Most excellent news! Biden threatens to cut funding if cancer trials conceal results!!!

Biden threatens to cut funding if cancer trials conceal results!!!

Click on the link above to read the Washington Post article for yourself!!!

For too long, tax payer dollars have funded studies at prominent, money making, hospital/research facilities, where some researchers, Big Pharma, and CEO's have been more interested in making money and a name for themselves rather than REALLY putting their heads, experience, and information TOGETHER with others...so that ALL findings can truly build on that which is learned by another researcher at another institution with another drug/drug company!!!!  When  you compound that difficulty by the fact that almost 50% of clinical trial results are NEVER PUBLISHED!!!!....we have a problem.  I wrote about how researchers uncovered that unfortunate circumstance back in 2013:  Almost 50% of results in cancer drug trials goes unpublished!!

Clearly, this is NOT okay!!!!  We as tax payers, consumers, and ratties need to know the result of clinical trials...the good, the bad and the ugly.  Researchers, institutions, and pharmaceutical companies MUST share data....all of it....so that real knowledge, bonafide treatments, and incredibly beautiful lives can go forward!!! The withdrawal of funding from those who fail to institute these simple, basic rules guiding the scientific method learned by the rest of us in fourth grade...combined with the tenants of fair play, shared effort and human kindness found on pre-school play gounds everywhere....may be the single most important step toward finding real cures for cancer.

Go, Biden, go!!!!   -c

Surgical management and adjuvant therapy for high risk melanoma....many questions...still waiting on answers!!!

Surgical Management and Adjuvant Therapy for High-Risk and Metastatic Melanoma. Akkooi, Atkins, Agarwala, Lorigan.  Am Soc Clin Oncol Educ Book. 2016

Wide local excision is considered routine therapy after initial diagnosis of primary melanoma to reduce local recurrences, but it does not impact survival. Sentinel node staging is recommended for melanomas of intermediate thickness, but it has also not demonstrated any indisputable therapeutic effect on survival. The prognostic value of sentinel node staging has been long established and is therefore considered routine, especially in light of the eligibility criteria for adjuvant therapy (trials). Whether completion lymph node dissection after a positive sentinel node biopsy improves survival is the question of current trials. The MSLT-2 study is best powered to show a potential benefit, but it has not yet reported any data. Another study, the German DECOG study, presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting did not show any benefit but is criticized for the underpowered design and insufficient follow-up. There is no consensus on the use of adjuvant interferon in melanoma. This topic has been the focus of many studies with different regimens (low-, intermediate-, or high-dose and/or short- or long-term treatment). Adjuvant interferon has been shown to improve relapse-free survival but failed to improve overall survival. More recently, adjuvant ipilimumab has also demonstrated an improved relapse-free survival. Overall survival data have not yet been reported due to insufficient follow-up. Currently, studies are ongoing to analyze the use of adjuvant anti-PD-1 and molecular targeted therapies (vemurafenib, dabrafenib, and trametinib). In the absence of unambiguously positive approved agents, clinical trial participation remains a priority. This could change in the near future. 

Here are the results of my Nivo/Opdivo study for 33 Stage IV, NED ratties:  Cest moi! Results in my Nivo/Opdivo trial published!!

That trial started in 2010!  Results were published in 2014.  I realize folks are waiting to see what will happen to us...but come on, researcher peeps!!!!  Let's get to tallying some more numbers and looking at what happens to us with no treatment as a comparator.   Plenty of folks need answers sooner rather than later!!!  Hang in there, ratties!!! - c

Intralesional PV-10 (Rose Bengal, y'all!!!) positive treatment for in-transit melanoma

I've certainly posted about intralesional therapies (including Rose Bengal/PV-10) before.  Here's just one link:  ASCO 2016 - New studies on intralesional therapy Treating in-transit melanoma can certainly be a challenge.  Now a report on one center's experience:


Intralesional PV-10 for in-transit melanoma-A single-center experience.  Lippey, Bousounis, Behrenbruch, et al.  J Surg Oncol. 2016 May 30. 

Patients with in-transit melanoma metastasis have longer median survival than patients with distant metastatic disease. Furthermore, local disease control is an important endpoint for symptom management. The treatment of unresectable loco-regional recurrence or in-transit disease has been historically managed with a combination of treatments including surgery, radiotherapy, isolated limb infusion or perfusion as well as systemic therapies. Intralesional PV-10 has been used at Peter MacCallum Cancer Centre since 2010, and the current report presents a retrospective analysis of patient outcomes, reporting the response rates, durability of responses, and observed toxicities.  Records were analyzed retrieving details of 19 patients treated with PV-10 over a 4-year period from 2010 to 2014. Medical records were reviewed for these patients and data extracted.  Nineteen patients with in-transit melanoma were treated with intralesional PV-10 between 2010 and 2014. Disease control (complete or partial response or disease stability) was achieved in 68% of patients with 26% having a complete response. This was achieved with minimal associated toxicity.  PV-10 is an effective, durable, well-tolerated treatment tool with an acceptable side effect profile for the management of unresectable in-transit melanoma.

Hopefully, when combined with pembro or other systemic treatments...the complete response rate can be bumped higher!!!  Hold onto your tails, ratties! - c

Happy Summer!!!

Berries B helped me pick!  He had so much fun!!!

Now SIX years old!!!

Beautiful hydrangeas my Peds Care Peeps gave me after surviving brain zappage and lung removal 6 YEARS ago!!! Thanks, guys!!! Time does fly!

And this, especially for my dear Ed!!!  Gotta say when running and picking berries today...felt like Satan's Armpit had crept north a bit!!!

Happy summer to all of you!!!  So glad to have each of you to share it with me!!! - love, c

Sew Chaotically! - Mother's day fabric...now a pretty dress!!! - Simplicity 8125

For this past Mother's Day, B gave me a beautiful garden and fabric!!!  3 yards of a bright blue, leopard print (Yes, that is correct!) in a flowy cotton poly.  He was wise enough to take a pic of the info at the end of bolt with his phone for later use!  Not having a pattern that I thought would suit the fabric....he helped me settle on Simplicity 8125:

This is probably the most difficult pattern attempted, yet best job I have done of any of my sewing projects!!  It went together fairly well, though the facing of the bodice was a bit of a challenge!!!  There are many cute details, that this print covers a bit...like pleats on the sleeves, details of the bodice, and the side slit.  I made a straight 12 and it fits me perfectly!  No fiddling!!  I did shorten the sleeves just a bit...as I feared they would look like long sleeves made unfortunately short, had I left them as they were.  I will certainly be making another version with this pattern.  The shorter one with little flutter sleeves looks interesting!!!

The material had a bit of a linear horizontal and diagonal coloration to it that I think I dealt with well!!!

Bodice...

...and sleeve detail.

Have to go check on my garden!!

Sew Chaotically!!!  Especially when dealing with a blue leopard print!!! - c

PI3K/AKT - a pathway with potential for treating melanoma brain mets

Michael Davies, MD, discusses the biggest challenges in treating brain metastases, what is known about the connection to the PI3K/AKT pathway, and what his future plans are for research in this area.

http://www.onclive.com/web-exclusives/pi3kakt-pathway-potential-target-for-treating-brain-mets-in-melanoma/2 

If we could detect brain metastasis at an early stage, they could potentially be cured with focal radiation approaches or surgical approaches. For patients who have advanced disease with brain metastases, hopefully an improved understanding of the molecular pathogenesis of these tumors will lead to treatments that are not only rational, but more effective.

What are the next steps in your research?

There are many different ways to target the PI3K pathway, so one of the biggest questions is, “Which of those targets are most likely to be effective?” We are evaluating different strategies to target the pathway and, importantly, we are evaluating different strategies in combination with other therapies, including targeted therapy, immunotherapy, and radiation therapy.

We know that melanoma is a very complex disease, and the PI3K pathway is equally complex. It can be activated multiple different ways and it can have multiple different effectors. How it intersects with other oncogenic pathways that are clinically significant in this disease, remains an ongoing and important area of research.

Do you think that combination therapies will be key to successfully targeting the PI3K pathway?

Absolutely. What we generally see is that the PI3K pathway does not drive tumor growth by itself, but it compliments other pathways to make tumors much more aggressive and resistant to therapies.

Is a clinical trial investigating the use of PI3K in patients with melanoma who have brain metastases on the horizon?

The challenge with getting a clinical trial up and running is the hesitancy of pharmaceutical companies to include brain metastases in trials. This is something that is slowly changing, as we have now seen clinical trials with both BRAF inhibitors with ipilimumab and PD-1.

However, often trials are done after most of the other clinical testing has been completed. It’s an active area of work for investigators in the field and for patient advocates to try and encourage companies to develop earlier stage clinical trials for patients with brain metastasis. This remains a critical unmet need for patients with this disease.

Weber said acute toxicities that have been associated with TIL therapy include hemorrhagic cystitis, cytoxan-induced syndrome of inappropriate antidiuretic hormone, neutropenic fever/ sepsis, and hypotension/capillary leak. He said researchers have adjusted to these toxicities by limiting IL-2 to 6 doses after TIL infusion therapy. Chronic toxicities have included fatigue, neuropathy, vitiligo, and uveitis, Weber noted.

Looking Forward

One key challenge in TIL therapy that has been partially overcome, Weber said, is finding a better way to grow TILs.

The process used to take 6 or more hours, multiple incubators, and multiple technicians. Today, he said, with the use of bioreactors and a closed system, the process is more efficient and only requires one technician. There is still more work to be done to make the process even better, he noted. The approach is moving forward in the phase II, multicenter LN-144 study, which aims to assess the safety, feasibility, and antitumor activity of this treatment followed by IL-2 for patients with metastatic melanoma who are refractory to at least one systemic therapy.³ Researchers are seeking to enroll 20 patients.

For trial inclusion, patients must have measurable disease with at least one lesion that is resectable for TIL generation; that is, at least 1.5 cm in diameter and able to be removed with minimal morbidity. Exclusion criteria include prior cell transfer therapy that included a nonmyeloablative or myeloablative chemotherapy regimen, more than three brain metastases, and current use of a systemic steroid regimen.

This trial is an exciting early step, according to Steven A. Fischkoff, MD, chief medical officer of Lion Biotechnologies, Inc, a New York City–based company that is developing the TIL therapy under an orphan drug designation. He said that focusing on TILs is a forward-looking approach to immunotherapy. Weber, who is a member of Lion’s scientific advisory board, said the technology holds promise for a variety of tumor types. Besides melanoma, other cancer types that might prove amenable to TIL therapy include renal cell carcinoma, ovarian cancer, glioblastoma multiforme, lung cancer, and cervical cancer, he said.

“You can definitely grow TILs from a variety of tumors,” Weber said. “In the old days, people tried to do it and couldn’t figure out what to do. It turns out to be much easier to do than we thought.”

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- See more at: http://www.onclive.com/publications/oncology-live/2016/vol-17-no-7/tils-advancing-as-melanoma-immunotherapy-option/2#sthash.L6J2IajY.jORat1Jw.dpuf

Interesting to think about.  Here is a pic of the molecular pathways in melanoma.
Keep the thinking coming! -c

Weber said acute toxicities that have been associated with TIL therapy include hemorrhagic cystitis, cytoxan-induced syndrome of inappropriate antidiuretic hormone, neutropenic fever/ sepsis, and hypotension/capillary leak. He said researchers have adjusted to these toxicities by limiting IL-2 to 6 doses after TIL infusion therapy. Chronic toxicities have included fatigue, neuropathy, vitiligo, and uveitis, Weber noted.

Looking Forward

One key challenge in TIL therapy that has been partially overcome, Weber said, is finding a better way to grow TILs.

The process used to take 6 or more hours, multiple incubators, and multiple technicians. Today, he said, with the use of bioreactors and a closed system, the process is more efficient and only requires one technician. There is still more work to be done to make the process even better, he noted. The approach is moving forward in the phase II, multicenter LN-144 study, which aims to assess the safety, feasibility, and antitumor activity of this treatment followed by IL-2 for patients with metastatic melanoma who are refractory to at least one systemic therapy.³ Researchers are seeking to enroll 20 patients.

For trial inclusion, patients must have measurable disease with at least one lesion that is resectable for TIL generation; that is, at least 1.5 cm in diameter and able to be removed with minimal morbidity. Exclusion criteria include prior cell transfer therapy that included a nonmyeloablative or myeloablative chemotherapy regimen, more than three brain metastases, and current use of a systemic steroid regimen.

This trial is an exciting early step, according to Steven A. Fischkoff, MD, chief medical officer of Lion Biotechnologies, Inc, a New York City–based company that is developing the TIL therapy under an orphan drug designation. He said that focusing on TILs is a forward-looking approach to immunotherapy. Weber, who is a member of Lion’s scientific advisory board, said the technology holds promise for a variety of tumor types. Besides melanoma, other cancer types that might prove amenable to TIL therapy include renal cell carcinoma, ovarian cancer, glioblastoma multiforme, lung cancer, and cervical cancer, he said.

“You can definitely grow TILs from a variety of tumors,” Weber said. “In the old days, people tried to do it and couldn’t figure out what to do. It turns out to be much easier to do than we thought.”

---

- See more at: http://www.onclive.com/publications/oncology-live/2016/vol-17-no-7/tils-advancing-as-melanoma-immunotherapy-option/2#sthash.L6J2IajY.jORat1Jw.dpuf