Beautiful music - from a dear friend I have never met

Melanoma has stolen much from me.  I have lost the concept of my future, of being the "master of my fate" that I once held.  Over 20 surgical scars and vitiligo combine to create all the insecurities such damage places on ones sense of self - of beauty.  Nerve damage and all sorts of nifty residuals from treatment are just part of my daily routine.  I must take care as I start conversations or report results from an endless relay of scans and follow-up appointments to dear ones lest I send them into a panic, as it is not only I who have lost the usual comfort and optimism one might otherwise have in my "health".  I have cost my family a fortune in dollars, time, and worry.  I have witnessed the devastation that melanoma can unleash upon its victims and their families.  The stress and strain of such a diagnosis is not easily borne.  My heart aches for the dear ones I have lost to this wretched disease.

Still, I have gained as well.  I am perhaps more resilient than I would have else wise been.  My loved ones and I have learned what REALLY matters.  I like to think that I take more care to actively appreciate what I do have.  My delight and joy in "the little things" might be considered extreme!  I am more determined than ever to remain strong. Cause after all ~ F@*$ MELANOMA!!!!  But the greatest gift melanoma unwittingly shared is all the amazing people I have "met" from across the globe.  Some in person, some only virtually. They have brought me love, laughter, and a camaraderie for which I am eternally grateful.

One such soul, is my dear Anne-Louise.  She has had an incredible fight with the beast and experienced side effects from her treatment that would have left a lesser soul completely debilitated.  But, not her.  She hails from Australia and, among other things, is Associate Principal Viola for the Sydney Symphony Orchestra.  I have long told her that I wanted to hear her play her fiddle one day!!!  With B's desire to visit Australia I had a real hope that I could make it happen.  But, with the crazy that is the world in general today - the promise of a visit became even more tenuous.  Until now...

Today, Anne-Louise posted this on MPIP, the patient forum for the Melanoma Research Foundation:

Music For Bubbles ~ 

Hi All.  Since we're probably not going to see each other personally for maybe years, I wanted to dedicate this performance to Bubbles who is so helpful, knowledgeable and tireless on all of our behalves. (Plus I'm trying to get more likes than my colleagues hehe!)

Hope you enjoy it.

Love to all and stay safe, Anne-Louise

She included this link:  Anne-Louise Comerford plays Vieuxtemps' Capriccio

Please, please, please give her performance a listen.  It is so beautiful.  Brent and I sat at the kitchen table this morning, listening.  Tears in our eyes.  Touched by the sheer loveliness of the music, the wonder that a human can bring such sounds from wood and string, knowing how much Anne-Louise has endured yet continues to have the strength of spirit to share her talents with the world.

Thanks so much, my friend.  For sharing.  For your music.  For being you.  We may no longer be the "masters of our fates", but we remain very much the "captains of our souls".

Love, les

P.S. Hit that LIKE button, y'all.  Cause, you know - F@*$ MELANOMA!!!!

A walk in the woods ~

In the second week of June, B and I headed to Cades Cove and our favorite walk - Lead Cove Trail to Bote Mountain to Finley Cane Gap Trail for a 8 mile loop.  No people. No bears.  It was lovely.  We were doubly blessed to find the wild rhododendrons in full bloom.

May your Sunday be a lovely path toward peace and joy.

Much love. ~ les

Sew Chaotically! ~ Sewing Quarantine-while = Summer Scrap Busting!

Waste not, want not.  Figured I might as well turn these bits and bobs into some breezy summer tops.

Roo really liked the Merchant and Mills fabric I used for their Dress Shirt, so I turned my last smidge into a Polly Top, a FREE pattern from By Hand London, for her! 

Had to cut two pieces for the back, rather than cutting one on the fold and had to piece one of those at that.  The solid front section is pieced as well!!  Still, it should keep my girl cool and cute while she is working in her yard!

Here's a double save.  I shortened a little rtw tank I never wore into a cool crop top for Rosie and used what I think must have been a silk table runner, part of some pieces Kay gave me when clearing out some of her fabric stash, to make up a Wrap skirt, another FREE pattern!  This one is courtesy Peppermint and The Fabric store.

The tie is pieced...and a little bit too stiff for the skirt...but hey - that's what I had on hand!

This project was useful for turning scraps into a cool summer top, but also served as a wearable muslin! I used the last bit of a lovely shirting I used in making Freddo's Christmas shirt ~

~ to stitch up The Basic Blouse (a shortened version of The T-shirt Dress) from the Nani Iro Sewing Studio book.  Consistent with the theme here, I had to piece the back!

But, I have a wearable top and discovered that the s/m of this pattern is aces.  I did drop the front neckline just a tad and lengthened the sleeves.  I think my plans for the dress will work out well, as the intended fabric is even more fluid.

A strange mish mash of makes which seems appropriate for the crazy mish mash that is our world just now.  At any rate, working on them kept me occupied and the finished products should provide some useful wear.  Stay cool.  Stay safe.  Keep your distance.  WEAR A MASK!!!  And as always ~ live and sew chaotically! - les

Colitis in melanoma patients treated with immunotherapy - biopsies to check bowel that looks normal may be important!

Colitis is unfortunately a fairly common, and sometimes persistent, side effect folks treated with immunotherapy deal with.  This may be helpful to those with symptoms who keep getting told their bowel "looks fine"!!!

Five-year review of corticosteroid duration and complications in the management of immune checkpoint inhibitor-related diarrhoea and colitis in advanced melanoma.  Favara, Au, Clark, et al.  ESMO Open.  July 2020.

Background: Immune-related diarrhoea/colitis (ir-D/C) is a common adverse event of immune checkpoint inhibitor (ICI) therapy. Guidelines recommend corticosteroid (CS) treatment; however, the average treatment duration for ir-D/C remains poorly defined.

Methods: All advanced melanoma patients treated with ICI therapy at the Royal Marsden Hospital between 2011 and 2016 were reviewed to identify ir-D/C cases alongside clinical variables. 

Results: 117 any-grade ir-D/C episodes occurred in 109 (21%) patients out of a total of 519 patients treated (ipilimumab=77 episodes, anti-PD1=17 (nivolumab or pembrolizumab), ipilimumab and nivolumab=23 (ipi+nivo)) (seven patients had ir-D/C more than once on different lines of treatment) and greater than/=grade 3 ir-D/C occurred most frequently (63/519 patients (12%) vs 29/519 (5%) grade 1, and 25/519 (5%) grade 2). Median onset (days) of all-grade ir-D/C after starting ICI therapy was 41 for ipilimumab (IQR 24 to 59, n=77), 91 for anti-PD1 (IQR 46 to 355, n=17) and 45 for ipi+nivo (IQR 24 to 67, n=23). In 71/117 (61%) patients, ir-D/C episodes were treated with CS (17% grade 2; 79% grade 3/4): 54 being steroid-responsive; 17 being steroid-refractory and received additional anti-tumor necrosis factor (TNF) treatment. Median grade 3 ir-D/C CS duration was similar across treatments, averaging 58 days. Median overall CS duration (days) was longer in the grade 3/4 D/C steroid-refractory group (94 vs 45 days). Infection developed in 11/71 (15%) CS recipients and in 6/17 (35%) anti-TNF recipients. In 65/117 (55%) patients, ir-D/C episodes were investigated with flexible sigmoidoscopy. Of these patients, 38/65 (58%) had macroscopic colitis and 12/65 (18%) had microscopic colitis. The steroid-refractory group had more macroscopic changes, 13/17 (76%), than the steroid-responsive group, 22/41 (54%). 

Conclusion: Rates of grade 3 ir-D/C were higher than reported in clinical trials. The 58-day median duration of CS therapy for grade 3 ir-D/C places a significant number of patients at risk of complications. We demonstrate that microscopic colitis is an important subgroup, advocating biopsies in ir-D/C even with macroscopically normal bowel.

For what it's worth. - c

Late addition.  Not really news, but ~

Workup and Management of Immune-Mediated Colitis in Patients Treated with Immune Checkpoint Inhibitors.  Singh, Marshall, He.  Oncologist. 2020 Mar;25.

As the use of immune checkpoint inhibitors for several different malignancies becomes more mainstream, their side-effect profile raises new challenges. In 2011, the Food and Drug Administration approved the first checkpoint inhibitor for the treatment of advanced melanoma, and since then, checkpoint inhibitors have demonstrated efficacy in many other tumor types. Given the frequent use of immune checkpoint inhibitors in a wide range of cancers today, the diagnosis and management of their immune-mediated toxicities need special attention. One of the most common is immune-mediated colitis. Workup and management of immune-mediated colitis can be challenging and is the purpose of this review. KEY POINTS: Rate of immune mediated colitis differ from different kind of immune checkpoint inhibitor treatment. To work up immune-mediated colitis, tests to rule out infectious etiologies of diarrhea, colonoscopy and abdominal image will help to differentiate immune mediated colitis from colitis from other etiology. Patients with mild colitis can be managed with supportive therapies alone, but more severe cases may require immunomodulators such as steroid. Refractory cases may require tumor necrosis factor (TNF) inhibitors, such as infliximab in addition to steroid treatment.

- c

Sew Chaotically! ~ A lovely first excursion! Cades Cove Loop and the Petula Top, by Republique du Chiffon

In this crazy time, we have stayed put.  B picks up groceries curbside from Wally World after ordering on-line.  I've been out only for a couple of required doctor visits - my 3 month recheck which included an abdominal ultrasound due to ascites on my last CT.  B hypothesized at the time that it was fluid accumulation secondary to the 9 zillion biopsies that were done during a follow-up  colonoscopy just prior to the CT.  And so it must have been as it was resolved on ultrasound.  The subsequent MD visit was uneventful and all labs, including protein markers for my ex-goblet cell adenocarcinoma, were all normal.  So....enough of that biz for three months anyway.

We have visited all the kiddos in a weird quarantine-while sort of way.  Going up to Knoxville to visit Fred and Irina a couple of times - socially distancing, while sharing a meal outside on separate tables outdoors.  The same when going over to Roo and the Jamester, or having them here.  We sit outside one place and they sit in another.

In an early spring visit to Freddo, we did take a driving tour of Cades Cove Loop.  It was lovely as ever and I got wear a new light as air blouse.  The Petula by Republique du Chiffon in pink dotted Swiss.

I probably could have gone down a size, but made a 40 with no mods in that regard.  However, I did make the sleeve cuffs and front placket as one piece that I folded, rather than two pieces sewn together as the pattern recommends.  And one more time ~ why no seam allowance Republique du Chiffon?  WHY?????  The pants were made in 2017 from a pattern I wore in high school - M2077.  Still going strong!

It makes a pretty little top, doesn't it?

Yes.  We saw a bear!  I mean, you'll have to take my word for it!  HA!  It was in a different field from the one I was in!  Keeping our distance from dangerous creatures - those that are visible and those that are not!

Stay safe.  Much love and virtual hugs! - les

Encorafenib/Binimetinib ~ BRAF/MEK inhibitor combo in patients with V600E/K mutant tumors

I've provided reports on this BRAF/MEK inhibitor combo before.  Here's a link to some of the posts:  Encorafenib/Binimetinib  Here's a link to reports on the COLUMBUS study in particular:  COLUMBUS

For this study, inclusion criteria on the Clinicaltrial.gov website notes:  "Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation"

A phase 1b/2 study of the BRAF inhibitor encorafenib plus the MEK inhibitor binimetinib in patients with BRAF V600E/K-mutant solid tumors.  Sullivan, Weber, Patel, et al.  Clin Cancer Res. 2020 Jul 15.

This open-label, dose-finding phase 1b/2 study reports the safety and activity of the first combination use with BRAF inhibitor (BRAFi) encorafenib plus MEK inhibitor (MEKi) binimetinib in patients with BRAF V600E-mutant solid tumors. (NCT01543698). 

In phase 1, the recommended phase 2 doses (RP2D) were established (primary objective). In phase 2, the clinical activity of the combination at the RP2D was assessed (primary objective) in patients with BRAF-mutant metastatic colorectal cancer (mCRC), BRAFi-treated BRAF-mutant melanoma, and BRAFi-naïve BRAF-mutant melanoma. Results 126 patients with BRAF mutant solid tumors were enrolled (phase 1: 47 patients; phase 2: 79 patients). The RP2D was encorafenib 450 mg QD plus binimetinib 45 mg BID and pharmacokinetic (PK) data suggest that drug-exposures of each agent were similar in combination compared with single-agent studies. In the phase 2 cohorts, confirmed responses were seen in 2 of 11 (18%) evaluable mCRC patients, 11 of 26 (42%) evaluable BRAFi-pretreated melanoma patients, and 28 of 42 (67%) BRAFi-naïve melanoma patients. The most common grade 3/4 adverse event in phase 2 was increased alanine aminotransferase. 

The combination of encorafenib (450 mg) plus binimetinib (45 mg) showed acceptable tolerability and encouraging activity in patients with BRAF V600-mutant tumors, which led to the dose selection for the melanoma COLUMBUS study. The safety profile of the combination was consistent with other approved BRAFi plus MEKi regimens, with several differences, including lower rates of dose-limiting pyrexia, arthralgia, and photosensitivity.  

For what it's worth.  - c

Sew Chaotically! ~ Merchant and Mills fabric and The Dress Shirt!

This pattern and fabric combo is a Merchant and Mills double win!  The pattern is their Dress Shirt made up in 'red red wine', a light cotton block print with a stitched line running through it from their shop in Rye. Both are soooooo good!  I made up a straight size 12, with an inverted front pleat, in the longest length.  I cut the bib in one piece across the grain so as to make the most of the stripe.  I did assemble things in a slightly different order than the pattern recs so as to have clean finishes inside.

Oddly enough, I've been in Rye!!!  Years ago we had a fabulous trip to London with the kiddos and made a circular excursion via the train with stops in Bath and Rye!  We had a lovely visit in the old town and even shopped along the main streets, including at stop at "My Sweet Old Etc." (Yes, it was named after the E.E. Cummings poem!!!!  I asked!) But, I didn't even notice this amazing fabric shop!!!!  Who knew years later I would love it so - albeit from afar????!!!!

And because such good material can't go to waste - I made a matching headband...

...along with quite a few others!  They are a bit addictive!  They are made using a FREE pattern from Isabella of What Bella Made She makes many beautiful things, so be sure to check her out!!!

Just a few more for a dear friend!!!

In the midst of all the crazy, there is still beauty in the simple things!!!    Sew chaotically! ~ les