TRACERx: unstable chromosomes predict lung cancer relapse - 1290668

onthemark
Posts:258

There's been a lot of news coming out recently about lung cancer. TRACERx is a study in the UK to analyze the genetic heterogeneity of lung tumours and to follow tumour DNA in circulating blood after surgery to predict relapse before any scan can detect growth.

Here is a nice article summarizing the two papers, one published in the New England Journal of Medicine and the other available ahead of publication at Nature:

https://www.technologynetworks.com/cancer-research/news/unstable-chromo…

I am wondering if there are any similar clinical trial efforts for lung cancer in North America.

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Reply # - May 1, 2017, 10:05 AM

catdander
Posts:

Hi Onthemark, I hope you are doing fine. I'm sorry it took so long to respond but I wanted to read the piece and look around a bit then storms took out our power for several hours last night. So,

This work is really exciting for those who have had biopsies, repeat biopsies and biopsies that were undiagnosable and people like me who are the loved ones on the sidelines. The forward steps in liquid biopsies have been in testing for T790M mutation from EGFR tki resistance. There is lots of work going on this fast moving subject. Following is a link to Clinical trials on liquid biopsy in nsclc, https://clinicaltrials.gov/ct2/results?term=liquid+biopsy&type=&rslt=&r…

I think these lines from the article says it best, ‘Professor Charles Swanton, the study's lead researcher based at the Crick, said: "The TRACERx study is Cancer Research UK's single biggest investment in lung cancer, and for the first time we've revealed new insights into how tumours evolve and evade treatment, a leading cause of cancer death.

"We believe that this invaluable data generated during TRACERx will be seized upon by research teams across the world, helping us to answer more questions about lung cancer biology. We've only scraped the surface in terms of what is possible by looking at tumour evolution in such detail.” ‘

This appears to be the latest info we have on the subject of liquid biopsy, we’ll have to see if Jim finds newer for he’s the best at mining info. The first is from a video at last June’s ASCO meeting the others are a couple of years old.

http://cancergrace.org/lung/2016/07/13/urine-or-blood-testing-instead-o…
http://cancergrace.org/search-results?q=serum%20testing

All best
Janine

Reply # - May 1, 2017, 11:16 AM

catdander
Posts:

My first post isn't showing up so here it is again:

Hi Onthemark, I hope you are doing fine. I'm sorry it took so long to respond but I wanted to read the piece and look around a bit then storms took out our power for several hours last night. So,

This work is really exciting for those who have had biopsies, repeat biopsies and biopsies that were undiagnosable and people like me who are the loved ones on the sidelines. The forward steps in liquid biopsies have been in testing for T790M mutation from EGFR tki resistance. There is lots of work going on this fast moving subject. Following is a link to Clinical trials on liquid biopsy in nsclc, https://clinicaltrials.gov/ct2/results?term=liquid+biopsy&type=&rslt=&r…

I think these lines from the article says it best, ‘Professor Charles Swanton, the study's lead researcher based at the Crick, said: "The TRACERx study is Cancer Research UK's single biggest investment in lung cancer, and for the first time we've revealed new insights into how tumours evolve and evade treatment, a leading cause of cancer death.

"We believe that this invaluable data generated during TRACERx will be seized upon by research teams across the world, helping us to answer more questions about lung cancer biology. We've only scraped the surface in terms of what is possible by looking at tumour evolution in such detail.” ‘

Following is the latest info we have on the subject of liquid biopsy, the first is from a video at last June’s ASCO meeting the others are a couple of years old.
http://cancergrace.org/lung/2016/07/13/urine-or-blood-testing-instead-o…
http://cancergrace.org/search-results?q=serum%20testing

All best,
Janine

Reply # - May 4, 2017, 07:36 PM

onthemark
Posts: 258

Thanks for your reply Janine.

I am not an expert but my understanding is that in addition to looking at single 'point mutations' or markers (like the egfr or T790M) they are also looking at copy numbers for large areas of the genome, of a certain kind of 'deraingement' that explictly includes genetic heterogenity within the tumor (or i guess also between tumors if there is more than one), and does so in a quantifiable way to make a 'risk assessment' etc. This is put into a likelihood model for the cancer to relapse after surgery.

I am wondering if there are any similar clinical trial efforts that look at this new kind of data for lung cancer (beyond point mutations) in this hemisphere that I could be enrolled into.

Reply # - May 5, 2017, 09:23 AM

catdander
Posts:

Hi Onthemark, You're welcome for any info I can give. I'm sorry I didn't find much on that specific subject outside the tracerx trial. I contacted Dr. West but he didn't have any info on the subject. I look at clinicaltrials.gov which has most trials worldwide and didn't come up with other matches. I don't know if you've tried but you may give clinicaltrials a try if you've not done so. I noted the links in my previous post to share what we do have on Grace and what I found with my limited knowledge of the subject online. My guess is I'm either not using the right search terms or the tracerx is a unique trial. It may be helpful to ask you oncologist to do a search for or even with you. Maybe take out your phone at an appointment and start a search to get her/him started on ideas of where and for what to look. I'm sorry I can't be of more help.

Please keep us posted on info you find and I'll ask Jim to give a look at this thread.

All best,
Janine

Reply # - May 5, 2017, 09:46 AM

onthemark
Posts: 258

Thanks for looking into this Janine. It has made a big splash with publications in NEJM and Nature and my understanding is that it's the UK's biggest cancer clinical trial in terms of long term funding. I get notices into my email whenever something is posted in this thread so if down the road someone comes across anything informative please do share.

I wrote to my oncologist about this. It will be 3 months til I see him again so hopefully by that time he's had a chance to look into it. He's also in charge of all cancer clinic trials here so there is hope.

If it is unique now it won't be unique down the line... I believe this is a big advancement.

Reply # - May 5, 2017, 10:10 AM

onthemark
Posts: 258

Here is another not too technical article and makes the point about copy number mutations as well as a number of other points.

"In preliminary analyses, TRACERx researchers also found that patients who carried a high proportion of subclonal copy-number alterations had almost a fivefold higher risk for recurrence or death than patients with a low proportion of subclonal copy-number alterations, at a hazard ratio of 4.9, a difference between the two groups that was highly statistically significant.
Indeed, "the median time until recurrence or death was 24.4 months in the higher risk group of patients compared with a median that was not reached in the lower risk group," they emphasize. This difference remained significant after adjusting for multiple confounders, they add."

http://www.medscape.com/viewarticle/879410?pa=g8G5A9NqcZ1P83TE3PuYEG7b6…

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