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A searchable blog on DIPG research, DIPG news, recent publications, DIPG Foundations, DIPG researchers, clinical trials as well as other issues relating to Diffuse Intrinsic Pontine Tumors- both Diffuse Intrinsic Pontine Gliomas (DIPGs) and Atypical Pontine Lesions (APLs).

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Saturday, May 9, 2009

FDA Public Hearing on Biopsy of Children with DIPGs- Part 3

Stereotactic Biopsies

Although typical DIPGs (without focality or exophytic components) can not even be partially resected because the tumor tissue intertwines with normal tissue in an area that houses most critical functions of the body in a small space, it is possible to biopsy these lesions via an open or a stereotactic technique. Dr Michael Handler, pediatric neurosurgeon from Children’s in Denver, presented an overview of stereotactic biopsy technique and a review of the literature specific for brainstem biopsies.

Stereotactic neurosurgery is a minimally invasive procedure where tumor imaging is used in conjunction with external reference points on the head (either with a frame or frameless via fiducial markers) to develop a three dimensional image to precisely localize a location within the brain. The idea of this technique has been around for more than a century. Horsley and Clarke used a frame on experiments with monkeys in analyzing the cerebellum back in 1906. Stereotactic biopsies for humans really did not take off until the 1970’s with the advent of CT scans which allowed for detailed imaging and 3D localization. The technique rapidly adapted to MRIs when this technology became readily available.

Dr. Handler pointed out that during the 80’s there was a rapid expansion of experience. It was found that-

  • The safety of this technique became well established.
  • This technique was applicable to deep lesions in the brain.
  • Questions about sample adequacy subsided
  • It was found to be an unquestionably effective technique.

Dr. Handler presented the results of 13 different studies on stereotactic brainstem biopsies to try to give background on the ability to get diagnoses from a small sample, morbidity and mortality. Some of the most interesting articles include-

Brainstem stereotactic biopsies sampling in children.Neurosurgery 2006 Feb;104 (2 supplement): 108-114In this study 10 children underwent frameless biopsy. All samples were diagnostic and there was one case of transient diplopia.

Stereotactic biopsy of brainstem masses: decision analysis and literature review.Surg Neurol 2006 Nov; 66(5): 484-90This was a metanalysis of 378 patients. The results included-- 6.6% transient complications,. 1.5% permanent new deficit and a 0.5% mortality.

Prospective feasibility study of outpatient brain biopsies. Neurosurgery 2002 51 (2): 358-361In this series of 76 patients which were slated for outpatient brain biopsies only 3 got admitted. One was for IV antibiotics after an infection developed and the other was a failed biopsy (a hard lesion which the needle could not penetrate).

“Prospective feasibility study ofIf the reader is interested, this would be most easily reviewed from Dr. Handler’s slides referenced at the bottom (slide 10-17).

Dr Handler ended his presentation with a quote from Dr. Andrew Brodbelt commentary in the British Journal of Neurosugery last October regarding this controversy.“It surprises us treating adults with brainstem tumours that there appears to be reluctance in the paediatric world to perform biopsies….We owe it to current and future patents to biopsy brainstem tumours.”


April 27th, 2009 FDA joint PAC/ODAC public meeting on DIPG BiopsyAll presentation slides including Dr. Handler’s are available at the site http://www.fda.gov/ohrms/dockets/ac/09/slides/2009-4431s1-00-Index.html

A Short History of Stereotactic Neurosurgery

Brainstem stereotactic biopsies sampling in children.
Neurosurgery 2006 Feb;104 (2 supplement): 108-114

Stereotactic biopsy of brainstem masses: decision analysis and literature review.
Surg Neurol 2006 Nov; 66(5): 484-90

Prospective feasibility study of outpatient brain biopsies.
Neurosurgery 2002 51 (2): 358-361

Commentary on diffuse brain stem glioma in children
Br J Neurosurg. 2008 Oct;22(5):625.