CtDNA

[ramsesthenice]

How many of your partnering oncologists are regularly following circulating tumor DNA during post treatment surveillance? I’m seeing a lot more of this and honestly don’t like it.

Surprise! Your cancer is back. We can’t do anything about it, but at least we know early. Right?

Don’t get me wrong, I think they will be a powerful bio marker eventually but this seems very premature for regular clinical practice at this point in time to me.

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[seper]

None at all in my region (large metro Midwest).

 

[Haybrant]

Anyone with a general summary on the state of this tech? Can it help increase the proetest probability of lung nodules for empiric sbrt?

 

[thecarbonionangle]

Yes about 50 pct of the med oncs are getting these, not always but more than one would think. I don’t really see why because we don’t have anything concrete on how to alter treatment or surveillance based on it. Most recently, i saw it at breast tumor board, i don’t treat breast but I showed up for the free fish, and i covered it for a colleague.

 

[Chartreuse Wombat]

Cynical maybe but is there a perverse incentive for MOs to order this test?

 

[Radonc90]

Data on ctDNA from Stanford and UNC looks interesting.
We don't order it (yet).

It basically boils down to 2 basic questions:

1. Can it accurately predict tumor recurrence?
Location, location and location matters: local vs distant...

2. Is there anything to offer in terms of therapy?
In other words, HN and lung cancers are not seminoma or HL, where there is effective salvage Rx.

 

[RickyScott]

How many of your partnering oncologists are regularly following circulating tumor DNA during post treatment surveillance? I’m seeing a lot more of this and honestly don’t like it.

Surprise! Your cancer is back. We can’t do anything about it, but at least we know early. Right?

Don’t get me wrong, I think they will be a powerful bio marker eventually but this seems very premature for regular clinical practice at this point in time to me.

Just seen it used for liquid biopsies. Was tempted to order it after definitive chemo/xrt for head neck or lung.

 

[ramsesthenice]

Data on ctDNA from Stanford and UNC looks interesting.
We don't order it (yet).

It basically boils down to 2 basic questions:

1. Can it accurately predict tumor recurrence?
Location, location and location matters: local vs distant...

2. Is there anything to offer in terms of therapy?
In other words, HN and lung cancers are not seminoma or HL, where there is effective salvage Rx.

As I said above, I agree with you about potential. your points are good. This is a big part of our future. Also easy to imagine a role in patients with oligometastatic recurrences. You know the (seemingly) relatively favorable cases that beg for surgery or RT in patients who really don’t want more chemo. I think we would all feel better about using focal therapy only if we had a good bio marker to evaluate treatment responses.

I just don’t love doing this routinely off trial (or as a prospective evaluation) at this day in age. Until we know why to do with the information and how to intervene, I think ignorance really is bliss. Lots of anxiety with little upside at this moment in time.

 

[Chartreuse Wombat]

As I said above, I agree with you about potential. your points are good. This is a big part of our future. Also easy to imagine a role in patients with oligometastatic recurrences. You know the (seemingly) relatively favorable cases that beg for surgery or RT in patients who really don’t want more chemo. I think we would all feel better about using focal therapy only if we had a good bio marker to evaluate treatment responses.

I just don’t love doing this routinely off trial (or as a prospective evaluation) at this day in age. Until we know why to do with the information and how to intervene, I think ignorance really is bliss. Lots of anxiety with little upside at this moment in time.

Best i can tell APM has not category for CTDNA so still FFS in this context...sweet

 

[MegaVoltagePhoton]

what kind of cancers are they using it in? i imaging insurance is a big issue? would love to use it in my patients with locally advanced cervical cancer....of course if it ever comes up, its for prostate patients with oligomets who dont want to do adt, and not for the young lady with a t3 bulky cervix looking at outback chemo...

 

[ramsesthenice]

Just to expand a bit, we appear to be talking about a couple different technologies here. The point is the same with all of them.

A lot of what is out there assesses viral DNA load (HPV or EBV). Data is pretty promising it’s a pretty good metric for assessing treatment response for viral mediated tumors.

There are also companies that will run PCR for a panel of common human oncogenic sequences and market as a liquid biopsy.

Some of the (in my opinion) better ones actually sequence the patients tumor and design a personalized panel at initial diagnosis/recurrence (whenever you have tissue).

There are also next gen circulating tumor cell assays as well. some of them look pretty good with far greater sensitivity/specificity than CellSearch. You can’t amplify cells so in my opinion these will lose the surveillance battle to DNA based assays but there is information to be gleaned from whole cells so I could see these complimenting each other nicely at some point.

 

[evilbooyaa]

Some situations this is valuable - EBV DNA assessment after Nasopharynx treatment (given that that's what HN-001 was stratifying on)

The issue with ctDNA is that while it does have some evidence of being prognostic (fair amount of research out of UNC with Bhisham Chera and Gaorav Gupta's labs in at least Ophx if not various H&N cancers), HN-001 is the first situation that it is being studied as driving treatment decisions. So, no, I don't see the point of ordering it outside of a potentially prognostic determination.

That being said, this is an interesting area of research and if anyone is aware of reseach for it either 1) being predictive of response to additional therapy or 2) trials looking at changing therapy (similar to HN-001), I'd love to read up more on it.

 

[Lamount]

Just to expand a bit, we appear to be talking about a couple different technologies here. The point is the same with all of them.

A lot of what is out there assesses viral DNA load (HPV or EBV). Data is pretty promising it’s a pretty good metric for assessing treatment response for viral mediated tumors.

There are also companies that will run PCR for a panel of common human oncogenic sequences and market as a liquid biopsy.

Some of the (in my opinion) better ones actually sequence the patients tumor and design a personalized panel at initial diagnosis/recurrence (whenever you have tissue).

There are also next gen circulating tumor cell assays as well. some of them look pretty good with far greater sensitivity/specificity than CellSearch. You can’t amplify cells so in my opinion these will lose the surveillance battle to DNA based assays but there is information to be gleaned from whole cells so I could see these complimenting each other nicely at some point.

As I understand it, it is bit like the wild wild west. Those panels are a fishing expedition and can give false positives, as people can acquire tissue-specific somatic mutations that never result in cancer. The most reasonable application involves doing PCR for mutations that are specific to the patient's cancer. Sometimes this is easy (e.g. EGFR mutant NSCLC, prototypical oncogenic KRAS mutations) and sometimes not so much (SCLC). Making PCR probes for a patient's unique oncogenic somatic mutations is not currently cost effective.

Down the road these may be helpful but I don't think it should be used off trial, as no one really knows what to do with the results... and I would be pretty skeptical of someone who blindly orders this.