Thursday, February 22, 2018
For BRAF positive melanoma patients, targeted therapy with a BRAF inhibitor combined with a MEK inhibitor can have amazing results in the destruction of melanoma! Response rates are around 70-80%!! While there are a few exceptions, the problem with this targeted therapy is that the benefit often evaporates around 6-9 months, with sinister melanoma developing the ability to work-around the treatment. These peeps then go on to other treatments. Sometimes those work, sometimes they don't. If they don't, will taking BRAF/MEK again work?????
Now, there's this:
Rechallenge with BRAF-directed treatment in metastatic melanoma: A multi-institutional retrospective study. Valpione, Carlino, Mangana, et al. Eur J Cancer. 2018 Jan 19.
In this study, 116 peeps who had taken BRAFi (a BRAF/MEK combo) for an average of 9.4 months stopped taking it for a variety of reasons ~ and had roughly 8 months of: immunotherapy (72%), other treatment (17%) and drug holiday (11%). They were then rechallenged with a BRAF/MEK combo. Response rate for the rechallenge was 43% with 3% attaining a complete response, 39% a partial response and 24% gaining stable disease, although 30% had progressive disease and 4% were apparently lost to follow-up. Of the 83 peeps who stopped BRAFi initially due to disease progression, 31 responded to the rechallenge - 30 with a partial response and 1 with a complete response. Median OS from BRAFi retreatment was 9.8 months and PFS was 5 months.
Given the results of this study, the answer to the initial question I posed, is: YES, a rechallenge with BRAF/MEK can work with a response rate of about 43% generally and 37% in those who progressed on BRAFi the first go round. Response rates are not as high nor as complete as those attained with the initial treatment....but....they are there!!! Repeating treatment with BRAF/MEK is certainly an option in kicking melanoma in the teeth a bit, while seeking more effective, durable treatment.
It's something. Thanks, ratties. - c
Monday, February 19, 2018
If you've read this blog for 10 minutes, it's pretty clear that B spoils me rotten. However, every once in a while, something happens to his brain. About 18 years ago, despite having my 90 pound, pound puppy Ruff Ruff (Yes. He really was from the pound, some thick lab/shepherd mix, named by a 4 year old.) in the back yard, I told Bent that it would be super awesome if we got an inside puppy. He looked at me....and said...."No!" What the???? Not, "Okay, baby. We'll see." Or, "Really, sweetie? Well, we'll think about it." He. Said. NO!!!!!!!!!!!!! Well!!!! I didn't speak to him for days. But, then, on a cold, rainy November morning in 2000, B brings me a cup of coffee in bed (What a jerk!! Right????) and says, "There's a puppy outside." I think my response was something like, "Kiss my ass!" He just looked at me sadly and said, "No. Really. There's a puppy outside." Feeling that I am being tricked somehow...I looked out the front door. Sure enough. There was a beagle-esq, shivering, pup. Foot pads, cut and bloody. Skinny. Trying to stay under the eave, out of the rain. Well. In about two seconds, he was cuddled up in my robe. Scrubbed free of his fleas and such. And welcomed INSIDE! A new puppy (somewhere between 6 and 16 months per the vet) named....KARMA! B's. Not mine. He was the sweetest. Never peed or pooped in the house (until recently). LOOOOVED the kids. Would run and bite Fred on the bootie on command. Would lie like a contented snoring unconscious thing on his pillow. THEN! You see that the toast or chicken or cake is eaten - the shoe is destroyed - the potted plant is UN and dirt is every where! You look back! The Karm is still snoring on his pillow! HOW did this happen???? He would look at you sweetly and say, "Wasn't me!" He was my worst trained dog ever. He never "came" or "heeled". But, he never barked. He LOOOOVED Ruff Ruff and later Zeno. He wanted so much to run with the big dogs. The only noise he ever made was to yoddle happily when on a walk with all his peeps and the big dog! On meeting him, Ruff looked up at me and said, "Really, mom? We have to keep him? I could do away with this THING in a single bite?!" My Ruff WAS well trained and believed me when I said, "Yes. He needs a home."
|Happy with his Freddo!|
|The fierce beastie!!!|
|Karm and Roo!|
|You see Zeno staying with his peeps and Karma just going his own way????|
|...and his dog.|
|He was always a good walking buddy and LOVED all my makes!!!|
Sunday, February 18, 2018
SPRING is sprung!!! She's coming! I know you may still be snow blow'n....but she is on her way. Here is a first taste of mine...
|Maybe I should eat it? Or make it into a paste? Everything Cures Melanoma!!! (And yes, we're up to installment #9 - with no actual cure!) I think I'll just love it!|
|She may not look like much right this minute (speckled leaf to the right) but I am pleased to see her. She is one of two trout lilies I have planted along the edge of my creek. They have yet to bloom, but they have come back every year.|
|Here's one in Cades Cove doing her thing!!!|
If you want a bigger and even more beautiful look at SPRING in what I also consider "my backyard" ~ check this out: April in Cades Cove, 2015.
"I see trees of green, red roses, too. I see friends shaking hands, saying 'How do you do?' They're really saying, 'I love you!'" ~ Oh, YES!!!! - les
Saturday, February 17, 2018
Circulating tumor DNA to help differentiate true progression of melanoma vs pseudoprogression in patients treated with anti-PD-1
I've been yelling for some time about the need to develop, refine and put into practice valid, reliable blood assays....whether they are measuring circulating DNA, tumor cells, various other tumor makers, white blood cells, any other floating bits and bobs...in order to diagnosis melanoma, determine the most effective treatment, and recognize progression and/or effectiveness of that treatment. Here is a link to a zillion of those reports/rants: Blood assays, tumor markers, circulating DNA, you name it!!!!
In fact, the report below is a follow-up report and specific look at pseudoprogression from this study: 2017: Circulating DNA predicts response to anti-PD1
Now, there's this -
Association Between Circulating Tumor DNA and Pseudoprogression in Patients With Metastatic Melanoma Treated With Anti-Programmed Cell Death 1 Antibodies.Lee, Long, Menzies, et al. JAMA Oncol. 2018 Feb 8.
Longitudinal circulating tumor DNA (ctDNA) has been shown to predict response and survival in patients with metastatic melanoma treated with anti-programmed cell death 1 (PD-1) antibodies. Pseudoprogression, defined as radiologic finding of disease progression prior to response, has been a challenge to clinicians.
To establish whether ctDNA at baseline and up to week 12 of treatment can differentiate between the radiologic findings of pseudoprogression and true progression in patients with metastatic melanoma.
This explorative biomarker study examined circulating BRAF and NRAS mutations in a cohort of 125 patients with melanoma receiving PD-1 antibodies alone or in combination with ipilimumab between July 3, 2014, and May 24, 2016. Pseudoprogression was defined retrospectively as radiologic progression not confirmed as progressive disease at the next radiologic assessment. Plasma samples of ctDNA at baseline and while receiving treatment were taken for analysis prospectively over the first 12 weeks of treatment. Favorable ctDNA profile (undetectable ctDNA at baseline or detectable ctDNA at baseline followed by greater than 10-fold decrease) and unfavorable ctDNA profile (detectable ctDNA at baseline that remained stable or increased) were correlated with response and prognosis.
Early differentiation of pseudoprogression from true progression using longitudinal ctDNA profile.
According to guidelines by Response Evaluation Criteria in Solid Tumors (RECIST), progressive disease occurred in 29 of the 125 patients (23.2%). Of the 29 patients, 17 (59%) were 65 years or younger, 18 (62%) were men, 9 (31%) had pseudoprogression, and 20 (69%) had true progression. Of the 9 patients (7%) with confirmed pseudoprogression, all patients had a favorable ctDNA profile. At a median follow-up of 110 weeks, 7 of 9 patients (78%) were alive. All but 2 patients with true progression had an unfavorable ctDNA profile. Sensitivity of ctDNA for predicting pseudoprogression was 90% and specificity was 100%. The 1-year survival for patients with RECIST-defined progressive disease and favorable ctDNA was 82% vs 39% for unfavorable ctDNA. Overall survival was longer in patients with a partial response (54 of 125 patients [43%]) compared with patients with progressive disease and a favorable ctDNA profile (11 of 125 patients [9%]).
The results demonstrate that ctDNA profiles can accurately differentiate pseudoprogression from true progression of disease in patients with melanoma treated with PD-1 antibodies. Results of this blood test performed at regular intervals during systemic treatment reflect tumor biology and have potential as a powerful biomarker to predict long-term response and survival.
Here researchers looked at 125 melanoma patients with BRAF and NRAS mutations treated with anti-PD-1 alone or in combination with ipi between July 2014 and May 2016. They drew their blood before and during the first 12 weeks of their treatment and correlated those findings with the patient's response and prognosis. Per the RECIST scale, progressive disease occurred in 29 of the 125. 9 had pseudoprogression and 20 had real progression. "All but 2 of the patients with true progression had an unfavorable ctDNA profile. Sensitivity of ctDNA for predicting pseudoprogression was 90% and specificity was 100%." The 1 year survival for the folks with RECIST defined progression but WITH the favorable blood test ctDNA was 82%, while for folks with an unfavorable ctDNA it was only 39%. "The results demonstrate that ctDNA profiles can accurately differentiate pseudoprogression from true progression of disease in patients with melanoma treated with PD-1 antibodies."
I think we've yammered about this stuff enough. Consistent, available, defined blood assays need to be made readily available for melanoma patients!!!! C'mon man!!!! - c
Thursday, February 15, 2018
One Hell of a day! And, yes. Fredda Branyon is STILL a criminal!!! So is Mathew Anderson, Kurt Adams and Mathew Adams in Tampa!!!
Okay. I have the best family and friends EVER!!! My dear sweet love, D, taught my husband in college when B was only 18+. Need I say more??? This man (D) is clearly a saint! I've been dealing with B after maturation at age 40! Girl! It's been real!!! D was not only B's professor but mentor. Paths diverged, but realigned when they found each other again 20+ years ago. Since then we have been forever bonded. We are hiking buddies. We are parents and grandparents. We are dinner companions. D sat with B through my surgeries. D takes care of my children, even though they are now 25 and 27. Hell! D takes care of ME!!! WE are FAMILY!!! Today a fucking asshole scammed my dear D. Calling him...saying, "Hey, this is your grandson!" To which D responded, "What?" But, then he assumed it was my son. In the end scammer asshole said my son, D's dear grandson, was in jail due to unfortunate circumstances in Tampa, Florida and needed $1,485.00 in order to make bail. My dear sweet friend, went as fast as he could to the nearest Moneygram office and sent the money. This ass first called posing as my son, then, as soon as it sounded as though D would help, he called again - posing as a person (Matthew Anderson) from the Public Defender's Office in Tampa who needed the money sent to Kurt Adams in the office of Bail Bonds Roche at 1906 Orient Road, Tampa, Fla. Kurt Adams took the money.
Not only did he take the money....he called dear D back later that afternoon. Shockingly, he needed more money to settle the entire situation. Well, dear D didn't have that money. So, he came over. Needless to say, he had promised his grandson that he wouldn't tell us of all the difficulties...but when the funds were such that he couldn't meet the need...he felt horrible...but came to tell us. Well! We called our son. No, he was not in Tampa. And, No! None of the things alleged had happened!!!! But, we went to town on Matthew Anderson/Kurt Adams/Matthew Adams!!! (And, I am not done!!!)
A quick google of the number: 1-800-388-6514 (Please call it! One thousand times. Over and over. Leave a message that you are ready to wire money for your dear one!!!!) shows that many folks have been scammed in a similar way. See this post: https://www.facebook.com/celeste.morris.140 where I added to the message the Lucas County Sheriff's Office has put out.
Thankfully, Moneygram....somehow, someway....despite paying out the initial sum....figured out this asshole is a scammer. They are to refund my dear sweet D his money. But....I am not done! I will be contacting the Hillsborough County Sheriff's Department in the morning. I have already reported the crime here in TN. I have let the Bail Bond Company know that their name and address are being used by an ass. I am not done! Be ware and help me if you can. I HATE BULLIES!!! And thieves. And liars!!!!!!!!!!!!!!!!!!!!!!!!
On that topic....Fredda Branyon. Remember her???? Check out this post if you don't: Quack Watch!!! - Jerks who try to take advantage of the word "cancer"! And this one: Jenny Hudgeson, Kim Burns, and Fredda Branyon...different or the same???? This bitch and her minions (or just herself with poor English and weirdness) posted on MY blog!!! Then, with a little research, I discovered she was posting on any blog with "cancer" in the title!!!!!! What a horrible person!!! As if that was not enough, I learned this: Stem Cell Smuggler Pleads Guilty
Basically, it says this:
A former Arizona laboratory owner has pleaded guilty to selling unapproved stem cells across state lines. Fredda Branyon, the former owner of Global Laboratories in Scottsdale, AZ, faces up to three years in jail and up to $10,000 in fines. Appearing before a US district judge on August 18, Branyon admitted that in 2009 her company sold stem cells for non-research purposes without FDA approval.
Specifically, she admitted to selling 183 vials of stem cells to an individual in Brownsville, TX on 27 separate occasions between April 2009 and February 2010 for approximately $300,000. This individual then treated patients suffering from autoimmune diseases with these stems cells.
The stem cells were not created under FDA guidelines or in an FDA-approved facility. Instead, Branyon created the stem cells from the umbilical cord tissue purchased from a Del Rio, Texas midwife. Because Branyon did not have an experience creating stem cells, she hired a Charleston, SC medical school professor to assist her.
“It’s a real disservice to people who are really trying hard to follow rules, and perhaps overly strict rules because of the misinterpretations of what stem cells are. To do something like that just makes it harder and harder for those therapies to become actualized,” said Broad Institute stem cell researcher John Rinn.
In 2009, Branyon announced that her Branyon Integrative Medical Group (BIMG) would perform a study on the treatment of HIV-related illness using umbilical cord-derived stem cells. The study was designed as a six-month program to be overseen by Mexican physician Edgar Payan Arechiga. It is not known if this study was actually conducted. The BIMG, formerly known as the New Hope Medical Center, was founded by Branyon to offer alternative treatments for patients suffering from cancer and other chronic illnesses.
“It’s just too easy to make money off of sick people, and some of these [stem cell] clinics are taking real advantage,” says stem cell clinic watchdog Barbara Hanson. After a bad experience in a Tijuana stem cell clinic that promised to cure Hanson and her friend’s chronic obstructive pulmonary disease (COPD), the two women co-founded the online forum Stem Cell Pioneers in 2007. The forum gives patients interested in stem cell therapies a place to share information related to stem cell treatments, doctors, clinics, and results.
In 2007, Hanson posted information on the forum about Branyon’s background, pointing out that Branyon was not an accredited doctor in the US. At that time, Branyon wrote in an e-mail to Hanson, “Because of pulling in many many types of treatments from around the world (some not FDA approved) for other MDs and DOs I decided not to become licensed. I never lost a license because I never had one to loose [sic]. With the type of research that I have donated my life to, I could in no way have done it with a license.”
So many fucking assholes!!!!!!!!!!!!!!!!!!!!!!!!!! You make money off of men of integrity who love their children. You make money off desperate cancer patients. Are you kidding me????
But...I digress. Fredda still thinks she is awesome. Her doctor-less self who lied, stole, broke the law, used cancer patients....still thinks she has an audience!!! Here is her blog: Dr. Fredda Branyon My life's mission is to Educate people about the power of Hope STILL calling herself a DOCTOR...no less....and hijacking HOPE!!!!!!!!!!!!!!!!!!!!
What the hell????? I. AM. NOT. DONE!!!!!!!!!!!!!!!!!!!!!!!!!!!!! Help me if you can. I try to be a beacon of light. But, I am sick of this shit!!!
Where are the people in charge??? Where are the Medical State Boards??? Arizona???? Seriously??? We got kids killing kids. We got an orange man telling us we need to recognize kids in need of help. I DO!!! EVERYDAY!! And guess what? There are NO services! Kids living with friends because their parents are dead, or in jail, or don't care...don't have insurance. And even if you do have insurance....have you tried to access mental health services? Or ANY services???? This kid was pitiful...horrible....despicable...tortured...evil...broken. Whatever you want to call it. Whatever it really was. If he hadn't had a gun he couldn't have killed 17 innocent people. PERIOD.
My heart hurts. My head hurts. And I have lost nothing. But...I. AM. NOT. DONE!!!!!!! - c
Wednesday, February 14, 2018
I am absolutely, hands down, the luckiest girl in the world!!! All because of THIS guy ~
|Yes, Bentie had just about knocked his leg off hopping into place after setting the camera! See the concern on all our faces????|
|He cleans up nice, doesn't he???|
|Is very colorful!!!|
|Knows how to let loose!!!|
|Is good in close spaces!|
|Does NOT like to be a hot little donkey!!|
|Will deal with animals that he doesn't wish to know if it makes little people happy.|
|Is the best son, caretaker, and friend EVER!|
|Is basically a BAD ASS!!!|
|An amazing hiking buddy!|
|And if all of that, and YEARS of dedicating his life to the care of children were not enough, he is out in the community daily - speaking out for the rights of children and their families to have safe, clean spaces in which to play!|
|Even today! There he was, fighting for: Air you can breathe! Water you can trust! Climate you can live in! Dirt you can play in!|
|And to confirm that I am lucky in even more ways ~ I had a most beautiful visitor!|
|As well as a super fun and lovely visit from Roo this past weekend, where we made TWO fun tops. This little Sorbetto in a crazy "CHEMISTRY" print...|
|...and a fun cropped LINDEN sweatshirt out of remnants of a soft moleskin scuba I recently used in a jacket and a nice black knit from a skirt for Roo to be!|
|Added lovely tulips to my pretty desk...|
|...and surprised me with beautiful art he had made just for me, which now hangs above my kitchen door!|
|How lovely is that???? Hope flies on dragonfly wings....|
I love you Rose and Freddo! I adore you, my Bentie! You are my heart, on Valentine's Day and every day in between. - les
Sunday, February 11, 2018
For Jubes...and the rest of us!!! An anti-rheumatic drug that increases the effect of vemurafenib and selumetinib????
The minute B found this article he was yelling, "Oh, this might be important to Jubes!!!" Well, I hope not!!! Many (actually - probably most!!!) folks who take immunotherapy deal with some amount of arthralgias (joint pain). However, my sweet Anne-Louise dealt with significant arthritis/spondylitis due to her immunotherapy treatment for melanoma! However, after prednisone and other meds like infliximab she got her joint pain under control and threw melanoma to the curb!! But....immune disease and side effects with immunotherapy remain a significant double decker problem.
First....what if you already know you have an immune disease like rheumatoid arthritis? Can you still take immunotherapy? The short answer is YES!!! You can!! Here is a recent post on the subject with more links within: Immunotherapy for melanoma with a pre-existing autoimmune disease??? YES!!! You can!
Here's another report: Patients with preexisting immune disease, melanoma, and treatment with Anti-PD-1? Yes, this can be done. Yes, autoimmune flares should be treated with immunosuppressive therapy while on immunotherapy. And YES!!!! These patients can still attain a response!
Second...there are the folks who didn't have arthritis or other autoimmune diseases (that they knew of) at the start of treatment...but end up with all sorts of immune related side effects caused by their immunotherapy. What should we do with them???? Treat them! Sometimes with a break of their immunotherapy, but with prednisone and other drugs as needed. Right then, right there! And, YES!!! They can still go on to have a response and rid themselves of melanoma in the process! (Just like Jubes!!!) Here are related posts: One more time: Immunosuppressive therapy to manage side effects to immunotherapy does NOT affect response! New report.
And this: Immune related side effects from immunotherapy can and SHOULD be treated!!!!
And this: Side effects and how to manage them in targeted and immunotherapy for melanoma
And finally...this post with a treatment algorithm for neuro side effects and links to algorithms for other immune related side effects: Neurologic side effects to immunotherapy with treatment algorithm
Okay! You'd probably like me to get to a point! What if there was a drug that helped folks with their rheumatic disease AND helped get rid of their melanoma???? Well now, there's this:
The anti-rheumatic drug, leflunomide, synergizes with MEK inhibition to suppress melanoma growth. Hanson, Robinson, Al-Yousuf, et al. Oncotarget. 2017 Dec 17.
Cutaneous melanoma, which develops from the pigment producing cells called melanocytes, is the most deadly form of skin cancer. Unlike the majority of other cancers, the incidence rates of melanoma are still on the rise and the treatment options currently available are being hindered by resistance, limited response rates and adverse toxicity. We have previously shown that an FDA approved drug leflunomide, used for rheumatoid arthritis (RA), also holds potential therapeutic value in treating melanoma especially if used in combination with the mutant BRAF inhibitor, vemurafenib. We have further characterized the function of leflunomide and show that the drug reduces the number of viable cells in both wild-type and BRAFV600E mutant melanoma cell lines. Further experiments have revealed leflunomide reduces cell proliferation and causes cells to arrest in G1 of the cell cycle. Cell death assays show leflunomide causes apoptosis at treatment concentrations of 25 and 50 µM. To determine if leflunomide could be used combinatorialy with other anti-melanoma drugs, it was tested in combination with the MEK inhibitor, selumetinib. This combination showed a synergistic effect in the cell lines tested. This drug combination led to an enhanced decrease in tumor size when tested in vivo compared to either drug alone, demonstrating its potential as a novel combinatorial therapy for melanoma.
In this study, researchers say that leflunomide...a drug used to treat rheumatoid arthritis...seemed to have "therapeutic value" when it was combined with vemurafenib (a BRAF inhibitor) as well as when it was combined with selumetinib (a MEK inhibitor)...in both BRAF positive and BRAF wild type patients! So far, it seems that this is in petri dishes and real live furry ratties. However, if this works this could be super cool for getting rid of melanoma as well as a boon for folks already dealing with arthritis...or perhaps debilitated by arthralgias due to their melanoma treatment.
It's got a ways to go before we can get too excited. But, I like the direction!!! As for my dear Anne-Louise....I hope that she NEVER needs another melanoma or arthritis treatment....EVER!!!! And...I do hope to hear her play her fiddle someday!!!
Hang in there, ratties! (Those that are furry and those who are not so much!) - c