Lame, lazy PhD student!

Found this posted on my blog...twice:  

"Greetings, My name is Dr. Dana Hansen, Assistant Professor of Nursing at Kent State University. You can learn more about me by visiting my faculty web page at http://www.kent.edu/nursing/facstaff/bio/~dhansen1/ We are contacting you because you are listed as the contact person of the blog. My research team and I are interested in learning about the family caregiver’s experience with reading their loved one’s illness blog. A family caregiver is someone who provides emotional, spiritual, or physical care or support to a loved one. I was inspired to conduct this research during my sister-in-law’s journey through breast cancer. After interacting on her blog, I began to wonder what it was like for her husband (family caregiver) to read her blog. The family caregiver of the person who is writing the illness blog can find out more about our study by going to our study website: https://nursing.kent.edu/caretaker. There is a screen for you to share your contact information if you are"

On the surface, that all seems a worthy process, innocuous at best, if poorly written.  I have had the incredibly horrible, beautiful, emotional experience of helping families allow their children to die.  It was difficult for me and other staff.  I cannot begin to imagine how dreadful and heart rending it was for the families...even though I was there, watching, working, and supporting patient and family as best I could.  When you add that to my own life experiences, I am more than aware of the the need for nurses and other providers to know what the family and patients truly need and feel during those difficult times.  Yet, something about this chick's approach and the description of her own work...at odds with what is posted in her message....rankled!  So....I wrote her this!!!

Dear Dana,

So, let me get this straight:  You are working on your PhD.  And in your own words:  "The purpose of my research is to explore family interactions and relationships at the end life.  Often, families are uncertain of what to say or how to interact with their dying loved one during this difficult and stressful time.  Ultimately, I hope to discover important and unique aspects of family relationships at the end of life that will improve care of both the patient and family."  

 So, it would seem like you would bother to read at least a bit of the blog you are posting your lazy (no actual links to your addresses, exactly the same blurb used repeatedly) message on, to ascertain if there is really someone DYING (more rapidly than you are, for instance) on the blog in question!!!  But, no.  You didn't.  I am heartened only by the fact that looking at your bio, you don't appear to provide patient care.  That is a really good thing.  Sadly, if you actually attain your PhD you may have access to nursing students and curriculum development.  That would be a shame indeed.  However, I will be reaching out to your professors at Kent State.  If their motto is "Excellence in Action" this is it's antithesis!

And in case you are wondering who I am, since I am certain you haven't bothered to keep a record of the blogs you have left your message on, or the number of times you left that message, I am Celeste Morris, RN, MSN C-PNP.  I have taught nursing students how to provide complete, thoughtful, compassionate care with integrity.  I also provide pediatric care daily utilizing basic nursing skills, the knowledge of development and disease in children, and 30 plus years of experience, never failing to remain cognizant of my responsibility to respect the LIVES of my patients and their families, rather than assuming they are at the END of theirs, no matter what their diagnosis may be.  And, yes, I have Stage IV melanoma.

Your work could be valuable.  Your approach is lame and lazy.  You have a typo in your consent form and eligibility criteria as well as a missing word in your mission statement. Sad.  Perhaps this will jog your memory of who I am and teach you something about how great a nurse can really be, especially to a person with Stage IV disease.

My blog and a real nurse

Perhaps your PhD work will prove a learning experience after all.  C

SO!  Ruthie, Rosie, Freddo and B!! Sign up. Go for it.  https://nursing.kent.edu/caretaker/consent 
Get your 50 bucks!!!  You've certainly wasted plenty of time reading my crap!!!  You have my blessing alive and well, but I'll be dead someday...so make the big ones while you can.  Any other peeps out there who can meet this criteria????????

Eligibility: You are eligible for the study if you meet the following criteria: 

• Your and your loved one are 18 years or older; 
• The blogger must have a diagnosis of cancer, congestive heart failure (CHF), chronic obstructive lung disease (COPD), or human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS);
• The blogs must be written in English with a minimum of 1 posting per month;
• The family caregiver must participate in the blog by responding to the blog or reading the blog.

Make fifty bucks!  I am serious as a heart attack in an AID's patient having trouble breathing while dying of cancer!!!!  Good thing I view most of life as funny as hell!!  Hope I made you laugh.  Lord knows, we all need to.  So, thanks, "Dr." Dana!  I'll be in touch!!! - c

Spring/Summer Sewing! Lisette Passport and the Morris Blazer!!!

This is the story of the Lisette Passport dress and jacket, beautiful material that Ruthie gave me for my 50th birthday, and the Morris Blazer!!!!!

This T-shirt dress, blogged about before, is made from the same birthday stash.  The beautiful panel print gave me heart palpitations to cut into...but I lived and am very proud of the dress for it's matched sides, print placement, etc!!!  The matching jacket was somewhat of a coincidence, apart from my love of those particular colors!  It was to be a "muslin" of a jacket I would later make from additional amazing fabric Ruthie gave me.  It is the jacket from the PassPort pattern above.  On researching the pattern, folks said the pattern ran small. In retail world, I wear a 4-6 depending on brand.  In pattern world, I am generally a 10.  Given the internet sewists' advice I made a straight 12.  It fit perfectly! 

This dress is from the PassPort pattern as well. I looked the pattern over and made another straight 12. The pleats (that don't show up very well in this photo) are really awesome.  However, the side seams were tricky.  A quarter inch seam would have been perfect and easy enough, except for having to incorporate a side zip!! YIKES!!!  But, dealt with.  Not terribly noticeable here, but the flowers on top have a little green center that matches the jacket perfectly!

Next rendition:  Got a bit wiser and cut an ever so slightly wider side seam so that normal 5/8th's stitching and the side zip could be accommodated easily.  Perfect!

But, got to thinking.  The jacket above, which I will certainly make again (came together perfectly, fits great) has two pieces on each front side and three in the back.  Not an easy plan for a busy Ikat print (example jacket on the pattern sleeve not withstanding!!!)!  Then, Ruthie, to the rescue.  Just as my feeble brain was coming to grips with this reality...she emailed me a blip about the Morris Blazer!!!  How simple!  My esthetic!!  Fewer pieces!  The NAME!!!  PERFECTION!  And.....it is. I made this one as a muslin.  Despite matching my new purple dress and having a lovely hand...the fabric proved persnickety...prone to raveling and pulls.  The pattern went together very easily, as advertised by various sewists.  However, as someone with zero spatial relations skills, I had to go on faith that the pieces would actually form a blazer!  BUT!!!  They did!  And...I didn't have any trouble with step #15, placing the hem facing, etc.  Possibly because of warnings from sewist world or...because I'm awesome!  Hee hee!  At any rate, Morris Blazer = good. Though the jacket called for 2 pieces for the back, I cut one piece on the fold here as a test case for my upcoming print.  It worked perfectly and I see no reason to look back!

 Ta-dah!!!  The MORRIS Blazer in my special, celebrating 50 big ones, Ikat print!!!  Awesome, no?  Cutting the print made me nervous.  But, the results made me proud!  FYI:  Just to keep things super confusing...I made a straight size 8 in this pattern after peering nervously at pattern pieces on my mannequin and since that matched my measurements.  It worked!

And because I had more fabric than I realized.  A cute swingy top (McCall's 6960) that went together very well and had a neat way of approaching the inner facings that worked perfectly.

Happy sewing...or whatever you enjoy!!  Purple wardrobe, anyone??? - c

PD-L1 positive? Which immunotherapy is best? Same song, second verse...

Differential activity Nivolumab, Pembrolizumab, and MPDL3280A according to the tumor expression of Programmed Death-Ligand (PD-L1):  Sensitivity Analysis of trials in melanoma, lung, and genitourinary cancers.  Carbognin, Pilotto, Milella, et al.  PLos One.  June 18, 2015.

The potential predictive role of PD-L1 expression on tumor cells in the context of solid tumor treated with checkpoint inhibitors targeting the PD-1 pathway represents an issue for clinical research.  ORR was extracted from Phase I-III trials investigating nivolumab, pembrolizumab, MPDL3280A [an anti-PD-L1 product] for advanced melanoma, NSCLC, and genitourinary cancer...  Interaction test according to tumor PD-L1 was accomplished, and analysis performed.  Twenty trials (1,475 patients) were used.  A significant interaction per tumor PD-L1 expression was found in the overall sample with an ORR of 34.1% in the PD-L1 positive and 19.9% in the PD-L1 negative population.  ORR was significantly higher in PD-L1 positive in comparison to PD-L1 negative patients for nivo and pembro, with an absolute difference of 16.4% and 19.5% respectively.  A significant difference in activity of 22.8% and 8.7% according to PD-L1 was found for melanoma and NSCLS, respectively with no difference for gu cancer.  Overall, 3 antibodies provide a significant differential effect in terms of activity according to PD-L1 expression on tumor cells.  The predictive value of PD-L1 on tumor cells seems more robust for anti-PD-1 antibody (nivo and pembro) and in the context of melanoma and NSCLC.

Thoughts:
1.  Background info on MPDL3280A:  Anti-PD-L1 for melanoma phase 1 trial
2.  Note that you can still respond, even if PD-L1 negative.  Is that true?  Does that reflect action of the medication?  Or, is the current test for PD-L1 not terribly accurate?
3.  Let's standardize testing tumors for the presence of PD-L1 and make it available to all melanoma and NSCLC patients so treatments can be chosen more wisely!!!  NOW!!!  Prior rant on my tumor testing for PD-L1:  Info on test for PD-L1 from 2012!
4.  I think we ratties have given you enough intel over many years.  Researchers and FDA weirdo's...get with it!  Make this happen, TODAY!!!

Don't make me come back there!  c

Combo's looking good....but if PD-L1 positive...just do nivo!!??

What's new in melanoma?  Combination!  Ascierto, Marincola, Atkins.  J Transl Med.  Jul 4 2015.

Melanoma was again a focus of attention at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, in particular the use of combination treatment strategies involving immunotherapies and/or targeted agents. New data on targeted therapies confirmed previous findings, with combined BRAF inhibitor (vemurafenib) plus MEK inhibitor (cobimetinib) improving progression-free survival (PFS) compared to vemurafenib monotherapy in patients with BRAFV600 mutation-positive tumors (CoBRIM trial). Positive results were also seen with combined dabrafenib and trametinib in patients with BRAF V600E/K metastatic melanoma and encorafenib plus binimetinib in BRAFV600-mutant cutaneous melanoma. Even more interesting news centered on the use of combination immunotherapy, in particular the randomized, double-blind CheckMate 067 study in which median PFS with nivolumab plus ipilimumab was 11.5 months, compared to 2.9 months with ipilimumab alone and 6.9 months with nivolumab alone. Of interest, in patients with ≥5% PD-L1 expression, median PFS was 14 months with the combination or with nivolumab alone compared with 3.9 months in the ipilimumab group, while in the PD-L1 negative cohort, the combination remained superior to both monotherapies. Given that combination therapy was accompanied by a high occurrence of side-effects, this raises the suggestion that combination therapy might be reserved for PD-L1 negative patients only, with PD-L1 positive patients achieving the same benefit from nivolumab monotherapy. However, overall survival data are awaited and the equivalence of single agent to the combination remains unconvincing. Interesting data were also reported on the combination of T-VEC (talimogene laherparepvec) with ipilimumab, and the anti-PD-1 agent MEDI4736 (durvolumab) combined with dabrafenib plus trametinib. Emerging data also suggested that predictive markers based on immunoprofiling and mismatch repair deficiency may be of clinical use. In conclusion, the use of combination approaches to treat patients with melanoma, as well as other cancers, is no longer a just a wish for the future but is today a clinical reality with a rapidly growing evidence-base. Moreover, the most exciting consideration is that this is far from the end of the story, but rather a fantastic introduction.

Thoughts:
1.  What I've been saying....COMBO's!!!!
2.  But, which one???
3.  If you are BRAFV600 positive and are ready for BRAFi...these combo's are doing very well:  vemurafenib with combimetinib, dabrafenib with trametinib, and encorafenib plus binimetinib.
4.  Combo immunotherapy:  CheckMate 067 showed us PFS of 11.5 months on the ipi/nivo combo vs 2.9 months on ipi alone and 6.9 months on nivo alone.  BUT!!!!!  In PD-L1 positive patients PFS was 14 months on just nivo vs 3.9 months for ipi.  In PD-L1 negative patients the ipi/nivo combo was better than either monotherapy.  SO!  Since the ipi/nivo combo has more side effects but gives you no better results if you are PD-L1 positive....it probably makes more sense to just do nivo alone!
5.  T-VEC with ipi and yet another anti-PD1 product (MEDI4736/durvolumab) with dabrafenib plus trametinib seem promising as well.
6.  Here's hoping that markers and combo's become more clarified and APPROVED very soon.
7.  Thanks, ratties!!!
c

BRAFi: What predicts resistance? Discontinuation after complete remission? Dabrafenib/trametinib combo and quality of life?

The status of PD-L1 and tumor-infiltrating immune cells predict resistance and poor prognosis in BRAFi-treated melanoma patients harboring mutant BRAFV600.  Massi, Brusa, Merelli, et al. Ann Oncol, June 2, 2015. 

BRAF inhibitors improve survival in metastatic melanoma patients but the duration of clinical benefit is limited by development of drug resistance.  Here, we investigated whether the expression of Programmed Death-Ligand 1 (PD-L1) and the density of tumor-infiltrating mononuclear cells (TIMC) predict the occurrence of resistance, hence affecting the clinical outcome in BRAFi-treated melanoma patients. 
PD-L1 expression (cut-off - 5%) and TIMC were analyzed...from 80 consecutive melanoma patients treated with BRAFi at a single institution.  46 and 34 patients received vemurafenib and dabrafenib, respectively.  Membraneous expression of PD-L1 was detected in 35% of patients.  After analysis:  ABSENCE of tumoral PD-L1 staining and the presence of TIMC were associated with a better response to treatment.  Median PFS and OS were 10 and 15 months respectively.  Additionally, analysis demonstrated, PD-L1 expression and absence of TIMC correlated with SHORTER PFS.  Our results provide the first proof-of-principle evidence for the predictive and prognostic relevance of PD-L1 expression and density of immune cell infiltration of BRAF V600 mutated melanoma treated with BRAFi.

Thoughts:
1.  The study used a 5% cut-off for PD-L1 expression, while many studies use 1%, not sure that matters.
2. According to this study, patients treated with BRAF inhibitors did better if their tumors were negative for PD-L1 and loaded with TIMC.
3.  Now...these results can't (yet) be determined to mean that BRAFi was undermined by the presence of PD-L1 or facilitated by the presence of TIMC.  It is just one more study that demonstrates the presence of PD-L1 and absence of TIMC are bad prognostic indicators...unless...at least in the case of the PD-L1...you are taking anti-PD1 drugs.
4.  Notice...one more time...PD-L1 was present in 35% of patients.
5.  Clearly, we have lots to learn.

Complete remission of metastatic melanoma upon BRAF inhibitor treatment - what happens after discontinuation?  Tolk, Stzger, Mohr, et al.  Melanoma Res. June 8, 2015.

Treatments with BRAFi leads to complete remission in 3-6% of patients with BRAF mutant melanoma.  In cases of complete remission, it is unclear whether BRAFi therapy should be continued.  We retrospectively analyzed the clinical course of patients with metastatic melanoma who discontinued BRAFi therapy after achieving CR.  In 12 patients, CR of melanoma was diagnosed after a median BRAFi treatment duration of 13 (0.3-32 months) months.  Reasons for d/c were side effects in 7 and patient demand in 5.  Six patients are still in CR after a median 17 months (2-26 months) after discontinuation of BRAF inhibition.  Six patients developed a melanoma recurrence after a median of 3 (range 2-17) months of discontinuation of BRAFi therapy.  Subsequently, these patients were again treated with a BRAFi, which resulted in 3 CR, one stable disease, and one progressive disease, and one patient who could not be assessed.  Melanoma patients achieving CR during BRAFi therapy represent a heterogenous group.  Discontinuation of BRAFi therapy after CR has to be balanced carefully with the potential risk of nonresponding to BRAFi retreatment in the case of relapse.

Thoughts:
1.  While BRAFi provides a beneficial response in approximately 70-80% of BRAF positive patients, apparently only 3-6% of those gain complete remission.
2.  But, if you do....it seems that half of those will maintain remission (for at least 17 months...so far) after discontinuation of BRAFi.
3.  The half who do recur after stopping BRAFi, appear to have a 50% chance of regaining complete remission on retreatment. 
4.  These are very small numbers...but something to think about.

Health-related quality of life impact in a randomized phase III study of the combination of dabrafenib and trametinib vs dabrafenib monotherapy in patients with BRAF V600 metastatic melanoma.  Schadendorf, Amonkar, Stroyakovskiy, et al.  Eur J Cancer, March 17, 2015.

The COMBI-d trial that combined dabrafenib and trametinib vs dabrafenib monotherapy showed that patients taking the combo experienced significantly prolonged progression-free survival.  These same patients were evaluated regarding quality of life using an established questionnaire.  Questionnaire completion rates were more than 95% at baseline, less than 85% to week 40 and less than 70% at disease progression.  Baseline scores across both arms were comparable for all dimensions.  Global health dimension scores were significantly better at weeks 8, 16, and 24 for patients receiving the combo during treatment and at progression.  Pain scores were improved and meaningful in patients receiving the combo for all follow-up assessments vs those receiving monotherapy.  For other symptoms (nausea, vomiting, diarrhea, dyspnea, constipation) scores trended in favor of monotherapy.  This analysis demonstrates that the combo of dabrafenib and trametinib provides better preservation of quality of life measures and pain improvements vs dabrafenib monotherapy, while delaying progression.

Thoughts:
Given the better results and decreased side effects noted in the COMBI-d study when dabrafenib was combined with trametinib...improved quality of life is not really a surprise, but still nice to know.  For a refresher regarding BRAFi:  BRAFi for melanoma - dabrafenib, vemurafenib, and the dabrafenib/trametinib combo  For more info:  Data on BRAFi combo's

Wishing you all my best. - c

ASCO 2015: IL2 followed by anti-PD1 = GOOD!!!!

Overall survival of metastatic melanoma treated with high dose IL-2 followed by ipi.  J CLin Oncol 33, 2015.  Wong, Morse, McDermott, Kaufman, et al.

PROCLAIM is an IL-2 observational registry with over 40 participating sites consisting of a retrospective (n=70, locked) and prospective cohort (n greater than 343, ongoing). Previously, we reported a median overall survival of 20 months with a median f/u of 37 months in melanoma patients treated with HD IL-2 between 2007 and 2012 from a retrospective cohort (ASCO 2014).  We report this time,  analysis of 240 prospective patients. Patients must have received at least one dose of HD IL-2 prior to 2014.  Survival is current to Jan 2015.

For the 240 prospective patients, the median overall survival is 17.9 months and overall response rate is 15.2% at a median f/u of 20.1 months.  The 1 year survival rate of patients receiving anti-PD1 or ipi after HD IL-2 is 100% and 68% respectively, compared to 58% in IL-2 only group.  The median overall survival for these patients is 25.1 (n=20), 18.4 (n=75), and 14 months (n=112), and the median f/u is 24.2, 20.6, and 17.4 months respectively.  Of the 20 anti-PD1 patients, 12 received ipi first, 4 anti-PD1 first, and 4 anti-PD1 only.  The median time between the last IL-2 dose and start of ipi/anti-PD1 is 3.8 months.  There were no differences in IL-2 treatment intensity between these 3 groups.  Ten of 73 ipi patients suffered treatment-related autoimmune disease in post treatment f/u compared to 0 in the 20 anti-PD1patients.  There were no treatment-related deaths in the combined retrospective and prospective cohorts (n=578).

Conclusion:  The median overall survival for melanoma patients receiving anti-PD1 after HD IL-2 is significantly prolonged over either treatment with IL-2 only, or ipi therapy following IL-2.  The small 'n' for anti-PD1 group and intrinsic shortcomings of registries limits a definitive conclusion about the optimal sequencing of immunotherapies.  Checkpoint therapy after IL-2 appears to be well tolerated, does not impact therapeutic activity and provides a path forward for trials designed to enhance durable, unmaintained IL-2 responses.

Thoughts:
1.  Most researchers feel that combination therapy will hold the key to improved response rates for melanoma patients in the future.  Clearly the Ipi/Nivo combo is demonstrating that, albeit with increased rates of side effects.
2.  Here too, when IL-2 is followed by either ipi or anti-PD1, 1 year survival hits 68% after ipi and 100% after anti-PD1 vs 58% in patients given IL-2 alone. 
3.  Ipi remains the tricky component regarding side effects here...much as it is in the ipi/nivo combo.
4.  That 100% 1 year survival stat in patients having had IL-2 followed by anti-PD1 is AMAZING!!! 
5.  But....so far, that is in small numbers.
6.  And...patients selected for IL2 tend to be in pretty good health in order to be allowed to take the harsh regimen that it is.
7.  Will these numbers for the IL2/anti-PD1 combo end up beating the results for the ipi/nivo combo?
8.  Given the side effect profile and requirement for hospitalization with IL-2 administration...will the results be sufficient to make it worth the difficulty as a first line therapy?
9.  Will these results hold true for patients given anti-PD1 first....and IL-2 later?

Very interesting.  Keep up the good work, ratties.  Best - c

Opdivo/Nivo approved as firstline treatment in EU!

http://m.news.bms.com/press-release/european-commission-approves-bristol-myers-squibbs-opdivo-nivolumab-first-and-only-pd-

How wonderful is that??!! According to the article Opdivo has been given a rapid approval for use in previously treated melanoma patients AND as a first line therapy! The article goes on to describe various studies demonstrating the benefits and side effects of anti-PD1(Opdivo in particular). Stuff we already know as many of us were ratties in the fun and games. I can only assume that given this status, Opdivo is being covered by European payor sources. NOW! What the heck is going on here in the US? Hopefully, the tide will turn here very soon as well and we will all see anti-PD1 as a covered first-line treatment option!

Fingers crossed! -c