Prenatal DIPG- a case report!

On May 16th the jounal Pediatric Radiology published an unsual case report of a a pre-natal DIPG written from the department of neurosurgery and diagnostic imaging t Brown University.

In this situation a 33 year female who had previously delivered 3 children without complications had an ultrasound at 33 weeks gestation.   Unfortunately the ultrasound revealed a markedly enlarged head of a size more than 40 weeks but with an abdominal circumference and femur length of 33 weeks.   There was also triventricular hydrocephalus without evidence of spina bifida.

A fetal MRI was then obtrained which showed a mass with the epicenter in the pons extending into the midbrain, medulla and cerebellar peduncles.  The expansile mass had poor margins.  There was severe hydrocephalus.  No abnormalities were seen outside the brain.   A diagnosis of diffuse pontine glioma was made.  

The chid was delivered at 36 weeks, 4 days becaue of the big head and had Apgar scores of 7 and 9.  A repeat MRI was preformed and confirmed the prior findings.   The boy underwent placement of an extraventricular drain because of signs of increased intracranial pressure.   The child died from respiratory failure at day 3.

At autospy the lesions was found to be primarily an infiltrative anaplastic oliogdendroglioma with areas of astroctyoma grade IV differentiation.

Although I have posted on neonatal tumors in the past (click here for prior blog post), the rarity of brainstem lesions in the neonatal period makes it difficult to know exactly what to do.   Ther have been a few cases that have done well in the very young.  There are other resports of the typically horrendous course of DIPG in the neonatal period.  As researchers attempt to understand more about DIPG, this case adds to the library of knowledge regarding DIPG.  The authors sugggest that autopsy studies should be strongly encouraged to learn more about this atypical situation.   I would add that perhaps including this in the DIPG registry would also be helpful.

Reference-
Prenatal MRI characterization of brainstem glioma
in Pediatric Radiology
http://www.ncbi.nlm.nih.gov/pubmed/23677423

Spontaneous regression of a diffuse brainstem lesion in the neonate.  Report of two cases and review of the literature
http://www.ncbi.nlm.nih.gov/pubmed/16206736

Lesion Regression
http://www.ncbi.nlm.nih.gov/pubmed/?term=AIREWELE+brainstem

Diffuse intrinsic brainstem tumors in neonates.  Report of two case.
http://www.ncbi.nlm.nih.gov/pubmed/18447673

Case Report- Two Children with Prolonged Survival

During time period between June 2008 and June 2009, Children’s Healthcare of Atlanta treated three children diagnosed with DIPG with radiation followed by temozolomide and avastin.   Two children were still alive at 37 and 47 months from diagnosis.  The other child had progression free survival for 12 months followed by rapid deterioration with death at 14 months from diagnosis. 

Here is the recent case report of these two children who have surpassed the 3-year mark since diagnosis of a DIPG and were still going strong at the time of publication.

Patient 1- was described as an 11-year-old male with a 2 month history of weakness on the left side as well as walking and swallowing difficulties.   The initial MRI showed a 4cmx3.5cmx3cm non-enhancing tumor of the pons and medulla.  

Patient 2-was described as an asymptomatic 7-year-old female who was found to incidentally have a 3cmx2.3cmx2.6cm pontine mass after head trauma.   She was observed closely with serial MRIs.  Two MRIs showed increased tumor size and at 8 months from initial presentation she deteriorated developing a facial palsy, right sided weakness and hydrocephalus.  The tumor was 4.2cmx4.3x3.8cm with new focal areas of enhancement.

The children were treated with temozolomide 200mg/2d/d for 5 days ever 28 days and avastin 10mg.kg.dose every 14 days.   In both patients a 65% decrease in tumor size was seen.   No steroids were needed after 10 weeks from radiation.   The therapy was tolerated well.  At publication both children were doing well and continuing on treatment.  The paper notes that the boy was going to school and playing soccer at 37 months.  

 (Note- the actual paper has several MRI images provided both initially and later for both children.)

The authors speculate that the combination of temozolomide and avastin might deliver more temozolamide to the tumor because avastin might normalize the tumor vasculature.    As support for this theory the authors point to cilengtide altering perfusion which allowed for increased temozolamide delivery  for gliomas.    Perhaps avastin has a similar effect.

An additional advantage of this combination might be the decreased need for steroids.

The authors recommend consideration of an expanded DIPG clinical trial with this combination.

By the way, the female child appears to be atypical both in presentation and focality in her tumor.   On the other hand, the male child seems to have a very typical presentation for DIPG.

Reference:

Prolonged survival after treatment of diffuse intrinsic pontine glioma with radiation, temozolamide, and bevacizumab: report of 2 cases.

J Pediatr Hematol Oncol. 2013 Jan;35(1):e42-6.

http://www.ncbi.nlm.nih.gov/pubmed/23249962