Thursday, March 15, 2018

More shoo shoo! Or...intestinal flora and melanoma

I've posted on all things dietetic and the flora in our gut in particular for YEARS!!!  Here was my latest round-up just this January:  Microbes again...and how they may be associated with improved response to anti-PD-1 for melanoma patients...and you might even laugh!!!

I do recommend healthy eating and exercise.  I do take 2000 iu of vitamin D daily.  I do eat lots of foods with active cultures in them - yogurt, kefir, sauerkraut, etc. I eat them because I like them and we have learned that cooties in our gut are important whether they really do anything when we take anti-PD-1 and deal with melanoma or not.  I wish that making immunotherapy effective for everyone who takes it were as simple as a diet change.  However, as I've noted in prior posts...this pendulum continues to swing back and forth and the data is far from conclusive.

Now, there's this ~

The gut microbiota and immune checkpoint inhibitors. Humphries and Daud.Hum Vaccin Immunother. 2018 Mar 1.

Although immunotherapy has been remarkably effective across multiple cancer types, there continues to be a significant number of non-responding patients. A possible factor proposed to influence the efficacy of immunotherapies is the gut microbiome. We discuss the results and implications of recent research on the relationship between the gut microbiome, our immune systems, and immune checkpoint inhibitor therapies including anti-CTLA-4 Ab and anti-PD-1 Ab. While the investigations all exhibit interesting results and conclusions, we find little congruence in the specific bacteria that were found favorable for antitumor responses. It is unclear whether the inconsistencies are due to differential approaches in study design (pre-clinical or clinical subjects, anti-CTLA-4 Ab or anti-PD-1 Ab), experimental methods and measurements (metagenomics sequencing and clustering variations) or subject population dynamics (differential cancer types and baseline characteristics). Moreover, we note studies regarding particular bacterial commensals and autoimmune diseases, which challenge findings from these investigations. We conclude that with the current research, clinical investigators can appreciate the critical role of gut microbiota in mediating immunostimulant response. However, prospective research exploring the biochemical mechanisms which commensal bacteria communicate with each other and the immune system is imperative to understand how they can be adjusted properly for higher immunotherapy response.

For what it's worth.  Hang tough.  Be well. - c

Wednesday, March 14, 2018

Sew Chaotically! - Another afghan. "Soft grey and white with story books!"

A dear one of mine shared with me the sweetest news!!!  She's having a little boy this summer!!!  I screeched and danced and asked, "What are you thinking for the nursery?"  "Soft grey and white with a story book theme, " she answered.  I got busy...

I love books, good children's books in particular!!!  So, it was hard for me to choose, but this selection includes three of the top faves of my own children!

All done and ready for cuddles and stories!!  Pretty close on my yarn reckoning, don't you think?  Loving my project bag this same sweet little mama gave me (It was fate that hers be the first project it held!!!) along with the collection of crochet needles and tools Ruthie gave me!  Ready for a new project!!!  Sew chaotically!!! Happy pi day!!!!  - c

Monday, March 12, 2018

BRAF/MEK before surgery as well as after is MUCH better, than just AFTER surgery for melanoma!! Plus trial still recruiting resectable stage III/IV melanoma peeps.

We have long known that BRAF positive melanoma peeps can respond almost magically to BRAF inhibitors, and do even better, with fewer side effects and less tumor work-around, when those medications are combined with a MEK inhibitor.  However, we also know that far too often, despite the combo, tumors can still learn to rear their ugly heads after that initial response.  For that reason, BRAF/MEK inhibition is often used to lower tumor burden quickly, then start the patient on immunotherapy.  Lot's of studies are also looking at pairing this targeted therapy with immunotherapy and a host of other drugs that will boost the durability of these responses.  Here are a zillion BRAF inhibitor related posts:  More than you ever wanted to know about BRAF inhibitors/targeted therapy in melanoma

With all that being noted...the next great way to treat melanoma is through adjuvant care.  Meaning - after the patient is rendered "free of disease" (usually these are Stage III or IV patients whose tumors are removed surgically and/or treated with radiation, whose follow-up scans of the irradiated area show no viable tumor) they can then be treated with immunotherapy or targeted therapy to try to make sure that their melanoma does not come back.  This was the premise of the study arm I was in, taking nivo from 2010-2013.  We know adjuvant care, whether you use ipi, anti-PD-1, or BRAF/MEK, works for many in melanoma!!!  Here are a zillion posts on that:  Adjuvant treatments WORK in melanoma!!!

Now....with all that said...we are also learning about NEOadjuvant treatment.  This treatment is where you find out the patient has melanoma.  THEN you start them on their meds.  THEN you remove the tumor and continue the treatment.  Here are some reports on neoadjuvant studies looking at BRAFi as neoadjuvant, along with the the OpACIN trial which used ipi/nivo as neo-adjuvant for Stage III melanoma patients.  Note:  you will have to scroll through some of the posts as some of the NEO-adjuvants articles are interspersed. - Neoadjuvant studies in melanoma

Researcher Amaria (lead author of the article below), has figured largely in the published data for BRAF/MEK as neoadjuvant.  Now, there's this:

Neoadjuvant plus adjuvant dabrafenib and trametinib versus standard of care in patients with high-risk, surgically resectable melanoma: a single-centre, open-label, randomised, phase 2 trial. Amaria, Prieto, Tetzlaff, et al. Lancet Oncol. 2018 Jan 17.

Dual BRAF and MEK inhibition produces a response in a large number of patients with stage IV BRAF-mutant melanoma. The existing standard of care for patients with clinical stage III melanoma is upfront surgery and consideration for adjuvant therapy, which is insufficient to cure most patients. Neoadjuvant targeted therapy with BRAF and MEK inhibitors (such as dabrafenib and trametinib) might provide clinical benefit in this high-risk p opulation.

We undertook this single-centre, open-label, randomised phase 2 trial at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). Eligible participants were adult patients with histologically or cytologically confirmed surgically resectable clinical stage III or oligometastatic stage IV BRAFV600E or BRAFV600K (ie, Val600Glu or Val600Lys)-mutated melanoma. Eligible patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, a life expectancy of more than 3 years, and no previous exposure to BRAF or MEK inhibitors. Exclusion criteria included metastases to bone, brain, or other sites where complete surgical excision was in doubt. We randomly assigned patients (1:2) to either upfront surgery and consideration for adjuvant therapy (standard of care group) or neoadjuvant plus adjuvant dabrafenib and trametinib (8 weeks of neoadjuvant oral dabrafenib 150 mg twice per day and oral trametinib 2 mg per day followed by surgery, then up to 44 weeks of adjuvant dabrafenib plus trametinib starting 1 week after surgery for a total of 52 weeks of treatment). Randomisation was not masked and was implemented by the clinical trial conduct website maintained by the trial centre. Patients were stratified by disease stage. The primary endpoint was investigator-assessed event-free survival (ie, patients who were alive without disease progression) at 12 months in the intent-to-treat population. This trial is registered at, number NCT02231775.

Between Oct 23, 2014, and April 13, 2016, we randomly assigned seven patients to standard of care, and 14 to neoadjuvant plus adjuvant dabrafenib and trametinib. The trial was stopped early after a prespecified interim safety analysis that occurred after a quarter of the participants had been accrued revealed significantly longer event-free survival with neoadjuvant plus adjuvant dabrafenib and trametinib than with standard of care. After a median follow-up of 18·6 months (IQR 14·6-23·1), significantly more patients receiving neoadjuvant plus adjuvant dabrafenib and trametinib were alive without disease progression than those receiving standard of care (ten [71%] of 14 patients vs none of seven in the standard of care group; median event-free survival was 19·7 months vs 2·9 months. Neoadjuvant plus adjuvant dabrafenib and trametinib were well tolerated with no occurrence of grade 4 adverse events or treatment-related deaths. The most common adverse events in the neoadjuvant plus adjuvant dabrafenib and trametinib group were expected grade 1-2 toxicities including chills (12 patients [92%]), headache (12 [92%]), and pyrexia (ten [77%]). The most common grade 3 adverse event was diarrhoea (two patients [15%]).

Neoadjuvant plus adjuvant dabrafenib and trametinib significantly improved event-free survival versus standard of care in patients with high-risk, surgically resectable, clinical stage III-IV melanoma. Although the trial finished early, limiting generalisability of the results, the findings provide proof-of-concept and support the rationale for further investigation of neoadjuvant approaches in this disease. This trial is currently continuing accrual as a single-arm study of neoadjuvant plus adjuvant dabrafenib and trametinib.

In this study of only 21 stage III/IV patients who had never taken BRAF/MEK, whose tumors were BRAF positive, and could be removed surgically, were divided in 2 groups. Folks with "metastases to bone, brain, or other sites where complete surgical excision was in doubt" were excluded.  7 got standard of care:  complete excision of their tumor and "consideration" of adjuvant therapy.  21 got the BRAF/MEK combo (dabrafenib and trametinib) BEFORE surgical removal of their lesion as well as AFTER!  Ten of the 14 treated with BRAF/MEK before and after excision were alive without disease progression "vs none of seven in the standard of care group"These results were deemed so good that this phase of the trial was stopped and only the neoadjuvant/adjuvant arm is continuing, and in fact, recruiting.

This is great news.  However, I do see several flies in this report.
1.  You researchers left out some folks in serious need of care...folks with brain, bone and other mets that you didn't see as a winning ticket.  I've been one of those peeps and was given adjuvant care.  Those folks need neo-adjuvant/adjuvant care as much (or more!!!!) than anybody!!  Here's a small tirade on their being left out of clinical trials:  A really good review of treatment data for Melanoma Brain Mets!!! (And this is from 2015!!!!!!!!)
2.  These are really small both arms.
3.  The fact that the 7 in the standard care arm were eligible for "consideration" of adjuvant care is pretty lame.  That language tells me that some chose to forego adjuvant care!!!  So OF COURSE!!! ~ those who had no additional care did less well!!!!  To provide greater clarity and benefit, the authors should have clearly defined the standard of care group in regard to whether they actually utilized BRAF/MEK after resection or not.
4.  Finally, I really don't care for the major drama, yet lack of real information, posed in this categorization of the 7 peeps in the standard of care group:  "more patients receiving neoadjuvant plus adjuvant dabrafenib and trametinib were alive without disease progression than those receiving standard of care (ten [71%] of 14 patients vs none of seven in the standard of care group".  At first blush it seems that all of the 7 are dead, along with the 4 out of the 14 in the neo/adjuvant group!!  Come on, Amaria!  You have better writing skills than this!  Some of these peeps may well have passed, but it is also possible that ALL these folks are alive, albeit with disease progression.  Clarification of that could easily have been included in this abstract and is hopefully made more clear in the actual published article.

Now...despite that critique...I am a huge fan of neoadjuvant treatment.  More and more, it is looking as though melanoma peeps treated in this way do better.  But, if nothing else, neoadjuvant treatment (treatment BEFORE surgical resection) provides decreased tumor bulk, therefore minimizing the invasiveness of the surgical resection.

You know me, Keep'n it💯!!!!!!!!!!  ~ les

Saturday, March 10, 2018

Sew Chaotically! - Pillow cases...again...for REALZ!!!

Some dear young peeps of mine are embarking on a lovely life together and found a sweet house, that reminds me a great deal of the one (both built in 1900!!) Brent and I started our crazy journey together in!!!  I thought it might be fun to offer up some pillow cases (or robes....though I would strongly recommend the pillow cases!!! HA!) as a house warming gift.  The idea was met with enthusiasm and I was sent a pic of bedding to match and a request for two standard sized pillow cases and two covers for 18 inch square throw pillows!!  Sew exciting!!!!

The bedding to match is to the left.  And this is what I picked.
I can't tell you why the burgundy looks different
depending on the photo...but it really
does match the little flower in the print to the left!

The finished products!!!
Replete with envelope style closures on each!
Life has its own ideas at times so through a misunderstanding, the pillow cases were sent to the WRONG address!!!  Yes, my poor shy intended peep went to the WRONG address to seek sent cases, left notes, but to no avail.  Gone they are!!  Perhaps they are making someone happy and slightly guilty all at the same time!!  At any rate, we begin again...

Back to the matching board!
Here's the fabric selection for this go round as the other was no longer available at my JoAnn's.  I think I might like it better!
2 standard sized cases.  2 to fit the throw pillows (fingers crossed)!!  All with their envelope finished ends!
There they be!  Practice makes perfect, no???
I have been informed that the last set arrived at the proper place and worked out well!!!  YAY!!!  Congrats you two!!  May you share many laughs, lovely moments, and brilliant bedding in your new home!!!  Much love, cess

Friday, March 9, 2018

CONCURRENT radiation and immunotherapy for brain mets is BEST!!!! (yes, AGAIN!!!)

"I know, I know!!!!"   I keep ranting about this.  And I will continue until it seeps into the pores of all melanoma (as well as NSCLC and renal cell carcinoma) patients and docs!!! Here are just a few zillions rants, posts, and data:  Yes, you SHOULD COMBINE radiation and immunotherapy!!!!
Now, there's this ~

Concurrent Immune Checkpoint Inhibitors and Stereotactic Radiosurgery for Brain Metastases in Non-Small Cell Lung Cancer, Melanoma, and Renal Cell Carcinoma. Chen, Douglass, Kleinberg, et al.  Int J Radiat Oncol Biol Phys. 2018 Mar 15. 

To characterize the effect of concurrent stereotactic radiosurgery-stereotactic radiation therapy (SRS-SRT) and immune checkpoint inhibitors on patient outcomes and safety in patients with brain metastases (BMs).

We retrospectively identified metastatic non-small cell lung cancer, melanoma, and renal cell carcinoma patients who had BMs treated with SRS-SRT from 2010 to 2016 without prior whole-brain radiation therapy. We included SRS-SRT patients who were treated with anti-cytotoxic T-lymphocyte-associated protein 4 (ipilimumab) and anti-programmed cell death protein 1 receptor (nivolumab, pembrolizumab). Patients who were given immune checkpoint inhibitors on active or unreported clinical trials were excluded, and concurrent immune checkpoint inhibition (ICI) was defined as ICI given within 2 weeks of SRS-SRT. Patients were managed with SRS-SRT, SRS-SRT with nonconcurrent ICI, or SRS-SRT with concurrent ICI. Progression-free survival and overall survival (OS) were estimated using Kaplan-Meier survival curves, and Cox proportional hazards models were used for multivariate analysis. Logistic regression was used to identify predictors of acute neurologic toxicity, immune-related adverse events, and new BMs.

A total of 260 patients were treated with SRS-SRT to 623 BMs. Of these patients, 181 were treated with SRS-SRT alone, whereas 79 received SRS-SRT and ICI, 35% of whom were treated with concurrent SRS-SRT and ICI. Concurrent ICI was not associated with increased rates of immune-related adverse events or acute neurologic toxicity and predicted for a decreased likelihood of the development of greater than/= to 3 new BMs after SRS-SRT. Median OS for patients treated with SRS-SRT, SRS-SRT with nonconcurrent ICI, and SRS-SRT with concurrent ICI was 12.9 months, 14.5 months, and 24.7 months, respectively. SRS-SRT with concurrent ICI was associated with improved OS compared with SRS-SRT alone and compared with nonconcurrent SRS-SRT and ICI on multivariate analysis. The OS benefit of concurrent SRS-SRT and ICI was significant in comparison with patients treated with SRS-SRT before ICI or after ICI.  
Delivering SRS-SRT with concurrent ICI may be associated with a decreased incidence of new BMs and favorable survival outcomes without increased rates of adverse events.

Here folks looked at patients suffering from brain mets due to NSCLC, melanoma, and renal cell carcinoma.  Between 2010 and 2016, these peeps were treated with SRS-SRT and given either ipi, nivo or pembro.  CONCURRENT immunotherapy was defined as the meds having been given within 2 weeks of the radiation.  There were three groups:  1) those treated with radiation alone, 2) those treated with radiation and NON-concurrent immunotherapy, 3) and those treated with radiation and CONCURRENT immunotherapy.  260 patients were given radiation to 623 brain mets.  181 had radiation alone.  70 patients got radiation and immunotherapy with 35% of those attaining radiation concurrent with immunotherapy.  Overall survival for radiation alone = 12.9 months.  OS for radiation and NON-concurrent immunotherapy = 14.5 months.  OS for radiation with CONCURRENT immunotherapy = 24.7 months.  This was true no matter if the radiation was given before or after the immunotherapy....AND....wait for it....CONCURRENT administration of immunotherapy and radiation did NOT cause increased immune side effects NOR an increased rate of neurologic problems!!!!!!!!!!!!!!!!!!!  However, CONCURRENT immunotherapy and radiation DID decrease development of additional brain mets later!!!!

Come on folks!!!  This matters.  This is important.  This changes SAVES lives!!!  Do NOT settle for less.  If you have brain mets, demand CONCURRENT immunotherapy and SRS!!!!  There is more than enough proof.  It makes a positive difference!!! - c

Sunday, March 4, 2018

March Forth ~ My FAVORITE day!!

March Forth.  The day hope springs eternal.  The day mother nature shows us the beauty that life really is ~ and is yet to become. 

All in all, a day of hope and promise and love for you and yours!!!
Yes, I am strange.  And yes, I've thought that MARCH FORTH should be the REAL meaning of this day on the calendar since I was a child.  If this solitary day left you inspired, but wanting even more, this really is YOUR day!!!  Here is a March Forth retrospective, just for you!

I live chaotically.   You may live any way you like!  Just LIVE!!!!! - love, les

Friday, March 2, 2018

Sew Chaotically! - Le Laboratoire Familial's Celestine Jacket

Sew....Bentie secretly got me this pattern, Le Laboratoire Familial's Celestine Jacket, when he ever so sweetly emailed and basically drove the nice ladies of this company crazy because I wanted their lovely Scarlett blouse boss!  He managed it and I got both patterns!!!!  Is he and Le Laboratoire awesome or what????  From the start, I was set that this jacket be made up in quilted pink.  I have to admit that when I found this fabric in London on Goldhawk Road, I was super excited and a little frightened!!  I fear the little man who had to climb up a very tall ladder to fetch it may have believed me a tad deranged!!! Lord have mercy, it is PINK!!!!!!! (And very shiny!!!! Like the crazy person that I am....though I LOVE the Scarlett blouse more (and have the most lovely piece of blue shirting for it!!!)...the challenge of this piece made me want to make it first!!!!  I looked at reviews.  I studied the pattern.  B helped with translation.  I ended up getting some suede-like ??? scuba knit (It is super soft and buttery!  I used the remnants of it in Rosie's Linden!) to tone down the pinkness for use in the trim and sleeves.  I debated the pockets, the lining, zip front vs buttons.  In the end, here's what I did:
Since my quilted fabric is finished on both sides and the knit feels lovely, I decided to skip the lining.  That settled, I debated les poches!!!  (See how much French I learned???)  I was a bit intimidated by the slash pockets, never having made them.  Plus with no lining, I wasn't sure how they would work out just hanging there.  So, I was struck by one of my craziest but best ideas ever!!!  I would use the pattern and instructions from Tessuti's Demi Pants to make the pockets!!!

Warm and soft and buttery on the inside!
Sleek and perfect on the outside!!!
Isn't that awesome????

I admit to some considerable concern that I might look like an extra for Grease!  But, when something is already too much ~ it just needs MORE!!!!
Enter...the FROGS!!!!  Pink ones, no less!

Well, the frogs took away some of the Grease and added a taste of Geisha ~ or something!!!  No worries!  I loooove it!
Have to say, I'm pretty proud of the stitchery!!!

This whole experience has been an enormously fun adventure.  A pattern from France, with pockets from Australia. Fabric from London. Frogs from a lady who claims she gets them from a maker in Hong Kong.  Crazy from inside my brain, and much patience and sweetness from my B!!!  I'm thinking that alone is good!!  But, I figure I can rock it out Rihanna style with army green skinnies and boots, jeans may be a bit tricky given my Grease phobia.  Kinda liking my black slacks and velvet slippers!!!  Life is just a party, baby!  Cheers!

Sew Chaotically! - love, les