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

Tolerating immunotherapy for melanoma DESPITE prior diagnosis with rheumatologic disease

The fear by docs and patients alike, that those with a pre-existing autoimmune disease would experience an extreme flare of their disease should they take immunotherapy....which we know will stimulate the patient's immune response...seems quite reasonable!!!  BUT!  Thanks to some super brave ratties who went where others feared to tread....we have learned:

Patients with preexisting immune disease, melanoma, and treatment with Anti-PD-1? Yes, this can be done. Yes, autoimmune flares should be treated with immunosuppressive therapy while on immunotherapy. And YES!!!! These patients can still attain a response!

...a post with multiple links to prior reports within.  And, more recently....this:  Immunotherapy for melanoma with a pre-existing autoimmune disease??? YES!!! You can!

Now there's this:

Cancer immunotherapy in patients with preexisting rheumatologic disease: the Mayo Clinic experience. Richter, Pinkston, Kottschade, et al. Arthritis Rheumatol. 2018 Jan 24.

To determine the risk of rheumatologic disease flare and adverse effects in patients with preexisting rheumatologic disease receiving checkpoint inhibitor therapy.

A retrospective medical record review was performed to identify all patients who received checkpoint inhibitor therapy at Mayo Clinic, Rochester between 2011 and 2016 (approximately 5,200 patients). Those with preexisting rheumatologic disease were identified using specific diagnostic codes.

Sixteen patients were identified (81% female, median age 68.5). The most common rheumatologic diseases were rheumatoid arthritis (5), polymyalgia rheumatica (5), Sjogren's syndrome (2), and systemic lupus erythematosus (2). Seven patients were receiving immunosuppressive therapy or glucocorticoids for their rheumatologic disease upon initiation of a checkpoint inhibitor. The primary malignancies were melanoma (10), pulmonary (4), or hematologic (2). In most cases checkpoint inhibitors were offered only after failure of several other therapies. Immune-related adverse effects (IRAE) occurred in 6 patients and all were treated successfully with corticosteroids and discontinuation of therapy. There were no significant differences in time from cancer diagnosis to immunotherapy, duration of immunotherapy, age, or sex between the patients with and without IRAEs.

To our knowledge, this represents the largest single-center cohort of patients with rheumatologic diseases who were exposed to modern cancer immunotherapy. Only a minority of these patients experienced a flare of their preexisting rheumatologic disease or any other IRAE. 

In these 16 patients with preexisting autoimmune disease there were some immune-related side effects.  However, just like melanoma peeps who have unfortunate immune related side effects thought they do NOT have a preexisting rheumatologic disease, these adverse events were handled with corticosteroids and break in therapy.  

Hang tough peeps!  Hang tough! - c

Sew Chaotically! - Sew bots????!!!

B shared this video from the Wall Street Journal with me today:  WSJ series - Moving upstream: How sewing robots may put humans out of work

The sewing and textile industry has always been an amazing utilitarian and artistic venture while simultaneously being one that often abuses, underpays, and mistreats its employees, who are, and have historically been, predominantly women.  In New York City in 1911, 145 workers died in the The Triangle Shirtwaist Fire ~ a sweatshop that employed about 600, mostly non-English speakers, who worked 12 hours a day, 7 days a week, for $15.000 per week.  There were 4 elevators in the building; only one worked.  The fire escape was narrow and dilapidated.  One exit door was locked and the other opened inwardly.  When the fire started in a box of rags, the manager discovered the fire hose was rotten and the water valve rusted shut.

Sadly, I'm not sure 'we've come a long way baby'!  Although the fashion industry has provided families, through the employment of the women in them, a wage that lifts them out of the most devastating poverty, these women remain frequent victims of demanding work quotas in poor working conditions for very little pay.  They are often illiterate, lacking in education generally and math in particular.  As the video at the top notes, today in Bangladesh, these women are lucky to make $164.00 per month.  As if that were not enough, here come the machines and bots - machines that can knit a sweater for Zara faster than human hands.  The video details machines used in a Japanese prison where workers with as little as one day of training create guard uniforms.  In Arkansas and Japan completely automated bots are being developed to sew a variety of garments.  Check out the video to see how machines sew perfect pockets and distress your latest jeans!!!

MY Creative Corner!!!

Sew-bots!!!  Part of me LOVES this!!!  And, it is a fact, that we home sewists wouldn't be making OUR garments without OUR machines!!!  My sewing improved in gigantic leaps when B got me Bernie and Sergie!!! But, this needn't be a one sum game!  Why can't we utilize the best that  machines provide while keeping the human touch?

Afghan #9 zillion and one for a special baby on the way!!!

Here's the thing.  In 2018, why DO we have illiterate people on the planet?  Why do we have people in poverty?  Children with insufficient food?  Girls (as well as boys) with NO opportunity for a basic education?  I actually know some of the answers.  Basic greed and power covers most of it!!!  So, I guess the better question is:  Why do WE ALLOW this circumstance?????  And folks...it IS a "WE"!  You and ME!!!  If the human brain and spirit can invent self driving cars, shoot rockets (and cars ~ what a waste of a Tesla!!!!!!!!!!!!!) into space, along with machines that can create garments with no need for human hands, we can feed and educate the world's people!  This kind of entrepreneurship, creative genius, and absolute brilliance can do SEW much more!!!  There really is no reason for the women of Bangladesh to be impoverished or left behind as automation, as it surely will, moves forward!!!

We can do better!  Let's start now!!! Sew and live chaotically! ~ les 

Simple blood tests that tell us how melanoma patients are responding to therapy and identify their disease in the first place....AGAIN!!!!

Yep.  It's me again, Margaret.  I'm still yelling about simple blood draws that can provide critical information related to the diagnosis of, feasibility of treatment for, response to treatment, and prognosis generally in melanoma patients!  Just last week I posted this:  More blood tests to determine prognosis as well as response to therapy in melanoma patients!!!

Now, there's this....

Clinical response to PD-1 blockade correlates with a sub-fraction of peripheral central memory CD4+ T cells in patients with malignant melanoma. Takeuchi, Tanemura, Tada, et al.  Int Immunol. 2017 Dec 23.

Cancer immunotherapy that blocks immune checkpoint molecules, such as PD-1/PD-L1, unleashes dysfunctional antitumor T-cell responses and has durable clinical benefits in various types of cancers. Yet its clinical efficacy is limited to a small proportion of patients, highlighting the need for identifying biomarkers that can predict the clinical response by exploring antitumor responses crucial for tumor regression. Here we explored T-cell responses associated with clinical benefits using peripheral blood mononuclear cells (PBMCs) from patients with malignant melanoma treated with anti-PD-1 monoclonal antibody (mAb). Pre- and post-treatment samples were collected from two different cohorts (discovery set and validation set) and subjected to mass cytometry assays that measured the expression levels of 35 proteins. Screening by high dimensional clustering in the discovery set identified increases in three micro-clusters of CD4+ T cells, a subset of central memory CD4+ T cells harboring CD27+FAS-CD45RA-CCR7+ phenotype, after treatment in long-term survivors, but not in non-responders. The same increase was also observed in clinical responders in the validation set. We propose that increases in this subset of central memory CD4+ T cells in peripheral blood can be potentially used as a predictor of clinical response to PD-1 blockade therapy in patients with malignant melanoma.

Here researchers looked at the blood of folks before and after patients with melanoma were treated with anti-PD-1.  They found that a particular type of CD4+ T cell increased in long term survivors and clinical responders...but NOT in non-responders.

That seems pretty straight forward to me!  But, there's more....

A high neutrophil to lymphocyte ratio prior to BRAF inhibitor treatment is a predictor of poor progression-free survival in patients with metastatic melanoma. Finon, Zaragoza, Maillard, et al. Eur J Dermatol. 2018 Jan 16.

Some studies have shown that a high neutrophil/lymphocyte ratio (NLR) greater than or = to 4 before initiating ipilimumab treatment is an independent prognostic indicator of poor survival in patients with metastatic melanoma (MM). To determine whether the NLR before starting BRAF inhibitor (BRAFi) treatment in patients with (MM) is associated with progression-free survival (PFS). This retrospective study included 49 patients consecutively receiving BRAFi for MM between July 2012 and December 2014. Cox proportional hazards regression was used to analyse the relationship between NLR and other factors, such as lactate dehydrogenase (LDH), performance status, BRAFi as first- or second-line therapy, and corticosteroid intake with PFS. The NLR before starting BRAFi was significantly associated with PFS based on univariate analysis and multivariate analysis adjusted for potential confounding factors, such as LDH activity, ulceration, performance status, first-line therapy, and corticosteroid intake. A high NLR (continuous variable) was associated with short PFS, and NLR greater than or = to 4 was associated with shorter PFS . Corticosteroid intake was not associated with short PFS based on multivariate analysis. An NLR greater than 4, before starting BRAFi treatment, is an independent prognostic indicator of poor progression-free survival.

SO.....again ~ folks with a high NLR (greater than or = to 4) did worse!!!  This is NOT news people.  I've been yelling about this since 2015!!!

That fact was valid when the NLR was tested in folks without metastatic disease ~  Neutrophil-to-lymphocyte ratios as a predictor of death from melanoma in patients with NONmetastatic disease
That fact was valid when the NLR was examined in regard to ipi (as noted in the above article) ~  Neutrophils as a prognostic predictor in patients trated with ipi/Yervoy
That fact was valid when first postulated in 2015 ~  Lab values that may predict response to Ipi/Yervoy????

Do we really need to examine that any further???  There is also this...

Development and validation of a plasma-based melanoma biomarker suitable for clinical use.  Van, Lincoln, Van Laar.  Br J Cancer. 2018 Jan 23.

In Australia, more money is spent on skin cancer than any other malignancy. Despite this, the mortality rate of melanoma, the deadliest form, has steadily increased over the past 50 years. Diagnostic imprecision and a lack of complimentary molecular biomarkers are partially responsible for this lack of progress.

Whole-microRNAome profiling was performed on plasma samples from 32 patients with histologically confirmed melanoma and 16 normal controls. A classification algorithm was trained on these data and independently validated on multiple previously published microRNA data sets, representing (i) melanoma patient- and normal-blood, (ii) melanoma and nevi biopsy tissue, and (iii) cell lines and purified exosomes.

38 circulating microRNAs had biologically and statistically significant differences between melanoma and normal plasma samples (MEL38). A support vector machine algorithm, trained on these markers, showed strong independent classification accuracy (AUC 0.79-0.94). A majority of MEL38 genes have been previously associated with melanoma and are known regulators of angiogenesis, metastasis, tumour suppression, and treatment resistance.

MEL38 exhibits disease state specificity and robustness to platform and specimen-type variation. It has potential to become an objective diagnostic biomarker and improve the precision and accuracy of melanoma detection and monitoring.

Here folks looked at blood samples for microRNA whose presence helped define the difference between melanoma and normal plasma.  

I have endless posts regarding the examination of tumor DNA in the blood of melanoma patients, allowing for the identification of disease, BRAF status, progression, response, etc.  Earlier this month, I posted this:  Circulating tumor DNA to help differentiate true progression of melanoma vs pseudoprogression in patients treated with anti-PD-1  Here are about a zillion additional posts:  Circulating melanoma DNA

Really people!  Can someone not do a definitive study on a larger scale...rather than piecemeal this and that....without sharing data...to come up with a valid and specific melanoma panel???  We have simple lipid panels that help guide heart health.  We have lab draws and tests that help diagnosis and monitor diabetes.  No set of labs is an absolute for ANYTHING.  BUT!!!!  They are incredibly important tools in diagnosing, treating and managing a wide variety of disease processes.  They can do that for melanoma, too!!!   We have learned that we can look at T cells, other basic blood cells, tumor DNA, RNA, all sorts of bits and bobs....floating in the blood of patients with melanoma, to provide meaningful information that could allow melanoma patients and their doctors a mechanism for making better choices in their treatment and care.

Radiologic scans expose us to radiation, "find" lots of red herrings, and are a huge financial burden.  They also have limits regarding what they can see.  Sub-centimeter tumors, not to mention little demon melanoma cells floating about, are not visualized.  Additionally, imaging studies are cumbersome and have a built in time lag that can delay needed therapy or a change in current therapy as patients wait for "their next scan" to be compared to a prior one in order to define disease status.  Determining pathology from tumor samples is often confusing.  I had to have my initial slides examined by 3 pathologists to gain consensus that I was in fact dealing with melanoma.  Folks need and deserve answers. A basic algorithim that incorporates all forms of investigation including blood markers, nuclear, radiographic, and tissue examination needs to be established for melanoma. NOW!!!

Seriously..NOW!!! - c

Living Chaotically!!!!

I know you will be surprised to learn that I've been running about chaotically!!!  Working a bit extra.  Getting back into shape after my sicknesses!!!  How can things slide so quickly?!  Oh, well.  I've pretty much returned to normal with my runs, elliptical, and workouts with Roo.

Brent and I prepped our garden beds.  Seeded our early spring garden with radishes, sweet peas, broccoli, various lettuces, chard, and carrots!  We've also made plans for adding another shrub/flower bed in the front.

I know, I know!!!  They are itty bitty!!  But they're there!!!  I've learned to enjoy what I can when I can!!!!

I've scrubbed all the window frames free of the gunk they magically accumulate over winter. Tidied closets.  Gone through clothes.  Caught up the ironing.  Had my teeth cleaned.  The cheek lesion my hygienist found (Story here:  October 2017: Trick or Treat!!!!) and that subsequent evaluations by my local oncologist and ENT determined to be nothing/vitiligo on a scar from all my prior oral lesions that were side effects of my nivo - remains about the same.  Nothing else to discuss.  Boring is GOOD!!!

My Lenten Roses have begun to peek out.  Such funny little flowers!!!

Recently I've had difficulty getting my glasses clean!  They seemed to have a film that I just couldn't remove.  Suddenly, a thought came to me.  What if the problem is not with the glasses???  I crack myself up!!!!  I had my eyes examined.  And....uh, yeah.  I need a new scrip.  Nothing bad.  Just a bit older.  Another year that I will embrace happily!!! I'll really embrace better vision when my new glasses arrive in a couple of weeks!!!

I whipped up some spice blends for Roo and J as well as myself!

I just love this book!  It has great information on spices generally, fabulous recipes for spice mixtures, and additional recipes using them in dishes.  YUM!!!

I have a zillion exciting sewing projects in process and in my head.  I am working with B on planning some fun trips.  We miss our Karmie every day.  Silly little bugger!!!  I am enjoying rediscovering my flower friends as spring seems to have sprung here on the mountain.  In case she has not yet come to your part of the world, here's a bouquet for you:

Daffy-down-dilly has just come to town, with a yellow petticoat and a pretty green gown!
Enjoy chaotically!!! - love, les

More blood tests to determine prognosis as well as response to therapy in melanoma patients!!!

It is becoming more and more clear (at least to me!!!!!!!!!) that there are all sorts of ways of looking at blood markers in order to diagnose, predict progression and response, as well as evaluate response to a particular treatment in melanoma patients.  Here is my latest post with a zillion links within:  Circulating tumor DNA to help differentiate true progression of melanoma vs pseudoprogression in patients treated with anti-PD-1  Now, there's this ~

Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. Zager, Gastman, Leachman, et al.  BMC Cancer. 2018 Feb 5.

The heterogeneous behavior of patients with melanoma makes prognostication challenging. To address this, a gene expression profile (GEP) test to predict metastatic risk was previously developed. This study evaluates the GEP's prognostic accuracy in an independent cohort of cutaneous melanoma patients.

This multi-center study analyzed primary melanoma tumors from 523 patients, using the GEP to classify patients as Class 1 (low risk) and Class 2 (high risk). Molecular classification was correlated to clinical outcome and assessed along with AJCC v7 staging criteria. Primary endpoints were recurrence-free (RFS) and distant metastasis-free (DMFS) survival.
The 5-year RFS rates for Class 1 and Class 2 were 88% and 52%, respectively, and DMFS rates were 93% versus 60%, respectively. The GEP was a significant predictor of RFS and DMFS in univariate analysis , along with Breslow thickness, ulceration, mitotic rate, and sentinel lymph node (SLN) status . GEP, tumor thickness and SLN status were significant predictors of RFS and DMFS in a multivariate model that also included ulceration and mitotic rate .

The GEP test is an objective predictor of metastatic risk and provides additional independent prognostic information to traditional staging to help estimate an individual's risk for recurrence. The assay identified 70% of stage I and II patients who ultimately developed distant metastasis. Its role in consideration of patients for adjuvant therapy should be examined prospectively.

Think how great this sort of information would be when trying to determine whether or not to utilize adjuvant therapy!!!

But, that's not all!  There's also this ~

Molecular signatures of circulating melanoma cells for monitoring early response to immune checkpoint therapy.  Hong, Sullivan, Kalinich, et al.  Proc Natl Acad Sci U S A. 2018 Feb 16.

A subset of patients with metastatic melanoma have sustained remissions following treatment with immune checkpoint inhibitors. However, analyses of pretreatment tumor biopsies for markers predictive of response, including PD-1 ligand (PD-L1) expression and mutational burden, are insufficiently precise to guide treatment selection, and clinical radiographic evidence of response on therapy may be delayed, leading to some patients receiving potentially ineffective but toxic therapy. Here, we developed a molecular signature of melanoma circulating tumor cells (CTCs) to quantify early tumor response using blood-based monitoring. A quantitative 19-gene digital RNA signature (CTC score) applied to microfluidically enriched CTCs robustly distinguishes melanoma cells, within a background of blood cells in reconstituted and in patient-derived (n = 42) blood specimens. In a prospective cohort of 49 patients treated with immune checkpoint inhibitors, a decrease in CTC score within 7 weeks of therapy correlates with marked improvement in progression-free survival and overall survival. Thus, digital quantitation of melanoma CTC-derived transcripts enables serial noninvasive monitoring of tumor burden, supporting the rational application of immune checkpoint inhibition therapies.

Wouldn't it be great to know where you stand 7 weeks into therapy?  You wouldn't waste time (and in melanoma world that "time" can make all the difference!!!) with a therapy that is not working for you!!!

Blood draws with more detailed info than repeated radiological studies!!!  C'mon man!!!  Let's get some consensus and make these tests available for patients in need! - c

Rechallenge with BRAF/MEK combo in melanoma

For BRAF positive melanoma patients, targeted therapy with a BRAF inhibitor combined with a MEK inhibitor can have amazing results in the destruction of melanoma!  Response rates are around 70-80%!!  While there are a few exceptions, the problem with this targeted therapy is that the benefit often evaporates around 6-9 months, with sinister melanoma developing the ability to work-around the treatment.  These peeps then go on to other treatments.  Sometimes those work, sometimes they don't.  If they don't, will taking BRAF/MEK again work?????

Now, there's this:   

Rechallenge with BRAF-directed treatment in metastatic melanoma: A multi-institutional retrospective study. Valpione, Carlino, Mangana, et al. Eur J Cancer. 2018 Jan 19.

Most metastatic melanoma patients treated with BRAF inhibitors (BRAFi) ± MEK inhibitors (MEKi) eventually progress on treatment. Along with acquired resistance due to genetic changes, epigenetic mechanisms that could be reversed after BRAFi discontinuation have been described. The purpose of this study was to analyse retrospectively outcomes for patients retreated with BRAF-directed therapy.

One hundred sixteen metastatic melanoma patients who received BRAFi-based therapy and, after a break, were rechallenged with BRAFi ± MEKi at 14 centres in Europe, US and Australia were studied, respectively. Response rate (RR), overall survival (OS) and progression-free survival (PFS) from the start of retreatment were calculated.

The median duration of treatment was 9.4 months for first BRAFi ± MEKi treatment and 7.7 months for the subsequent treatment (immunotherapy 72%, other 17%, drug holiday 11%) after BRAFi discontinuation. Brain metastases were present in 51 (44%) patients at BRAFi retreatment. The RR to rechallenge with BRAFi ± MEKi was 43%: complete response (CR) 3%, partial response (PR) 39%, stable disease (SD) 24% and progressive disease 30%, 4% missing. Of 83 patients who previously discontinued BRAFi due to disease progression, 31 (37.3%) responded (30 PR and 1 CR) to retreatment. The median OS from retreatment was 9.8 months, and PFS was 5 months. Independent prognostic factors for survival at rechallenge included number of metastatic sites , lactic dehydrogenase, while rechallenge with combination BRAFi + MEKi conferred a better OS versus BRAFi alone.

Rechallenge with BRAFi ± MEKi results in a clinically meaningful benefit and should be considered for selected patients.

In this study, 116 peeps who had taken BRAFi (a BRAF/MEK combo) for an average of 9.4 months stopped taking it for a variety of reasons ~ and had roughly 8 months of:  immunotherapy (72%), other treatment (17%) and drug holiday (11%).  They were then rechallenged with a BRAF/MEK combo.  Response rate for the rechallenge was 43% with 3% attaining a complete response, 39% a partial response and 24% gaining stable disease, although 30% had progressive disease and 4% were apparently lost to follow-up.  Of the 83 peeps who stopped BRAFi initially due to disease progression, 31 responded to the rechallenge - 30 with a partial response and 1 with a complete response.  Median OS from BRAFi retreatment was 9.8 months and PFS was 5 months.

Given the results of this study, the answer to the initial question I posed, is:  YES, a rechallenge with BRAF/MEK can work with a response rate of about 43% generally and 37% in those who progressed on BRAFi the first go round.  Response rates are not as high nor as complete as those attained with the initial treatment....but....they are there!!! Repeating treatment with BRAF/MEK is certainly an option in kicking melanoma in the teeth a bit, while seeking more effective, durable treatment.

It's something.  Thanks, ratties.  - c