40% of melanoma patients stop ipi/nivo due to side effects...BUT...efficacy is about the same!!!

Many patients have to stop the ipi/nivo combo due to side effects. This report is pretty much a new take on a prior one, which is summed up in the title:  ASCO 2016 - Nivo plus ipi, CheckMate 069 trial....18 month OS similar even if you stop meds due to side effects!!     Here's the new version:

Efficacy and Safety Outcomes in Patients With Advanced Melanoma Who Discontinued Treatment With Nivolumab and Ipilimumab Because of Adverse Events: A Pooled Analysis of Randomized Phase II and III Trials. Schadendorf, Wolchok, Hodi, … Chesney, Robert, Grossmann, McDermott, … Postow. J Clin Oncol. 2017 Aug 25: [Epub ahead of print]

Approximately 40% of patients with advanced melanoma who received nivolumab combined with ipilimumab in clinical trials discontinued treatment because of adverse events (AEs). We conducted a retrospective analysis to assess the efficacy and safety of nivolumab plus ipilimumab in patients who discontinued treatment because of AEs.

Data were pooled from phase II and III trials of patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, every 3 weeks for four doses, followed by nivolumab monotherapy 3 mg/kg every 2 weeks (N = 409). Efficacy was assessed in all randomly assigned patients who discontinued because of AEs during the induction phase (n = 96) and in those who did not discontinue because of AEs (n = 233). Safety was assessed in treated patients who discontinued because of AEs (n = 176) at any time and in those who did not discontinue because of AEs (n = 231).

At a minimum follow-up of 18 months, median progression-free survival was 8.4 months for patients who discontinued treatment because of AEs during the induction phase and 10.8 months for patients who did not discontinue because of AEs . Median overall survival had not been reached in either group. The objective response rate was 58.3% for patients who discontinued because of AEs during the induction phase and 50.2% for patients who did not discontinue. The vast majority of grade 3 or 4 AEs occurred during the induction phase, with most resolving after appropriate management. 

Efficacy outcomes seemed similar between patients who discontinued nivolumab plus ipilimumab treatment because of AEs during the induction phase and those who did not discontinue because of AEs. Therefore, even after discontinuation, many patients may continue to derive benefit from combination therapy.

In this report, efficacy is emphasized.  Here's the deal -
40% of melanoma patients who take ipi/nivo have to stop due to side effects during the "induction phase" (the first 12 weeks when ipi and nivo are given together).
This study looked at 409 patients.
Efficacy (effectiveness) was assessed in all randomly assigned patients:  96 who had to discontinue treatment because of adverse events and 233 who did not.
Minimum average f/u was 18 months.
Median progression-free survival was 8.4 months for patients who had to stop treatment.
Median PFS was 10.8 months for those who did not stop.
Median OS was not reached in either group.
Response rate in those who stopped treatment due to side effects was 58.3%.
Response rate was 50.2% in those who did not discontinue.
Most AE's resolved with appropriate management.

As I concluded in the initial report....it's just me....but it seems clear that we are giving the ipi combo portion of this therapy too long!!!  For what it's worth. - c

Melanoma Intel: A primer for current standard of care and treatment options

I answer questions on melanoma boards or via email about treatment options at least every other week. It suddenly dawned on me that putting the information together in a blog post would save me repeated re-writes and help folks in the process.  HOWEVER, this is not an all inclusive listing. Rather, this is a basic guide to use in starting your research or discussions with your provider regarding melanoma care.  It is also primarily directed toward those of you who are Stage III/IV.

As recently as 2010, NONE of the current, most effective treatments for melanoma were FDA approved. And no matter what option you think fits you best, it is essential that you be seen by an oncologist who specializes in...or at the very least, has treated many patients with...melanoma.  Here's the down and dirty:

SURGERY

Surgery remains a good choice for melanoma. Clearly this is the case for new cutaneous lesions!!! Once a lesion is gone...it's gone!! This results in an immediate decrease in your tumor burden – always a good thing. However, if by chance you are looking for a clinical trial (though these days, especially for newly diagnosed Stage 3b and Stage IV patients, there are many viable treatment options without resorting to that) they sometimes require “measurable disease” so leaving at least one tumor in place would be required. This would also be the case if you were looking to utilize 'intralesional therapies' {info below}.

RADIATION

Radiation, when combined with immunotherapy, can be a very good treatment option for melanoma. Together, radiation and immunotherapy, illicit responses in melanoma that are greater than either treatment used as a single agent. However, targeted radiation (SRS – stereotactic radiation or Gamma Knife) is the most effective whether you are talking about brain tumors or lesions located elsewhere in the body. We have learned that whole brain radiation (WBR) is not effective in melanoma and can lead to debilitation. While there are those who avail themselves of this treatment due to extreme circumstances, it should not be the recommendation right out of the box for those with brain tumors. Even multiple tumors can be treated simultaneously with SRS.

IMMUNOTHERAPY

These are treatments that push our immune systems into action. Side effects (as you might imagine) are usually related to an 'over activation' of our immune system. Common side effects include – fatigue, rashes, joint pain. More complicated side effects are inflammation in the lungs (pneumonitis) and colon (colitis) with difficulty breathing and wheeze or diarrhea and abdominal discomfort, respectively. Patients can experience problems with thyroid function and other glands of the endocrine system. Responses take time. Experts are known to advise other docs to be “patient with the patient!” Immunotherapy works best with the lowest tumor burden.

Old school immunotherapy

Interferon

Discovered in 1957, interferons are a type of signaling proteins released by cells in response to viruses, bacteria, parasites, and tumors that help rally the immune response of the body against these invaders. In the early 1980's researchers and pharma were finally able to produce interferon for use as a medical therapy. There are many forms, used in treating various conditions (some more effectively than others) from multiple sclerosis to leukemia to melanoma. Often given as subcutaneous injections (though there are eye drops and inhalation forms), interferon causes significant side effects with fatigue, flu-like symptoms, hair loss, pain, depression and increased risk of infection due to neutropenia (decreased white cells) being common. Unfortunately, we have learned that in melanoma, interferon has a clinically insignificant effect on progression free survival as well as overall survival.

IL-2 (Interleukin 2)

Similarly, IL-2 is a signaling molecule that directs the actions of white blood cells in getting rid of invaders. Isolated in 1979, by the early 80's pharma (Ceta, Amgen, Roche) were in a mad dash to get a drug to market. It was FDA approved in 1992. It has been used in the treatment of HIV, renal cell carcinoma, and melanoma. Though it can be injected subcutaneously on an outpatient basis, in melanoma it is most often given in an IV infusion, with side effects (extreme swelling, rash/peeling skin, hallucinations, among other horrors) such that patients must be in the hospital, in an intensive care setting, for infusions that are given every 8 hours for up to 15 doses as the patient can tolerate. It is also used in a low dose regimen with old school TIL therapy as a way to jump start the immune system after chemo has been given to eradicate existing regulatory T cells and new T cells grown from the patient's tumor have been infused.  It is also being studied as an intralesional (see below). Ultimately, we now know that the use of high dose IL-2 in melanoma can produce a complete response in about 5-6% of the patients, with some of those responses being durable (lasting).

Current Immunotherapy (also referred to as Check Point Inhibitors)

Ipilimumab (Brand name = Yervoy, slang = 'ipi') – anti-CTLA-4 monoclonal anti-body

Ipilimumab is a monoclonal anti-body that is used to restart the immune system by targeting CTLA-4, a protein receptor that actually turns the immune response OFF!!! It was approved for melanoma (Stage IV or unresectable Stage III) in 2011. It was approved as an adjuvant treatment for melanoma in 2015. Ipi is administered via an IV infusion every 3 weeks, for a total of 4 doses, at 3mg/kg for Stage IV patients and 10mg/kg for adjuvant therapy. Some adjuvant treatment plans continue ipi at that same dosage but every 12 weeks for up to 3 years. Melanoma patients given ipi can attain a response rate of about 15%. Responses can be durable.    Here are two resports:  Melanoma patients...alive and kicking 10 years after ipi!  and  Ipi for melanoma...the data keeps pouring in...and it's pretty good!  Patients experience more side effects with ipi than they do with anti-PD-1 products.  Ipi at 10mg/kg produces more side effects than ipi at 3mg/kg.  Ipi is also FDA approved in combination with nivolumab (2015) and is being studied currently in combination with pembrolizumab. {More info below.}

Anti-PD-1

      

First you have to understand that PD-1, also called programmed cell death protein 1, is a membrane protein and a T cell regulator, first discovered to be an immune checkpoint in 2000.  PD-1 is expressed on the surface of activated T cells, B cells and macrophages (white cells that can be involved in tissue repair or digestion of debris or pathogens). Compared to CTLA-4, PD-1 is keyed to specific tissues with the PD-L1 ligand, while CTLA-4 is less specific.

PD-L-1 is a ligand present on the surface of melanoma tumors (as well as some others) that can bind to infiltrating t-cells and turn them off!!

  

ANTI-PD-1 (the drugs) are monoclonal antibodies that block the switch on T cells so that PD-L1, on the surface of melanoma tumor cells, does NOT bind with them and turn them off....thereby allowing these cells to carry on and destroy melanoma tumors.

Sometimes pictures tell the story better:

    Nivolumab: (Brand name = Opdivo, slang = 'nivo') - anti-PD-1 monoclonal antibody

I wrote a little story about the development of nivo (You can read it here!!), but basically, in 2014 Nivo was approved for the use in advanced melanoma patients AFTER they had failed ipi, and if BRAF positive, BRAF inhibitors as well.  In November 2015 it was approved as a first line drug for unresectable or advanced melanoma BUT you had to be BRAF positive.  (A cosmically ridiculous judgement since we already had studies proving that BRAF status made little to no difference in response!!)  Finally, in 2016, based on the results of the Checkpoint-067 study, nivo was approved for use alone or with ipi, in advanced melanoma patients, no matter BRAF status.  It gained approval in 2017 as an adjuvant treatment option for patients with melanoma!  This is seriously good news!!!  It means even if you are Stage IV with all tumors removed (or zapped)...you can still take nivo.  Or...if you are Stage III with melanoma that went to your lymph nodes...you can take nivo!

From the November 2015 link - Here are more ways Opdivo has been approved and is helping others:

• Advanced renal cell carcinoma (11/23/2015)
• Advanced non-squamous non-small cell lung cancer - after platinum based chemo (10/9/2015)
• In the Nivo/Opdivo with Ipililmumab/Yervoy combo for BRAF V600 advanced melanoma (10/1/2015)
• Advanced non-small cell lung cancer - after platinum based chemo (3/4/2015)
• For melanoma, after failing ipi, and if BRAF positive, BRAFi (12/22/14) 

     Pembrolizumab: (Brand name = Keytruda, slang = 'pembro') - anti-PD-1 monoclonal antibody

Pembro was similarly approved for melanoma in 2014.  Since then it has been approved in various algorithms for NSCLC and head and neck squamous cell cancer

Response rate and side effects for advanced melanoma patients:

Both anti-PD-1 drugs effect about a 40% response rate in melanoma. They can work in the brain and the body.  Median time to response is about 3 months.  But, there are outliers, with documented responses, that do not occur until 6 - 9 months.  Here's a cool graph...

Here's a post with more info:  Time to Response...Ipi vs Nivo and ipi

Responses can be durable!!!  There is every reason to expect that responses to anti-PD-1 will be at least as durable (and probably more so) than those to ipi.  This post includes neat charts regarding response and durability to Pembro:  Dr. Daud reviews ASCO 2016 - immunology updates for melanoma

Side effects are similar for both drugs and are those typical for immunotherapy, but less severe than those encountered with ipi. On the topic of side effects...they SHOULD be treated!!!  As quickly as possible, often with a break from medication and immunosuppressive drugs as required.  While oncologists not familiar with immunotherapy may fear decreased therapeutic response if steroids are used...THIS IS NOT THE CASE!!!  Here's a post (with multiple links within related to treating immunotherapy side effects:  Yep! Immunotherapy can work in the brain...and pseudoprogression can be real!!

Dosing:

Pembro is dosed at 200 mg IV every 3 weeks.  Nivo is dosed at 240 mg IV every two weeks or 480mg IV every 4 weeks, endpoints vary per doc, patient and institution. When ipi is combined with nivo, response rates in melanoma rise to 50+%, though side effects do as well, though mostly due to ipi.  For the combo, dosage is:  nivo at 1 mg/kg followed by ipi  at 3 mg/kg on the same day, every 3 weeks for 4 doses, then nivo alone at 240 mg q 2 wks or 480 mg q 4 wks. Many patients cannot tolerate all 4 doses of the ipi/nivo combo due to side effects.  However, outcomes can be good even if you have to stop early. Here's a report from ASCO 2016:  Nivo plus ipi, CheckMate 069 trial....18 month OS similar even if you stop meds due to side effects!!!  Additionally, most folks can go on to tolerate nivo alone, once their side effects are brought under control with a medication break and/or steroids.  Pembro in combination with ipi is being studied.

TARGETED THERAPY

At this point in melanoma, the only approved targeted therapy is for patients whose tumor is positive for the BRAF V600 mutation.  About 50% of melanomas are.  However, researchers are looking at drugs that could target other points in the molecular pathway of melanoma.  This diagram shows what I mean by "pathway"...

A Melanoma Molecular Disease Model (See the link below for credit and more info)

Here's just one example from March of this year:  What tangled 'paths' we weave: Nilotinib for KIT mutated melanoma and Buparlisib for the PI3K pathway in melanoma brain mets

But....for current purposes....I am focusing on the BRAF mutation.  Here's a post I made a bit ago that really breaks down what BRAF is, what it means in melanoma, and how the drugs work:  BRAF inhibitors for melanoma: Dabrafenib, Vemurafenib, Dabrafenib/trametinib combo. Answers!!!!!

Usually when we combine drugs, we end up with increased side effects. However, in the case of BRAF targeted therapy we now know that BRAF inhibitors should ALWAYS be given with a MEK inhibitor.  Strangely enough, when the combo is given, patients experience better response rates, DECREASED side effects, and DECREASED rates of tumor work-around.

DRUGS, administration, and side effects:

BRAF inhibitor (BRAFi) drugs include:  Vemurafenib (Zelboraf), Dabrafenib (Tafinlar), Sorafenib (Nexavar), and Encorafenib
MEK inhibitors (MEKi) include:  Trametinib (Mekinist), Cobimetinib (Cotellic) and Binimetinib (not yet given a brand name)

These drugs are administered orally.  So that's super cool.  Dosing depends on the particular drug.
Side effects include joint pain, rashes, extreme sun sensitivity, development of benign skin cancers, fevers and sometimes liver toxicity.

EFFECTIVENESS and tumor work-around:

For patients who are BRAF positive, BRAF inhibitors combined with a MEK inhibitor have impressive response rates, clearing tumors rapidly, and often completely, in about 70-80% of patients and are effective in the brain and body. However, those responses are not very durable, with most tumors learning to work around the inhibition in about 7-9 months. BUT!!!!  By using an "alternate dosing schedule" (one that is varied, rather than absolute with an 'every so many hours daily' dosing pattern), combining BRAFi with MEKi, as well as the development of the newer drugs (Here's a post out of ASCO this year:  Encorafenib/binimetinib, a BRAF/MEK combo = 14.9 month PFS) that time can be stretched out a bit.  Furthermore, despite the statistics, there are some melanoma peeps whose melanoma has been successfully managed for years on BRAF/MEK combo's!!  Finally, some melanoma specialists use BRAF/MEK combo's in BRAF positive patients, to rapidly decrease the tumor burden, then switch the patient to slower acting, but more durable immunotherapy.  And...in the realm of 'the latest and greatest', researchers are working on combining BRAF/MEK with immunotherapy.  Here's a recent post on the topic with more links within:  ASCO 2017: Atezo (anti-PDL1) with Cobimetinib (MEKi) and Vemurafenib (BRAFi) for BRAF V-600 melanoma

DECIDING on immunotherapy vs targeted therapy in the BRAF positive patient - can be tricky! Here is a post addressing that issue via a discussion between melanoma experts:  Pick your poison: Weber and Agarwala discuss combination therapy for melanoma

INTRALSIONAL (also referred to as 'intratumoral') THERAPY

Intralesional drugs include (but are not limited to):

CAVATAK - derived from the Coxsackievirus
T-VEC - also called OncoVEX, Imlygic,  or Talimogene Laherparepvec - uses the herpes virus with GM-CSF
PV-10 - derived from Rose Bengal
HF10 - also derived from HSV
SD101 - a TLR9 agonist
IL-2 - see note above, is also being used

These drugs are injected directly into a relatively superficial melanoma tumor.  They have been found to be effective in not only eradicating the tumor into which they have been injected, but 'by-stander' lesions as well. Researchers feel that they have the most promise when they are combined with a systemic treatment like immunotherapy.  I summarized response rates, side effects, and pretty much everything else current about these drugs in this post from this year's ASCO reports on all of them: All things intralesional/intratumoral

FUTURE TREATMENT OPTIONS

Despite the success that these therapies have had for many melanoma patients, myself included, they are insufficient for far too many!  Luckily, research and drug development continues.  Many researchers have noted that combo's are likely to be the future of melanoma treatment.  Work is ongoing on IDO inhibitors, ERK inhibitors, vaccines (though I fear we are not there yet), new anti-PD-1 and anti-PD-L1 drugs, anti-LAG-3, CD47 blockers, HDAC inhibitors, and more.

I hope this primer will be helpful.  What has served me best in attaining effective treatment for my melanoma has been seeking out a melanoma specialist and never being afraid to ask questions. Asking this question of my doctor may have been the most beneficial:  "What treatment would you recommend if it were YOU or your brother, sister, wife, father, mother.... in need?"

I wish you all my very best. Hang in there.  And....thanks, ratties! - love, c

P.S. If all the acronyms are driving you crazy, here's a post that defines at least some of them:  Melanoma abbreviations ~ and random thoughts on posting melanoma crap-ola....
P.S.S.  A sense of humor really does help!!  - c

Lucky Me!!! I'm 53! Living with melanoma and HOPE!!!

There is no sarcasm in the title.  None.  I have known unfortunate souls who bemoaned growing older, some when they were much younger than I am today!  I am not one of those!  Can aging result in loss of strength and ability?  Sure, you don't see many Olympians or Super Bowl stars on the field over the age of 30! Certain diseases and conditions are present ONLY in the elderly.  I am not one to believe that a mind set can change everything.  I don't buy the idea that you can think yourself young if you are old, cancer free if you are not!  I do contend that a positive attitude makes anything a lot more manageable!!!  Besides, getting older beats the hell out of the alternative!!!

So, yeah....Lucky me, I'm 53!!!

I will never consider myself lucky to have melanoma.  But, I AM lucky to have responded well to the interventions I have been fortunate to attain.

I am lucky I have grown children, who are bright and strong and healthy...who are working hard in love and life.  Learning that things are not always easy.  Standing tall for themselves and for others. Demonstrating a generosity of spirit to those around them.  Making a difference.  Living lives that make me proud to call them my friends.

I am lucky to be able to offer help and health to the children and families I work with daily.  Even more blessed to share laughs, fist bumps and slobbery kisses with my toddlers as well as shy admissions of future plans from teens I've had the honor to watch grow.

I am lucky to be in the position to provide basic, understandable information about melanoma to those in need, while, perhaps, offering a bit of hope in the process.

I am lucky to be able to maintain my running and other exercise endeavors.  Grateful to have a sweet daughter willing to invite me to join her in a weekly "barre" workout.  (If it doesn't kill us, Roo....we're going to be awesome!!!!)

I am lucky to have been able to spend this summer tackling and completing fun sewing projects. Baby Boy Brewer's afghan made it into his mom's arms before he did!  My 3 garments for the Summer of Basics Make-Along were completed before the August deadline.  I managed to keep Ruthie's special top a secret AND got it done in time for her special day!!

Dental checks, car tags, yard work, household projects, annual continuing education requirements for my licensure...have been recently checked off the to-do list.  Yes, I count the ability to take care of the mundane - lucky!!!!

I am lucky to have read the Complete Short Stories of Ernest Hemingway this summer. Yes, it took a couple of months...which is a bit uncharacteristic of me.  The stories were not terribly complicated or long, but the emotional scale took me a minute to ponder, digest, and deal with. This 'short' story, most often attributed to Hemingway, is an example of what I mean ~   "For sale:  baby shoes, never worn."

I am lucky to have had the time and energy to work extra for a fellow provider who needed to be off.

I am lucky to have been able to contribute my small part, with my one voice, to speak out for those who cannot, in the battle to attain, continue, and improve healthcare for all.

I am lucky to have been able to enjoy nature and friendship with my best bud, on ever so many walks over the years, but the beauty we recently shared in Shenandoah was particularly poignant.

I am lucky to have my now annual scans scheduled for the end of this month, ostensibly approved by the wise and wonderful folks at Blue Cross Blue Shield, who have often balked at covering my care, but have had no trouble whatsoever cashing my premium payments monthly since I was 18 years old.

I am lucky to be looking forward to ringing in 29 years with my B at the end of this month!

I am lucky to have managed to find a way, gathered the strength, foolishly believed enough....I don't really know...to continue to create and enjoy small plans and hope for my future.  It has not been easy, as I wrote in this post Looking Forward, from 2010.  There I mentioned I have always told myself and my kids, "Live each day as though there will be no other, and you will have no regrets."  As such, I keep working on my own possibilities.

I am lucky to have dear ones, "...who keep ever burning before my vagrant steps, the kindly light of hope."

Hope - that enigmatic force that allows us to believe that tomorrow can be better, that our words and actions can make a difference, that while all things may not be perfect, there can be joy and beauty for us - still.

Ruthie, shared this with me a bit ago....

"Your opponents would love you to believe that it's hopeless, that you have no power, that there's no reason to act, that you can't win.  Hope is a gift you don't have to surrender, a power you don't have to throw away."                  ~  Rebecca Solnit, from:  Hope in the Dark.

Yes, lucky indeed to be 53!  Living with hope today...looking forward to what's next. - c

Anti-PD-1 and radiation...good combo for brain mets.....AGAIN!!!!! Again.....

Y'all know I've been yelling about the improved outcomes patients can attain for brain mets when targeted radiation (SRS or Gamma knife) is paired WITH immunotherapy:  Here's just a few of my rants and LOTS of data:  Radiation and Immunotherapy...better together!

Now there's this:

Radiation and PD-1 inhibition: Favorable outcomes after brain-directed radiation. Pike, Bang, Ott, et al. Radiother Oncol. 2017 Jun 26.

Patients with metastatic melanoma, renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC) are increasingly treated with immune checkpoint blockade targeting the programed death (PD)-1 receptor, often with palliative radiation therapy. Outcome data are limited in this population. We retrospectively reviewed consecutive patients with metastatic NSCLC, melanoma, and RCC who received radiation and anti-PD-1 therapy at four centers.

We identified 137 patients who received radiation and PD-1 inhibition. Median survival from first PD-1 therapy was 192, 394, and 121  days for NSCLC, melanoma, and RCC patients. Among 59 patients who received radiation following the start of PD-1 blockade, 25 continued to receive PD-1 inhibition for a median of 179days and survived for a median of 238 additional days. Median survival following first course of radiation for brain metastases was 634 days. Melanoma patients received brain directed radiation relatively less frequently following the start of PD-1 inhibitor treatment.

Incorporation of palliative radiation does not preclude favorable outcomes in patients treated with PD-1 inhibitors; patients irradiated after the start of PD-1 inhibition can remain on therapy and demonstrate prolonged survival. Of note, patients irradiated for brain metastases demonstrate favorable outcomes compared with historical controls.

It is still not easy nor perfect....but it's something!!! - c

Sew Chaotically! - ANOTHER Tessuti Annie Dress/top! For me!!!

My OWN Tessuti Annie Tunic!!  With a different slow fashion approach to the front yoke!

I was so excited when making this top for Ruthie!!!  In fact, I enjoyed it so much that I began to formulate great plans for my own!

To back up a step ~ I discovered the writings of Pearl Buck in my hometown library around the age of 12.  Voracious reading of all her novels took me far away from my own surroundings to a place of beauty, rice paddies, pagodas, chop sticks, intricately embroidered kimonos.  Through her stories I could live in a world and culture completely foreign to anything I had ever known.  I became fascinated with all things of the Orient.  When my sisters were both stationed in Japan, they sent me a beautiful kimono and figurines I treasure still.  When I discovered Sashiko embroidery I was in love!!!  Sashiko, literally -  'little stabs', is an ancient embroidery style, originally used to mend, reinforce, quilt blankets, embellish and winterize garments for warmth and thriftiness, for Japanese fishermen and their families. I think it is incredibly lovely.  This tutorial on The Thread from Fabric-Store.com and  this amazing blog, Radiant Home Studio, by Sara Curtis, which is awesome in many ways, are particularly helpful and inspiring when thinking about tackling a Sashiko project.

This photo of a Sashiko quilt Sara posted on her blog (link above), is sooooooo amazing!!  It is titled:  Sashiko by volunteers, 2012, Textile Museum of Canada.  Isn't it beautiful???  I'm going to make one myself when I grow up!!!

After much research and daydreaming....I began!!!  As others have mentioned (in said research) getting pattern to fabric is almost the hardest part!  I tried putting the pattern on paper with iron-on pencils.  But, having found only a brownish-burgundy colored pencil, it showed up not at all on my navy linen.  Chalk wasn't precise enough for this curved pattern, plus it dusts away pretty quickly.  I ended up tracing over the pattern with a pencil, over carbon paper, and therefore onto the cloth.  Tedious.  But, it worked pretty well.  I applied some interfacing to the back of the fabric before starting as some in my reading had suggested.  I was glad I did as it kept the fabric more stable than it would have been otherwise.  The curved pattern was said to be more difficult than the more linear ones, so it may have been a foolish choice to start with, but I thought it was the most perfect design for the bodice of this top!  

I am really pleased with how it turned out.  Traditionally, Sashiko thread has no sheen and is more twisted than our usual embroidery floss, as it is not meant to be separated.  It is usually white, worked onto indigo fabric.  Given I had to utilize what I could find at JoAnn's, I used a thicker embroidery thread, without separating the strands, in a pale grey blue.  I love the contrast of white and blue, but was a little worried about possible inconsistent fading of my blue linen onto pure white thread in the wash.  All in all, I think I made good choices all around! 

This fabric did not necessitate a lining...but still... No. Ugly. Insides.

Easy and pretty!!

Not as zen as I probably should be!!!  But, I'll take joyful any day!

I lurve it!!

For my melanoma peeps, more of the latest and greatest research on the way.  Today....I  needed a day of joy celebrating the simple, the silly, and the satisfaction of a pretty, positive idea come to fruition. If I can make a shirt...think what we could do when we put our industry and creative spirits together!!! - les

Travel Chaotically! - To Spain with love

In September of 2013, I was blessed to experience a beautiful trip through Spain. It began with a trip to Tampa for my 3 month post nivo trial follow-up visit. But, with clear scans and the promise of no doctors for 6 months - we were off - flying from Tampa to JFK to Madrid. Finding the bus to Atocha was managed - by me and MY Spanish!!! - culminating in our arriving at the best little B and B, Lope de Vega, run by the sweetest young couple.

We fell into the Spanish tradition of half raciones with 'dos canas' very happily!!  Pulpo a la gallega (octopus and potatoes, B's fav!), toastados with gambas al ajillo, and patatas bravas!  Followed by strolls through Plaza del Sol and Plaza Mayor.

Night life in Spain is an amazing, friendly, delicious, family affair!

Next morning we shared breakfast with Australians who enjoyed talking about themselves a great deal, but were entertaining enough.  Then out to a beautiful explore of Madrid and the Royal Palace.

Yes, we did.  We went to the famous and rather hokey, Botin!  Hey!  It's a landmark!!  Touted to be the earliest restaurant in the world, founded in 1725.  We enjoyed roasted ham and lamb with Sangria!!  Not bad, not a'tall bad!!  Followed by a walk along the Passeo del Prado with music from an amazing guitar player on the steps of the Prado floating through the air.

Next morning, after a run in the Parque de el Retiro, which reminded me more of green spaces in France than Britain or the US, with sculpted trees, fountains, fine graveled paths filled with runners, bikers and dog walkers - and another breakfast with Aussies who, "though they dove deeper, came up dryer!!!" -  we were off fabric shopping.  I had not sewn very much at that point, but I wanted to get something beautiful for Ruthie.  And at Ribes and Casals, there it was, a lovely Chanel-like tweed with brilliant pinks that was perfect!!  From my journal that day:  "B was all for it and got the attention of a guy who thought I knew all about sewing AND Spanish - both completely untrue!!!.  B persevered. I did my best to answer the many questions flying back and forth - 'quantos suficiente' and 'tejidos por pocket' (which I took to mean lining!!) all in rapid fire Castilian Spanish with a bit of a slur- not exactly the Spanish dialect I am used to!!!  Questions  about Libya and Syria came up!  Oh, Lord!!  B still managing!!!  Suddenly, a final question left us stumped and lost - as the entire shop came to a stop and all eyes turned to us.  An older lady ahead of us in the check out line repeated the question more slowly.  "¿Por qué estás comprando tela aquí?"  B, thinking quickly replied, "Porque no podemos conseguir tejido de esta belleza y calidad en casa!"  Big smiles all around.  And, thankfully, all involved returned their attention to their own affairs!!!"

(THIS!  The dress Ruthie made from the fabric!!!)

We spent the afternoon wandering through Reiana Sofia ~ Picasso's Guernica!!!  The Prado ~ Velazquez (especially Las Hilanderas and Las Meninas)!!!  Leaving me simultaneously filled with wonder inspired by the incredible beauty, intelligence, talent and horror of man.

A short walk to the marvelous madness that is the Market of San Miguel!!!

Verms!!!! Well, technically - eels!!  Angulas!  (FYI - they tasted like tough spaghetti with garlic sauce.) Chorizo! Croquetas!  Gildas!   

When in Rome!!  Or Spain!!!

Seriously, plazas, restaurant displays, and nightly adventures are a beautiful way of life!!

Waiting on the train to Barcelona!  I love watching new sights fly by train windows.  The landscape leaving Madrid was much more arid and brown than expected, though it was September.  To our left were canyon like formations in the foreground with mountains in the distance.  Patches of olive trees quilted the hillsides, giving way to more verdant fields dotted with wind turbines as we neared Barcelona.  

Another interesting B and B - La Casa de Marcelo.  Don't you love the doors in these buildings???  At Bar del Pla we first experienced berenjenas con miel.  So, so, good!!!  Basically, fried egg plant drizzled with cane syrup.  Afterwards, we tried it in many places and LOVED all versions!!  We took in the sights and markets as we wandered through lovely Barcelona.

We enjoyed tapas at Segardi Euskal Taverna.  Look at all the yummy Basque pintxos!!  Little toasts/tapas, with a wide variety of fillings and toppings - all skewered with a toothpick.  When you are done...your toothpicks are counted, with the size and quantity determining your bill!! 

Thanks to reading Rick Steves' travel book, I was eager to try txakoli (cha-kolee), which according to him, was a sparkling wine served from great barrels poured at a height.  I ordered it, and indeed, it was a most delicious sparkling wine, although disappointingly poured from a glass bottle. A bit later, B was off to chat with the Fred-like waiter and order the beverage from the "wall". 

Blech!!!  Mr. Steves, you are most confused or have a serious typo in your book.  The barrels are cider.  It was okay.  Just not quite what I expected. Live and learn!  I adore txakoli!!  Cider...despite its romantic barrels...not as much!

Next morning, we had a lovely run toward la Playa and Barceloneta, down the boardwalk.  Saw a woman rinsing herself at a fully exposed public shower - naked as a Jay Bird.  Don't know if she was a visitor or a local.  If visitor, perhaps she is part of the reason behind recent complaints regarding tourists (in addition to the unfortunate jacking of property rents and prices) in that area!!!
I love markets.  All shapes, all sizes, all sorts!!!  I like to pretend, "If I really lived here ~ what would I eat, where would I shop, what would I do?" Were I a resident of Barcelona, I would certainly avail myself of Las Ramblas!  (At least for things that fit my budget!!) The pedestrian walk is a destination in and of itself!  Flower vendors. Butchers with chicken, tripe, kidneys.  Every fish and mollusk. Hams - priced from 60 to 200 euros.  Sausages, cheese, eggs.  Boxes of saffron, large and small! 

Jamon!!!

Next day, after another beach run, we took a walk to experience 'Barri Gotic', a metro ride to Sagrada Familia (Incredible!!!), and the metro back to Barceloneta.  The fish displays outside the restaurants reminded me of those in Greece. 

We settled on one that smelled delicious with a lovely view of the beach.  B had fish.  I had shrimp. On admiring the ring of our server, I got his first real smile.  He was from Morocco and the ring was from his family, his homeland.  He took our pic.  

As we walked back from the sea, the moon shown bright as day.  A beautiful finish to many treasured moments in this magnificent city.

Back on the train - on our way to Sevilla.  From the train windows there were garden plots, vineyards - giving way to sandy grey soil with olive trees and terraced fields.  In two hours more, acres and acres of sunflowers!!! Followed by reddish fields with more green, fruit trees, and vineyards.  After a warm walk...we found the - Street???  Path??  Corridor???  that led to our hotel.  Our requisite evening paseo took us down Constitucion and back, with a giant church, amazing facades, sangria, chipironies a la plancha and espinacas con garbanzos for supper!!

Next morning, I slept in, but B brought me hot chocolate and churros for breakfast.  A walk to Mercado Arenal brought us:  pale green zucchini, pears of all shapes and sizes!  Fish, lobsters, cigaretellos, langostines AND shrimp!!!  Razor clams, snails, dorado with their golden noses, hake, chicken, eggs, and ham!!  More espinacas con garbanzos and my first experience with ensaladilla Rusa!!!  YUM!!! On to the Cathedral, though by now B was rather tired of "God on a stick" and a bit like a well behaved though sighing 4 year old.  But, I had a plan!!!  Here you could climb 330 feet up in the bell tower...to take pictures!!!  So.  We did!  More wandering, admiring the amazing tile work throughout the city and dinner at what may have been the best restaurant of the trip:   El Jardin de las Tapas.  Barbadillo Blanco!!!  Two different types of gazpacho, one lighter with bits of pepper, onion and herbs on the side to add as you wish and another richer version with ham (salmorejo).   Lamb with gravy and potatoes.  Peppers stuffed with merluza (hake).  Followed by a Flamenco show down the street.  B was a happy man!!!

After our morning run on a Sunday, we meandered down to the river.

I would live in the blue house!!!

After exploring the lovely streets and neighborhoods along the river, we landed at Taberna Miami!!  Oh my goodness!! Here you need an appetite for crazy as well as delicious food.  I was befriended (as are many) by the exuberant owner and filled to the top with my Frito Pescado (bright red shrimp, a whole little flounder, big pieces of fried cod, pieces of what must have been merluza, calamari rings, topped with what at first appeared to be thin shreds of fried onion - but on closer inspection tiny little eyes were visible -  angulas - delicious!!) B's oxtails were amazing.  And B's increasingly proficient Spanish won him this story from the proprietor:  "I've worked hard in life, but I have played hard as well.  Take the road to adventure.  In doing so, along the way, the women have been the best."  In the end, B was not sure if he was encouraging a lech or if, in fact, women are simply of 'mi corazon'!

Further exploration of Triana led us to Alcazar.  Beautiful tiles and arches.  Reflecting ponds. Koi and carp.  B took incredible pictures that I will have to share sometime. The tile work there and throughout Sevilla is truly one of the most beautiful artistic accomplishments humanity has ever produced.

An early breakfast (check the pic in the mirror) before heading to the taxi stand.  In much of Spain, bars (where you may find a group of older ladies, families with children....not your usual "bar"!!!) from the night prior, are the breakfast places of the morning. Cafe con leche and pan con tomate.  Usually with salt, pepper, and olive oil to add as you like.  All a growing girl needs!  Off at a mad pace in the taxi with the usual white knuckle, in and out of traffic drive to the train station.  Jovial young gent, with a love of 90's pop music...plus Kansas, Dust in the Wind...judging by the radio, was our driver.  Such an efficient drive to the station gave us time to review our plans for Granada.  Our 2 hour train ride (its duration due mostly to 11 stops along the way) showed arid fields with drying sunflowers.  Others were plowed or newly mown.  Occasional impressive haciendas with white stucco walls, red Spanish tiled roofs.  Olive groves as far as the eye could see.  Landing at the smallest (and sadly, dirtiest) train station of the trip, we found our hotel rather easily and discovered, when grabbing a bit of lunch at the last moment before siesta, that Granada actually embraces the premise of 'tapas' as a "free plate"  - an appetizer you get with your beverage - much more seriously than the rest of Spain.  Elsewhere you may get a little bowl with 5 olives with your beer.  Not bad!!  But here, we were given a good sized bowl of chicken cooked with peppers and potatoes!!  Really delicious!

Up early next day for a trek to a different hotel to catch a bus to take us to the Alahambra.  Bus and taxi rides are often the most 'exciting' part of our travels.  This was no exception.  Imagine.... People hopping on and off. School children scattered in the melee. Huge bus - narrow streets, through which the only car I would willingly drive would be a Smart Car, as a Mini Cooper would be over large!! Motorcycles and pedestrians whiz about in all directions.  In order to make the turn around a square, the driver and another girl actually leave the bus to lift a parked motorcycle out of the way.  Mid-maneuver, an alarmed looking guy walks over, deciding the better part of valor is to hop on his bike and zoom away, though the girls must now shoo a taxi out of their path!!!  We careen around other obstacles and roar up the hill to the Alahambra.

Incredible tile work. Gardens. Fountains.

Reportedly painted in brilliant colors years ago...still unbelievably beautiful.

In awe of all that we had seen, we wandered back on foot.  Because we never mind walking, and in the chaos of arrival, we didn't see any way to find the bus we were supposed to return on!  Discovered camarones al pil pil for dinner.  

Modern art. We saw many lovely examples of 'artful' graffiti!!  Next morning, walked back to the train station.  Now knowing the lay of the land, we realized it was not far from our hotel.

Cordoba.  With streets smaller than ever, we determine them to be pedestrian only...when a car came barreling along, tires rubbing along both sides of the curb!  Bright and hot.  We procure tickets to another Flamenco show.  Attending that evening, we realize we are in the presence of an incredible dancer, clearly ballet trained as was noted in her bio.  The guitarist and singer made it an impressive trio.  Stopped by a little place after for a glass of wine, manchego and chorizo.  Speaking with each other almost completely in Spanish.  A sweet waitress asked that we complete a survey. B wrote a glowing recommendation but added, all in Spanish, that it would, perhaps, be better if the servers would sing.  The girl got tickled with that one, and told Brent, "No, no, no. No puedo cantar."  But, a bit later, as a male waiter cleared the last few dishes, he burst into song!  Earning a big hand and nice tip!!  Such fun! 

It was in Cordoba that I saw what remains the most beautiful thing I have ever witnessed in all my travels and years on this planet.  Cordoba's Mezquita.  The architecture of this mosque, built between the 8th and 10th centuries, is an exquisite example of Moorish architecture.  850 columns made of jasper, marble, granite, and onyx are placed in such a way to make the space a most beautiful forest.  Founded in 785, the mosque was completed in 987.  Yet, the Mezquita has also served as a cathedral since 1236, when King Ferdinand reconquered Cordoba.  And here's the even more beautiful part of the story ~  rather than destroy the beauty of the mosque, only 16 columns were removed and replaced with Gothic arches to create a chapel within.  Meanwhile, Muslims have been repeatedly denied their petitions to be allowed to pray in the cathedral since the 2000's.  If folks back in 1236 can be wise enough to reconcile their differences and avoid destruction of a building representing the beliefs and heart of those they now controlled (invasion and war not withstanding)...can't we become wise today? I know it's a long shot, but wouldn't it be a deflating kick in the pants to those who would work to do evil by hijacking a religion that has nothing to do with them or their evil agenda, if Muslims were again allowed to worship here?  Just say'n!

I have held Spain and its joyful people in my heart since this visit.  I have long meant to put this post together.   The pictures of the horror evil individuals brought to this lovely place yesterday, broke me as I recognized the patterned side walks of Las Ramblas and pushed me to share your country's beauty today.  For all of you who have lost dear ones, or have those you hold close hurt and in pain, I am ever so sorry.   Despite the limited support coming from some in this country who have access to loud headlines...many more of us are holding you in our heart.  Love, c