Sunday, August 28, 2016

Melanoma antigens in blood are prognostic of OS and correlated with response to ipi!

I've talked about biomarkers before.  Here's a post from earlier this year (with additional links within - including one to another study that found blood biomarkers associated with response to ipi):  Biomarkers - blood components, circulating tumor cells AND of the tumor itself 

A valid and specific blood draw that could help diagnose, determine the presence of a response to therapy, and be used as follow-up (instead of scans!) would be sooooooooooo  awesome!!!!  Now there's this:

Melanoma antigens are biomarkers for ipilimumab response.  Arenberger, Fialova, Gkalpakiotis, et al.  J Eur Acad Dermatol Venereol. 2016 Aug 24. 

Novel immunotherapy modalities significantly improve survival of patients with metastatic melanoma. However, CTLA-4-blocking monoclonal antibody ipilimumab is effective only in a small proportion of patients. Biomarkers for prediction of treatment response are indispensably needed.

To determine the utility of multimarker detection of circulating melanoma cells as prognostic and pharmacodynamic biomarker in patients with metastatic melanoma treated with ipilimumab.

Patients (n=62) with metastatic melanoma in unresectable stage III or metastatic stage IV treated with ipilimumab were recruited prospectively. The values of 4 melanoma markers on circulating cells Melan-A, gp100, MAGE-3 and MIA prior to the treatment and within the therapy were compared to the data collected at baseline - after the melanoma surgery.

The immunotherapy pretreatment marker level was found to be prognostic of overall survival, lower levels were linked to longer survival time. Moreover, longitudinal follow-up of melanoma markers in patients treated with ipilimumab correlates with therapy response. A decline of marker levels by greater than 30% at week 6 (in 83% of the responding subjects) to week 9 (in all responders) of ipilimumab administration was associated with response to therapy. Elevation of the tumor markers during the treatment precedes clinical progression and gives an early warning of treatment failure. 

Melanoma circulating cells hold potential as predictive and pharmacodynamic biomarker of immunotherapy.

Come on researchers.  Let's make this happen!  Soon!!! - c

Friday, August 26, 2016

Happy anniversary, baby.....


....got you on my ~ mind!!!  Twenty eight years????  OMG!!!!  Two kids, 4 dogs (6 if you count Lucy and Clown!), 2 apartments, 3 houses, lost count of cars and hamsters, buckets of tears, loads of laughter (Cause you know I'm funny!!!), 13 years of melanoma (Now, that's been fun!!!), a bazillion patients, dear friends, foreign lands, lots of 'Spranch', crazy travels, fun dinners, gardens of flowers....hmmmm....

Some weird doc I know, along with a real live radiologist, pronounced me melanoma free late yesterday.  So listen to this...I guess I'll die, another day!

I'm gonna wake up, yes and no
I'm gonna kiss some part of
I'm gonna keep this secret
I'm gonna close my body now
I guess I'll die another day
I guess I'll die another day

Sigmund Freud
Analyze this
Analyze this

I'm gonna break the cycle
I'm gonna shake up the system
I'm gonna destroy my ego
I'm gonna close my body now


I think I'll find another way
There's so much more to know
I guess I'll die another day
It's not my time to go
For every sin, I'll have to pay
A time to work, a time to play
I think I'll find another way

It's not my time to go!
~ Madonna ~ Die Another Day

Guess you're stuck with me a bit longer! Ready for 28 more?????? love, les

Thursday, August 25, 2016

Sentinel lymph node disection ~ "important diagnostic procedure and might be of therapeutic benefit re: DFS and OS!"



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.

Here is a post from 2013 with some articles discussing the odds of having a positive node:  With melanoma, you can never be too rich or too thin!

Here is a post from this year, with several links within, addressing risks for positive nodes in females specifically:  Women and melanoma risk

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!!!


Now there is this:
 
The impact of sentinel node dissection on disease-free and overall tumor-specific survival in melanoma patients: a single center group-matched analysis of 1,192 patients.  Geimer, Sattler, Flaig, et al.  J Eur Acad Dermatol Venereol. 2016 Aug 24.

Sentinel lymph node dissection (SLND) is considered a standard staging procedure providing important prognostic information on melanoma patients. It remains a matter of debate, whether SLND and hence removal of potential lymph node micrometastasis will alter survival outcome.

The aim of this group-matched analysis was to compare survival data of a large cohort of melanoma patients who were treated by wide local excision only (WLE) and nodal observation (WLE group) to a group of patients treated with WLE plus sentinel lymph node dissection (SLND group) to investigate the potential therapeutic benefit of SLND in the treatment of patients with melanoma.

A total of 596 consecutive patients who had undergone WLE plus SLND between 1996 and 2003 were assessed. As a historical control group 596 patients treated with WLE and nodal observation but without SLND between 1986 and 1995 were selected. The groups were matched according to sex, age, Breslow tumor thickness and localization of primary tumor. The adjuvant treatment and follow-up examinations were performed according to protocols of the German Dermatologic Cooperative Oncology Group (DeCOG) and applicable study protocols that our clinic participated in and hence subject to change over time.

Kaplan-Meier testing revealed significant differences in survival in favor of the SLND group. Mean overall tumor specific survival (OS) was 102.7 months in the SLND group vs. 97.0 months in the WLE group, respectively. Disease-free survival (DFS) and time to lymph node progression also differed significantly between the two groups.

SLND is not only an important diagnostic procedure, but might also be of therapeutic benefit in terms of disease-free and overall tumor-specific survival of melanoma patients.

See what I'm saying?  Nothing in melanoma is easy. Absolute therapeutic effect of SLND may not be that impressive, though still a positive in this study, but SLND seems rather essential for diagnostic purposes.  At least this part seems pretty clear to me.  Good luck to all of you and whatever you decide.  - les

Wednesday, August 24, 2016

Sooo....MRI for tomorrow....approved...just now!!!! This afternoon!


Have I mentioned how much I hate insurance companies?  Oh, yes.  I have.  But, really!!!   I HATE insurance companies!!!  As I mentioned previously....normal (except....NOT normal...cause all us melanoma brain and lung met peeps used to die in short order!!!), ANNUAL (Like...shouldn't we be celebrating?????) follow up CT's of neck, chest, abd and pelvis with MRI of brain were ordered by my oncologist.  MRI = DENIED...so decreed Michele Awobuluyi, MD of Blue Cross Blue Shield, cause after 5 years with my "Stage 2 to 4 skin disease" I don't need them any more, don't you know???!!!  Per the insurance demands, I saw my oncologist, BEFORE getting the scans.  A waste of my time and hers.  A waste of my copay.  A waste of BCBS money.  Because....until I get my scans, we don't really know what we are dealing with now do we?  My doc appealed Dr. Awobuluyi's decision.  DENIED!!!  So today....after my doc did a "peer to peer petition"  (Now, that's a joke isn't it?  Peer to peer?  Seriously?  Normal, average docs, with 2 brain cells would not categorize metastatic melanoma as "skin disease"!!!  So, my onc is no peer of Dr. Awobuluyi!!!) Finally - BCBS has, in all their wisdom, authorized the MRI of my brain.  This afternoon.  For an MRI scheduled for tomorrow!  Can you say A$$ HOLE$?????

Yet, I'm sure they think I should be ever so grateful. Sorry.  Rant over.  For now.  I am in a much luckier position than many.  #firstworldproblems.  Still....  Now you all know what I'll be doing tomorrow!!!!  Think I'm gonna just sit and look at my cute shirt for a minute while taking deep cleansing breaths!!!! - c

Sew Chaotically! - Vogue 1440 - such a cute top!!

Another sewing post...just for fun!!!  Here's the pattern.  I have to say...from looking at the directions and pieces...the jacket could easily turn into a hot mess...but the top...
...how cute it that back??????
Material...from who knows where and sadly when!  When she was little, I used to pick up anything "rosebud" for the Rose Bud...though clearly, this never made it into her wardrobe!!!  I was going to pair it with a pink I had, but the Brentster, with his incredible color skills picked this combo!  Awesome, right?
Hey, if you have a cute design....make it show up, right????

Made a size 12, just had to carve a bit off both side seams.  Didn't want to mess with the substantial darts running down the front!
Proud of my top stitching!!!!

Lurve it!!!  Happy day to you...even if it sneaks up on you from behind! - c

Tuesday, August 23, 2016

Anti PD-1 and Anti-PD-L1 treatments rarely confer durable remissions for metastatic uveal melanoma (and poor responses in acral and mucosal mel as well!)


As many of you know, I am frequently contacted by folks with melanoma (or those with peeps who are suffering) looking for answers, treatments, explanations.  I help as best I can.  In that capacity, I have discovered many who are facing more than just cutaneous melanoma and are gradually coming to realize that they or their loved one, is probably dealing with uveal, acral, or mucosal melanoma given the history, location, or results of testing.  Unfortunately, while we have made a great deal of progress since 2011 in the treatment of melanoma generally, these sub-types are notoriously unresponsive to the now conventional melanoma treatments.  For instance, this is a report out of ASCO this year: ASCO 2016: Anti-PD1 for acral and mucosal melanoma , where unfortunately it was demonstrated that rather than the more typical 40% response rate to anti-PD1 in treatment naive cutaneous melanoma, folks with acral melanoma had only a 32% ORR, while folks with mucosal attained only a 23% ORR....albeit these peeps were heavily pre-treated and perhaps that contributed to the lower response rates as well.
  
Additionally, these types of melanoma are less likely to be BRAF positive, removing yet another treatment option from their arsenal.  Here's data from a discussion between two melanoma specialists:  Pick your poison: Weber and Agarwala discuss combination therapy for melanoma
Here they note the following expected mutation rates -
Mucosal = 9% BRAF, 12% NRAS, 25% KIT
Acral = 22% BRAF, 16% NRAS, 24% KIT

The disconcerting aspect for me has been this response, "Oh, no.  We aren't [or - the doc isn't] calling it that! If that happened, she wouldn't be eligible for the trial!!"  I can hear the fear and desperation in their voice.  I really do understand!  I spent many years, even as a Stage IV patient, in melanoma land BEFORE the FDA approval of the BRAF inhibitors, anti-PD1, or ipi. I fully recognize the desperation and search for an effective treatment.   However, when you are allowed placement into a trial or treatment that we now KNOW provides little to no benefit for your particular mutation....what has been accomplished?  To my mind, time has been wasted, suffering continues, while other possibly more effective options go untapped.  Some Melanoma Big Dogs recently came together in this report regarding uveal melanoma response rates to anti-PD1 and anti-PDL1:

Clinical outcomes in metastatic uveal melanoma treated with PD-1 and PD-1L antibodies.  Algazi, Tsai, Shoushtari, ... Daud, Sosman, Carvajal, Chmielowski, Postow, Weber, et al.  Cancer. 2016 Aug 17.

Antibodies inhibiting the programmed death receptor 1 (PD-1) have demonstrated significant activity in the treatment of advanced cutaneous melanoma. The efficacy and safety of PD-1 blockade in patients with uveal melanoma has not been well characterized.  Fifty-eight patients with stage IV uveal melanoma received PD-1 or PD-1 ligand (PD-L1) antibodies between 2009 and 2015 at 9 academic centers. Patients who were evaluable for response were eligible for the analysis. Imaging was performed every 12 weeks and at the investigators' discretion. Safety and clinical efficacy outcomes, including the best overall response, progression-free survival (PFS), and overall survival (OS), were retrospectively determined.  Of 56 eligible patients, 48 (86%) had received prior therapy, and 35 (63%) had received treatment with ipilimumab. Three patients had an objective response to ipilimumab, and 8 had stable disease as their best response. Thirty-eight patients (68%) received pembrolizumab, 16 (29%) received nivolumab, and 2 (4%) received atezolizumab. Objective tumor responses were observed in 2 patients for an overall response rate of 3.6%. Stable disease (greater or = to 6 months) was observed in 5 patients (9%). The median PFS was 2.6 months, and the median OS was 7.6 months. There was no association between prior treatment with ipilimumab or liver-directed therapy and PFS or OS. Treatment was well tolerated, and only 1 patient discontinued treatment because of toxicity.  PD-1 and PD-L1 antibodies rarely confer durable remissions in patients with metastatic uveal melanoma. Clinical trial enrollment should be prioritized in this population.

A sad acknowledgement to be sure.  These response and OS rates are really no different than those I was facing prior to the existence anti-PD1!  Frustrating and powerless do not begin to cover the feelings that this data engenders!!!  However, it is something I would want to know, if I were dealing with uveal melanoma.  For what it's worth.... - c

Saturday, August 20, 2016

Titanium....

Rough day....rough week.  More for others than myself. Just when I think it is too much....I know....I am titanium...

Sia/David Guetta - Titanium

You shout it out,
But I can't hear a word you say
I'm talking loud, not saying much
I'm criticized but all your bullets ricochet
Shoot me down, but I get up

I'm bulletproof, nothing to lose
Fire away, fire away
Ricochet, you take your aim
Fire away, fire away
You shoot me down but I won't fall
I am titanium
You shoot me down but I won't fall
I am titanium

Cut me down
But it's you who'll have further to fall
Ghost town and haunted love
Raise your voice, sticks and stones may break my bones
I'm talking loud not saying much

I'm bulletproof, nothing to lose
Fire away, fire away
Ricochet, you take your aim
Fire away, fire away
You shoot me down but I won't fall
I am titanium
You shoot me down but I won't fall
I am titanium
I am titanium
I am titanium

Stone-heart, machine gun
Firing at the ones who run
Stone heart loves bulletproof glass

You shoot me down but I won't fall
I am titanium
You shoot me down but I won't fall
I am titanium
You shoot me down but I won't fall
I am titanium
You shoot me down but I won't fall
I am titanium
I am titanium                        ~ David Guetta


...and so are you.  Love, c