January 28, 2010
Charlotte starts her Temodar tonight. Her UPC (urine protein creatinine) ratio is still too high to restart her Avastin. Her labs yesterday showed her UPC ratio, instead of steadily decreasing and getting better since her last Avastin, had increased from 2.9 to 3.6 just in the past week. I believe her kidneys (e.g. Avastin) are a large contributor to the problems that she has been having during the past 30 days. Last month she started using her mother's cane in order to walk. When we saw Dr Spier this past Monday, Charlotte asked for a wheelchair. She also used one for her labs yesterday.

She had a brain MRI and a cervical spine MRI on the 22nd. I don't have the written reports yet, but this is what Dr Spier said on Monday. First, her cervical spine MRI did show some problem areas, but probably not enough to account for Charlotte's numbness in her right arm and leg. The brain MRI was stable in the T1, T2 and FLAIR sequences, but the technician used "fat saturation" in all of the contrast sequences that made them useless for comparison.

Charlotte now wants to see her chiropractor, Dr Iris Lowe, once a week. Last Thursday Charlotte walked into Dr Lowe's office using her cane, and walked out without needing it. She did walk a long way with her cane last Friday for her MRI before asking for the wheelchair on Monday. Dr Lowe wanted a "lumbosacral with femurs" MRI. That will be done along with a brain MRI and a brain MRA in 30 days. The MRA (magnetic resonance angiography) is for diagnosing a possible bulging artery/vein.

For the past 30 days I have seen a decrease in both Charlotte's walking and speaking ability. Dr Spier says it can be the result of tumor progression and/or the effects of Charlotte's radiation and chemo treatments. The walking and speaking problems could be the early clinical signs that appear before the MRI reveals tumor progression.

Charlotte awoke this morning looking tired, and I asked her what was wrong. She was worried that her walking ability would continue to deteriorate, and that she would end up being paralyzed. Those thoughts are only natural to have, but I just hope her attitude continues to be one of her greatest assets.

She finished a sculpture last night, and just began another one this morning.
I told her that says more right now than anything else.

December 31, 2009
Charlotte will start her Temodar tonight. Her UPC ratio is still too high for receiving Avastin. She has been having numbness in her right arm and leg. The numbness does not seem to be related to any loss of strength on her right side, which would indicate tumor progression. She does feel more comfortable walking with her mother's cane now.

She is scheduled for a cervical spine MRI along with her normal brain MRI on Jan 22nd.
Her last MRI was moved from Dec 28th to Dec 19th. It was read as "stable".

December 3, 2009
Charlotte will start her Temodar tonight, but she did not receive Avastin today. Her UPC (urine protein creatinine) ratio rose from 2.37 to 4.1 in the past week. On Monday, I convinced Dr. Spier to lower the Avastin dosage from 2.5 to 2.0 mg/kg and to raise the UPC ratio threshold from 2.4 to 2.5 in order for Charlotte to receive Avastin. My hope in changing these numbers was to keep her from missing an Avastin date.

The good news is that Charlotte read poetry last Saturday night at the Julian Christmas Tree Lighting Ceremony. It was cold with rain and snow (white dots in pictures), but she did a wonderful job. To attend and to read poetry was important to her, since it was two years ago at the same poetry reading that she started to slur her words.

Charlotte's brain seems to go through a "rebooting" two to three times a year now. When this happens, her speech becomes almost unintelligible. The good news is that she is aware something is wrong, and always says "what is wrong with me"? After a good night's sleep, her speech is back to "normal". This happened again on Tuesday, but I feel she has only regained about 80% of her speech. Her reading ability has also suffered about the same amount. She has also been "sick" for the past two days with a constant low grade headache and fatigue. If she gets any worse, I'll take her to the ER. She has always been good at letting me know when she needs to go to the ER. Most of the time she tells me "this too will pass with rest..."

Her labs yesterday were slightly improved over last week, except for her UPC ratio. I just e-mailed her nephrologist with an update on her blood pressure. I hope to increase one of her existing BP meds and try to stop her newest BP med (clonidine) that she has been taking for two weeks. I think the clonidine might be a big contributor to some of her latest symptoms.

Charlotte's Nov 24th MRI was read as stable. Clinical symptoms will probably be the first signs of tumor growth, especially when she is on Avastin. Clinical symptoms would be changes her speech, memory, walking, energy, etc. I think Charlotte's next MRI on Dec 28th will be very important to us.

November 19, 2009
Charlotte had her Avastin today. Her labs yesterday showed both her platelets and her WBC count have rebounded. Her GFR (glomerular filtration rate) also rebounded from 57 to 86 in one week. Her chest cold and coughing have also slightly improved.

Her labs next Wednesday will be day 21 of her Temodar cycle, which means all of her blood counts will be at their nadir. That sometimes is not always the case, but it is something to keep in mind after receiving decent lab results this week.
Her next MRI is next Tuesday at 9:30pm. Hopefully I can get my disk copy sometime on Wednesday, just before Thanksgiving. There have been a few clinical changes in Charlotte since her last MRI, so I will be interested in what it shows. The lower dosage of Avastin (2.5mg/kg) seems to have kept the toxicity to Charlotte's kidneys at an acceptable level for now. I just don't know how well the tumor is being controlled at this lower dosage.

Nancy Grossmann (R.N.) and Kristine, both from oncology at Kaiser, attended Tom Oppenheimer's memorial service yesterday. Nancy said it was quite touching, and had brought back two pamphlets for everyone to see. I know Tom made a great impact on our lives, and from Nancy's description of his memorial, he had touched numerous other lives as well. We miss you Tom.

Nancy gave Charlotte a big hug as we left Avastin. She kindly held Tom's pamphlets behind her back as she hugged Charlotte since I had just told her that I had not informed Charlotte yet. Nancy's eyes began to swell as she hugged Charlotte. Not only have Charlotte and I been blessed to have known Tom and Mary for the past two years, but we have also been blessed to have had Nancy and her staff take care of us. There have been some very special people, both patients and staff, that we have met in the chemo room that have touched our lives. Thank you.

November 12, 2009
Just a short update on Charlotte, and then a tribute to our very dear friend Tom Oppenheimer.
Charlotte's labs yesterday contained both good and bad news. The good news is that her WBC count and platelets have risen since last week. The bad news is that her GFR (glomerular filtration rate) has fallen to 57, which is the lowest it has ever been. When her filtration rate fell below 60, she went from mild to moderate kidney damage. The other bad news is that she now has my chest cold that has been with me for three weeks. The chest cold manifests itself with uncontrollable coughing. The only good news is that she does not have a temperature.

Now to Tom and Mary Oppenheimer. Both Tom and Charlotte entered the Kaiser-UCLA trial study back in November of 2007. Their surgeries, radiation treatments, Temodar and Avastin treatments, MRIs, etc, were almost on identical dates. Some of our appointments with Dr Spier coincided, so we would have long talks and share information. They even went "off-study" within days of each other, Charlotte because of kidney toxicity due to the Avastin, and Tom's MRI showed he had tumor growth. At about the same time I was beginning to see what I thought to be tumor enhancement in Charlotte's MRI. Her PET scan on Sept 14th confirmed tumor growth, not in her old tumor bed, but in a different location.

Charlotte and Tom were the longest surviving participants in the Kaiser-UCLA trial study here in San Diego.
I just received an email from Mary Oppenheimer that Tom passed away on November 10th. He passed away quietly with Mary by his side.
God bless you both.

November 5, 2009
Charlotte had her Avastin and Temodar today. Her labs came back yesterday showing a UPC (urine protein to creatinine) ratio of 2.38. Dr Spier and I finally agreed that Charlotte could receive Avastin if her UPC ratio was 2.4 or lower. We also agreed that Charlotte would receive a new lower dosage of Avastin equal to 2.5 mg/kg. Her last Avastin was 5mg/kg. I'm trying to control the tumor while still keeping the toxicity to her kidneys low. All these numbers are arbitrary, so I have no idea what the results will be.

The labs also showed Charlotte's WBC count and platelets to be extremely low. In fact, my records show they haven't been this low for the past 20 months. That goes all the way back to March of 2008 when she was extremely sick due to the high dosage of Temodar at that time. These levels were a complete surprise to me, and obviously I am very concerned. Charlotte also woke up with a sore throat this morning.

October 28, 2009
I wanted to wait until Charlotte had her labs today before I wrote a short update.
The written MRI report by the neuroradiologist is not done yet, so the following are just my observations.
Charlotte's MRI on Monday looked "improved" to me. "Improved" means that her areas of enhancement did not look as bright, and in some cases, the enhanced areas were "almost gone". I say "improved" and "almost gone" because after hours of review, I just got the feeling that everything was still there, but was just being cloaked by the Avastin.
If the Avastin is ever stopped, I think everything will return.

I did find the new tumor that was first shown by the Sept 14th PET scan did in fact first appear on Charlotte's Aug 27th MRI. It appeared on that MRI as a very tiny white wisp, that then turned into a very small white dot on both her Sept 28th and her Oct 26th MRIs. That dot seems unaffected by the Avastin. I guess a more accurate statement would be that it's size has remained basically the same. It is located either in or next to her left hippocampus.

Charlotte has had more hypertension since restarting the Avastin, so it was not a surprise that her UPC (urine protein to creatinine) ratio had risen from 2.4 to 2.9 in just the last week. At some ratio, the Avastin will be stopped again. We have an appointment with Dr Spier on Monday, Nov 2nd. I want to discuss lowering the Avastin dosage even further. We need to find the correct dosage for Charlotte that will both control the tumor and spare her kidneys. There are so many variables that I can think of right now which could alter finding that correct dosage.

Clinically, Charlotte is doing fine. As I'm writing this, she's gluing the bails on more newly created fused glass pendants. She just finished a kiln shelf of Christmas decorations last weekend at the gallery. Hopefully I'll get those fired in the kiln sometime soon.

October 22, 2009
Charlotte had her Avastin today. Last Tuesday, we again drove up to the Kaiser complex on Sunset and Vermont in northern L.A. This time we had an appointment with Dr Michael Miller, another radiation oncologist. About 10 days before this meeting, I had received two emails from Dr Joseph Chen saying first that he agreed with Dr Spier that Charlotte should go back on Avastin, implying to me that radiosurgery was not an option. Later that same day, he wrote me again saying "I will have you and Charlotte come back to our radiosurgery clinic in Los Angeles so that we can discuss with my radiation colleagues. Will see you soon."

Dr Miller is Dr Chen's colleague, and basically that was how the consultation was conducted. We talked for an hour about Charlotte's MRI, SPECT and PET scans, what I thought were Charlotte's deficits (her short term memory and not being able to sometimes say the correct word), etc, etc. Dr Miller asked her about her artwork at the end of the meeting. For ten minutes Charlotte spoke flawlessly about Mary Oliver, Emily Dickinson and Walt Whitman, and how their poetry has influenced her sculptures. Go figure! Basically, the only thing that was definitely decided was just for everyone to wait until Charlotte's next MRI which will be this Monday, Oct 26th. Charlotte's BP at Avastin two weeks ago was 117/77. Today it was initially 151/101 before the Clonidine BP pill. Her UPC ratio has risen to 2.4, but her GFR (glomerular filtration rate) has gone from >89 to 64 (higher is normal). A level of 61 is the lowest it has ever been, and you don't want it to fall below 60. Again, all this has happened in only two weeks of being on Avastin.

I also have no idea what to expect on her next MRI. Obviously I don't want to see further enhancement, but if I do, maybe that could be pseudo-progression caused by the Avastin. The other extreme would be a scan that showed some decrease in the tumor, which one would think would be good. But Avastin can also "cloak" tumors, so I can not truly trust what the MRI is showing me. Obviously I would rather see a cleaner MRI than an enhancing one on Monday. That's why Charlotte's clinical status is so important to me. It tells me more, and sooner, exactly what the tumor is doing long before the MRI.

The picture below was taken by Donna today during Charlotte's Avastin.

October 8, 2009
Charlotte began her Temodar tonight.
We have had quite a few doctor meetings since the PET scan and the MRI. The MRI was read "abnormal" only because the same neuroradiologist had read the PET scan earlier and had seen the "hot spot", otherwise he said he probably would have read the MRI as "stable". The "hot spot" on the PET did coincide with a very small spot on the MRI which could have been easily missed.

To some of us though, the tumor that was located in the original site looked like it was starting to mobilize again. The tumor shown on the PET scan was more medial, and not located within the original tumor site. Our first option when the tumor grew again was to have surgery to remove the mass. We just never wanted to hear the two phrases: "it's location makes it inoperable", or "it's now a diffuse tumor".

Our first meeting last week was with a neurosurgeon who was willing to remove the new tumor revealed by the PET scan. We left his office feeling good, because our plan seemed to be on track. Surgery was an option, and we didn't hear the two phrases mentioned above. On Monday, we met with Dr Spier for the Temodar prescription, and she again suggested that Charlotte have fractionated radiation and to resume Avastin. These had been suggested to her by Dr Cloughesy at UCLA. Dr Pikul, our neurosurgeon in L.A., called me Wednesday after consulting with Dr Green, the neuro-oncologist in L.A. Dr Pikul told me that he would not perform the surgery because of the tumor's location, and that Charlotte needed a more "global" approach because the tumor was looking diffuse.

Today, we met with Dr Ijaz, a radiation oncologist, that performs IMRT radiation. He thought Charlotte's first choice should be to have radiosurgery performed by Dr Chen in L.A. That contradicted what Dr Chen had told us, and what Dr Spier had heard from Dr Cloughesy at UCLA. Charlotte was to restart Avastin tomorrow at 5mg/kg vs 10mg/kg. I cancelled that appointment because Avastin makes the brain more susceptible to bleeding if you have radiosurgery. I emailed Dr Spier to perhaps have a teleconference with Dr Ijaz, Dr Chen and Dr Cloughesy to try to get everyone on the same page regarding re-irradiation.
As Dr Ijaz pointed out today, we now have the following options:
1. Some type of re-irradiation, which I think none of the doctors want to do because of the possible side effects
2) Change/add a new chemo, which will be Avastin, which I don't want to do because of the possible side effects.
3) Do nothing.
The picture below was taken today a Tio Leo's with Charlotte's rosemaling on the booths. We did these booths 30 years ago.

September 24, 2009
I just received the written reports on Charlotte's PET and SPECT scans.
The SPECT scan was of low quality, but showed no definite or obvious abnormalities.
The PET scan showed a 7mm recurrent neoplasm.
I emailed Dr Pikul (awake craniotomy), Dr Chen (radiosurgery), and Dr Spier (neuro-oncology). Dr Pikul is out of his office until next week, so I will not have his opinion or suggestions until he returns. Dr Spier is also out of her office. I expressed my order of preferences to each of them. They are:

1. Surgery with Dr Pikul along with a biopsy and chemosensitivity testing from the tumor.
   I don't know if 7mm of tumor will allow all of that testing.
2. Radiosurgery by Dr Joseph Chen.
3. Stronger chemo from Dr Spier.

Charlotte's next MRI is coming at a good time. It is scheduled for Monday, Sept. 28th.

September 10, 2009
Charlotte starts her Temodar tonight. Her lab tests yesterday showed her serum sodium was again at 137. Normal is 135-145. Her serum chloride had risen from 100 to 106 during the past week. Normal is 101-111, so that also looked good.

Charlotte is scheduled to have her PET scan on Monday, Sept 14th.
She will have the MRSpect on Thurs, Sept 17th.
Her 30 day MRI will be on Sept 28th.
All the above dates are still subject to Dr Pikul's approval.

September 4, 2009
Charlotte has had some busy days lately. On Sept 1st, she had labs done at Vandever. They had been ordered as a follow-up to her ER visit on Aug 27th, plus she had some normal chemo labs that were due. Later that day, we saw Dr Lin to discuss her labs, plus I had other questions about her kidneys and hypertension. All of her electrolytes were normal, and most of her other urine tests looked good, with a few exceptions. Dr Lin did not know why her serum sodium fell so much in just one week, and then recovered just as fast. He thinks her kidneys are in good shape, and that the Avastin is still causing her existing problems.

We saw Dr Joseph Chen Sept 3rd in northern L.A.
From Charlotte's notes, Dr Chen thought:
1. Radiosurgery may not provide the best results for a GBM.
2. He sees some enhancement, but doesn't know whether it is tumor or necrosis. He suggests that we request a PET scan and a MRSpect from Dr Spier.
3. Surgery by Dr Pikul will give us a sample for biopsy, which radiosurgery will not.
4. He thinks Charlotte's tumor is very slow growing as compared to a normal GBM.
5. He will do radiosurgery, but can not guarantee any long term benefits.
6. Necrosis may become more of a factor in this enhanced area after radiosurgery.

We saw Dr Spier on Sept 4th. She had sent me an email earlier in the week giving me a list of treatment options for Charlotte's enhancement. She also had called Dr Lai and Dr Cloughesy at UCLA to inquire about what we could add to Charlotte's Temodar. Dr Lai had done Charlotte's molecular testing. Both Dr Lai and Dr Cloughesy informed Dr Spier they thought Charlotte should go back on Avastin if we approved and if her nephrologist, Dr Lin, approved. They also said they would not recommend radiosurgery for Charlotte. Dr Spier also ordered the PET scan and the MRSpect that Dr Chen had suggested. She also ordered Charlotte's next MRI for the week of Sept 28.

Dr Pikul called me later that day and said he wanted the PET scan and MRSpect done and the results back by the end of next week. He was going to email Dr Spier to see if she personally could expedite these tests for him down here in San Diego. If not, Dr Pikul said he could order them done within a week up in L.A. Unfortunately, we would have to drive 250 miles for each test. I said "no problem".

The below picture is one that Charlotte walked two city blocks to have taken outside Kaiser at Sunset and Hollywood. It's for Donna!

August 27, 2009
I took Charlotte to the ER this morning. Over the past few days, she has been having increased mental confusion, an inability to speak correctly, nausea, fatigue and muscle weakness. She vomited at 4:30 this morning, and that was the determining factor. Her blood tests showed a serum sodium level of 122, normal being 135 to 145. A sodium level below 130 is known to cause all of the above symptoms, along with swelling in the brain. She was diagnosed with hyponatremia, and was given a sodium drip. She also had a temperature of 100.3 and high blood pressure. Charlotte was due for another MRI on August 31st, so they did the MRI today to rule out any tumor growth that might be effecting her speech. Dr Nordling read the MRI as stable. I talked with him while Charlotte was having the MRI and had expressed my concerns over certain views on the last two MRIs. I was able to get his written report later that day. He always writes the best MRI reports at Kaiser, but this one seemed to address some of my concerns. I will get my own disc copy tomorrow for comparison to the previous MRIs.

In the late afternoon, we were given the option by the attending ER physician, Dr Chen, to either take Charlotte home, or to keep her in the hospital overnight with an I.V. drip. Charlotte's nephrologist, Dr Lin, even came by the ER for a visit. Charlotte was eager to come home, but my concern was that I had read the only way to raise serum sodium was through a controlled sodium I.V. drip, especially in brain patients, and not through diet. Both Dr Chen and Dr Lin assured me that a diet higher in sodium would slowly raise Charlotte's serum sodium. We still don't know whether Charlotte's fever is being caused by an infection, or why her sodium level fell from 134 to 122 in just one week. She had only occasional vomiting during her last chemo, which is one of the main culprits of sodium loss. Dr Lin wants to see her next Tuesday for more tests. Dr Chen told me earlier that Charlotte's kidneys may not be able to hold in the sodium. Next Thursday we still have a consultation in northern L.A. for possible gamma knife surgery. That is going to be a long trip in Charlotte's condition. I think I'm beginning to see early signs of cachexia, so that will have to be discussed with her doctors.

August 13, 2009
Charlotte starts her Temodar tonight. Her MRI on August 3rd came back "stable". However, I have noticed some enhancement in her June 13th MRI and some further enhancement in her August 3rd MRI. We met with Dr Spier yesterday for Charlotte's Temodar prescription, and we went over the MRIs together. She agreed with me, and gave us a referral to see Dr Chen in northern L.A. He is in the same building as Dr Pikul, who said Charlotte would be a candidate for an awake craniotomy when the time comes. Dr Chen specializes in radiosurgery using the gamma knife. We see him on Sept. 3rd, and hopefully he will say that Charlotte is a good candidate. As Dr Spier pointed out yesterday, she wants to "nip this in the bud" before it gets out of hand.

The reason Charlotte's last two MRI's have been read as stable is that the enhancement that I see is mainly in only one view (saggital post gadolinium). Dr Spier said that before the neuroradiologist says "enhancement", they usually want to see it appear in two different views (e.g. saggital, axial and/or coronal).

I also just happened to read on the brain tumor research site yesterday about another GBM patient that thought she had seen some enhancement in her March MRI, but it too was read as stable. Her latest MRI shows the tumor has spread to the other side of her brain. She said that before a neuroradiologist says "enhancement", they must see reoccurrence at "above clinical levels", which she thought was enhancement of 24% or more. Yikes!

Charlotte's enhancement might be necrosis, scar tissue, or other things besides tumor growth, or some combination of the above.

Two good links:
Video of an awake craniotomy.
Meet Batman, a mixed breed german shepard with brain cancer.

July 16, 2009
Charlotte started her Temodar tonight. There have been both good and not so good clinical symptoms over the past month. The not so good have been her intolerance to both warm weather and especially the sun. She literally has to run from the sun. The good has been her appetite, and her ability to gain some weight. The small weight gain unfortunately has not transformed itself into muscle mass. She is still losing too much protein through her kidneys for that to happen. Clinical signs for GBM patients will probably present themselves long before a MRI picks up tumor growth. I judge her clinical condition by some obvious signs, and I think last week was one of her best weeks in a long time. Donna picked up on this change quite a few weeks ahead of me. Charlotte's alertness, reading, and speech have all been good. She even did her hair differently yesterday! Her physical activity, due to her muscle loss because of her kidneys, is probably my biggest concern now.
Most of the above is a good report, but that doesn't mean Charlotte won't be in the emergency room tomorrow. Nobody knows what change tomorrow, or next week, will bring.

In the last update I talked about visiting with Dr Pikul in L.A. for an awake craniotomy. I had to write myself another note and stick it to my computer to make sure that if she does have another surgery, that Dr Pikul sends the tumor off to Duke University for molecular testing and to Woodland Hills for chemosensitivity testing. This was scary to me because I have four three inch binders full of internet printouts, and I can not even remember some of these important facts. If the tumor is discarded, a lot of valuable information is lost.

Since tumor growth is so fast, as mentioned in my last update, one should also keep an up-to-date file on all family assets. Make sure all deeds and personal property titles show the correct owner names, etc. Charlotte and I may opt for an outside clinical study trial, and unfortunately Kaiser will not pay for any outside costs. We may have to get a loan ASAP to cover the costs, and having all the paperwork in one place is very important.

A quick note to all GBM patients needing financial help. Social Security passed "a compassionate disability act" (not sure of the wording) about a year ago for those people who have qualified for Social Security, but probably will not be around to collect it because of a life ending disease. It sounds good, and I recommend that every caregiver look into this program. Unfortunately, they have some weird "compassionate" rules, along with some very rude employees, so Charlotte did not qualify. I am a firm believer in "only positive thoughts" for cancer patients, and it was quite obvious how upset Charlotte was for days after this meeting. It was a big mistake on my part for putting her through this ordeal.

Charlotte's next MRI will be on Aug 3rd. Dr Pikul will initially read the MRI, since our neuro-oncologist will be on vacation until Aug 14th.

July 9, 2009
Charlotte and I went up to northern L.A. yesterday to see Dr. Pikul, who specializes in awake craniotomies. It was just a consultation about an option that Charlotte may have when her tumor returns. The visit started with Charlotte being given some speech and eye tests. We were very impressed with Dr Pikul, and I think he was impressed with Charlotte. He was great at going over Charlotte's last two MRI's with me, and listening to my concerns of what I had seen on her last MRI. He said it was appropriate to ask for her next MRI to be a week earlier. He does want me to call him on the day of Charlotte's next MRI. That statement by him was towards the end of the visit so I didn't get an explanation. He also kept emphasizing how important it was to get Charlotte back up to him for surgery as soon as possible when there is tumor growth. He said he has seen tumors double in size in just one week.

Charlotte is now off Avastin and officially off the UCLA study trial. She is presently just on Temodar. The other "star patient" of this study was enrolled at the same time as Charlotte back in Dec 2007. Mary Oppenheimer told me a few days ago that her husband Tom is now off-study due to tumor reoccurrence. Mary and I had a long talk about Tom and what to do next. She knows about my research. I told her that after all of my research, my hopes were that I would have a "Plan A or a Plan B" when we heard the words "the tumor has returned". I told her that unfortunately I didn't have those plans, and that I would probably follow whatever our neuro oncologist suggested. That is what Mary is doing with Tom.

My research has definitely increased my knowledge about this disease, and has changed my thinking about the various ways one might try to "control" this disease. But as I told Mary, both Charlotte and Tom went on and off the study trial at the same time, so who really knows the best treatment plan.

No one really knows who will be a long term survivor.
In the end, we can only do what we think is correct for our individual situation.

June 18, 2009
Charlotte started her Temodar tonight. Her Avastin is still being held because her UPC is still greater than 2.0. The UCLA study trial will only allow someone to be off Avastin for 90 days before they are dropped from the study. June 30th will be 90 days for Charlotte. I think Charlotte has clinically improved since being off Avastin, and her nephrologist is concerned about the long term effects that Avastin is having on her kidneys, so going off Avastin at this time is not so traumatic for us. Charlotte also had an MRI on June 13th. I have questions concerning some of the images, but I don't have the written report yet. The written report could change my mind about dropping Avastin.

Charlotte, Donna and I went to the Del Mar Fair today for 4 hours. Charlotte was, in Donna's words, just "awesome". She participated in an aerobics demonstration, had her picture taken with some show dogs, watched while Donna ate a cinnamon roll, and sat with me at the flower show. Charlotte did more in 4 hours at the Fair than she has done in the past year and a half!

Charlotte's energy medicine is named "Donna". There has always been a very special relationship between them for the past 40 years, and I have really observed it's effects every Thursday since Charlotte's journey began a year and a half ago. Every Thursday begins with the "normal Donna and Charlie", but by day's end, they both have enough vitality and exuberance to make it through the following week.
They are true soulmates!

May 21, 2009
Charlotte will begin her Temodar tonight. She came down with a "flu-like" viral infection on Monday, May 11th. She had a low grade temp, nausea, and most concerning, a low grade headache that was constant for seven days that even Tylenol would not relieve. The only food that she could handle was Ensure. On the sixth day, her fever finally went away, and she was able to eat some solid food. Her headache went away a few days later.

She obviously missed her chemo last week, so she is restarting her Temodar today. Her labs yesterday showed a UPC (urine protein creatinine) ratio of 2.1, and they will not restart Avastin until it is below 2.0. Her MRI came back stable and another test was not definative on telling us whether Charlotte's residual tumor
(what we actually see on the MRI) is actually tumor or radiation necrosis. I was hoping for that information, so without it, she will probably be restarting Avastin when the trial study allows it. Charlotte and I have some deep concerns about restarting Avastin.

The echocardiogram results showed some enlargement of Charlotte's heart. Just like the proteinuria, the Avastin increased her BP to the point that it was damaging both her kidneys and heart. We do have her BP under control for now, but only due to some very powerful BP meds that have their own side effects.
Right now, it is a toss up whether I'm more worried about the tumor, or the side effects of the chemo, radiation, and all of her other meds.

Brain cancer link.
I have Charlotte enrolled in the Virtual Trials case history and treatment section.
It's a good basic site to begin your journey.

April 30, 2009
Charlotte did not have her Avastin today. Sorry for my confusing update last time. When she does resume the Avastin, it will be at the lower dosage of 5 mg/kg. The Avastin will be held until Charlotte's urine protein creatinine ratio is less than 2.

Her urine protein creatinine ratio did fall from 8 to 6.8. At least we are heading in the right direction. I'm still getting some very high BP readings, but I'm also getting some normal readings too. Charlotte had an EKG yesterday and the cardiologist said the abnormalities were probably due to her high BP. She will have an echocardiogram tomorrow.

She will also have her MRI next week. I have noticed some clinical changes in her, so the MRI is coming at a good time. Hopefully these changes are not from the tumor, and being off of Avastin, but are from her radiation treatments, BP and proteinuria problems, etc.
I have received a lot off feedback concerning my links to other GBM information.

The first one is about MRI imaging analysis of GBM patients which contained nice images. Too technical for most, but was one of the best links that I have found.
This second link is just a touching story.

April 16, 2009
Charlotte will have her Temodar tonight, but we were notified yesterday that Avastin will be held due to the level of protein in her urine. I don't know if we will be able to continue with the UCLA Avastin and Temodar study trial. I did officially ask them to lower the Avastin dosage to 5 mg/kg from 10 mg/kg. The UCLA regulatory board is evaluating my request, but I am not optimistic for their approval.

Charlotte did see a nephrologist last week. Even with changes in her BP meds, her urine protein creatinine ratio jumped from 1.7 to almost 8.0 in the past two weeks. Her renal and BP problems have made her very tired. There are other other side effects that I am not happy seeing. We saw Charlotte's neuro-oncologist, Dr. Spier, last Monday. She was great about saying "O.K." to all of my requests.

While writing this update, I just learned that UCLA did approve the 5 mg dosage of Avastin. The following are two emails I just wrote, instead of rewriting this update:-

Hello Dr. Spier,
I just sent this to Nancy.
Even though we would not lose you if we went off study, sometimes doctors are not thanked often enough by their patients. I appreciate your help during the teleconference with UCLA.
Thank you for everything!

Hi Nancy,
What a surprise about the 5 mg dose of Avastin!
I had a massive headache yesterday, plus a feeling that things were starting to slip in a direction that I did not want. I have had a love/hate relationship with Avastin for the past three months, but that really was not my fear yesterday. My biggest fear was that if we did go off study, we would lose you.
I don't think you know how much we are truly grateful for you, and the work you do for us.
Thank you,
Brent and Charlotte

April 2, 2009
Charlotte had her Avastin today. Her lab tests yesterday showed her UPC (urine protein creatinine) ratio had risen to 2.9, up from 1.7 two weeks ago. The study trial will hold the Avastin treatments when the ratio reaches 3.5, so today was probably her last Avastin for a while. I have asked to see a cardiologist and a nephrologist ASAP. I hope these specialists will have more knowledge about Avastin, and the effects it has on BP and proteinuria. Charlotte's BP is out of control, and this was an avoidable situation.

I want to thank Nancy Grossmann (R.N.) at Zion Kaiser, and her study trial staff, for all of their conscientious and professional help.

March 19, 2009
Charlotte had her 14th cycle of Avastin and Temodar today. Her UPC (urine protein creatinine) ratio has risen from about 1.1 to 1.7 in the last two weeks due to the Avastin. Her last MRI results came back "stable" again.
We had a wonderful visit with her brother Gary and his wife Lorie last weekend. The picture below shows all of us on the sofa in the gallery.
Last week my update included information on Avastin. This week it is mainly about Temodar. Again, these are random lines from random posts from random people taken during the past two weeks. I thought these would be of interest to those of you that are fighting this terrible disease. (Thank you to all the authors.)
--------------------------------------------------------------------------------------------------------------------
Something else to worry about: "Temozolomide, a standard treatment for brain cancer, may boost the aggressiveness of surviving cancer cells, making tumor recurrence more likely, a new study suggests." This study is from Memorial Sloan-Kettering Cancer Center.
Re: Temodar promotes bad stem cells? Here's the link to the full paper

"Clinically, what we see with patients with glioblastoma is that after surgery, radiation and chemotherapy with temozolomide, they live longer and a subset of them will actually live a year, two years or even longer. And then pretty much 100 percent of the patients relapse and no one knows why."
"When you treat mice with temozolomide they develop recurrent diseases even quicker, so temozolomide make the cells that survive act in a more aggressive manner." "Temozolomide actually increased the number of drug-resistant cells. Because temozolomide doesn't target ABCG2, it may render surviving cells more resistant to treatments that do target the ABCG2 protein."

A paper presented at the last ASCO conference (google: asco 2008 Quant) concluded that once Avastin has failed that there is little benefit in trying other agents in combination with Avastin...

I also don't know if cediranib has been tried after Avastin but, personally, I think that's a reasonable idea, since it's an anti-angiogenic with a somewhat different mechanism than Avastin. I think that combining cediranib with lomustine (CCNU) also makes sense, since CCNU is a cytotoxic agent, although the toxicity always needs to be considered. "A safe bet: cediranib will be most effective with CCNU."

It's been a busy month for news already! In tomorrow's issue of the JCO (Journal of Clinical Oncology), an update on a study I've been following for 3 years will appear with very encouraging results. The regimen is essentially standard GBM therapy with an added dose of CCNU (lomustine) once a month. The results compared to standard therapy are remarkable. The new update in tomorrow's JCO. Moreover, I think this regimen could be a top choice for any newly diagnosed grade IV patient who does not get into a Novocure or vaccine trial, especially those outside the U.S. with a methylated MGMT promoter gene.

As another TMZ option for recurrent GBM, go to p863 at link to download Strik et al's full paper. One recent study that produced data re diffuse recurrence was Naranya et al.

Conclusions: Antiangiogenic therapy using bevacizumab appears to improve survival in patients with recurrent high-grade glioma. A possible change in the invasiveness of the tumor following therapy is worrisome and must be closely monitored.

This may be a rather simplistic explanation but here goes: my husband has no progression around the original tumor area. Instead he has what has been termed a delicate invasive spread of the tumor cells in a quite large area- they barely even show on the MRI. These cells do not depend on making blood vessels the way that the GBMs usually do. Instead these cells live off of pre-existing blood vessels. They have taken different pathways that the Avastin is not blocking as they have mutated or learned to escape the stronghold that Avastin used to starve them. I don't think the Avastin "drives" the invasiveness. It's just what happens as the tumor cells find their way around the Avastin.

There are a number of angiogenesis compounds that can be secreted by cells when under distress due to shortage of oxygen and nutrients. Avastin targets only one of them: VEGF-A. My understanding is that if the cell is not 'satisfied' with the results of emitting VEGF-A, then nature has programmed the cell to begin to release other angiogenesis agents (I think there may be as many as 10 that have been identified). These other 'second-line' signaling agents may be giving the tumor a different growth pattern.

I agree that Avastin is very scary, but when faced with inoperable tumors, and if failure on TMZ happens, other than vaccine trials what options are out there?

"A new 600-page book entitled "Integrative Oncology" just came out, and I highly recommend it:"

March 5, 2009
Charlotte had her Avastin today. On Tuesday, her teeth were cleaned by her friend Grace Hansen. The picture below shows the two of them before the cleaning.

I would like to thank our friend Leena Hannonen for updating our website. She is presenting a series of mosaic workshops in Julian. Please visit her website. You can see all of the information at artelitedesigns.com

Charlotte's labs continue to show the effects of the Avastin on her body. There has been mention of Avastin (bevacizumab) on some of the brain tumor sites with some linked studies. Below are just random lines from random posts from random people during the past week. This is obviously not my usual update, but I thought this change was important. (Thank you to all the authors.)
................................................................................................................................................
We tried several other options but avastin was the only thing that was successful - even if only for 6 months. It gave him a chance to spend quality time with our children and grandchildren and to celebrate one more
Christmas.

So my bottom line is that I hope patients still consider using Avastin, but keep the emerging pitfalls in mind, and explore dosing schedules, combination therapies, and potential prophylactic treatments which maximize
the benefits while limiting the side-effects.

He likes to remind patients that "everything works in mice, but you are a human".

He is hugely full of hope, and truly believes we face chronic diseases, not terminal ones, and treats accordingly.

I don't think the article should be viewed as a universal condemnation of such therapies or Avastin in particular.

Patients should recognize both the known strengths and weaknesses of Avastin at the time of decision-making and avoid blanket statements which limit their options.

One of the general principles of cancer biology is that if one growth path is blocked, the cancer will try to find another path. In the specific situation of Avastin failing, we're in uncharted territory. However, given cancer biology, I would suggest going after 2 or more other growth factors, using something like Tarceva or a new multi kinase inhibitor. This is just a guess, however, in an area we clearly need suggestions!

This kind of aggressive treatment strategy may best be obtained from Duke, in keeping with what I understand is their reputation. You now need to move beyond using NIH as consultant.

The tumor is like a diffuse cloud.

Diffuse tumors tend to co-opt existing vessels rather than spawn new ones. That could be how the tumor is surviving - Avastin won't kill off normal existing vessels. Has anyone on these lists been able to effectively control their tumor once it has escaped the Avastin stronghold? If so how long has it been and what
have you used?

My son is in the same spot--he has failed Avastin. The tumor is spreading diffusely around, affecting his sight and speech. He is in a bad spot.

This news release in Science Daily addresses "angiogenesis inhibitors— succeeds at first, but then promotes more invasive cancer growth". Nothing new, for those of us who have been tracking the bevacizumab
story.

Has anyone on these lists been able to effectively control their tumor once it has escaped the Avastin stronghold? If so how long has it been and what have you used?
High vascularization of glioblastoma typically predicts poor prognosis.
Neovascularization (vasculogenesis and angiogenesis) is essential for tumor growth and invasion.
Vascular endothelial growth factor (VEGF) is a critical proangiogenic factor in almost all solid tumors. However, its expression and role in human carcinoid development and progression remain unclear.

The sometimes controversial cancer drug Avastin can cause kidney damage by doing what it's supposed to — but in the wrong place, a study shows. Edema is generally associated with tumor progression. Avastin has a half-life of about 20 days, and CPT-11 is less than a day, so if it's been longer than 20 days, your husband is officially off treatment.

These data indicate that stem cell-like tumor cells can be a crucial source of key angiogenic factors in cancers and that targeting pro-angiogenic factors from stem cell-like tumor populations may be critical for patient therapy. My understanding is that the cancer stem cell hypothesis is still under investigation and debate.

How bad is that? Well his tumor suddenly looks like a diffuse ghost spreading up through the frontal lobe and also crossing over a little into the other side of his brain. It's amazing that his scans were absolutely clean last time and now it's sort of everywhere. If it helps, Barbara, mine is in, and crossed the corpus, and is slightly into the right side, all that area is diffuse (not the lump seen elsewhere)

Are they absolutely sure that it is tumor? I assume that the changes that they are seeing on the MRI are on the T2 FLAIR images. But T2 FLAIR enhancement can also be from radiation/treatment related effect too. It can sometimes be very difficult to distinguish between the two on MRI images alone. If they are seeing mass effect, then tumor is likely.

He has been on avastin/temodar treatment and suddenly developed extensive FLAIR enhancement surrounding the right frontal tumor cavity, crossing the corpus callosum to the other side. It was very scary looking on the scan. The differential diagnosis at that time was radiation related change versus infiltrating tumor. He had no
symptoms. There was also no mass effect on the MRI. We went for a Dopamine PET scan at UCLA which was cold, so it was decided that the changes were not tumor after all.

The use of various contrast agents in MR imaging is becoming a challenging field of neuroradiology research. Iron oxide nanoparticles shorten T1 and T2 relaxation times, so they can be used in MR imaging of malignant brain tumors...

You have been quite an inspiration to all of us. May God be with you and my prayers are there for your fast and successful recovery.

Just because it is back again, does not mean it's going to win!!! The GBM has already tried to get me in 2000, 2004, and 2007 and never got the best of me! Now in 2009 I am going to beat the battle again. I'm ready for the
challenge.

Yes, blood glucose levels do make a big difference, both in prevention and treatment of most cancers (if not all). This is why so many researchers are interested in ketogenic diets, the IDH1/IDH2 genes, and other aspects of glucose metabolism.

I am so sad to read this - yet another challenge for you all to face. Diffuse tumors are so hard to measure. Maybe this can explain some of the clinical symptoms he has been having.

Also, here's a paper on aerobic glycolysis...

How to get the wacky stem cells under control!

O.K., I exhausted everything you have up that I hadn't already read.

Here's a decent article in Newsweek which I just stumbled across. It overviews cancer research, and largely echoes the findings of a previous article in Fortune by Clifton Leaf. www.newsweek.com

Here's a mini-lesson in chemo drug metabolizing. You can generally look up the metabolism of any drug by Googling the drug's scientific name and the words "metabolism" or "pharmacokinetics."
....All of these potentially cause drug interactions through interference with a key metabolizing enzyme called CYP3A4, part of the main family of metabolizing enzymes called cytochrome P450 (abbreviated "CYP").
.....Temozolomide (TMZ) is a prodrug, meaning that it is inactive by itself and only takes on its therapeutic qualities when it is metabolized. TMZ is hydrolyzed at physiologic pH to the active compound, MTIC,
without the aid of metabolizing enzymes. TMZ is essentially 100% bioavailable.

You might create some sample (food) menus of what a high grade brain tumor (patient) might take.

If metronomic TMZ has failed at 50 mg/m2, I'd be reluctant to try it at 75 mg/m2 because you would add toxicity and might not add to efficacy, though I could certainly be wrong.

Unlike P53 or PTEN mutations, IDH mutations only cause glioma but not any other cancers. Why it is so specific is with no doubt under intense investigation in academics. For us as patients, I care about how to make use of the findings in my treatment.... My first thought was IF (a big if) the loss-of-function mutation causes accumulation of isocitrate and a deficiency of alpha-ketoglutarate, and IF (another big if) alpha-ketoglutarate-deficiency indeed drives tumor progression, supplementing glioma patients with alpha-ketoglutarate may do the trick. This sounds like a crazy idea. It can not be this simple, can it?

Fatigue and balance issues are common in GBM for many reasons ranging from chemo to radiation to seizure medications to tumor progression. It's very difficult to pinpoint the cause.

I'm glad we have an international group here!

Malignant gliomas are highly lethal cancers that depend on angiogenesis for malignant progression

The base of pneumocytis pneumonia is a yeast, in the candida family. Steroids and antibiotic and temodar all can aide and abet this fungus. Candida in many forms is a HUGE issue for cancer patients, especially with meds and treatments and steroids.

I also recommend checking out the lively panel discussion on molecular oncology which can be found here.

Ultimately, your doctor is not responsible for your treatment and health. You are. Nobody is going to care more, or have a bigger vested interest in your survival, than you. And sometimes that means you have to think outside the box, and seek out evidence-based treatments on your own.

Thank God you guys are dedicated toward fighting this monster!

The following article explains the Avastin kidney damage (proteinuria) issue.

I just got my last MRI at UCSF last Friday. At that time I was told "It all looks good -the same and clear, no seen tumor". I drove home happy. Today I got a phone call from my Neuro-oncologist at UCSF.....

With Peace, Love and Hope...
God Bless...
Tons of love to you...
Wishing you strength....

February 19, 2009
Charlotte had her Avastin and will start her Temodar tonight. Lab tests show that her white blood cell count remains low, and Avastin is still making her kidneys produce protein in her urine. Another side effect of the Avastin is to cause her to have hypertension. Her blood pressure seems to have stabilized over the past few weeks, so we have not had to immediately go back on a third B.P. medication. Her sodium and chloride are still a tad below normal since she was discharged from the hospital.

We have had some inclement weather during the past two weeks, so instead of going for walks, she has been going up and down our back stairs. It is definitely more of an aerobic exercise than walking, and works a different set of muscles in her legs. It works her heart a lot more than just walking, which I like.

For the past couple of weeks, she just seems more tired than usual. Plus I think she has lost another four pounds, which does not make me happy. But I know her drugs are cytotoxic, and are influencing the tone of her muscles.

There are a lot of the doctors and nurses out with the flu, so I am trying to protect Charlotte from getting sick. She was out with me this past weekend trying to get fallen trees cut up. Over my objections, she told me that we have always worked together as a team, and this was no different. I finally convinced her to throw the ball for the dogs, in between supervising me.

February 5, 2009
Charlotte had her Avastin today and then we had our usual "get together" lunch with Donna and friends.
Charlotte's lab yesterday showed that her blood sodium level was still slightly low and her potassium level slightly high. These electrolyte levels are about the same since she was released from the hospital about ten days ago. Her neuro-oncologist pointed out that giving Charlotte "salt tablets", which she has been given in the past, could be dangerous. Raising the sodium level too fast in a brain patient could do more harm than good. I filed that away somewhere in my head because Charlotte has different doctors that prescribe medications for her different conditions. Comments and statements either get a little red flag (meaning I do not totally agree) next to them in my head, or a check mark (meaning it could be good upon further research). A little red flag went up about two weeks before Charlotte was admitted to the hospital on Jan 18th, and I blame myself for not looking into matters further.

The attending physician in the ER did make a comment about Charlotte's nausea and vomiting during her chemotherapy, and her statement received a little check mark. After confirming her statement, I decided to give it a try. Charlotte started her twelfth Temodar and Avastin cycle on January 22nd. It was the first time in a year that she did not have any chemo related nausea and vomiting. That allowed us to walk, work, etc., during this normally bad time of the month. We will see if next month produces the same results.

Looking back over the past year, there were two major things that made me feel so helpless. One was the sound of her vomiting during chemotherapy. That is why the above paragragh is such good news for us. The other was when I had to inject her with Neupogen to stimulate her bone marrow. The shots were given for three consecutive days, and she had to have them twice during the past year. The big side effect of the shots was to make her bones very achy. Waking up in the middle of the night hearing your wife moan and cry just to turn over in bed is something I will never forget.

On a happier note, Charlotte has expressed interest in writing a book about her brain tumor journey. She feels she has a lot to offer to her fellow comrades, especially with breast and brain cancer. I do not know the logistics of doing something like this, but I do think it would be a truly remarkable book.
I vividly remember going out and buying Dr. Susan Love's "Breast Cancer Book" with Charlotte right after her breast cancer diagnosis in 2001. We took turns reading it aloud to each other while trying to determine the best course of action.
Today, the type of cancer is obviously different, but the techniques remain the same for me. Learn as much about this disease as possible. Unfortunately, there is not one definitive book like Dr. Love's that we can go buy on brain cancer. Thank goodness for all the scientific sites like PubMed on the internet. There are a lot of things that I have learned that I wish I would have known a year ago, and those would be my contribution to Charlotte's book. Treatments are always changing, but one must know where to go to at least begin. I did not even know this in the beginning. I would like to pass this knowledge on to others.

I truly believe that with a glioblastome multiforme brain tumor, you only get one window of time to control this type of cancer. Obviously my job, along with others, is to learn how to keep that window open.

January 22, 2009
Charlotte started her Avastin and Temodar today.
Charlotte had a low grade nausea for most of last week and was accompanied by some vomiting as the week progressed. Charlotte's blood pressure also increased dramatically Friday night, and then her brain temporarily misfired. She had a somewhat similar condition right after brain surgery while staying in the hospital in December 2007. I asked her my name, her date of birth, and the names of our dogs. She could not say them, but unlike a year ago, she knew that she was unable to speak the correct words. She kept saying, "What is wrong with me, why won't the words come out?" She became very frightened. This "word to mouth" pathway has become noticeably more difficult for her. Realizing this, and knowing that I thought she did know all the names but just could not say them, I gave her a pen and paper on which to write. She proceeded to write the correct answers to all of my questions. I told her not to worry, it is just a matter of some physical therapy to retrain certain pathways in her brain. I do not know what caused this incident, but the positive is that she kept communicating to me that she knew what was happening to her. A wonderful book given to me by Mary is "My Stroke Of Insight" by Dr Jill Bolte Taylor: A Brain Scientist's Personal Journey. Charlotte's episode could have been an addendum to her book.

Then on Sunday morning she awoke with a headache, which meant an immediate trip to the emergency room at Kaiser. She was diagnosed with having a very low sodium level due to her vomiting and to a diuretic that she had recently been prescribed for both her BP and her kidneys. She was also diagnosed with a bladder infection. Charlotte was hospitalized after our ER visit, and on Monday she had a brain MRI to rule out any tumor growth or edema. Her MRI came back stable, so she was discharged late Monday, which helped us keep her next appointment at 8:30am on Tuesday with her neuro-oncologist. We also had an appointment today after the Avastin with her primary care physician to evaluate her blood pressure and her proteinuria, but was cancelled by his office early this morning. It will be rescheduled when he returns to his office.

Yesterday, after going to the lab for more tests and then off to pick up a copy of her latest MRI, she was able to put the finishing touches on a sculpture, dance with me in the kitchen to a Billy Joel song, and hug and kiss me about eighteen times.

What a beautiful and inspirational woman!
I am the luckiest man in the world....and I know it.

January 8, 2009
Charlotte had her Avastin today. Yesterday's lab work showed she had an increased level of protein in her urine. That is the third weekly lab that showed an increase. Right now we are just watching the level and hoping it does not get worse. Proteinuria describes a condition in which urine contains an abnormal amount of protien. Avastin can cause proteinuria, which can progress into kidney failure. Proteinuria has been associated with cardiovascular disease. High blood pressure can also cause proteinuria. Avastin also contributes to her high blood pressure.

It seems like it is a vicious circle, trying to control the tumor while still keeping the rest of her body healthy.
I remember reading some articles written by professional caregivers. The gist was more patients eventually succumbed to the side effects of their treatments than from their cancer. I do not know if that is true, but I still try to remember that everyday. It is so easy to live from one "stable" MRI to the next, and to forget about the rest of the body.

We are back walking twice a day, which is so important to her overall health. The rainy weather had reduced the number of walks for a period of time. I think her stamina is as good as it has ever been during the past year. Most importantly, she looks and feels great. Her ability to find the correct word when she speaks remains her biggest problem.

The wonderful pleaure she has is to wish her sister Donna a very, very
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!Happy Birthday!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

December 26, 2008
Charlotte's MRI on Dec. 15th came back "stable". She started her Avastin and Temodar today.
This has been one of the hardest months for her after her last Avastin and Temodar. She started with more nausea and vomiting, and her "chemo fog" has been with her for most of the time. Problems with her short term memory and her ability to find the correct words when speaking, seemed to have all slightly increased. All of this does not worry me at this time. We actually start laughing at her new language. She usually knows her wording is incorrect before I realize it. We will see how she does this coming month. I have read about patients receiving "stable" MRIs but also have clinical deterioration while on Avastin. That is something that would concern me, but her overall appearance and actions are still very good. Plus she can still play her flute and read out loud perfectly. Her artwork is getting more exquisite!

Last week I received a copy of all of Charlotte's MRIs on a disk. There were a total of ten MRIs dating back to November 26, 2007. I am trying to compare all of the MRIs to each other, and then compare each MRI to each written report. I have found a few good sites on the internet concerning how to interpret MRIs of GBM patients. My first big learning experience has come from comparing each of Charlotte's MRIs. I do not know the meaning of what appears on the MRI, but I can say that her brain has not been static during the past year. I asked a doctor if some of these "white wispy clouds" (axial T-2 FLAIR) meant more tumor, ischemic problems, brain softening, edema, or effects of treatments. This is something that I will try and learn myself, or through my long list of contacts.

I would like to thank Dr. Lai and Dr. Cloughesy at UCLA, and Dr. Polikoff, Dr. Spier, Dr. Silbert and Dr. Nordling at Kaiser in San Diego. I especially want to thank my brain researcher friends "Hong" and John Williams for helping me interpret some of Charlotte's tests. John, your wealth of knowledge is truly over-whelming, and your kindness in sharing is enormously appreciated. Your understanding and awareness of seemingly every GBM scientific abstract, both in vivo and in vitro, and the time that you must spend doing this research and then answering your emails from people like me, is just astonishing!
Finally, thank you Nancy Grossmann(RN) and your staff at Kaiser.

December 11, 2008
Charlotte had her Avastin this afternoon. The past two weeks have been very busy and sometimes confusing for us. First, we had Charlotte's teeth cleaned by our very dear friend, Grace Hanson. She reminds me so much of Charlotte. She is very competent, intelligent, and has that certain beauty both inside and out.
Charlotte's Avastin and Temodar just seemed to be a lot harder on her this month.
That has also been reflected in some of her blood counts. Some months seem overly good, such that I can not really trust them, and then some months they drop to a new low. Her blood pressure was extremely high again this morning. That has always been a constant battle.

Our philosophy, from both our personal experience and the experiences of others, is that you just have to take one day at a time. And as a caregiver, you must be aware conditions can change very fast. I am still haunted by the line from a friend's email that stated "I wish I would have done more for him". That is something that I never want to feel. Charlotte is on a cancer diet that may or may not be effective, and that is also why I had her teeth cleaned. Sadly these were never discussed in the beginning. But eating right, and trying to stop secondary infections from entering her body through her gums just seems to be the correct decision for us.
I still spend hours reading as many scientific abstracts that my mind can "comprehend" each day and night. Actually, when I first started one year ago, it was like reading a foreign language. I spent more time looking up and then writing down the definitions of these words. About two months ago, I sort of had an epiphany. I realized things were sort of making sense to me for the first time.

Emphasize "sort of"! I now have a new respect for all medical professionals and researchers, and all of their training. They are also in a field that brings forth new knowledge everyday. I personally can not understand how one individual can be fully informed in each of their specialties.

I want to mention that Charlotte had heart palpitations and vomiting last Sunday at 3AM. She had an EKG on Wednesday, but we have not received the results. Charlotte's next MRI is scheduled for Monday, December 15th. Those following five days are becoming more and more stressful for me. It usually takes about a week to get the results if the tumor is stable. But our neuro-oncologist will personally call us during those days if new growth should appear. I know the facts, and know our chances of avoiding that phone call lessen with time.
Charlotte's next Avastin and Temador will start December 26th.

We want to wish everyone a Merry Christmas, and a "thank you" for your love and prayers during the past year. Everyone has been so kind and generous that I do not know where to begin. I will not even try, except to say that I know that each and everyone of you have helped Charlotte fight her battle. And for that, I am truly humble.
Merry Christmas. Be well everyone. Love, Charlotte and Brent

November 30th, 2008
Charlotte had her Avastin on Friday, and we started her Temodar that night. She was suffering from a bad headache that was brought on by the Avastin for all of Friday. She told me late Friday that she felt that it would probably be best if we did not go up to Julian. For her to say that seemed very unusual to me. As I mentioned in the last update, it was one year ago at the Julian Christmas Tree lighting ceremony that she read some poetry. That is when we knew something was wrong. On Saturday morning she felt better, and decided that she wanted everyone to see and hear her reading poetry again.

She did a beautiful and inspiring reading of three poems on Saturday night! Unfortunately we had to return to San Diego early Sunday due to the side effects of the Temodar. We want to thank the wonderful Julian Library for inviting her to participate again.

Also, a very special "thank you" to Leena Hannonen of ArtElite (www.artelitedesigns.com) for designing our website and for posting our updates over the past year. Her expertise and friendship has made this past year endlessly more helpful and comforting for Charlotte and me. Thank you Leena for your many hours of work that you have generously given to us.
From Leena: It's been my plasure to be able to do this for you and I treasure your friendship.

November 18, 2008
Charlotte had her Avastin last Thursday, and will have her next Avastin and Temodar on Friday, November 28th, the day after Thanksgiving. Hopefully she will be able to attend the Julian Christmas Tree lighting ceremony the day afterwards, on Saturday November 29th. It will mark her "one year anniversary". It was at last year's tree lighting that she also read some poetry, and she started to have slurred speech. The next day she was diagnosed at Kaiser as having a brain tumor.

The attached five photos are a record of our progress over the past year. Obviously the first photo was taken before her diagnoses. The following photos show her at different times as she progressed during the year, ending with a photo that was taken just a few weeks ago. It's been quite a journey. One cancer researcher that comes to the gallery told me that many cancer patients have to reach their nadir before they seemingly get better. I would like to look at the pictures with that in mind. But, then days like yesterday happen. Charlotte woke up with a severe headache and was vomiting. That was very unusual. Always thinking of the worst first, I thought of possible bleeding in the brain from the Avastin. After watching her closely, and talking with her during the day, it turned out to be just another bump in the road that we've come to live with in the past year.
I've been busy trying to learn as much as possible about Glioblastoma Multiforme. Currently, I've been reading Charlotte's MRI reports from the past year and trying to educate myself on the terminology in the reports. Her latest MRI show that she has "chronic ischemic (inadequate supply of blood) small vessel disease" and a "contrast enhancing mass associated with postoperative encephalomalacia (softening of brain tissue by vascular changes). Then there is the residual tumor with "slight rim enhancement".



Every night I read more scientific abstracts on numerous GBM topics. It is over whelming, and sometimes quite discouraging, but I've always believed that knowledge is power. There is a whole world of information out there, from cancer diet to cancer therapies, that caregivers must research and learn.
One example is Ben Williams (teaches at UCSD) who was diagnosed with glioblastoma in 1995. The following is from his website.

“Treatment for GBMs and other high-grade gliomas is changing rapidly. Until the last five years there was a standard treatment in the USA , including surgery, radiation, and chemotherapy with a nitrosourea, either BCNU alone or CCNU combined with procarbazine and vincristine (known as the PCV combination). While this treatment has worked for a small minority of people, its 5-year survival rate has been only 2-5%. Alternatives to this traditional treatment regimen are imperative if GBM patients are to have any realistic hope of surviving their disease. Fortunately, new treatments are now being introduced at a rapid rate. But unfortunately, most still are not available outside of clinical trials and there is no consensus about what is the best treatment for this deadly disease.

"There are two general premises to the approach to treatment that will be described. The first of these is borrowed from the treatment approach that has evolved in the treatment of AIDS. Both HIV and cancer involve biological entities that mutate at high rates. This implies that unless a treatment is immediately effective the dynamics of evolution will create new forms that are resistant to whatever the treatment may be. However, if several different treatments are used simultaneously (instead of sequentially, which is typically the case), any given mutation has a much smaller chance of being successful.

"A second general principle is that any successful treatment will need to be systemic in nature because it is impossible to identify all of the extensions of the tumor into normal tissue. Moreover, cancer cells are typically evident in locations in the brain distant from the main tumor, indicating that metastases within the brain can occur, although the great majority of tumor recurrences are within or proximal to the original tumor site. Localized treatments such as radiosurgery may be beneficial in terms of buying time, but they are unlikely to provide a cure. Even if the localized treatment eradicates 99.9% of the tumor, the small amount of residual tumor will expand geometrically and soon will cause significant clinical problems.

"Until recently, the only systemic treatment available has been chemotherapy, which historically has been ineffective except for a small percentage of patients. An important issue, therefore, is whether chemotherapy can be made to work substantially better than it typically does. Also becoming available are new systemic treatments that are much less toxic than traditional chemotherapy. The availability of these treatments raises the possibility that some combination of these new agents can be packaged that is substantially less toxic and yet provides effective treatment based on several different independent principles. Thus, the AIDS-type of combination approach is now a genuine possibility whereas it would not have been ten years ago. Because oncologists have been slow to appreciate the significance of the increased availability of these relatively nontoxic treatments, patients learn about them piecemeal if at all. Thus, patients themselves need to become familiar with these new agents and the evidence available regarding their clinical effectiveness. It is possible, although by no means proven, that some combination of these new agents offers the best possibility for survival.

"Patients may or may not learn about the treatments that will be described from their physicians. To appreciate why this may be, it is important to understand how American medicine has been institutionalized. For most medical problems there is an accepted standard of what is the best available treatment. Ideally this is based on phase III clinical trials. Treatments that have been studied only in nonrandomized phase II trials will rarely be offered as a treatment option, even if the accepted "best available treatment" is generally ineffective. What happens instead is that patients are encouraged to participate in clinical trials. The problem with this approach is that most medical centers offer few options for an individual patient. Thus, even though a given trial for a new treatment may seem very promising, patients can participate only if that trial is offered by their medical facility. An even more serious problem is that clinical trials with new treatment agents almost always study that agent in isolation, usually with patients with recurrent tumors who have the worst prognoses. For newly diagnosed patients this is at best a last resort. What is needed instead is access to the most promising new treatments, in the optimum combinations, at the time of initial diagnosis.

"Physicians rarely will inform a patient about clinical trials being conducted elsewhere. Moreover, the idea that several different agents from separate phase II clinical trials might be combined will be met with great resistance. Patients themselves will therefore need to become informed about what options are available, and which kinds of combinations seem most promising. In addition to the information that will be presented here, other information, especially about which new clinical trials are available, are available elsewhere on this website (address: www.virtualtrials.com ).”

October 30, 2008
Charlotte had her Avastin this morning and will start her Temodar tonight. We will be trying to attend our "Julian Open Studio and Gallery Tour" at our gallery this weekend. Hopefully the nausea caused by the Temodar will be kinder to her this weekend so that she can enjoy her friends. Charlotte right now has a slight headache from the Avastin, but is in very good spirits. We actually have a few people to thank for that.

First, her sister Donna, for always being there at the Avastin treatments, and then bringing laughs and smiles to our faces during lunch. Lunch was at Tio Leo's again today, and thank you again Pete for making it so enjoyable.

And a very special thanks again to Nancy Grossmann, R.N., at Kaiser Permanente for putting up with my never ending questions while Charlotte is getting her Avastin. I can not say enough about how much she means to us.

Another thank you to Dr. Iris Lowe for doing her chiropractic work so that Charlotte is able to continue to walk, and even work, without her being in pain. Walking is so important for patients that are on Avastin to avoid blood clots. One gallery Charlotte wants to visit again is Gallery 21 in Spanish Village in Balboa Park. First, she has so many friends in Spanish Village that she would love to visit again. Dr. Lowe is also currently in a show "Friends of the Chinese Brush" now at Gallery 21 (October 30 -November 17) from 11-4pm . Unfortunately we will not be able to attend the reception this Sunday (4-6pm). But seeing the show and all of her friends in Spanish Village will fit nicely into one of our "walking routines".

Finally, the news about Charlotte's last brain MRI was that her tumor is "stable".

October 20, 2008
Charlotte had her Avastin last Thursday (Oct.16th). We had another appointment with Charlotte's chiropractor, Dr. Iris Lowe, that same evening to help Charlotte with some hip, shoulder and neck problems. Dr. Lowe felt Charlotte's upper vertebra were starting to fuse together, which kept her from walking in an upright position. She came out of there looking, and most importantly, feeling like a new woman.

Charlotte and I worked together at the gallery over the weekend because Mary had a beautiful wedding to put on for a dear friend. It was good to see Charlotte interact with all of the customers, and then find time to work on a small sculpture. Charlotte had a 7am appointment at Kaiser on Monday (Oct, 20th) for her bimonthly MRI. I think there have been some policy changes at Kaiser because now they make you wait about a week for the "official" MRI report if everything is stable. They do a cursory look within 24-48 hours to see if something abnormal appears, and will let you know. But for some reason, as we were leaving because our 20 minutes were up with our neuro-oncologist, I believe she happened to mention that she no longer reads the MRI ahead of time. It's too bad because I think she is, in my opinion, the most qualified to read the MRI. She has seen things that the regular neuro-radiologist has not seen. We fully trust and respect her. I get the feeling that Kaiser is starting to demand some policy changes from their doctors that are not necessarily in the patient's best interest, but I could be wrong. Anyway, I guess we are now in the routine of "no news is good news" for the week. Which, for a proactive husband with a wife with brain cancer, is troubling. I receive emails from other patients and they asked me about this new delay in finding out about their MRI. I told them just what I said above, but that I didn't question it during the visit. I know the clock is running during our appointment, so I told them that I always prioritize my questions before entering.

I must mention, the one true angel since day one, when no other doctors or nurses were around to respond to my urgent emails, etc., is Nancy Grossmann, RN, at Kaiser (Zion). She is the liaison nurse between the study trials and the patients in oncology. She has always returned my phone calls or emails, and helped us in so many ways. Kaiser, give her a pay raise, but don't give her any vacation time! I panic when I know she is not there!

My main job for the last three months has been trying to weigh our options for when Charlotte's tumor returns. As previously mentioned, usually the tumor comes back with a vengeance, and is usually no longer responsive to chemo drugs. Also the Avastin may cloak the tumor so that the MRI looks great, but the clinical condition of the patient declines. Avastin may also make the tumor come back in a more diffuse pattern, so surgery may not be an option. These are just a few of the things that have come out concerning Avastin. I think for Charlotte her best option would try to get into a vaccine trial at UCLA. I've emailed Dr Linda Liau who is charge of the program. The big restriction (besides the cost) is that Dr Liau would need to do another resection on Charlotte for a fresh tumor sample in order to make the vaccine. Due to UCLA's policy and regulations, this surgery can only be done at UCLA, not Kaiser. Our neuro-oncologist thought that the trial could cost us $100,000. Another option for us would be If Charlotte's tumor comes back as an operable mass that could be resected at Kaiser, I could then send the tissue sample to the Weisenthal Cancer Group in Huntington Beach for tumor cell profiling. They would test Charlotte's cancer cells against 20-30 chemo drugs (and combinations) to see which might be most effective. But again that's chemo, and after Avastin, chemo may not be effective. Plus, I've seen it first hand, the body can take only so much chemo. I think the vaccine would be a lot easier for her. Another limiting factor for Charlotte is that most trials want newly diagnosed GBM patients. Charlotte will now be classified as a patient with a recurrent GBM. That limits my options for finding a trial study even further. I don't even know if Charlotte would qualify for the above vaccine trial. There are so many limiting factors to consider (trial cost, trial location, Charlotte's health at the time of reoccurrence, etc.). I just hope Kaiser will give me answers to my questions in a timely manner so that I can further decide what options are actually viable for us.



Charlotte working on "Hope"

October 2, 2008
Charlotte had her Avastin and Temodar today. She had to have a special blood pressure medication (Clonidine) just before the Avastin because her blood pressure was too high. Generally, this has been a month with problems for her, but yesterday she looked magnificent to me. Her normal blood pressure medicine has been increased, and a new blood pressure medicine has been added. She seemed to have her "chemo fog " for all of the month instead of just a week following the Temodar. Her speech and memory have just slightly regressed. But she reads her Mary Oliver, Sarah Teasdale and Walt Whitman poetry out loud every night, along with playing her flute. To me, all of these are inspiring and well done. And of course her sculptures are exquisite. I even had her help me with some Internal Revenue Service forms and some California State Board of Equalization forms. It was sort of a test, since the "math" side of her brain was where most of the GBM (glioblastoma multiforme) was located. She still managed to do a good job.

I have learned you can not just ask her questions in order to find out exactly how she is doing. Some things are obvious, but usually I have to be more intuitive. I remember when she came out of surgery at Kaiser Permanente, the nurse was testing her and asked her who the President of the United States was. She couldn't say "President Bush", but she answered that she could draw his face for the nurse. Today, if she met either Senator Obama or Senator McCain, she would shake their hands, complement them both equally, and tell them each to have a wonderful day. She does that to everyone now. I think that is what aggressive cancer brings out in the truly special people of this world. She has this very strong belief that every person is precious, and needs to be acknowledged. She has always felt this way, but these feelings seem to grow in intensity with each passing day.


Charlotte working on a sculpture last week.

See the archives here.

Please come back to this page for updates on Charlotte's new journey.

Charlotte Mitchell - Poetry In Glass

The love of words inspires artist Charlotte Mitchell to create sculptures mostly out of her favorite material - glass; a wonderfully, colorful medium. However, she augments glass with many other materials such as new ceramics and metal and precious, recycled fire fragments; filling the creations with strength and beauty - inside and out.

Charlotte loves poetry, which has caused her to create her art. She has created beautiful works based on the imagery which fills her mind when reading poetry, song lyrics or other words-well-done. Her inspirations may take her to another part of the world or another time in history. One of the first poems that inspired such works was the last line of "The Summer Day" by Mary Oliver, an unfamiliar poet’s work which Charlotte found taped near the front of a friend’s computer —"Tell me, what do you plan to do with your one wild and precious life..." The imagery of Mary Oliver’s poetry has sent Charlotte’s mind to the forests of Massachusetts, and has lead her straight to Tibet. Mary Oliver is now one of Charlotte’s favorite poets. Walt Whitman’s powerful words has led Charlotte onto the Sea, or onto the Grass. Many sculptures are related to old-time hymn lyrics such as "Amazing Grace", or "old-seeming" lyrics by Sting - "Fields of Gold". All of these go directly to the hearts of people who enjoy beauty or who can regain joy from visions of both the words and sculptures.

One of the largest pieces is called "Something There Is" from Robert Frost’s "Mending Wall". Fire-flashed glass, metal, ceramic faces , and recycled oddments frame a seven-foot wall which wants to crack open as the glass swirls up and out the top of the wall. Built after the 2003 Cedar Fire, this piece has made a tremendous impact on viewers.

Charlotte Mitchell finds the showing of her artwork at the Julian Library both a honor and a privilege. She hopes to show what words and art can do to our lives.

See the archives here.

Visit The Mitchell Studio Gallery
4336 Highway 78 (at Wynola Rd), Julian, CA
760-765-1102
Hours will depend on her health, so please call ahead.

It is a bright yellow 110 year-old building
with lots of flare, love, and grace!
Enjoy!
See more photos from the gallery here.