How NOT to give salvage radiation after primary radiation failure

Recently, we commented on a couple of small studies where radiation re-treatment was used effectively and with acceptable toxicity. In one study, we saw that SBRT has been used after external beam radiation failure. In the other study, low dose rate brachytherapy was used after brachytherapy failure. Here we have a case study in how not to give salvage radiation after primary radiation failure.

Zilli et al. report on 14 patients treated at Geneva University Hospital in Switzerland. The patients had a presumed local recurrence after failure of primary external beam radiation therapy (EBRT) alone or a combination of EBRT with a brachytherapy (BT) boost.

• ·        Original median dose of 74 Gy (range 66-98.4 Gy)
• ·        Median time to first radiation failure: 6.1 years (range 4.7-10.2 years)

Re-treatment was given between 2003 and 2008. The salvage radiation treatment consisted of:

• ·        Salvage dose of 85.1 Gy (range 70-93.4 Gy)
• ·        10 patients received salvage EBRT + BT
• ·        4 patients received salvage EBRT only
• ·        12 patients received ADT for a median of 12 months

There were no serious acute side effects of treatment. However, after a median follow-up of 94 months (range 48-172 months):

• ·        21% of patients suffered serious (grade≥3) genitourinary (GU) side effects
• ·        43% of patients suffered serious (grade≥3) gastrointestinal (GI) side effects
• ·        4 patients (29%) suffered combined life-threatening (grade 4) GU and GI side effects
• ·        35% were free of biochemical relapse after 5 years
• ·        50% were free of local relapse after 5 years
• ·        86% were free of distant metastases after 5 years

The conventional wisdom is that there is a lifetime maximum radiation dose of about 80 Gy. After that, the repair mechanisms that healthy tissues use to recover after radiation become compromised, and the tissues become necrotic. There are ways of pushing the maximum dose higher by using methods like SBRT or HDR brachytherapy that increase the biologically effective dose without undue radiation exposure to healthy tissue. Using advanced image guidance technologies, we are able to push the limit up a bit too, sometimes as high as 86 Gy for IMRT. Focal salvage brachytherapy is able to push the limit by restricting radiation exposure to a very small area of the prostate.

It’s hard to imagine what the researchers were thinking. Perhaps they imagined that after a median of 6 years, the tissue recovery was complete. As we see, it wasn’t. These patients were given 159 Gy, and some possibly more than that in total. The injury they suffered was to the late-responding tissues of the bladder, urethra and rectum, which are known to be particularly susceptible to these kinds of doses. And to add insult to injury, the re-treatment failed in 64% of patients. This is perhaps attributable to the limited distant-metastasis detection methods available at that time.