Saturday, January 30, 2016

Sew Chaotically! - or - Chaotic Crochet Christmas surprise!!!

Now that all crocheted projects have been distributed to their proper owners, I can show you my Chaotic Crochet Projects!!!  Soft woody greens for Dan.

Autumnal reds and oranges for Roo.

Bundled up and ready to go!

Darker greens and browns for Carla.

With a pillow for fun.

Bright purples and golds for Irina.

Ta'dah!!!  It was fun.
Hope all my peeps will stay cozy and warm this winter!!!  Much love, c

Wednesday, January 27, 2016

Sew Chaotically! - Just say NO!!! To advice on sewing prep from Singer 1949!

My friend Connie sent me this, asking (tongue in cheek) if this was indeed how I prepped for a sewing session.  I feel confident you all know the answer to that one!!!!  French chalk????  We've come a long way, baby!!!  Thank goodness.  Now lets move forward a bit more!  You know?  Equal pay for equal work ~ just for grins and giggles!  Let's go girls...and boys!  love, c

Sunday, January 24, 2016

Nivo/Opdivo now first line for ALL melanoma patients! BRAF positive or negative! Alone or with ipi!


FDA expands Nivolumab as first line for V600 BRAF positive patients!

In 2014, Nivo was FDA approved for use in advanced melanoma after patients had failed ipi and if BRAF positive, the BRAF inhibitors as well. In November of 2015, it gained additional approval for use as a first line drug for melanoma patients!!  BUT only if you were BRAF V600 wild type!!!!  This, in spite of numerous studies demonstrating that the response to anti-PD1 (Nivo or Pembro, actually) was the same no matter BRAF status! Here's a link with the history of Nivo/Opdivo approvals!

Now!  Check out the link at the very top. FINALLY! In all its wisdom, the FDA has recognized the results of the Checkmate-067 study in which patients treated with the nivo/ipi combo had "a reduced risk of progression by 58% compared with ipi alone in patients with advanced melanoma" while nivo alone "reduced risk of progression by 43% vs ipi" and whose outcomes for Nivo's use as a single agent or in combination with ipi were similar NO MATTER the patient's BRAF status.

Basics of the study:  945 untreated unresectable melanoma patients.  They were treated with:  Nivo 3mg/kg q 2 wks (n=316).  Ipi 3mg/kg every 3 wks (315). Ipi/nivo combo with nivo at 1mg/kg with ipi at 3mg/kg every three wks for 4 doses followed by nivo at 3mg/kg alone q2wks (314).

At 9 months:  Median PFS = 11.5 mo for combo, 6.9 mo for nivo, 2.9 mo for ipi.

PD-L1 positive patients  - PFS of 14 mo for both nivo arms vs 3.9 mo with ipi only.
PD-L1 negative patients - combo was better than single agent - with PFS of 11.2 mo with combo vs 5.2 mo with nivo alone and 2.8 mo with ipi alone.

Overall response rate:  50% with combo.  40% for nivo alone.  14% for ipi alone.
Complete response rate:  8.9% for combo. 8.5% for nivo alone.  1.9% for ipi alone.
BRAF mutant melanoma:  For combo median PFS = 11.7 months.  For nivo alone PFS = 5.6 mo.  For ipi PFS = 4 months.
BRAF wild-type:  For combo median PFS = 11.2 months.  For nivo alone PFS = 7.9 mo.  For ipi PFS = 2.8 months.

Most common side effects were the usual players:  diarrhea, colitis, increased lipase and ALT/AST levels....all to a greater extent with the combo.

Then today in the UK  there was this: Opdivo approved for advanced melanoma in England and Wales (although it is still not approved for NSC lung cancer there, yet).

About bloody time!!!!  NOW!!!!  Let's get some more approvals for Stage III/IV NED folks, shall we?????
Big thanks to Eric for finding and sharing!!  He beat B on this one!!!  - c

Saturday, January 23, 2016

Sew Chaotically! - Lisette B6244 Blanket Coat


Here we go!!!  Click here for a great sew-along!  There's some pretty good info at the start, then just scroll down until you get to the section titled 'Join Us' and click the link "here".  This takes you to a page with various comments.  Below that is a nice step-by-step instruction guide!  I found this pattern review very helpful as well:  Girls in the Garden: Butterick 6244 coat 
Some basic stitching info:  This pattern uses flat felled seams which were a new skill for me...  After a napkin lesson from Ruthie and a peek around the internet... here's a good flat felled seam tutorial, I practiced on scraps of my fabric until I was comfortable with the process.  It's really not difficult and looks very neat and professional.  I did have to adjust my tension a little and moving the needle over one or two clicks and increasing stitch length did improve the look.  This coat also requires a folded hem, that needs to look really neat, given its exposure (back and front) around the entire circumference of the coat.  Lori's suggestion from her review on her blog, Girls in the Garden, (above) was very much worth it!!  "The Lisette sewalong, suggests for the hemming to baste a 5/8" line to help keep an accurate hem.  I did this on the front, hem and sleeve hem but also added a 1/4" stitch line.  I felt that made it even more accurate to turn under 1/4" and then again at that 5/8" mark." 

Beautiful burgundy double faced wool B found from Jo Ann's. Great note holder to keep my stitching recipe straight for my seams and hems, from my friend Connie, handily placed!  Bernie set!  Ipad with sew-a-long at the ready.  Liquid reinforcement. (Hey!  The tutorial even recommends a glass!) Practice complete. No more excuses!  Do have to tell you...that while the sew-a-long indicates folks will be worried about putting in a couple of darts at the start....  They are no problem.  However, the next step of attaching the "collar" made me a nervous wreck!!!  It works.  I managed it with no puckers or re-do's. (You can see it in the pic below to the left of the sleeve.) But, it was the most difficult part of the whole thing!

When folks review a pattern and say it's great but they added this and didn't do that....it tends to get on my nerves!!!  Did you actually make this pattern or didn't you?  So...here I go!!!  Telling you what I did differently!!!  Oh, well....  I did not stitch up my sleeves and the sides of the coat and THEN install the sleeves as the pattern directed.  The sew-a-long even mentioned that there was a lot of ease to deal with and some of the coats folks displayed on-line had a fair amount of unintended puckers in their sleeve caps.  I did NOT want puffed sleeves on an already voluminous blanket coat if I could help it!!!  So...despite my trepidation never having placed sleeves this way before....I installed my sleeves using a flat method.  I also used Ruthie's tip of ease stitching along almost all of the sleeve-cap rather than just in the little section of the cap indicated, so I had more room to maneuver.  The sleeve went in easy-peasy!! I also serged the long edges of my sleeves, so they would be neatly finished, before I even started.  (The pattern called for the long seam to be flat felled!  Lovely, if accomplished, to be sure.  But lots of sewists noted the understandable difficulty of this and I decided not to risk mucking up my fabric, my psyche, or my sleeve!!!)

After the sleeve was stitched in place, with edges trimmed and finished (I just used my machine's zig-zag since I have better control with that over my serger.) I stitched together side seams and sleeve in one long seam.

So incredibly pleased!!! Not one puffy pucker!!!


Nicely fitted behind!

Pretty draped front!

Why double faced fabric and neat hemming is important as the coat shows both!!!

Dressed up!

And down!
 
And, yes!  There was snow!


      On the photog, at least!!!  Thanks, B!  I just love my coat.  I am SEW proud of it!!  Sew Chaotically! - c       

Wednesday, January 20, 2016

BRAFi as neoadjuvant - Now we're talk'n!!!


BRAF inhibition for advanced locoregional BRAF V600E mutant melanoma:  a potential neoadjuvant strategy.  Sloot, Zager, Kedchadkar...Weber, Sondak, Gibney.  Melanoma Res. 2/2016.

"Selective BRAF inhibitors (BRAFi) yield objective responses in 50% of patients with metastatic BRAF V600E mutant melanoma. Adding an MEK inhibitor increases this response rate to 70%. Limited data are available on the outcomes of unresectable stage III patients, and it remains unclear whether BRAF-targeted therapy can be utilized as a neoadjuvant strategy. Data on patients with advanced locoregional BRAF V600E mutant melanoma treated with BRAF-targeted therapy at Moffitt Cancer Center were analyzed to determine response rates, subsequent resection rates after tumor downsizing, pathologic responses, and patient survival. Fifteen patients with locoregional disease treated with BRAF-targeted therapy, either BRAFi alone (vemurafenib; 11 patients) or a combination of BRAFi and an MEK inhibitor (dabrafenib plus trametinib or placebo; four patients), were identified. The median age was 50 years; the median follow-up was 25.4 months. The median BRAF-targeted therapy treatment duration was 6.0 months. Response Evaluation Criteria In Solid Tumors-based evaluation demonstrated objective response in 11 patients (73.3%). Six patients underwent resection of the remaining disease after therapy. Pathological analysis showed complete pathologic response (n=2), partial pathologic response (n=2), or no pathologic response (n=2). Four of six patients undergoing surgery have been alive for more than 2 years, including three patients currently free from active disease. No complications attributable to BRAF-targeted therapy were observed in the perioperative period. Dose reduction or discontinuation because of toxicities occurred in 10/15 patients. Neoadjuvant BRAF-targeted therapy may be effective in advanced locoregional BRAF V600E mutant melanoma patients in increasing resectability, yielding pathological responses, and achieving prolonged survival."

Adjuvant treatment provides positive benefits!  Here's more adjuvant trial results:  From my NED nivo/Opdivo trial as well as one with ipi!

Here are a few amazing quotes:  

 From the Nivo trial (published Dec 2014!!!) ~ "Our data suggest that nivo is clinically active in resected stage IIIC/IV melanoma, based on low rate of relapse (10 of 33), impressive relapse-free survival - estimated RFS of 47.1 months, and median overall survival not yet reached with over 32 months of follow up."

And this from the ipi ~ "Adjuvant ipi significantly improved recurrence-free survival for patients with completely resected high-risk stage III melanoma."

What are we waiting on???  Come on researchers!  FDA?!!!  Drug companies????!!!!  Hang in there, Ratties.  You rock! - c 

Monday, January 18, 2016

Adjuvant treatment in melanoma: Limited options....still

With many on the boards worried, and others contacting me via email, about adjuvant treatment options for NED Stage III/IV melanoma, where despite the relatively recent and fairly numerous FDA approved treatment options, adjuvant treatments remain few and far between.....I remembered that I had worked on this post several months ago:

Adjuvant care for melanoma patients with no evidence of disease, no matter if you are talking about node biopsy, complete lymph node dissection, or treatment with current melanoma therapies, is very tricky.  It is easy to provide "treatment X" to a patient with measurable tumor burden, repeat scans looking to see what happened to their tumor after the treatment and write that down.  When the person has nothing to measure at the start, seeing how "treatment X" affects them takes time.  Sometimes....if the patient is lucky....a very long time.  Humans, drug companies, docs - don't like waiting a long time.  But that's the deal.

In a 2014 op ed written about whether to do sentinel lymph node biopsy:  sentinel lymph node biopsy in melanoma are we sufficiently informed...
(Though to me, the real elephant in the room regarding SLNB is - if you don't do it...you may not realize that you are walking around with melanoma growing in a lymph node!!!!  Just say'n!!)  ...the article talks about some of the relevant data, but the most important line to me is this: "The introduction of active drugs for metastatic disease (BRAF inhibitors and check-point blockers) provides hope that effective adjuvant therapies for SLN+ patients will be identified in the near future; however, until that time..." 

Yep....exactly that.  And that time should be getting ever closer.  My fellow ratties and I started our NED arm of a Nivo (Opdivo)/vaccine trial in 2010.  But....you have to wait and see what happens to us.  Will we all progress in the end?  Will more of us FAIL to progress than our statistical histories would indicate???  (So far...YES!!!!  Many more of us are alive and well than the data shows we otherwise would be!!!)  The same waiting game must be played for the Pembro, Ipi/nivo, and BRAFi trials and even surgical procedures that are also now ongoing for NED/Stage IV/Stage III patients (though most are not currently accruing patients).

There is a good deal of data showing that all of these treatments help Stage III/IV patients prevent disease progression in melanoma. Especially for surgery...as "cherry picking" (ie surgical removal of lesions as they crop up) for melanoma has been going on the longest and has worked for many. But....can anybody tell you for certain treatment 'x' will work for YOU? Or me?  Sadly, no.

Another huge factor when providers treat ANYBODY for ANY disease is cost vs benefit.  I am not referring to monetary issues (though sometimes, unfortunately, that figures in as well).  I am talking about side effects of the process vs positive effects on the patient's disease.  All the things I've listed as treatments above come with risk and side effects.  Is that a risk worth taking if you are Stage III?  Maybe.  Maybe not.  Until very recently, that was a big reason why these adjuvant therapies were offered only to Stage IV patients.  However, researchers are feeling better about the good and valuable effect these treatments are having on Stage IV patients with disease and otherwise, so they have decided it is at least worth testing in Stage III patients.  But...that is the rub.  Side effects vs value.  Ribas and Weber discussed this specifically in regard to the ipi/nivo combo.  Whether you are a patient with measurable disease or not....this combo treatment has some of the best response rates going...but also has a good number of side effects likely.  Risk vs benefit.
Here is a post that addresses a lot of this....including the results (now published) of my NED trial:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2015/04/ipi-vs-nivo-trial-as-adjuvant-for-stage.html

But...no.  No one can tell me that because I did 2 1/2 years of Nivo/Opdivo and have had surgical removal as well as SRS to melanoma tumors I will remain melanoma free.  I cannot tell you what would be best for you.  However, for me....as someone who was 7 years out from their first melanoma primary, despite sentinel node biopsy, bilateral axillary lymphadenectomies (no lymphadema still, by the way) and STILL progressed to Stage IV with melanoma tumors in my lung, brain and tonsil....all in rapid succession in a 6 month period, I knew I had to do SOMETHING!  I had brain zapped, lung and tonsil lesions surgically removed.  Completed my nivo trial.  I have had no disease recur since 2010.  Will that hold?  Don't know.  Would I do EVERY bit again?  Yep...pretty sure what I did initially gave me my disease free interval....and the nivo has kept me here today.  I'll just have to see what happens to me tomorrow and deal with whatever that may be as best I can.

Perhaps the coming  DNA/RNA blood testing for tumor markers (These will happen!  I promise!  Hopefully, sooner rather than later!!!) will help not only clarify what treatment will work best for whom, but treatment response as well...even at early stages...even when ostensibly NED.  Ratties are awesome. Lack of adjuvant care is unacceptable to me!!!  Hang in there! - c

Friday, January 15, 2016

Sew Chaotically! - Plaid A-line skirt, M3341


I made this plaid skirt and vest for Rosie a couple of months ago and now it was time to make mine!!!  Using the same M3341 A-line skirt pattern and same type of fabric, a plush 100% cotton that looks like wool and feels so very soft, from Jo-Ann's - by the second time around I had learned a few things.  However, this fabric piece too, was a little stretched out of shape.  Since I am very familiar with sewing the pattern generally, my personal challenge was to do better with my print matching.  I guess it is mostly common sense, but here is a tutorial I found that was really helpful:  Sewaholic - How to match prints along seams

And we're off:
Happy with print placement here!  Though you can see how the plaid wants to "drift".  But...you can't see my darts!!!
Super happy with both side seams!!!  I cut carefully using info from the tutorial and then hand basted the seams before machine stitching.

This is my only source of sadness.  Since I install zippers by stitching the entire seam (using a large stitch in the area for the zipper and regular stitch for the rest of the seam) I basted and then sewed it together just as I did for the side seams.  It was perfect!!!  However, when I actually sewed in the zipper (even though I had basted it in place) the fabric stretched out a bit (See the bottom right area of the zipper?) and lost some of my perfection!!!!  Ha!!  This would probably have been the proper occasion to use a bit of seam stabilizer along the seam in the area of the zipper before installing it as this fabric is so soft.  Oh, well.  Live and learn.  I could have taken it out and tried again, but I figured nobody was going to be looking that closely at my bootie and once this fabric is stretched, I don't think there's any going back!!!


Anyhow, I love this skirt.  It is cozy and pretty and I feel I met my personal challenge of trying to either learn a new skill or perfect an existing one with each garment I make.  It was fun! Although with all the viewing of tutorials and hand stitching...B was getting suspicious that I was simply procrastinating in order to delay cutting into this behemoth!!!  

Double faced wool...the most expensive material I have dealt with so far!!!

Lions, tigers, and bears!  Oh, my!!!

Sew Chaotically!!! - love, c

Wednesday, January 13, 2016

The Problem with Clinical Trials


While the clinical trial I participated in probably saved my life, the truth remains that clinical trials are very poorly run often using drugs known to be ineffective as benchmarks, costly to PATIENTS (in time, treasure, and lives at risk), fail to focus on the individual, lack transparency, frequently apply results in a rigid, pseudo-scientific manner by drug companies and the FDA alike, and the role of the NIH produces more questions than answers.  Opdivo's latest approval is one more example of both the wonder and sad realities of FDA approvals and Big Pharma.

Clinical trials are designed to answer questions about the effectiveness and safety of drugs.  However, trials...set up by medical researchers, institutions, and pharma....utilize rigid old-school statistical methodology that fails to allow a comprehensive look at data from multiple trials and more often than not, pits older, clearly ineffective drugs against new, obviously superior ones.  Rarely are top shelf drugs placed one against the other.  In melanoma world, interferon and dacarbazine have been the benchmarks against which everything from ipi to anti-PD1 to BRAF inhibitors have been placed.  Why?  In very preliminary testing all three of those drugs/categories were superior by miles.  This approach wastes time.  Time in which real people suffer and die.  Meanwhile, the FDA takes clinical trial design as a literal reflection of the real world.  Obviously, it is not.  And all of this begs the question:  Who are these trials designed to help?  Patients?  Or Big Pharma?

For instance, in the latest Opdivo approval, only patients with BRAF wild type mutation can utilize the drug as a first line option.  Folks with BRAF positive lesions are still relegated to trying ipi and failing, then BRAF inhibitors and failing, before advancing to Opdivo.  Why?  Multiple studies clearly demonstrate equal effectiveness of the anti-PD1 drugs no matter BRAF status.  But, the FDA's commitment to basing approvals entirely upon the trial at hand dictates this "logic".  The trial upon which this approval was based used only BRAF wild type patients...so that is how Opdivo was approved.  All other concomitant trial results be damned.  So?  Does pharma set trials up this way so that older drugs must continue to be used?  So that coin for those treatments can continue to fill their coffers?  Now, will docs allow their patients to suffer through greater side effects and a decreased rate of success by prescribing ipi first, rather than trying one of the anti-PD1 products?  Will insurance companies prefer to pay for a drug that helps fewer patients and causes more complications that they will also have to put out money to take care of, only to have to pay for the NEXT drug as well?  Time will tell.

The FDA's tunnel vision and literal interpretation of singular trial data one by one is the equivalent of this scenario:  Say a trial for a new drug to treat fractures is set up so that it allocates patients with left arm fractures to the test drug and those with a right arm fracture to an old one.  Miraculously, the folks given the new drug for their left arms were healed within days while those with right arm fractures derived no benefit from their drug.   The FDA approval comes out as:  This amazing fracture drug is now available!!!  BUT....only for folks with fractures to their left arms!  Pretty silly, right?  Yet, that is the system we currently embrace.  Obviously, when only one type of trial or circumstance of use is available for a drug in question, that is the way it should be approved.  However, when other data exists and common sense dictates what is good for the left arm is also good for the right, that information should figure into FDA approvals.  To do otherwise makes trial development look as though it was designed for niche marketing rather than improved patient health.  An argument can easily be made that the primary focus of clinical trials and FDA approvals seems to be to produce proprietary treatments for big profits rather than a cooperative effort to help as many individuals as possible.

Then we have the poor little rich pharma companies, complaining of, yet endlessly touting, their exorbitant research and development costs.  First of all, the figures touted are much inflated.  Numerous studies, including one recently out from Doctors Without Borders, dispute and provide clear evidence against Big Pharma's numbers.  Secondly, ratties (and their insurance companies) pay for much of the research.  Clinical trials are not free!!!  I paid for everything from scans to needles to tubing to lab to doctor visits to transportation to institutional charges for bed space and nursing services.  BMS provided the drug and a few "research labs"....period. Thirdly, Big Pharma receives federal support in the form of research grants from NIH that provide the nidus of basic discoveries.  And guess who pays for that?  YOU!!!  The taxpayer.  And fourth, Big Pharma makes humongous profits...billions of dollars.  Do wall street reports talk about major pharmaceutical companies operating in the red?  NO!!!  They report financial gains and incredible mergers like the recent purchase of  Allergan by Pfizer for 160 BILLION dollars!!!  See what I'm saying?????

In order to be of real benefit and utilized by science for the good of all, it is essential that data and information gleaned from clinical trials be transparent at all levels.  Patients need, deserve and have a right to their OWN information.  All clinical trial information should be readily available to all trial participants.  However, this is not how it works.  Doctors withhold information to protect themselves and sometimes under the erroneous assumption that they are protecting the patient. Pharma withholds information because they think they OWN it.  I have never been told, nor have any of the other ratties in my trial, the results of our PD-L1 testing.  This is important stuff.  The rattie needs to know anything that is learned about them.  It may impact later treatment options or choices they make. The data needs to be readily available for other researchers, too - even if they work for different organizations.  A different set of eyes may find patterns and trends not apparent to the initial investigators, thereby elevating what is 'known' to a new level.  Even failed or negative study results need to be available.  People died for it.  Think of the data you have learned in your own life experience.  I know I certainly learned as much from my failures as I did from my successes!!!  Yet, almost 50% of cancer trial data goes unpublished!!!  Here's a link to that report:  Almost 50% of results are NOT published - 2013
 
So, why is everything a secret? Trial information is proprietary so that Big Pharma can protect their market share and inflate their bottom line or the drug price.  It is proprietary in order for researchers and their institutions to protect future patent rights, potential material gains, both financial and in PR.  It is proprietary to produce big profits, promote careers, and effectively block cooperative efforts that would ultimately help as many individuals as possible at the least cost....in dollars as well as suffering.

The monolithic system in which current clinical trials operate, under the banner of "safety and science" while more often seeming to advance proprietary products for profits, needs to give way to the humanitarian system of creative thought, mutual aid, transparency, and the commitment to the individuals affected - each and every one.  Many will still suffer.  Some will die.  But in an open system, where reasonable drugs are used as comparators, ALL data is available for ALL to see (the good, the bad and the ugly) all of us....researchers, institutions, Big Pharma, and Ratties... will be doing their best for each other.

Wishing you all my best, Les....Rattie, Mom, sister, friend, Pediatric Provider, researcher, and Melanoma survivor for almost 13 years with great help from my dearest love and coauthor - B....Daddy, care giver, friend, Pediatrician, linguist, researcher.....with a combined 71 years between us, spent in the care of children and their families.

Sunday, January 10, 2016

Sew Chaotically! - Skirts - A-line and pencil!

 From whence the scraps for the last Rosie skirt cometh:


Good 'ol M3341 A-line!  What can I say?  Super easy and fits well.
Ditto!  M3830 pencil.


Not the most exciting wardrobe/sewist additions...but needed and now I have two perfect fitting, tried and true basics!  Leaving room for more excitement to come! Sew chaotically!!! - c

Saturday, January 9, 2016

Auditory light and happiness for a drizzly, January day ~ Mariachi Flor De Toloache!!!


They are the cutest mariachi band ever!  No they're jazz/blues club singers with harmonies better than Destiny's Child!  No they are playing flamenco - including a horn on a par with the brass in Gloria Estefan's band, The Miami Sound Machine. Wait it's swing!  No mariachi!  Did I mention....ALL girls?????  And they are awesome?????  Give them a listen!!!

Mariachi Flor De Toloache ~ by way of the NPR Tiny Desk Concert Series

May they brighten your day!  Thanks Bentie for finding and sharing!  - c

Thursday, January 7, 2016

BRAFi after BRAF inhibitors...Can you still gain a response?


In this post, see the second article noted:  BRAFi, What predicts resistance?
Researcher, Tolk et al., report that in those patients who recurred after initial remission in response to BRAFi, upon retreatment with BRAFi those patients experienced a 50% chance of regaining remission.  Along the same lines....another group of researchers offer this:

BRAF inhibitor rechallenge in patients with advanced BRAF V600-mutant melanoma.  Roux, Pages, Malouf, et al.  Melanoma Rex.  2015 Sep 22.

"In around 50% of melanomas, the BRAF V600 mutation, resulting in activation of the MAP kinase pathway, is detected.  BRAF inhibitors have shown remarkable activity on the disease.  However, efficacy is short-lived in most cases, with a median disease-free survival of 6 months.  This short duration of response could be explained by the acquisition of resistance mechanisms.  Some cancers show sensitivity to the reintroduction of previously active drugs after disease progression.  We carried out a retrospective monocentric study on patients with BRAF V600-mutated melanoma who were re-challenged with BRAFi that were previously beneficial, but in whom the disease had progressed.  9 patients were included.  5 patients showed a subsequent partial response, 2 showed a dissociated response leading to clinical improvement, and 2 showed no radiological nor clinical response.  8 patients who had received re-challenge BRAFi had received an intercurrent treatment with ipilimumab.  These cases suggest that intermittent treatment with BRAFi could provide clinical benefit and that sequential therapies should be further evaluated in clinical trials."

Well, not too much beneficial info here....other than the fact that in these 9 patients....7 did gain at least some response from their BRAFi re-challenge.  The implication of response after treatment with ipi is not made clear since we are not told which patients did what (though that info may be present in the complete article).  This post from 2014 offers several articles:  Data on BRAFi combos and effects of ipi before and after  , where in the last study, the only conclusion I could draw was this:  
"... for all their numbers, there was apparently no statistical difference in response whether you took BRAFi followed by ipi or vice versa."

Still with much to learn it seems!!!  Hang in there, ratties! - c

Monday, January 4, 2016

Part 2 ~ Ratties and Hope!


As Jeanne noted, Roo shared, when "I tried to write a book about cancer, I ended up writing about dragonflies.  According to legend, the last thing that came out of Pandora's box was hope in the shape of a dragonfly".


 Hope flies on  dragonfly wings.
                 Thin glitter
     whisked with the breeze.
                         Such a tiny, delicate song.

The trumpeting of the heart is so very loud.
                   Garish.
              Grating the soft meadows
                       with harsh hot and cold.

Together, the soft and the weak,
                   the proud and the overpowering,
can make such a melody
          to soothe
                 the sadness
          that lingers in our
                 tired,
                        tired hands.                                   ~  C. Rose Morris

Then....this Christmas...thanks to the combined efforts of B and Roo...there was this:
Who would make such a T-shirt?  Ratties AND dragonflies????!!!!  What the tub?  How did they ever find such a thing?????

So it has been.  The dragonfly still came with all the hurt and ills that Pandora's box released.  But, she did bring hope...in some fashion...all the same. 


Then, against all odds....there are the Ratties.  Definition previously established as: Rattie (per the Les Lexicon) - noun; humans who participate in often demeaning and difficult clinical trials out of desperation and hope...so named mostly because of my love of The Rats of N.I.M.H., by Robert O'Brien.)
And while this particular rattie seems to be holding out for something better...most of us grab whatever chance is offered.  I know I did.  I am hoping that pickings will not be so slim for ratties of the future.  Never has a group of individuals inspired me more.  I will be forever thankful for those who allowed me hope.  And for all my peeps who let me be me...even if it is a little...shall we say...out there!!!
Happy 2016.  May the dragonflies (and ratties) light your way. - c

Saturday, January 2, 2016

Part 1 ~ Immunotherapy....The Original Super Heroes and Ratties!!!!


You needn't have looked at this blog very long to recognize my penchant for Super Heroes and Ratties. (According to the Les Lexicon:  Rattie - noun; humans who participate in often demeaning and difficult clinical trials out of desperation and hope...so named mostly because of my love of The Rats of N.I.M.H., by Robert O'Brien.) There was this...after all:  The Melanoma Avengers

But now, with thanks to NPR and Rebecca Davis...as well as the research of Dr. David Levine, director of archives at the Hospital for Special Surgery in New York, we have the details of the real Super Heroes and Ratties who brought us the first inkling of the power of immunotherapy.  (My synopsis follows...)  npr.org: Cutting edge cancer treatment has its roots in 19th century medicine

In 1890, Dr. William Coley examined a new patient, 17 year old "Bessie" Elizabeth Dashiell, whose complaint was a small painful lump to her hand.  Despite thinking it was nothing more than a simple infection, Coley took a biopsy.  He found malignant sarcoma.  In those days, before radiation or chemo, Coley did all he could.  He amputated Bessie's right arm below the elbow.  Within a month tumors had spread to Bessie's vital organs and all over her body.  She died a painful death January 23, 1891...just months after her first visit with Dr. Coley.

The rapid decline and loss of his young, healthy patient made a huge impression on Coley.  He started searching through hospital records - looking for some clue that could provide greater understanding - while thinking back on his early lessons from the work of Charles Darwin.  "Pay attention when there is biological exception." Coley found that exception.  A German immigrant, Fred Stein, had been a patient 8 years prior with a persistent neck tumor that doctors had attempted to remove repeatedly with no success.  He was expected to die of his disease.  However, after his last surgery, he was stricken with a skin infection due to strep.  It appeared that this would certainly be his end.

It wasn't.  Not only did he survive his life threatening infection - his tumor disappeared!!

In 1891, Coley began a search of the Lower East Side of Manhattan.  Could Fred still be alive?  After weeks of searching, Coley found Fred Stein - alive and cancer free - with a distinctive scar to his neck.

What had happened? Coley postulated that the strep infection had somehow reversed Stein's cancer.  Coley tried purposefully giving infections to an Italian immigrant, Zola, who had sarcoma like Bessie, but was so advanced that there were tumors in his throat....such that he could hardly breathe or swallow...and death was imminent.  For months Coley attempted to give Zola an infection by rubbing superficial cuts with bacteria.  There would be minor effects in his tumors, but nothing impressive.  Coley attained a more virulent bacterial sample.  He succeeded in making Zola violently ill.  While the infection itself could have killed him, in 24 hours Zola's "orange sized tumor began to liquefy and disintegrate".  He went on to a full recovery...from both his sepsis and cancer!

Coley continued his work, experiencing much success, but the American medical establishment remained skeptical.  No one knew how "Coley's Toxins" worked - why they worked sometimes and not others - not even Coley.

The immune system, with its T-cells, checks and balances, obscure pathways....was much more of a mystery then than now.  With the advent of radiation therapy in the early 1900's, Coley's Toxins were pushed into the shadows and upon his death were no longer pursued at all.

Had his daughter, Helen Coley Nauts, not looked through his papers after her father's death, finding 1,000 files of patients her father had treated with toxins, his brilliant, intuitive work may have died with him.  She sought experts to study her father's work.  Finding none, she decided to do it herself.  After years of analyzing the cases, she knew her dad had been on to something.  In 1953 she started the Cancer Research Institute.

In the 125 years since Coley first met Bessie, the study of the immune system has unlocked many mysteries related to infection, allergy, immune related disease, and cancer.  Treatments like ipi and anti-PD1 actually harness the power of our own immune systems to fight cancers as disparate as that of the stomach, lung, kidney, leukemia and melanoma.

There is still much that we do not understand, but without Super Heroes Coley, his daughter and his Ratties - it is hard to imagine that I would still be here today.  More to come.  Stay tuned. - c