Evaluation of multiple institutions’ models for knowledge-based planning of volumetric modulated arc therapy (VMAT) for prostate cancer

In this study, five institutes (A–E) were enrolled. These institutes treated patients with T1–T2c prostate cancer using VMAT. Table 1 shows the definition of gross tumor volume (GTV), margins to define the clinical target volume (CTV) and PTV in each direction. In each institution, the dose constraints are shown in Table 2. The five institutes had different plan designs.

In each institute, the model for KBP was created using the VMAT plans for clinical use at each institute before April 2017. The number of registered cases in institute A, institute B, institute C, institute D, and institute E were 123, 53, 20, 60, and 100, respectively.

Users performed three main steps to create models for KBP. In the first step, dose volume histogram (DVH) estimation model configuration, > 20 plans that had been used in clinical settings were registered. The next step was the extraction phase. In each OAR of registered plans, dosimetric and geometric information was imported in the model. The last step was the training step, based on the information from the extraction phase. In this step, in each OAR of registered plans new DVH curves were generated. Upper and lower limits of the estimated doses (ED) were obtained. These dose limits were saved in the form of DVH in the model. To attain the ideal dose distribution, the parameters, except line objects shown in Table 3, were set in some institutes.

These data were read from an .xml file exported to the website of Model Analytics (https://​ModelAnalytics.​varian.​com). The file also contained basic information on the model, such as original and estimated DVH data and OAR volume, and the ratio of an OAR’s volume overlapping with PTV to the whole organ volume (V_overlap/V_whole). To evaluate the performance in reducing the dose to rectum and bladder in each model, the original DVH, and upper and lower limits of ED, were extracted from the file.

To investigate whether KBP was performed correctly, two sets of CT data and structures of patients at institute B were anonymized and delivered to other institutes. Written informed consent was obtained from all patients, and the Institutional Ethics Committee approved this study (Kindai University review board number: 29–133). The thickness of the CT sections was 2.5 mm and the field of view was 50 cm. The target and OARs were contoured by a physician according to the protocol of institute B. The bladder in one case (case I) had a volume of 83.8 cm³, in another case (case II), bladder volume of 181.8 cm³. V_overlap/V_whole of the rectum and bladder were 9.8% and 11.1% in case I and 5.9% and 5.9% in case II, respectively.

At each institute, the planners who participated in this study had experience with inverse planning for IMRT or VMAT with the Eclipse (Varian Medical Systems, Palo Alto CA, USA) treatment planning system (TPS). They attended a special lecture (RapidPlan Clinical Advisory Board) on Rapidplan held by the manufacturer in Tokyo in June 2017. In KBP using Rapidplan, single optimization was performed. Next, in the manual optimization planning, the optimization was repeated until it achieved the institutional ideal dose distribution. In manual optimization, the generalized equivalent uniform dose (gEUD) was not used in all institutes. In KBP and manual optimization planning, the same calculation parameters and beam parameters were used. The photon optimization was used with 2.5 mm grid size. The calculation algorithm was Anisotropic Analytical Algorithm ver. 13.0 (Varian Medical Systems, Palo Alto CA, USA).

The mean ± SD of the PTV registered for each model were 91.4 ± 26.0 cm³, 99.5 ± 35.6 cm³, 82.0 ± 16.9 cm³, 136 ± 35.1 cm³, and 95.3 ± 24.5 cm³ for institutions A, B, C, D, and E, respectively. In the original OAR’s volume registered in each model, the mean ± SD of the rectal volume were 50.1 ± 13.7 cm³, 59.7 ± 24.9 cm³, 50.3 ± 14.2 cm³, 54.3 ± 21.9 cm³, and 45.2 ± 14.1 cm³ for institutions A, B, C, D, and E, respectively. The mean ± SD of the bladder volume were 151.3 ± 69.2 cm³, 165.1 ± 98.4 cm³, 179.5 ± 63.4 cm³, 80.7 ± 44.9 cm³, and 172.8 ± 101.7 cm³ for institutions A, B, C, D, and E, respectively. The mean ± SD of the rectal volume overlapping with PTV were 5.0 ± 1.4 cm³, 3.2 ± 1.4 cm³, 2.9 ± 1.2 cm³, 3.6 ± 1.3 cm³, and 4.6 ± 1.8 cm³ for institutions A, B, C, D, and E, respectively. The mean ± SD of the bladder volume overlapping with PTV were 8.3 ± 3.3 cm³, 12.5 ± 7.0 cm³, 8.9 ± 3.9 cm³, 5.9 ± 2.1 cm³, and 12.6 ± 4.4 cm³ for institutions A, B, C, D, and E, respectively. The mean ± SD of the V_overlap/V_whole for the rectum were 10.4% ± 3.0%, 6.0% ± 2.7%, 5.8% ± 2.2%, 7.2% ± 2.8%, and 10.5% ± 3.8% for institutions A, B, C, D, and E, respectively. The mean ± SD of the V_overlap/V_whole for the bladder were 6.4% ± 3.1%, 8.7% ± 3.9%, 5.1% ± 2.3%, 9.2 ± 10.2%, and 9.0% ± 4.4% for institutions A, B, C, D, and E, respectively.

In the original DVH data registered for each model, the mean ± SD of the rectal volume ratio receiving 90% of the prescribed dose (V90) were 11.2% ± 3.2%, 11.3% ± 3.3%, 5.7% ± 2.5%, 1.4% ± 1.3%, and 15.4% ± 3.6% at institutions A, B, C, D, and E, respectively. The mean ± SD of the rectal volume ratio receiving 50% of the prescribed dose (V50) were 37.5% ± 7.0%, 37.8% ± 9.1%, 25.2% ± 6.4%, 69.2% ± 12.6%, and 45.3% ± 6.5% at institutions A, B, C, D, and E, respectively. The mean ± SD of V90 of the bladder were 6.4% ± 3.1%, 16.4% ± 6.0%, 9.1% ± 3.6%, 5.8% ± 4.0%, and 10.9% ± 5.0% at institutions A, B, C, D, and E, respectively. The mean ± SD of V50 of the bladder were 27.9% ± 11.4%, 42.0% ± 14.9%, 24.5% ± 8.7%, 62.6% ± 20.1%, and 34.3% ± 14.3% at institutions A, B, C, D, and E, respectively. The box plots of the rectal and bladder dose are shown in Fig. 1. The median of each rectal dose for institute E were the highest among the sites. Those for institute C were the smallest. The median of each bladder dose for institute B was the highest.

In the rectal and bladder doses calculated by KBP and manual optimization planning, V90 and V50 are shown in Fig. 2 (a), (b), (e), and (f). In the V90 of the rectum, the mean ± SD of difference between KBP and manual optimization planning was 0.4% ± 1.6% and − 0.1% ± 1.5% in cases I and II, respectively. A negative value implies that dosimetric values for KBP were higher than those for manual optimization planning. In the V50 of the rectum, the mean ± SD of difference between KBP and manual optimization planning was 2.2% ± 6.9% and 2.6% ± 8.0% in cases I and II, respectively. For the V90 of the bladder, the mean ± SD of difference between KBP and manual optimization planning was 1.3% ± 2.0% and 1.0% ± 0.9% in cases I and II, respectively. For the V50 of the bladder, the mean ± SD of differences between KBP and manual optimization planning was 4.8% ± 5.0% and 3.6% ± 0.9% in cases I and II, respectively.

The dose received by at least 95% of the volume (D95) for the OARs is shown in Fig. 2 (c) and (g). For the D95 of the rectum, the mean ± SD of differences between KBP and manual optimization planning was 0.5% ± 1.9% and 0.1% ± 2.7% in cases I and II. For the D95 of the bladder, the mean ± SD of differences between KBP and manual optimization planning was 1.4% ± 2.0% and 1.2% ± 2.0% in cases I and II. There were no significant differences in each dosimetric parameter between the cases.

The dose received by at least 2% of the volume (D2) for the organs is shown in Fig. 2 (d) and (h). In the D2 for the rectum, the mean ± SD of the difference between KBP and manual optimization planning were − 0.5% ± 0.8% and − 0.9% ± 1.8% in cases I and II. In the D2 for the bladder, the mean ± SD of difference between KBP and manual optimization planning were − 0.1% ± 0.8% and − 0.2% ± 1.3% in cases I and II. There were no significant differences in each dosimetric parameter between the cases.

Various dosimetric values were calculated by KBP among institutes even if they used the same dosimetric parameters. Among institutions, the maximum differences in V90 for the rectum were 6.7% and 6.7%, V50 for the rectum were 39.0% and 41.9%, V90 of the bladder were 18.2% and 9.9%, and V50 of the bladder were 12.5% and 6.7% in cases I and II, respectively. These results suggested that each institutional KBP was useful in that particular institute regardless of the number of registered plans in the model, but the performance varied widely among the institutes.

Figure 3 shows the relationships between the upper limit and lower limit of ED and V_overlap/V_whole for the rectum and the bladder, in institutes A and B. Dotted lines are quadratic regression curves between EDs and the V_overlap/V_whole. The black dots are dosimetric values calculated by KBP in cases I and II. Black dots were compiled with regression curves for each organ. The dosimetric values that were calculated by KBP were between curves of the upper and lower limits of ED or slightly lower than the curve of the lower limit of ED. In each organ, coefficients of determination (R²) of each dosimetric value and V_overlap/V_whole for the rectum and the bladder are shown in Table 4. The R² values of V90 were greater than those for V50, except at institution B for the rectum. In the bladder, the R² of V90 were more than those for V50 at all institutions.

Quadratic regression curves between lower limit of ED and V_overlap/V_whole for the rectum with the formulas for all institutes are shown in Fig. 4 (a), (b). In the V90 of the rectum (Fig. 4 [a]), four institutes except institute B had regression curves that tended to increase with increasing V_overlap/V_whole for the rectum. In institute B, the regression curve was almost horizontal. The V90 dose in institute E was the highest of all V_overlap/V_whole for the rectum. When V_overlap/V_whole for the rectum was about 10%, the difference in the lower limits of ED between institutions D and E was > 8%. In the V50 for the rectum (Fig. 4 [b]), Institute D had the highest lower limit of ED in all V_overlap/V_whole for the rectum. When the V_overlap/V_whole for the rectum was 10%, the difference in lower limit of ED between institutes C and D was > 50%.

In the V90 and V50 for the bladder (Fig. 4 [c], [d]), the lower limit of ED curves for all institutes tended to show increases with increasing V_overlap/V_whole for the bladder. In the V90 for the bladder (Fig. 4 [c]), when V_overlap/V_whole for the bladder was 10%, the slopes of lower limits of ED for institutes B and C were steeper than those for institutions A, D, and E. In the V50 for the bladder (Fig. 4 [d]), V_overlap/V_whole for the bladder was approximately 10%, the lower limits of ED were almost the same for institutes A, C, and E. The slope of the curves varied according to facilities. In among institutions, the maximum differences for lower limit of ED of V90 for the rectum were 8.2% and 5.7%, V50 for the rectum 53.5% and 45.0%, V90 for the bladder 15.1% and 9.4%, V50 to the bladder 33.1% and 26.0% when overlap volume with PTV was 10.0% and 6.0%, respectively.