Late rectal toxicity: dose-volume effects of
conformal radiotherapy for prostate cancer
Eugene H. Huang, International Journal of Radiation Oncology-Biology-Physics, 2002;
54:5 : 1314-1321
We retrospectively analyzed the dose-volume histograms and clinical
records of 163 Stage T1b-T3c prostate cancer patients treated between 1992 and 1999 with
3D-CRT, to a total isocenter dose of 74–78 Gy at The University of Texas M. D.
Anderson Cancer Center. The median follow-up was 62 months (range 24–102). All
late rectal complications were scored using modified Radiation Therapy Oncology Group and
Late Effects Normal Tissue Task Force criteria. The 6-year toxicity rate was assessed
using Kaplan-Meier analysis and the log-rank test. A univariate proportional hazards
regression model was used to test the correlation between Grade 2 or higher toxicity and
the dosimetric, anatomic, and clinical factors. In a multivariate regression model,
clinical factors were added to the dosimetric and anatomic variables to determine whether
they significantly altered the risk of developing late toxicity.
Results: At 6 years, the rate of developing Grade 2 or higher late rectal toxicity was
25%. A significant volume effect was observed at rectal doses of 60, 70, 75.6, and 78 Gy,
and the risk of developing rectal complications increased exponentially as greater volumes
were irradiated. Although the percentage of rectal volume treated correlated
significantly with the incidence of rectal complications at all dose levels , the absolute
rectal volume appeared to be a factor only at the higher doses of 70, 75.6, and 78 Gy .
The following variables also correlated with toxicity on the univariate analysis: maximal
dose to the clinical target volume, maximal dose to rectum, maximal dose to the rectum as
a percentage of the prescribed dose, and maximal dose delivered to 10 cm3 of the rectum.
Of the clinical variables tested, only a history of hemorrhoids correlated with rectal
toxicity . Multivariate analysis showed that the addition of hemorrhoids increased the
risk of toxicity for each dosimetric variable found to be significant on univariate
analysis
Classification and regression tree analysis identified the optimal cutpoints that
differentiated patients at high risk of late toxicity from those at low risk. The
cutpoint
for the percentage of the volume of the rectum irradiated to 60, 70, 75.6, and 78 Gy was
40.6%, 26.2%, 15.8%, and 5.1%, respectively. The
cutpoint for the
absolute volume of the rectum irradiated to 75.6 and 78 Gy was 3.8 and 1.4 cm3,
respectively. The 6-year rate of rectal complications was 54% for patients
who had >26.2% of rectum irradiated to 70 Gy vs. 13% for those who had < 26.2%
irradiated to 70 Gy.
To reduce the risk of late toxicity, <40% of the defined rectal volume should receive
60 Gy, <25% should receive 70 Gy, <15% should receive 75.6 Gy, and <5% should
receive 78 Gy. At the higher dose levels, <4 cm3 of the absolute rectal volume should
be irradiated to 75.6 Gy and <2 cm3 to 78 Gy. The percentage of rectal volumes and the
maximal rectal dose were the dosimetric variables that correlated most significantly with
late toxicity. Since our preliminary report of the 3D-CRT dose-escalation trial our
institution has been using <25% of the rectum receiving 70 Gy as a principal DVH
constraint, although it has been increasingly recognized that the DVH is a continuum of
relationships and not a single dose point.
Other investigators have previously reported the dose-volume effects related to late
rectal toxicity after 3D-CRT, particularly at doses of >60 Gy. Schultheiss reported
that patients with rectal shielding on the lateral fields for the final 10 Gy of treatment
(total doses of 77–80 Gy) had significantly less Grade 2–4 rectal toxicity, 13%
vs. 43%. Wachter found that Grade 2 rectal complications were associated with
patients who had >57% of the rectum irradiated to 60 Gy. Similarly, Boersma
reported that the percentage of rectum irradiated correlated significantly with
Grade 3 rectal bleeding. Finally, in a series of 41 patients treated at the Massachusetts
General Hospital using a proton boost to a total dose of 75.6 Gy, rectal bleeding
correlated with a range of dose-volume combinations from 60 Cobalt Gray Equivalent to
>70% of the anterior rectal wall to 75 Cobalt Gray Equivalent to >30% .
Conclusion: Dose-volume histogram analyses clearly indicated a volume effect on the
probability of developing late rectal complications. Therefore, dose escalation may be
safely achieved by adherence to dose-volume histogram constraints during treatment
planning and organ localization at the time of treatment to ensure consistent patient
setup. Our data suggest that it is the percentage of rectal volume, rather than
the absolute volume, that correlates more significantly with late toxicity. If possible,
the percentage of rectal volume irradiated to 60, 70, 75.6, and 78 Gy should be limited to
40%, 25%, 15%, and 5%, respectively. |