Saturday
[Journal not posted until Sunday morning at 8:45 AM.]
High-Level Journal Summary: A specific example of a study that is early in the clinical trial process. In taking a close look at Irreversible Electroporation (IRE), I get a much better understanding of how a study evolves into a clinical trial that can be done with human beings.
I was able to get my hands on a PowerPoint Presentation which better explains what is happening with IRE. This helps to get beyond the technical language of White Papers that speaks in the language of doctors. Instead, this presentation provides information in a language that patients and caregivers can understand.
In any case, this quick review of Irreversible Electroporation (IRE) helps to paint a picture of how treatments for brain cancer are being developed far down in the pipeline, before they can be used on human beings and before more attention is given to them.
This may be seen as unsexy research, but this is the kind of determined effort that is needed to eventually develop new treatments for brain cancer that have efficacy. As such, I think this is an interesting "case study" for better understanding this entire process. It certainly helps me to contextualize how this all works.
Countdowns:
1.) Day 20 of 28 in my 26th 5/23 Temodar chemotherapy cycle. I've been at Virginia Tech in Blacksburg, Virginia for the past two days, and meeting with so many people has had two qualities. First, it has been great to reconnect with so many people. Second, it has been exhausting. I am reminded how much I need to be somewhat introverted during chemotherapy. I can only handle a few hours at a time. After that, my gas tank gets empty pretty quickly. I'm getting this lesson again, which is in conflict with my desire to catch up with a few of my friends and former professors.
2007 Seizure Activity:
1.) Last Simple Partial Seizure, or SPS, was 7 days ago.
2.) In 2007, I have had 69 SPS's in 293 days. This is an average of 1 SPS every 4.2 days.
Actual Journal: In my 10/19/07 online journal entry, I wrote about a new brain tumor treatment being studied at Virginia Tech and Wake Forest University. As it turns out, this was my first opportunity to meet with a team of doctors and scientists who have a new concept for treating brain tumors which is early in the clinical trial process. That is, this treatment is being used on animals prior to being used with human beings in a Phase I clinical trial.
On 10/19/07, I wrote about my overall impressions of going behind the scenes like this for the first time. I think this is a good example of a study that is early in the clinical trial process. As such, I want to keep exploring Irreversible Electroporation (IRE) -- all for the sake of better understanding how a study evolves into a clinical trial.
A case study: better understanding Irreversible Electroporation (IRE)
I am unable to properly interpret the White Papers which have been published about IRE. I have them, but they are in a technical language which prevents me from reducing them to pap. So, I want to share information about Irreversible Electroporation that I got from a Microsoft PowerPoint Presentation prepared by Dr. Raphael V. Davalos. These excerpted details about IRE are shared verbatim.
Please note that the purpose of exploring this information is to see how a research team is approaching a new treatment for brain cancer in humans. For me, there is insight about how new treatments are being developed.
Man's best friend … in health and disease
The Virginia Tech-Wake Forest University Brain Tumor Team
1.) Why study cancer in dogs?
• #1 cause of death in aged dogs (45%)
• Dogs are outbred – like humans
• Cancer is spontaneous
• Dogs share the same environment
• Cancer progresses more rapidly, allowing study to endpoint, including necropsy
• Morally acceptable and imperative to try novel therapies
• Genomic, physiologic, immunologic, and metabolic similarities of dogs, humans
• Lifespan is sufficient for meaningful study
• Reasonable size for therapy
2.) Brain tumors in dogs
• Spontaneous primary brain tumors are common in dogs, accounting for 1-3% of all deaths in aged dogs where necropsy is performed
• An incidence rate of 14.5 cases/100,000 dogs at risk was reported (imprecise actuarial data is not collected on dogs at the time of death.
• Over 70% of primary tumors occur in dogs aged 6 years or more, a period in lifespan comparable to middle age in humans.
• Astrocytomas, oligodendrogliomas and meningiomas are most common, with astrocytomas accounting for approximately 10% of primary brain tumors in some series.
• Astrocytomas classified as grades II-IV in the revised WHO Classification system have been recognized and reported in dogs, and are histologically identical to similarly graded tumors in humans.
• Most canine astrocytomas occur as cortical lesions, with many forming in the temporal and frontal regions.
• An increased incidence of gliomas has been noted in brachycephalic breeds (Boston Terriers, Boxers, Bulldogs) as well as in the Golden Retriever, Doberman Pinscher, Scottish Terrier and Old English Sheepdog breeds.
• Clinical presentation and progression of these astrocytomas is similar to humans.
• Unfortunately, patterns of survival are also similar, likely a combination of limitations in providing therapy to veterinary patients and inherent tumor behavior. (Most dogs with high grade astrocytomas are immediately euthanized.)
3.) Clinical presentation - astrocytoma
• Man: Headache, Cognitive defects, Proprioceptive defects, Seizures, Altered consciousness
• Canine: ?, Cognitive defects, Proprioceptive defects, Seizures, Emergent and unpredictable behavior (aggression)
Canine astrocytoma -- necropsy specimen
4.) Pathologic features - astrocytoma
• Man: Large necrotic areas, Vascular proliferation, Poorly defined borders, Edema and inflammation, Glial pseudopalisading
• Canine: Large necrotic areas, Vascular proliferation (+/-), Poorly defined borders, Edema and inflammation, Glial pseudopalisading (+/-)
5.) Clinical summary (University of Tennessee cases)
• Clinical summaries on 34 dogs
• Average age – 7.8 years
• 19 breeds represented in database
• Three top breeds; Boxer (9/34), Boston Terrier (7/34), Staff Terrier (2/34)
• Sex demographic: M (18/34), F (16/34)
6.) Primary Brain Tumor (PBT) pathology study - classification
• University of Tennessee collection
- Low grade astrocytoma, including pilocytic astrocytoma (4)
- High grade astrocytoma – GBM (16)
- Low grade oligodendroglioma (8)
- Anaplastic oligodendroglioma (+/-) GBM (5)
- Typical/atypical meningioma (5)
- Ganglioglioma (2)
• Cornell collection – evaluation starting (200 Primary Brain Tumors)
• Animal Medical Center of New York collection – evaluation starting (26 astrocytomas)
7.) Breed genomics are important
8.) Breed genomics from the Veterinary Cancer Registry Database (July, 2005)
• 6409 canine case entries
• 23 clinical summaries of astrocytoma (9/23 cases in brachycephalic dogs)
• 10 clinical summaries of oligodendroglioma (5/10 cases in brachycephalic breeds)
NOTE: Brachycephalic dogs are very sensitive to high temperatures
9.) Where are we?
• Clinical profiling completed on 140+ Primary Brain Tumor cases at Virginia-Maryland Regional College of Veterinary Medicine (23 astrocytomas)
• Clinical profiling 80% complete on 39 presumed astrocytoma cases at the University of Tennessee
• Histopathology completed on 45 presumed astrocytomas
• Immunohistochemistry Panel (IHC panel) developed and in use
• Image analysis and computational routines for MRIs and histopathology developed and tested
• 226 clinical/pathology cases being acquired
10.) Where do we go?
• Complete acquisition, staining, and analysis of 50 canine astrocytoma cases
• Merge dataset with Vet Neuro-oncology astrocytoma dataset / publish (75-80 cases total with Histopathology and IHC panel)
• Collaborator institutions/practices in place
11.) Veterinary institutional collaborators
• Virginia Tech
• University of Tennessee
• Ohio State
• Cornell University
• North Carolina State University (Vet Neuro-oncology Group)
• Animal Medical Center of New York
• Veterinary Specialty Practices of San Diego
Putting this into perspective
Again, the purpose of exploring this information is to see how a team is approaching a new treatment for brain cancer in humans. For me, there is insight about how new treatments (which may one day impact my brain cancer treatments) are coming along in the pipeline of development.
