Living Chaotically ~ Refashion #3 ~ (albeit a couple of months ago!!!!)

While other sewists are doing some amazing things refashioning previously made garments into useful, beautiful pieces,  (Check out this incredible remake in which Sasha converted pants into lovely,  heart warming, wearable art: THE REFASHIONERS! / Burda 110-06.2017) I continued my utilitarian efforts to refurbish and refashion around the house this summer.  My last project involved outdoor light fixtures!  After hanging around for 20 years, they were peeling, sad, and dirty!  In need of a little refashion...or refurbishment...to say the least!

All told there were 4 to deal with.

B took them down for me.  Then, I attacked with sandpaper, wire brushes, screw drivers, and other improvised scraping devices, to remove all the debris and loose paint.

Do not ask me how, in 20 years I failed to notice how different and how much BIGGER the two fixtures at the front door were compared to the rest!!!!  Those curly do-dads were a B!!!  After the sanding, they all got a good wash in warm soapy water made with dish soap and left to dry really well for at least a day.

I taped the glass with painter's tape.

Not selling anything, but I used this paint which is available in several shades and it worked well.

After touch-ups a day after the initial coat and allowing to dry another 24 hours, the tape was peeled away.

Gotta say - though this turned into a bigger project than I anticipated, the fixtures turned out better than I thought they would, so I am well pleased!!!  All it cost me was some elbow grease, two cans of paint, a bit of sandpaper, tape left-over from prior projects, and some roughed up hands and nails!!  Totally worth it!

Something in need of a little refashion at your place?  You can do it!!!   Live chaotically! - c

Raw. Who am I? Round 2!

My dear sweet Ashia, touched my very soul when she wrote this:

I'm sorry that you are going through this! I love reading about what you're doing whether it's hiking some mountain I have never heard of or planting flowers in some random persons yard you make life seem so adventurous! With all that is going on now I know it may sound crazy (coming from someone who has never been sick other than common stuff) but I want to encourage you because all those side effects don't have to be yours! You said something powerful when you first started your blog some years ago. "Who am I"? You gave us (readers) all the things you knew yourself to be. And then you said you would leave space for us (your friends) to fill in! Well Celeste you are one of the most amazing Women that I know! You are so multi purpose that you pass Super Woman! You can teach a rock to talk lol!! Know that this too shall pass my friend I love you like I love cake! You are a phenomenal Woman❤️😘

Between her sweet words, the amazing support from all of you, and the generosity of those of you who have helped me with concrete discussions of the nitty gritty that are my options ~ as promised ~ I have been thinking.

I don't believe in undue focus on the past.  Still, I've found that looking forward often requires a quick glance back.  I have felt uncharacteristically down over these past weeks.  I mean, I've had a lot of shit to deal with, but what's been so jarring is that I never plumed these depths when I had "a lot of shit to deal with" BEFORE!!!  As Tam Bo put it during one of our discussions,

You are more down and discouraged than I've ever seen you.   I feel like even more than when u had brain cancer.  I get it though.  It's the physically sickest u have ever been and have taken so long to recover.  Add to that the bad cancer news and no wonder u r discouraged.  I know you have done well because of the strong fighter you are.  Is it still F'd up that u gotta do it again?  Hell, ya it is.  Unfair.

I've written of my crazy journey before, particularly here in an Essay for Health Monitor Magazine  When diagnosed with Stage III melanoma in 2003 I was horrified, frightened, pissed.  Brent and I had tearful, hard conversations about what to do (NOTHING!  We knew interferon was not a valid treatment option even then!!), what to think, what my chances of survival were, all that stuff.  BUT!!!  I didn't have TIME to dwell on my fate.  I had a 10 and 12 year old.  I had a husband with a busy medical practice.  I was in the middle of my NP/Master's degree at UAB, a three hour commute from my home!  So - the night before going in for my complete lymph node dissection, a routine procedure at the time since I had a positive sentinel node, was family night - in a very weird and wonderful way.  Knowing I was going to be out of the game for a bit in order to recover, my professors allowed me to take an incomplete for my current semester, with the understanding that when I returned for the NEXT semester, I would complete new classes as scheduled as well as all work that remained from the one I bailed on!  A bit daunting, to say the least!!  One major project required was a video of me completing a head-to-toe, in depth, physical on a child.  As it was not due for a bit, I was not very well prepared.  But, B, always my best advocate and (as he puts it) Balls-to-the-Wall Warrior, was adamant - we were gonna get her done!!!  Fred-o, the 'patient', was laid out on the ever so comfy dining room table covered with a sheet.  Roo held up helpful posters just off camera.  (Sorry, Dr. Ivey, but a girl's gotta do what a girl's gotta do!!!)  B directed with camera rolling!  We did it!  Even if Fred did become a consummate actor in demonstrating reflexes I don't think I hit once during his exam!  With a post-op drain in my right arm pit, I started working on rehab exercises to regain movement and strength as soon as it was allowed.  When the next semester began, I hit the ground running to complete 2 semesters in one.  But!  NONE of that was my real focus.  My children were.  I was laser locked on making sure their lives changed as little as possible.  Of course they knew what was up.  We were honest as possible within the confines of our knowledge and their age.  Nevertheless, they were NOT going to miss soccer or dance.  They were NOT going to spend days in sadness instead of joy.  Not if I could help it.

In 2007 B planted three lovely cherry trees just months before my five year anniversary. Suddenly, another cutaneous melanoma lesion appeared on my left arm.  Still busy people!!!  Working as an NP.  Kids still my life!  Surgeries done.  No positive nodes this time.  Rehab exercises completed.  Back to work.  Miserable, but feeling a bit like a bullet had been dodged, as things were no worse.  2010.  Lung, brain and tonsilar melanoma mets in rapid succession.  Still working with my kiddos.  Fred off in college.  Roo graduating high school with all the pressure of heading to Ga Tech.  Brain met zapped with radiation.  Right upper lobe of my lung removed surgically, as was right tonsil.  No meds or treatments available.  We were sick at heart.  I knew I was in a frighteningly bad spiral.  But, what more was there to do?  B finds a trial with an experimental immunotherapy.  I admit to being somewhat opposed!  What a waste of time, money, and effort for an enormous question mark!!  Yes, B almost lost his mind.  I capitulated and thankfully, Weber knew what he was talking about.  With my last dose of immunotherapy in June of 2013, right up to this last set of scans in August, I remained NED - having no evidence of disease.  15 years with melanoma.  8 years as a Stage IV patient.  8 years alive and well after brain and lung mets.  Nothing short of a miracle in melanoma world.

In fact, B reached out to Dr. Weber just before my most recent scans.  While the plan of care for melanoma peeps like me is being written as we go, BY peeps like me, B asked what Weber recommended going forward?  He replied, "Get these last scans, and celebrate!"  Damn!  This from a man who has spent years being incredibly cautious, reticent, when discussing my future.  Hesitant to use the word "cure" or let me off the hook from future monitoring.  B was thrilled.  I tried hard to be careful, not wanting to make too much of those simple words.

Wary.  Guarded.  These are words that describe me far more than some who know me incredibly well may realize.  Children raised in volatile circumstances become watchful - acutely attuned to those around them.  Hyper aware of changes in tone and facial expression.  They also become fearful, but simultaneously hardened, strong, Teflon coated.  That strength evidenced by the ability to stand perfectly still, never flinching or moving to wipe away spittle that lands upon their face, while those they want most to love them rant and scream.  Their Teflon surface allows them to let various horrors fall away so that when the storm has passed, they carry on.  Smiling.  Finding joy in what they can.  Participating in regular kid stuff with school and friends.

I have come to terms with many things over the past 54 years.  I have become someone of whom I am relatively proud.  I have played some small role in rearing two amazing adults.  I think I have been a good friend to my dear ones, a healthcare provider who practiced with love and integrity, an honest person who tries to help others when I can.  But, I know that that painfully thin, fearful, towheaded girl, despite her steely spine and Teflon surface, remains within me as well.  In some ways, those skills, particularly when combined with my observant, vigilant nature, have stood me in good stead!! And despite what I thought was a careful, measured response to Dr. Weber's words, I think I allowed them to cause cracks and unattached corners, that I did not immediately rush to super glue, in the cheap, house trailer Formica that constituted my armor.

On thinking about the crushing funk in which I've somewhat uncharacteristically found myself over the past 6 weeks, here's what I've come up with:  Despite what I have endured physically in the past, these two abdominal surgeries combined with the adverse reactions to medications have been a misery far greater than I previously experienced.  Most detrimentally however, it frighten me.  Fear.  Something that I thought surviving my childhood and melanoma had banished from my emotional vernacular.  I was wrong.  Now it is all too easy to fear that more of the same will be my ultimate fate.  An aversion to three additional months of abdominal misery with nausea and vomiting seems rational.  And I HATE that!  Being afraid makes me feel weak.  Persistent pain and my malnourished, anemic state, though improving daily, has certainly not helped my mood.  Nor has considerable sleep deprivation, having not had a full night's sleep since August 29.  But ultimately, I think I fell for a fairy tale.  For all these years, I never ONCE let myself think that I was cured, or well, or free.  I kept my Formica carapace intact.  It was lame.  It was cracked, often peeling up at the corners.  But, as I held it together, I was protected.  My guard was up.  I was ready, no matter what.  Until, I wasn't.  I let myself believe that I was done.  I had my scans.  We ate our hair filled breakfast.  I wasn't worried.  I was happy.  I was normal. I could live.  WE were free.  Free to have a new life.  Free to just be.  So when this round hit.  I was not prepared.  I had not battened down the hatches.  I let that shitty, ugly, white with a gold squiggly thread running through it, house trailer Formica suit of armor be ripped away, leaving me raw and exposed.

So here we are.  I have love.  I have dear ones who are more than willing to light the way when my own light is dim.  I realize that fear is not something I can dismiss in a moment.  But, through what each of you have shared with me and what I can now see about myself...I know it is something I can master....rather than the other way round. Like I've told hundreds of parents over the years, peer pressure is not always a bad thing.  Kids sit down and eat their veggies if they see the other "cool kids" doing it.  They get out their books and work to read, because their teachers and friends do so.  Similarly, my dear ones, I want to be the woman you say you know.  I want to be strong.  I want to teach a rock to talk!  And, with your help - I really think I can.  - love, les

REHAB - Part 3 Nourishment for the body, and even more for the soul.

I really am eating!!  Quite a lot and well!!  Here are some recent meals!

This recipe was really for steak with miso butter, but I figured a tuna steak would hold up equally well, and it did!  Yummy!  I am free to eat whatever I like per my surgeon, but we are still taking fiber and seedy things slowly.  I begged for the asparagus, so B agreed as long as I ate only the tender tops!  Damn!  Who ain't gonna agree to that??!  Poor goofy boy ate all the stems!!!

This recipe was for chicken and sesame noodles.  But, you know me.  Always making changes.  I used left over tuna from the dinner above in place of the chicken and it was really good.  Simple too!  You basically make a dressing of red wine vinegar, soy, honey, sesame oil, and tahini (sesame paste) to toss your "chicken" and noodles in.  

BLECH!  Tan food from Cracker Barrel on the way home from Nashville.  Passed up Ethiopian, Mexican, and Thai restaurants for this!!!  Oh well, feared my tummy might not be ready for the other.  Beige though it was, it was food!

Last night was pork chops and baked sweet potatoes.  The night prior, I made Cioppino.  A fish stew with tomato, celery, onion, garlic, bay leaf and thyme.  You can add as much or as little of your choice of fish that you like.  This one just had a bit of cod and shrimp.  Pretty good, if I say so myself!

Since man cannot live by bread alone, in between the strange errands we have had to embark on (Today's ta-dah was getting a flu shot...since I can't get it while on chemo and one certainly doesn't want flu combined with neutropenia if this is where we are going!!!!!), sweet visits from Don and the kiddo's, puttering about, reading and writing....I did get started on this...

A sweet dress for my purple durple Roo!  I think it is going to be so pretty on her!!!

And just this morning...B was a busy chef, prepping my second breakfast after my first of tea and toast!

Now you see it!  Kefir smoothie with banana, tea, egg, bacon and cute little pancakes!

Now it's gone!!!

But more than all these things, the tangible love and support, the unconditional belief in me and whatever path I choose, from all of you, have surpassed anything I ever expected or knew my heart could hold. I am beyond touched.  I am humbled and grateful.  I am incredibly blessed to have such a beautiful family of dear ones.  I am thankful for the absolute sweetness and positivity you have provided.  I am filled with gratitude for the effort so many of you have made in helping me really hash through the pros and cons, and realities of my options.  The heartfelt encouragement, in real words, straight from your hearts, have lifted me up and given me hope that if YOU can believe in me, then maybe I can, too!  I am thinking hard.  I am taking an unvarnished appraisal of myself.  I am  trying to be the woman that you believe me to be.  And I don't see that as undue pressure or a bad thing!!!   I think we all find our better selves when we look beyond ourselves.  So, with love and guidance from all of you - I am finding my way back - to me.  Nourishment for the soul, indeed. ~ with much love, les

Melanoma madness links!! ASCO and others....

Hey guys! Don't have the time or energy to give you my usual print out and assessment on these just now!  However, in the spirit of access and knowledge, I still wanted you to have them.

So....here you go:

Galectin's GR-MD-02 Positive in Phase Ib Study With Keytruda

Why Yervoy's Resurgence Will Gain Momentum

Adoptive transfer of tumor-infiltrating lymphocytes in melanoma: a viable treatment option

Lifestyle Modifications and Policy Implications for Primary and Secondary Cancer Prevention: Diet, Exercise, Sun Safety, and Alcohol Reduction

New Era in the Management of Melanoma Brain Metastases

Combination Immunotherapy Development in Melanoma Practice-Changing Developments in Stage III Melanoma: Surgery, Adjuvant Targeted Therapy, and Immunotherapy Patterns of Response and Progression to Immunotherapy Emerging Strategies in Systemic Therapy for the Treatment of Melanoma Challenging Cases: Management of Immune-Related Toxicity The Role of Completion Lymph Node Dissection for Sentinel Lymph Node-Positive Melanoma. Hieken, Kane JM, Wong.  Ann Surg Oncol. 2018 Oct 3.  Completion lymph node dissection (CLND) for sentinel lymph node (SLN)-positive melanoma patients has been guideline-concordant standard of care since adoption of lymphatic mapping and SLN biopsy for the management of clinically node-negative melanoma patients more than 20 years ago. However, a trend for omission of CLND has been observed over the past decade, and we now have randomized, controlled clinical trial data to help guide treatment recommendations. Publication of these data prompted an American Society of Clinical Oncology-Society of Surgical Oncology 2018 clinical practice guideline update for these patients. Systematic review of current evidence supports a selective, individualized approach to CLND for SLN-positive melanoma. For low-risk, low-volume micrometastatic disease, SLN biopsy may be both diagnostic and therapeutic, and close clinical follow-up with imaging or CLND are reasonable options for appropriately selected patients. For higher-risk patients, omission of CLND requires careful consideration of risks versus benefits, relevant histopathology, and individualized patient discussion. This should address patient comorbidities and life expectancy, the predicted likelihood of additional positive nodes, availability of imaging surveillance, likelihood of adherence to imaging and clinical follow-up, consequences of regional recurrence, and the prognostic value of complete nodal staging and its impact on adjuvant therapy recommendations or clinical trial participation. Data on long-term outcomes, cost, and patient-reported quality of life measures are not yet available. Prognostic Value of Low Tumor Burden in Patients With Melanoma. Poklepovic, Carvajal.  Oncology (Williston Park). 2018 Sep 15. The therapeutic landscape for cutaneous melanoma has dramatically advanced in the last several years with the development, validation, and approval by the US Food and Drug Administration of several new therapies that have proven effective in treating metastatic disease. Considerable effort has been put into identifying prognostic and predictive markers of therapeutic response to better delineate the patient populations most likely to benefit from treatment. Baseline tumor burden has been described as a common clinical factor associated with treatment response: lower tumor burden at the time of therapeutic intervention is associated with improved responses and survival outcomes on several therapies. Some therapies have shown efficacy as adjuvant interventions in patients with subclinical disease following definitive treatment, further supporting their role in patients with minimal tumor burden. The increasing evidence that patients with lower tumor burden may be the ones who derive maximal benefit from several melanoma-directed therapies points toward the critical need for risk-tailored surveillance to permit early identification of melanoma metastasis in patients at high risk for recurrence.   Predictors of Sentinel Lymph Node Positivity in Thin Melanoma Using the National Cancer Database. Conic, Ko, Damiani, et al.  J Am Acad Dermatol. 2018 Sep 18.  Following melanoma excision, patients often receive sentinel lymph node biopsy (SLNB) for further staging. Limited data regarding predictors of SLNB positivity in thin melanoma are available.  To evaluate predictors of SLNB positivity in thin melanoma.  Patients with cutaneous melanoma, Breslow thickness great than/= to 1.00 mm who received a SLNB were identified from the National Cancer Database in the period from 2004-2014 (n=9,186). Predictors of SLNB positivity were analyzed using logistic regression.  In a multivariate analysis, patients with age less than 60 and Breslow thickness greater than 0.8mm were at increased risk for positive SLN. Moreover, on multivariate analysis, presence dermal mitoses increased odds of SLN positivity by 95%, ulceration by 63% and Clark level IV-V by 48%. Patients without ulceration but with dermal mitoses had 92% increased SLN positivity.  Limited survival data available.  Younger age, Breslow thickness greater than 0.8 mm, presence of dermal mitoses, ulceration and Clark level IV-V are positive predictors of positive SLN. While the new AJCC system has removed dermal mitotic rate from staging, continued evaluation of dermal mitotic rate could be valuable for guiding surgical decision making about SLNB.   Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis. Wang, Salem, Cohen, et al.  JAMA Oncol. 2018 Sep 13. Immune checkpoint inhibitors (ICIs) are now a mainstay of cancer treatment. Although rare, fulminant and fatal toxic effects may complicate these otherwise transformative therapies; characterizing these events requires integration of global data.  To determine the spectrum, timing, and clinical features of fatal ICI-associated toxic effects.  We retrospectively queried a World Health Organization (WHO) pharmacovigilance database (Vigilyze) comprising more than 16 000 000 adverse drug reactions, and records from 7 academic centers. We performed a meta-analysis of published trials of anti-programmed death-1/ligand-1 (PD-1/PD-L1) and anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) to evaluate their incidence using data from large academic medical centers, global WHO pharmacovigilance data, and all published ICI clinical trials of patients with cancer treated with ICIs internationally. Anti-CTLA-4 (ipilimumab or tremelimumab), anti-PD-1 (nivolumab, pembrolizumab), or anti-PD-L1 (atezolizumab, avelumab, durvalumab). Timing, spectrum, outcomes, and incidence of ICI-associated toxic effects. Internationally, 613 fatal ICI toxic events were reported from 2009 through January 2018 in Vigilyze. The spectrum differed widely between regimens: in a total of 193 anti-CTLA-4 deaths, most were usually from colitis (135 [70%]), whereas anti-PD-1/PD-L1-related fatalities were often from pneumonitis (333 [35%]), hepatitis (115 [22%]), and neurotoxic effects (50 [15%]). Combination PD-1/CTLA-4 deaths were frequently from colitis (32 [37%]) and myocarditis (22 [25%]). Fatal toxic effects typically occurred early after therapy initiation for combination therapy, anti-PD-1, and ipilimumab monotherapy (median 14.5, 40, and 40 days, respectively). Myocarditis had the highest fatality rate (52 [39.7%] of 131 reported cases), whereas endocrine events and colitis had only 2% to 5% reported fatalities; 10% to 17% of other organ-system toxic effects reported had fatal outcomes. Retrospective review of 3545 patients treated with ICIs from 7 academic centers revealed 0.6% fatality rates; cardiac and neurologic events were especially prominent (43%). Median time from symptom onset to death was 32 days. A meta-analysis of 112 trials involving 19 217 patients showed toxicity-related fatality rates of 0.36% (anti-PD-1), 0.38% (anti-PD-L1), 1.08% (anti-CTLA-4), and 1.23% (PD-1/PD-L1 plus CTLA-4). In the largest evaluation of fatal ICI-associated toxic effects published to date to our knowledge, we observed early onset of death with varied causes and frequencies depending on therapeutic regimen. Clinicians across disciplines should be aware of these uncommon lethal complications.

Systematic Review and Meta-analysis of the Prognostic Significance of miRNAs in Melanoma Patients.

Sabarimurugan, Madurantakam Royam, Das, et al.  Mol Diagn Ther. 2018 Sep 27. 

Melanoma is the most aggressive and deadly form of skin cancer. The molecular variability involving microRNA (miRNA) expression plays a significant role in melanogenesis, which leads to poor prognostic effects in melanoma. Since there is a scarcity of comprehensive data on the prognostic role of miRNAs in melanoma patients, this study focuses on filling this knowledge gap through a systematic review and meta-analysis.

The included studies were extracted from several bibliographic databases between 2012 and 2018 using multiple keywords according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The hazard ratios (HRs) and 95% confidence intervals (CIs) for different survival endpoints were compared to the high and low expression levels of miRNAs. The mean effect size of HR values was estimated using a random-effects model of meta-analysis. Inverted funnel plot symmetry was used to assess publication bias. Subgroup analysis was carried out individually for multiple miRNAs across different studies.

A total of 24 studies across eight countries were included, of which 16 studies were eligible for meta-analysis. Twenty-five miRNA expression levels were studied from 2669 melanoma patients to estimate the association between the prognostic role of miRNAs and survival outcome in these 16 studies. The overall pooled effect size (HR) for up- and downregulated miRNAs was 1.043, indicating that the miRNA expression increased the likelihood of death in melanoma patients by 4.3%. Subgroup analysis for miRNA10b, miRNA16 and miRNA21 showed a poor prognosis. The quality assessment revealed that 16 studies were good quality and eight studies were of fair quality. 

This is one of the first pooled meta-analysis studies on the role of miRNAs in the prognosis of melanoma. Our findings are inconclusive but suggest that miRNA expression could predict poor survival in melanoma patients. Therefore, miRNA expression could act as promising prognostic marker for melanoma.  

Induced Vitiligo due to Talimogene Laherparepvec Injection for Metastatic Melanoma Associated with Long-term Complete Response.

Iglesias, Ribert, Barreiro,   Acta Derm Venereol. 2018 Oct 3. 

Tumor-derived microRNAs induce myeloid suppressor cells and predict immunotherapy resistance in melanoma.

Huber, Vallacchi, Fleming  et al.  J Clin Invest. 2018 Sep 27.

The accrual of myeloid-derived suppressor cells (MDSCs) represents a major obstacle to effective immunotherapy in cancer patients, but the mechanisms underlying this process in the human setting remain elusive. Here, we describe a set of microRNAs (miR-146a, miR-155, miR-125b, miR-100, let-7e, miR-125a, miR-146b, miR-99b) that are associated with MDSCs and with resistance to treatment with immune checkpoint inhibitors in melanoma patients. The miRs were identified by transcriptional analyses as being responsible for the conversion of monocytes into MDSCs (CD14+HLA-DRneg cells) mediated by melanoma extracellular vesicles (EVs) and were shown to recreate MDSC features upon transfection. In melanoma patients, these miRs are increased in circulating CD14+ monocytes, plasma and tumor samples, where they correlate with the myeloid cell infiltrate. In plasma, their baseline level clusters with the clinical efficacy of CTLA-4 or PD-1 blockade. Hence, MDSC-related miRs represent an indicator of MDSC activity in cancer patients and a potential blood marker of a poor immunotherapy outcome.  

Epacadostat Plus Pembrolizumab in Patients With Advanced Solid Tumors: Phase I Results From a Multicenter, Open-Label Phase I/II Trial (ECHO-202/KEYNOTE-037).

Mitchell, Hamid Smith, et al.  J Clin Oncol. 2018 Sep 28.

Tumors may evade immunosurveillance through upregulation of the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme. Epacadostat is a potent and highly selective IDO1 enzyme inhibitor. The open-label phase I/II ECHO-202/KEYNOTE-037 trial evaluated epacadostat plus pembrolizumab, a programmed death protein 1 inhibitor, in patients with advanced solid tumors. Phase I results on maximum tolerated dose, safety, tolerability, preliminary antitumor activity, and pharmacokinetics are reported.

Patients received escalating doses of oral epacadostat (25, 50, 100, or 300 mg) twice per day plus intravenous pembrolizumab 2 mg/kg or 200 mg every 3 weeks. During the safety expansion, patients received epacadostat (50, 100, or 300 mg) twice per day plus pembrolizumab 200 mg every 3 weeks.

Sixty-two patients were enrolled and received one or more doses of study treatment. The maximum tolerated dose of epacadostat in combination with pembrolizumab was not reached. Fifty-two patients (84%) experienced treatment-related adverse events (TRAEs), with fatigue (36%), rash (36%), arthralgia (24%), pruritus (23%), and nausea (21%) occurring in greater than/ = to 20%. Grade 3/4 TRAEs were reported in 24% of patients. Seven patients (11%) discontinued study treatment because of TRAEs. No TRAEs led to death. Epacadostat 100 mg twice per day plus pembrolizumab 200 mg every 3 weeks was recommended for phase II evaluation. Objective responses (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) occurred in 12 (55%) of 22 patients with melanoma and in patients with non-small-cell lung cancer, renal cell carcinoma, endometrial adenocarcinoma, urothelial carcinoma, and squamous cell carcinoma of the head and neck. The pharmacokinetics of epacadostat and pembrolizumab and antidrug antibody rate were comparable to historical controls for monotherapies.

Epacadostat in combination with pembrolizumab generally was well tolerated and had encouraging antitumor activity in multiple advanced solid tumors.

Predictive Biomarkers for Checkpoint Immunotherapy: Current Status and Challenges for Clinical Application.

Tray, Weber, Adams.  Cancer Immunol Res. 2018 Oct;6.

Immune-checkpoint blockade (ICB), in particular PD-1 inhibition, has rapidly changed the treatment landscape and altered therapeutic paradigms across many tumor types, with unprecedented rates of durable clinical responses in a number of cancers. Despite this success, only a subset of patients responds to ICB and, as a result, predictive biomarkers would be useful to guide the selection of patients for these therapies. This article highlights currently used biomarkers, as well as several promising novel candidates, and also discusses the challenges involved in establishing their analytic validity and clinical utility. Progress is being evaluated in melanoma and non-small cell lung cancer, for which PD-1 ± CTLA-4 inhibitors have become standard therapy, to other malignancies for which PD-L1 inhibitors remain investigational. Although single biomarkers have substantial limitations, a combination of biomarkers that reflect the interaction of host and tumor will likely be needed to provide a reproducible surrogate for the benefit of checkpoint modulation.

And because y'all know I've been yelling about biomarkers for years, here are links to my prior posts on the subject:  

Better melanoma outcomes with a lower NLR, neutrophil-to-lymphocyte ratio! (Again...)  

MHC proteins and how they work if you are taking anti-CTLA4 (ipi) or anti-PD-1 (Opdivo or Keytruda) in melanoma  

Simple blood tests that tells us where we are with our melanoma....AGAIN (and again, and again, and again)!!!

And here is an update on the Columbus Trial....with my prior notes:

March 2018 - Encorafenib plus binimetinib better than vemurafenib or encorafenib alone in melanoma! Well, duh!!! We already knew that a BRAF/MEK combo is better than a single agent!!!!

Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial. Dummer, Ascierto, Gogas, et al.  Lancet Oncol. 2018 Sep 12.

Encorafenib plus binimetinib and encorafenib alone improved progression-free survival compared with vemurafenib in patients with BRAF^V600-mutant melanoma in the COLUMBUS trial. Here, we report the results of the secondary endpoint of overall survival.

COLUMBUS was a two-part, randomised, open-label, phase 3 study done at 162 hospitals in 28 countries. Eligible patients were aged at least 18 years with histologically confirmed, locally advanced, unresectable, or metastatic cutaneous melanoma, or unknown primary melanoma, BRAF^V600E or BRAF^V600Kmutation, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and were treatment naive or had progressed on or after first-line immunotherapy. In part 1 of the study, patients were randomly assigned (1:1:1) by use of interactive response technology to receive oral encorafenib 450 mg once daily plus oral binimetinib 45 mg twice daily (encorafenib plus binimetinib group), oral encorafenib 300 mg once daily (encorafenib group), or oral vemurafenib 960 mg twice daily (vemurafenib group). Randomisation was stratified by the American Joint Committee on Cancer stage, ECOG performance status, and BRAF mutation status. The primary outcome of the trial, progression-free survival with encorafenib plus binimetinib versus vemurafenib, was reported previously. Here we present the prespecified interim overall survival analysis. Efficacy analyses were by intent to treat. Safety was analysed in patients who received at least one dose of study drug. Part 2 of the study was initiated at the request of the US Food and Drug Administration to better understand the contribution of binimetinib to the combination therapy by comparing encorafenib 300 mg once daily plus binimetinib 45 mg twice daily with encorafenib 300 mg once daily alone. Results of part 2 will be published separately. This trial is ongoing and is registered with ClinicalTrials.gov, number NCT01909453, and EudraCT, number 2013-001176-38.

Between Dec 30, 2013, and April 10, 2015, 577 of 1345 screened patients were randomly assigned to receive encorafenib plus binimetinib (n=192), encorafenib (n=194), or vemurafenib (n=191). Median follow-up for overall survival was 36·8 months (35·9-37·5). Median overall survival was 33·6 months (24·4-39·2) with encorafenib plus binimetinib and 16·9 months (14·0-24·5) with vemurafenib. The most common grade 3 or 4 adverse events did not change substantially from the first report; those seen in more than 5% of patients treated with encorafenib plus binimetinib were increased γ-glutamyltransferase (18 [9%] of 192 patients), increased blood creatine phosphokinase (14 [7%]), and hypertension (12 [6%]); those seen with encorafenib alone were palmar-plantar erythrodysaesthesia syndrome (26 [14%] of 192 patients), myalgia (19 [10%]), and arthralgia (18 [9%]); and with vemurafenib the most common grade 3 or 4 adverse event was arthralgia (11 [6%] of 186 patients). One death in the combination treatment group was considered by the investigator to be possibly related to treatment.

The combination of encorafenib plus binimetinib provided clinically meaningful efficacy with good tolerability as shown by improvements in both progression-free survival and overall survival compared with vemurafenib. These data suggest that the combination of encorafenib plus binimetinib is likely to become an important therapeutic option in patients with BRAF^V600-mutant melanoma.

The ASCO Educational Book looks like it might be helpful to melanoma peeps...so you might keep that in mind as an additional resource in the future.  Remember to read critically.  Use your common horse sense.  Don't fall for everything everybody is selling.  Take good care and remember I love you.  - C

REHAB - Part 2 What the heck do we do now????

For someone with nothing to do and little strength to do it, the past several days have been pretty busy around here!!!  Of course, when it takes a couple of hours to just get up, get going, get a shower and get dressed....your day fills up pretty quickly!!!

Had to have the car serviced on Tuesday, no big deal, and B could have done that, but we also needed all the records from my recent crazy to take to the specialist in Nashville.  In order to attain those, they required my presence, my signature, and my ID.  Thanks to a nice, efficient lady in the records department, things went much more smoothly and rapidly than I had anticipated.  Kinda weird to read a clinical report of your surgery and process!  Discovered that my hemoglobin reached an in-hospital low of 7.3, so I guess my current (as of last week) 9.3 is pretty good indeed.

Yesterday - up bright and early and off to Nashville for our consultation with Dr. Berlin at Vanderbilt.  The trip was pretty easy.  Yes, I drove.  I like to drive and actually having the steering wheel to support me, plus being better able to anticipate the bumps and curves as the driver, actually decreased my pain and discomfort.

We began by waiting to sign our life away in an impressive waiting room.  Large.  Well appointed.  Fairly clean.  Interior designer completely swept away with a leaf motif.  There were leaves on the carpet, carved into the backs of chairs, embedded in glass panels inserted into walls, in watercolors that were framed and hanging on the walls.  It was a good idea taken one (maybe 12???)  step(s) too far!!!  It really has to be seen to be be- LEAVED!  (I crack myself up!!!)

You see what I'm say'n????  And there was actually much more!!!

We didn't have huge waits.  Folks were very nice and helpful.  Here's how it all went down....

To start, little background ~  as most of you can well imagine, B has already done his homework and then some.  Melanoma is not a terribly common cancer as it is ranked 19th in frequency of occurrence, but even so, the Pub Med data base on melanoma contains more than 121,000 abstracts.  For my current condition, there are only 6,000. (Of which B has read more than half!)  Melanoma occurs at a rate of 3 per 100,000 peeps, or 30 cases per every million humans per year .  My new and special cancer has an incidence of 0.12 cases per million humans per year.  As such, there are not a lot of peeps with "adenocarcinoma ex-goblet cell carcinoid" and certainly not a lot of peeps studying it.  In the US, Dr. Reid at Emory has a report on 77 patients.  Dr. Taggart at MD Anderson has reported on 142 patients.  Dr. Tang at Memorial Sloan Kettering has 63.  Dr. Berlin at Vanderbilt now has 30, if you count me.  And understand, these numbers do NOT reflect their patient population collected as of this year or even last year!  These are patients both actual and reviewed retrospectively through their institutional data bases over MANY YEARS!!!

You may ask, "What so about adenocarcinoma ex-goblet cell carcinoid???"  {Phraseology from my childhood!!}  It's complicated.  Regular old colon cancer is referred to as "adenocarcinoma".  It sucks.  It is treated with surgery, sometimes radiation and the same old school chemo I talked about in a prior post:  Now what?? FOLFOX and FOLFIRI????  My cancer, "adenocarcinoma ex-goblet cell carinoid" is rare, has been given a lot of different names at different times, is categorized differently depending on who is doing the categorizing, and is a bit of a combo.  A combo of goblet cell carcinoid, a condition in which your goblet cells...the little do-dads that produce the mucus in your gut....go a bit nuts and produce a bunch of mucus and grow in a chaotic manner - and regular old adenocarcinoma type colon cancer.  FYI - with plain goblet cell carcinoid - patients do really well, considering, even when found in late stages.  Okay.  Back to the combo.  If you have my fancy schmancy cancer combo...the thing you look at next is percentages.  Meaning, the percentage of goblet cell mess vs colon cancer nastiness.  The more colon cancer crap your tumor has, the worse off you are.  My pathologist, dear Ox, reports my cancer to be Stage 2a (based on clear margins, negative nodes, etc) and on a cellular level to be not the best combo, nor the worst, but not great either with 75% of the material being adenocarcinoma and 25% being goblet cell carcinoid and mucus material.

But on to our visit ~ Shortly after being placed in an exam room, we were met by Dr. Das.  He is in the process of completing his fellowship in hem/onc under Dr. Berlin and will be joining the faculty at Vandy in the next few months.  Turns out he was also very kind and extremely knowledgeable.  Whatever B threw at him regarding this study by so-and-so where no difference in those who were treated and those who were not, vs this study by the-other-fellow where blah, blah, blah...he could discuss intelligently.  He treated us with respect and was aware of my history when he entered the room.  So...bottom line:

• No.  There are no reports of folks who did treatment vs folks who declined treatment to really see who did better and determine if the "treatment" really had a positive effect.
• I have a 75% chance of never having a recurrence if I do nothing.  Or...to put it another way, I have a 25% chance of recurrence if I do nothing.
• His best opinion is that with treatment, I will decrease the odds of my having a recurrence by 10%.  In other words, decrease my chance of recurrence from 25% to 15%.
• He did have some "news" from this 2013 study:  The IDEA (International Duration Evaluation of Adjuvant Chemotherapy) Collaboration: Prospective Combined Analysis of Phase III Trials Investigating Duration of Adjuvant Therapy with the FOLFOX (FOLFOX4 or Modified FOLFOX6) or XELOX (3 versus 6 months) Regimen for Patients with Stage III Colon Cancer: Trial Design and Current Status  in which it was determined that folks who were treated with only 3 months of chemo (given every 3 weeks for a total of 4 rounds) did just as well as those who did FOLFOX for 6 months.  AND this 3 month regimen used only 2 meds:  Capecitabine (an oral pill given twice daily for 2 weeks and then one week off) as well as Oxaliplatin (an IV infusion given in the office every three weeks).
• Now, when you read the nitty gritty of the study, turns out that most folks can't tolerate the entire 6 months of the FOLFOX mess anyway and have to quit due to side effects.  On the flip side, these drugs (while pretty awful) are not quite as awful as those used in the FOLFOX and FOLFIRI regimens.  Additionally, the 3 month regimen as noted above, had slightly better outcomes - as best as they can tell.
• Most common side effects of Capecitabine:  decreased white count, rash and pain to palms and soles, diarrhea, fatigue, nausea, vomiting.
• Most common side effects of Oxaliplatin:  Peripheral neuropathy (numbness and tingling of hands and feet, often triggered by cold), nausea, vomiting, diarrhea, mouth sores, low white count, fatigue, decreased appetite.  It can also rarely cause angina which can make you feel as though you are having a heart attack!  You're not really having one...you just feel like it!  Weird, right???  And, 3% of patients experience hair loss.
• On the good side, for both drugs, if you are having side effects, a decrease in the dose often decreases the side effects in the process.  Additionally, though 90% of folks (per a couple of studies) DID experience neuropathies with Oxaliplatin, most of these resolved with resolution of the treatment.
• Another positive, given that there is just the one infusion, I wouldn't need the pump scenario I was told of when I discussed FOLFOX with my local onc.  Additionally, side effects are cumulative.  Meaning, the more drug you take, the more likely you are to have side effects.  So the 3 month plan helps (in theory - though they do use a higher dose in the 3 month regimen) limit side effects when you compare it to taking the drugs for 6 months.
• So. A lot to take in.  And when nausea and vomiting are pretty consistent side effects across both meds...and you can't take meds like phenergan and zofran that are typically used to control those very things....what are you supposed to do???????????

On that note, B also did some research into dyskinesia with these drugs!  It's a thing y'all!!!  It doesn't happen with everyone, by any means.  But it happens.  Enough to be in lots of case reports and op-eds!!  Check out what happened to this lady who went in for a simple gall bladder removal:

This chick was having jerking of her arms, was confused and didn't know what was happening, and had jerking movements of her head and neck!!  Sound familiar????

• Thankfully, Dr. Das didn't treat us as though we were psycho when we reported the side effects I had experienced on phenergan and zofran.  Nor did he throw up his hands like Mr. ER Doc.  Instead, he immediately started brain storming about how we could deal with it!!!  I like this guy!!!
• He suggested that I could take aprecitant (emend) as an IV infusion when I got my infusion of Oxaliplatin and its effects would work for about 3 days.  B knew of this drug, though I did not, and get this!  It has been considered in and of itself as a treatment for both melanoma and colon cancer!  Crazy, right?
• Das also suggested that I could use ativan and/or marinol (the marijuana derivative I took as pre-op) as needed for nausea at home.  B also came up with decadron as a possibility if needed.  Knowing that there are SOME options to deal with nausea and vomiting certainly made me feel better.
• By the time Dr. Berlin arrived, we really had hashed through a lot of territory and Dr. Das had answered most of the questions we had.  Dr. Berlin was very nice and informed as well.  He admitted their lack of absolutes, but said the plan as laid out by Dr. Das was what they felt was best under current circumstances.  He acknowledged that this treatment plan is really that used to treat basic colon cancer.  But, when that is 75% of your problem, that's the best they've got at the moment.
• He and Dr. Das noted that it would be a perfectly acceptable choice to do nothing more than observation - which would consist of a CT of the chest, abd and pelvis with contrast, 6 months from diagnosis and then annually, as well as some basic schedule of colonoscopies.  This cancer does not typically metastasize to far distant places, preferring the abdominal cavity and the surrounds....going occasionally to the lung.
• When I looked directly at them and asked, "What would you do if you were in my shoes?"  Both promptly replied that they would do the 3 month chemo regimen...hoping to gain an additional 10% of protection against recurrence.
• Both gave me the song and dance about lots of veggies and exercise in order to protect my colon and my health.  You can imagine the eye roll.
• Both did not feel that I needed to travel to Vandy for this treatment, saying that my onc in Chattanooga could manage this perfectly well.   Simultaneously reassuring me that I was now a patient there and was welcome to return or call should there be a need.
• And finally, I thought to ask, "Should I opt for this treatment, when should I start?"  Dr. Berlin was adamant, that sooner was better.  I was a little startled by that, not sure why.  But, he made it clear that starting within 4 weeks was much better than even 8 weeks out.  So ~ WOW!
• They are going to have a Vandy pathologist they feel is especially skilled at analyzing these sorts of tumors review my slides on Friday.  On Tuesday they will review my case with the tumor board.  They will call us with their final thoughts at that time.  Dr. Das apparently spoke with my local onc today to review their recommended plan of care.

So, damn!  I know that folks survive hard core chemo hell for years at a time.  I know that compared to some regimens, this one is pretty brief and mild.  But, geeze.  I am so tired of this shit.  So very, very tired.  Not that it is what ANYBODY plans on dealing with, but this is NOT what I thought I would be facing just now.  I'm supposed to be in Italy right now.  Vernazza to be precise.  Oh, well.  A pity party won't do me much good.

B is a man possessed.  Trying to learn everything about everything.  He says he would do it if it were him, but that I can decide whatever path I choose with his full support.  He's a nervous wreck about dealing with me being sick and not eating and keeping me warm because apparently cold can trigger the neuropathies.  As in....you are warned not to drink things with ice, pick things up out of the freezer, breathe cold air.  So. Very.  Weird.  And while everybody uses their hands for everything, I had been thinking, "Okay, I'll just sit and sew and write for three months."  That may not be so easy with numbness and tingling in your hands as the skin peels off!!!  Geeze!

I lost another pound today, but I am still losing a great deal of fluid off my belly so it is hard to tell when that is going to settle out so that I can actually start demonstrating weight gain!  I am eating well, I promise.  Was going to share pics of what I've been eating and up to apart from this drama.  But, this has droned on for so long, you are probably as tired reading it as I am writing it...so I will give that report tomorrow.   Interested in all thoughts.  Much love, les

Tales from the Crypt??? Nah! That's not right! Tales from REHAB - Part 1!

Thanks in large part to all of the love and encouragement that has been sent my way from all of you, I am beginning to see some light!!!!  I have been eating quite well.  Ruthie set me on a great path and B has been taking good care of me in that department!  Plus, we have been working together on some meals out of Chrissy Teigen's two cookbooks, just for fun.

This cod with miso butter was really delish.  We made ours with squash because B was worried about too much fiber in the snap peas just now.

Another supper out of the book was this amazing cheesy polenta (with mozzarella, cream, AND Parmesan, guys!!!) topped with a perfectly fried egg by Bentie, along side sauteed mushrooms  and spinach!  Soooo yummy!!

I keep forgetting to take pics of my amazing Bentie breakfasts.  I am too greedy and just eat them up!!  There has been plenty of kefir or yogurt with fruit, lots of eggs all sorts of ways, and are these little pancakes not the cutest??  Tasty too!!!  I'm taking my multivitamin and iron supplement every morning.  Other positive news I forgot to include in my last report ~ though my hemoglobin was 8.1 at hospital discharge it had already increased to 9.3 at my oncology visit Wednesday.

I have been blessed by good visits with the kiddo's.  (Which included meatloaf and mashed potatoes when Fred-o was here and chicken salad sandwiches when Roo came by!!!)  I know this has been a rather traumatic slap in the face for them.  Yet, they have been consistently strong and cheering for me - rather than the other way round.  We have had good talks about everything...politics, me, as well as the good and the difficult in their own lives.  That may not sound that significant.  But, as one who has been in tenuous health positions before, I've found that lots of people fear being "real" around the "victim".  I am thankful that they are comfortable in sharing their lives with me, period.  But, even more grateful that they continue to do so in our current circumstance.  I am so proud of both of them.  They are strong, generous, hard working adults, who are doing their best to make their way in a world that is not always kind or rational.

Yesterday, B tamped down his own worries and fears and helped me putter about the yard!  My entire family, for years, have said,  "There she goes!  Cleaning the woods again!"  Well.  Maybe.  But, I have spent 20 years turning this plot of wooded land into a garden.  Having been abandoned for a month, which included a good deal of rain and storms, there was certainly cleaning to be done.  B, has often said HIS yard would consist of gravel spray painted green, but works tirelessly to help me effect any yard work I so desire just the same.  So yesterday, I walked slowly and carefully about - pointing out sticks and limbs to be collected, tomato vines to be taken down, cages to be stored.  Small steps...but steps nonetheless.

Sweet Ruthie came fully ready to provide not only cheer and sustenance during her visit, but "activities" as well!!  (We like our "activities"!!!)  We watched the first season of Big Little Lies together.  Man!  Those peeps and their crazy will definitely take your mind off your troubles!!  And, she came set to help me embark on a project she has heard me go on and on about!  Making pillows with cases covered with Sashiko embroidery for my couch!!!

She finished hers, on the right, and it looks awesome!!!  Mine is a basket weave pattern on the left, that looks like shite!!!  But, I'll get her done and see how she looks in the end.  I think I should claim I was on major drugs during the process, but y'all already know that ain't so!!!  HA!

During this grand convalescence I have also managed to complete a Pediatric Primary Care module, required annual continuing education credits for my pediatric NP certification and license, take the test, and make 100%!!!!  Guess, I came out of this with no greater brain damage than I already possessed!!

And finally, though B has promised to help me get situated and hopefully do a bit of sewing today, when a sewist ain't sewing, she can be studying up on it via her laptop, right????  And this is the awesomeness I've come up with!!!!

I am quite excited about this little dress hacked by The Fabric Store using the In the Folds, Ruffle Sleeve Top - a free download from the Peppermint Magazine!!!  I think it will be perfect for a little piece of Liberty cotton that I have from my Paris fabric shopping!!!
Here's the link so you can see it for yourself:  The Fabric Store Blog ~ Ruffle sleeve dress pattern hack

I'm in LOVE with this Llira dress by Pauline Alice!!  B has already ordered the PDF for me and has promised to work his magic soon!!!

I was much tempted by this Faura top/dress, also by Pauline Alice...

...but when I saw this Honeycomb Shirt/Dress by Cocowawa Patterns, I knew it was perfect for me!!!

I think it will work better on my less curvy frame.

I just love the little collar and the detail on the long sleeved version!  And yes, Bentie is on it!!!!

I still have a long way to go.  It feels really strange not to have exercised in a month.  It goes against my grain to move so slowly, to have to ask for and accept help, for stupid things!!  Perhaps these road blocks I keep hitting is Mother Nature's way of teaching me grace, humility, and patience???  Okay, B!#CH!  I got it!!  Enough, already!!!

In case you were wondering - my answer remains unchanged.  I do NOT feel I have become a better person for having had cancer - TWICE!  I am NOT AT ALL thankful to have been attacked in this way!  I am seriously pissed!  For myself, and even more so for the hell that my dear ones keep having to endure on my behalf.  Still, I am forever grateful to all of you who have blessed me with your love and kindnesses ~ to "keep ever burning before my vagrant steps - the kindly light of hope".  Much love, les