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

Tuesday, October 6, 2015

Approval of PD-1 compassionate use.

Isabella was finally approved for the compassionate use of PD-1 immunotherapy!! Woo hoo!! Dr. Mason is finishing the paperwork for the FDA and Institutional approval. Isabella should be starting the PD-1 immunotherapy sometime in the next couple weeks.

 Isabella, left Saturday morning, to visit her Dad for 2 weeks. It's really hard being away from her right now, but she is doing wonderful, especially since she is almost completely off her steroids. Lol!!
Decadron is a steroid they use to decrease edema in the brain. They administer it after brain surgery or when you have a tumor that is causing increased pressure in the brain. Although,  it's very effective in reducing edema, it can also make your child very agitated, anxious, angry, hungry etc. etc.
Needless to say, after a few hours of, Isabella, being placed on Decadron, I was counting down the days and hours until the doctors weened her off of the, "Monster Med's" (aka. Decadron). I cant wait to have my sweet, kind and usually polite little girl back!! She's almost back....only 3 days...72 hours until she is done with the medication. LOL. Yah!! Happy Dance! 

Helpful tip-sometimes Physican's forget tell you the side effects of Decadron. I have spoken to many family members whose loved one is battling brain cancer. Many times, no one has told them the possible emotional side effects and personality change that can be caused by Decadron. It's important to know they cannot control the anxiety, anger, frustration and eating everything in sight, caused by this medication. Don't take it personal. If your loved one is experiencing suicidal thoughts contact your doctor immediately. Your doctor can prescribe a medication called
Cylexa, or a similar anti-depressant, that can reduce the emotional side effects of Decadron. Also, your loved one should be on Pepicid, or some type of acid reducer, to help with the digestive side effects of Decadron.
 I'm not a Phycisian....just a Mom  and a nurse. Lol.

We are waiting for Dr. Tabori, in Toronto, to finish testing her tumor samples to see what immunotherapy drugs will be the most effective against her cancer. He is very hopeful the PD-1, will be beneficial in killing her brain tumor. 
Isabella has approximately, 13,634 mutations in her tumor. The hypothesis is...the PD-1 immunotherapy will boost her immune system, the immune system will then recognize the massive amount of mutations in her tumor and begin attacking it. The more mutations the more hope for success!
We are completely humbled by the all the cards and packages that were sent to Isabella!! I cannot even begin to express how thankful we are for all the love and kindness shown to our daughter!  She has been SO HAPPY, opening and reading every single card sent. Thank you, thank you, Thank you....from the bottom of my heart! 

Friday, September 25, 2015

Miracle MRI results!!

Isabella was discharged from the hospital this afternoon. She is doing so much better. 
We found out yesterday afternoon that the surgeon was able to remove over 95% of Isabella's tumor...which is considered a full resection!!! Hallelujah!! Thank you everyone for your prayers... They are working!!

Tuesday, September 22, 2015

Out of ICU.. Woo hoo!!

Isabella is finally out of the ICU as of last night and is feeling so much better! She had a rough few days in the ICU...On top of brain surgery, not being able to eat, high doses of steroids, not being able and bed rest took a toll on her. Also worth mentioning, she can't believe there is no playroom in the ICU. Lol.

Isabella will be in the hospital until at least Friday. They are giving her prophylactic IV antibiotics due to a breach in the sterile field during surgery. The Infectious Disease Doctor, thinks her risk of infection is very low. It's better to be safe than sorry. 
The MRI results looked good, although they noted a small hemorrhage in the tumor cavity. We are waiting to speak with Dr. Mason to find out exactly what his interpretation is of her post surgical MRI results.
Thank you, thank you, thank you for all the prayers, cards, love and support!!

Exciting news: Immunotherapy and Lynch Syndrome!!

A Surprising Match: Mismatch Repair and Immunotherapy. 

Mismatch repair genes have long been a source of fascination to basic biologists. Normally, these genes serve to fix the small glitches that occur when DNA is copied as cells divide. Most of the original work was done in bacteria, with no expectation of medical relevance. But, as often happens, basic science studies can provide a profoundly important foundation for advances in human health. The relevance of mismatch repair to cancer was dramatically revealed in 1993, when teams led by Bert Vogelstein of Johns Hopkins School of Medicine, Baltimore, and Richard Kolodner, then of Harvard Medical School, Boston, discovered that mutations in human mismatch repair genes play a key role in the development of certain forms of colorectal cancer [1, 2].

That discovery has led to the ability to identify individuals who have inherited misspellings in these mismatch repair genes and are at high risk for colorectal cancer, providing an opportunity to personalize screening by starting colonoscopy at a very early age and, thereby, saving many lives. But now a new consequence of this work has appeared. Vogelstein and his colleagues report that mismatch repair research may help fight cancer in a way that few would have foreseen two decades ago: predicting which cancer patients are most likely to respond to a new class of immunotherapy drugs, called anti-programmed death 1 (PD-1) inhibitors.

In a small, proof-of-principle study recently published in The New England Journal of Medicine [3] and presented at the American Society of Clinical Oncology’s annual meeting, the Johns Hopkins researchers reported that they could predict the benefit of an anti-PD-1 inhibitor called pembrolizumab (Keytruda®) by scanning patients’ tumor samples for defects in mismatch repair. Regardless of their type of cancer, patients whose tumors were mismatch repair deficient were more likely to respond to the immune-boosting, anti-PD-1 drug than those with tumors proficient in mismatch repair. In fact, the worse the tumor cells were at repairing DNA, the better the patients fared on anti-PD-1 therapy!

This may all sound counterintuitive. However, researchers say it supports the hypothesis that immunotherapy may be most effective against tumors with many mutations. (In the new study, the tumor cells deficient in mismatch repair contained more than 20 times as many mutations, on average, than tumor cells proficient in mismatch repair.) The idea is that the greater the number of DNA glitches in a tumor cell, the more abnormal proteins it will produce—and the more abnormal proteins that are generated, the greater the odds that the body’s immune cells will regard the tumor cells as “foreign” and target them for destruction.

To test this hypothesis, Vogelstein, Luis Diaz, Jr., and their colleagues initiated a phase II clinical trial to evaluate pembrolizumab, which is already approved by the Food and Drug Administration for treating certain patients with melanoma [4], in 32 patients with advanced colorectal cancer. Some of the patients had tumors that were mismatch repair deficient; others had tumors proficient in mismatch repair. The researchers also enrolled nine people with cancers of the pancreas/bile duct, uterus, small bowel, and stomach that tested positive for mismatch repair defects. The patients, all of whom had not responded to at least one previous cancer treatment, were administered the anti-PD-1 drug intravenously every two weeks.

After at least 20 weeks of anti-PD-1 therapy, the researchers found that colorectal tumors shrank in about 40 percent of patients in the mismatch repair deficient group, compared to none in the mismatch repair proficient group. Furthermore, 78 percent of the mismatch repair deficient group was free of tumor progression at 20 weeks, compared to 11 percent of the mismatch repair proficient group.

According to the researchers, the average overall survival time for colorectal patients in the mismatch repair deficient group has not yet been reached because some are still responding well to anti-PD-1 therapy, more than a year after the study started. In contrast, average overall survival among patients in the mismatch proficient group was reported to be only 5 months.

As for the patients with other types of mismatch repair deficient cancer, their tumors shrank at rates similar to those seen in mismatch repair deficient colorectal cancer. However, such patients tended to respond faster to anti-PD-1 therapy than the colorectal cancer patients. And, unlike the colorectal group, a complete remission of cancer was observed in one patient—a woman with uterine cancer. No treatment-related deaths occurred in the study, with the most serious adverse reaction being pneumonitis (inflammation of the lung) in one patient.

The team will continue to follow these patients and enroll more volunteers to see if their findings hold up in a larger study. They also hope to start similar trials for some of the many other types of cancer, such as prostate and ovarian, known to contain mismatch repair deficiencies in a small percentage of tumors. Another area of scientific exploration is whether patients whose tumors contain other types of DNA repair deficiencies, such as those caused by POLD, POLE, and MYH mutations, might also benefit from anti-PD-1 therapy.

This research is just one of many outstanding examples of how decades of research by NIH-supported basic, translational, and clinical scientists continue to move us towards the era of precision medicine. NIH’s National Cancer Institute recently took a major step in that direction by announcing the Molecular Analysis for Therapy Choice, or NCI-MATCH trial. This pioneering clinical study will precisely match patients from as many as 2,400 sites across the country to one of more than 20 targeted drugs or drug combinations based on the particular molecular abnormalities of their individual tumors [5]. With this and many other new efforts envisioned by the Precision Medicine Initiative, it seems as though a future of more precise, individualized approaches to the diagnosis, treatment, and prevention of cancer and many other diseases is now within sight.

Friday, September 18, 2015

Out of surgery!!!

Isabella is out of surgery. She is doing really well. The doctor estimated she removed 50-75 percent of the tumor. We will know more tomorrow after her MRI. The Neurosurgery team does not see any deficits after her surgery...Thank you, GOD!! Dr. Greene ( her surgeon) also had the lab come down during surgery to prepare the tumor samples and send  them immediately to Dr. Tabori, in Canada. Dr. Tabori, is going to test multiple immunotherapy drugs on Isabella's tumor samples to find out which drug has the most hope to treat Isabella's brain cancer. 
We also found out today that Isabella is more than likely approved for the compassionate use of the immunotherapy drug, PD-1. If everything goes as planned, she should be able to start the PD-1 sometime in the next 2-4 weeks. I found out today, the doctors in Toronto, have a patient with Bell's gene mutation that is doing extrodinary on the PD-1 immunotherapy. I still believe in heart is filled with Hope...And I know with God all things are possible! 

Surgery update

They took Isabella back for surgery at 10:30 am. Surgery will take anywhere from 2-5 hours.  She was in really good spirits. She went back to the operating room with a smile on her face. I am so incredibly proud of her unwavering faith and courage!
On the phone right before they took her back for surgery.

Surgery this morning at 9:15 am

Isabella had a seizure last night. They took her to Pittsburgh Children's Hospital by ambulance. Surgery is scheduled for 9:30 this morning. The surgeon is going to resect as much of the tumor as she can, safely out of her left parietal lobe,  Please pray Isabella has a safe and successful surgery with no deficits. Thank you for everyone's continued prayers and love for our little girl!! I can't thank you enough!!