some advice from 3rd party retired doctor

One of Mark's sister's friend's dad had GBM several years ago (1995) and we talked to his doctor about his thoughts on standard treatment and upcoming trials. He is now retired, but at one time worked alot with BNCT.
A transcription of our conversation is below.

Name: Dr. Merle Greibenow (retired)
Date: 01/02/06

Has been following Dr. Friedman’s success, he has a fair amount.

Contact a neuro surgeon in Japan to see if he could be treated with BNCT, but cultural differences are rather shocking. Facility in NY where many BNCT patients were treated, but not a particularly good design because it had 4-5 damaging contents in beam, was OK for dogs. Had one patients that lived 9years 5months with most of his functionality. Japan does not have an ideal nutron source from with to extract a beam. Need high energy neutrons. Low energy neutrons with boron damage the scalp and tissue near tumor. This treatment is good for treating the cavity and the surrounding area. The brain has 5 fluid chambers called ventricles. As tumor grows, it can displace this fluid that allows the brain to be able to handle a tumor 5-6cm before symptoms. Many treatments cause swelling, so the tumor has to be resected to make room for the treatment. xrays come in along beam line, does same amount of damage all along axis of each beam. Braggs peak…proton relies on this to some degree, when charged particles pass through tissue at speed of light they don’t do as much damage, when they slow down they can do the most damage which is how they can control the depth and pinpoint where the beams do the damage (work done at Berkely) It is superior to standard treatment, (Loma Linda, Berklely) can’t change the mass of the particle, so you don’t have as much control over where it can release its energy. Gamma knife has a narrower beam of xray. You don’t know where the tentacles are…with xray therapy, they focus on the area that has edema that surround tumor mass, data suggests that the isolated tumor nests will be in this region. Isolated tumor cells left behind. Gliasite has some advantages, because it can effect the areas that are close to the cavity and effects some of the area with the edema, marginal improvement over stereotatic methods. Normal brain tissue more easily damaged by xrays than tumor cells. Glioblastomas are grade 4 in series of types. Can start out as less aggressive and transition to high grade. Pathologist looks throughout tumor and categorizes by the most aggressive cells he sees. Rarely does he look through, 2 classified as high grade and 48 low grade, but will say it is the high grade. Two grading standards (WHO & Nelson schema) WHO requires three physical characteristics and Nelson requires a fourth (micro necrosis). Stay away from Dr. Berzinski. Geminsto feature seen? If so, it may determine if tumor will do well with radiation. Neurons don’t divide. Objective of radiotherapy is to injur cells so they can’t divide and can no longer grow. The more rapidly dividing the cells, the more easily to be damaged by radiation, slow growing is not good for low grade. The cells in the inner walls of the blood cells, do divde and are the most radio sensitive cells within the brain which are the ones at greatest risk. These cells will be pushed to the limit. External beam radiates a large area of the brain. In clinical trials, they may only want patients that hadn’t yet been damaged by other treatments. May get a compassionate waiver to get treatment but not be part of trial. 4 phases regulated by FDA…objective of phase 2 is to show you can provide treatment without damaging patient. Braggs peak or brachytherapy leave behind tumor bed nests. Culture tumor cells and see how they will react to agents before using them. Agents can’t cross blood brain barrier many times, maybe put through brain directly instead of through bloodstream? Clinical trials been done for 15 years, but not great results yet, killed many more than helped. T-cel is a great hope, but it is difficult in the brain. Immune system depleted particularly with chemo, there are some drugs that help the body build back its immune system. Chemo agents damage organs, blood stem cells in bone marrow are at risk…MD Anderson, UCSF, etc…probably not relevant in this case. Study done by (10 years ago) team gather survival time on 1600 GBM etc patients and looked at every parameter that could effect patient surivial, there were only a few patients whose survival team were effected by their treatment (included standard radiation and chemo agents) Immune agents don’t get in brain. Blood brain barrier only in brain and spinal cord, physically made up of andiphilio cells lines the entire circumfrance of the capillary. Series of these short straw sections..they don’t fuse to each other, but they but up to each other and make like a seal and physically doesn’t allow fluid or other things from the blood stream to get in. In other parts of the body there are gaps where things can get through. If you put something in tumor cavity it will be pass the blood brain barrier and effect brain/spinal fluid. Bulk diffusion can only reach isolated tumor cells through fluid which depends on lots of factors. Can only do damage by ionization, iodine 131 only has a short pathway and probably won’t reach tumor beds. Two boron drugs, one is a small molecule that leaks through blood vessels where there is edema in areas surround tumor cavity, you have to wait (some time) to get this to make its way to other areas. If nests get more than 5-6 cells, they damage blood brain barrier angiogenesis (blood supply to tumor) as blood supply is formed, it lacks the barrier, but only during this time. Boron gets in through bulk diffusion & another drug that has active transport to get boron into bad cells through blood vessel wall. Boron drugs are not toxic. Boron activated by nutron, beam effects nothing other than region of interest. Low energy neutrons destroy scalp before they destroy tumor and cause reactions in blood vessels near the surface of the brain. Higher energy neutrons can get through and slow down to react with the boron at a greater depth. Japan doesn’t have high energy beams and would use low energy during operation to avoid scalp damage. Now have neutrons with higher energy, but still looking for the ones that won’t damage scalp/blood vessels. Don’t seem to be the right beam available anywhere at this point. Nurosurgeon @ National Kagawa Childrens Hospital – Dr. Nakagawa (he’s a Quaker?) in Zencujiju City 01-81-877620885 fax 625384 (check time difference, may want to send him a fax first) President of Society of Nutron Capture Therapy,
Some people associated with UCSF and Livermore that have been working on an accelerator. Not very successful for Felix Cochran he was 3rd patient treated. Would need to come in every few years for treatment because there is a huge volume of these nests and it would be impossible to get them all in 1 treatment. 10to6th boron for cell. Binomial statistics. Can’t control radio sensitizer/protector distribution for the brain.