This hopeful moment...

Hope, like the dragonfly from Pandora's Box, often arises from our darkest moments.  Similarly, the light of hope I feel today relieves the darkness that has been spinning around us for the past four years.  Do not be fooled.  Hope does not erase imperfections.  But it does allow us to move forward, to improve and grow.  Our national moment of hope, as we dare release our breath and smile as there is dancing and gladness in the streets across our nation, reminds me of the top I wear today.  Using a scrap of shirting a bit too stiff for the pattern I tested with its use.  The back pieced together with material too nice to waste.  A trial run that allowed me to adjust the neckline, create the hem I wanted.  Far from perfect, but functional, useful.  And then ~ I ruined it.  In my own inattention, I splashed it with bleach.  I considered tossing it.  After all, it was just remnant used in a test run. Or was it?  I decided my work deserved more than that.  Though the damaged spots would never be erased, I could still render this patchwork into something beautiful, serviceable.  I picked up my needle, selected thread, and stitched part of me - into the blemishes, the irresponsible splatters.  

It seems that is what most Americans have decided to do as well.  We can take this nation, quilted together via a grand outline in its Constitution that - despite its lofty fabric - failed to include ALL the nation's people, and stitch by stitch, repair the tears, the stains, the holes through which too many have been allowed to fall.  As a nation, we have made mistakes.  Yet, we continue to piece it together.  NO!  One man should never own another.  YES!  Women can vote, own property, hold political office.  NO!  The color of your skin should not determine your right to vote, to go to school, your seat on the bus.  YES!  Marriage is a legal option no matter who you choose to love.  As a nation, we have had some spectacular blind spots. The past four years have shown a klieg light on significant flaws in the fabric of our society.  The very lives of George Floyd, Breonna Taylor, and so many others, were lost due to our blinders and inattention.  Divisive rhetoric from those we trusted to lead us to a better place built walls.  Rage against a common enemy can build an unstoppable force for change.  Anger turned one against the other exacerbates the smallest of scratches into festering wounds.  Mother Nature, in the form of violent storms, raging fires, and a viral pandemic harshly taught us our economy, schools, and healthcare systems were woefully unprepared for her wrath.  Societal injustices were further highlighted as we watched marginalized communities suffer exponentially greater harm than those on higher rungs of the societal ladder.  As thousands die and millions become infected in OUR country, from a pandemic others are dealing with much more efficiently, we realize the necessity of leaders who rely on science and calls to action as well as the egregious harm when those in power pointedly ignore medical advice; choosing instead to mislead and misinform in an act of political calculus.  

As we cast our votes for new leadership, Americans have demonstrated the desire for a different path.  A new direction.  The seeds of division and hatred, systematically sown and tended for the past four years will not be removed from our land without backbreaking work.  Ingrained practices of systemic racism will not be magically erased.  Equal rights and mutual respect will not suddenly be bestowed.  Neither climate change nor a global pandemic will be easily controlled.  Our course correction will not instantly provide jobs to the 50 million Americans who, through no fault of their own, find themselves unemployed.  It will not return the more than 238,000 Americans who have died from COVID-19 to those whose hearts ache for them.  It does not remove the misery of the more than 10 MILLION Americans who have been infected.  It will not bridge the chasm that has eroded relationships between neighbors and within families the past four years of vitriol, hate and mistruths - spewed from the highest office in our land, from the balconies and gardens of the People's House - has caused.  But, together ~ we can.  

Together we can take this country, so full of promise, filled with citizens with fine hearts, littered with noble ideals, and repair its pulled threads.  Correct its crooked seams.  Patch the holes, so that all of us, especially the least among us, are protected.  In this hopeful moment, we can create a country that fits us like our favorite jeans.  That comforts us like our coziest sweater.  That protects us from storms and bitter winds like the strongest coat.  The stains and patches will remain.  But, together in hope, we can make something much stronger and more beautiful, than it was before.

Join me.  Won't you? - love, les

Ketchup! (For Jeanne - who always remembers.)

Yep.  Ketchup.  Certainly not Catsup!   The condiment and when sharing the latest and greatest with friends.  Despite my proud penchant for a prodigious vocabulary and particular passion for proper pronunciation ~ it's never 'catch up' ~ it's ketchup!

When you navigate the planet for 56 years - replete with two cancers, their requisite surgeries, treatments and rechecks - you accrue lots of amazing and odd anniversaries!  Babies and weddings. Graduations and proud accomplishments.  Special trips and beautiful every days with family and friends.  B remembers ALL my "dates" - while I do not.  There is one exception. This one.  About this time ten years ago, despite a clear PET scan the week prior, my throat felt full.  Strange.  I took a peek.  Yep.  A black lump was peering round one of my tonsils. Tammy B's horrified expression after she agreed to take a look at work said it all.  Melanoma.  Surgery was quickly scheduled.  That Saturday I had the affected right tonsil and surrounding tissue removed.  My fourth melanoma met since my diagnosis in 2003.  Left forearm in 2007.  Brain and lung in April 2010.  Not the trend you want ever, but especially unfortunate when there are NO effective FDA approved treatments available.  No clinical trials available either as they required measureable disease, which - luckily - I kept having removed!  We (briefly) considered leaving the tonsillar met in place until it was of sufficient size to allow me entry into a trial for ipi!!!  Craziness!  This time of year, always reminds me of that particular nuttiness.  Surgery had been scheduled so quickly that it was too late to change the fact that B was scheduled to staff the late clinic that evening.  So, a rather haggard mute lady gave out candy to all the little Trick-or-Treaters that year.  Cancer peeps have some strange anniversaries!!  Though we had little hope and no way of knowing it at the time, 10/30/10 marked the start of my now 10 years with no evidence of disease from melanoma.  No small thing.

I had a follow-up oncology appointment earlier this month.  Unfortunately, it was the usual waste of time.  Hidden in a prior hiking post, you may have noticed my colonoscopy roughly 6 months ago, replete with numerous biopsies, was clear.  Strangely though, the routine follow up CT scan of my abdomen a few days later showed ascites (fluid accumulated in my abdomen).  Weird.  At that appointment, it was decided that prior to my next visit, an abdominal ultrasound would be done to recheck.  On that inspection, all fluid had miraculously resolved.  Perhaps ascites happens after lots of colonoscopies?  We just don't usually have a CT afterward that finds it?  Anyhow, I see the oncologist or her NP every three months with lab work, annual colonoscopies and a rather random schedule of CT's that we make-up as we go along.  No one knows what to do with me.  Not even me!  Stage IV melanoma in which you SURVIVE lung and brain mets (as well as a phase 1 trial and a few other sundries) for 17 years is crazy enough.  When you add Stage II ex-goblet cell adenocarcinoma of the appendix, folks REALLY have no clue!  After all my abdominal surgeries in 2018, I did chemo typically used for colon cancer, though its effectiveness for the tumor I had is really unclear.  Three proteins (CEA, C-125, and C19-9) via a blood draw are evaluated at my quarterly doctor visits.  In theory, these would be elevated in the presence of cancer.  Unfortunately they are not terribly specific for my cancer type.  None have ever been elevated. At this visit, when B posed some questions about testing my existing stock of tumor specimens for the presence of mutations for which drugs have been developed to target, the NP went red and defensive, visible despite her mask.  B as Fredo put it, did go "all Rainman on her" as there is no data pertinent to ANY of his patients that this man fails to commit to memory.  Simultaneously, it was clear the NP knew little about it.  NO BIGGIE!!!!  As a provider - or just any human really - if you don't know, say you don't know.  Don't defensively blab, make up numbers and get your nose out of joint.  I always told my patients what I knew and was very honest about what I didn't, while assuring them I would work to find out what was needed to help them.  I think my patients were better served and respected me more for it.  No such sentiment was provided on my visit.  It was awkward.  I was put in the position of smoothing feathers.  Seriously, is that what the cancer PATIENT is supposed to be doing at their check-up???  Good grief!  B felt bad.  Afterwards when discussing how uncomfortable the NP had been, and how difficult it had made the visit for us, I felt even worse when he stated quietly, "She would want me advocating for her if SHE had cancer!"  Indeed she would.

But to finish the useless visit...  B became quiet.  I dealt with the remaining questions.  "Yes. I feel fine."  (No.  I didn't bother to tell her that recently the neuropathies to my hands and feet have worsened.  Not as bad as they were during and after my chemo.  But strangely and suddenly worse again.  The feeling is a bit hard to describe.  Palms and soles burn.  Especially at night.  The most unpleasant sensation is when my feet turn into what I call 'cinder blocks' on a run.  They feel as though they weigh a ton.  I feel unsteady.  Every step hurts.  Doesn't happen all the time.  It's rather random.  Like the penitent patient, I have tried to determine, "What I'm doing to cause this! Is it worse because I ran?  Is it because I did that hand stitching?  Is it because I wore those shoes when I mowed?" The answer is NO!  Nothing I do makes a difference.  As Trump likes to say, "It is what it is!"  I think recently colder weather may be a factor.  But mostly, it is just the shitty result of chemo - lots and lots and lots of patients deal with it.  Docs have no real answers, no real solutions, and no particular interest in listening to a patient drone on about it.  So, I didn't.)  When it was time to finish up and plan the next visit I asked whether or not CT's would be scheduled.  Once again, she didn't know, so she said, "Well, you've had lots of scans over the years, so we are trying to limit that.  So, as long as you are feeling well, with no pain or other symptoms, we'll just see."  I did venture to mention I had NEVER felt unwell or any notable sensation at all due to cancer (tonsillar adventure being the one exception).  Brain met?  Check.  Not one headache, dizzy moment, or nausea.  Lung met?  Sure.  No wheezing, shortness of breath, or respiratory distress of any kind even though we watched it sit there for over 6 months!  Abdominal cancer?  Yep!  Not one stomach cramp, no bloating, no loss of appetite - nothing.  "Hmmm....", she replies.  "Well, as long as you are feeling well, we'll just go with that."

It was incredibly hard not to shout my favorite Billy Connolly line from 'Mrs. Brown', "Are you deaf, or stupid?!!!"

My oncologist called a few days later.  My labs were normal.  No, we will not do any testing on my tumor samples.  Insurance is unlikely to cover it and we would need to repeat it should I recur.  So there you go.  I'm fine with that.  My personal Donkey (on the edge) is - resigned.  For now.

So, yeah.  Ketchup.  It's handy in life and in the cupboard.  I'm not one to put it on my eggs and everything else.  But, it's perfect on burgers and dogs.  A great stand in for tomato paste in soups, stews, meatloaf, and such in a COVID pinch.  Speaking of meatloaf and burgers - here's the BEST ketchup topping - created by moi!

Lessy's Meatloaf with Caramelized Onion Topping2

1 1/2 pound ground meat (I often use ground turkey or beef.  Freddo's fav is made with 1/2 beef and 1/2 ground pork.)

3/4 - 1 cup bread crumbs       2 eggs, beaten        1/3 c Ketchup

2 T dried mustard (you could use regular)           1 T Worcestershire sauce 

1/2 tsp dried thyme         S/P to taste       1-2 ribs celery, chopped fine 

1/2 onion, chopped fine        Splitch of hot sauce as desired

Have meat at room temp.  Preheat oven to 350 degrees.  Beat eggs.  Sauté onions and celery in a bit of olive oil til tender.  Let veggies cool a bit.  Add them and all other ingredients to meat.  If too dry, add a splash of milk.  If too wet, add more bread crumbs.  Don't over mix.  Form either in a ring or loaf in a baking dish.  Bake loaf for 50-60 minutes.  Bake ring for 30-40.  Topping will be applied when about 15 minutes of baking time remains.

Topping:        2 onions, thinly sliced         olive oil         1 c ketchup     

1/4 c honey, syrup or brown sugar       1 tsp mustard      2 tsp Worcestershire

Sauté onions in oil.  Cook at medium high heat until onions are soft and a rich golden color.  Add ketchup, honey, mustard and Worcestershire.  Add hot sauce if desired.  Heat until mixture is thickened and shiny.  Apply to meatloaf or burgers!  Enjoy!!!

There you go!  As Jeanne says, "Slurp!"  Ketchup!!!!  It's good stuff.  In all its forms.  More ketchup in the form of Quarantine-while activities and recent reads coming soon!  Love, les

A promise, a celebration of love, and a beautiful journey - just begun. A love story.

A year ago today, I was blessed to share in their joy as Roo and her Jamester celebrated their marriage.  It was a lovely party filled with friends and gladness.  None of us imagined the challenges the world would face in the coming year - a global pandemic, devastating storms and fires spurred by climate change, racial divisions, political chaos.  On a personal level, Roo was happily teaching MATH to teens (Yikes!!!!) in her classroom one day, only to arrange her living room to film videos for online study the next.  Jamie was working to finish grad school assignments in the midst of a shut-down and attain a counseling position during a hiring freeze.  A long planned summer trip evaporated.  Today, they consider themselves lucky as they are both working hard to help the children and families they serve in their respective schools.  Masks are a normal part of their world.  They help their neighbors and visit parents outdoors, socially distanced.  Though my heart has ached for them, and so many others, during the insanity of this year, I am beyond proud of them both.  So, in their honor...

May your laughter always flow ~

~ like the sweetest mountain stream.

May your hearts stand strong, side by side ~

~ forever together, along the same path.

May your hearts be always bust'n ~

 ~ with the intricate beauty afforded by small things.

May your love possess the power and persistence of water ~

~ to power nations, to carve paths to a better place, to trickle gently over tender souls.

Stronger together.  I love you both.

To many more beautiful years to come ~ Mommy

New follow-up data confirms effectiveness for targeted and immunotherapy as adjuvant in melanoma patients!!!

Since my role as an original rattie in an adjuvant arm of Stage IV melanoma peeps using MDX1106 - today's nivolumab (Opdivo) - in 2010, I haven't stopped yelling about the need for adjuvant treatment for other melanoma patients for one minute!!!  Here are 9 zillion pertinent posts from this blog:  Adjuvant therapy for melanoma  I am particularly proud of yelling this in 2017 - 

FRIDAY, OCTOBER 13, 2017

Adjuvant treatments in melanoma - They WORK!!! Now, let's make sure people can get them!!!!!

It was certainly good news when the FDA (FINALLY!!!) approved ipi as an adjuvant treatment for melanoma.  And....it works!  ASCO 2017: Ipi 3 mg vs 10 mg in advanced melanoma and as adjuvant

We also KNOW that anti-PD-1 works EVEN BETTER, with fewer side effects, as an adjuvant treatment in melanoma. The trial that I and my fellow ratties started in 2010 proved that...and so have other studies since:  Nivo better than ipi as adjuvant treatment for melanoma! Surprise, surprise, surprise!!!

We also KNOW that BRAF/MEK inhibitors are extremely effective as an adjuvant therapy in patients with BRAF positive melanoma:  2016: Straight Outta Boston!!! Latest melanoma research ~

It is with a mixture of satisfaction, frustration, smug back patting, and hope - that I share these recent results that CONFIRM - ADJUVANT THERAPIES WORK FOR MELANOMA!!!!! 

Five-Year Analysis of Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma.  Drummer, Hauschild, Saninami, et al.  New England Journal of Medicine.  September 17, 2020.

In the previously reported primary analysis of this phase 3 trial, 12 months of adjuvant dabrafenib plus trametinib resulted in significantly longer relapse-free survival than placebo in patients with resected stage III melanoma with BRAF V600E or V600K mutations. To confirm the stability of the relapse-free survival benefit, longer-term data were needed.

We randomly assigned 870 patients who had resected stage III melanoma with BRAF V600E or V600K mutations to receive 12 months of oral dabrafenib (at a dose of 150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos. The primary end point was relapse-free survival. Here, we report 5-year results for relapse-free survival and survival without distant metastasis as the site of the first relapse. Overall survival was not analyzed, since the required number of events to trigger the final overall survival analysis had not been reached.

The minimum duration of follow-up was 59 months (median patient follow-up, 60 months for dabrafenib plus trametinib and 58 months for placebo). At 5 years, the percentage of patients who were alive without relapse was 52% with dabrafenib plus trametinib and 36% with placebo. The percentage of patients who were alive without distant metastasis was 65% with dabrafenib plus trametinib and 54% with placebo. No clinically meaningful between-group difference in the incidence or severity of serious adverse events was reported during the follow-up period.

In the 5-year follow-up of a phase 3 trial involving patients who had resected stage III melanoma with BRAF V600E or V600K mutations, 12 months of adjuvant therapy with dabrafenib plus trametinib resulted in a longer duration of survival without relapse or distant metastasis than placebo with no apparent long-term toxic effects.

Good.  Now.  Enough with the placebo crapolla!!!

Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-MG/KEYNOTE-054 Trial.  Eggermont, Blank, Mandala, et al.  J Clin Oncol.  September 18, 2020.

We conducted the phase III double-blind European Organization for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial to evaluate pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. On the basis of 351 recurrence-free survival (RFS) events at a 1.25-year median follow-up, pembrolizumab prolonged RFS compared with placebo. This led to the approval of pembrolizumab adjuvant treatment by the European Medicines Agency and US Food and Drug Administration. Here, we report an updated RFS analysis at the 3.05-year median follow-up.

A total of 1,019 patients with complete lymph node dissection of American Joint Committee on Cancer Staging Manual, stage IIIA (at least one lymph node metastasis greater than 1 mm), IIIB, or IIIC (without in-transit metastasis) cutaneous melanoma were randomly assigned to receive pembrolizumab at a flat dose of 200 mg (n = 514) or placebo (n = 505) every 3 weeks for 1 year or until disease recurrence or unacceptable toxicity. The two coprimary end points were RFS in the overall population and in those with programmed death-ligand 1 (PD-L1)-positive tumors.

Pembrolizumab (190 RFS events) compared with placebo (283 RFS events) resulted in prolonged RFS in the overall population (3-year RFS rate, 63.7% v 44.1% for pembrolizumab v placebo, respectively;) and in the PD-L1-positive tumor subgroup. The impact of pembrolizumab on RFS was similar in subgroups, in particular according to AJCC-7 and AJCC-8 staging, and BRAF mutation status.

In resected high-risk stage III melanoma, pembrolizumab adjuvant therapy provided a sustained and clinically meaningful improvement in RFS at 3-year median follow-up. This improvement was consistent across subgroups.

Again.  Good.  Enough with placebo!!!!

There is also an update on the CheckMate 238 trial.  Here are my prior posts on that study as it progressed from 2017 and 2018 - Reports on CheckMate 238  Now, this:

Adjuvant nivolumab versus ipilimumab in resected stage IIIB-C and stage IV melanoma (CheckMate 238): 4-year results from a multicentre, double-blind, randomised, controlled, phase 3 trial.  Ascierto, Del Vecchio, Mandala, et al.  Lancet Oncol.  September 18, 2020.

Previously, findings from CheckMate 238, a double-blind, phase 3 adjuvant trial in patients with resected stage IIIB-C or stage IV melanoma, showed significant improvements in recurrence-free survival and distant metastasis-free survival with nivolumab versus ipilimumab. This report provides updated 4-year efficacy, initial overall survival, and late-emergent safety results.

This multicentre, double-blind, randomised, controlled, phase 3 trial was done in 130 academic centres, community hospitals, and cancer centres across 25 countries. Patients aged 15 years or older with resected stage IIIB-C or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) to receive nivolumab or ipilimumab via an interactive voice response system and stratified according to disease stage and baseline PD-L1 status of tumour cells. Patients received intravenous nivolumab 3 mg/kg every 2 weeks or intravenous ipilimumab 10 mg/kg every 3 weeks for four doses, and then every 12 weeks until 1 year of treatment, disease recurrence, unacceptable toxicity, or withdrawal of consent. The primary endpoint was recurrence-free survival by investigator assessment, and overall survival was a key secondary endpoint. Efficacy analyses were done in the intention-to-treat population (all randomly assigned patients). All patients who received at least one dose of study treatment were included in the safety analysis. The results presented in this report reflect the 4-year update of the ongoing study with a database lock date of Jan 30, 2020. This study is registered with ClinicalTrials.gov, NCT02388906.

Between March 30 and Nov 30, 2015, 906 patients were assigned to nivolumab (n=453) or ipilimumab (n=453). Median follow-up was 51·1 months with nivolumab and 50·9 months with ipilimumab; 4-year recurrence-free survival was 51·7% in the nivolumab group and 41·2% in the ipilimumab group. With 211 (100 [22%] of 453 patients in the nivolumab group and 111 [25%] of 453 patients in the ipilimumab group) of 302 anticipated deaths, 4-year overall survival was 77·9% with nivolumab and 76·6% with ipilimumab. Late-emergent grade 3-4 treatment-related adverse events were reported in three (1%) of 452 and seven (2%) of 453 patients. The most common late-emergent treatment-related grade 3 or 4 adverse events reported were diarrhoea, diabetic ketoacidosis, and pneumonitis (one patient each) in the nivolumab group, and colitis (two patients) in the ipilimumab group. Two previously reported treatment-related deaths in the ipilimumab group were attributed to study drug toxicity (marrow aplasia in one patient and colitis in one patient); no further treatment-related deaths were reported.

At a minimum of 4 years' follow-up, nivolumab demonstrated sustained recurrence-free survival benefit versus ipilimumab in resected stage IIIB-C or IV melanoma indicating a long-term treatment benefit with nivolumab. With fewer deaths than anticipated, overall survival was similar in both groups. Nivolumab remains an efficacious adjuvant treatment for patients with resected high-risk melanoma, with a safety profile that is more tolerable than that of ipilimumab.

So, there you go.  ALL of these adjuvant therapies provided Stage III/IV melanoma patients whose obvious disease was removed via surgery or radiation better results - no matter if they were treated with ipi, nivo, pembro or the dabrafinib/trametinib combo - than when they were left untreated.  Per these reports, here's how things panned out ~

Dabrafinib/trametinib - at 5 years, stage III melanoma patients alive without relapse was 52% with treatment vs 36% with placebo.

Pembrolizumab (Keytruda) - at 3 years, Stage III melanoma patients with recurrence free survival was 63.7% when treated with pembro, vs 44.1% for placebo.

Ipilimumab (Yervoy) - at 4 years, in Stage III and Stage IV melanoma patients, 4 year recurrence free survival was 41.2%.  4 year overall survival was 76.6%.

Nivolumab (Opdivo) - at 4 years, in Stage III and Stage IV melanoma patients, 4 year recurrence free survival was 51.7%.  4 year overall survival was 77.9%.

My thoughts:

The fact that Stage IV patients were included in the study looking at adjuvant ipi and nivo (CheckMate 238 trial) is HUGE!!!!!!  It makes comparison to the studies using pembro and the dabrafinib/trametinib combo as adjuvant in Stage III peeps ONLY, difficult to say the least.   I would really like to see an adjuvant study in Stage III melanoma patients where Keytruda and Opdivo are compared head to head, using the exact same result parameters and time frames.  I doubt there would be any significant difference in results as that has already been found to be the case when those agents are used in treatment of Stage IV melanoma patients - but still.  And finally, while the numbers for adjuvant ipi weren't that bad, and certainly much better than placebo, the side effects were greater - so I don't find ipi as a single agent a good choice for adjuvant therapy given the other options.

For what it's worth and with great appreciation to all the ratties ~ les

P.S.  FYI - time frames of follow-up matter.  As time goes on, more peeps have a chance to progress.  So data at three years may be better than outcomes reported at five years.

For instance in this article:  2017 - Nivo better than ipi as adjuvant  The data (drawn from Stage III AND Stage IV melanoma patients who took the drugs as adjuvant) demonstrates this:

Recurrence free survival at 12 months:

70.5% for nivo                    60.8% for ipi

Recurrence free survival at 18 months:

66.4% for nivo                    52.7% for ipi

That is why it is important to compare apples to apples in all aspects.  c

Sew Chaotically! ~ Plaid top M7890

This little project was a fun challenge.  In going through my stash for bits and bobs suitable for mask making I ran across this fabric that has probably been sitting on a shelf for about twenty years!  Too thin for masks.  Not sure why I made the purchase.  But...  It was a nice quality woven plaid in jewel tones. What to do?

I decided I could make it work as a wearable toile of McCall's 7890; a shirt dress with a diagonal button placket that I picked up on a whim in a $1.99 pattern sale but then felt unsure about.  Decision made and it was off to the races.

I stitched up a size 12.  Given my limited yardage and desire for pattern matching, cutting it was a bit of a challenge!  I obviously shortened it.  I was forced to take some of the volume out of the sleeves and had to piece the button band.  Technically the plaid at the top of the sleeve is "up-side-down" compared to how it is utilized in the bodice - still - I think it works!!  The pattern calls for the sleeves to be finished with a small cuff or elastic, but I decided I liked them simply hemmed.

Still not sure if the asymmetric button placket would drive me crazy in a dress, but it hangs nicely and is not distracting in this top. 

Happy to have had a fun diversion in this crazy time.  Glad to have transformed a piece of fabric from my shelves into a useful, pretty garment.  Stay safe!  VOTE!!!  - les

After progression on anti-PD1 / anti-PDL1 treatment of melanoma

While many patients attain a response to immunotherapy (about 40% to either anti-PD1 product and about 60% to the ipi/nivo combo) and many of THOSE responses are durable, it is clear that way too many patients are left with an inadequate response or progression after those therapies.  So, then what?  Here is a recent post containing reports on how to address that scenario:  How to deal with recurrence on or after anti-PD-1 as adjuvant or treatment for active melanoma disease

Now, there's this ~

Outcomes after progression of disease with anti-PD-1/PD-L1 therapy for patients with advanced melanoma.  Patrinely, Baker, Davis, et al.  Cancer. 2020 August. 1.

Greater than one-half of patients with melanoma who are treated with antibodies blocking programmed cell death protein 1 receptor (anti-PD-1) experience disease progression. The objective of the current study was to identify prognostic factors and outcomes in patients with metastatic melanoma that progressed while they were receiving anti-PD-1 therapy.  The authors evaluated 383 consecutively treated patients who received anti-PD-1 for advanced melanoma between 2009 and 2019. Patient and disease characteristics at baseline and at the time of progression, subsequent therapies, objective response rate (ORR), overall survival, and progression-free survival were assessed.  

Of 383 patients, 247 experienced disease progression. The median survival after progression was 6.8 months. There was no difference in survival noted after disease progression based on primary tumor subtype, receipt of prior therapy, or therapy type. However, significantly improved survival after disease progression correlated with clinical features at the time of progression, including normal lactate dehydrogenase, more favorable metastatic stage (American Joint Committee on Cancer eighth edition stage IV M1a vs M1b, M1c, or M1d), mutation status (NRAS or treatment-naive BRAF V600 vs BRAF/NRAS wild-type or treatment-experienced BRAF-mutant), decreasing tumor bulk, and progression at solely existing lesions. After progression, approximately 54.3% of patients received additional systemic therapy. A total of 41 patients received BRAF/MEK inhibition (ORR of 58.6%, including 70.4% for BRAF/MEK-naive patients), 30 patients received ipilimumab (ORR of 0%), and 11 patients received ipilimumab plus nivolumab (ORR of 27.3%).   

The current study identified prognostic factors in advanced melanoma for patients who experienced disease progression while receiving anti-PD-1, including lactate dehydrogenase, stage of disease, site of disease progression, tumor size, and mutation status.

There is also this:

Patterns of failure after immunotherapy with checkpoint inhibitors predict durable progression-free survival after local therapy for metastatic melanoma.  Klemen, Wang, Feingold, et al.  J Immunother Cancer.  Jul 2020.  

Background: Checkpoint inhibitors (CPI) have revolutionized the treatment of metastatic melanoma, but most patients treated with CPI eventually develop progressive disease. Local therapy including surgery, ablation or stereotactic body radiotherapy (SBRT) may be useful to manage limited progression, but criteria for patient selection have not been established. Previous work has suggested progression-free survival (PFS) after local therapy is associated with patterns of immunotherapy failure, but this has not been studied in patients treated with CPI.  

Methods: We analyzed clinical data from patients with metastatic melanoma who were treated with antibodies against CTLA-4, PD-1 or PD-L1, either as single-agent or combination therapy, and identified those who had disease progression in 1 to 3 sites managed with local therapy. Patterns of CPI failure were designated by independent radiological review as growth of established metastases or appearance of new metastases. Local therapy for diagnosis, palliation or CNS metastases was excluded.  

Results: Four hundred twenty-eight patients with metastatic melanoma received treatment with CPI from 2007 to 2018. Seventy-seven have ongoing complete responses while 69 died within 6 months of starting CPI; of the remaining 282 patients, 52 (18%) were treated with local therapy meeting our inclusion criteria. Local therapy to achieve no evidence of disease (NED) was associated with three-year progression-free survival (PFS) of 31% and five-year disease-specific survival (DSS) of 60%. Stratified by patterns of failure, patients with progression in established tumors had three-year PFS of 70%, while those with new metastases had three-year PFS of 6%. Five-year DSS after local therapy was 93% versus 31%, respectively.  

Conclusions: Local therapy for oligoprogression after CPI can result in durable PFS in selected patients. We observed that patterns of failure seen during or after CPI treatment are strongly associated with PFS after local therapy, and may represent a useful criterion for patient selection. This experience suggests there may be an increased role for local therapy in patients being treated with immunotherapy.

Melanoma sucks great big green hairy stinky wizard balls!  Hang tough, peeps.  Hang tough! - c

Sew Chaotically! ~ T shirt dress, Nani Iro Sewing Studio Pattern

I stitched up my T shirt dress, from the Nani Iro Sewing Studio Book, using a Merchant and Mills light weight cotton block print.  I used the S/M size, dropping the front neckline just a tad as I did in the blouse I made from the same pattern as a toile.  I added many inches in length as I wanted to enjoy all the beauty of this fabric!!  I had fun deciding pattern placement and am pretty stoked with my choice and stripe matching at the shoulder.

I think it worked!! Sew Chaotically! ~ les