How to calculate spinal cord tolerance with BD fractionation?

[drnick098]

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Do you guys know how to do this calculation? I've gone thru Hall and not found anything relevant. Joiner and van Der Kogel's textbook has a formula but the result doesn't match what we seem to do in clinical practice.

Case:
Patient with limited stage SCLC receives 45Gy in 30 fractions (1.5Gy twice daily, around 6 hours between the two fractions) as per the Turissi protocol. The spinal cord receives Dmax = 27Gy.
1 year later, the patient develops spinal cord compression with the level of compression at the site that received 27Gy. The patient is not a surgical or chemotherapy candidate and requires further radiation.

How do you calculate how much more dose you can give?

And how did Turissi come up with the spinal cord max dose of 36Gy for his protocol? Is this based on a radiobiological calculation, patient data (e.g. CHART), or just picked arbitrarily???

 

[Palex80]

Do you guys know how to do this calculation? I've gone thru Hall and not found anything relevant. Joiner and van Der Kogel's textbook has a formula but the result doesn't match what we seem to do in clinical practice.

Case:
Patient with limited stage SCLC receives 45Gy in 30 fractions (1.5Gy twice daily, around 6 hours between the two fractions) as per the Turissi protocol. The spinal cord receives Dmax = 27Gy.
1 year later, the patient develops spinal cord compression with the level of compression at the site that received 27Gy. The patient is not a surgical or chemotherapy candidate and requires further radiation.

How do you calculate how much more dose you can give?

And how did Turissi come up with the spinal cord max dose of 36Gy for his protocol? Is this based on a radiobiological calculation, patient data (e.g. CHART), or just picked arbitrarily???

You can easily use a calculator, taking into account the factor for incomplete repair (time calculation).
For example someting like this:
http://www.radiotherapy.com/calculate/

On the other hand, you can use a pretty straightforward approach. Since the cord dose was 27 Gy and you used the Turissi schedule, single dose to the cord was 0.9 Gy / fraction.
Thus you have a total of 1.8 Gy / d to the cord, given in two fractions.

This means your cord dose of 27 Gy is probably somewhere around 22-24 Gy (my guess) given in 2 Gy single fraction per day.

You can easily retreat the patient with a full palliative dose, since spinal cord tolerance will not be exceeded. Look at the Nieder papers for more info.
http://www.ncbi.nlm.nih.gov/pubmed/17084560
http://www.ncbi.nlm.nih.gov/pubmed/15708265

 

[drnick098]

You can easily use a calculator, taking into account the factor for incomplete repair (time calculation).
For example someting like this:
http://www.radiotherapy.com/calculate/

Thanks for the link. That calculation however does not incorporate incomplete repair. It only has tumor kinetics (Tko etc).

On the other hand, you can use a pretty straightforward approach. Since the cord dose was 27 Gy and you used the Turissi schedule, single dose to the cord was 0.9 Gy / fraction.
Thus you have a total of 1.8 Gy / d to the cord, given in two fractions.

This means your cord dose of 27 Gy is probably somewhere around 22-24 Gy (my guess) given in 2 Gy single fraction per day.

If we don't include incomplete repair, 27Gy at 0.9Gy per fraction would be:
EQD2 = 27 * (0.9 + 2) / (2 + 2) = 19.575 Gy
How do you add incomplete repair to this?

And if we get up to cord tolerance according to Turissi, that would be 36Gy at 1.2Gy per fraction which would be:
EQD2 = 36 * (1.2 + 2) / (2 + 2) = 28.8Gy

This is supposedly equivalent to 45Gy at 2Gy fractionation right? Is incomplete repair supposed to add an extra ~150% to the dose?

 

[deleted4401]

The cord can take a fair amount, especially after a 1 month gap. If you go with 30 Gy in 15 fx or 30.6 in 17 fx, I think you'll be safe. I'm quoting myself, only because I ended up reviewing the literature for what sort of BED the spine could take and it's pretty good evidence to re-treat: http://www.ncbi.nlm.nih.gov/pubmed/19640634.

I think you don't have to over think the BED calc for what you've already given because it was given in small fractions, not palliative treatment (30 Gy in 10) and if you gently fractionate the cord compression, the chance for toxicity is very small.

 

[Palex80]

Thanks for the link. That calculation however does not incorporate incomplete repair. It only has tumor kinetics (Tko etc).

True. Sorry about that. I looking into my radiobiology book and found this:

EQD2 = D x [d(1+Hm) + (a/b)] / [2 + (a/b)]

Let's suggest an incomplete repair factor Hm of 0.25 for 2 fractions per day, kept 8 hours apart (that's what my book says).
With an a/b=2, a d=0.9 and a D=27 you get a EQD2 of 19,74375 Gy.

That's even less than I thought!

And if we get up to cord tolerance according to Turissi, that would be 36Gy at 1.2Gy per fraction which would be:
EQD2 = 36 * (1.2 + 2) / (2 + 2) = 28.8Gy

Turissi's tolerance is probably over-conservative and addressing the worst case scenario, which means that both 1.5 Gy fractions reach the cord (which actually can't be, since you are supposed to give 45 and not 36 Gy to the tumor). Forget about his constraints.
The spinal cord tolerance for 1.2 fractions given BID is not 36 Gy. It's considerably higher. According to the equation (and with a cord tolerance of 45 Gy EQD2) it's 46.1538 Gy.

 

[Gfunk6]

The spinal cord tolerance for 1.2 fractions given BID is not 36 Gy. It's considerably higher, probably somewhere around 44-46 Gy.

CALGB 30610 quoted 41 Gy with Turrisi's regimen. I would not go beyond this personally either in practice or on boards.

 

[deleted4401]

Right, so that's for a curative case, because the spinal cord is one of the organs where we don't use TD5/5 - that would be a really unreasonably high rate of toxicity to the cord and paralyzing that many people not a great idea. But, for a re-treat, until you hit a BED of 100-120, it's just not that high a risk. And, the life expectancy of someone with symptomatic spinal cord compression is not very high...

 

[deleted4401]

When you have one first author publication in a second rate journal to your name after 4 years residency which included 9 months of research at an institution that is in the top tier in terms of articles published per resident, you end up hanging a lot of hats off of it...

 

[drnick098]

Thanks for all the replies. I was thinking about how a few patients got myelopathies from the CHART pilot study & did some calculations:

54Gy in 36 fractions at 3 fractions / day
With cord Dmax at 42Gy a few patients developed myelopathies.
Lets say the cord gets 42Gy / 28 fractions (1.5Gy/fraction) and then the beams go "off cord" after the 28th fraction
Without incomplete repair:
EQD2 = 42 * (1.5 + 2) / (2 + 2) = 36.75 Gy
With incomplete repair:
EQD2 = 42 * (1.5 * [1 + 0.555] + 2) / (2 + 2) = 45.49 Gy

Which is still not that high. I would've thought that the EQD2 should be >50Gy to get a few myelopathies.

So in a re-irradiation scenario, how many people would give 1.2Gy twice daily fractionation to try to take advantage of the fraction sensitivity of the cord? If you don't consider incomplete repair, you may have an advantage with 1.2Gy BD. If you consider incomplete repair, you might be at a slight disadvantage. If you consider the myelopathy cases in CHART 3X daily fractionation or the Turissi 36Gy constraint, you may be at a major disadvantage by giving 1.2Gy BD. Yet I've seen a few people give this for reirradiation. Thoughts? Are we deceiving ourselves with these models?

 

[Palex80]

I have given 1.2 BID for reirradiation before.
The maximum I have done is 36 Gy BID with 1.2 Gy/fraction for a a patient, who had receved 10 x 3 Gy more than a year ago.

I see the advantage of BID only in cases, where there may be a relevant benefit in lowering the risk of myelopathy, since you first treatment already delivered a high dose to the cord (60+ Gy BED).
Otherwise, you can safely treat with 2-2.5 Gy/d to moderate doses like 35-40 Gy.
This is easily doable, if the cord only received something like 20-25 Gy in the first series (with a small fraction size).