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"GET SMART": GENES, MUTATIONS, CONTROL, CHAOS

When last I posted, my man was continuing to receive the onivyde plus 5-FU for metastatic pancreatic cancer; however, there have been a number of developments over the last several months that led to a welcome change in treatment. As I mentioned, he was hospitalized last November with sepsis of unknown origin - and even though he fully recovered the hospitalization led to a pretty significant loss in weight and overall generalized weakness. I realize in retrospect that we were experiencing a profound loss of control: of his disease, his gait, his bladder and bowels. He became much less steady on his feet and began to fall again (thankfully, only around the apartment and not outside on the concrete sidewalk) - something that had not happened for over a year. He barely made it to the toilet on time - and occasionally did not. Dr O'Reilly could see that the chemo was wearing him out, and recommended that we test his tumor (a second time) for any targetable genetic mutations. We were glad to do so - hoping that a new line of testing would perhaps lead to further and better-tolerated treatment options. And so it did. 

His tumor (a piece of the specimen removed during the Whipple surgery in January 2010) had been tested perhaps five years ago by a company called Foundational Medicine. No mutations were found at that time and so he continued with conventional gemcitibine-based pancreatic cancer chemotherapy. Sometimes the gem was administered alone; at times with xeloda; other times with abraxane. Slowly, it became evident (as his tumor metastasized from the pancreas to the lungs to the peritoneum) that he had run out of gemcitibine-based chemo options - and it was at that point that Dr O'Reilly suggested we commence a second round of genetic testing of his tumor. Frankly, we were surprised. Who knew they saved the yucky thing for so many years? (I'm guessing that at some point prior to surgery we authorized the retention of his tumor, gallbladder, part of the pancreas and other tissue that had been surgically extracted, but I'm in a bit of a fog on this point. Naturally, we were a bit unhinged by the pancreatic cancer diagnosis at the time, and careful reading of hospital admission paperwork was not a huge priority). So MSKCC (not a private for-profit company this time) did another round of tests, this time on germline cells. I'm unclear as to whether Foundational Medicine did germline testing the first time around and inadvertently got a false negative, or whether germline testing had been developed and/or improved in the intervening years between Foundational's first testing and MSKCC's second go-round. For whatever reason, MSKCC's germline tests revealed a significant mutation - one that has had profound therapeutic implications. 

Here's a brief primer as I understand it: The DNA of each cell in the body contains genes (there may be as many as 30,000 different genes in each cell) that control how the cell functions - including how quickly it grows, how often it divides, and how long it lives. Genes are located on 46 chromosomes, which are arranged in two sets of 23 chromosomes - one set of inherited from each parent. Genes control cell function by making proteins that have specific functions and act as messengers for the cell, and in order to function properly each gene must have the correct instructions or "code" for making its protein. Cancer may occur when one or more genes in a cell are mutated, which creates either an abnormal protein or a lack of protein that causes cells to multiply uncontrollably. There are two basic types of genetic mutations, Acquired and Germline. Acquired mutations occur from damage to genes during a person’s life - such as from smoking, untraviolet rays, viruses, etc. Germline mutations are found in every cell of a person’s body, including reproductive cells; accordingly, these mutations pass from generation to generation.

My man was found in the germline testing done by MSKCC to have the BRCA-1 mutation - the same mutation many of you may recall caused Angelina Jolie to make the difficult decision to have prophylactic mastectomies to reduce her chances of contracting hereditary breast cancer. BRCA is a Tumor Suppression gene - something that limits cell growth by monitoring how quickly cells divide, repairing DNA, and controlling when a cell dies. Mutations in these genes may cause cells to divide uncontrollably, with the result, of course, being a cancerous mass. It is estimated that cancer caused by germlne mutations accounts for roughly 5-10% of all cancers; indeed, BRCA-1 mutations have been known for some time to be linked to hereditary breast and ovarian cancers. During the last several years, a number of new treatments designed to target specific mutations such as BRCA-1 and BRCA-2 have made their way through FDA approval to the patient population marketplace - and many of these treatments have been true game changers in their ability to control otherwise virulent cancers. 

Lynparza (Olaparib) is a PARP inhibitor found to be an effective treatment for breast and ovarian cancers in patients with the BRCA mutation. It has been studied in other cancers as well and will most likely be FDA-approved for pancreas cancer in the future. PARP inhibitors are drugs that stem the production of a substance known as poly ADP ribose polymerase (PARP), which is an enzyme that is conducive to the formation of many cancers. Since these cancers are dependent on PARP to survive, anything that inhibits the production of the PARP enzymes may be, according to our Dr O'Reilly, a viable treatment option for BRCA-positive pancreatic cancer. We are regularly astonished at how lucky we are to have an oncologist who thinks outside the box and opined that my man might benefit from the use of a breast/ovarian cancer drug! Even better: lynparza is an oral chemo that can be taken at home (we definitely needed a break from the constant wait to be called to the chemo infusion suite at MSKCC). The challenge: insurance coverage, naturally. Not only were we facing insurance issues in the off-label use of a breast/ovarian cancer drug for pancreatic cancer, we ran into another difficulty when we discovered that there was but one dispensing pharmacy for individual patients in the entire country for this drug. There were several hellish weeks where I was spending every spare moment on the phone with either the insurance people or the pharmacy people. Coverage was initially denied and an appeal taken. Particularly galling was a short-lived period of celebration when we we informed that (finally!) insurance coverage for the lynparza had been approved - only to be served with notice from the pharmacy that they would be requiring a "dispensing fee" of several thousand dollars for each delivery cycle. When I called to give them a piece of my mind, they actually tried negotiating me down from several thousand to a couple of thousand. 

Kudos to Dr O'Reilly's amazing staff at MSKCC who spent as much time as we did dealing with the insurance and pharmacy via telephone, email, and snail mail. It took alot of time and effort, but thankfully it all worked out and the upshot is that he is taking the lynparza, it is fully covered by insurance (including the World Trade Center Fund), it is dispensed and delivered at no charge to us, and it is working beautifully. His April CT scan showed marked disease regression in both areas of metastases (lungs and peritoneum) and the July scan showed even further regression. The peritoneal disease is practically wiped out, and the lung metastases are as small as they were five years ago when first diagnosed in August 2012. On the other hand (because there is ALWAYS another hand), he is noticeably more tired; still requires hydration via infusion (we have a visiting nurse to access his port; a company called Coram delivers the supplies and we infuse him at home); still has the occasional fall (caused by weakness more than anything else); has even less bowel and bladder control than he did one year ago; continues to suffer from occasional confusion and chemo brain; gets very little exercise, largely due to the fact that alot of his treatment and care is now being managed at home. Indeed, the cancer is so well controlled on the lynparza that I find myself gratefully thinking that our biggest challenges right now are typical long-term survivor challenges: keeping up his weight; dealing with cognitive lapses caused by treatment but made worse with normal ageing; reminding him that there's nothing intrinsically ghastly about having to wear a diaper (it saves alot of time and effort in cleanup); keeping him as fit and active as possible. In short: he's going to be around for a long, long time if his recent scan history is any indication - and so we are finally permitted to shift our daily focus from trying to gain control of his disease to keeping him as fit, strong, mentally agile and personally fulfilled as is possible within it's imposed constraints. 

The takeaway: genetic testing and tumor profiling may result in the discovery of a targetable mutation that allows for greater disease control. GET SMART and GO FOR IT. 

 

3 people like this post.
Thomas threw a punch at your cancer.
3 people sent you a hug.
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So glad you did the second testing and found treatment that is working! I am a firm believer in tumor testing and hopeful I will find my matching treatment. God bless
Thomas likes this comment
Thank you, Betsy. I am sure with all the advances in testing that a targeted treatment will be found for your disease before too long. Fingers crossed; thoughts and prayers......💪🏽
Thomas likes this comment
Wow, what a battle. I'm so glad that you are finally able to make progress against the disease! Genetic technology is advancing so rapidly these days. I know he's still very weak, but that's got to lift your spirits. Prayers for continued progress!
Thomas likes this comment
Thank you, Sterling. You were able to read between the lines enough to know that he really IS very weak and every day is still a challenge. But this new era of tumor profiling and genetic testing gives me alot of hope - and I just had to share good news with everyone here. Hope all is well with you! 💪🏽
Thomas likes this comment
This is incredible news Susan! Good to finally hear that advancements in treatment continue to accellerate and help more people regain health. The fact is, most people don't have such a perceptive and effective advocate as you are. Best of luck to both of you as this story plays out in the future, and keep us posted. Love...Lucky
Thomas likes this comment
Thank you, Lucky! I've been wanting to share this news for months and never found the time - proof that caregiving continues to take up so much of my time and energy. These new mutation-specific treatments really ARE game changers......but there are still side-effects to contend with. And we are extremely lucky that we finally got approval through a combination of insurance and the WTC Fund: most people might not have as many options as we did. Hope all is well with you! 💜💪🏽
Thomas likes this comment
Well, forget the guilt...you DID share, and we're all the better for it. Yes, you are lucky in many respects, not the least of which is your ability to get things done, care for your man, and still find the time to write about it. And the two of you obviously share a lasting and inspiring love. Thank you both.
WHAT A STORY!!! And what a wonderful finale! More than 7 years out since diagnosis, he must be a figure for the record books! HUGS to you both!!
Thomas likes this comment
January will be eight years since diagnosis. We actually thought he might be Dr O'Reilly's longest surviving pancreatic adenocarcinoma patient - but we found out recently that she treats a woman who is a ten-year survivor. Thanks for slogging through this post (which I just re-read and it put me to sleep!) XO 💜💪🏽
Thomas likes this comment
Hi Susan: I am just beginning this journey. My father was just diagnosed with PC stage 4. there will be no operating at this point. 2 questions: What have you heard, if anything about sloan Kettering for treatment? and did you use any integrative/alternative methods along with the conventional treatments? Thank-you in advance....Helen.
My husband is treated by Dr Eileen O'Reilly at MSKCC. She is phenomenal. There is also another fantastic young physician there who occasionally steps up for Dr O if she is on vacation or traveling to one of her many international speaking engagements. Her name is Maeve Lowery. They are both superb clinicians as well as researchers. Good luck! I've blogged about our entire journey here at BFAC - so you may wish to go back and read some of the older posts. 💪🏽
I just love this post Susan. What you just discussed above is amazing and wonderful and proof that there are folks working very hard and long hours on making cancer a chronic, non-lethal, live-a-normal-lifespan disease. We still want those cures too. I'm so impressed with this second testing; perhaps there are now better ways of determining genetic markers than there were in 2010. I have so much faith in Sloan-Kettering. 😘 💐👏🏻
Thomas likes this comment
The results of the second test really had us gobsmacked - and the more I think about it the more I realize that there must have been great strides made in testing protocols between the first and second tests, or else why would Dr O have suggested the second test? Never would I have believed seven years ago that he would still be here and we would be looking at the possibility of a normal life span (with pancreas cancer?!) but it seems that goal is within reach. All I ever wanted was for him to keep hanging on long enough for the researchers to stay one step ahead of his disease - and I think he's really pulled it off. I share your fervent wish that cancer become a chronic diabetes-like disease for all patients (although I agree that a cure would sure be nice!). Thanks for your always heartfelt support, Marcia. 💜💪🏽
Wow... this almost reads like a piece of investigative journalism. I had to put my concentration cap on to stay focused on your descriptive narrative.

Thank you for such an in-depth description of the background behind the treatment because I find it extremely interesting and like to follow the biology and chemistry of what is going on

I'm sure that is a welcome shift of concentration for you from battling disease progression to planning for dealing with a chronic condition and not having to worry so much about disease progression. That has to be a relief of sorts

Of course I also can't help but wishing I had pushed harder for further analysis of Emily's tumor and possibly a similar approach might have been utilized since although she did not have the surgery she also had metastasis to her lungs but be that as it may it is history and hopefully as you say others will also get the testing done so that if alternative treatments are available they can benefit from them

I am so happy for you. I know you still do not have it easy but it's a little less pressure knowing that so far the disease progression has been contained

I am sure that narrative took some work sometime some doing and I want you to know how much I appreciate the detail that you put into that

Thank you for telling your story your husband's story

Thomas likes this comment
Yes, I wish others who had shorter lives had had the same opportunity we were given to have the tumor tested. It begs several questions: do they need a large sample (such as tissue from the Whipple) to do the tests? Why is such testing only offered once conventional treatments have ceased to be effective? I mean, suppose Emilee had the BRCA mutation? Did they do a lung biopsy on her? If so, was there enough tissue to test for mutations? If she had the mutation, wouldn't the first choice chemo then be something like Lynparza rather than the traditional gemcitibine-based options? All these "What Ifs...." Obviously, I feel grateful - but wonder why this mutation wasn't discovered earlier. It might have saved him many years worth of extremely debilitating chemo. We just put so much hope and faith in doctors, but I will tell you this right now: if anyone I know gets diagnosed with cancer I am going to tell them that the first thing to tell their oncologist is that they want their tumor tested for genetic mutations straightaway - because the answer to that question should guide treatment FROM THE BEGINNING of the journey - not only when all else has failed. Thanks for your thoughful comment, Neal.
I agree completely...the testing should happen as soon as the person is diagnosed
Wow!! That is really wonderful news!!
Thomas likes this comment
Thank you! We are very, very lucky - and I'll never take that for granted. Imagine: feeling lucky to have a genetic flaw that explains why you had a predisposition to cancer because that same flaw also means better treatment options. Pretty bizarre!
What fabulous news, Aunty! *high paws* We are so grateful to those working tirelessly to find a way to help cancer fighters live healthier and longer while they find a total cure. We reckon that pretty soon the arsenal of cancer-fighting drugs will be so huge and powerful, that pancreatic cancer will be considered as a chronic disease that can be controlled for a normal lifetime. We're so happy for Uncle (and you). We are sending Uncle strengthening vibes and many face licks. Hugs! :*)
Oh boy! Face licks from my handsome doggie pal! Thank you, dear Thomas - I just want to cuddle you so much right now! 💜🐶💜🐶💜🐶💜🐶💜🐶💜🐶💜🐶💜🐶
Thomas likes this comment
Thank you for sharing such detailed information regarding your Man's trials and tribulations in the world of personalized medicine. I am glad to hear he is having a positive response to this new treatment plan.
Thank you, Laura. My fervent wish is that these sorts of genetic profiles, tests and interventions become initial standard protocols for all cancer patients - or at the very least those with challenging cancers that typically don't respond well or for long to traditional chemotherapy. If my man's condition continues to improve, I see myself perhaps moving in the direction of advocacy on this point. Thanks for your continued support and comments! 💜💪🏽
Thank you for such a great post. This is such good news. I am so happy for the two of you. Being in a household dealing with appointments and chemo sessions I know how it can take over your life. But, amazing, I'm stunned, I'm beside myself. We are at the point that we are trying to live with it and still do the things we like to do when we can. Like today, we went on a scenic 4 mile hike along the coast of Maine. I think Roger is in better shape than me and the dog. I will try an upload a picture of the way he looked today. He's happy and healthy in many ways so life goes on.

I can't help but wonder, as I'm sure you are thinking about this too, how could thorough genetic testing be done with each patient sooner. Did you say your husbands first test was done at a for-profit hospital. It shouldn't make a difference. Did you know their test would be any different from what other hospitals test for. Did you know that a second genetic test was even an option. I'm guessing the answers are mostly no. They are analyzing Roger's tumor at Dana Farber but they said it was for research and not treatment. The doctor said it would also be useful if he is ever involved in clinical trials. They were clear with us that they will be looking for mutations. If found, they would offer our kids services for early detection. So is he saying he will only look at results when Roger has run out of options, and that only has clinical trials.

These are all good questions. We all have to work on it to be solved or improved. Yes, happy dance, I'm so glad for you.
The first test was arranged by MSKCC in 2012 and it was performed by a for-profit company called Foundational Medicine. It was primarily for research purposes, but we were told that we would be informed if any significant targetable mutations were found. We received a report about three months later showing no targetable mutations - and so we thought that was the end of it. My belief is that IF a mutation had been found our Dr O'Reilly would have tried to tailor and personalize treatment at that point - because she is a world-class researcher as well as a superb clinician. I think it really pays to be seen by a major cancer center, because they will always be thinking out of the box and be up to speed on the latest science. Dr O has always offered us new approaches - even when conventional chemo was still working. She offered a clinical trial of nivolumab in early 2014, but he was doing so well that we decided to pass. I really do feel that tumor testing should be made available and the results utilized immediately when making initial treatment decisions. I realize this is a very costly undertaking, so perhaps initially it should be made available for the most recalcitrant cancers. As for the second test by MSKCC, we had no idea that a second test was even an option - but Dr O'Reilly was astute enough to realize that advances in testing or advances in germline testing specifically made it worth the expense. And again....it cost us nothing. We simply allowed them to use anything they found for research purposes. Dr O'Reilly really kept our expectations low - said she didn't expect to find any targetable mutations the second time around, and not to get our hopes up. Well, you should have seen the grin on her face when she told us the news! Thanks for your update and insights, Deborah! 💪🏽
Wonderful news! Emsnana's gem treatment has quit working, and we are working on alternatives. She had the BRCA test and it was negative. We are now involved in a clinical trial at Emory for which we have a lot of hope. One feature of clinical trials I had not appreciated is that you get followed intensively by an expert! So at least someone is paying attention.
Yes, we interviewed for a trial at MSKCC in January 2014 and I was really impressed by how thorough they are in their care. We opted not to go ahead with it, because at the time his gemcitibine was still working. I'm so glad you found a clinical trial! Do you know what phase trial it is? Is it testing different drugs in combination? Is it immunotherapy? I'm so interested in the science, Laren: do keep us informed!
Best of luck, thoughts and prayers to you and Emsnana. I know how difficult caregiving can be, and you are about as supportive a spouse as I've ever had the pleasure to meet (even if the meeting is online!). Stay strong!! 💪🏽💜
It's BBI608, a team cell antagonist of some sort. It is still Phase I for,pancreatic cancer, but it has moved to Phase III for,other cancers. The good think is they already know the maximum dosages.
Susan J likes this comment
"Boston Biomedical is focused on targeting cancer stem cell pathways. Its lead product BBI608 is in a Phase III trial in combination with paclitaxel in patients with gastric and gastro- esophageal junction cancer. The trial is scheduled to complete in 2017. BBI608 is designed to inhibit cancer stem cell path- ways by targeting STAT3, a protein that plays a fundamental role in converting normal cells to cancerous cells."
Sounds promising, Laren! Good luck!! 💜💪🏽
Susan, it always gives me "warm fuzzies " to read anything you have written. I am so glad your man was able to find a drug that suppresses the tumor. I am sorry about the fatigue. I know how depressing that can be. I was reading a post on lack of support after punching that little button saying 'I will support you". I feel so guilty but with each day the smallest things like reading can become overwhelming.
Hoping that life brings you a chair of bowlers or at least a bowl of cherries 🍒
Actually, Nana, I'm impressed by all the traveling and other activities you've managed to accomplish in the past couple of years while battling this beastly disease! I always hold you up as a beacon to my man: "If Nana can do it, so can you!" (I think he's just being lazy half the time). Good luck on your clinical trial at Emory - and your comment about the warm fuzzies really made my day: I live to make people feel good. Funny what you mentioned about a chair of bowlers, because about a week ago my father gave me an old bowler hat in gorgeous condition (made by Burberry in Britain) that had belonged to my grandfather and asked me if I wanted to sell it on ebay or donate it to a theatrical costume shop or something. Weird, right? Are you a bit psychic?
Great good luck, thoughts and prayers to you and Laren. Keep us posted. 💜💪🏽
glad the lynparza is helping some. Hopefully he will begin to gain some strength adventually. Atleast you got the testing done and found out somethings. God bless you both.
Thank you, Nancy. We are cautiously optimistic that his cancer may remain controlled; on the other hand, the side effects and general overall decline have me a little worried that we're not doing enough in terms of helping him to regain strength. Everything in it's own time, I guess. Thanks for your support. - and stay strong yourself! 💜💪🏽
Unbelievable! The advances in cancer treatment are so hopeful. Best to you & your man and for increased health and recovery. xoxo Lisa
Thank you, Lisa! (Everytime I see your beautiful photo I smile). You're so right about the changing cancer landscape: so many advances in so many different areas of research. We should all be very hopeful. Thanks for your continued support, and hope all is well with you! 💜💪🏽
Amazing news, Susan! I'm always happy to see an update from you and this is especially good news.

What an amazing doctor you guys are blessed with. Hopefully this is the future for all patients. Genetic testing and targeted therapy instead of a one size fits all approach. Hopefully the Hulk can start getting his strength back soon. Hugs to you both!
Thank you, Stefanie. We are indeed blessed to have the amazing Dr O'Reilly - a true healer in every sense of the word. Hope all is well with you! 💪🏽💜
if I understand pancan I have to have another biopsy which is difficult to do when the cancer is localized in pancreas. I was thinking about the molecular profiling? Is this essentially the same that your man had done? Dr. told me thay cant biopsy it either.
My guy had an endoscopic biopsy way back in 2010 before his Whipple. Did they really tell you that there is no way for tissue to be obtained? That doesn't sound right to me. But I'm not a doctor, so perhaps you should get a second opinion, Nancy.
they told me they could not biopsy it where it is located. It would be a great risk for me.
I was thinking about the molecular profiling with pancan. They need a new biopsy and they can not do one according to the doctors due to location and pancan says it is difficult to do also when localized to pancreas. Is this what your man had done, molecular profiling?
they also want tissue under a year old and mine is 2.5 years. I am so tired of everything and wish it would end but it wont.
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Vital Info

Posts

January 12, 2014

New York, New York

Loved One is a Cancer Survivor/Fighter

Cancer Info

Pancreas Cancer

Adenocarcinoma

January 7, 2010

Stage 4

Yes

The uncertainty. And with Pancreas Cancer, the knowledge that there really is no cure.

Strong relationships get stronger

Lungs, 2012. Peritoneum, 2015.

Memorial Sloan Kettering

Hundreds of new treatment protocols are being tested in Clinical Trials as I write, and drugs offering better outcomes and improved survival hit the market frequently. Don't give up hope.

Unrelenting pain in the upper belly

Radiation followed first course of chemotherapy, and was given for 28 days in September 2010

I support the Lustgarten Foundation for Pancreatic Research; the Pancreatic Cancer Action Network; Memorial Sloan Kettering Cancer Center.

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