LDR vs HDR brachytherapy

In the only randomized comparative study I'm aware of, they're both about equal on that dimension in the long term.

Grills et al. said...
Biochemical control was 97% and 98% for LDR and HDR, respectively.

HDR brachytherapy alone was associated with decreased acute rates of:
• grade 1 to 3 dysuria (67% versus 36%)
• urinary frequency/urgency (92% versus 54%), and
• rectal pain (20% versus 6%).

Selected chronic toxicities were also decreased with HDR, including long-term:
• urinary frequency and urgency, 32% (HDR) vs 56% (103Pd)

There were no differences in the rates of:
• chronic dysuria
• urinary incontinence
• retention or
• hematuria.

Urethral stricture rates were 8% in the HDR alone group vs 3% for 103 Pd (not statistically different).

The 3-year actuarial impotence rate was 45% for the LDR group and only 16% for HDR.

High dose rate brachytherapy as prostate cancer monotherapy reduces toxicity compared to low dose rate palladium seeds.

In the short term, UW Seattle, arguably the best, reported 43% acute urinary retention in 2002 -- I don't know if they've improved on that or not since then. Washington U reported a similar rate - 34%. HDR (Demanes] reported 13% Grade 2 & 3 urinary retention (10% & 3% respectively). FYI, Katz using SBRT reported no urinary retention requiring treatment (acute or late, with only 4% Grade 2 urinary SEs).

Long? It all depends on which machine they're using. Mine were done in 5 five-minute sessions. I had it done at UCLA by the RO who first started it for PCa back in 2003 (he was at Stanford then). He uses a souped-up Novalis Tx RapidArc machine now, but started it with a Accuray CyberKnife machine on which each session can be over 45 minutes. The newer CK machines do it in less than half an hour. The newer Varian TrueBeam machines can do each session in about 2-3 minutes. There's a new system from Brainlab & Mitsubishi called Vero which is like a multidimensional RapidArc on steroids. Elektra has an SBRT system too. Because they deliver such concentrated doses in such a short time they have to have sub-millimeter accuracy, and have to have great intra-fractional image tracking systems.

Like HDR brachy, SBRT takes advantage of the fact that prostate cancer cells have a lower parameter of something called an alpha/beta ratio compared to the healthy cells of the nearby organs. This spares the healthy tissue while killing the cancer with about half the total dose of radiation.

- Allen

It's complicated and I've had a stiff drink, but here goes...

Radiation kills cancer cells according to a linear-quadratic model, which means that some of the cancer cells are killed as a linear function of the radiation dose (the alpha part), while some are killed as a quadratic function of the radiation dose (the beta part). If a particular cancer has a low alpha/beta ratio, it is killed more effectively by a few concentrated doses (the beta kill dominates) than by a long series of low doses (the alpha kill is relatively less important). The typical IMRT schedule of 2 Gy per fraction x 40 fractions (= 80 Gy) was based on the supposition that prostate cancer, like most other cancers, had a relatively high alpha/beta of around 10. In the late 1990s, however, it was discovered that prostate cancer cells actually had a very low alpha/beta, now estimated to be about 1.5. This creates a multiplier effect to delivering radiation in fewer more concentrated doses (called hypofractionation).

To see how this multiplier effect works, if you want to calculate the biologically equivalent dose if a particular dosing schedule had been given at the typical 2 Gy/fraction schedule, the formula is:

Equivalent dose=n*d*(d+a/b)/(2+a/b)

where n=number of fractions
d=dose per fraction
a/b= alpha/beta ratio

So for the SBRT schedule I had, n=5 fractions, d=8 Gy per fraction, and a/b=1.5 -- so that would have been equivalent to the radiation cancer cell killing of 109 Gy if it had been delivered at the typical IMRT rate of 2 Gy per fraction. The typical dose-escalated IMRT schedule only delivers 80 Gy (2 Gy per fraction x 40 fractions). So because of the alpha/beta multiplier effect, I got 36% more cancer cell killing while only exposing myself to half the total dose (40 Gy = 8 Gy x 5 fractions).

I hope that made some sense. I'll look at it tomorrow when I'm less inebriated.

And I vastly simplified that. Now that I'm more sober, I can see that I left out the main advantage of hypofractionation, which is to spare healthy tissues. Tissues in the rectum and bladder have a/b ratios of about 10. Using that formula, you can see how little effective killing dose those healthy tissues are getting with a hypofractionated regime (HDR or SBRT).

For LDR... well, it's complicated. LOL. The radioactive seeds start out by delivering a high dose, just as HDR or SBRT does. This is consistent with a high beta component, and therefore a low alpha/beta ratio. Based on the low alpha/beta ratio of prostate cancer, it does an excellent job of killing those bad guys quickly. However, the seeds exponentially decay, so they are soon delivering only very low doses of radiation. This is consistent with a high alpha component, and therefore a high alpha/beta ratio. What this means practically is that the seeds become more toxic to healthy tissues. This would explain the higher acute toxicity vs HDR that we see. Eventually, their radioactive output becomes negligible and effectively inert.

For LDR, we look for radioactive isotopes that give up their x-ray energy very quickly. In general, this correlates with half-life. There are 3 isotopes now in use:
• I125 has a half-life of 60 days and gives up 90% of its dose in 204 days.
• Pd103 has a half-life of 17 days and gives up 90% of its dose in 58 days
• Cs131 has a half-life of 10 days and gives up 90% of its dose in 33 days

But how well the seeds are placed has a much larger effect on oncological effectiveness and toxicity. I would rather have Dr. Peter Grimm place I125 seeds, which he is familiar with, than have Dr. Leo Spaceman place Cs131 seeds.

If you like math, you might enjoy the subject of radiobiology. I have lots more complex formulae and charts full of curves. If you want to study them, send me an email.

- Allen

Tall Allen,
You probably didn't have enough to drink since your explanation made sense to me; ok, I only scanned your post. Probably the main point that shocked me was that HDR treatment results in only 16% impotence. I can only hope that members and lurkers who have not had treatments yet can only review your many threads and posts regarding cure rates and side effects of the different treatments; I don't desire to create a "firestorm", but I can see a time in the future when "surgery" is just another option instead of a "standard"..Keep up the good work!
Bill

The dose for both LDR and HDR are much higher than for IMRT alone. Basic dose for IMRT is 81 gy and for seeds 110 to 150 gy.

Newguy, this is a zombie thread, started and ended 6 years ago. I am going to start a new thread for you and move your post there. You will likely get more comments that way. Here is where you will find the new thread....

https://www.healingwell.com/community/default.aspx?f=35&m=4159106&g=4159107#m4159107