CTC: prognostic marker in early stage BC

http://www.mdanderson.org/newsroom/news-releases/2012/md-anderson-research-finds-predictive-value-of-circulating-tumor-cells.html

The next step is to be able to molecular characterize the CTCs (Her2, ER/PR, other receptors, mutations) and guide treatment strategies realtime and accelerate clinical trials.

This sentence gave me pause: "Of those, 15 per cent experienced a cancer relapse and 10 per cent died during the study period" in 5 years study period 2005-2010.   5 year mortality rate of about 66% among these early breast cancer patients with 1 + CTCs.   This is at MD Anderson.

"For women with three or more circulating tumour cells in their blood sample, the outcomes were much worse: 31 per cent died or experienced a relapse." 

This is why the research for MBC cure needs to accelerate.   20 years, the improvement in MBC mortality rate has gone from 97% to 66%.   MBC is not "chronic" like AIDS or diabetes.   AIDS or diabetes patients can expect to live a full life span.   MBC is a killer with no cure.  and no early stage patient is really cured till MBC has a cure.

CTC test is not without problems.

CTC test needs special tubes and needs mixing the blood carefully after blood draw.   Also it needs to be run 2-3 days after the blood draw.   

Also,  CTC has high false-negative rate.  ie, only a portion of metastatic patients get positive CTCs.   The next generation of CTC test hopefully will lower that false negative rate, and become more accurate.

But for fast clinical trials, CTC can be an useful tool.   Say you take only patients with 5+ CTCs, gave them experimental medicine and see whether the CTC drastically drops and stay dropped.   Patient commitment: a course of experimental medication.   Researcher gets results in a few days/weeks can go on to the next iteration of experimentation with dosage or drug design.   Cost would be much less than current clinical trial cost design.   There will be more drug companies testing more drug candidate for cheaper.   End result:  the cure.

I'm sure the doctors would say "this is not ready for prime time".   Doctors can be as cautious, caution being the intersection of  lawsuit and scholarship cultures.   But hey, 10 years later when it's ready for prime time,  a lot of patients would have died for want of the cure, and MBC mortality rate would drop from 66% to 50%?

Dying patients do not wait for prime time. 

Do you want data integrity or save patients lives?

Very interesting article on the trade-off:

www.forbes.com/sites/matthewhe...

However, I am not sure it covers all the costs of a more lengthy process that tries to ensure data integrity.   Faster, cheaper processes leads to faster/cheaper drugs, and ultimately more effective drugs.   The cost in delaying the process (more data integrity) lies in

I think this article does not cover all the costs of a more lengthy process that tries to ensure data integrity. Faster, cheaper processes leads to faster/cheaper drugs, and ultimately more effective drugs. The cost in delaying the process (more data integrity) lies in

1.  the patients' lives endangered,

2. more difficult recruiting of patients into randomized clinical trials.  Patients who put their lives on the line to go through the blinded trials.  When they hear the preliminary data that's highly promising but may be just a little short, they need to make the choice of dropping out of clinical trials if they are in the control arm vs staying in the control arm, and die to make the OS (overall survival) data true.   That is difficult choice for patients and physicians, and difficult for any future double blind clinical tials to recruit.

3. in the ultimately higher cost of drugs.

Note how almost all the drugs that had early terminated drug trial end up being highly effective and lifesaving.    If a couple of drugs later turned out to be less effective than originally thought, it's not a big deal.    The statistically significance standard for treatment for end-stage cancer with no other options  should take into account the benefit for patients, and be different than the standard for treating something less deadly.  

Thermodox

This article explains why thermodox could be very useful for liver cancer and metastasis:
http://seekingalpha.com/article/607921-celsion-is-ripe-for-a-long-position

Thermodox is a heat-activated form of doxurubin.    Combining thermodox with hyperthermia/RFA treatment could help deliver doxurubicin at higher concentration into liver metastasis (possibly kidney, pancreas)  locally.   As a result, side effect to heart is minimized while cancer gets its full of this powerful drug.

"Studies in a rabbit tumor model also showed that heat-activated ThermoDox delivered 10-fold more doxorubicin to the tumor, than conventional injections of doxorubicin. And although ThermoDox did accumulate to high levels in the kidney and spleen, it was not higher than conventional injections of doxorubicin. Finally, the 2008 Phase 1 trial for ThermoDox in liver cancer showed that an optimal dose of 50mg/m² extended the time-to-progression from 1 month to 6 months and, very importantly, the "dead zone" within the tumor kept expanding for 3 months after the radiofrequency ablation treatment, suggesting that heat-activated ThermoDox was killing the presumed chemo-resistant tumor cells with long-lasting effect. In contrast, the "dead zone" shrunk over time with radiofrequency ablation treatment alone. "

Metastasis: Rude Awakening

2 great articles on nature.com. The first, "Metastasis, Rude Awakening" highlighted the tragic lack of progress on MBC treatment plus problem of long term relapse from hidden metastasis:
http://www.nature.com/nature/journal/v485/n7400_supp/full/485S55a.html#/ref 7

nature.com is not the most popular science magazine in america.   If even nature.com readers need a "rude awakening",  metastatic breast cancer patients have a real problem.   The public, including early breast cancer patients and other well educated people who should know better, have been lulled into a false sense of security and think metastatic breast cancer is a "chronic" disease like diabetes or AIDS.   When in fact, MBC patients life expectancy is measured in years, even months, while diabetes/AIDS patient can expect a normal life expectancy, which is 70-80 years old.

The other article explained why current clinical trial design fails so many potentially good drugs, and how clinical trial process itself should be changed:
http://www.nature.com/nature/journal/v485/n7400_supp/full/485S58a.html


Different clinical trials should be conducted, with different end-point. The ultimate goal is to make the turn-around-time fast. So scientists can try a drug, wait a few days/weeks for results; tweak it to improve it, wait a few days/weeks for results; repeat above.

Currently the scientists must wait years and years for results every single human related iteration of drug design. No wonder effective treatments are few and far in between and very very expensive.   

Imagine one day there is a CTC test similar to blood glucose test, where patients can poke their fingers in morning/lunch/dinner time and get 3 data points.    Patients/physicians can see in real time how CTC is changing with new treatment/exercise regimen, and this data can be used to forecast patients' real response to medication and used in clinical trials, which takes a few months to run, instead of years and years.    Patients need not put their lives on the line to join a randomized clinical trial.  And 100% advanced breast cancer patients can join a clinical trial that generate a valid data point without having to make a commitment for years till death (for the OS benefit) .  Then we can say truly, that MBC is a chronic disease, like diabetes.  And its cure would not be far off.

Why scans are good.

Brain surgeon buried his proposal ring in the sand...  Then he lost it...
After hours of searching (with volunteer help), he called a ring detector service.   Metal detector shows up and find the ring in no time:
http://news.yahoo.com/blogs/lookout/marriage-proposal-goes-awry-brain-surgeon-loses-ring-164800976.html

This is why we need scans, and CT/US assisted surgeries.   And the girl said yes.

Massive Parallel Gene Study on ER+ tumors

I live in interesting times.    Massive Parallel Gene Study on ER+ tumors:

http://abstract.asco.org/AbstView_114_95183.html


NK immune cells genetic profiling predicting early/late relapse on early breast cancer
http://abstract.asco.org/AbstView_114_99068.html

Cabozantinib

Cabozantinib (cabo) is an oral, potent inhibitor of MET and VEGFR2.

 

results:

abstract.asco.org/AbstView_114...

recruiting phase II trials

clinicaltrials.gov/ct2/results...

From Wiki:

Positive data from clinical trials indicate cabozantinib is particularly beneficial in metastatic advanced prostate cancer. 97% of patients either had stabilization or improvement in bone malignancies. The median time to disease progression was 29 weeks. 

 

Wow.   Breast cancer trials have not gotten as good a result, but not far behind.