In 1993 Albright et al.1 published a manuscript that changed the course for the treatment of children with diffuse intrinsic pontine gliomas (DIPGs). The point of the paper was that if a child presented with a short clinical history, had cranial nerve findings and long-tract signs, and had the typical MR imaging appearance of a diffuse pontine glioma, there was no difference in treatment or outcome in that patient population based on biopsy findings. At that time, 11% of the children who underwent stereotactic biopsies developed new neurological deficits as a consequence of the surgery. Since that time, biopsy of brain stem tumors has been relegated to cases involving atypical MR imaging features or those involving an atypical clinical picture. Two decades later, despite numerous clinical trials, children with DIPGs fare no better. We have learned that children with focal brainstem tumors commonly have a low-grade histology and long-term event-free survival after either complete tumor resection or focal irradiation. In our institutional review reported last year, of 66 children with focal brainstem tumors, all biopsy proven, treated with either resection or focal irradiation, 85% are alive and doing well at a mean follow-up of more than 7 years (Sanford R, Chavez A, Boop FA, Armstrong GT, Klimo P: Focal brain stem gliomas. Paper presented at the 39th Annual Meeting of the AANS/CNS Section on Pediatric Neurological Surgery, Cleveland, Ohio, December 3, 2010). Recently, there has been a resurgence of interest in obtaining a biopsy sample of diffuse brainstem gliomas in hopes that molecular profiling of these tumors will lead to novel biological therapies. This has proven to pose an ethical dilemma, by placing a child at risk to gain research knowledge without using the individual’s data to determine a treatment strategy for the benefit of that child. To this end, the National Cancer Institute is holding a consensus conference on this subject later this year. In their study, Dellaretti and co-workers3 report a retrospective review of 44 children in whom stereotactic biopsies was performed for various brainstem tumors. The patients were divided into groups based on MR imaging findings. Patients were defined as having either focal or diffuse lesions, enhancing or nonenhancing. As one might anticipate, those children with focal nonenhancing tumors tended to have low-grade histology and a more indolent clinical course. Those with diffuse nonenhancing tumors documented on MR imaging all had DIPGs, and 90% of those with diffuse enhancing tumors had DIPGs. Thus, the authors have provided a nice validation of Albright’s 1992 study.1 They were able to obtain diagnostic tissue in 93.1% of patients, although the study does not address the issue of sampling error. Nine percent of children developed new neurological deficits following biopsy. At the 1-year follow-up, the survival rate was 80.4% in cases of low-grade glioma and 48.6% in cases of high-grade glioma, although the intergroup difference did not achieve statistical significance. The article does not mention whether treatment of the children was altered based on the biopsy results. They do indicate that in the future they hope that new therapies will be developed for patients such as these, based on biopsy results. The authors conclude that stereotactic biopsy of brainstem tumors is low risk and should be standard of care in children with enhancing brainstem lesions. When one considers that the current complication rate for clipping a small anterior circulation aneurysm is 1.9%2 and the likelihood of a new neurological deficit following resection of a Spetzler Class A arteriovenous malformation is 2%,4 one might question whether the 2 cases of hemiparesis and 2 cases of facial palsies are truly “insignificant.” Furthermore, based on the data provided, the results of the biopsy in these children did not appear to influence treatment or make a statistical difference in their outcome. Thus, the authors take us back to the status of this disease prior to 2 decades ago, as reported in Albright’s article.1 There is no question as to the value of having a tissue diagnosis in any child with a brainstem tumor if that data will stratify the child’s treatment within a defined study protocol. For that we can reach consensus. But to conclude that “Stereotactic biopsy of brainstem tumors... should be regarded as standard of care in children with enhancing brainstem lesions” based on Class III data and outside of a well-defined treatment protocol is not supported by the authors’ study and it is not to the benefit of children afflicted with this terrible disease.
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Jan 1, 2012
Lisa M Ruiz + 1
Open Access
