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.
