Association between incidental dose outside the prostate and tumor control after modern image-guided radiotherapy

Abstract

Background and purpose: External beam radiotherapy for prostate cancer deposits incidental dose to a region surrounding the target volume. Previously, an association was identified between tumor control and incidental dose for patients treated with conventional radiotherapy. We investigated whether such an association exists for patients treated using intensity modulated radiotherapy (IMRT) and tighter margins.

Materials and methods: Computed tomography scans and three-dimensional treatment planning dose distributions were available from the Dutch randomized HYPRO trial for 397 patients in the standard fractionation arm (39 × 2 Gy) and 407 patients in the hypofractionation arm (19 × 3.4 Gy), mainly delivered using online image-guided IMRT. Endpoint was any treatment failure within 5 years. A mapping of 3D dose distributions between anatomies was performed based on distance to the surface of the prostate delineation. Mean mapped dose distributions were computed for patient groups with and without failure, obtaining dose difference distributions. Random patient permutations were performed to derive p values and to identify relevant regions.

Results: For high-risk patients treated in the conventional arm, higher incidental dose was significantly associated with a higher probability of tumor control in both univariate and multivariate analysis. The locations of the excess dose mainly overlapped with the position of obturator internus muscles at about 2.5 cm from the prostate surface. No such relationship could be established for intermediate-risk patients.

Conclusions: An association was established between reduced treatment failure and the delivery of incidental dose outside the prostate for high-risk patients treated using conventionally fractionated IMRT.

Keywords: Dose modelling; Freedom from failure; Incidental dose; Prostate cancer; Radiotherapy.

Fig. 1

Dose differences by failure mapped around the prostate in axial view with delineated structures bladder (yellow), prostate (cyan) and rectum (magenta). Light and dark gray lines indicate q-values of 25% and 50%, respectively. Global p-values were based on random patient permutations. 1a Intermediate-risk CF; 1b high-risk CF; 1c intermediate-risk HF; 1d high-risk HF. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Axial (top) and coronal (bottom) slices through the CT set (left) and the anatomy based on cryo slices (right) of the Visible Human data set with delineated structures bladder (yellow), prostate (cyan) and rectum (magenta). Light and dark gray lines indicating q-values of 25% and 50% correspond to the results in Fig. 1b for high risk CF patients. Dose values at the location of the cyan cross at 2.5 cm from the delineated prostate were used for subsequent survival analysis and logistic regression. Abbreviations: bl: bladder, fm: femur, hb: hip bone, oi: obturator internus, pr: prostate, rc: rectum, sv: seminal vesicles. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Kaplan Meier curves (free from tumor progression) for high risk patients in the conventional treatment arm, using 45 Gy and 55 Gy dose cut-off levels in the location marked with a cyan cross in Fig. 2. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

Mean and standard deviation of dose distributions mapped around the prostate in coronal view for high-risk patients treated with conventional fractionation (top rows) and hypofractionation (bottom rows), using physical dose and EQD_2Gy with α/β = 3 Gy and α/β = 1 Gy (columns left to right). Delineated structures are prostate (cyan) and rectum (magenta). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)