Kylie, Olivia, Cody, Isabella and Averi - June, 2010. We now know Cody, Averi and Isabella all suffer from Lynch Syndrome III

Saturday, November 28, 2015

Faces of Lynch Syndrome and success of PD-1 immunotherapy!

Curtesy of

Leta Withers – CRC Immunotherapy Pioneer

Leta was a happy wife & mother of 3 boys, aged 9, 13 & 16 when she first experienced the symptoms of colon cancer at only 46 years old.  As is often the case for patients under 50, her symptoms were mistakenly attributed to other causes until she insisted on a colonoscopy.  She had been warned that due to her age, insurance probably wouldn’t cover it – but Leta insisted since she had just had two friends under 45 diagnosed with CRC.  Leta doesn’t back down easily when she sees an opportunity she knows she has to take.

They found an egg sized tumor in her right colon.  11 of 23 lymph nodes were positive for cancer so she was classified Stage 3C.  After 4 months of the grueling cytotoxic XELOX/CAPOX chemotherapy cocktail, her scans were clean. Unfortunately only 3 months later, tumors were found in her lung, chest lymph node, ovary, and peritoneum.  She was now declared inoperable Stage IV – or as I prefer to say, she was at that point declared currently incurable…

She was terrified in private.  She knew what the prognosis for inoperable Stage IV CRC was.  She flew to MD Anderson for a second opinion.  It was there that she first heard about the “MSI-high” biomarker and the good responses they were seeing there in PD-(L)1 inhibitor trials. Leta is in the group of 10-15% of sporadic CRC patients who are MSI-high.

While researching an offered clinical trial combining two checkpoint immunotherapies: a PD-1 inhibitor Opdivo (nivolumab) + a CTLA-4 inhibitor Yervoy (ipilimumab) Leta started the standard second line cytotoxic chemo cocktail for CRC called FOLFIRI + Avastin (bevacizumab).  Her tumors were responding to the treatment but she had a lot of “down days”. The treatment was rough on her.

Looking at her current quality of life and having performed a lot of self-education on checkpoint inhibitor immunotherapies & MSI-high CRC – Leta decided to do the clinical trial instead.  Slots were very limited so she had to call many times over multiple months.  She finally was offered a slot – but she needed to decide without delay whether to take the “Clinical Trial plunge” or continue standard chemo. She decided to go for the trial.

Leta signed the required paperwork and started the trial within days.  In her own words: “It was nothing like the chemo I had endured. I left the chemo chair feeling terrific. No nausea, no pain, no fatigue! I was hungry and felt like myself! After the first treatment, I had wine and cheese and went shopping! Just a tad different than previous chemo.”  The only side effect she has endured is elevated liver enzymes. She has had 3 scans so far – they have showed shrinkage or stability in all her lesions.

To close with her own words: “I credit this drug hugely with both my favorable scans and mostly the amazing quality of life it has given me back. I feel like my old self again. I don’t feel sick, and I have no down days anymore. I feel like I drew the lucky card to be MSI-high and have the chance to be on this trial!”

Stephen Estrada – CRC Immunotherapy Pioneer

Stephen was diagnosed with Stage IV CRC at the very young age of 28. He was fresh out of school and excited to start his career.  Life was fantastic until GI-symptoms became too great to ignore.  Because of his young age, his symptoms were not taken seriously even during two trips to the ER.  Thankfully his primary care physician took his concerns seriously and a tumor was found in his colon – but at the time of diagnosis it had already metastasized to his mesentery.

He underwent surgery followed by 6 months of the difficult FOLFOX cytotoxic chemotherapy cocktail.  The chemo was very rough – his weight bottomed out at 110 lbs and he looked obviously very sick to everyone that saw him.  A radiosurgery was attempted to remove a remaining tumor but it failed.  Before his 30th birthday, Stephen was declared inoperable Stage IV.  At that point, declared currently incurable.

He transferred his care to the University of Colorado Cancer Center.  As is often the case in patients diagnosed that young, genetic testing revealed that Stephen has Lynch Syndrome – and he is also MSI-high.  His new oncologist was familiar with good preliminary clinical trial results being seen with PD-1 pathway checkpoint inhibitors in MSI-high CRC patients.  Based upon his new doctor’s advice, Stephen started a Phase 1 clinical trial of the PD-L1 inhibitor MPDL3280a (atezolizumab) + Avastin (bevacizumab).

In Stephen’s own words: “As I received my first infusion, I was overcome with severe back pain that lasted about two days…but after it left up, I realized that all my tumor induced pain seemed to have already faded away. The second infusion landed me in the hospital for 5 days when I started running a fever of 104. The strange thing is…I never felt very sick…just hot. A whole barrage of tests were ordered to see if there was an infection attacking me. Nothing ever came up and the fever was attributed to the MPDL3280a revving up my immune system and recognizing the cancer.”

Stephen has had 3 scans while on trial – after an initial shrinkage of his tumors, the 2 follow-up scans show stable disease.  To close with his own words: “Besides my disease being held in check, the best thing is…I feel wonderful. I have gained about 40 lbs, I am able to be in the gym about 5 days a week, and I am currently in the process of returning back to work. Without this drug, I would be thin, ill, and potentially not alive.”

Pictured below are 1.) Stephen during chemo contrasted with him currently on PD-L1 immunotherapy.

Friday, November 20, 2015

Out of the Hospital!!!

Bell and her Daddy at the park.

Bell is out of the hospital!! Her Dad, Ashley, Kylie, Olivia and Mercedes are her visiting. She is on a high dose of Steroids to help with the inflammation in her brain, caused from PD-1. They are slowly decreasing the dose...and are hopeful the swelling from the PD-1 will be stable in the next 2-3 weeks. 

Isabella is still unable to walk by herself. She is also having a hard time finding her words. She can move her right arm and leg a little better, but is still very weak.
We are continuously praying that Isabella responds as well as the few other children who have been given this drug! With God all things are spite of losing Cody and Averi, we continue to put our trust in the Lord. We will NEVER EVER stop praying, believing, fighting and searching the world for a cure for Isabella and every single person and family  impacted and suffering from this disease called cancer!! 

I pray for the day....the day, cancer
is just a word....a word used in History books, taught to students...students, who will never ever feel its destruction or be touched by it's pain. 

I pray for the day, the day I can scroll through my Facebook newsfeed...a newsfeed that no longer shows, the beautiful faces of cancer...suffering so.

I pray for the day, the day ribbons are only used to for a decoration, a decoration on Christmas trees, wrapping paper and presents. 

I pray for the day... The day we can scream through the streets...they found a cure for cancer, as tears of joy, gently roll down our cheeks! 

Olivia helping Bell walk.

Her daddy brought her cat from Florida as a surprise!

Monday, November 16, 2015

Isabella admitted to the ICU

Bell was placed in the ICU last night. Her heart rate was in the 50's and the CT scan showed substantial swelling and a slight mid line shift in her brain. The doctors started her on a course of steroids to control the swelling and alleviate her symptoms while the PD-1 continues to work. 
The doctor's continue to be very optimistic that the PD-1 is working. Her rapid neurological decline since her first Infusion is what they predicted, from the swelling associated with the immune system attacking her tumor....I just didn't realize, it would get this bad. 
Dr. Tabori had told me a couple of his cmmrd patients, had to be hospitalized in the beginning, so it was good we didn't live far from the hospital. 
Since starting the steroids, she can move her right arm and leg, she's eating and no longer has a headache. Unfortunately, the steroids make her feel horrible and emotional...but they are saving her life!!
Thank you for your continued prayers and support!! 

Friday, November 13, 2015

Extreme neurological decline in last 13 days.

Bell and her Aunt Anni.
Bell and Anni at the hospital yesterday, for Bell's second PD-1 infusion.

 Isabella's neurological state has extremely declined in the last 13 days, since her first PD-1 infusion. Even though the doctors continue to reassure us that this is expected, it rips our heart out to see her like this. She needs assistance walking, complains of painful headaches, nausea, fatigue and is still having seizures. The seizures are not as intense as before. Due to a second seizure medication that they put her on to help control seizures from the inflammation caused by the PD-1. She continues to be so brave in spite of feeling so horrible. 
I pray the inflammation in her brain does not get worse...and cause more pressure. Dr. Tabori, says the other 3 patients with cmmrd, had initial flare up then stability within 1-2 months. The Doctors are watching Isabella very close to make sure she does get hydrocephalus. Please, Please continue to pray for Isabella as she endures this very difficult time!!

Friday, October 30, 2015

1st PD-1 infusion

Isabella had her first dose of the PD-1 immunotherapy, six days ago. She was really scared, but she pushed through it. I'm so incredibly proud of her! It was an hour long infusion that she will get every 2 weeks. Uncle James, and Stella were there to cheer her on. It was such a blessing to have James, Christopher and Stella here visiting for a few days! Waking up to Stella's beautiful smile every morning...Priceless.
Bell has been sleeping more and has had 3 small seizures since starting the PD-1 therapy. We know the doctors expect initial swelling during the beginning of her treatment....which will make her symptoms appear worse.  She also has right sided weakness and numbness which makes it harder to get dressed by herself. 
I try really hard not to over analyze every single thing, which I am trying hard to do better in that department....does her face droop more she sleeping more than she should she going to have a seizure today, if she does should I call the ambulance....what if I'm not with her every single second and something happens....what if she falls and hits her head when walking down the steps.. These are just a few of the things I worry about every second of everyday! When I get like this...I just pray and pray and pray! I know God is in control and I have to put it all in his hands! 
Me, Stella and Bell during PD-1 infusion.

With Uncle James, on our way to the 1st infusion.

We try to have fun and find humor in all situations!
Playing with Stella during the infusion. She wearing the awesome TEAM ISABELLA bow, sent to her by a classroom in Burlington, Iowa!  Thank you so much! She loves it!!

Sleeping with her cousin, Stella on the way home from an exhausting day at the hospital.

Saturday, October 24, 2015

Conversation with Dr. Tabori...never give up HOPE.

Isabella first PD-1 infusion is rescheduled for tomorrow, Friday, October 30th. 

I spoke with Dr. Tabori, on Friday. First of all, I'd like to say how absolutely amazing and grateful I am to him and his team at Sick Kids, in Toronto, Canada. 
Dr. Tabori's relentless determination to bring awareness and push for a cure for CMMR-D gives HOPE to children and families where hope never existed before. Most children with CMMR-D, do not survive it to adulthood. 

From what I understand, after speaking with Dr. Tabori, Isabella's new tumor sample shows 21,700 mutations!  Which is a good thing because the Pd-1, should trigger the immune system to recognize all the mutations and begin killing them. Isabella   is the 5th CMMRD patient on the PD-1 immunotherapy. They have seen miraculous results. The first patient that received PD-1, just had his 5 month MRI scan...with amazing results. Dr. Tabori was quick to point out, this is all new and every patient responds differently. 
After speaking on the phone for several minutes, Dr. Tabori said, "Mrs. Mading, there is HOPE, and with CMMRD patients, hope never existed before...all we can do is pray and hope."
I felt my eyes filling with tears...knowing there is finally HOPE!
...Hope for my youngest child, at age 3 and 4, spent months in and out of the hospital, with her only brother. She was by his side as he struggled to breathe the last 7 hours of his life. Isabella was holding Codys hand, when he took his last breathe and entered heaven.

....Hope for my 5 year old child, that had to stay behind, when we traveled to Spain and Indiana in search for a miracle that could save her sister's life. 

....Hope for my sweet little girl, who watched her parents 20 year marriage fall apart from unspeakable grief of losing their son, and fear of losing their daughter. 

...Hope for my little Bell, who would happily empty her sister's cathedar bag, and be the first one to offer Averi help changing her illeostomy bag. 

...Hope for my sweet 6 year old, Button (my nickname for Bell), who spent many long nights and days at Hospice House, the last month and a half of Averi's life. 

...Hope for my Brave baby girl, who on Christmas Eve morning, sat courageously by her sister side, as Averi's body began to shut down...watching and praying quietly, for six excruciating hours..until her sister took her her last breathe.

...Hope for my heartbroken child, that I painfully carried out of her older sister's Hospice room for the very last she hysterically begged and pleaded with me to "Mommy, Please, please take me back to my sister."
...Hope for Isabella, who has dreams of dancing, going to school and becoming a Nurse when she grows up! 

Isabella in her Cop Costume, getting ready to go Trick or Treating.

Thursday, October 22, 2015

On our way home. PD-1 scheduled for next Thursday.

Bell is doing so much better! No fever for a day and a half. All her blood cultures were negative for infection and her C-diff test (she had terrible diarrhea) was also negative. She woke up yesterday and asked me where she was!! 
The last thing she remembers is being with her Grandma and Dad, at Walmart, before her flight! I think it was a combination of seizures, high doses of benzodiazepines (to stop her seizures) and a high fever. Which I guess is a good thing because she has never been this sick in her life.
PD-1 doesn't start until next Thursday!! 
I'm not very happy about it but, there is nothing I can do to make the process go faster. I tried! Institution approval should be finished tomorrow and then the company has to ship the medication to Pittsburgh. 
The Neurologist placed her on a second  seizure medication due to brain swelling that is expected 1-2 weeks after starting immunotherapy. The PD-1 therapy will cause her immune system to attack the brain tumor which will in return cause the tumor to swell. Dr. Tabori, said his first PD-1 patient took 3 months to see stability in tumor progression. I'm slightly worried we may not have that much time...but we continue to put our trust in God! It's in his hands!  Excessive Worrying does not do anything but cause   unnecessarily anxiety and stress! Reminder to self!!! Lol.

Philippians 4:6-8New King James Version (NKJV)

Be anxious for nothing, but in everything by prayer and supplication, with thanksgiving, let your requests be made known to God; and the peace of God, which surpasses all understanding, will guard your hearts and minds through Christ Jesus.

 Reasons Isabella gave Dr. Randy, on why she should go home today instead of tomorrow. I think number 6 is what worked!! Lol.