Brody Had A Very Rough Weekend But is Doing Better Now

Brody was admitted to the hospital on Thursday last week for chemo.  He felt okay during the chemo administration and for the first night.  He did not have to vomit even once that day or night.  This was a relief since in the past when he has gotten IV cyclophosphamide, it most certainly involved a lot of vomiting.  He did have significant diarrhea and was running to the bathroom about every 15 mins for several hours Thursday night.  He did not let this upset him though.  He remained in good spirits through it. 

Friday afternoon, Brody started having pain from a whole new problem.  His groin and legs were extremely swollen with excess fluid.  It was very painful and uncomfortable for Brody.  He was admitted on Friday night due to the fluid overload.  Brody had to receive a lot of fluids with the IV cyclophosphamide because this medication can sometimes cause bleeding of the bladder otherwise.  Unfortunately, Brody was not able to handle this much fluid very well.  He seems to have developed nerve damage in his bladder and now may have neurogenic bladder.  A bladder scan was performed on Brody on Friday night.  It showed that Brody's bladder was full and then he was asked to empty his bladder.  Brody was able to urinate but he was not able to fully empty his bladder.  The bladder scan showed that there was 250ml of urine in his bladder before attempting to void and then 119ml left in the bladder after the attempt to empty it.  Brody seems to have lost the ability to sense or feel that his bladder is full and also the ability to fully empty his bladder.  A bladder scan was repeated again on Monday this week and showed the same problem again.  To deal with this situation and help Brody get rid of excess fluids, we now have to remind Brody about every 2 hours to attempt to pee.  We have to do this even in the middle of the night.  This seems to be working.  He is feeling much better and the swelling is much improved.  However, we are all very tired from getting up every 2 hours trying to convince Brody to pee.  Bill and I are able to split the nights into shifts for each of us to cover but poor Brody has to be woke up every time, of course.  Last night we decided to try doing every 3 to 4 hours during the night and then today I have been having Brody pee every 2 hours still.  I did not notice an increase in swelling doing this.  So hopefully, we will be able to begin to stretch it little longer at night time at least. 

Brody had labs done on Monday.  His counts were pretty low on Monday.  I am expecting he will likely need blood tomorrow.  He goes in tomorrow morning (Thursday morning) for a lab check and for chemo again.  Brody will be starting back on the daily Neupogen injections this week to help his white counts recover sooner.  He has had to take these shots in the past but it has been quite some time ago.  He does very well with them though, fortunately. 

I have been continuing to seek alternative treatment ideas for Brody.  Cincinnati Children's hospital does have some clinical trials for kids with recurrent rhabdomyosarcoma that offer a different approach than what we have tried previously for Brody.  So we are moving forward with things at Cincinnati Children's hospital (which just happens to be the #1 pediatric hospital in the country by the way and close to our family).  Unfortunately, it sounds like for the few kids that have participated in these trials with recurrent rhabdomyosarcoma, the results were not good.  But just because it did not work out for these children does not mean it may not still help Brody.  I do not yet know if we will enter one of the trials at Cincinnati Children's Hospital.  We are waiting to be scheduled for a consult there first.  We will know more after this consult.  In the meantime, I have decided that we have to give molecular profiling a try.  I contacted GeneKey in California.  GeneKey analyzes the whole genome and expression profile of cancer tumor samples and samples of the patient's normal tissue and compares the difference between the two, and evaluates what potential drug therapy may be best based on these results.  The drugs considered are not limited to chemotherapy agents.  Investigational agents and drugs not typically used as chemotherapy are considered.  This analysis is then shared with us and our physician during an in person meeting.   The analysis done by GeneKey is more involved than other labs offering molecular, genomic and cellular profiling of cancer cells.  Other labs are only looking for set biomarkers rather than the whole genome.  Research is currently being done to identify and establish biomarkers for embryonal rhabdomyosarcoma but much more work still needs to be done with this.  Molecular profiling using biomarkers is much less expensive than what is offered at GeneKey.   Unfortunately, the services at Genekey are very expensive and not covered by insurance (cost of $37,000.00 to $39,000.00).    Also, it's possible that we may not get anything useful from their analysis.  It's possible that it will not lead to a new treatment strategy idea or treatment strategy idea that actually works.  However, it's also possible that successful treatment options may be learned from this analysis that we would never have known otherwise.   We are moving forward with GeneKey ASAP.  It may take up to 2 months to have the results back from them and so we have to get moving quickly if we are going to give this a try.  We are hoping to have the payment to GeneKey and biopsies sent sometime next week.  I am hoping it really will not take a full 2 months though. I don't know if Brody has this long.  We need options sooner rather than later.  GeneKey said that often times they can get back with results in less than a month but they did not want to make this promise. 

Here is a link to GeneKey's website for those wanting more information.

http://www.genekey.com/

Besides considering the trials offered at Cincinnati Children's Hospital and waiting for results from GeneKey, I am also very interested in trying a treatment strategy suggested as  "particularly promising" in the scientific journal,  Cancer Cell on Dec 9th, 2013.  The name of this article is "Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma."  The findings in this article are the results of the molecular profiling analysis done collaboratively by St. Jude Children's Research Hospital in Memphis TN, Nationwide Children's Hospital in Columbus OH, UT Southwestern Medical Center in Dallas TX, Seattle Children's Hospital, and The Genome Institute in Washington DC.   Whole genome sequencing of the tumor and normal genomes for 13 patients with rhabdomyosarcoma was conducted.  Two of these patients had recurrent embryonal rhabdomyosarcoma.  The article discussed the differences found in the recurrent tumors vs. those that had not recurred and also the importance of considering the changes that happen to the genome of tumors that have been exposed to chemotherapy.  During this investigation it was discovered that embryonal rhabdomyosarcoma is particularly sensitive to oxidative stress.  (at least this appeared to be the case for the tumor samples they were analyzing).  Oxidative stress is caused when oxygen-free radicals and other byproducts of cell metabolism build up in cells. Skeletal muscle cells and cancer cells have high levels of reactive oxygen species (ROS) because of their unique metabolic demands.  Therefore, it was reasoned that a cancer with features of skeletal muscle (rhabdomyosarcoma) may have even higher levels of ROS than other cancer cells and be particularly sensitive to therapeutics that increase oxidative stress.  The genomic data from the tumor analysis indeed suggested that there were transversions in G-T that would lead to higher ROS and increases in expression of genes in the p38MAPK pathway.  There were also Chromosome 8 gains and deregulation of the MCU/MICU1 expression.  These can lead to mitochondrial dysfunction and oxidative stress.  Also, several genes involved in regulation of metabolism, mitochondrial function, and oxidative stress were differentially methylated in rhabdomyosarcoma, including PTK2, COX7A1, NOSIP, NOS1, ATP2A3, DDAH1, GLRX, and TXNDC12.  Due to amount of genomic data suggesting oxidative stress as a target, embryonal rhabdomyosarcoma xenografts were exposed to medications that were suspected to increase oxidative stress in this cell type.  The results indicated that this was indeed a mechanism that was effective against embryonal rhabdomyosarcoma on the xenografts.  Several of the medications used to test this theory were not chemotherapy agents and indeed some of them were effective.  The authors of this article stated, "Taken together, these genomic, molecular, and cellular data suggest that therapeutics that increase reactive oxygen in rhabdomyosarcoma may be particularly effective and may contribute synergistically to current standard of care using vincristine, actinomycin, and cyclophosphamide.  The synergistic effects of carfilzomib or alvocidib with HDAC inhibitors is particularly promising."

After reading the article about targeting oxidative stress in rhabdomyosarcoma, it compelled me to go ahead with starting Brody on hemp oil with a very high CBD content (18% -24%CBD).  (This is something not covered by insurance and is also extremely expensive by the way).  I had read a few other articles that talked about the various mechanisms by which CBD can be effective against various types of cancer.  One of these mechanisms that was shown to be involved with the anti-tumor effects of CBD is via increasing oxidative stress.  I decided if hemp oil can increase Brody's appetite, decrease pain, and possibly fight his cancer too and all without any major side effects then it's most certainly worth trying.  I just wish it didn't cost so much.  A 60-day supply costs about $2500.00.  Brody has been doing well with the hemp oil.  It has definitely increased his appetite and improved neuropathy pain and I hope we find that it helps slow down the cancer too.  He does not seem to be having any side effects from the hemp oil.  It's  nice to be able to give him something helpful without so much toxicity involved. 

For those that want more info on hemp oil.  Here is a link to the website from which we order it from.  We are using a highly concentrated gel that comes in a 10gram tube.  Each gram of the gel provides 240mg of CBD.  We squeeze out 1/2ml of the gel into an empty size #1 capsule.  Brody then swallows the hemp oil gel inside this capsule.  This way he does not need to taste it.  He gets about 120mg of CBD in each capsule and we have him take 1 capsule twice a day.  We order the empty capsules online separately from a different company than where we buy the hemp oil.   You can order CBD capsules and CBD gum and CBD drops too.  But these do not provide as much CBD. 

http://realscientifichempoil.com/products/

I am planning to ask our oncologist tomorrow to consider adding the carfilzomib and an HDAC inhibitor to Brody's regimen. (This is the combo that was suggested as particularly promising to add to standard therapy).  Brody is no longer taking standard therapy but  he may be able to add these medications to his current chemo regimen.  I am worried about the increased side effects especially with the carfilzomib.  It is a chemotherapy agent and like most, it has quite the list of side effects.  It does seem to be one that would not be super harsh on his kidney.  This is always a worry since Brody only has 1 kidney.  As for the HDAC inhibitor, Depakote (valproic acid) is a powerful HDAC inhibitor.  This medication is usually used to treat epilepsy but has several other uses also.  One of these other uses beside a possible anti-cancer agent that would be particularly useful for Brody is to treat neuropathy.  Depakote can work very well to lessen and treat neuropathy.  Brody is dealing with a significant amount of neurapathy.  I have noticed that his pain with the peripheral neuropathy is definitely improved since starting the hemp oil (he was very sensitive to the slightest touch and often experienced pain when somebody lightly touched him) but he certainly needs some more assistance with treating nerve damage.  Depakote is not the HDAC inhibitor that was mentioned in the targeting oxidative stress in embryonal rhabdomyosarcoma article though.  I think it may be worth considering to use it instead though due to less side effects and the other potential benefits too.   And, it is very strong HDAC inhibitor. 

Sorry for maybe the abundance of details on possible therapy options in this blog post.  (Believe me this is just a very short rambling of the many thoughts that have been going through my mind these last few months regarding therapy for Brody).  I thought I should share a little more detail though for the folks I know that are reading this blog who also have a child battling this devastating disease.  I read many other blogs of other children battling rhabdomyosarcoma and I know other Moms are out there reading mine too. 

Thanks to everyone again for your continued prayers and support.  We definitely need it. 

Watch "The boys with their new hamsters" on YouTube

https://www.youtube.com/watch?v=nbpy1H5Ou48&feature=youtube_gdata_player

Brody's CT scan on Wednesday Showed Brody's Tumor has Gotten a Little Bigger Again

Brody had a CT scan on Wednesday.   Unfortunately the tumor has gotten a little bit bigger again.  Obviously it is not a good thing that each  CT scan lately is showing the tumor continuing to get a little bigger each time.  The tumor is gaining ground.

We had planned on proceeding with the molecular guided therapy trial in Grand Rapids, MI if we got news on this CT scan that the tumor was still growing.  I called on Wednesday to get moving along with this plan only to discover that the trial had just closed and they are not accepting anymore patients.  Talk about pulling the rug right out from under someone.   Seriously!  Ugh!  So now the big question is what do we do at this point???

For the past 6 weeks Brody has been taking Vinorelabine and Temsirolimus each week at the hospital and then cyclophosphamide as tablet daily at home.   There has been debate about whether it's  better to do IV cyclophosphamide in high dose as a single dose every three weeks or the daily low dose cyclophosphamide.   It is not clear which way is more effective.   So for now we have decided to switch  over to the IV cyclophosphamide instead. 
Brody started week 1 of his new regimen today.   He did pretty well with it today.    Brody has had high dose IV cyclophosphamide before (in 2010 with different combo of meds) and back then it made him extremely ill.   He had lots of nausea,  vomiting,  and diarrhea.   Today,  (knock on wood) he did not throw- up at all. He is having significant diarrhea (headed to the potty every 10-15mins) tonight and he is not urinating very much at all considering the amount of fluids he is receiving by IV.  I think all the liquid is being lost in his stool.   Brody has an amazing tolerance for bathroom issues.   His tumor has made these functions difficult for so long Brody doesn't really think too much of having to head to bathroom so much.  I am hoping it settles down very soon so he can get some sleep tonight though. He is crazy tired but just has to keep going to the bathroom. 

Anyhow,  we plan to try the IV Cyclophosphamide with the Temsirolimus and Vinorelabine for a couple 3 week cycles and then getting scans again to determine if it's working to control the tumor or not.  And,  then in the meantime we are seeking second,  third,  fourth etc opinions as to how to proceed if this change in regimen does not work.  

Brody's records were sent today for a consult from Dr. Wexler at Memorial Sloan Kettering in New York City.  

I also contacted Cincinnati Children's Hospital today.   They do have some clinical trials there that offer a different means of targeting rhabdomyosarcoma than what we have tried.   Dr. Turpin called me this evening to discuss Brody's history and gave some very general insight as to what could be offered there.   He also concurred with our oncologist that the high dose IV cyclophosphamide with Temsirolimus and Vinorelabine that Brody just started today is worth a try and that we should pursue this option before anything else right now.   He also said that he could offer Molecular Guided Therapy at  Cincinnati Children's too.   He said,  it generally takes about 2 months for them to get this analysis back though to guide therapy. He explained that it doesn't always pan out either though as far as the guidance. He said that sometimes you may have an analysis that indicates a high liklihood that a particular drug should be effective for a particular cancer and then you give this drug to the patient and it's not effective at all.   Basically he seemed to think that as promising as molecular guided therapy sounds it can be disappointing.   And,  I do agree there are certainly many limitations.  But I still want to do it.  It might give us a better idea of what trial/or drug maybe to lean toward if we have already exhausted all standard options already.   We are seriously running out of options.   There is not much left to try or do at this point.   Also not all molecular profiling is the same. Some are far more extensive and analyze more markers or whole genome or more signaling pathways or more drugs than others.   The expense varies tremendously and timing of when you can get the results.  It seems it can take anywhere from 1week to 2months for results to come back to the oncologist.

We have just recently started giving Brody hemp oil with a high CBD content.  There is some encouraging but still limited evidence that CBD  may help fight his cancer plus relieve significant pain and increase appetite. He just started it yesterday (Wednesday).   And,  so far I would have to say his appetite has definitely increased which is a very good thing. Getting Brody to eat is normally a daily HUGE challenge.

Please continue to pray for Brody.   Pray for a miracle healing.  

An Update

Brody and all of us had a wonderful Christmas together.   Brody felt great and was full of energy for Christmas Day.   After Christmas we enjoyed a visit to Cincinnati area to see my Uncle Rob who had come home from London,  England.   Brody felt pretty good for most of this trip and we enjoyed our time with Rob and the rest of the family. 

Brody has continued to feel well most of the time these past couple of weeks.   However,  recently (over the past week) he has been having frequent leg cramps and some very bad sudden headaches.   His legs get tired and hurt very quickly with activity.   He was doing better in this regard since switching to the new chemo regimen but more recently he seems to be declining with regards to these symptoms.   Keeping Brody extremely well hydrated seems to help lessen the leg cramps but he does still have them frequently even when hydrated well.   Brody's tumor impairs blood flow to his legs significantly.   Slight changes in the size of his tumor can greatly effect Brody's leg pains (and many other problems too).  

Brody will be headed to the hospital for chemo this week on Wednesday followed by a CT scan next week.    This next CT scan will let us know how the new chemo regimen is working.   Symptoms and palpitating his abdomen to feel size of the tumor don't provide enough information.   As far as symptoms go though,  he is definitely doing better now than he was prior to switching to the new chemo regimen.   But,  this past week he seems to be getting worse (not quite as bad as previously but getting worse rather than better this week).  

Brody really wanted to play in the snow with his brothers and his friend,  Lucy today.   He was really trying to but he kept having leg cramps.   He came back inside and rested and drank LOTS of water and then tried to head back out again.  He did better in that he wasn't having leg cramps but his legs would get too tired  and start to ache very quickly.   He kept having to sit down and rest after every few steps.   He decided to just sit in one spot and make a bunch of snowballs.   He waited for his brothers to come running by and he launched his attack.   Geordi and Jaden were nice and kept running by just close enough that Brody could stay sitting where he was and manage to keep hitting his brothers with his snowball stash.   He had a great time with the snowball fight.   He got tired and very cold pretty quick though and decided he would rather go inside and watch his brothers from the warm house while enjoying some hot chocolate.  

Brody continues to amaze me.  It's insane all the difficult and painful things he has to deal with every day.  But Brody does not let it all crush his spirits.   He is a very happy boy.   He does not dwell on the tough stuff.   He just gets through it and doesn't waste any time getting back to just having fun.   He is not a worrier and continues to live in the moment and truely just enjoy so many wonderful moments.   I strive every day to be more like him.

Snow Fort Taking Shape

The beautiful snow-covered woods behind our house

Geordi and Jaden are so proud of their nose-picking snowman...

Geordi,  Jaden,  and our friend,  Lucy,  all had a great time playing in the snow today.   They built snowman families,  snow forts,  enjoyed snow ball fights and making snow angels.   They stopped periodically for some hot chocolate,  popcorn,  and fresh-baked cinnamon rolls.   Right now they are all warming up in the hottub.   Brody tried to join in on the winter-time fun but his legs hurt too bad.   He's enjoying the hottub right now though and he did like watching his brothers and Lucy play in the snow.   The snow has been coming down so fast it is fun just watching it snow.  

Brody playing arcade games at Qzar after a game of laser tag

Brody and his brothers had a good time with their friends Jimmy,  Joey,  and Levi at Qzar laser tag yesterday.   We all went after Saturday morning bowling league.   Brody's legs were too tired for more than one game of laser tag.   All the other kids played three laser tag games.   Brody rested up after the first game and then had a great time in the arcade while the other kids went back in for 2 more rounds.