned as toxic and without benefit and with toxicity.” Even high dose chemotherapy with autologous bone marrow rescue has failed.
Given the terrible track record and significant lack of specific tumor biology knowledge, why do we not biopsy these tumors?
The most influential paper that changed the standard method of diagnosing diffuse intrinsic pontine gliomas from biopsy to MRI was published by Albright in 1993 [1]. This paper reviewed the results of a brainstem trial (CCG-9882). In this paper the authors recommended that biopsies not be done because they added nothing to the diagnostic precision of MRI. Dr Foreman noted complication rates were not included as part of the justification for this position, and there was actually no surgical mortality in this study.
In a commentary on the Albright paper, Dr Fred Epstein (a pioneer in the field of pediatric neurosurgery – especially in the brainstem) stated, “Routine biopsy should be relegated to neurosurgical history.”
This is where we are today. As opposed to adults where biopsy of diffuse brainstem masses is common as there is are a greater variety of etiologies, biopsy of pediatric DIPGs is currently only recommended for atypical cases. Yet more and more, authors are publishing such comments as, “Given the lack of efficacy of conventional drugs, a better understanding of the biology of this tumor is the key to more targeted therapy.” [2]
In an attempt to address whether science has progressed sufficiently to warrant a change in philosophy toward DIPG biopsy, the committee debated the following scientific question:
“Based on your discussion, has the state of the science in drug targeting research progressed to where there is a reasonable expectation of success in identifying drug candidates to move into early phase clinical trials for DIPG?”
The vote was 16 yes, 7 no and 1 abstention. (The reason given for this abstention was inadequate knowledge of this subject.)
Reference-
1. Magnetic resonance scans should replace biopsies for the diagnosis of diffuse brain stem gliomas: a report from the Children's Cancer Group.
Neurosurgery. 1993 Dec;33(6):1026-9; discussion 1029-30
2. Brainstem gliomas in children and adults.
Curr Opin Oncol. 2008 Nov;20(6):662-7
3. April 27th, 2009 FDA joint PAC/ODAC public meeting on DIPG Biopsy-Slides
