Sunday, September 24, 2017

LIVING with cancer. The need for psycho-social services. Pati continues to lead the way


B came upon this abstract today.  It touches on something elemental...the psychosocial aspects of a cancer diagnosis.  Having 'cancer' affects the patient, the family, everything.  We are not who we once were.  But, in the midst of trying to survive our cancer (with the simultaneous need to learn a completely new, and often foreign, cancer language - fit in doctor appointments, surgeries, radiation, oncologic therapies, manage pain and fatigue, not to mention bills and family obligations) - LIVING with cancer is a topic that is almost never addressed, while patients and their families try to soldier on with little to no psychological support or effort by institutions or medical providers to teach needed skills and coping mechanisms for the new cancer reality in which we now live.

A very dear one of mine has written:

Psycho-Oncology: A Patient's View. Garcia-Prieto P. Recent Results Cancer Res. 2018;210:57-66. doi: 10.1007/978-3-319-64310-6_4.  

Culturally the most important, valued, and less stigmatized part of cancer care is the medical part: The surgeon cutting the tumors out and the oncologist leading the strategic decision-making of the medical treatments available. The least valued and stigmatized part of cancer remains the psychosocial care. This chapter describes-through the eyes of an academic, psychologist, stage IV melanoma patient, and patient advocate-how one patient navigated changing psycho-oncological needs from early stage-to-stage IV through a whole range of psychological interventions available. Her voice joins that of all cancer patients around the world whom are urgently calling for psycho-oncological care to be fully recognized as a central part of cancer treatment.

I have tried to address this need, this world ~ many times:
2011:  Chemo Limo
2012:  My Life with Cancer
2014:  Tears and melanoma...they're not always sad...
2015:  Long term melanoma survivors....MARCH FORTH!!!!!
2015:  What to say and do....and NOT!!...for a cancer FRIEND (not patient)!
2015:  Health Monitor Magazine interview
2016:  Don't give up. Don't ever give up.
April 2017:  The Mental Price of Melanoma
June 2017:  ASCO 2017: Friends in need are friends indeed! Here's to the caregivers!!!

Yes, LIVING with cancer is not for sissies.  Luckily, we have had many advocates and dear cancer friends who, as beacons of light, have helped guide our way...even if current medical systems across the globe fail to address psychosocial needs as best they might.  Not the least of these amazing peeps is the author of the article highlighted above ~  Patricia Garcia-Prieto.

If you do not have time or interest in perusing my links above...I understand completely!!!  But, please!  Do have a peek at this one.... My Ode to Pati....a fallen comrade  especially her video, What's one life worth? [linked within].

You remain in my heart, Pati.  You continue to lead the way.  I hope your husband and sons are doing well.  love, les

Saturday, September 23, 2017

I like me some shrimp!!! Now their micro-RNA can suppress the stem like qualities of some melanoma cells???!!!



Me and Bubba, man! "... like I was sayin', shrimp is the fruit of the sea. You can barbecue it, boil it, broil it, bake it, saute it. There's uh, shrimp-kabobs, shrimp creole, shrimp gumbo. Pan fried, deep fried, stir-fried. There's pineapple shrimp, lemon shrimp, coconut shrimp, pepper shrimp, shrimp soup, shrimp stew, shrimp salad, shrimp and potatoes, shrimp burger, shrimp sandwich. That- that's about it."          ~ Forest Gump

Who knew those little shrimpies could demonstrate another route through which to target and defeat melanoma?????

Shrimp miR-S8 suppresses the stemness of human melanoma stem-like cells by targeting the transcription factor YB-1.  Yang, Wei, Shang, et al.  Cancer Res. 2017 Aug 30. 
Cross-species regulation of gene expression by microRNA is a possible untapped opportunity for miRNA-based therapy. In this study, we report a novel approach to ablate melanoma stem-like cells by targeting the transcription factor YB-1, which is significantly and selectively upregulated in these cells in melanoma. Silencing YB-1 expression was sufficient to significantly inhibit the stemness of melanoma stem-like cells. In exploring YB-1 targeting, we discovered that the shrimp microRNA miR-S8 could suppress human YB-1 expression in melanoma stem-like cells. Mechanistic investigations revealed that miR-S8 recognized the 3'UTR of YB-1 mRNA and mediated its degradation. In tumor cell and xenograft experiments, miR-S8 suppressed the tumorigenic capacity of melanoma stem-like cells by targeting human YB-1. Overall, our results illuminated a novel aspect of miRNA-mediated cross-species gene expression and its use in regulating cancer stem-like cells.
Oh, yeah!!  If this works out....I'll really be like'n some shrimp!!! - c

Thursday, September 21, 2017

Vitamin D and melanoma


We've long known that higher vitamin D levels provide a better prognosis in melanoma.  Here is a link (with others within) discussing Vitamin D:  Vitamin D and melanoma - folks with higher levesl do better - again!!!

Now there is this ~

On the role of classical and novel forms of vitamin D in melanoma progression and management. Slominski, Brozyna, Skobowiat, et al. J Steroid Biochem Mol Biol. 2017 Jul 1.


Melanoma represents a significant clinical problem affecting a large segment of the population with a relatively high incidence and mortality rate. Ultraviolet radiation (UVR) is an important etiological factor in malignant transformation of melanocytes and melanoma development. UVB, while being a full carcinogen in melanomagenesis, is also necessary for the cutaneous production of vitamin D3 (D3). Calcitriol (1,25(OH)2D3) and novel CYP11A1-derived hydroxyderivatives of D3 show anti-melanoma activities and protective properties against damage induced by UVB. The former activities include inhibitory effects on proliferation, plating efficiency and anchorage-independent growth of cultured human and rodent melanomas in vitro, as well as the in vivo inhibition of tumor growth by 20(OH)D3 after injection of human melanoma cells into immunodeficient mice. The literature indicates that low levels of 25(OH)D3 are associated with more advanced melanomas and reduced patient survivals, while single nucleotide polymorphisms of the vitamin D receptor or the D3 binding protein gene affect development or progression of melanoma, or disease outcome. An inverse correlation of VDR and CYP27B1 expression with melanoma progression has been found, with low or undetectable levels of these proteins being associated with poor disease outcomes. Unexpectedly, increased expression of CYP24A1 was associated with better melanoma prognosis. In addition, decreased expression of retinoic acid orphan receptors α and γ, which can also bind vitamin D3 hydroxyderivatives, showed positive association with melanoma progression and shorter disease-free and overall survival. Thus, inadequate levels of biologically active forms of D3 and disturbances in expression of the target receptors or D3 activating or inactivating enzymes, can affect melanomagenesis and disease progression. We therefore propose that inclusion of vitamin D into melanoma management should be beneficial for patients, at least as an adjuvant approach. The presence of multiple hydroxyderivatives of D3 in skin that show anti-melanoma activity in experimental models and which may act on alternative receptors, will be a future consideration when planning which forms of vitamin D to use for melanoma therapy.

For what it's worth! - c

Tuesday, September 19, 2017

Patients vs Docs: Choices in melanoma treatment


I've touched on this topic before.

Here, in Jan of this year:  Patients vs Docs - Treatment goals for cancer patients, in which researchers stated:  In our sample of 81 patients and 91 physicians63% of patients preferred the therapy with durable survival compared to 30% of physicians. The average patient preferred the therapy with durable survival even if the nonvarying treatment had 13.6 months longer average survival.  The presence of more severe AEs did not change these preferences.   In contrast, the average oncologist preferred treatments with fixed survival unless the survival had 7.5 months shorter average survival compared to the treatment with durable survival gains. These findings suggest patients value therapies that provide a chance at durable survival, and this result holds even when compared to therapies with more severe AEs.

Where I concluded:  Doctors should evaluate patients, explain their condition, work to find all available treatment options and present them, but PATIENTS should have the ultimate choice in the treatment they find right for them. Because it doesn't seem that docs and patients agree - and docs aren't the ones who could lose.

And here in April:   Perception....patient vs doctors in cancer care   Here, researchers noted:   "Patients place a high value on therapies that provide a chance of durable or "tail-of-the-curve" survival, whereas physicians do not. "  While my conclusion read in part:   A patient's perspective should be INCLUDED (at the very least) in their own health care decisions AND in research/trial development and implementation!!!  

Now there's this:

Patient and oncologist preferences for attributes of treatments in advanced melanoma: a discrete choice experiment.  Liu, Witt, Ebinghaus, et al.  Patient Prefer Adherence. 2017 Aug 14.

To examine and compare patient and oncologist preferences for advanced melanoma treatment attributes and to document their trade-offs for benefits with risks.
 
A discrete choice experiment (DCE) was conducted among advanced melanoma patients and oncologists. Qualitative pilot testing was used to inform the DCE design. A series of scenarios asked stakeholders to choose between two hypothetical medications, each with seven attributes: mode of administration (MoA), dosing schedule (DS), median duration of therapy (MDT), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and grade 3-4 adverse events (AEs). Hierarchical Bayesian logistic regression models were used to determine patients' and oncologists' choice-based preferences, analysis of variance models were used to estimate the relative importance of attributes, and independent t-tests were used to compare relative importance estimates between stakeholders.

In total, 200 patients and 226 oncologists completed the study. OS was most important to patients (33%), followed by AEs (29%) and ORR (25%). For oncologists, AEs were most important (49%), followed by OS (34%) and ORR (12%). An improvement from 55% to 75% in 1-year OS was valued similar in magnitude to a 23% decrease (from 55% to 32%) in likelihood of AEs for oncologists.

Patients valued OS, AEs, and ORR sequentially as the most important attributes in making a treatment decision, whereas oncologists valued AEs most, followed by OS and ORR. In comparison, patients differed significantly from oncologists on the importance of ORR, AEs, and PFS, but were consistent in OS and the rest of attributes.

So - when choosing treatment options, the issues in order of importance to patients were: Overall survival results, risk of side effects, overall response rates.  While oncologists considered side effects, then OS, then ORR to be the greatest priority.  Now....I could be decidedly uncharitable and assume that side effects are important to docs because if they treat patients with therapies that have fewer side effects, then they have less work to do and fewer problems to deal with!!!  But, I am not going to assume that.  What I AM going to say to oncs is this:  All treatments suck.  Melanoma can kill me if I don't get the best treatment I can.  I want to live.  And, I should  get to choose the treatment that suits MY level of tolerance for risk....NOT YOURS!!!!

Patient advocacy.  THAT is my job. - c

Monday, September 18, 2017

Sew Chaotically! - Striped Shirt Dress



I first made this shirt dress here:  Sew Chaotically! - Little denim shirt dress - Simplicity 8014!


This dress went together very well and I've made other renditions of it.  So....I decided to do one more!

I got this fabric a LOOOOOOOOG time ago, we're talking back in the 90's, with the idea of making some wide legged palazzo pants.  However, kids and college and kids and more college and work and melanoma and various other sundry events and activities intervened!!!  No worries.  Things come around.  Plus....the fabric turned out to be a FAKE!!!  After washing, the nice smooth sheen that is sometimes applied to make cheap cottons seem more luxurious washed away!!!  I was left with fabric that was much stiffer, unwieldly, more rumpled, now possessing an almost seersucker quality.  Probably not what I would have wanted in the imagined pants - but fine enough in this little dress.

No surprises in the pattern this time...as I have experienced all of them before!!  I did add length...as the original was pretty short.

I actually made the fabric belt for this version.

I can see this dress with flip flops on the beach, with tights and brogues, or boots and a jacket in cooler weather.

One more piece in the stash, turned into a useful garment!!!
Another example demonstrating that spending a bit more on "good" fabric, can be sewwwwww worth it!  I live and learn!!!  Sew Chaotically!!! - les

Friday, September 15, 2017

T-VEC (Talimogene laherparepvec, Imlygic...whatever you want to call it) - oncolytic virotherapy may improve the efficacy of anti-PD-1 by changing the tumor microenvironment!!


Those of you who have hung around this site for more than ten minutes know I have long been yelling about the benefits of intralesional/intratumoral therapies, especially when combined with systemic thereapies.  This synopsis of the latest ASCO report covers much of the data:  ASCO 2017: All things intralesional/intratumoral

Now there's this:

Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. Ribas, Dummer, Puzanov, ...Hodi, Long. Cell. 2017 Sep 7.  

Here we report a phase 1b clinical trial testing the impact of oncolytic virotherapy with talimogene laherparepvec on cytotoxic T cell infiltration and therapeutic efficacy of the anti-PD-1 antibody pembrolizumab. Twenty-one patients with advanced melanoma were treated with talimogene laherparepvec followed by combination therapy with pembrolizumab. Therapy was generally well tolerated, with fatigue, fevers, and chills as the most common adverse events. No dose-limiting toxicities occurred. Confirmed objective response rate was 62%, with a complete response rate of 33% per immune-related response criteria. Patients who responded to combination therapy had increased CD8+ T cells, elevated PD-L1 protein expression, as well as IFN-γ gene expression on several cell subsets in tumors after talimogene laherparepvec treatment. Response to combination therapy did not appear to be associated with baseline CD8+ T cell infiltration or baseline IFN-γ signature. These findings suggest that oncolytic virotherapy may improve the efficacy of anti-PD-1 therapy by changing the tumor microenvironment. 

The more we know....  Hang in there, ratties!!!  - c

Tuesday, September 12, 2017

Nivo better than ipi as adjuvant treatment for melanoma! Surprise, surprise, surprise!!!


For those of you who don't know...back in 2010 I joined 33 other ratties with resected Stage IV melanoma in a trial of nivo (with peptide vaccines that did NOT help).  I had had 2 cutaneous lesions, a positive node, went on to have a resected lung met, SRS to a brain met, and surgery for a tonsilar met, but was NED at entry to my trial.  There were 30 ratties in an advanced melanoma arm as well. Eventually that trial morphed into many, many different arms to include:  folks with prior use of ipi, to stop requiring the vaccines and HLA positive typing, the ipi/nivo combo and all sorts of things.
However, here are the results of my NED 33:  C'est moi!!! Results from the 33 ratties in my Nivolumb/Opdivo trial...published!

With my thoughts:  My Nivo (Opdivo) trial - first dose - 4 years ago 12/29/2010 - thoughts...
FYI:  I was treated with only 1mg/kg of nivo, every 2 weeks for 6 months, then every 3 months for 2 more years.

Now there is this:

Adjuvant Nivolumab vs Ipilimumab in Resected Stage III or IV Melanoma. Weber, Mandala, Del Vecchio, et al. NEJM. September 10, 2017.

Nivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence-free and overall survival rates that were higher than those with placebo in a phase 3 trial. We wanted to determine the efficacy of nivolumab versus ipilimumab for adjuvant therapy in patients with resected advanced melanoma.

In this randomized, double-blind, phase 3 trial, we randomly assigned 906 patients who were undergoing complete resection of stage IIIB, IIIC, or IV melanoma to receive an intravenous infusion of either nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks (453 patients) or ipilimumab at a dose of 10 mg per kilogram every 3 weeks for four doses and then every 12 weeks (453 patients). The patients were treated for a period of up to 1 year or until disease recurrence, a report of unacceptable toxic effects, or withdrawal of consent. The primary end point was recurrence-free survival in the intention-to-treat population.

At a minimum follow-up of 18 months, the 12-month rate of recurrence-free survival was 70.5% in the nivolumab group and 60.8% in the ipilimumab group. Treatment-related grade 3 or 4 adverse events were reported in 14.4% of the patients in the nivolumab group and in 45.9% of those in the ipilimumab group; treatment was discontinued because of any adverse event in 9.7% and 42.6% of the patients, respectively. Two deaths (0.4%) related to toxic effects were reported in the ipilimumab group more than 100 days after treatment.

Among patients undergoing resection of stage IIIB, IIIC, or IV melanoma, adjuvant therapy with nivolumab resulted in significantly longer recurrence-free survival and a lower rate of grade 3 or 4 adverse events than adjuvant therapy with ipilimumab

Here is a link to the full article:  Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. Weber, et al. NEJM

So here's the deal:

Stage IIIB, C, or Stage IV melanoma patients were allowed...even those with brain mets...as long as all were completely resected.

Patients joined from March 2015 to November 2015

There was a 5% cutoff for PD-L-1 staining (ie positive for PD-L-1 staining on tumors)

Nivo was given at 3mg/kg every 2 weeks or ipi was given at 10/mg/kg every 3 weeks for 4 doses then every 12 weeks.  Either drug was given for one year.

Patients were assessed via CT's of body and MRI of the brain every 12 weeks for 2 years, then every 6 months until year 5.

905 patients were studied, none of whom were still getting the drug by the final report.
Only 397 of these patients completed the full year of drug treatment.
Of the 452 in the nivo arm, 275 completed the year.  Of the 453 in the ipi arm, 122 completed.

Nivo outcomes were better than ipi no matter the patient's age, sex, disease stage, or BRAF status.  Nivo had fewer side effects.

In prior studies, ipi has demonstrated a pretty consistent 60% recurrence free survival in Stage III NED patients when used as adjuvant.  That number held in this study even when Stage IV patients were included.

Recurrence free survival at 12 months:
70.5% for nivo                    60.8% for ipi

Recurrence free survival at 18 months:
66.4% for nivo                    52.7% for ipi

Median distant metastasis free survival was not reached in either group.  However, it was longer in the nivo group with mets developing in 93 of the 369 peeps in the nivo group and in 115 of the 366 ipi group.

OVERALL recurrence free survival was 70.5% for the nivo group (vs 60.8% for ipi) at 1 year...but...when you pull out the Stage IV folks the number was 63% for nivo vs only 57% for ipi.

Back to me and my ratties, as of September 2015...of the 33 Stage IV ratties enrolled, only 10 of us had relapsed.  That is a recurrence free survival percentage of 69%....but with longer time out from treatment.  Interestingly, in my study....only 2 of the 10 brain met patients had relapsed.  

And finally, I am asked at least weekly by someone via email, MPIP, or my blog...
"So, when will I be safe?  If I make it out 1 year (2, 3, etc) I'll be free of melanoma, right????"

That is the zillion dollar question if you are lucky enough to have made it this far, isn't it?  Sadly, it is one that we do not yet have an answer to....though we ratties are doing our best to give you some great numbers with the treatments at hand.  

Here is one such discussion with references to other arms developed in my study:  9 months after Nivolumab trial...stats, f/u, what we learned....  

I have listened to B and Weber discuss Kaplan Meier curves until I thought my brain would develop ANOTHER tumor!!!  B arguing for 2 years being the point they flatten out....Weber hedging his bets and noting 3 years as that magical point.  Bottom line:  Every day out is one day better.  Researchers agree now, pretty much across the board, that one year out with no disease is great, 2 years out is amazing and 3 years out there is a plateau which may mean....a CURE!!!!    We shall see.  Melanoma is a sneaky bitch.  However, every day forward is another day.  Another day to live and enjoy. Another day down the road to a cure....whether via current treatments already attained...or even better ones that may save even more dear ones.

Here's to the ratties!!! - les