radiation kills by increasing heart V5 and V30

[seper]

What do you all think of full 0617 manuscript? Surprisingly, low-level heart exposure was the strongest predictor of death within 2 years of f/u. Hard to think of possible pathophysiology. I suspect methodological error.

http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)71207-0/abstract

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[thaddeus]

Seems to me that heart dose is probably a pretty good dosimetric marker of extent of mediastinal disease (i.e. larger mediastinal fields = higher heart dose). And of course patients with more extensive nodal disease would be expected to do worse. I agree it doesn't make sense this would be caused by cardiac toxicity within 2 years....

 

[napoleondynamite]

This finding is consistent with the breast literature - Darby et al published in NEJM a couple years ago showing mean cardiac dose of only 1Gy increased risk of coronary events by 7% with no apparent threshold..thus the excitement for DIBH or prone technique to limit dose.

 

[radiaterMike]

The Darby paper had much longer follow up in a population with anticipated long term survival. The risk of cardiac toxicity (outside of pericardial effusions which are rare) will not manifest itself so early as other posters have mentioned.

 

[thesauce]

Seems to me that heart dose is probably a pretty good dosimetric marker of extent of mediastinal disease (i.e. larger mediastinal fields = higher heart dose). And of course patients with more extensive nodal disease would be expected to do worse. I agree it doesn't make sense this would be caused by cardiac toxicity within 2 years....

This is a good point. Heart dose also is a marker of the amount of lung disease as the paper discusses: "Thus, when trying to limit normal lung exposure during treatment planning, the heart volume was likely to receive generous doses of radiation therapy in both groups."

I'm interested to see what the final analysis shows with regard to the way the heart was contoured and whether specific portions of it would be more important to spare.

 

[seper]

Thanks... Having said all that, what heart V30 you'll now find unacceptable in stage IIIB NSCLC? I've signed plans where it was close to 80%.

 

[medgator]

Thanks... Having said all that, what heart V30 you'll now find unacceptable in stage IIIB NSCLC? I've signed plans where it was close to 80%.

Honestly, what is the endpoint here when you consider time to CAD/heart issues vs expected survival in a IIIB NSCLC pt? I agree with thaddeus above.

 

[Haybrant]

This finding is consistent with the breast literature - Darby et al published in NEJM a couple years ago showing mean cardiac dose of only 1Gy increased risk of coronary events by 7% with no apparent threshold..thus the excitement for DIBH or prone technique to limit dose.

There are problems with the darby paper; we dont really know how much dose those patients received, these are simulated plans. Also, the risk of coronary events reported is a relative risk. The absolute increase in risk of MI is somewhere around 1.5%. Important to limit cardiac dose, yes, but that is over a long period of follow up. Wouldn't extrapolate it for locally advanced lung ca patients

 

[seper]

Honestly, what is the endpoint here when you consider time to CAD/heart issues vs expected survival in a IIIB NSCLC pt? I agree with thaddeus above.

Well, the reason that brought up this topic, is heart V30 trumped everything with regard to survival at 2 years. Unless there was a statistical error, we should start to prioritize heart dose over prescription dose and lung DVH.

 

[medgator]

Well, the reason that brought up this topic, is heart V30 trumped everything with regard to survival at 2 years. Unless there was a statistical error, we should start to prioritize heart dose over prescription dose and lung DVH.

That still doesn't address the possibility of a correlation/causation fallacy. I personally am not going to sacrifice lung or cord constraints to meet a lower heart v30.

For the occasional stage IIIB pt with humongous volumes upfront where I think this will be an issue, I'll probably discuss a few cycles of chemo upfront to shrink things down before I get started

 

[seper]

OK agree, I will hold off changing my DVH goals until RTOG follows up with updated dosimetry analysis of 0167.

 

[HepatoSite]

Agree with the likely scenario of increased bulk of mediastinal disease in patients with higher heart doses. Total conjecture, but maybe there is a subset of patients with very poor coronary microvasculature where heart dose has a more meaningful impact in the short term...rather than the long term risks we usually think of with heart dose (breast patients, HL patients, etc.).

 

[Palex80]

I also don't "buy" this... Think of all the Hodgkin's patients being treated in the 2D-era with mantle fields... Did they die because of RT 5 years later? Not really... And they were getting 30 Gy to 60%+ of their hearts on regular basis.
Surely there are tons of patients series reporting long term toxicity because of 2D-irradiation for lymphoma patients, but none of these series showed such a remarkable increase in cardiac mortality so early after treatment.