NeuroBites – Does Size Matter with Glioma?

 

 

Every week, the BVNS neurologists, residents and interns convene to discuss a human or veterinary neurology/neurosurgery article.

NeuroBites is a digestible synopsis written by Dr. Bush of the article covered in journal club.

Welcome to NeuroBites.


MacLellan, JD et al. Association of magnetic resonance imaging–based preoperative tumor volume with postsurgical survival time in dogs with primary intracranial glioma
J Am Vet Med Assoc 2018;252:98–102

Click HERE for the full article.


Glioma is a type of brain tumor with a notoriously bad reputation. People with this disease typically live only 18 months once they are diagnosed despite chemotherapy, radiation and surgery – and historically dogs live for days to weeks. In this week’s journal club, Dr. Stallings reviewed an article where the authors asked whether size matter in terms of tumor size and prognosis following surgery and vaccine therapy.

How was tumor size measured?
MRI images in 3 planes were reviewed and a volume measurement taken as a percentage of calvarial volume – in other words the size of the tumor was expressed as a percent of brain volume. Tumors size ranged from about 1-12% of brain volume.

So, what do you think, does size matter, do larger tumors have a worse prognosis when treated with surgery?
Turns out size of the tumor had no association with 6, 12 or 24 months survival.

Could this finding change the way we practice?
Probably the best answer is not clearly. Although Dr. Young is working on a really innovative surgical solution for this tumor type, we rarely entertain tackling these tumors surgically. We often recommend radiation and it is uncertain whether tumor size has a bearing on prognosis.

Can it be predicted which tumors would respond to radiation?
Very interestingly Dr. Young discussed a potential collaboration with Dr. Kevin Woolard who believes that testing the DNA of the tumor can predict whether there will be a response to radiation and/or the most common chemotherapy, temozolomide.

Does anyone remember when Kevin was at NIH he would come to our practice and perform necropsies for us – he is a very hard working and successful scientist trying to solve the glioma problem.

You may be aware that we send tumors out for histopathology. What does histopathology mean?
Histopathology is the microscopic examination of a tumor.

Why bother to perform histopathology?
Tumors are often characterized under a microscope in 2 ways. They get a name and a grade. The name and often the grade are thought to have prognostic importance. Higher grade tumors typically have shorter patient survivals.

Size was examined as a prognostic indicator in this paper but was grade or tumor type analyzed?
Nope. The authors only seemed interested in answering the age old question of whether size matters or not.
Due to study design, there were very few low grade tumors so statistical analysis to try to see if low vs. high grade determined outcome was impossible according to the authors.

Besides size and histopathology, are there other factors that might predict response to therapy for glioma?

  1. Neurological grade and initial response to therapy –  the dogs in this study had a useful response to steroid therapy and antiepileptic drugs. Dogs with poor function or poor response were euthanized and never even made it to surgery. This is why some studies show a mead survival time of 9 days.
  2. Location – brainstem tumors are not even thought to be amenable to surgery whereas tumors in the forebrain often spark life threatening seizure.
  3. DNA make-up of the tumor – glioma have many nasty characteristics that allow them to grow unchecked by the immune system and these characteristics are revealed by the tumor’s DNA. It is hoped that biopsy and genetic study of tumors will soon direct therapy.

These dogs also got immune therapy – what is that?
You take some of the tumor and inject it back into the patient to generate an immune response against the tumor. It is thought or hoped that the immune response can cross the blood brain barrier and attack the post-operative remains of the tumor. Most simply, you vaccinate the patient with their tumor.

How long did patients in this study live?
Patients lived between 2 and 802 days with an average survival of 185 days. The 3 lower grade tumors lived for 532,727,802 days suggesting it is not only size that matters.



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