Your life should not be in danger because of the quantity of melanin in your skin!

Ironic title for someone with Stage IV melanoma, no?  But, each day headlines in America, land of the free, proves that what SHOULD be the case, is too often not.  I have been through a few things. But, I have always, in all circumstances, even in my cancer care - - NO!  Especially in my cancer care - - recognized my privilege.  I had access to melanoma specialists across the nation and beyond.  I had the money and support system that allowed me to travel for my care.  I had attained an education that allowed me to render the incomprehensible understandable.  So many in our great country have none of that, and very often that lack is directly correlated to the color of their skin.  The more melanin, the greater chance that their children have inadequate educational opportunities.  Those with brown skin suffer far greater health disparities - lack of access to medical care, lack of insurance, lack of being taken seriously when they do go to the doctor with complaints of illness, lack of outreach and help with basic needs that promote health like good nutrition, help with addiction, and mental health issues - than other groups.  Black and brown communities have almost no care for the silent killers of hypertension, obesity and diabetes.  Yet, those same folks work in jobs of greatest risk - for injury, for minimal wage, for less adherence to safety requirements, for long hours, for exposure to communicable disease.  In fact, the coronavirus pandemic has laid bare these inequities.  As of the first week of May, more than 80,000 people had died in the US due to COVID.  Of the nearly 65,000 deaths due to the virus for which race and ethnicity data was noted in the 39 states that compile such information, 17,155 African Americans had lost their lives to COVID-19.  Put another way, though African Americans make up only 13% of the population in those states, they make up 27% of the deaths.  When you flip those numbers, whites make up 62% of the population in those areas, but only 49% of the deaths.  In Albany Georgia, African Americans make up 90% of the deaths from COVID-19.  Why?  Because of this:

Those injustices, disproportionately meted out due to the greater content of melanin in your skin, should be enough, right?  But, like the graph above, they are only the tip of the iceberg.  Young men have died, their names making news banners yet again, at the hands of white men, simply because they were black.  They were all unarmed.  They were not committing any crimes.  They are dead.

Trayvon Martin                                 Darrell Cabey
Ahmaud Arbrey                                Barry Allen
James Ramseur                                 Troy Canty
Emmett Till
This is NOT an all inclusive list.

Police in this country are under paid and under appreciated.  Their jobs are dangerous and we all need their presence.  However, there are those among them who are not serving the public nor their fellow officers in good stead.  Racism, overt and perhaps that which even they leave unrecognized, guides their actions.  Black men die at the hands of these officers.  Police officers, Chiefs, Mayors, leaders of all stripes, and us - YES!  You and I!!! - must lead the way in removing these individuals along with the attitudes and prejudices that sustain them from our police forces so that ALL people of this nation attain the respect and protection they deserve.  The names that follow are black men who were shot and killed in recent years by police in this country.  Almost all were completely unarmed.  Many were already cuffed or had their hands in the air.  Police were on the scene due to reasons as various as a stalled car or because they - those who were soon to become victims of a police shooting - called for help due to domestic violence inflicted upon them.  Some were demonstrating clear signs of mental illness and erratic behavior while posing NO imminent threat.  Many had provided military service to our country.  Some of the names are familiar.  Far too many are not.

Sean Reed    Steven Taylor    Ariane McCree    Terrance Franklin 
Miles Hall    William Green     Samuel Mallard    Kwame Jones
Tamir Rice    Botham Jean    E J Bradford    Michael Brown
Michael Dean    Jamee Johnson    Darius Tarver    De'von Bailey
Christopher Whitfield     JaQuarnion Slaton    Antwon Rose
Stephon Clark    Yassin Mohamed    Fairan Berke 
Anthony Hill    Eric Logan    Jamarion Robinson    Gregory Hill
Ryan Twyman    Brandon Webber     Jimmy Atchinson    Willie McCoy
Walter Scott    D'ettric Griffin    Jemel Roberson     DeAndre Ballard
Rumain Brisbon    Anthony Smith    Robert White    Remarley Graham
Wendell Allen    Kendrec McDade     Larry Jackson    Jonathan Ferrell
Jordan Baker     Victor White    Dontre Hamilton    John Crawford
Ezell Ford     Dante Parker    Kajiene Powell    Laquan McDonald
Akai Gurley    Jerame Reid    Charly Keunang     Tony Robinson 
Walter Scott    Brendon Glenn    Samuel DuBose    Christian Taylor
Jamar Clark    Danny Thomas    DeJuan Gillory    Patrick Harmon 
Jonathan Hart     Maurice Granton    Julius Johnson    Mario Woods
Quintonio LeGrier    Gregory Gann     Akiel Denkins    Alton Sterling
Philando Castile    Terence Sterling    Keith Scott
Alfred Olango    Jordan Edwards     Stephon Clark    Michael Dean

This is not a complete list.           

Then there are those who died, while under arrest.  For crimes they may - or may NOT - have committed.  Died - while under arrest - under police PROTECTION.

Eric Garner and Freddie Gray readily come to mind.  Now, George Floyd has joined their ranks.
THIS is NOT a complete list.

Life while being black and brown does not have to be this way.  But it WILL continue in this manner until we - we privileged white people - we in the unaffected majority - make it otherwise.

Are you willing to recognize the problem?  Because that is where we must start.  Are you willing to do something about it?

For all the lives lost, for all the families who have buried dear ones for no other reason than their skin had more melanin than mine, I send you this -

- with the promise, that I see you.  I hear you.  I ache for you.  I am sorry.  I will do what I can to make your lives, and therefore the lives of everyone in this country - better.  ~ love, les

How to deal with recurrence on or after anti-PD-1 as adjuvant or treatment for active melanoma disease

Current melanoma treatment options are nothing short of a miracle to those of us who survived the Melanoma Dark Ages when there were literally NO effective treatments available.  Still, melanoma treatment remains far from clear or easy.  Should one who is BRAF positive choose immunotherapy or targeted therapy?  Does one opt for anti-PD-1 as a single agent or combined with anti-CTLA-4 (ipi)?  [Noting that the combo is not yet approved for Stage III patients.] And if those puzzlers are not enough, what do you do if you respond to anti-PD-1 initially, but then progress either while still on it or after having been on it?  Research has been trying to grapple with these questions ~

2018:  Melanoma patients treated beyond progression with anti-PD-1  - with the conclusion that:  "Treatment beyond progression with anti-PD-1 antibody therapy might be appropriate for selected patients with unresectable or metastatic melanoma, identified by specific criteria at the time of progression, based on the potential for late responses in the setting of the known toxicity profile."

2018:  anti-PD-1 after progression - In this report, after progression on stopping anti-PD-1 the authors conclude:  "Our data suggest that anti-PD(L)1 therapy should be resumed if progression occurs after a planned anti-PD(L)1 interruption. Further prospective studies are needed to confirm these results. "

and I note: "Small numbers here and not all are melanoma patients.  But, some responses on the re-do."

A bit of a review in 2019:  Anti-PD-1 results in melanoma patients: outcomes plus responses to retreatment where the new data presented ended up with mixed and unclear results on retreatment.

This post in 2020:  Response after discontinuation of anti-PD-1 in melanoma patients whether due to disease progression, side effects or choice - presents articles that try to address what happens to patients who stop anti-PD-1 therapy.

So, as you can see, many patients and their docs are unclear as to what path is best if a patient progresses or recurs while on or after anti-PD-1 therapy.

Now, there's this:

Management of early melanoma recurrence despite adjuvant anti-PD-1 antibody therapy.  Owen, Shoushtari, Chauhan, et al.   Ann Oncol. 2020 May 6.

BACKGROUND:

Anti-PD-1 antibodies (PD1) prolong recurrence-free survival in high-risk resected melanoma; however, approximately 25-30% of patients recur within one year. This study describes the pattern of recurrence, management and outcomes of patients who recur with adjuvant PD1 therapy.

PATIENTS AND METHODS:

Consecutive patients from 16 centres who recurred having received adjuvant PD1 therapy for resected stage III/IV melanoma were studied. Recurrence characteristics, management and outcomes were examined; patients with mucosal melanoma were analysed separately.

RESULTS:

Melanoma recurrence occurred in 147 (17%) of ∼850 patients treated with adjuvant PD1. In those with cutaneous melanoma (n=136), median time to recurrence was 4.6 months (range 0.3-35.7); 104 (76%) recurred during (ON) adjuvant PD1 after a median 3.2 months, and 32 (24%) following (OFF) treatment cessation after a median 12.5 months, including in 21 (15%) who ceased early for toxicity. Fifty-nine (43%) recurred with locoregional disease only and 77 (57%) with distant disease. Of those who recurred locally, 22/59 (37%) subsequently recurred distantly. Eighty-nine (65%) patients received systemic therapy after recurrence. Of those who recurred ON adjuvant PD1, none (0/6) responded to PD1 alone; 8/33 evaluable patients (24%) responded to ipilimumab (alone or in combination with PD1), and 18/23 (78%) responded to BRAF/MEK inhibitors. Of those who recurred OFF adjuvant PD1, 2/5 (40%) responded to PD1 monotherapy, 2/5 (40%) responded to ipilimumab-based therapy, and 9/10 (90%) responded to BRAF/MEK inhibitors.

CONCLUSIONS:

Most patients who recur early despite adjuvant PD1 develop distant metastases. In those who recur ON adjuvant PD1, there is minimal activity of further PD1 monotherapy, but ipilimumab (alone or in combination with PD1) and BRAF/MEK inhibitors have clinical utility. Retreatment with PD1 may have activity in select patients who recur OFF PD1.

These researchers looked at 850 Stage III and IV melanoma patients who had their disease removed and were treated with anti-PD-1.  17% (136 patients) recurred.  Average time to recurrence was about 5 months.  76% of those patients (104) recurred while they were still taking anti-PD-1 after about 3 months.   24% of that same subgroup (32 patients) recurred in about 12 months after coming off anti-PD-1.  89 patients were given systemic therapy.  Of those who recurred while ON anti-PD-1 ~ none responded to anti-PD-1 as a single agent, 24% responded to ipi alone or in combination with anti-PD-1, and 78% responded to targeted therapy.  Of those who recurred AFTER anti-PD-1 ~ 40% responded to retreatment with anti-PD-1, 40% responded to ipi, and 90% responded to targeted therapy.  Therefore, their conclusion is as noted above.

There is also this:

Ipilimumab (IPI) alone or in combination with anti-PD-1 ((_( + PD1) in patients with metastatic melanoma (MM) resistant to PD1.  Da Silva, Ahmed, Lo, et al.  ASCO Meeting Library, 2020.

PD1 induces long-term responses in approximately 30% of MM pts, however 2/3 are resistant (innate or acquired) and will require further treatment. A subset of these pts will benefit from IPI or IPI+PD1, but these pts are yet to be identified. We sought to determine; i) response rate (RR) and survival to IPI+/-PD1 after PD1 progression, and ii) clinical predictors of response and survival to IPI+/-PD1.

MM pts resistant to PD1 and then treated with IPI+/-PD1 were studied. 

Of 330 MM pts resistant to PD1 (median time to prog 2.9 months [0.5 – 42.3], 12% adjuvant, 88% metastatic; 70% innate, 30% acquired), 161 (49%) had subsequent IPI and 169 (51%) had IPI+PD1. Characteristics at start of IPI+/-PD1 were similar in IPI vs IPI+PD1 groups (stage M1D 27% vs 34%; elevated LDH 38% vs 40%), except IPI group had more ECOG greater than/= to 1 (60% vs 34%) and less BRAF mutation (mut) (21% vs 37%). Median follow-up from start of IPI+/-PD1 was 22.3 months (19.8 - 25.8); RR was 22%, higher in IPI+PD1 (31%) vs IPI (12%). PFS and OS at 1 year were 20% and 48%, respectively; better with IPI+PD1 (27%/57%) vs IPI (13%/38%). PD1 setting (adjuvant/metastatic) and response did not impact response to IPI+/-PD1. Most pts progressing on adjuvant PD1 had IPI+PD1 (88%) and RR was 33%. Neither the interval between PD1 and IPI+/-PD1 nor use of other drugs affected response to IPI+/-PD1. RR was similar in BRAF WT (23%) vs BRAF mut (RR 21%) pts. In BRAF WT pts, RR was higher with IPI+PD1 vs IPI (38% vs 9%), while RR was similar with IPI (24%) or IPI+PD1 (19%) in BRAF mut pts. One third of BRAF mut pts had BRAF inhibitors (BRAFi) prior to IPI+/-PD1 and lower RR (13%) vs those without BRAFi (RR = 25%). High grade (greater than/= to G3) toxicity (tox) was similar with IPI+PD1 (30%) or IPI (34%), and was not associated with response. Stage III/M1A/M1B, normal LDH and treatment with IPI+PD1 were the best predictors of response. These factors, in addition to sex (male), ECOG PS = 0, BRAF mut, progressed/recurred greater than 3 months on PD1, and absence of bone mets were the best predictors of longer OS.

In pts resistant to PD1, IPI+PD1 has higher RR, longer survival, yet similar high grade tox than IPI alone. Predictive models of response & survival will help select pts for IPI+/-PD1 after progressing on PD1.

This study looked at patients who did not attain long term durable response to initial anti-PD-1 therapy - about 70% of patients.  They followed 330 melanoma patients who had progressed on or after anti-PD-1 therapy and were then treated with either ipi alone or ipi combined with anti-PD-1. Overall, patients retreated or changed to the ipi/anti-PD-1 combo had higher response rates and longer survival.

For what it's worth. - c

Happy Memorial Day - during this crazy COVID time....

I have certainly had my own frustrations during this insane and challenging time, but they are nothing compared to those who have lost loved ones.  Nothing compared to those who have lost jobs and struggle to feed their families.  I worry about the future of our nation, our world.  I grieve for the simple pleasures that my children - and so many others - have been deprived of this spring and summer.  I am anxious about the future of all our children - their fears, their education, how this crazy time has impacted their families, their sense of well being.  I am supremely irritated - angry - that my own infirmities limit my ability to assist my fellow humans.  While some of our nation's leaders have done exemplary jobs in this unprecedented circumstance, others at the highest level have failed us dismally.  Not being content with a simple lack of leadership and a cohesive plan to work together at home and across the globe to deal with a pandemic that has killed 350,000 across the world - 99,805 of those souls lost here in the United States - they have instead promoted dangerous behaviors, promulgated outright lies and misinformation.  I have no ability to understand those who demand the "right" to be "mask free" with no recognition of or desire to protect themselves, their own loved ones, or their neighbors through the use of very simple measures that would go such a long way in keeping everyone safe and well.  To keep more dear souls healthy, here with us to share love and laughter, able to to see and smell the flowers for years to come.  It is all so much...

Yet, I am lucky.  I have food in my pantry.  My kids are healthy and handling all the crazy incredibly well despite tremendous personal challenges. I have a beautiful garden of my very own. To walk in beauty.  To breathe clean air.  Today, I will share it with you in the only way I can ~

I fell in love with peonies during a visit to London and Kew Gardens.  So tickled that I now have several lovely varieties to enjoy here at home!  Thanks, Bentie!

These pink Knock Out roses, only in their second year, have been so lovely this spring!

These vivid purple irises are so delicate and lovely.  Gifts from my friend Trina's garden!

The first peonies that B planted for me provide a bright beacon of hope.

Lovely poplar blossoms ~ appreciated only once they have fallen to the ground.

Blue berry pie to-be in July - if I get to them before the birds and squirrels!

Sheets of blossoms on the "Ruff Ruff Wood".  A thoughtful gift from Ruff's dog walker, Jill, at his passing.  It has brought us smiles and sweet memories for many years.

Admired so often on our walks in the Smokies, I am happy to have two varieties of wild ginger, with its funky little flower, in our woodland garden.

Loving all the pinks of these Peonies and Sweet William.

Isn't this peony lovely?

Be patient with each other.  Be brave.  Be considerate.  Wear a mask.  Even if you think it is stupid.  Even if you think it is an intrusion in the way you wish to live.  Of course it is.  But it will not be forever.  It is a small thing, that may mean everything, to the person you walk by.

From my garden to you.  Much love.  ~ les

Sew Chaotically! ~ Adrienne Blouse by Friday Pattern Company

Lots of sewists have been tickled with this pattern - The Adrienne Blouse from the Friday Pattern Company.  It is really simple to stitch up.  I made a medium with no adjustments other than making sure the length of the elastic in the shoulders suited my frame.  I used a rather ethereal knit (also used for a Monroe Turtleneck here).  Given its transparency I made the bodice in a double layer, using a single layer in the sleeves.  Once complete, I had a personal adventure of testing it out with a variety of handmades I already had in my closet!

Paired here with one of my all time fav pants patterns, McCall's 7726, wide legged faux paper-bag waist trousers!!, made in early 2018.

Next up, The Berlin Skirt from Orageuse, also stitched in early 2018 from a luxurious corduroy I picked up in an amazing fabric shopping adventure on Goldhawk Road in London.

Then, in this amazingly smooth and drapey bird print sweet Ruthie gifted me, there is this Hollyburn skirt (a really great pattern I've made several times) that due to some personal obstacles and our current crazy times, has not seen the wear it deserves!

And finally, rather back where we started, though with a new make, the slim legged version of the McCall's 7726 trouser!!

So, YES!!!  I can pair this top with many makes!!!  You probably can, too!  Thankss for a great pattern, Friday Pattern Company! ~ Sew Chaotically! ~ les

Quarantine-while! ~ A birthday party!!!

I've added a new segment to the blog ~ totally and unabashedly lifted from Stephen Colbert!!!  Sign of the times, in so many ways.  I don't think he'd mind? 

Having a birthday party in this crazy time, like so many other things, doesn't have the same flare it once did.  But, we colluded with the Jamester to give Roo a party with some festivity!  There was food picked up from Ms Betty's (The Acropolis - a fav eatery of her childhood), served carefully on separate tables, outdoors, more than six feet apart.  And there were outfits!  Of a variety of styles!  Made with some concern as the sewist couldn't do any fittings or touch her bitty body!!!

First up - a fun little summer top made from the The Maria Apron Pattern, from Maven Patterns shortened per my own imagination!  She happens to be wearing it with a little knit skirt I made her a bit ago.

It's made of a really pretty eyelet with large embroidered flowers that don't show up very well in photos from Cali Fabrics.  I've gotten several lovely pieces from them at very good prices.  The only down fall of their stock is that it can be limited in yardage.  I don't know if this is usual for them or an effect of the current pandemic.  I underlined the front with a purple remnant and used bias binding to finish the edges.  I think it turned out pretty cute!!!

Speaking of celebrations and Cali Fabric - a few weeks prior, Jamie graduated with his masters degree!!  So proud of him!  Once again, celebrations were the best we could do under the pandemic circumstances with an outdoor dinner, our place this time, and a breezy linen shirt.  Fabric also from Cali and my usual go-to for men's shirts M6044.

I thought it turned out quite pretty.  Was pleased the fit was good, given the same restrictions applied!

Then, to mix things up, some quarantine fun lounge wear!  In a crazy cheetah (?) print in fabric gifted from Kay!!

Roo was a sport about it!  HA!!  The little crop top, made using the ever dependable free Colette, Sorbetto, used every scrap I had left (had to piece the back) after making up another pair of the Purl Soho, city gym shorts!  Just the sort of thing you need to chi'lax in during quarantine, no?

Or for dancing and gymnastic moves!

Then, for work - or play....

I made her ANOTHER Veronika Circle Skirt, from Megain Nielsen Patterns in a lovely drapey knit crepe from Joann's.

The top was super fun to imagine and put together from the McCall's 6924 dress pattern!  It calls for a lining, but I finished the seams with bias binding.  So pleased with the fit!!!  I thought it was super cute!

Still, we did manage to let them eat cake!!!  They put together the masterpiece you see the night before.  We added a slice of ooey gooey chocolate cake from Ms Betty of Roo's childhood and one of baklava cheesecake!  Thanks for helping make it happen, Jamie!

Happy birthday, girlie!  So proud of how you and the Jamester are managing all of this!!  Love you both so much! - mommy

The ipi/nivo combo WITH radiation to melanoma brain mets leads to improved overall survival!!!!

I feel like I have been yelling about this for TEN YEARS - because I have!  Immunotherapy COMBINED with radiation leads to better results for melanoma patients than does either therapy alone!!!  Here is a testament to my yelling: Radiation AND immunotherapy does a body good!

Now, this: 

Combined immunotherapy with nivolumab and ipilimumab with and without local therapy in patients with melanoma brain metastasis: a DeCOG* study in 380 patients.  Amaral, Kiecker, Schaefer, et al. J Immunother Cancer. 2020 Mar 8. 

Nivolumab combined with ipilimumab have shown activity in melanoma brain metastasis (MBM). However, in most of the clinical trials investigating immunotherapy in this subgroup, patients with symptomatic MBM and/or prior local brain radiotherapy were excluded. We studied the efficacy of nivolumab plus ipilimumab alone or in combination with local therapies regardless of treatment line in patients with asymptomatic and symptomatic MBM.

Patients with MBM treated with nivolumab plus ipilimumab in 23 German Skin Cancer Centers between April 2015 and October 2018 were investigated. Overall survival (OS) was evaluated by Kaplan-Meier estimator and univariate and multivariate Cox proportional hazard analyses were performed to determine prognostic factors associated with OS.

Three hundred and eighty patients were included in this study and 31% had symptomatic MBM (60/193 with data available) at the time of start nivolumab plus ipilimumab. The median follow-up was 18 months and the 2 years and 3 years OS rates were 41% and 30%, respectively. We identified the following independently significant prognostic factors for OS: elevated serum lactate dehydrogenase and protein S100B levels, number of MBM and Eastern Cooperative Oncology Group performance status. In these patients treated with checkpoint inhibition first-line or later, in the subgroup of patients with BRAFV600-mutated melanoma we found no differences in terms of OS when receiving first-line either BRAF and MEK inhibitors or nivolumab plus ipilimumab. In BRAF wild-type patients treated with nivolumab plus ipilimumab in first-line or later there was also no difference in OS. Local therapy with stereotactic radiosurgery or surgery led to an improvement in OS compared with not receiving local therapy, regardless of the timepoint of the local therapy. Receiving combined immunotherapy for MBM in first-line or at a later time point made no difference in terms of OS in this study population.

Immunotherapy with nivolumab plus ipilimumab, particularly in combination with stereotactic radiosurgery or surgery improves OS in asymptomatic and symptomatic MBM.

Again, if you have a melanoma brain met (though we have learned in many other reports that these facts are true for the rest of the body as well) the ipi/nivo combo WITH radiation provides the best overall survival in both symptomatic and asymptomatic patients.  I still get reports from patients for whom this combination has not been provided.  From institutions that should definitely know better.  Sighs, eye rolls, and screaming continues.  But here you go ~ again.  For what it's worth.  - c

Outcomes of acral, mucosal, and uveal melanoma with treatment from checkpoint inhibitors - spoiler alert - get the immunotherapy combo!!!!

As I've said many times, Melanoma sucks great big hairy green stinky wizard balls.  Sadly, ocular, mucosal, and acral (think -fingers, palms, soles, nail beds) sucks even more.  Here are some prior reports:  https://chaoticallypreciselifeloveandmelanoma.blogspot.com/search?q=mucosal+melanoma

Now, there's this ~

Survival after checkpoint inhibitors for metastatic acral, mucosal and uveal melanoma.  Klemen, Wang, Rubinstein...Sznol.  J Immunother Cancer. 2020 Mar 8.

Checkpoint inhibitors (CPIs) are thought to be effective against cutaneous melanoma in part because of the large burden of somatic mutations (neoantigens) generated from exposure to ultraviolet radiation. However, rare melanoma subtypes arising from acral skin, mucosal surfaces, and the uveal tract are largely sun-shielded. Genomic studies show these sun-shielded melanomas have a paucity of neoantigens and unique biology; they are thought to be largely resistant to immunotherapy. It has not been definitively shown that CPI improves survival in metastatic sun-shielded melanoma.

We reviewed a single institutional experience using antibodies against CTLA-4, PD-1 and/or PD-L1 to treat patients with metastatic melanoma. Primary tumor histology was categorized as cutaneous, unknown, acral, mucosal, or uveal. We studied demographic data, treatment characteristics, and overall survival (OS) after CPI.

We treated 428 patients with metastatic melanoma from 2007 to 2019. Primary tumors were cutaneous in 283 (66%), unknown in 55 (13%), acral in 22 (5%), mucosal in 38 (9%), and uveal in 30 (7%). Patients with metastatic disease from cutaneous primary tumors had median OS after CPI of 45 months compared with 17 months for acral, 18 months for mucosal, and 12 months for uveal. For all patients with sun-shielded melanoma (n=90), first treatment with anti-PD-1 or anti-PD-L1 was followed by a median OS of 9 months compared with 18 months after anti-CTLA-4 and 20 months after combination therapy. There were 21 patients who achieved actual 3-year survival; 20 received both anti-CTLA-4 and anti-PD-1, either sequentially or in combination. Over 80% of 3-year survivors with progressive disease were treated with local therapy after CPI.

Long survival in patients with metastatic melanoma from acral, mucosal, and uveal primary tumors was associated with receipt of both anti-CTLA-4 and anti-PD-1 antibodies. Complete responses were rare, and local therapy was frequently employed to control disease progression. While sun-shielded melanomas exhibit worse outcomes after CPI than cutaneous melanomas, with an aggressive multidisciplinary approach, 5-year survival is still possible for 25%-32% of these patients.

In this report 90 patients with "sun shielded melanoma" (either acral, mucosal, or uveal) first treated with anti-PD-1 or anti-PD-L1 had median survival of 9 months vs OS of 18 months with anti-CTLA-4 vs 20 months OS with combination therapy.  21 of these 90 patients achieved 3 year survival, with 20 of those getting both anti-CTLA-4 and anti-PD-1 either sequentially or together.  80% of the 3-year survivors were also treated with local therapy after immunotherapy.

My take - if you have this sort of melanoma.  Get the combo - from the start!!!

For what it's worth.  Take care.  - c

Late addition:  

Ipilimumab plus nivolumab for patients with metastatic uveal melanoma: a multicenter, retrospective study.  Najjar, Navrazhina, Ding, et al.  J Immunother Cancer.  June 2020.

Background: Uveal melanoma (UM) is the most common intraocular malignancy in adults. In contrast to cutaneous melanoma (CM), there is no standard therapy, and the efficacy and safety of dual checkpoint blockade with nivolumab and ipilimumab is not well defined.

Methods: We conducted a retrospective analysis of patients with metastatic UM (mUM) who received treatment with ipilimumab plus nivolumab across 14 academic medical centers. Toxicity was graded using National Cancer Institute Common Terminology Criteria for Adverse Events V.5.0. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier methodology.

Results: 89 eligible patients were identified. 45% had received prior therapy, which included liver directed therapy (29%), immunotherapy (21%), targeted therapy (10%) and radiation (16%). Patients received a median 3 cycles of ipilimumab plus nivolumab. The median follow-up time was 9.2 months. Overall response rate was 11.6%. One patient achieved complete response (1%), 9 patients had partial response (10%), 21 patients had stable disease (24%) and 55 patients had progressive disease (62%). Median OS from treatment initiation was 15 months and median PFS was 2.7 months. Overall, 82 (92%) of patients discontinued treatment, 34 due to toxicity and 27 due to progressive disease. Common immune-related adverse events were colitis/diarrhea (32%), fatigue (23%), rash (21%) and transaminitis (21%).

Conclusions: Dual checkpoint inhibition yielded higher response rates than previous reports of single-agent immunotherapy in patients with mUM, but the efficacy is lower than in metastatic CM. The median OS of 15 months suggests that the rate of clinical benefit may be larger than the modest response rate.

For what it's worth - c

Sew Chaotically! ~ For the Love of Landers!!!

I've had this post ready for a while - but the current crazy of disease and loss around the globe put me off sharing such things for a while.  But, joy helps.  In whatever form you prefer.  So, here it is....

I love my Landers, pattern by True Bias.  They are perfect.  Keep the pockets for fun and utility. Lose them, fit them a bit tighter, and you basically have The Persephone Pants without buying another pattern!  BTW - the 1 inch seam allowance provided in the pattern's side seam makes fitting them a dream!  The pattern is incredibly well drafted and there is an excellent sew along on the website!

My first pair, in a fairly light weight twill.

My second in a thick wide rib cord.

And if those weren't enough - I made TWO more - in denim for Roo and myself!

The button fly goes together like a dream and the insides lend themselves to cute bindings and pocket interiors!

In honor of my birthday girl, looking at her Momma, like she's crazy, cause she is!  BAHAHA!  Shown wearing her Landers with her numbers top B5895!

My pair from a lighter weight and Roo's in a heavier denim.  Except for length, they measure exactly the same in all other dimensions.  Both are size 8 and stitched at the 1 inch side seam.  HOWEVER!!  For mine I took in an additional 1/4 inch to both sides, grading to nothing at the top of the pocket.  For Roo's I pinched out an equivalent amount at the back center seam!  THE POWER OF SEWING for a perfect fit!!!!  I used a curved waist band for both pairs.

My Landers are worn with the Nikko Top, also by True Bias, another great pattern!

Happy, happy, birthday my sweet Roo!  I loooooooove you!  Hopefully we'll get to play TOGETHER again soon!  Happy day to each of you as well. - les

Sew Chaotically! ~ Romero Trousers - With so much love and thanks to Mary Anne...

Today is Melanoma Monday.  So dubbed to kick off the Melanoma Awareness Month of May.  Wearing orange to represent!  The top is the Kalle Shirt from Closet Case Patterns, made last summer.  A make I have really enjoyed.  But the bottoms and the love that went into them is the real story today.

They are the Romero Trousers, pattern from Pauline Alice.  I first made shorts from the pattern for Roo last summer:

 

Both versions are size 40, made with no changes other than using a self-drafted contoured waistband and 1/2 inch pinched out at centerback.  The pattern is very well drafted and a lot of fun to make. Here are the deets from making her a previous pair:   Roo's Purple Romeros

But, the two Romeros made for Roo are NOT where these pants started!  They started with a dear friend and her love, her willingness to put forth no small effort in the midst of her busy life as a nurse, homemaker, mother to three active boys, daughter, friend to many, wife to a busy pastor and therefore his church - And that's just the tip of her iceberg! - for me.  On seeing this somewhat whiny post of mine, back in September 2018 as I worked to rediscover my strength and place in the world as I recovered from my second cancer diagnosis and two abdominal surgeries:  Tales from REHAB - Part 1!, inspired by the lovely Lliria dress, by Pauline Alice  I pictured in that post, Mary Anne went out of her way to encourage me to carry on and make me smile - with hope.  Sending this:

From the minute I got that card and those amazing buttons, I knew that they would become my Mary Ann Romero Trousers.  Thank you my dear friend.  It has taken a minute for me to get it together.  The gift you gave has been more sustaining through those minutes than you know.  I now have a suit of armor, fastened with bright red love and strength, that protects me and makes me smile with every wear.

And that Lliria dress?  I have the fabric.  Had to get some slightly smaller buttons.  But, I think you will approve.  Can't wait to show you my Mary Anne Lliria!!!  We cannot all be the amazing woman you are.  But, you have shown me the incredible power that reaching out to those in need has to transform and inspire.

I have been blessed with more kindnesses from my dear peeps than I deserve.  I am ever so grateful to each of you.  Thanks for a gift so much greater than buttons, my dear Mary Anne! ~ love, les

Sew Chaotically! ~ Honey Comb Dress

It feels like a lifetime ago when I made this dress.  Long before Roo's wedding in October!!

It is the COCOWAWA Crafts Honeycomb Dress.  The well drafted pattern comes as both a shirt and dress.  I made a size 4 with no adjustments other than adding 2 1/2 inches to the skirt length and elastic to finish the sleeves rather than the pattern's ties.  Cause, well ~ me.  I can see sleeve ties being dragged through spaghetti sauce, garden soil, and dish water suds in rapid succession and not necessarily that order!

It is made up in a lovely grey double gauze from Fabric.com.  The bodice fits very nicely and the ties at the waist give it even more flexibility.

It is easy to dress up or down.  In fact, I first wore it to Roo's official wedding ceremony! (The day before her big shin dig!)

It is a pleasure to wear, especially since it is now attached to such precious memories.  With leggings and an undershirt, it has been a comfy dressed down outfit for these cool spring days.

Happy May!  And in honor of Melanoma Awareness Month:

Skin Cancer Blog

Protect yourself and those you love by following these tips:

•Seek the shade, especially between 10 AM and 4 PM.

•Do not burn.

•Avoid tanning and UV tanning booths.

•Cover up with clothing, including a broad-brimmed hat and UV-blocking sunglasses.

•Use a broad spectrum (UVA/UVB) sunscreen with an SPF of 15 or higher every day.
For extended outdoor activity, use a water-resistant, broad spectrum (UVA/UVB)
sunscreen with an SPF of 30 or higher.

•Apply 1 ounce (2 tablespoons) of sunscreen to your entire body 30 minutes before going outside.
Reapply every two hours or immediately after swimming or excessive sweating.

•Keep newborns out of the sun. Sunscreens should be used on babies over the age of six months.

•Examine your skin head-to-toe every month.

•See your physician every year for a professional skin exam.

Take care.  Love, les