Live chaotically!!! ~ Refashion #2 ~ and a buried lead from weird, wacky, melanoma world!!!!

In the (lately) ongoing series of posts that are the height of crunchy, artiness combined with the mother of invention (necessity) and a bit of elbow grease (often icky effort) there is this ~ Need something to hold your music now that you're gonna revive your piano skills???

Well, you have this slightly moldered and faded basket (now cleaned and left in the sun for a couple of days)!!!

Apply some stain.  Let dry.  Rub (repeatedly) with a clean dry cloth when it doesn't "dry"!!!!

And there she be!!!  Quiet, unassuming, utilitarian.  But pretty and useful just the same!

Have an asparagus fern outgrowing its previous situation?  Got an old stool?  This one was from a local yard sale.  Failed to get a pic of the original. But, a couple of coats of blue paint and you are set!!!

In the refashioning of me ~ I've been out of work in Greenland for two weeks!!!  There was a to-do list!  You would not believe the stuff that's been accomplished around here!!!  I was so excited that it had only two more items left to complete before an amazing Italian vacay...leaving several weeks of reading, music and sewing!!!!  Well, when you live in weird, wacky, melanoma world, you never know what might happen next.

Monday, I had my now ANNUAL brain MRI and CT's of neck, chest, abdomen and pelvis.  I didn't even have to go ballistic on some A$$hole at BCBS!!!  All studies were approved with no talk of, "These studies are not needed due to your history of 'skin disease'!"  Three sticks and one sluggish lab tech later - while driving home after a late breakfast that included a large hair, unlike mine,  laying across the potatoes that accompanied a bacon, egg and avocado sandwich from First Watch, I got a call from my local oncologist.  "Hello!  Oh my goodness!!  Ummmm.  I mean, your scans were fine and your brain was fine in regard to melanoma, but you have an acute appendix."  I'm like, "No, I don't.  I don't even have a stomach ache (and that's saying something after a lot of contrast medium and the late breakfast I just had!!), much less a fever, vomiting, diarrhea...".  "No, really", she replied.  "I'm calling the surgeon now."

So, yesterday....I saw the surgeon.  The same dear one who set things straight years ago after a botched job with my initial primary in 2003 and dealt with my next melanoma crazy in 2007.  Now, just so you understand the wacky world that is melanoma follow-up, ditzelville as B calls it, after all the scans that I have had for the past 15 years, I now know that I have:
1.  Sparkly nodules in my thyroid.
2.  A shit ton of gall stones.
3.  A hole in the back of my head that no one can explain.  You can choose sequelae from a really bad fall down the stairs vs a brain met that resolved before it was noted.
4.  A uterine fibroid.
5.  Along with a few other bits and bobs that wax and wane over time.
BECAUSE....when you get scans....while looking for things that may do you harm, you inadvertently find doo-dads that may be important or just red herrings, that - if you lived in a normal world - you would never deal with at all, since you were not having any problems that warranted investigation!!!

Lots of folks in melanoma world freak the F@CK out when they get news of such things!  (Hell, lots of folks with nothing wrong with them or their lives stay in FREAK out mode!!!)  I've been here a long time.  And, I'm weird.  I don't freak out.  It's not fun to work through these things.  But, freaking out requires energy that I don't possess.  So, when Dr. Weber freaked out about my gall stones when I developed rectal bleeding and diarrhea - I had them evaluated.  They were fine and so was I.  In that vein - today I saw the surgeon.

He noticed the gall stones.  With no problems, didn't want to touch 'em with a ten foot pole.  The appendix, well....  Probably should come out.  It's bigger than on prior scans.  Probably a mucocele.  Often caused by 'nothing'.  Sometimes related to another icky, though less aggressive cancer.  And with my history, possibly related to melanoma...though...still...unlikely.

So, appendectomy scheduled for Thursday.  What the heck?!?  I'm between jobs and countries.  Let's get her done!

Refashion.  It's a thing.  I'm gonna miss you my dear little mucoid appendix!  Planning on some quality time together tomorrow!!! - c

Sew (and live) Chaotically! - Danita, an Inari, and love

I believe in soul mates.  They are not always lovers.  They are not always blood relatives.  But they are real.  People who get you - from the start. Who have your best interest at heart.  Who share - the good, the bad, and the ugly.  Who listen to the same from you.  Who know you - warts and all. 

I have had the incredible blessing to have more than my fair share of these wonderful souls in my world.  And my dear Danita is certainly one.  We clicked from the moment we met.  We have cried together and laughed so hard that tears ran down!  She is a soul sister indeed.  When she admired my Inari Tee  dress, I wanted to make a special one for her!  So...I did!!!

The Inari I made for myself (link above) had a bit more structure.  But I thought this super soft brushed cotton woven from JoAnns would be perfect for D!!!

I think it works!!  Isn't she the cutest?????

And in case my happy place wasn't happy enough.....

....she and her talented husband made me this!!!!

Exactly.  Your spirit is forever in my heart, my dear sweet Danita.  Thanks for being you.  My life is ever so much better for having you in it.  Much love, c

Live chaotically!!! - To my B

Only in my crazy, wonderful world with B does every bit of this make perfect sense!!!

Happy anniversary, baby!!!  30 years!  Not nearly enough.  Summer linen peeps toes!!!????  Still cracking me up.  My crazy boy.  My true love.  Because you got me.  Because you were the best.  Because you were beyond kind and true.  Because - you were you.  And, I was right.  I love you more.  ~ les

Immunotherapy works in the brain!!! Surprise, surprise, surprise! NOT!!!

How long have I been yelling about this????  Let's just say it's been a while!

Here is a post from 2014 (NOT my first one on the topic that really explains the whole deal - with pictures and all!!!!!  Anti-PD1 in melanoma: T-cells, the brain, and EVERYWHERE ELSE!!!!

Here are about a zillion more posts with articles documenting response in the brain when immunotherapy is used:  Immunotherapy and melanoma brain mets

In the process of utilizing immunotherapy to treat those poor ratties with brain mets, we also learned that when immunotherapy is combined WITH radiation, the response is even better.  Which brings us to today.

Here is a link to Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. Tawbi, Forsyth, Algazi, Hamid, Hodi, et al. New England Journal of Medicine. August 23, 2018.  Which says in part:

METHODS  In this open-label, multicenter, phase 2 study, patients with metastatic melanoma and at least one measurable, nonirradiated brain metastasis (tumor diameter, 0.5 to 3 cm) and no neurologic symptoms received nivolumab (1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for up to four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks until progression or unacceptable toxic effects. The primary end point was the rate of intracranial clinical benefit, defined as the percentage of patients who had stable disease for at least 6 months, complete response, or partial response.  

RESULTS  Among 94 patients with a median follow-up of 14.0 months, the rate of intracranial clinical benefit was 57% (47 to 68); the rate of complete response was 26%, the rate of partial response was 30%, and the rate of stable disease for at least 6 months was 2%. The rate of extracranial clinical benefit was 56%. Treatment-related grade 3 or 4 adverse events were reported in 55% of patients, including events involving the central nervous system in 7%. One patient died from immune-related myocarditis. The safety profile of the regimen was similar to that reported in patients with melanoma who do not have brain metastases.  

CONCLUSIONS Nivolumab combined with ipilimumab had clinically meaningful intracranial efficacy, concordant with extracranial activity, in patients with melanoma who had untreated brain metastases. 

Now.  The sad thing is, immunotherapy, ipi/nivo in this case, does not work on anybody, anywhere, 100% of the time.  As you can see from the data above, outside the brain, 56% of these 94 patients gained clinical benefit.  In the brain, clinical benefit was attained in 57% of these patients.  Another sad point is that side effects are nothing to sneeze at, with grade 3/4 events reported in 55% of the patients and one passing due to inflammation of the heart.  Another very important point here, is that while the response numbers in the brain are basically the same as in the body, prior research demonstrates that when immunotherapy is combined with point specific radiation, like gamma knife or SRS, the response is better and more durable than with either treatment alone and the poor ratties in this study were required to have "at least one measurable, nonirradiated brain met".

And....we know this is real cause...oh, yeah!...We've gone mainstream!!!  Here's a link to a report on the findings in The New York Times, where Tawbi cedes the points I mentioned above and confirms that while these responses to immunotherapy alone were good, radiation is still a critical treatment component for most:  Immunotherapy Drugs Slow Skin Cancer That Has Spread to the Brain

("Skin Cancer"!!!?????  Really Denise Grady?  Seriously?  That is the description of MELANOMA you use and your editors approved to headline this story??????????????????)

Well, despite the ubiquitous "skin cancer" line, we've come a long way baby!!!!  Immeasurable thanks to all the ratties who have paved the way.  NOW!!  Let's stop pondering whether immunotherapy works in the brain!  Let's lose the old notion of "it can't cross the blood brain barrier" BS that one self-proclaimed expert on one particular melanoma forum has erroneously claimed - for YEARS!!!  Let's push all docs to realize that immunotherapy is enhanced when combined with radiation with no deleterious effects (at least no greater than the crappy crap that can go with melanoma and immunotherapy in the first place!!!) and move on to finding treatment solutions that work for greater than 50 odd percent of my melanoma peeps!!!!  Okay.  I'll breathe now.  Thanks J and F.  Thanks ratties.  Much love, c

Elderly in need of immunotherapy? Can they tolerate it? Can they gain a response? YES, they can!!!

I've noted that elderly patients can not only tolerate but respond to immunotherapy as well as the rest of us before:  Elderly melanoma patients and immunotherapy

Now, there's this:

Older melanoma patients aged 75 and above retain responsiveness to anti-PD1 therapy: results of a retrospective single-institution cohort study.  Ibrahim, Mateus, Baz, Robert. Cancer Immunol Immunother. 2018 Jul 28.  

The utility of immunotherapy in elderly melanoma patients is debated. We aimed in this study to evaluate the efficacy and tolerability of immunotherapy among elderly patients.

This is a retrospective single-institution cohort study. Patients aged 75 years and above who had been treated with nivolumab, pembrolizumab or ipilimumab for advanced or metastatic melanoma, were included. Patients and disease characteristics were collected using electronic medical records. Objective response was determined according to the immune-related response criteria. Drug-related toxicities (DRT) were graded according to the CTCAE v4.03.

99 patients were included with a mean age of 80 years. One patient received nivolumab and ipilimumab combination, but died because of drug-related diverticulitis. Median PFS on pembrolizumab, nivolumab or ipilimumab were equal to 11.9, 1.4, and 2.8 months, respectively, while objective response rates were equal to 51.6, 12.5, and 17.3%, respectively. Median OS was not reached in patients who received only pembrolizumab, 8.7 months in the ipilimumab only group, and 23 months in patients receiving several immune therapies sequentially. Pembrolizumab, nivolumab, and ipilimumab grade 3-4 DRT rates were equal to 24.2, 62.5, and 32.7% respectively, while discontinuation rates were equal to 43.5, 62.5, and 28.8%, respectively.

Our study suggests that immunotherapy is effective and well tolerated in the elderly. The PFS on pembrolizumab was greater than expected, a finding that needs to be investigated further.

Ok.  Don't know why they are confused by their pembro results...they seem in keeping with what we know already and this is a small sample.  But, so be it.  The elderly peeps tolerated and responded to immunotherapy as well as ratties in other age groups! 

There is also this:

The efficacy and toxicity of immune checkpoint inhibitors in a real-world older patient population. Sattar, Kartolo, Hopman, et al. J Geriatr Oncol. 2018 Aug 10.

Immunotherapy has emerged as an effective treatment option for the management of advanced cancers. The effects of these immune checkpoint inhibitors in the older patient population has not been adequately assessed.  To understand the impact of aging on CTLA-4 and PDL-1 inhibitors efficacy and immune-related adverse events (irAE) in the context of real-world management of advanced solid cancers.

This retrospective study involved all non-study patients with histologically-confirmed metastatic or inoperable solid cancers receiving immunotherapy at Kingston Health Sciences Centre. We defined 'older patient' as age greater than/= to 75. All statistical analyses were conducted under SPSS IBM for Windows version 24.0. Study outcomes included immunotherapy treatment response, survival, as well as number, type, and severity of irAEs.

Our study (N = 78) had 29 (37%) patients age less than 65, 26 (33%) patients age 65-74, and 23 (30%) patients age greater than/= than 75. Melanoma, non-small cell lung cancer, and renal cell carcinoma accounted for 70%, 22%, and 8% of the study population, respectively. Distributions of ipilimumab (32%), nivolumab (33%), and pembrolizumab (35%) were similar in the study. The response rates were 28%, 27%, and 39% in the age less than 65, age 64-74, age greater than/= to 75 groups, respectively. Kaplan-Meier curve showed a median survival of 28 months (12.28-43.9) and 17 months (0-36.9) in the age less than 65 and age 64-74 groups, respectively; the estimated survival probability did not reach 50% in the age greater than/= to 75 group. There were no statistically significant differences found in terms of irAEs, multiple irAEs, severity of grade 3 or higher, types of irAEs, and irAEs resolution status when comparing between different age groups.  

Our results suggest that patients age greater than/= to 75 are able to gain as much benefit from immunotherapy as younger patients, without excess toxicity. Our findings suggest that single agent immunotherapy is generally well-tolerated across different age groups with no significant difference in the type, frequency or severity of irAEs. Future studies evaluating aging and combination immunotherapy are warranted.

Again, elderly peeps gained responses and dealt with side effects to immunotherapy in a fashion similar to previously studied populations.

Ratties are ratties, no matter their age!!!  Good to know if you or your loved one "of a certain age" are in need! - c

Sew Chaotically! - Paris top by Orageuse and a-line skirt combo! It's awesome!!

Sew!  This post is long in coming in all sorts of ways!!!  I got this border, eyelet print cotton from Mood over a year ago, thinking I would make some sort of boho top using the scalloped edge as the hem.  When it arrived it was lovely, but there was much MORE to the border than anticipated, so it sat.  Over the winter, I fell in love with everything Orageuse and B was sweet enough to purchase, print and put together a bunch of them!!!  They have been AWESOME!!!  Here is the Berlin skirt!  Here is the lovely Bristol dress!  And I have their Bruges cut out!!!!  When spring arrived I was set on making the Paris top!  So.....I did!

I considered so many things!  The aforementioned top.  A dress.  Then it hit me!  The "top" of the fabric as the Paris top and the bottom - a simple skirt.  Perfect together!  Perfect as separates!!  I know this goes against the Oona Balloona grain, and I love her for it.  But, it works better for my life and style!  Cheers, to us both!!!

Thus far...the size 40 has been working perfectly! I had to make this top a little shorter than indicated due to fabric limitations. All patterns have gone together well, explain any adjustments that you may need to make, and have interesting details I love.  Although on this one, the zipper is not needed for wearability (so I left it out) though I may well use on another version to up the cuteness quotient!

I think this simple top really does exemplify "Parisian chic"!

The neckline is so pretty, and while facings can be the bane of the home sewist's existence as a red light that shouts "Holly Hobby Homemade"!!!!  These lay very nicely and add to the structure of the neckline, rather than jack it up!!!

I LOVE this little shoulder detail!

For the skirt I used this basic pattern, adding on seam side slits on both sides.  Easy peasy!

I've worn this to work several times and it is a very "workable" outfit that got lots of compliments with each wear!

Poor B was tasked with snagging a few pics before we were off to errands.  Fashion poses in the garden!  Bahahaha!!!

Simple.  Pretty.  Useful.  Mix and match!  I like it!  Sew chaotically!! - les

SLNB and CLND....in melanoma patients!! Again!

The topics of sentinel lymph node biopsy (SLNB) and complete lymph node dissection (CLND) have been more than covered here!!  But, melanoma is a scary world to say the least, and folks are most frightened right at the time they are having to make these decisions! So, there was this:

SLN biopsy. Delay of 40 days = WHAT???? (Plus some general guidelines)

And this:

CLND - Complete lymph node dissection in melanoma - the whole shmegegge!!!!!!!!!!!

Now there's this:

Risk stratification of sentinel node-positive melanoma patients defines surgical management and adjuvant therapy treatment considerations. Verver, van Klaveren, van Akkooi, et al. Eur J Cancer. 2018 Apr 13.

In light of the evolving landscape of adjuvant therapy in melanoma and the recently confirmed absent survival benefit of completion lymph node dissection (CLND), it becomes important to explore possible consequences of omitting CLND, and whether it is possible to adequately stratify positive sentinel node (SN) patients solely based on information retrieved from the melanoma up to the sentinel lymph node biopsy (SLNB).

A retrospective cohort from nine European Organization for Research and Treatment of Cancer Melanoma Group centres was used. Patients were staged based on SLNB and CLND result according to the American Joint Committee on Cancer (AJCC) criteria and stratified by ulceration and SN tumour burden. These were incorporated in Cox regression models. Predictive ability was assessed using Harrell's concordance index (c-index) and the Akaike information criterion (AIC).

In total, 1015 patients were eligible. CLND led to upstaging in N-category in 19% and in AJCC stage in 5-6%. The model incorporating only ulceration and SN tumour burden performed equally well as the model incorporating substages after CLND. The model incorporating substages based on SLNB had the lowest predictive ability. Stratifying by ulceration and SN tumour burden resulted in four positive SN groups from which low-, intermediate- and high-risk prognostic classes could be derived.

Adequate stratification of positive SN patients was possible based on ulceration and SN tumour burden category. The identification of low-, intermediate- and high-risk patients could guide adjuvant therapy in clinical practice. Omitting CLND seems to have little consequences.  

This report simply reiterates what prior studies have shown.  SLNB is important for staging.  And looking at what the sentinel node shows as far as tumor burden, esp when you consider whether or not the initial lesion was ulcerated,  can be very helpful in evaluating risk and decision making regarding adjuvant treatment.  CLND did not really impact results.

Good luck, ratties!  You can do this! - c

Live chaotically! - REFASHION! (It covers a lot!)

"REFASHION!!!"  It's become a thing! A verb AND a noun!  Who knew?  But, hold up!!  Is this new (or news)????  NOPE!  Those of us who didn't have the where-with-all to attain the latest style learned years ago how to change that old prom/bride maid's dress into something we could wear on a date, sewed on that grosgrain ribbon to make like a prep-ster, and appropriated "men's wear" straight out of our man's closet.  Scarlet wasn't even the first refashioner when she yanked down those curtains and grabbed the tail feathers out of a rooster to create an amazing gown and a fascinator with southern charm!!!  Despite the cutting edge the latest "refashioners" like to think they're on, I love the idea and have lived it for years!!!  I hate waste and have often lacked the resources to purchase my ideals in sewing, cooking, gardening, home decor - you name it!  Plus, I love the creative nature of the process.  How do you turn trash into treasure?  Bunch of broken crayon nubs?  Make a candle! Empty wine bottle?  Nope!  That one is a beautiful carafe for vinegar.  The other one is a lovely vase.  Kid outgrows their favorite t-shirt?  Make them a pillow!  Got scraps?  Braid them into a rug.  Make them into a pot holder.  Sew up a warm throw for a bunch of freezing runners at those late night meets.  Veggies a bit too limp to stand up in a salad?  Girl, you got the makin's for soup!  Turn those potato peels into new flowers and veggies by composting!  The nifty cloth packaging from the same material purchased sheets and pillowcases often come in these days make lovely matching throw pillows with just a bit of "refashioning"!!!  So, despite my surprise at the smugness of this latest "refashionista" craze....I've got a few "refashion" stories of my own to share!!! 

What to do when your office of 13 years believes in team building through lots and lots and lots of t-shirts????  Well, there's a throw...that turned out larger than anticipated....

And tees revamped into racer-back work out tops...

...with one from a river rescue clean up for Roo!

Previously there was the little Polly top made out of a floral scarf and a fabric scrap...

When 'refashion' is used to refer to changing ready made garments into a more usable/beautiful piece in the eyes of its new owner, there is no one better than Sarah Tyau!!!  Check out her insta!!!!!

Seriously!  These renovations are nothing short of amazing!! 

B has gotten into the refashion craze as well...

...bending an overgrown crepe myrtle to his will!!!

A refashion of our yard, that added several "new" flower beds and plantings this spring and summer led to this:

This pepper plant has been crazy productive!!!

For all of that, sometimes a 'refashion' is even more personal.  After 13 years in my office where, by the grace of ever so many amazing parents, I was given the incredible blessing and privilege of caring for their precious children, the time has come for a change.  It has been one of the best and most gratifying experiences of my life.  But, as the office manager put it....

"Many moons ago, a Nurse Practitioner came to Peds Care hoping to find a practice where she could give great patient care to the children of this community...and she did just that and then some!!!!!  However, just as everything in life, this chapter is closing so new chapters can be written.

A quote from Lao Tzu says, "When I let go of what I am, I become what I might be."  I think this describes Celeste in its entirety!  She is letting go of what she has been for a very long time and venturing out to see what she might be for the next phase in her life.

Celeste, we bid you farewell but wish you the best in all your future adventures...and we know you will have many!!  LOL!!"

My heart is full.  I treasure the moments I have spent with every baby, toddler and teen. Every giggle and every tear will stay with me always.  I will forever wish my best to all the moms and dads I have had the privilege to help in our most important job ~ caring for our critters. 

Yes.  My heart is full.  But, the thing I've learned about hearts is that they can always grow to hold more.  Let's see what I can 'refashion' out of me!!!  Much love to all my dear PC peeps.  ~ love, c

Research that makes you scratch your head - brain power to kill cancer and sleep disordered breathing, relative to melanoma outcomes??? Ummmm, okay.

I don't know how to introduce these reports any better than as "head scratchers"!!!  Here we go!

Modulation of anti-tumor immunity by the brain's reward system.  Ben-Shaanan, Schiller, Azulay, et al.  Nat Commun. 2018 Jul 13.

Regulating immunity is a leading target for cancer therapy. Here, we show that the anti-tumor immune response can be modulated by the brain's reward system, a key circuitry in emotional processes. Activation of the reward system in tumor-bearing mice (Lewis lung carcinoma (LLC) and B16 melanoma) using chemogenetics (DREADDs), resulted in reduced tumor weight. This effect was mediated via the sympathetic nervous system (SNS), manifested by an attenuated noradrenergic input to a major immunological site, the bone marrow. Myeloid derived suppressor cells (MDSCs), which develop in the bone marrow, became less immunosuppressive following reward system activation. By depleting or adoptively transferring the MDSCs, we demonstrated that these cells are both necessary and sufficient to mediate reward system effects on tumor growth. Given the central role of the reward system in positive emotions, these findings introduce a physiological mechanism whereby the patient's psychological state can impact anti-tumor immunity and cancer progression.

Hmm... Okay...
1.  We have known for years that fewer MDSC's is a positive sign when dealing with melanoma.  Here's a bunch of posts and data on myeloid derived suppressor cells (MDSCs) and their role in melanoma .  In fact, I noted this in 2014 in regard to outcomes in my trial:

"MDSC  (myeloid derived suppressor cells)
"There was a trend towards lower baseline MDSC levels in non-relapsing patients compared to relapsing patients."  This bit of stuff and such along with other Treg/Tcell data comes your way thanks to us ratties sitting through leukapheresis twice during the trial. However, this is a bit I'm pretty psyched about.  There is talk among melanoma big dogs that combining anti-PD1 with MDSC or T-reg depletion would make it more effective.  I think that holds real promise.  Though...once again...despite my blood and services having been rendered....I have no idea what my MDSC levels were.  Still...I think this could be a real boon to future patients."

2.  In the entire article, linked here if you choose to read it ~  Modulation..., the authors note: 

"Epidemiological evidence supports a connection between the patient’s mental state and cancer survival, Nevertheless, many of these studies have yielded inconsistent results, and our understanding of the central neuronal mechanisms underlying the effect of emotional states on cancer is limited. Moreover, most research in this field has been focused on negative emotional states, such as stress and depression, while the impact of positive mental attributes on cancer biology is largely unknown."  

Don't get me wrong, I believe in "HAPPY"!!!  We all feel better and do better when all is right in our world!  Duh!!!  However, keeping your ass happy when dealing with the reality of a deadly disease, the pain and cost of treatment, the pain and emotional cost to loved ones, the economic and personal value lost due to unemployment when you are too sick to work... I could go on!  Melanoma is NOT easy.  Putting on a happy face, no matter how real (or not) it may be, will not cure your melanoma nor protect you from it!!!  Here's some real data and a bit of a rant:  ASCO 2017: Friends in need are friends indeed! Here's to the caregivers!!!

3.  But, I digress.  In this study, researchers gave real live little ratties either a type of lung cancer or melanoma.  And because we already know that part of our immune system serves us well in fighting cancer (our CD8 t cells and natural killer [NK] cells for instance) while other parts (like the MDSCs) actually SUPPRESS anti-tumor responses and let tumors thrive...the researchers note:  "...by depleting and adoptively transferring MDSCs, we showed that these cells are both necessary and sufficient to mediate the effects of reward system activation on tumor growth."  In order to test that, very roughly, they made a happy drug ("...we used Designer Receptor Exclusively Activated by Designer Drugs (DREADDs) to specifically control reward system activity...") which they got into these poor little ratties heads {for realz!!!} by attaching it to a cold virus and zapping it into their brains with SRS.  Damn!  It sucks to be a rattie!!!  For the control, they did all the same stuff, just minus the happy pill.  So, according to these researchers, this process allowed the zapped with the happy pill ratties' dopaminergic neurons to get busy with their secretions and stimulations - ultimately impacting the bone marrow, which impacted the MDSC's, making them LESS immunosuppressive.  There.  By the way, the effect was less in the melanoma injected ratties than it was for the lung cancer ratties....so the researchers actually abandoned the melanoma critters mid-way the study and just used the lung cancer critters.

4.  All in all, this is probably much ado about nothing as it relates to us human melanoma ratties.  EXCEPT!!!  As I said above and in 2014:  "There is talk among melanoma big dogs that combining anti-PD1 with MDSC or T-reg depletion would make it more effective.  I think that holds real promise.  Though...once again...despite my blood and services having been rendered....I have no idea what my MDSC levels were.  Still...I think this could be a real boon to future patients."   So, if this is part of the process to get us there - so be it!!

Now, this...

Sleep-disordered breathing is independently associated with increased aggressiveness of cutaneous melanoma.  A multicentre observational study in 443 patients.  Martinez-Garcia, Campos-Rodriguez, Nagore, et al.  Chest.  2018 Jul 27.

Sleep-disordered breathing (SDB) has been associated with a greater incidence and mortality of cancer, although such findings are inconsistent. However, no large studies are currently available to investigate this association in patients with a specific type of cancer. This study seeks to assess potential relationships between SDB severity and aggressiveness markers of cutaneous melanoma.

443 patients with a diagnosis of melanoma underwent a sleep study within 6 months of diagnosis. General demographics were collected, along with melanoma characteristics and polygraphic parameters consisting of apnea-hypopnea index (AHI) and indices of both continuous and intermittent night-time oxyhemoglobin desaturation (DI4%). Exploration of independent relationships between SDB and various objective melanoma aggressiveness markers (Breslow index, presence of ulceration, presence of regression, mitotic index, stage of severity, damage to the sentinel lymph and spreading of the melanoma) was performed.

Patients in the upper tertiles of AHI or DI4% were 1.94 and 1.93 times more likely, respectively, to present with aggressive melanoma (Breslow index greater than 1mm) than those in the lowest tertiles of these sleep attributes after adjustment for age, gender, tumor location and body mass index. This association was particularly prominent among patients less than 56 years with Breslow index greater than 2 mm. The presence of the additional markers of aggressiveness was also associated with higher AHI and DI4% values.  The severity of the SDB was independently associated with greater aggressiveness of cutaneous melanoma, particularly among younger patients.

Hmmmm.....well.  
1.  Maybe folks who are more worried about their melanoma sleep less well!!!  And sleeping less well about having a potentially deadly disease is completely legit!!!  
2.  Then again, maybe these particular melanoma peeps are less happy about their life and therefore invite melanoma in, like the sad rats in the previous study???  (Y'all know that is NOT what I think!!  Right????)  
3.  Maybe younger folks with melanoma lesions of greater than 2 mm in depth were at greater risk anyway!!!!  Cause that's a thing!!!!  With melanoma: You can never be too rich or too thin! But, you can be too young!!!
4.  Finally, no matter what you think of this report (and I don't think much!!!!) ain't no way insurance is going to pay for sleep studies just because you've been diagnosed with melanoma.  It's hard enough to get them to pay for scans we actually need!!!

Head gett'n itchy yet???  Sometimes we have to think, laugh, yawn, and plain out hope researchers are getting SOMEWHERE that will actually make a difference where we need it!!! Hang tough, ratties!!  c

Trial testing MAGE-A3 as adjuvant for Stage III melanoma patients....STOPPED.

If you hadn't heard or were considering MAGE-A3 for your Stage IIIB/C melanoma, there's this: 

MAGE-A3 immunotherapeutic as adjuvant therapy for patients with resected, MAGE-A3 positive, stage III melanoma (DERMA):  a double-blind, randomised, placebo-controlled, phase 3 trial.  Dreno, Thompson, Smithers...Kirkwood.  Lancet Oncol.  2018 June 13.

Despite newly approved treatments, metastatic melanoma remains a life-threatening condition. We aimed to evaluate the efficacy of the MAGE-A3 immunotherapeutic in patients with stage IIIB or IIIC melanoma in the adjuvant setting.

DERMA was a phase 3, double-blind, randomised, placebo-controlled trial done in 31 countries and 263 centres. Eligible patients were 18 years or older and had histologically proven, completely resected, stage IIIB or IIIC, MAGE-A3-positive cutaneous melanoma with macroscopic lymph node involvement and an Eastern Cooperative Oncology Group performance score of 0 or 1. Randomisation and treatment allocation at the investigator sites were done centrally via the internet. We randomly assigned patients (2:1) to receive up to 13 intramuscular injections of recombinant MAGE-A3 with AS15 immunostimulant (MAGE-A3 immunotherapeutic; 300 μg MAGE-A3 antigen plus 420 μg CpG 7909 reconstituted in AS01B to a total volume of 0·5 mL), or placebo, over a 27-month period: five doses at 3-weekly intervals, followed by eight doses at 12-weekly intervals. The co-primary outcomes were disease-free survival in the overall population and in patients with a potentially predictive gene signature (GS-positive) identified previously and validated here via an adaptive signature design. The final analyses included all patients who had received at least one dose of study treatment; analyses for efficacy were in the as-randomised population and for safety were in the as-treated population. This trial is registered with ClinicalTrials.gov, number NCT00796445.

Between Dec 1, 2008, and Sept 19, 2011, 3914 patients were screened, 1391 randomly assigned, and 1345 started treatment (n=895 for MAGE-A3 and n=450 for placebo). At final analysis (data cutoff May 23, 2013), median follow-up was 28·0 months [IQR 23·3-35·5] in the MAGE-A3 group and 28·1 months [23·7-36·9] in the placebo group. Median disease-free survival was 11·0 months in the MAGE-A3 group and 11·2 months (8·6-14·1) in the placebo group. In the GS-positive population, median disease-free survival was 9·9 months (5·7-17·6) in the MAGE-A3 group and 11·6 months (5·6-22·3) in the placebo group. Within the first 31 days of treatment, adverse events of grade 3 or worse were reported by 126 (14%) of 894 patients in the MAGE-A3 group and 56 (12%) of 450 patients in the placebo group, treatment-related adverse events of grade 3 or worse by 36 (4%) patients given MAGE-A3 vs six (1%) patients given placebo, and at least one serious adverse event by 14% of patients in both groups (129 patients given MAGE-A3 and 64 patients given placebo). The most common adverse events of grade 3 or worse were neoplasms (33 [4%] patients in the MAGE-A3 group vs 17 [4%] patients in the placebo group), general disorders and administration site conditions (25 for MAGE-A3 vs four for placebo) and infections and infestations (17 [2%] for MAGE-A3 vs seven [2%] for placebo). No deaths were related to treatment.

An antigen-specific immunotherapeutic alone was not efficacious in this clinical setting. Based on these findings, development of the MAGE-A3 immunotherapeutic for use in melanoma has been stopped.

So....disease free survival was no different between the melanoma peeps given a placebo and those treated with MAGE-A3.  To be honest, I don't know how this Phase 3 trial came to be as data I've seen for MAGE-3 has never been very convincing.  But, what do I know? Thanks, Ratties!  Hang tough!  - c

anti-PD-1 after progression

It is a question many ponder - "Now that I've responded to anti-PD-1, if I recur...what should I do???"  Here is a bit of info toward that answer.....

Outcomes of long-term responders to anti-programmed death 1 and anti-programmed death ligand 1 when being rechallenged with the same anti-programmed death 1 and anti-programmed death ligand 1 at progression.  Bernard-Tessier, Baldine, Martin, et al.  Eur J Cancer. 2018 July 30.

Long-term responders have been observed with anti-programmed death 1 and anti-programmed death ligand 1 (anti-PD(L)1). Optimal duration of therapy in responding and stable disease (SD) patients is unclear with various attitudes encompassing treatment until progression disease, stopping therapy after a defined time frame.

We report the experience of 13 patients who discontinued immune checkpoint inhibitor in phase I trials as per protocol while experiencing a tumour-controlled disease. According to protocols, patients could restart the same immunotherapy if radiological or clinical progression occurred.

Patients were treated for colorectal microsatellite instability-high genotype (n = 5), urothelial carcinoma (n = 3), melanoma (n = 2), non-small-cell lung cancer (n = 2) and triple-negative breast cancer (n = 1) for a median time of 12 months (range 10.6-12). Patients achieved 1 (8%) complete response, 10 (77%) partial response (PR) and 2 (15%) SD. The median progression-free survival 1 (PFS1) defined as the time from the first infusion until progression was 24.4 months (range 15.8-49). The median time free-treatment after discontinuation was 12.6 months (range 4-39.7). Eight patients experienced disease progression and were retreated. Best responses observed after rechallenging were 2 PR (25%) and 6 SD (75%). Median PFS2 defined from the first day of retreatment until disease progression or the last news was 12.9 months (range 5-35.4). No grade 3/4 events occurred during the study period.

Our data suggest that anti-PD(L)1 therapy should be resumed if progression occurs after a planned anti-PD(L)1 interruption. Further prospective studies are needed to confirm these results.

Small numbers here and not all are melanoma patients.  But, some responses on the re-do.  Hang tough, ratties!  Hang tough! - c

Sew Chaotically! - I scream, you scream for Sewaholic's Hollyburn!!

I've made two Hollyburn skirts already!  Sewaholic made an incredibly workable, flattering, and adaptable skirt with this pattern.  And this one for Roo was SEW much fun in this art gallery cotton, 'I scream, you scream', print!!! 

Not sure my efforts in pattern placment made that much difference, but I'm happy with it!

I used a contoured waistband made as described in the link above.

Isn't she the cutest???  She totally deserves a new back-to-school outfit, even if she is the teacher!!!

And when she's not expanding the craniums of her students with algebra II, pre-cal and calculus, she's off to the races...running in the 5 mile Chattanooga Heroes Run!

So proud of this amazing young woman!  I know you're going to have a great year, Roo!!! - love you, mommy

Better melanoma outcomes with a lower NLR, neutrophil-to-lymphocyte ratio! (Again...)

Yes, I've been yelling about this for a while!!  Here are tons of posts/articles:  More than you ever wanted to know on NLR - neutrophil-to-lymphocyte ratio!  In these data sets you will find:

• Increased baseline NLR was associated with poorer outcomes generally.
• Multiple studies demonstrate that an NLR less than 5 showed improved progression free survival.
• A retrospective review showed that increased NLR in high risk, NON-metastatic melanoma patients resulted in poorer outcomes, indicating that Stage III patients might take that measure into account when thinking about how aggressively they should treat their disease.  That result was replicated from a study at Huntsman, where they found that an NLR greater than 2.5 in Stage III patients was a strong predictor of recurrence. 

Now, there's this:

Baseline neutrophil-to-lymphocyte ratio (NLR) and derived NLR could predict overall survival in patients with advanced melanoma treated with nivolumab. Capone, Giannarelli, Mallardo, ... Ascierto .  J Immunother Cancer. 2018 Jul 16.

Previous studies have suggested that elevated neutrophil-to-lymphocyte ratio (NLR) is prognostic for worse outcomes in patients with a variety of solid cancers, including those treated with immune checkpoint inhibitors.

This was a retrospective analysis of 97 consecutive patients with stage IV melanoma who were treated with nivolumab. Baseline NLR and derived (d) NLR were calculated and, along with other characteristics, correlated with progression-free survival (PFS) and overall survival (OS) in univariate and multivariate analyses. ... In univariate analysis, increasing absolute neutrophil count (ANC), NLR, dNLR and lactate dehydrogenase (LDH) (continuous variables) were all significantly associated with OS. Only NLR and LDH maintained a significant association with OS in multivariate analysis. Patients with baseline NLR greater than/= to 5 had significantly worse OS and PFS than patients with NLR less than 5, as did patients with baseline dNLR greater than/= to 3 versus less than 3. Optimal cut-off values were greater than/= to 4.7 for NLR and greater than/= to 3.8 for dNLR. Using this greater than/= to 4.7 cut-off for NLR, the values for OS and PFS were overlapping to the canonical cut-off for values, and dNLR less than 3.8 was also associated with better OS and PFS. 

Both Neutrophil-to-lymphocyte ratio (NLR) and derived (d) NLR were associated with improved survival when baseline levels were lower than cut-off values. NLR and dNLR are simple, inexpensive and readily available biomarkers that could be used to help predict response to immunotherapy in patients with advanced melanoma.

So, the question seems to be, How low can we go???  Cause when it comes to NLR, it looks like the lower the better for our prognosis!!  Still, this is not the whole answer to melanoma care and therapy.  It is one thing to check and speak with your doc about when making the best possible treatment plan for your melanoma.  Hang in there, ratties!!! - c