This one's for you, Artie! Electro/chemo to zap tumors!

ELECTROCHEMOTHERAPY TO METASTATIC SPINAL MELANOMA: A NOVEL TREATMENT OF SPINAL METASTASIS?   Gasbarrini, Campos, Campanacci, et. Spine. 2015 Aug.

Electrochemotherapy is a new antitumor treatment that combines systemic bleomycin with electric pulses delivered locally at the tumor site. These electric pulses permeabilize cell membranes in the tissue, allow bleomycin delivery diffusion inside the cells, and increase bleomycin cytotoxicity. Previous clinical studies have demonstrated the effectiveness of Electrochemotherapy in the treatment of several primary and metastatic solid tumors. Treatment planning for electrode positioning and electrical pulse parameters was prepared for four needle electrodes. Mini-open surgery with a left L5 laminectomy was performed to introduce the eletrodes. The assessed follow-up period was 48 months after the Electrochemotherapy procedure. Neither serious Electrochemotherapy-related adverse events, nor bleomycin toxicity were reported. Overall improvement in pain, ODI [level of disability] and KPS [performance] outcomes was better. Our case represents, to our knowledge, the first one to test the potential role of Electrochemotherapy as treatment of spinal metastasis. Electrochemotherapy allowed a successful treatment of metastatic spinal melanoma. However, we believe that there is a strong scientific rationale to support the potential utility of Electrochemotherapy as a novel treatment of spinal metastasis, regardless of the histological types. Super new.  No impact on or survival data included.  Don't know where it is offered in the US. Melanoma doesn't usually respond to "normal" chemo.  But in this treatment methodology...zapping the tumor with electrodes first seems to make them more responsive to the chemotherapy....that was then administered systemically. (Wonder why they didn't try a local injection???) Reminds me a bit of the ADC therapy J tried where nasty ass chemo was linked to a monoclonal antibody that (in theory) would be drawn into the tumor cells only.  Once there, the chemo would be unleashed. Here's a post on that one:  ADC's - Antibody Drug Conjugate Unfortunately, while ADC therapy held tumors in check for some...there was pretty substantial chemo leakage that led to typical chemo side effects:  hair loss, fatigue, loss of appetite, neuropathy, etc.  So...don't know if you could even access this treatment, Artie....but it is one of the ways folks are trying to make old time chemo work for melanoma patients.  Warm wishes to you all - C

Positive response to Helper Peptide Vaccines for melanoma

Long-term Outcomes of Helper Peptide Vaccination for Metastatic Melanoma.  Hu, Kim, Blackwell, Slingluff.  Ann Surg. Sep 2015

 

The objective of this study was to compare the long-term outcome of patients with metastatic melanoma vaccinated with 6MHP to that of a group of unvaccinated historical controls. A multipeptide vaccine (6MHP), designed to induce helper T cells against melanocytic and cancer-testis antigens, has been shown to induce specific Th1-dominant CD4+ T cell responses. The 6MHP vaccine was administered to patients with metastatic melanoma. Circulating CD4+ T cell responses were measured by proliferation or direct IFN-gamma ELIspot assay. Overall survival of vaccinated patients was compared to a group of clinically comparable historical controls using multivariable Cox regression analysis and Kaplan-Meier survival analysis, taking into account age, metastatic site, and resection status. Across 40 vaccinated patients and 87 controls, resection status and vaccination were associated with improved overall survival. Forty pairs of vaccinated patients and controls were matched by metastatic site, resection status, and age within 10 years. Median survival was significantly longer for vaccinated patients (5.4 vs 1.3 years). Among the vaccinated patients, the development of a specific immune response after vaccination was associated with improved survival. Helper peptide vaccination is associated with improved overall survival among patients with metastatic melanoma. These data support a randomized prospective trial of the 6MHP vaccine. I was given 6 peptide vaccines IM every two weeks with every infusion of nivo I received for the first 6 months of my trial.  It was determined that they did no good and administration of them was ceased in patients who followed my cohort.  Link to the explanation of their use:  My anti-pd1/vaccine trial results 2012  However, in 2013, there was this out of MD Anderson:  Peptide Vaccines do not trigger effective immune response  BUT!  My vaccine was quite different from this one!!!  I still hold out hope that vaccines will be the answer to at least some, if not all, of the curing melanoma equation!!! Best to you all - c

Being female with low LDH, no ulceration in primary, and BRAF V600E positive = increased rates of survival with BRAFi for melanoma patients?!!!

Clinicicopathologic features associated with efficacy and long-term survival in metastatic melanoma patients treated with BRAF or combined BRAF and MEK inhibitors.  Menzies, Wilmott, Drummond, et al.  Cancer.  Jul 28, 2015.

For 142 consecutive immunotherapy - and MAPK inhibitor-naive patients with BRAF-mutant metastatic melanoma who were treated during clinical trials with BRAFi (n=111) or the combo of dabrafenib and trametinib (n=31), clinicopathologic factors were correlated with the response to MAPK inhibitors and survival.

Median f/u = 15.7 months.  The 2, 3, and 4 year overall survival (OS) rates were 43%, 24% and 24% respectively.  Statistical analysis demonstrated that the only clinicopathologic factors associated with longer Progression Free Survival (PFS) and OS were being female and a normal pretreatment serum lactate dehydrogenase (LDH) level.  BRAF V600E genotype and an absence of primary melanoma ulceration were also independently associated with longer PFS but not with OS.  The median OS was 23.5 months for patients with normal LDH levels and 7.3 months for those with elevated LDH levels.  Complete responders had the best survival, but disease progression still occurred in 2 of 7 patients.

We certainly need to figure out what treatment works for whom.  I think it is important to note that these patients were all treatment naive...apparently.  For whatever that is worth.  This provides the first real confirmation of the importance of a low LDH to outcome that I have seen.  It also provides one more bad mark for ulceration of primary lesion, as that has long been noted to be related to a poorer prognosis.  

Hang in there, peeps! - c

Leptomeningeal disease - a case study

Intrathecal administration of tumor-infiltrating lymphocytes is well tolerated in a patients with leptomeningeal disease from metastatic melanoma:  A case report.  Glitza, Haymaker, Bernatchez, et al.  Cancer Immunol Res. 2015 Jul 27.

Patients with leptomeningeal disease from melanoma have very poor outcomes and few treatment options.  This is a case of intrathecal administration  [an injection directly into the spinal fluid] of autologous tumor infiltrating lymphocytes (TIL) in a patient with leptomeningeal disease (LMD) which developed after prior treatment with surgery, high-dose bolus IL-2, and systemic TIL infusion and experienced radiographic progression after intrathecal (IT) IL2 therapy.  Pt was given weekly treatment with increasing numbers of IT TIL followed by twice weekly IT IL2.  Analysis of CSF demonstrated increased inflammatory cytokines following the treatments.  Subsequent imaging demonstrated stable disease and neurological deficits also remained stable.  The patient expired 5 months after the initiation of IT TIL therapy with disease progression in the brain, liver, lung and abdominal lymph nodes but, WITHOUT LMD progression.  These results demonstrate safety of IT TIL and support a prospective clinical trial to determine clinical benefit in these patients.

Very sad overall.  Though hopeful in the sense that while IL2 intrathecally didn't help...when combined with TIL it did.  This is a very difficult situation that some melanoma patients and their families face, so any treatment improvements will certainly be a boon.  Why this patient wasn't simultaneously or previously administered an immunotherapy is not mentioned.  But, it seems to me that might have been helpful as well.

Wishing you all my best.  - c

51 years, 51 years...and believe it or not...I'm still here!!!

What a beautiful surprise!  51 years! I am thankful for every one.  Not every  moment was perfect or pain free, but they all combined to build the person I am today.  I like that.  I tried to teach my children and students that while one could learn from perfect examples and textbook cases, there was much to be said for learning from those you didn't wish to emulate, experiences that were less than fun.  I hope I have lived up to my own advice. I am not certain what my future holds.  Is anyone?  I find myself still a bit desperate to "get things done".  There are those who would argue that that was the case for me since birth.  However, I know the change in how I  feel.  Since melanoma.  There is an urgency I can't shake.  And I don't think that's bad.  At first...I wanted to see my children through middle school.  With that accomplished, please....could I just help mentor them through high school?  Set them off to college or the next step they chose?  Once there...might I just help them settle into the lives they have built for themselves?  Not a bit greedy am I?  But, I am.  Greedy for these things and more....  Time with B.  Laughter with friends.  That special light at dusk. A walk in the woods.  The sound of rain.  A beautiful song.  A perfect verse.  A parent helped. The smile of a child.  A diagnostic puzzle solved.  Melanoma thwarted.

And there was my MONTH of BIRTHDAY.  Because I am spoiled ROTTEN!!  A beautiful table built by B.  A picture like a window...into sweet memories and a beautiful river.  A perfectly designed blouse.  Beautifully wrapped and explained sewing toys.  A trip to Moscow...in a cup.  Visits and art from those dear.  And then there was this...from a dear one...who knows me well....

An amazing classical Happy Birthday to YOU!!!

Thanks to all of you.  Celebrate YOUR days....as best you can.  Much love - c

Keeping you informed about the a$$hole: Dr. Dana Hansen from Kent State University

You may remember this post:  Lame lazy phd student 
It was in response to an A$$ HOLE who wanted to interview my peeps about reading the blog of a DYING cancer patient....replete with typo's and crass ass shenanigan's....who was stupid enough to post her shit on MY blog.  I sent her the letter published in the link. Surprisingly (not)...there was no reply.  Funny, Dana.  You liked posting on my blog before!  Well....you know I love my research!!!  Turns out....she's not a student!  She's a chubby weirdo who is actually PAID as an assistant PROFESSOR at Kent State!!!!!!!  Check her out:  http://www.kent.edu/nursing/profile/dana-m-hansen-phd-rn   (Dana, honey!!!  Did you not take diet, nutrition, and exercise classes in your nursing curriculum????)

Anyhow...Miss Dana...DID get my email.  How do I know?  Well, she deleted some of her bullshit...though it is preserved on my original post.  Some of her links in my message have been take down and typo's...at least some of them....have been corrected.  However, this is what I have also learned.....

She posted her crap here:  Blog: My Journey with Inflammatory Breast Cancer

And here:  I have cancer, but it won't have me...  I'm sorry, but does this sound like a dying person to you?

And she went there....here....Dried my tears and threw on my big girl pants  I mean really!!!  Read this post.  Would you post here that you wanted to interview the peep of the "dying" person????  But, a "NURSE" did!!!!!!!!

And this...on a post from 2014:  COPD thread

And here:  carcinoid syndrome flushing You thought THIS chick was dying?????!!!!

And she put this:  on someone's 2014 post!!!

This poor person is freaking out because she SURVIVED!!!!!  Yet Miss Compassionate Nurse Dana posted here too:  Sometimes i feel like i am falling apart

With a sense of humor like this....this lady is NOT on death's door....Don't worry, it's not ebola
Of course PhD Dana couldn't be bothered with figuring that out!!!

And this blogger, while going through some hard times, is training for a triathlon!!!!!  cancer cures life

Sadly...there are more.  However, I feel I have proven my point and wasted enough time.  You are one sick cookie, Miss Dana PhD Hansen.  And to all of us proud to be in the nursing profession...an extreme embarrassment.  Kent State...you pay this person????  Seriously?????  WOW!

(Oh, yea....my peeps.  I'll be forwarding this post to Kent State...and Ms Dana.  Don't you worry!!!)  As if having cancer wasn't enough!!!  - c

Itching and vitiligo associated with progression free survival after Pembro/Keytruda???!

Pembrolizumab cutaneous adverse events and their association with disease progression.  Sanlorenzo, Vujic, Daud, Algazi, et al.  JAMA Dermatol.  2015 Jul 29.

While immunomodulatory anticancer drugs, like anti-PD1 are promising....little is known about cutaneous adverse events caused..and their possible correlation with treatment response.  Single institution, retrospective medical record review, March 1, 2011 - May 28, 2014.  83 patients from 2 clinical trials...who had at least 1 dose of pembro and at least 1 f/u visit.  43 patients had 10mg/kg q 3 wks, 24 had 10mg/kg q 2 wks, and 16 had 2mg/kg q 3 weeks.  66 were melanoma pts, 15 were lung, 1 prostate cancer and another was treated for Merkel cell carcinoma.  

35 patients (42%) developed cutaneous AE's.  Most common = papular eruption (24[29%]), itching (10[12%]), hypopigmentation {vitiligo} (7[8%]).  All 7 pts who developed hypopigmentation were being treated for melanoma.  Survival analyses showed that patients who developed cutaneous AE's had significantly longer progression-free intervals in all 3 treatment dosage groups, compared to patients who did not develop cutaneous AE's.

CONCLUSION:  Pembro was associated with side effects related to the skin in 42% of patients.  The development of these cutaneous AE's, especially hypopigmentation in patients with melanoma, could point toward better treatment response.


Link to post describing general side effects from anti-PD-1 and why we get them:  Side effects of anti-PD1 (Nivo in this case, though data is very similar for Pembro)

Link to post from ASCO 2015:  How Nivo side effects are associated with survival

Link with info from 2015 with article demonstrating positive link between vitiligo and remission of melanoma, back ground info, and white patches:  Vitiligo a good prognostic indicator for melanoma

Pretty much what we've been hearing (and seeing!!) already.  There has got to be something going on between the CD8 T cells, dendritic cells and melanoma, especially since only the melanoma patients in the study developed vitiligo.  B's been screaming about this for years!!!  It is clear that a link between these things exists...but we don't yet know how to ELICIT the vitiligo response so that more melanoma patients GET a response!  Come on researchers!!!  We've got a vaccine for ebola, a reliable treatment for Hep C...let's do this!!!!! - c