In this study, we compared the plan quality of EDGE and CK in terms of dosimetric properties, delivery efficiency and predicted biological outcomes for prostate SBRT treatment. Both of the two techniques were able to produce clinically acceptable plans with adequate target irradiation and normal tissue sparing. Despite both systems were able to achieve excellent dose distribution according to the results above, EDGE had a little better performance in dosimetric results of conformity of PTV and better OAR sparing.
The EDGE plans were optimized using high definition HD120 MLCs (with minimum spatial resolution of 2.5 mm) on the X axis with even littler size of gap on the Y axis, while the CK plans were made by 1–2 circular cones with size of 20∼30 mm. The high resolution of MLCs make it easier to reach more conformal dose distribution of PTV for EDGE, which will largely reduce the number of sub-fields.
The main reasons for the normal tissue sparing differences were due to the different characteristics of the two systems, which could be explained in two aspects. First and foremost, the plan optimization processes of the Multiplan version 4.0.2 and Eclipse 13.5 are very different. In the Multiplan, we could only set the maximum doses of OARs as constraints and optimize the mean doses of OARs, while in the Eclipse, several constraints could be set on the DVH curves of each OAR. This is one of the major reasons for superior OARs sparing of EDGE system. Further improvement for CK plan is feasible, if the optimization algorithm of Multiplan® evolves. Secondly, the beam arrangements in the process of planning optimization may play important roles for the dose distribution. CK offers superiority of highly flexible angles, which delivered noncoplanar beams from all directions moved by the robotic arm while EDGE rarely used noncoplanar beams in the region of abdomen due to mechanical and geometrical limitations. However, the CK did not benefit from this advantage in this study because the beams of CK were mainly distributed in directions perpendicular to cranio-caudal (CC) direction in these plans, as the final results of beam-angle optimization in light of the anatomical position of the prostates. The most beneficial beam angles were similar to those from two full 360 rotation arcs (178 segments for each plan) of EDGE which were rotated around CC direction.
As noted above, EDGE had the shortened average delivery time and the fewer MUs largely, as displayed in Table 4. Lessening treatment time means less scatter dose, which may lower the probability of secondary malignancies. On the other hand, decreased delivery time of EDGE can potentially reduce the effects of intra-fractional motion, and make the patients more comfortable. The VMAT technique, which delivers from a large number of angles with fewer control points, has been showed to decrease the number of MUs significantly, along with even lower MUs for dual-arc VMAT plans under the same condition as reported by Quan et al . Moreover, EDGE system has 10FFF mode delivering the maximum high dose rate of 2400 MU per minute which severely shortens the beam-on time [18, 23].
The radiobiological parameters in terms of EUD and TCP (NTCP) were calculated from DVHs, as showed in Table 5. The results indicated that the EDGE plans have slightly reduced CTV EUD than the CK plans, the results of which were in agreement with these of dosimetric evaluation. The mean EUD were lower for the OARs such as bladder, rectum, urethral and penile bulk in the EDGE plans in accordance with the calculated lower NTCP values consequentially. Both groups of plans were able to maintain high EUD to the tumors and yield good tumor TCP while low NTCP of normal structures were obtained in relation to late toxicity effects. For predicted clinical benefits, this two treatment modalities can be considered to be safe.
Additionally, there also exists a concern for tumor and adjacent organs position variations throughout the course of treatment after the online match per fraction[41–43]. The intra-fraction prostate displacements were reported to be > 3 mm and > 5 mm were 24% and 5% of fractions respectively . In this case, the target localization and real-time tracking systems are necessary to improve confidence in radiation dosimetry. Previous studies showed that CK has the competitive in light of target localization to deliver accurately in comparing conventional linear accelerator . For the CK, two kilovoltage x-ray generators and two hereafter cameras are incorporated to finish fiducial tracking for prostate motion . Very small set-up errors were observed with 1.8 mm in the anterior posterior direction and 1.4 mm in the superior inferior direction . However, EDGE system, designed for SBRT or SRS, has been improved to integrate Calypso 4D system capable of monitoring target position on the basis of radiographic transponder locations. Calypso system was reported to present a treatment accuracy of average 3D difference of 1.5 mm in dose delivery . Thus EDGE has similar performance against motion uncertainties. For this reason, we delineated target margins for EDGE system according to the same protocols used for the CK. For all that, EDGE is lack of practical experience clinically by Calypso 4D system compared to CK.
Several limitations should be recognized in this investigation. Firstly, because the representative version of CyberKnife G4 system with the fixed cone is most commonly used, it was selected to compare to the latest EDGE system in our study. The latest generation of CK system M6™, with IRIS collimator and InCise MLC, may increase the output rate and conformal dose distribution as well as to reduce delivery time. Otherwise, the radiobiological parameters presented in this study are highly dependent on the model and related parameters. Therefore, the radiobiological responses could only be regarded as references when making clinical decisions. Further studies on clinical trials are required to collect practical experience and find out which is the valuable option for localized prostate cancer.