Saturday, February 18, 2017

Sew Chaotically! - Fit and Flare Dress M7244 - Second make...


I first made this dress for Rosie here:  Sew Chaotically! - McCall's Fit and Flare Dress 7244






It turned out really well and I think she has gotten many good, fun wears out of it!  I've been waiting to find the right material to make mine.  I happened upon this super soft, textured knit at JoAnn's and knew it would be perfect!

This pattern goes together very well.  My only changes were to leave off the back zip (which I had done for Rosie's as well) and take up a bit of ease out of the back before I placed the pattern piece on the fold, then I left off the facing to the lining that the pattern includes as you can see here in the version I made Roo...
Making it per pattern instructions you cut a facing of the dress material that you add before attaching the lining.  This added extra work and a seam that can show up nobbly-like on the right side!  I just didn't see the point!

For mine, I simply cut the lining pieces as replicas of the front and back.  Works for me!





Spring may be on the way, but it is still too cold to be out here without a coat, y'all!!  #sillysewingblogproblems
This is a cute comfy dress that I am currently wearing with tights or boots, but looking forward to wearing with Tennies or ballet flats once the weather is warmer!  Sew chaotically!!! - love, c

Thursday, February 16, 2017

Antibiotic use MAY decrease effectiveness of immunotherapy?????


The article which discusses a study that looked at renal cancer patients on various immunotherapies (anti-CTLA-4, anti-PD-1, anti-PD-L1 and nivo specifically) and efficacy when patients had and had not been exposed to antibiotics is noted below, but here's the link: http://www.onclive.com/conference-coverage/gu-2017/antibiotic-use-may-damper-the-efficacy-of-checkpoint-inhibitors.

I can only imagine the author intended to write "Dampen" rather than "Damper"!!!  (How is it that others are paid for writing this mess and I am not????  Hmmmm....) At any rate, data already theoretically supporting this premise is the idea that certain intestinal flora, bifidobacterium in particular, which would be killed off by certain antibiotics, promote the efficacy of immunotherapy...as was noted in this post:  Cooties in our gut keep us skinny, smart and cure cancer!?????

On the other hand...there is this on doxycycline....an old antibiotic...though this is strictly relative to melanoma itself...NOT the use of immunotherapy (see the 2nd and 3rd articles in this post): EVERYTHING cures melanoma....so why do we have it??????

But...here you go.......

Antibiotic Use May Damper the Efficacy of Checkpoint Inhibitors  Lisa Miller, writing for OncLive, Feb 13, 2017.

Use of antibiotics up to a month before treatment with a checkpoint inhibitor may decrease the efficacy of the immunotherapy agent, results of a retrospective analysis show. The analysis, presented during a presscast of the 2017 Genitourinary Cancers Symposium, raised suspicion of the relationship between gut microbiota and antibiotics and their effect on immune checkpoint blockade agents.

In patients with metastatic renal cell carcinoma (mRCC), patients who had received broad-spectrum antibiotics had a shorter median progression-free survival (PFS) rate when treated with checkpoint inhibitor immunotherapy than those who had not received antibiotics of 2.3 versus 8.1 months, respectively
.

Previous preclinical studies using mouse models have suggested an association between antibiotics and the efficacy of immune checkpoint blockade agents.
2 “This is the first analysis evaluating the impact of antibiotics on outcome in mRCC patients treated in the era of immune checkpoint blockade,” said investigator Lisa Derosa, MD, PhD candidate, of the Gustave Roussy Cancer Institute, Paris-Sud University in Villejuif, France.

Researchers analyzed 80 patients with mRCC who were being treated with checkpoint inhibitors on trials at the Gustave Roussy institute. Immunotherapy treatments included single-agent anti–PD-1/PD-L1 therapy (n = 67), a combination of a PD-1 inhibitor and a CTLA-4 inhibitor (n = 10), and a combination of anti–PD-L1 therapy and bevacizumab (Avastin; n = 3).

A majority of the enrolled patients were male (65%), 88% had a clear-cell histology, and 80% of the patients had prior nephrectomy. Twenty-one percent had favorable disease by International mRCC Database Consortium (IMDC) risk standards, 57% had intermediate IMDC risk, and 22% had poor-risk disease. Sixteen patients (20%) had received antibiotics up to 1 month prior to starting treatment with immunotherapy, including mostly beta-lactamases or fluoroquinolones.

At a median follow-up of 6 months, overall survival (OS) results were not yet able to be reached in the overall population, but a negative trend was already noted for patients who received prior antibiotics. The objective response rate also favored patients who had not received antibiotics
.

In a subgroup of 62 patients who were treated with nivolumab (Opdivo) monotherapy, patients who had not taken antibiotics showed a greater PFS rate, which also achieved statistical significance
. OS in the nivolumab monotherapy subgroup was also significantly higher in patients who had not taken recent antibiotics.

“Derosa shows that antibiotic therapy may have a direct impact on how well the PD-1 inhibitor nivolumab works in patients with kidney cancer,” said Sumanta K. Pal, MD, who moderated the presentation.

“Immune based therapies for cancer may have a complex interplay with the host’s microbiome,” commented Pal, an assistant clinical professor in the Department of Medical Oncology and Therapeutics Research and co-director of the Kidney Cancer Program at City of Hope in Duarte, California. “Antibiotics may influence the bacterial composition of our gut, and this could in turn impact how effective immune therapy is.”

Derosa stated that the data was preliminary but that it encouraged longer follow-up and further studies to confirm the hypothesis of the study.

“The observations that Derosa makes have some consistency with preclinical observation,” Pal said. “We may be able to offer some insights as to whether or not bacterial composition of the gut could affect clinical outcomes and that might help us guide antibiotic usage.” Pal also suggested that these findings are not yet mature enough to impact clinical practice. The researchers plan to enroll additional patients in this study to investigate the mechanism of action. Other studies exploring the relationship between antibiotics and the efficacy of immunotherapy agents in lung cancer and kidney cancer are ongoing.

Thanks for sharing, Eric!  You're 'da bomb!!! - love, c

Wednesday, February 15, 2017

TIL with Vemurafenib in melanoma - Good showing in small Pilot trial


A Pilot Trial of the Combination of Vemurafenib with Adoptive Cell Therapy in Patients with Metastatic Melanoma.  Deniger, Kwonf, Pasetto, et al.  Clin Cancer Res. 2017 Jan 15.

This pilot feasibility clinical trial evaluated the coadministration of vemurafenib, a small-molecule antagonist of BRAFV600 mutations, and tumor-infiltrating lymphocytes (TIL) for the treatment of metastatic melanoma.

A metastatic tumor was resected for growth of TILs, and patients were treated with vemurafenib for 2 weeks, followed by resection of a second lesion. Patients then received a nonmyeloablative preconditioning regimen, infusion of autologous TILs, and high-dose interleukin-2 administration. Vemurafenib was restarted at the time of TIL infusion and was continued for 2 years or until disease progression. Clinical responses were evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. Metastases resected prior to and after 2 weeks of vemurafenib were compared using TCRB deep sequencing, immunohistochemistry, proliferation, and recognition of autologous tumor.

The treatment was well tolerated and had a safety profile similar to that of TIL or vemurafenib alone. Seven of 11 patients (64%) experienced an objective clinical response, and 2 patients (18%) had a complete response for 3 years (one response is ongoing at 46 months). Proliferation and viability of infusion bag TILs and peripheral blood T cells were inhibited in vitro by research-grade vemurafenib (PLX4032) when approaching the maximum serum concentration of vemurafenib. TCRB repertoire (clonotypes numbers, clonality, and frequency) did not significantly change between pre- and post-vemurafenib lesions. Recognition of autologous tumor by T cells was similar between TILs grown from pre- and post-vemurafenib metastases.

Coadministration of vemurafenib and TILs was safe and feasible and generated objective clinical responses in this small pilot clinical trial.

Granted, this requires being BRAF positive...but still....it may be a good option for those peeps. Questions I do have:  Are these folks EVER going to get to come off BRAF....even with their complete response?  One would think so...but this study comes to mind:   Stopping BRAF/MEKi after a complete response? Case study of 12 melanoma patients...     
There is also this:  How are these patients dealing with side effects if they are given only a BRAFi, rather than BRAF/MEK, since we have learned that, oddly enough, the combo causes not only less resistance, but fewer side effects as well?  Guess the ratties will teach us all.  - c

Monday, February 13, 2017

Thoughts on Trials and Clinical Research by Melanoma Big Dogs


Y'all know I've been yelling about this for years:

Most recently here:  The trial of trials

And previously ~
2016:
The Problem with Clinical Trials

Medical studies in children go unpublished!!! Here we go AGAIN!!!

2015:
A beautiful lady, with eloquent, though heartbreaking words re: clinical trials....

2014:
Clinical Trials and Patient Rights...An oxymoron????

Patient rights in a clinical trial. An oxymoron???? Redux...

Challenges in Conducting Clinical Research on Patients With Advanced Melanoma.  Cancer J. 2017 Jan/Feb.  Sznol.

Unprecedented advances in the treatment of melanoma and the large number of investigational therapies entering clinical studies not only represent outstanding achievements, but also create major challenges for clinical research in melanoma. The challenges for accrual and for developing important new data in trials include the relatively low incidence of melanoma compared with other diseases, a shrinking pool of patients for trials because of the high efficacy of standard of care therapy, requirements for larger studies and longer duration of follow-up to detect signals of activity or establish efficacy, and suboptimal predictive biomarkers for the vast number of new combinations and new agents. The cost of new treatments remains a major concern, particularly because current standard of care involves doublets of targeted therapy or immune therapy, and clinically meaningful further increases in efficacy may require development of triplets or larger multidrug combinations. Toxicities of the current doublets, particularly for immune therapy, may limit development of some multidrug regimens or may require novel solutions such as sequencing or alternating schedules. The activity of first-line therapies may push development of new drugs or combinations into the second-line setting or into subgroups with suboptimal response to the first-line doublets as identified by predictive clinical variables or tissue biomarkers.


Clinical Trial Design and Endpoints for Stage IV Melanoma in the Modern Era.  Izar, Regan, McDermott.  Cancer J. 2017 Jan/Feb.
Immunotherapies and targeted therapies for the treatment of metastatic or advanced melanoma produce unique patterns of antitumor response. Conventional outcome measures, such as median progression-free and overall survival, may not be ideally suited to identify all patients who derive a benefit from such therapies. Therefore, the introduction of additional endpoint measures, such as milestone comparisons, may be necessary to characterize the potential benefit of such treatment approaches. Immune checkpoint inhibitors induce durable responses in a portion of patients that may continue after treatment cessation. Measuring the associated treatment-free interval, treatment-free survival, and associated patient-reported outcomes could provide important information when implemented in prospective clinical trials. In this article, we discuss the limitations of current endpoint measures and the potential advantage of using novel endpoints and how these might be used in designing clinical trials to address critical unanswered questions for patients with metastatic melanoma.  
YES!!!  While PFS and OS are certainly important milestones, as noted here:  After stopping anti-PD1 treatment...how long can melanoma patients maintain a complete response????    Identifying duration of response and patient outcomes are essential for progress and the development of intelligent treatment choices.
While wheels always turn more slowly than I'd like them to, I have to believe we will get it right....soon!  Thanks to all the ratties!  Hang tough! - love, c

Sunday, February 12, 2017

Travel Chaotically! - New York - Street Fair and Central Park


On day 4 of our stay, we woke to the knowledge that just the day prior some freak had tried to kill and maim with bombs set off in NJ and on streets we had just walked.  But on the way to The MET....



Uptown, downtown!  I got this!

...we found a street fair on Lexington!!  With Jerk chicken, rice and beans that were tasty....and the best Empanada I have ever eaten!!!

Food and products from all parts of the globe...

...enjoyed by all sorts of peeps....


...and kids....

...of every stripe!!!

With many interesting items!!!





Diversity and cute pinkness makes every girl want to twirl!!

Posh streets and hotels as we walked on toward central park....



We ended the day with a lucky turtle!!  On the following day, we took a nice walk through the drizzle to a big breakfast at a typical NY diner before taking more trains back out to the airport for our flight to Paris.  Thanks, New York!  You lived up to every description of the wonder of the Big Apple and Lady Liberty....“Give me your tired, your poor, your huddled masses, yearning to breathe free,” welcoming folks of every type...including a girl from Alabama/Tennessee! Take that, crazy man trying to hurt and frighten folks in NJ and NY!!  They (and we) are bigger and better than any meanness or horror you can try to create!  I look forward to my next visit!!  Still need to check out Harlem, The Bronx and some Singapore noodles!!!
 'Til next time, New York - c

Saturday, February 11, 2017

Travel Chaotically! - New York - Mulberry Street!


So much to see!!  While we used the metro a bit....B suspects that we walked at least 8-10 miles per day.  How else can you see it all??????


But....that can give a girl who brought old shoes on the trip with the bright idea that she would toss them before the trip back home, blisters!!!  And a NEED for NEW shoes!!!!  So....I got some!


But THEN.....I found THIS store!  Where ALL the shoes are awesome!  Yes, B got me 2 pairs!!!! Cause HE's awesome!

I love street people, street food, and.....



...Chinatown....no matter the city!








Lost is translation???????  Then again, maybe the most aptly named store ever!



Someday I am going to spend 2 weeks in a rented flat in Chinatown...either in NYC or San Fran....and I am going to cook and EAT all the things that I currently cannot name!!  You listening, Bentie????


And to think that I saw it on Mulberry Street!!!   Welcome to Little Italy!!!!
We really, truly walked the length of Mulberry Street, which runs from Chinatown through Little Italy!  Wow!!  THIS is what makes the wonderful melting pot of New York and the US sooooo amazing.  We can all share and enjoy our lives, made ever richer, by experiencing some of the tastes and beauty from the lives of others.



Oh, yeah!!  This shrimp was delish!!!




#DressLikeAWoman
I am a woman.  I got up and I got dressed!!!!  THAT's how you dress like a woman!  
"Be you, and be relentlessly you!" ~ Thanks, Gaga.



And if you think that was all the multicultural tastes that one street could contain...NOPE!!!  We ended the street and rested out feet in an amazing Spanish Tapas restaurant - Despana!!!  It took us right back to Barcelona!  Delicious tortilla (potato pie...not the bread!!), wine and other traditional tapas!!  Try it if you have the chance!!
Such a lucky girl!!  And to think that I saw it on Mulberry Street!!!! - les