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.

Radial Data Mining to Identify Density–Dose Interactions That Predict Distant Failure Following SABR

“…The counterintuitive result of Region 1 is explained by considering the mean EQD2 dose inside each of the regions identified by the dose parameter (Supplementary Figure 13). In region 1, the median value is 55 Gy with range 74-92 Gy, which is significantly higher than 9 Gy (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32) in R2 and 14 Gy (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41) in R3. Considering the difference in dose scales, a large SD in this region would not lead to underdosage of microscopic disease.…”

“…Overall, this study suggests that considering imaging or dose alone may underpower a study when there is biological rationale supporting that an interaction could be present ( 13 ). The link between microscopic disease and incidental dose is an example of a biological interaction, which could be relevant beyond lung cancer, for example in prostate cancer where a lower incidental dose outside the prostate has been linked to failure ( 39 ). Other examples of interactions could include the influence of genes linked to tissue radiosensitivity ( 40 ), or patient performance status on risk of experiencing a radiotherapy-related side effect ( 38 ).…”

Dosimetric and Hematologic Implications of Prostate-Only Versus Whole Pelvic Radiotherapy: Results of the Multicentric Phase 3 PROPER Study

“… 18 Also, for PORT with image-guided intensity-modulated radiotherapy (IMRT), an association between treatment failure and incidental dose outside the prostate has been suggested for high-risk PCa patients. 19 …”

Effect of the normal liver mean dose on intrahepatic recurrence in patients with hepatocellular carcinoma after receiving liver stereotactic body radiation therapy

“…However, despite excellent local control rates after receiving SBRT, tumor recurrence remains the major problem. Most patients suffer from treatment failures in the liver outside the PTV (outfield failure) [ 12 , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] ]. Few studies summarized the OutFFS and DMFS in SBRT-treated patients.…”

“…However, studies have shown that a lower radiation dose outside of the planning target volume (PTV) increases the risk of distant metastasis in the early-stage lung cancer treated with SBRT, possibly because of the microscopic diseases around the tumor that have not been eradicated [ 5 , 6 ]. For prostate radiotherapy, high incidental doses outside the tumor have shown a significant effect on reducing the treatment failure [7] . Similar studies have demonstrated the relationship between regional control and incidental dose in draining the lymphatics [ 8 , 9 ].…”