Happy New Year!! It's March Forth!!!

I'm weird.  I know it. But, I make complete and total sense...to me!!! My favorite day is here. MARCH FORTH!!  I am so incredibly blessed to be here to celebrate it....again.
Here's a review:

2011: 3/4/11 - March Forth!!!!

2012: anti PD1 update from Moffitt

2013: March Forth...again!!!!!

2014: My favorite day ~ March Forth...with a special pic/vid for J& F!!!!

2015: Long term melanoma survivors....MARCH FORTH!!!!!

2016: Endobronchial Melanoma "Little is known...." Hear ye, hear ye....MARCH FORTH!!!!!

Spring always seems the best time to celebrate and glory in the New Year. And while I have recently lost dear melanoma peeps, felt inadequate to remedy the hurt and pain of too many of my little charges at work, looked around and had the sinking feeling that the world and its leaders have gone completely mad - the beauty of nature, and love of family and friends surrounds me still.

In appreciation of all the gifts I have been given, I send warm sunshine, delicate blooms, and the intrepid spirit that Mother Nature gives and instills in all her living things...to each of you.
March Forth!  love, les

Study in support of PET/CT Surveillance in Stage III melanoma patients

How often to scan/monitor Stage III melanoma patients is a bit unclear and difficult to get insurance to pay for.  This post starts with my own rant about BCBS denying coverage (initially) of an ANNUAL (Finally!  Annual!  After years of CT scans to neck, chest, abdomen and pelvis with MRI's of the brain every 3 months!!!) MRI of my brain (ME!  A melanoma brain met survivor!!) but more importantly includes a message "The Need to Demand Scans in Melaland!" from an amazing lady, the Queen of Melanoma herself, dear Carol Taylor toward the bottom of the post: And then there's me....   

Diagnosed as Stage IIIB in 2003, my scan surveillance was rather random.  There were 2 or 3 PET scans here and there.  But, for the most part I was followed by roughly every 6 month chest X-rays. One such film in 2009 showed a glump of "something" in my bronchus...but since I was an asthmatic we watched and waited, because, as I was emphatically told, "Melanoma never looks like that."  Long story short, a bronchoscopy in 2010 told the tale, "Yes!  Melanoma CAN look like that."  A brain MRI just after showed a brain met as well.  I had NO symptoms.

Now there is this....

PET/CT surveillance detects asymptomatic recurrences in stage IIIB and IIIC melanoma patients: a prospective cohort study. Madu, Timmerman, Wouters, et al.Melanoma Res. 2017 Feb 20.

AJCC stage IIIB and IIIC melanoma patients are at risk for disease relapse or progression. The advent of effective systemic therapies has made curative treatment of progressive disease a possibility. As resection of oligometastatic disease can confer a survival benefit and as immunotherapy is possibly most effective in a low tumor load setting, there is a likely benefit to early detection of progression. The aim of this pilot study was to evaluate a PET/computed tomography (CT) surveillance schedule for resected stage IIIB and IIIC melanoma. From 1-2015, stage IIIB and IIIC melanoma patients at our institution underwent 6-monthly surveillance with PET/CT, together with 3-monthly S100B assessment. When symptoms or elevated S100B were detected, an additional PET/CT was performed. Descriptive statistics were used to evaluate outcomes for this surveillance schedule. Fifty-one patients were followed up, 27 patients developed a recurrence before surveillance imaging, five were detected by an elevated S100B, and one patient was not scanned according to protocol. Eighteen patients were included. Thirty-two scans were acquired. Eleven relapses were suspected on PET/CT. Ten scans were true positive, one case was false positive, and one case was false negative. All recurrences detected by PET/CT were asymptomatic at that time, with a normal range of S100B. The number of scans needed to find one asymptomatic relapse was 3.6. PET/CT surveillance imaging seems to be an effective strategy for detecting asymptomatic recurrence in stage IIIB and IIIC melanoma patients in the first year after complete surgical resection.

Melanoma should be battle enough for anyone.  However, all you melanoma peeps out there are going to have to fight for the care you deserve.  On a positive note, with immunotherapy, targeted therapy and myriad treatment combinations providing real hope of effective options that can render folks stable or NED for years, the plight of Stage III melanoma patients is FINALLY getting some attention from researchers.  Keep pushing peeps.  The Queen and I have been pushing for years. Come on in...the water's...well...wet!!  But, together we can make a difference.  We have to!!! - c  

SRS with any systemic therapy helps response in melanoma...but anti-PD-1 WITH SRS = best OS in brain mets

I have been yelling for the longest....Radiation WITH systemic treatment is an incredibly beneficial combo for melanoma ANYWHERE, but especially in the brain!!!  This link:  Radiation and Melanoma  will take you to about 9 million research reports!!!  Now there's a breakdown of how folks SURVIVE melanoma brain mets when radiation is combined with 3 different therapies...ipi, BRAF/MEK, and anti-PD-1....

Survival of patients with melanoma brain metastasis treated with stereotactic radiosurgery and active systemic drug therapies. Choong, Lo, Drummond, et al. Eur J Cancer. 2017 Feb 22.

With new systemic therapies demonstrating activity in melanoma brain metastasis, most of the previously reported stereotactic radiosurgery (SRS) data are superseded. In this study, we report the outcomes (overall survival [OS] and brain control [BC]) and identify factors that associate with such outcomes in the era of modern systemic therapy.

A total of 108 patients treated with SRS from 2010 to 2015 were included. Systemic treatment use within 6 weeks of SRS was noted. OS was defined as time from SRS to death or last follow-up...[statistical] analyses were performed on clinico-pathological prognostic features associated with OS and BC.

The median age was 64.3 years, and the median follow-up was 8.6 months. Seventy-nine (73.1%) patients received systemic treatment. The median OS were as follows: anti-CTLA4 - 7.5 months, anti-PD1 - 20.4 months and BRAF inhibitor (BRAFi) ± MEK inhibitor (MEKi) - 17.8 months. Median BC was as follows: anti-CTLA4 - 7.5 months, anti-PD1 - 12.7 months and BRAFi ± MEKi - 12.7 months. In multivariate analysis, age and type of systemic therapy were strongly associated with OS. Age, Eastern Cooperative Oncology Group performance status, Graded Prognostic Assessment (GPA) score, and presence of symptoms were associated with BC.  

Favourable outcomes are seen in patients treated with SRS and with the best survival seen in patients treated with anti-PD1. Known independent prognostic factors for survival such as age and performance status and GPA score remain relevant in this setting.

To reinterate:  Ipi with SRS = 7.5 month OS.  BRAF/MEK with SRS = 17.8 months OS.  Anti-PD-1 with SRS = 20.4 month OS.  I would assume that the ipi/nivo combo would provide an even longer OS when combined with SRS....though that treatment was not addressed in this study.  Wishing you well. - c

Ipi plus peginterferon = 45% rate of AE's and 45% ORR

Taking interferon alone has proven to be a dismal treatment option as was noted here: 

For Stage II/III melanoma patients: Interferon NO BETTER than observation!!!!

 So...to be fair...there was this....

A phase IB study of ipilimumab with peginterferon alfa-2b in patients with unresectable melanoma.   Brohl, Khushalani, Eroglu...Weber. J Immunother Cancer. 2016 Dec 20.

Ipilimumab and peginterferon alfa-2b are established systemic treatment options for melanoma that have distinct mechanisms of action. Given the need for improved therapies for advanced melanoma, we conducted an open-label, single institution, phase Ib study to assess the safety and tolerability of using these two agents in combination.Study treatment consisted of ipilimumab given every 3 weeks, for a total of four infusions, concurrent with peginterferon alfa-2b administered subcutaneous weekly for a total of 12 weeks. This was followed by maintenance therapy with peginterferon alfa-2b administered subcutaneously weekly for up to 144 additional weeks. The study was designed as a two-stage dose escalation scheme with continuous dose-limiting toxicity monitoring during the induction phase.  Thirty one patients received at least 1 dose of study treatment and 30 were assessable for efficacy endpoints. We found that ipilimumab at 3 mg/kg dosing with peginterfeon alfa-2b at 2 μg/kg/week was the maximum tolerated dose of this combination. The incidence of grade 3 drug-related adverse events (AEs) was 45.2%. There were no grade 4/5 AEs. The overall response rate was 40% by immune-related response criteria. Median progression-free survival was 5.9 months. The median overall survival was not reached with at a median follow-up of 35.8 months.  We report that the combination of ipilimumab at 3 mg/kg dosing combined with peginterfeon alfa-2b at 2 μg/kg/week demonstrated an acceptable toxicity profile and a promising efficacy signal. Further study of this combination is warranted.

Guess I'm just not clear on why you would want to experience a higher rate of adverse effects in order to attain results that may not be quite as good as those we can already attain with anti-PD-1 as a single agent??????  Maybe if you hadn't attained a response with Opdivo or Keytruda?  But, if possible, why not try the ipi/nivo combo with it's 50-plus % response rate???

For what it's worth! - c

Sew Chaotically! - Colette's Aster

I bought this pattern at FULL price and thought it was just the cutest thing ever!!!

I was so eager to play with it....I used this last bit of the flannel I purchased in NY at B and J's to make it up right away.  Not having quite enough for the entire top, I thought my remnants of this chambray paired nicely.  Per the pattern measurement indicated, I cut a size 6.

I was excited to continue plaid matching in fun ways and psyched about using the selvage from this woven cotton flannel as the hem.  However, after I messed around with all that and tried it on, I discovered that perhaps I had mucked it up!!!  The top was (though it doesn't look it on Mannie) WAY too small across my shoulders!  So much so, that I left the sleeves open to the elbow at the seams, in hopes that my arms would still be able to function while wearing it!!!  I worked to convince myself I could wear it.  I let Rosie try it on, but alas, she had problems fitting her own massive shoulders into it as well!!  So....I gifted it to a nurse I work with.  Hopefully, she (and her tiny, little self) can use and enjoy it!!

Not to be deterred - one must live and learn!!! My first thought, "Did I mess up the shoulder yoke when playing about with my plaid matching?" I looked up reviews.  Nobody else mentioned ANY problems with the proportions of the back yoke to the rest of the top.  Bolstered, I decided to try again.  I carefully checked the back yoke pattern piece against Mannie.  Low and behold...to get the width I needed for the back...I should cut the size 12.  Sooooo...after much measuring and re-measuring - I cut the 12 - for all of it.  But, then...pretty much as I expected, I had to take in the sides...back to the size 6. 

But, having done that, I don't know.  The proportions remain off.  Furthermore, the difficulty many had with the burrito method the pattern espouses when attaching the inner back yoke was something I experienced myself.  I ended up doing it my way on this second one, it is clean and neat and worked far better, for me anyway.  Ditto for the way you are to finish the cute little neckline at the facing for the buttons.  I did it differently on both, neither quite as advised by the pattern.  Specifically, the "circle" one is advised to clip to... really does not seem to be appropriately placed.

If you look closely at this review, sew2pro, you'll see that despite this sewist's very cute result, her shoulders are struggling in the space allowed as well!!

Apparently, Colette is designed for chicas with narrower shoulders and bigger tah tah's than I possess.  Luckily, Rosie's curves can work with this last version.  Perhaps with all the working knowledge I now posses I'll give this pattern one more go....but....I'm not sure!!!

For me the Aster was a bit of a disaster!!!  Hee hee!  All was not lost!  I learned a lot about using bias binding, had fun despite the struggles, and Julia and Rosie have new tops that will hopefully give them a bit of pretty fun.  And.....Colette redeemed themselves with their FREE Sorbetto  top...blog coming soon!!!   Sew Chaotically- Lord knows I do!!!! - c

Side effects of immunotherapy - Part 7

Previous post:  Side effects to immunotherapy: Part 6   Continuing....

 Persistently curly hair phenotype with the use of nivolumab for squamous cell lung cancer. 

 Dasanu, Lippman, Plaxe.  J Oncol Pharn Pract. 2016 Oct 18.

Increasing use of programmed cell death protein 1/programmed cell death protein 1 ligand inhibition for the treatment of patients with various malignancies such as advanced lung cancer, kidney cancer, and melanoma has resulted in valuable clinical responses, along with the occurrence of new and often puzzling side effects. Known cutaneous effects of CTLA4 and programmed cell death protein 1/programmed cell death protein 1 ligand inhibitors include generalized pruritus, vitiligo, maculopapular lesions, and lichenoid skin eruptions. Alopecia has been the only hair effect previously associated with this class of agents. We describe herein the first case of a persistent curly hair phenotype with the use of nivolumab in a patient with metastatic squamous cell lung cancer.

Vasculitic Neuropathy induced by Pembrolizumab.   Aya, Ruiz-Esquide, Viladot, et al. Ann Oncol. 2016 Nov 17.

Atrophic Exocrine Pancreatic Insufficiency Associated with Anti-PD1 Therapy.  Long, Hoadley, Sandanayake.  Ann Oncol. 2016 Nov 17. 

PD-1 Antibody-induced Guillain-Barré Syndrome in a Patient with Metastatic Melanoma.

Schneiderbauer, Schneiderbauer, Wick, et al.  Acta Derm Venereol. 2016 Oct 14. 

Autoimmune Cardiotoxicity of Cancer Immunotherapy. Cheng, Loscalzo. Trends Immunol. 2016 Dec 2.
Contemporary immunotherapies (e.g., immune checkpoint inhibitors), which enhance the immune response to cancer cells, improve clinical outcomes in several malignancies. A recent study reported the cases of two patients with metastatic melanoma who developed fatal myocarditis during ipilimumab and nivolumab combination immunotherapy; these examples highlight the risk of unbridled activation of the immune system.

Autoimmune Hemolytic Anemia as a Complication of Nivolumab Therapy. Palla, Kennedy, Mosharraf, Doll. Case Rep Oncol. 2016 Nov 7.

Recently, immunotherapeutic drugs, including PD-1 inhibitors (nivolumab, pembrolizumab), PD-L1 inhibitors (atezolizumab, avelumab), and CTLA4 inhibitors (ipiliumumab), have emerged as important additions to the armamentarium against certain malignancies and have been incorporated into therapeutic protocols for first-, second-, or third-line agents for these metastatic cancers. Immune checkpoint inhibitor nivolumab is currently FDA approved for the treatment of patients with metastatic malignant melanoma, metastatic non-small cell lung cancer, metastatic renal cell cancer, and relapsed or refractory classic Hodgkin's lymphoma. Given the current and increasing indications for these drugs, it is essential for all physicians to become well versed with their common adverse effects and to be observant for other less documented clinical conditions that could be unmasked with the use of such medications. A definite association between autoimmune hemolytic anemia and the immune checkpoint inhibitor nivolumab has not been clearly documented, although a few cases have been reported recently. We report a case of fatal autoimmune hemolytic anemia refractory to steroids in a patient treated with nivolumab for metastatic lung cancer, and reflect on the other reported cases of autoimmune hemolytic anemia after the use of nivolumab.

Sarcoidosis in the setting of combination ipilimumab and nivolumab immunotherapy: a case report & review of the literature. Ruess, Kunk, Stowman, et al. J Immunother Cancer. 2016 Dec 20.

We report a case of sarcoidosis in a patient with metastatic melanoma managed with combination ipilimumab/nivolumab. Sarcoid development has been linked with single agent immunotherapy but, to our knowledge, it has not been reported with combination ipilimumab/nivolumab treatment. This case raises unique management challenges for both the melanoma and the immunotherapy-related toxicity.  A 46 year old Caucasian female with M1c-metastatic melanoma was managed with ipilimumab/nivolumab combination. Patient experienced response in baseline lesions but developed new clinical and radiographic findings. Biopsy of new lesions at two different sites both demonstrated tumefactive sarcoidosis. Staining of the biopsy tissue for PD-L1 expression demonstrated strong PD-L1 staining of the histiocytes and lymphocytes within the granulomas. Monotherapy nivolumab was continued without progression of sarcoid findings or clinical deterioration.  Tissue biopsy for evaluation of new lesions on immunotherapy is an important step to help guide decision making, as non-melanoma lesions can mimic disease progression.

Not trying to alarm anyone!!!  With melanoma you gotta get treatment!  And sadly, knowledge of side effects cannot necessarily prevent them.  Still,  forewarned may allow you to be forearmed in recognizing a problem so that it can be dealt with before it causes additional harm!

All my best, c