Heavy heart, heavy lifting ~ for he was all of us...

My losses mount, as do my sorrows.  Almost 10,000 beautiful souls will die from melanoma in the United States this year.  Of those, there are dear ones who touched me personally.  Sadly, I've written similar posts before ~

2012 - Gavin Snow - If you're given a gift...

2012 -  My Life with Cancer

2012 - Oh, the people you'll meet

2013 - I miss Belgium

2015 - Melanoma kills...

2015 - Merde! - again

2015 - Artie, an amazing knight - a beautiful soul

2016 saw the loss of Santos, Ms. Ituah, Dfeng, and Nathan Jones.  Not even half way through 2017 the world lost Paul, John, Vince, Juan, Charles, and Tara.

And today - Jamie.

I'm glad that their suffering will be no more.  I ache for the empty space in the hearts and arms of those who loved them.  I have felt the crushing sadness and weight of what sometimes seems a burden too heavy, too awkwardly shaped with no edges for purchase; placement in a role for which I am too weak and weary to continue. But then I realize, I am not the one who has endured the truly heavy lifting.  My bits and pieces are minuscule when compared to the load endured by these true heroes and their families. In the end, I always return to this:

No man is an island entire of itself;
every man is a piece of the continent, a part of the main;
if a clod be washed away by the sea, 
Europe is the less, as well as if a promontory were, 
as well as any manner of thy friends or of thine own were;
any man's death diminishes me,
because I am involved in mankind.
And therefore never send to know for whom 
the bell tolls; it tolls for thee.                 ~ John Donne

For all that every loss, brings certain pain, these lives have become an incredible gift and integral part of mine.  As such, I must continue to do what I can.  I must put ALL my effort into LIVING every minute.  I must play and work and laugh and love...and cry...with all I have.  It will never be enough, but it is what I can do to honor the memory of all of these incredible folks, who live on in my heart.

In honor and remembrance of Jamie, and all my other dear ones....

"....he was my father and my mother, my brother, my friend.  He was you and me.  He was all of us."  ~  V for Vendetta

Sleep well my friends.  love, les

Smoking is associated with mets in sentinel nodes and ulceration in melanoma patients!!!

SURprise, surprise, surprise!!!  NOT!!!!!! ~

The Impact of Smoking on Sentinel Node Metastasis of Primary Cutaneous Melanoma. Jones, Jones, Stern, ...Faries et al. Ann Surg Oncol. 2017 Feb 21.

Although a well-established causative relationship exists between smoking and several epithelial cancers, the association of smoking with metastatic progression in melanoma is not well studied. We hypothesized that smokers would be at increased risk for melanoma metastasis as assessed by sentinel lymph node (SLN) biopsy.

Data from the first international Multicenter Selective Lymphadenectomy Trial (MSLT-I) and the screening-phase of the second trial (MSLT-II) were analyzed to determine the association of smoking with clinicopathologic variables and SLN metastasis.

Current smoking was strongly associated with SLN metastasis, even after adjusting for other predictors of metastasis. Among 4231 patients current or former smoking was also independently associated with ulceration. Compared with current smoking, never smoking was independently associated with decreased Breslow thickness in multivariate analysis and with a 0.25 mm predicted decrease in thickness.

The direct correlation between current smoking and SLN metastasis of primary cutaneous melanoma was independent of its correlation with tumor thickness and ulceration. Smoking cessation should be strongly encouraged among patients with or at risk for melanoma.

Don't smoke, guys!  Just.  Don't! - c

Sew Chaotically! - Me Made May - Week 4

Can't believe I've worn something Me Made every day for 4 weeks in a row!!!  You are all probably more than tired of it by now!  It will be over soon....but here's this week's recap....

FINALLY!!!!  Got this dress the way I want it.  The "bow" was so thick and large...it was driving me crazy!!!  Faux wrap dress - McCall's 6884  I cut it down and used a cute button I got from Maiwa during our Vancouver trip.

Still loving this dress!  Fit and flare dress - M7244

Quite excited about this little skirt, one of two I made just the other day on -
 Double Decker Skirt Day

There is no better light jacket for a suddenly cool spring day or over active air conditioning than
 A Morris Blazer

In a search for needed buttons....I got ALLLLLL the buttons!!!  Sew... I made another Sorbetto!

My efforts on Saturday were recovering this kitty attacked chair for Roo, using scraps from a skirt I've already cut out and the legs from two pairs of pants destined for the garbage bin.  Let's see what you do with this, Friday!!!

Ta dah!!!  Certainly my magnum opus of Me Made May!  Right proud of this one!!  Details to be blogged soon!

Enjoy your "me mades" every day!! - love, c

Chaotically conflicted ~ and sad....

This morning I got some news I didn't want to hear - or think about.  So... I walked my dog.  Dead headed roses...a LOT of roses.  Fed the birds.  Tidied the house....  Used "oxy-clean" on a load of whites that had been in winter storage, garnering a yellow tinge.  It was somewhat successful.  And since B was out working on saving healthcare for all of us... I did this:

Having helped Roo go through her clothes yesterday after work - putting aside things to trash, give away, and repair.  This skirt had a bit of damage at the waist and dead elastic.  Not anymore.  I cut off about three inches and made a new channel threaded with elastic.  Good as new.

This tunic had sentimental value, since Roo purchased it in Greece.  So, I "fixed" the neckline per her request.  My attempt at using my machine's Greek Key stitch worked great in practice but not so well on this thin knit.  Hopefully, she will find it okay.  At least I learned how to create some decorative stitches with my machine for future projects.

Most of the rest of my day was spent recovering this kitty attacked chair for Roo.  I used fabric left over from a skirt I've cut out and the legs from two pairs of pants she was going to toss.  I think it looks okay.  Let's see what you can do with that, Friday!!!

Sew.....why am I conflicted?
I often feel that my sewing is rather self-indulgent.  I mean really!!!  I don't NEED any of the clothes I make.  Children are starving.  People are being poisoned in Syria.  I should be there.  Doing something.  Our elders are living without running water so that they can purchase needed meds, pay their rent.  I should be helping with that.  I recycle.  I garden.  I compost!  I give to a food bank.  I make pretty things.  I work hard to take care of my little peeps and their families.  I read or have read, most books in your local library.  I know the names of plants.  I can cook most anything.  It doesn't mean shit. I want to work with folks like Doctors without Borders.  I want to write the next great American novel.  I want to make a difference.  I want to be Pickles the Fire Cat.  I want Jamie, and Paul, and Adriana, and Josh, and all my other melanoma peeps to be okay.  If I am okay, why can't they be okay?  And I can't do a damn thing.  Jamie was placed on hospice today.

B went through page after page of ASCO publications this afternoon. Forwarding to me those that are most significant.  I will go through them when I can.  Today - I can't.  Maybe tomorrow. - c

Sew Chaotically! - Button, button...who's got the button? Sorbetto, that's who!

Sew.....I needed some buttons for two shirts I have in the works.  B was sweet enough to accompany me to our ONLY fabric shopping option in our town....JoAnn's.  To my dismay, their limited button supply was cut by half as they appeared to be in process of turning that area into a different set of supplies altogether.  I found some buttons that I thought would do and was heading toward the checkout...when I suddenly let out a shriek and turned on my heel, to head in the opposite direction! B was not as surprised or panic stricken as you might imagine!  Sadly, the man is used to such events. He was a bit confused.  But, the light of recognition dawned!  I had spied two baskets of "clearance buttons"!!!  The "wall" that once was a button display was now relegated to baskets labeled "75 cents per card"!!!!  Now....they were in an unholy mess, but my B gamely helped me search through them until we were satisfied that we had found the best of the lot.  A mere couple of hours!!!  What better way to spend your time, right?????  So...with all these random buttons in my possession, what's a girl to do????????

Inspo sent by Ruthie..after seeing ALLLLLLL the buttons!!!

With that, you remember a bit of white linen and what could be better than your 5th
 Colette's Sorbetto??!!!

Need to make a cute summer top work appropriate while you survive overactive air conditioning?  Add 1 of your 4 Grainline Studio's Morris Blazers!!!

And...it works with your latest skirt!!  Win, win, win!!!

Sew and shop and live - chaotically!!! - love, c

Encorafenib/binimetinib, a BRAF/MEK combo = 14.9 month PFS

Since it was double skirt day....I decided to go ahead and make it a double post day!!!!
To continue the subject of BRAFi -

From The coBRIM trial - August 2016 we learned - that when cobinmetinib and vemurafinib were combined, the median overall survival (OS) was 22.3 months and the median progression free survival (PFS) was 12.3 months.

From this discussion of BRAF/MEK and immunotherapy (Nov 2016)  we learned = that generally treatment that was a combination of a BRAF inhibitor and a MEK inhibitor could illicit a response rate of 48-59%, even as much as 70% with some combo's and PFS of 11-12 months.

Now there's this (I've included most of the report, you may read it yourself via the link at the bottom, my comments are in red!):

Update Confirms Benefit of Encorafenib/Binimetinib Combo in Melanoma  Jason Broderick – Thursday, May 11, 2017 From OncLive

The combination of the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib reduced the risk of disease progression or death by 23% compared with single-agent encorafenib for patients with BRAF-mutant melanoma, according to findings from part 2 of the phase III COLUMBUS trial.  The median progression-free survival (PFS) for patients treated with the combination was 12.9 months compared with 9.2 months for patients receiving encorafenib alone.  Based on these data, along with previously reported findings from part 1 of the COLUMBUS trial, the developer of the combination, Array BioPharma, anticipates filing a new drug application with the FDA in June or July.

The COLUMBUS trial included 921 patients with locally advanced, unresectable, or metastatic BRAFV600-mutant melanoma. Prior treatment with immunotherapy was allowed. Those with untreated CNS lesions, leptomeningeal metastases, uveal melanoma, and mucosal melanoma were excluded from the trial. [Why the hell not???? You could put them in their own separate group, so as not to sully your results Array CEO person!!! And still give them access to the drug!]

In part 1 of the study, 577 patients were randomized in a 1:1:1 ratio to receive encorafenib plus binimetinib, encorafenib alone, or vemurafenib alone. In the combination arm, encorafenib was administered at 450 mg daily and binimetinib was administered at 45 mg twice daily. Single-agent encorafenib was given at 300 mg daily. Vemurafenib was administered at 960 mg twice daily.  Part 2 of the study randomized 344 patients in a 3:1 ratio to receive encorafenib plus binimetinib at 45 mg twice daily or encorafenib alone. Encorafenib was given at 300 mg daily.  “Part 2 was designed specifically to assess the contribution of binimetinib to the combination of binimetinib and encorafenib by reducing the dose of encorafenib to 300 mg in the combination arm to allow for a comparison of equal doses across arms,” Array wrote in a press release.
In Part 1 of the study, the median PFS was 14.9 months with the combination of encorafenib and binimetinib compared with 7.3 months for vemurafenib alone. The improvement in PFS represented a 46% reduction in the risk of progression or death. [That's good, but of course we have learned never to give vemurafenib, a BRAF inhibitor without a MEK inhibitor!!! So that's a bit of a false comparison!]
When single-agent encorafenib was compared with the combination arm the difference between the groups did not reach statistical significance. However, median PFS with encorafenib was statistically superior to vemurafenib. Findings for overall survival (OS) were not yet available. [hmmmmmm.....]

The objective response rate (ORR) with the combination was 63% versus 40% with vemurafenib. [Again...not comparing apples to apples...we KNOW that response rates are better with a BRAF/MEK combo!!!] With single-agent encorafenib, the ORR was 51%. [This fact can at least be compared to single agent vemurafenib response rate of 40%.]The complete response rate was 8% with the combination versus 5% and 6% with encorafenib and vemurafenib, respectively. The median duration of response was 16.6 months with the combination versus 14.9 months with encorafenib and 12.5 months with vemurafenib.

By local review, median PFS with the combination was 14.8 versus 7.3 months with vemurafenib. The ORRs by local review were 75% for the combination versus 49% and 58% for vemurafenib and encorafenib monotherapy, respectively.  In this assessment, the combination was superior to single-agent encorafenib. The median PFS with encorafenib was 9.2 months, which was also superior to single-agent vemurafenib.

All-grade AEs with the most variability between the two arms for the combination, single-agent encorafenib, and vemurafenib, respectively, were arthralgia (26%, 44%, 45%), pyrexia (18%, 15%, 28%), alopecia (14%, 56%, 37%), hyperkeratosis (14%, 38%, 29%), dry skin (14%, 30%, 23%), rash (14%, 21%, 29%), palmoplantar keratoderma (9%, 26%, 16%), and palmar-plantar erythrodysesthesia syndrome (7%, 51%, 14%). All-grade AEs of special interest with the combination included rash (23%), pyrexia (18%), retinal pigment epithelial detachment (13%), and photosensitivity (5%).

Grade 3/4 AEs were experienced by 58% of patients treated with the combination versus 66% and 63% with encorafenib and vemurafenib, respectively. [As previously demonstrated, side effects were DECREASED with a BRAF/MEK combo.]  The most common grade 3/4 AEs with the combination were gamma-glutamyltransferase, increased blood creatine phosphokinase, and hypertension. Time to first grade 3/4 AE was long with the combination, at 2.5 months versus 0.4 months for encorafenib and 1.3 months for vemurafenib.

In March, Array withdrew its FDA new drug application for single-agent binimetinib as a treatment for patients with NRAS-mutant advanced melanoma, based on feedback from the FDA during a preplanned review meeting.  [So I gather they are going to market this only for BRAF positive folks, rather than NRAS mutant.]  The application for binimetinib was based on data from the phase III NEMO study, which was presented at the 2016 ASCO Annual Meeting. In the open-label study, PFS with binimetinib was 2.8 versus 1.5 months with dacarbazine, representing a 38% reduction in the risk of progression or death; however, OS was not improved with the MEK inhibitor. [Pretty sad if you can't beat dacarbazine!]

Link to article:  http://www.onclive.com/web-exclusives/update-confirms-benefit-of-encorafenibbinimetinib-combo-in-melanoma

Okay.  My synopsis is this:  Generally, prior studies of BRAF/MEK combos demonstrate about a 12 month PFS.  This combo showed a PFS of 14.9 months.  Objective response rate was 63% with the comb0.  There was an ORR of 51% to encorafenib alone.  Objective response rates to BRAF/MEK combo's in other studies have ranged from 48-70%, depending.  OS data for encorafenib/binimetinib has not yet been reported.  OS in most other BRAF/MEK combo's is around 2 years.  The combo discussed here demonstrated fewer side effects than when the BRAFi component was used alone....which is consistent with other reports using a BRAF/MEK combo vs BRAFi alone.

PFS of 14.9 months is better than 12.  Wish they had allowed testing in a greater swath of patients. (But I say that about most all trials!!!)  We'll have to see what the OS data shows and if these current figures hold in future cohorts.  Hang tough ratties.  You will save us all. - c

Sew Chaotically! - Double Decker Skirt Day!!!

Double decker skirt day indeed!!!  I got this thick, almost scuba, knit from Metro Textiles and the infamous Kashi during Our New York Fabric Shopping!!

The fabric can look a little funky in the photos below...so here's a shot that's accurate.

I decided it would be perfect for this flippy little skirt (View C) for Miss Roo!!!

I think I was right!!!

I can't wait to give it to her!!!  I hope it fits her well!!!

And because, waste not want not...and I love pencil skirts....I made this one for me.

Poor Mannie!  Her bootie is a little sad!  But, the skirt is pretty cute on a human posterior!!!

It was a fun day of sewing.  And since I made two skirts to wear in the month of Me Made May...this has gotta be worth quadruple points!!!  Sew Chaotically!!! - love, c

Management of Adverse Events with Targeted Therapy (BRAF/MEKi)

BRAF inhibitors combined with MEK inhibitors have been an amazing targeted treatment option for BRAF positive melanoma patients (about half of us).  They rarely have durable responses, though occasionally they can remain effective therapy for years, but are incredibly useful in our treatment arsenal.

Here is a post that gives a basic primer on BRAF and targeted therapy:  BRAF inhibitors for melanoma

Here is a post on several BRAF/MEK combo's  The coBRIM trial with links to other reports

And of course....there are always side effects.  Here is a report from Weber and Agarwala:  Side effects and how to manage them

Now there is this with specific plans re management of adverse events.....

Management of Treatment-Related Adverse Events with Agents Targeting the MAPK Pathway in Patients with Metastatic Melanoma. Daud, Tsai. The Oncologist. May 18, 2017.

Tremendous progress has been made in the clinical landscape of advanced-stage BRAF V600–mutant melanoma treatment over the past 5 years. Targeted therapies that inhibit specific steps of the mitogen-activated protein kinase pathway have been shown to provide significant overall treatment benefit in patients with this difficult-to-treat disease. Combination therapy with BRAF and MEK inhibitors (dabrafenib plus trametinib or vemurafenib plus cobimetinib, respectively) has become standard of care. These agents are administered until disease progression or unacceptable toxicity occurs; thus, some patients may remain on maintenance therapy for an extended period of time, while toxicities may result in early discontinuation in other patients. Because the goal of treatment is to prolong survival with minimal impairment of quality of life, drug-related adverse events (AEs) require prompt management to ensure that patients derive the best possible benefit from therapy. Proper management depends on an understanding of which AEs are most likely BRAF or MEK inhibitor associated, thus providing a rationale for dose modification of the appropriate drug. Additionally, the unique safety profile of the chosen regimen may influence patient selection and monitoring. This review discusses the toxicity profiles of these agents, with a focus on the most commonly reported and serious AEs. Here, we offer practical guidance derived from our clinical experience for the optimal management of key drug-related AEs.  

Recommended dosage adjustments....

LATE NOTE:  Thanks to the sharp eyes of Mike Brooks and a note he left me....I think he is correct in having found a typo in the dose reduction chart above regarding the trametinib dose.  It appears they have simply copied the dose reduction for vemurafenib....which comes in 240 mg tabs and is usually dosed at 960 mg taken twice a day.  However, trametinib (Mekinist) comes in 0.5, 1 and 2 mg tabs and is usually dosed at 2 mg once a day, either alone or in combination with a BRAFi. Therefore, Mike is probably right that a dose reduction regimen is likely to be something along the lines of:  2 mg, to 1.5 mg, to 1 mg, to 0.5 mg. It takes a village!!!

Management of fever...

Management of rash....

Management of cardiac side effects....

Again, as I noted in my last post, I hope this is information for which you will find no need...but here it is....if you do. - c

Neurologic side effects to immunotherapy with treatment algorithm

I have been posting individual articles as well as collections of abstracts regarding possible side effect of immunotherapy for years.  I figure...forewarned is forearmed.  Here is the latest post with a link to prior:  The mice told us so...cardiotoxicity - with links to more articles related to the possible side effects of immunotherapy

Additionally, I've reported on what the experts tell us in regard to dealing with these side effects:
Here in a discussion:  Side effects and how to manage them - Weber and Agarwala

And this report that includes multiple charts with algorithms for treatments of GI, endocrine, pulmonary and hepatic side effects:  How to deal with side effects from anti-PD-1

Now there's this:

Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis.  Larkin, Chmielowski ... Hodi ...Weber, et al. The Oncologist. May 11, 2017.  

Despite unprecedented efficacy across multiple tumor types, immune checkpoint inhibitor therapy is associated with a unique and wide spectrum of immune-related adverse events (irAEs), including neurologic events ranging from mild headache to potentially life-threatening encephalitis. Here, we summarize neurologic irAEs associated with nivolumab and ipilimumab melanoma treatment, present cases of treatment related encephalitis, and provide practical guidance on diagnosis and management. Methods. We searched a Global Pharmaco-vigilance and Epidemiology database for neurologic irAEs reported over an 8- year period in patients with advanced melanoma receiving nivolumab with or without ipilimumab from 12 studies sponsored by Bristol-Myers Squibb. Serious neurologic irAEs were reviewed, and relationship to nivolumab or ipilimumab was assigned. Results. In our search of 3,763 patients, 35 patients (0.93%) presented with 43 serious neurologic irAEs, including neuropathy (n 5 22), noninfective meningitis (n 5 5), encephalitis (n 5 6), neuromuscular disorders (n 5 3), and nonspecific adverse events (n 5 7). Study drug was discontinued (n 5 20), interrupted (n 5 8), or unchanged (n 5 7). Most neurologic irAEs resolved (26/35 patients; 75%). Overall, median time to onset was 45 days (range 1–170) and to resolution was 32 days (2–8091). Median time to onset of encephalitis was 55.5 days (range 18–297); four cases resolved and one was fatal. Conclusion. Both oncologists and neurologists need to be aware of signs and symptoms of serious but uncommon neurologic irAEs associated with checkpoint inhibitors. Prompt diagnosis and management using an established algorithm are critical to minimize serious complications from these neurologic irAEs.

[with this algorithm]

I hope this is information you will never need....but if you do....I hope it helps. - c

Sew Chaotically! - Me Made May - Week 3

Me Made May!!! Week 3 ~

Pretty cool skirt pattern actually - Simplicity 2451

Just knowing how I acquired this fabric...and the folks who said, upon seeing the fabric [that I proudly had in my possession!!!], "You would never wear that!!!"  (Check out The best helper (in all things!!!) a girl could ever have!!! ) - makes me laugh!!!

'Cause,"YES, I  WOULD!!!" and do!  Modified version of this A-line skirt

Some days you don't have a lot of photog skillz!  Another me made McCall's 7093!

The happiest days are when you get a visit from your bestie!!!  AND she brings presents!!!  #sisters #colette #sorbetto  #ruthiemakesthebestmemadesever  Check out her newly minted (Hee hee!!) embroidered lawn (?) she got in NY from Mood and made into a sweet little summer dress!

Such a fun visit to the Atlanta Botanical Gardens. #rumi #christinehaynespatterns  How cool is Ruthie's maxi skirt in a fab Liberty of London print???!!!

Didn't get a pic on this day!  However, wore this little vogue dress, minus the shirt, to the DeKalb Farmer's Market.  We were too busy with our adventure and eating ALL the food!!!!

When your bestie has to go home...but you look cute anyway in the t shirt dress  you made with great fabric she sent you!!  And isn't that the cutest little Ruthie-made sundress in a panel print?????

Such a great way to end my week getting to play!!  Thanks for indulging us, Bent and Frankie!!  Sew and live chaotically!! - love, les

Proof of concept. CAR-T and Immunotherapy + mice and research = "containment" and "cure" for ratties!!!

Not exactly news....but sometimes it is nice to recognize how far we've come...

Current status of chimeric antigen receptor engineered T cell-based and immune checkpoint blockade-based cancer immunotherapies.  Hegde, Mukherji. Cancer Immunol Immunother. 2017 May 11.

Adoptive cell therapies with chimeric antigen receptor (CAR) engineered T cells (CAR-T) and immune checkpoint inhibition (ICI)-based cancer immunotherapies have lately shown remarkable success in certain tumor types. CAR-T cell-based therapies targeting CD19 can now induce durable remissions as well as prolong disease-free survival of patients with CD19 positive treatment refractory B cell malignancies and ICI-based therapies with humanized monoclonal antibodies against the T cell inhibitory receptors CTLA-4 and PD-1 as well as against the PD-1 ligand, PD-L1, can now achieve durable remissions as well as prolongation of life of a sizeable fraction of patients with melanoma and Hodgkin's lymphoma and non-small cell cancers. Most importantly, these immuno-therapeutic treatment modalities have raised the possibility of achieving long-term "containment" as well as "cures" for certain types of cancer. While this represents major advances in cancer immunotherapy, both modalities come with considerable toxicities, including fatalities. Although more work will be needed to bring CAR-T cell-based therapies to the bedside for most major cancers and a good deal more will be needed to make ICI-alone or in combination with other treatment modalities-work more consistently and across most major cancers, these two treatment modalities stand out as superb examples of successful translation of bench research to the bedside as well as represent real progress in the field of cancer immunotherapy.

We've come a long way, baby!  Thanks to the mice....AND the ratties!  Take care. - c

Prognostic markers in Stage IIIC melanoma

Not really news....but.....

Clinical prognostic markers in stage IIIC melanoma.  Madu, Schopman, Berger, et al.J Surg Oncol. 2017 Apr 15. 

Although the EORTC 18071-trial has shown a clear survival benefit for adjuvant ipilimumab, accurately selecting patients for this toxic adjuvant therapy is important. We aimed to identify prognostic factors for death and disease recurrence in AJCC stage IIIC melanoma patients.

Retrospective analysis of patients who underwent lymph node dissection (LND) for stage IIIC melanoma in our institution between 2000 and 2016. Baseline characteristics, melanoma-specific survival (MSS), and disease-free survival (DFS) were assessed, and prognostic factors for recurrence and survival were analyzed using uni- and multivariable analysis.
A total of 205 patients were included. Median follow-up was 20 months (interquartile range 11-43 months), median MSS was 28 months, and median DFS was 11 months. Five-year MSS was 33% and 5-year DFS was 23%. N3 (greater or = to 4 involved lymph nodes) and extracapsular extension (ECE) carried an increased risk of disease recurrence after LND and death by melanoma. Patients with both N3 and ECE had virtually no long-term survival.

Although survival for patients with stage IIIC is poor in general, patients with both N3 disease and ECE constitute the group with the worst prognosis and should be considered for adjuvant therapy with ipilimumab or any other future effective adjuvant therapy (study).

So....we already knew that folks with more positive nodes and melanoma extended beyond the nodes were certainly more vulnerable to progression.

However, we also know this:  Prolonged survival in Stage III melanoma treated with ipi as adjuvant!!!

Yet, when faced with this conundrum - this data would give me pause:  Sequential nivo then ipi = ORR of 41%. Ipi followed by nivo = ORR of 20%!!!! 

Hang in there ratties.  It pays to have long tails.  Wishing you all my best. - c

Immunotherapy with SRS does NOT increase risk of radiation necrosis in melanoma brain mets!!!

We already know that folks who get immunotherapy WITH (or as soon as possible relative to) SRS [stereotactic radiation] therapy for brain mets do best.  Here's a post with multiple links that covers that and then some: Anti-PD-1 works best with SRS for brain mets in melanoma, Don't wait to add anti-PD-1 to SRS for brain mets, etc, etc!!!!!

Yet, patients are STILL being advised BY THEIR ONCOLOGISTS, "Oh, my goodness, no!!  We can't do both immunotherapy and SRS to brain mets at the same time.!  It would be too toxic.  It would increase the risk of radiation necrosis!"

Now, radiation necrosis is a real problem.  It is a complication that arises for far too many.  However, combining radiation with immunotherapy does NOT increase the risk!  Check out this review of 137 patients and their 1,094 brain lesions:

Radiation necrosis with stereotactic radiosurgery combined with CTLA-4 blockade and PD-1 inhibition for treatment of intracranial disease in metastatic melanoma. Fang, Jiang, Allen, et al.  J Neurooncol. 2017 May 12.  

Immune checkpoint inhibitors have demonstrated remarkable benefits in cancer patients. However, concern regarding toxicity in the setting of stereotactic radiosurgery (SRS) is often raised. In this study, we characterize radiation necrosis (RN) following immunotherapy and SRS. Melanoma patients treated with SRS and anti-CTLA-4 and/or anti-PD-1 at our institution from January 2006 to December 2015 were retrospectively reviewed. Overall survival (OS) and time to RN were assessed using Kaplan-Meier analysis. Logistic regression and Cox proportional hazards analyses were performed to identify predictors of radiation necrosis-free survival (RNFS) and RN risk. One-hundred thirty-seven patients with 1094 treated lesions over 296 SRS sessions were analyzed. Median follow-up was 9.8 months from SRS. Rate of RN was 27% of patients with median time to RN of 6 months. Median OS from SRS treatment was 16.9 months. RNFS at 6 months, 1 and 2 years was 92.7, 83.0, and 81.2%. Treatment with chemotherapy within 6 months of SRS was associated with worse RNFS at 1 year. On multivariate analysis, chemotherapy within 6 months and increased number of lesions treated were predictive of increased RN risk, whereas immunotherapy type and targeted therapy were not predictive. Median target volume of lesions that developed RN was greater than that of lesions that did not. Concurrent treatment with chemotherapy, larger size and number of lesions treated were predictive of RN. Immunotherapy type and timing proximity to SRS were not associated with RN risk.

So, this review of real ratties demonstrates that having chemo (OMG????!!!!), larger sized brain lesions, and a greater number of lesions treated DOES increase the risk of radiation necrosis - giving immunotherapy (ipi or anti-PD-1) and timing proximity to SRS treatment does NOT!!!!!

Could we get some nit-wit oncologists/radiation oncologist to read their own professional journals....or this blog?  Well, if you get told something similar to the little talk outlined above....PRINT and DELIVER this report to them! Hang tough, dear ratties! - c

Sew Chaotically! - Me Made May - Week 2

Me Made May! ~ 2017   Week 2!

Loooove this fit and flare top.  B5890

Polka dot New Look 0926 and you know I love my Grainline Morris Blazer!!!

It ain't dinner if you don't add onions!!!  One of my favorite makes evah!!!  Grainline studio's Alder Shirtdress

Recently minted Funky vintage (?) men's wear (??) pants!

Downtown with my bestie and awesome advocate after a speech he gave in front of the Courthouse and a conspicuously absent Senator Lamar Alexander!!!  B fights for the health care rights of all of us.  And...oh yeah....me made Top from McCall's Dress 6886

After a fun breakfast with Roo and Jamie....

...a little walk with Karma in my Me Made cowl neck knit tee shirt dress, McCall's 6752

Happy Mother's Day to all you great moms out there.  Just chill'n in my me made, dead easy elastic waist skirt in a crazy knit.

Thanks for indulging me, B.  Thanks to all 4 of my peeps, for letting me "mother"!  Sew and live, chaotically! - c

Phenformin improves activity of anti-PD-1

I've talked about Phenformin before:

Here, in 2016:  A look at effect of routine meds used by patients when on ipi....    Where though metformin was among many of the meds folks on ipi were taking, "only PPIs were found to have an increased odds of experiencing a partial response or a complete response to ipilimumab on the basis of a case-control analysis".   However, one should remember this was 'metformin' NOT phformin.

Here, in 2017:  Phenformin (not metformin) can reduce growth of melanoma cells   In the first report it notes that thought phenformin has some effect on melanoma cells, metformin has none.  The second report notes:  Consistently, phenformin reduces melanoma cell viability and growth independently from SOX2 levels.

And now, there's this:

Phenformin inhibits myeloid-derived suppressor cells and enhances the anti-tumor activity of PD-1 blockade in melanoma. Kim, Li, Trousil, et al. J Invest Dermatol. 2017 Apr 19.

Biguanides, such as the diabetes therapeutics metformin and phenformin, have demonstrated antitumor activity both in vitro and in vivo. However, their potential effects on the tumor microenvironment are largely unknown. Here we report that phenformin selectively inhibits granulocytic myeloid-derived suppressor cells (G-MDSCs) in spleens of tumor bearing mice and ex vivo. Phenformin induces production of reactive oxygen species in G-MDSC, whereas the antioxidant N-acetylcysteine attenuates the inhibitory effects of phenformin. Importantly, co-treatment of phenformin enhances the effect of anti-PD-1 antibody therapy on inhibiting tumor growth in the BRAF V600E/PTEN null melanoma mouse model. Combination of phenformin and anti PD-1 cooperatively induces CD8⁺ T cell infiltration and decreases levels of proteins that are critical for immune suppressive activities of MDSCs. Our findings demonstrate a selective, inhibitory effect of phenformin on G-MDSCs-driven immune suppression and support that phenformin improves the anti-tumor activity of PD-1 blockade immunotherapy in melanoma.

When it comes to myeloid suppressor cells, remember I've posted reports from many sources that note that they stand in the way of a response for many:  Markers for response to immunotherapy: Increased eosinophils = good. Increased Myeloid Suppressor cells = not so good.

For what it's worth!  - c

Sew Chaotically! - McCall's 2077 - Pleated Funky Men's Wear (?) Pants

This was a crazy trip back in time. The pattern, McCall's 2077, was first used to make a favorite pair of pants I wore to death in high school!  This was back in the 80's, y'all!!!  They were made of a light weight woven of black and midnight blue floral. Girl, I was styl'n!!!  Anyhow, I was surprised to find it when organizing some of my older patterns as I have very few such blasts from my homemade past.

Remember this bias binding????

Vintage???!

I was quite pleased to work this waist band finish out, though it was not what the pattern called for, using my me-made bias binding.  NO UGLY INSIDES!!!

With my Sorbetto!

With rtw top and sweater.

With Karm!  This was a fun make. The pants are obviously quite voluminous and didn't require the bit of extra room I gave them when I cut them out.  The waist band sits at the waist, with darts in the back, pleats in the front and the closure is created via a flap over the pocket on one side.  (Much like it appears Megan Nielsen's Flint Pant does.) There are interesting darts both in front and behind at the bottom of each leg to create a somewhat pegged look.

Don't know if I will make them again just because how many pants of this style does one girl need? Plus, I have some other rather "baggy" pant patterns I want to try.  But, I'm really glad I made them as I learned new skills by using the binding on the waist band and have worn them several times already!!

Sew Chaotically!!!! - les