Springing forth like a wood poppy!!!

Things have been a bit rough around the edges in my world for a while now, but spring is springing!  And my sweet Bentie is making things happen!!!

When I say it might be nice to have a potting bench ~ He builds me the most amazing gardening work bench EVER!!!

When  we briefly discuss a foot path and a new flower bed for the front...

It appears!!!  Can you feel the beauty?  Soon it will not only be a lovely path, but one bordered by hosta, astillbe, irises, and coleus!!!  (I hope!!!)

In the back, I am so thrilled with the way my three little May Apples have multiplied!!! (I actually prefer to call them fairy pagodas!!!) Not to mention ALL the beautiful little wood poppies!!!!  I just loooooove them!

And because this fact seems unknown to some...

...just say'n!

Sadly, tonight some of my precious floral friends may feel the burn as it is to drop into the 20's!!!!!

B helped me cover as many things as we could.  Hang in there guys, life can get rough sometimes!!!

I am much inspired by my wood poppies.  They are adaptable, resilient, far stronger than they appear, filled with beauty and grace sweetly shared with any who care to look. 

I would like to be a wood poppy. Keep springing, everybody!!! ~ les

Clinical condition of melanoma peeps and associated outcomes when treated with anti-PD-1 vs anti-PD-1 and ipi

While this report is not exactly news...it is interesting and confirms prior data:

Clinical Correlates of Response to Anti-PD-1-based Therapy in Patients With Metastatic Melanoma.  Davis, Perez, Avoubi,...Sosman...et al. J Immunother. 2019 Mar 13. 

Anti-PD-1 agents, alone or in combination with ipilimumab, produce durable responses in some melanoma patients. Tumor features that correlate with response are not well defined. We collected clinical data from metastatic melanoma patients treated at 2 centers who received anti-PD-1 (n=303) or anti-PD-1+ipilimumab (n=57). We correlated number of metastases, diameter of largest tumor (tumor bulk), and organ involvement with response rate (RR), progression-free survival (PFS), and overall survival (OS). Patients with diameter of largest tumor less than or equal to 2 cm had a 53% RR, whereas those with largest tumor greater than 2 cm had a 38% RR. Those with liver metastases had lower RR (25% vs. 43%). RR to anti-PD-1 was greater in patients with less than or equal to 10 metastases compared with those with greater than 10 (39% vs. 27%). In multivariable analyses, size of the largest tumor was independently associated with PFS, OS, and RR, whereas AJCC stage, lactate dehydrogenase, liver metastases, ECOG performance status, number of metastases, and prior therapies were not. In patients treated with anti-PD-1+ipilimumab, however, tumor bulk was not associated with outcomes, although number of metastases was associated with PFS  and RR but not OS. Pathologic analysis did not reveal differences in T-cell infiltration in bulky versus small tumors. Tumor bulk, defined by diameter of largest tumor, was strongly and independently associated with clinical outcomes in anti-PD-1 but not in anti-PD-1+ipilimumab. In conjunction with molecular biomarkers, clinical predictors may help guide selection of immunotherapy agents.

So....this study looked at 360 metastatic melanoma peeps.  303 were given anti-PD-1 alone and 57 were treated with the anti-PD-1 plus ipi.  The researchers looked at response rate (RR), progression-free survival (PFS) and overall survival in the groups to see if there were any clinical consistencies between those results.  They found that (not surprisingly) patients whose largest tumor was less than or equal to 2 cm had a 53% RR while those whose largest tumor measured more than 2 cm had a 38% response rate.  Patients with less than 10 mets had a better RR than those who had more than 10 (39% vs 27%).  Folks with liver mets did less well, with RR of 25% vs 43%.  In a separate, overarching analysis, size of the largest tumor was independently associated with all parameters (PFS, OS, and RR) - while LDH, liver mets, # of mets, and prior therapies were not.  HOWEVER, with the ipi/anti-PD-1 combo, tumor size was NOT associated with out comes, though the NUMBER of mets was still associated with PFS and RR, but not OS.  Analysis of tumor pathology did not reveal any differences in T-cell action in bulky vs small tumors.

We have long known that immunotherapy works best with the lowest tumor burden.  Lots of research indicates that LDH is not a very reliable marker.  We know that liver mets are difficult to treat (early research link here).  We also know that there are no crystal clear parameters (YET!!!) that tell us who will do well on anti-PD-1 as a single agent vs those who need to be treated with anti-PD-1 combined with ipi.  AND ~ that is a hard decision, given the desire to rid ourselves of melanoma versus the unfortunate side effects the combo can trigger that are more easily avoided with anti-PD-1 alone.  BUT ~ given what we have long known and the information presented here....if I had lots of mets, large mets or liver involvement...I would be opting for the combo.  Just saying.  For what it's worth. - c

Sew Chaotically! ~ Two Sasha Basic InstincT's!!!

Two disparate sewing inspirations with the same perfect answer!!!  Sasha's Basic InstincT pattern! I first made this incredibly well drafted, versatile tee here, with another for Roo here, and have been planning others ever since.

When I came across this sparkly gold knit remnant at JoAnn's I knew I could combine it with this silky black jersey for a Basic InstincT for Roo - the world's best teacher who's always willing to support her kiddo's at pep rallies and games in the school colors of BLACK AND GOLD!!! 

For myself, I was inspired by this (incredibly overpriced) tee from Anthropology.  I liked the contrast neck binding and relaxed fit.  Again, Sasha's tee with a strip of pink cut from the bright pink striped knit I used for Roo's Valentine Top and the last of my grey jersey, previously used for my Nikko and Melrose combo/separates, would be perfect!

Both of these are stitched up in size small with no alterations.  For Rosie's, the gold is stitched as an overlay only in the front, so that it would not be next to her skin as it is a bit scratchy.

Yep!  This will work for pep rallies!  Or, pair it with skinny jeans and she's ready for a night out!

For mine, I simply cut the neckband as drafted in the pattern, making sure to cut and fold it such that only the a pink portion from the striped fabric I used in Roo's Valentine top showed on the outside.  On a whim I added pink bands to the sleeves as well.  I love how they both turned out!!!!

This tee can be used in so many ways - both as a base pattern and in your wardrobe once it's made!  Worn here with a RTW blazer and jeans that belonged to my son when he was 13!

 Thanks, Sasha!!!  #followyourbasicinstinct and Sew Chaotically!!! ~ les

CLND in melanoma patients is NOT associated with survival benefit

As effective therapies were developed for melanoma patients, folks began to take a harder look at whether or not the removal of all the lymph nodes in the nodal basin, after a positive sentinel lymph node, provided benefit.  With no effective treatment for melanoma, the argument for CLND made more sense.  These days, as ratties have proved the value of both targeted and immunotherapy as treatment for advanced disease as well as adjuvant (BRAFi and Yervoy were FDA approved for metastatic melanoma in 2011, anti-PD-1 was approved for same in 2014, and nivo was approved for use as adjuvant only in 2017) and are now furthering the examination of NEO-adjuvant treatments, we have learned better.  The research and recommendations have vacillated back and forth over the years and the topic has been more than covered in this space with a zillion articles and discussions.  Here's a brief review of the value and difference between SLNB (sentinel lymph node biopsy) and CLND (complete lymph node dissection) written in 2016:

I have long said that sentinel lymph node removal and testing in melanoma seems like a complete no-brainer to me!!!  It is done when you return for the needed wide excision around the tumor that was removed.  It is minimally invasive considering you're going to have the wide excision anyway.  It is the only way to know what stage you really are.  You may have only cutaneous disease and therefore are categorized as Stage 1 or 2....based on how thick your lesion was, the presence of ulceration, etc.  BUT....if you have a positive node to go with that....you are then Stage 3....and that is a very different place to be.  

1.  It's important to know that's where you are in melanoma land.

2.  It makes a world of difference in recommended follow up.

3.  It makes a world of difference in what insurance companies will cover for your follow-up.

4.  AND....it makes a world of difference in potential treatment options.

NOW....do NOT confuse sentinel node removal and biopsy with a complete lymph node dissection (CLND).  CLND is different.  A CLND is when, usually after having one or more positive nodes, all the lymph nodes are removed from the nodal basin (the area in which the positive node was located).  This IS invasive surgery and has the potential to cause nerve damage and/or lymphedema, among other things.  IF you had a positive sentinel node, this would be one of the things you would have to decide about doing or not.  The science and data surrounding whether this is helpful or not, worth the potential damage or not, is murky.  There are studies that say it helps and others that say is does not.  BUT whichever way you decide to go with this...this is a decision made AFTER the sentinel node dissection and separate from it!!!

The difference between the two procedures and reasons for them remains on point.  And while there are still occasional valid reasons to consider a complete lymph node dissections - now there's this:

Completion lymphadenectomy for a positive sentinel node biopsy in melanoma patients is not associated with a survival benefit.  Kleman, Han, Leong, ..., Sondak, et al.  J Surg Oncol. 2019 Mar 18. 

Completion lymph node dissection (CLND) for sentinel lymph node (SLN) disease in melanoma patients is debated. We evaluated the impact of CLND on survival and assessed for predictors of nonsentinel node metastasis (positive CLND).

Positive SLN melanoma patients were retrospectively identified in the Sentinel Lymph Node Working Group database. Clinicopathological factors were correlated with CLND status, overall survival (OS), and melanoma-specific survival (MSS).

There were 953 positive SLN patients of whom 831 (87%) had CLND. Positive CLND was seen in 141 (17%) cases and was associated with worse OS and MSS . CLND was not performed (No-CLND) in 122 of 953 positive SLN cases (13%), of whom 100 had follow-up and 18 (18%) developed a nodal recurrence (NR). No significant differences in OS and MSS were seen comparing CLND with No-CLND and comparing positive CLND with No-CLND NR patients. Gender, primary site, ulceration, and number of positive SLNs were correlated with nonsentinel node metastasis.

Performance of CLND provides prognostic information but is not associated with a survival benefit. Clinical variables can predict a positive CLND in patients who may be at high risk of recurrence.

In reviewing the records of 953 melanoma peeps with positive SLN, researchers found that there was no impact on overall survival or melanoma-specific survival, no matter if the CLND was done or not.  The usual risk factors of "gender, primary site, ulceration, and number of positive SLNs" were noted to coordinate with metastasis as studies I've reported on previously corroborate.  

As someone who has had two CLND's (to both axilla), the first in 2003 and the second in 2007, yet still progressed to Stage IV in 2010, watching the research on the topic unfold has been interesting to say the least.  However, given the advances in melanoma therapy, it is probably time to move on! - les

Sew Chaotically! ~ Scrap busting little knit top - M7574

Along the same lines as my last post, this little top was an exercise in using bits and bobs (a remnant of the striped knit I used to make my last Nikko top and a smidge of blue jersey that remained from a piece Ruthie gifted me that I used in making this dress - M6752) from my stash that seemed "too big to waste" yet were challenging to make a garment from.  Unlike the last make - my umpteenth version of the Linden sweatshirt - this endeavor offered the chance to make a "wearable muslin" of a pattern I had yet to try, McCall's 7574.  I think it turned out as cute as a bug!

Yes, when I say "scrap busting" I mean it!!  There was so little fabric left that I could not match the stripes on the back nor even make more than one back piece in ONE piece!  If you look closely, you will see the left back is finished off with two additional strips of fabric at the bottom!!!

BUT!  I'm okay with that!  I discovered I really like this pattern.  The method for putting in the sleeves is a little different!  It went together well.  I made a medium with no alterations. Interestingly, the pattern offered lots of information and in depth instructions on how to make adjustments for all sorts of needs...bust, waist, shoulder, length....which is all very well.  It's just that I found them a bit curious as this is a pattern specifically for quite forgiving stretch knits!  Still, they are there should you need them!  In the end, I got a cute little play/hiking shirt out of  - SCRAPS!!!

Sew and live chaotically!!! ~ les

Sew Chaotically! ~ Scrap busting for the love of Linden

As mentioned here, over the past several months I've organized my fabric and begun a variety of projects to utilize my "scraps"; embracing the challenge of using bigger remnants to fashion useful, fun garments including turning the remains from this Toaster sweater into a pretty and much needed gown.  My love for the ease and versatility of Grainline Studio's Linden Sweatshirt has been evidenced more than once!  I've used it to create a trio of sister sweatshirts that incorporated silk as well as knits, a workout top for Roo, a soft, comfy tee for myself, and a funky cropped top as well.  When I saw the little sweatshirt pictured to the right in an Eddie Bauer catalog, I knew exactly how to use a few more bits.  With fabric left from a previous version of another Toaster sweater and McCall's 7244 knit dress, I was ret tah go!

Yep, when you're using remnants creative piecing is sometimes required!!!

I think I did good, y'all!!!  A fun, usable play top from bits that would otherwise have languished on a shelf or ended up in the bin!  

Happy spring!  Sew chaotically and enjoy your own - #scrapbusting! ~ les

Circulating tumor DNA (ctDNA) as a way to predict survival in Stage III melanoma patients

If you have Stage III melanoma, trying to determine whether or not to embark on adjuvant treatment (treatment taken after all obvious melanoma has been removed) via either immunotherapy or targeted therapy is - at best - difficult!!!  Will such treatment really help?  Well, the data strongly supports - YES!!!  Here are a zillion such articles!  But, we also know that some folks can remain Stage III for years and years with no advancement of their disease.  Is the very real possibility of significant life changing side effects worth it?  Wouldn't it be great if you could do a simple blood test to see if you fall among the folks who are Stage III AND at increased risk for progression if you do not attain treatment?

Well!  Before we get to that, remember all my rants about simple blood tests that can tell us soooooooo much about our melanoma status?  Here are a few zillion of those - looking at circulating tumor DNA (little bits of tumor, floating around in our blood) in particular:  The many ways measuring circulating tumor DNA can help melanoma patients  Basically, that link takes you to tons and tons of data, with some of my explanations, about what measuring circulating bits of tumor via a simple blood draw can do to impact melanoma patients and their treatment choices.  I note: "There are many blood markers, all much easier to collect that actual tumor samples, that can be used to diagnosis melanoma, determine tumor type, prognosis and response to therapy." 

Here's the latest:

Pre-operative ctDNA predicts survival in high-risk stage III cutaneous melanoma patients.  Lee, Saw, Thompson, et al. Ann Oncol. 2019 Mar 12. 

The outcomes of patients with stage III cutaneous melanoma who undergo complete surgical resection can be highly variable, and estimation of individual risk of disease relapse and mortality remains imprecise. With recent demonstrations of effective adjuvant targeted and immune checkpoint inhibitor therapy, more precise stratification of patients for costly and potentially toxic adjuvant therapy is needed. We report the utility of pre-operative circulating tumour DNA (ctDNA) in patients with high-risk stage III melanoma.

ctDNA was analysed in blood specimens that were collected pre-operatively from 174 patients with stage III melanoma undergoing complete lymph node dissection. Cox regression analyses were used to evaluate the prognostic significance of ctDNA for distant metastasis recurrence free survival (DM-RFS) and melanoma specific survival (MSS).

The detection of ctDNA in the discovery and validation cohort was 34% and 33% respectively, and was associated with larger nodal melanoma deposit, higher number of melanoma involved LNs, more advanced stage and high lactose dehydrogenase (LDH) levels. Detectable ctDNA was significantly associated with worse MSS in the discovery and validation cohort and remained significant in a multivariable analysis. ctDNA further sub-stratified patients with AJCC stage III substage, with increasing significance observed in more advanced stage melanoma.

Pre-operative ctDNA predicts MSS in high-risk stage III melanoma patients undergoing complete LN dissection, independent of stage III subclass. This biomarker may have an important role in prognosis and stratifying patients for adjuvant treatment.

So ~ in this study researchers looked at one group of Stage III melanoma patients to see how many of them would have circulating tumor DNA present in their blood sample.  Then they took another group to determine the presence of ctDNA and its correlation to other risk factors and melanoma outcomes.  They determined that the presence of circulating bits of tumor in the blood was consistent across both groups at about 34%.  They found that ctDNA in the Stage III melanoma patient's blood was associated with those who had larger amounts of tumor in melanoma positive lymph nodes, a greater number of lymph nodes affected, advanced stage, and increased LDH levels.  In the end, when they looked at all the variables, ctDNA was significantly associated with melanoma specific survival.

Is the presence of ctDNA the end all, be all?  Of course not!  BUT!!!  If you knew where you stood in regard to bits of tumor floating in your blood - or NOT!! - then that could be critical in making a decision about whether or not to proceed with adjuvant treatment.  Further, if I were a Stage IIIb patient today, as I was back in 2003, and found I did NOT have measurable ctDNA, I might be comfortable in postponing adjuvant treatment.  HOWEVER, I would request serial blood draws to determine if that status changed over time, with the understanding that should ctDNA show up in my blood I would begin adjuvant therapy ASAP!  I believe (given all the data I've reviewed) that evaluating patients for ctDNA is a much more sensitive and sensible way to follow Stage III peeps for progression than repeated radiographic scans and (hopefully!!!) will be the wave of the future. 

So...what are we waiting for???????????  Lives are at stake!  Let's make measuring ctDNA a routine, accepted method of evaluating melanoma patients - TODAY!!!! ~  c

Leptomeningeal disease and melanoma

It's not news that melanoma sucks great big green, hairy, stinky wizard balls!  It is also not news that should it progress to leptomeningeal disease it sucks even more.  Here are prior reports on the topic:

August 2015: LMD - a case study, intrathecal admin of TIL's 
October 2015:  Intrathecal IL2 for LMD 
February 2018:  Retrospective review of IT IL2 in melanoma patients with LMD 

Though I ranted for years - and it is only partially rectified today - patients with ANY CNS involvement of their melanoma were long denied access to clinical trials.  Gradually, however, we ratties PROVED that both immunotherapy and targeted therapy work in the brain AND the body.  That same access is routinely denied to patients with leptomeningeal disease (LMD) - still.  THIS IS WRONG.  PERIOD!  FULL STOP.

Now, there's this:

Predictors of survival in metastatic melanoma patients with leptomeningeal disease (LMD).  Ferguson, Bindal, Bassett, et al.J Neurooncol. 2019 Mar 7.

Although the survival of most melanoma patients diagnosed with leptomeningeal disease (LMD) is short, some patients can have better outcomes and prolonged survival. A large retrospective cohort of patients was analyzed to identify features associated with survival with LMD from melanoma. Clinical characteristics, treatments and survival were collected for melanoma patients diagnosed with LMD from 1999 to 2015. The Kaplan-Meier method was used to estimate overall survival (OS) and Cox proportional hazards regression was used to test statistical significance of associations with survival. Multivariate analysis was performed using Cox proportional regression modeling.

178 melanoma patients with LMD were identified. Median age at LMD diagnosis was 51 years. Most (n = 153) patients received at least one treatment for LMD, including radiation (n = 98), chemotherapy (n = 89), targeted therapy (n = 60), immunotherapy (n = 12), or intrathecal (IT) therapy (n = 64). Median OS from LMD diagnosis was 3.5 months. One-, two-, and five-year OS rates were 22%, 14%, and 9%, respectively. Factors significantly associated with OS on multivariate analysis included Eastern Cooperative Oncology Group [ECOG] performance status greater than 0; neurological symptoms; absent systemic disease; and LMD treatment, targeted therapy, or IT therapy.

Despite their overall poor prognosis a subset of melanoma patients with LMD achieve longer survival. The factors associated with outcomes may be used to guide patient management and to inform the design of future clinical trials for this population.

Sadly, still with incredibly poor OS numbers.  But, at least folks are looking.  This doesn't prove much other than...treatment helps!!!!  So - let's provide treatment, shall we?????

This post in honor of sweet Adriana and her dear Rob.  You are both in my heart - now and always. ~ les

Sew Chaotically! ~ Nikko plus Melrose = fab 'dress' and separates for all your super woman needs!!!

AND - it's FREE!!!!

Sometimes a plan you didn't know you had comes together perfectly!!!  In this case, I had long been thinking of making a Melrose skirt by Aime Comme Marie (Like Like Mary) as well as a sleeveless Nikko top by True Bias and had both patterns ready to go!!  Then, B appeared with the gift of 3 yards of a soft, drapey, yet substantial grey knit jersey!!!  I love the ease of dresses ~ you throw it on and it's one and done!!!  So I was seriously tempted to use the fabric for a Nikko dress (and I know there will certainly be one in my future)!  But, how cool are separates as wardrobe extenders that allow the creation of TONS of outfit opportunities???  Thus the grand plan of a Melrose skirt to combine (or not!!) with a Nikko top!!!!


I posted my story of the Nikko top previously here.  It is as fab to wear and make as so many sewists have raved.  I've already worn the two I made a ton!!!  When combined with the Melrose skirt, the result is as easy and 'put together' as I had hoped!  The skirt was super easy to stitch up.  The only hiccough was the fact that in the process of stitching on the wide exposed elastic waistband - it stretched out a bit.  I fixed the problem by taking a wedge out of it and the waist of the skirt itself at the back seam.  Doable, just unanticipated.  I'm looking forward to using both pieces together and separately as the weather warms - worn here with tights and a jacket when heading out for errands!

As we celebrate the beauty and power of womanhood - wear what you want the way you want!!! 

For all strong women everywhere, making pennies to the dollars made by their male counterparts - who take care of their children, our children, and the world - most especially including all the dear amazing soul sisters who take care of me!! - HAPPY INTERNATIONAL WOMEN'S DAY!!!!  You deserve a day of celebration (along with equal rights, equal salaries, equal opportunities for education and leadership positions) and so much more!!! - love, les

KEYNOTE-001: Melanoma patients treated with Pembrolizumab (Keytruda) - 5 year survival outcomes

The KEYNOTE-001 study which administered Pembrolizumab (Keytruda) to melanoma patients with advanced disease and started back in 2011 has provided a great deal of data over the years.  Here are some of those reports:  KEYNOTE-001 reports over the years

Now there's this:

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001.   Hamid, Robert, Daud, Hodi,…, Wolchok,…, Weber,…, Ribas.  Ann Oncol. 2019 Jan 31.

Pembrolizumab demonstrated robust antitumor activity and safety in the phase 1b KEYNOTE-001 study (NCT01295827) of advanced melanoma. Five-year outcomes in all patients and treatment-naive patients are reported herein. Patients whose disease progressed following initial response and who received a second course of pembrolizumab were also analyzed.

Patients aged greater than/= to 18 years with previously treated or treatment-naive advanced/metastatic melanoma received pembrolizumab 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks until disease progression, intolerable toxicity, or patient/investigator decision to withdraw. Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated. Objective response rate and PFS were based on immune-related response criteria by investigator assessment (data cutoff, September 1, 2017).

KEYNOTE-001 enrolled 655 patients with melanoma; median follow-up was 55 months. Estimated 5-year OS was 34% in all patients and 41% in treatment-naive patients; median OS was 23.8 months and 38.6 months, respectively. Estimated 5-year PFS rates were 21% in all patients and 29% in treatment-naive patients; median PFS was 8.3 months and 16.9 months, respectively. Median response duration was not reached; 73% of all responses and 82% of treatment-naive responses were ongoing at data cutoff; the longest response was ongoing at 66 months. Four patients (all with prior response of complete response) whose disease progressed during observation subsequently received second-course pembrolizumab. One patient each achieved CR and partial response (after data cutoff). Treatment-related AEs (TRAEs) occurred in 86% of patients and resulted in study discontinuation in 7.8%; 17% experienced grade 3/4 TRAE.  This 5-year analysis of KEYNOTE-001 represents the longest follow-up for pembrolizumab to date and confirms the durable antitumor activity and tolerability of pembrolizumab in advanced melanoma.

Good news, especially back in 2011.  Good news regarding durability of response.  Good news regarding re-induction with a second course for those in need.  Still in need of treatments that garner a complete response in MORE melanoma peeps.  Thanks, ratties. - c

March FORTH ~ no matter the tempest that surrounds you...

We are here.  Together.  On my favorite day.  Lucky to be able to live and love and continue to March FORTH!!!  (Here's a retrospective/explanation with links and beauty within!)

Despite the ugly all too easily found in the world - across the globe and across the hall - we will MARCH FORTH!!!  Despite the hurt and injustices that dear ones experience all to often - we will MARCH FORTH!!!!  Despite the struggles with ill health, poor treatment, and lack of access that far too many experience - we will MARCH FORTH!!!  TODAY on this most hopeful of days, and all the others in between - WE WILL MARCH FORTH!!!!!!!!!!!!!!!

Marching through life is not easy.  Life doesn't roll that way.  But, no matter the tempest in your teapot, you are loved.  You are worthy.  You can - MARCH FORTH!!!  Knowing all the while, you will never March Forth alone.  ~ love, les