2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

CHILDREN WITH DIFFUSE INTRINSIC PONTINE GLIOMA
outraged by this and considered this a paternalistic void of
their rights.
Third, That All Alternatives to Performing Biopsies on
Children Should Be Considered
Basically what was being asked was whether there some
way of advancing knowledge and therapy without performing
biopsies, which would seem absolutely uncontroversial.
This statement and the failure of this proposal put many of
the parental advocacy groups firmly behind an effort to
obtain autopsy samples. This effort was strikingly successful
and has resulted in great advances in the knowledge base for
this disease. However it should be noted even in the recent
Nature Genetics article showing a potential driving muta-
KEY POINTS
● Diffuse intrinsic pontine gliomas are almost uniformly
fatal.
● There is considerable controversy over the ethics of
biopsying the tumor.
● The issue of direct benefit is central to this controversy.
● The issue of whether familial or societal benefit
should be considered when a biopsy on a child is
contemplated is controversial.
● The issue of who declares a procedure standard is
uncertain.
Author’s Disclosures of Potential Conflicts of Interest
Author
Nicholas K. Foreman*
*No relevant relationships to disclose.
Employment or
Leadership
Positions
Consultant or
Advisory Role
1. Albright AL, Packer RJ, Zimmerman R, et al. Magnetic resonance
scans should replace biopsies for the diagnosis of diffuse brain stem
gliomas: a report from the Children’s Cancer Group. Neurosurgery. 1993:
33:1026-1030.
2. Hankinson TC, Campagna EJ, Foreman NK, et al. Interpretation of
magnetic resonance images in diffuse intrinsic pontine glioma: a survey of
pediatric neurosurgeons. J Neurosurg Pediatr. 2011; 8:97-102.
3. Frazier JL, Lee J, Thomale UW, et al. Treatment of diffuse intrinsic
brainstem gliomas: Failed approaches and future strategies. J Neurosurg
Pediatr. 2009;3:259-269.
4. Anderson BD, Adamson PC, Weiner SL et al. Tissue collection for
tion in a specific histone gene in many autopsy samples, a
small number of upfront biopsies were used to suggest that
this was a driving mutation not a passenger mutation. 7 The
article did not say how these specimens were obtained.
Fourth, Declaration that a Procedure Is Standard
A participant who serves on an IRB pointed out that most
IRBs relied on local expertise to declare what was standard.
If an institution’s neurosurgeons declared that biopsy was
standard, then it was not in fact an IRB issue. This brings up
the whole question of what is a standard and whether its
determination at a local level should be influenced by national
consensus. Is there an obligation on the part of local
investigators when considering a procedure standard to
discuss with their IRB whether there is national controversy
about that standard? Do IRBs have an ethical obligation to
investigate what is “standard” or whether a therapy has a
“realistic” possibility of benefit?
As a Thought-Provoking Exercise
Let’s say that there had never been a statement in an
influential journal indicating that biopsies of typical DIPG
were not needed for diagnosis and should not be done.
Let’s say there were biopsies performed throughout the
1990s and an H3F3A mutation was identified in 1999
(purely hypothetical given technical considerations).
Let’s say that targeted therapy doubled survival time and
cured a small number (say 10% to 20%) by 2005.
Is it possible that fear of a biopsy (with a known very small
morbidity and mortality risk) resulted in shortening the
lives of many and even the loss of life?
Stock
Ownership Honoraria
REFERENCES
Research
Funding
Expert
Testimony
Other
Remuneration
correlative studies in childhood cancer clinical trials: ethical considerations
and special imperatives. J Clin Oncol. 2004;1:4846-4850.
5. U.S Food and Drug Administration. Minutes of the Joint Meeting of
the Pediatric and Oncology/Advisory Committee, April 27, 2009. http://www.fda.
gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Pediatric-
AdvisoryCommittee/UCM171523.pdfBrainstemgliomas. Accessed March 2, 2012.
6. Roujeau T, Machado G, Garnett MR, et al. Stereotactic biopsy of diffuse
pontine lesions in children. J Neurosurg. 2007;107(1 Suppl):1-4.
7. Wu G, Broniscer A, McEachron TA, et al. Somatic histone H3 alterations
in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas.
Nat Genet. 2012; 44:251-253.
635