Introduction

The inherent photon beam characteristics of different energies, such as penetrating power and penumbra, have provided planners with more options[1], but the choices also vary subjectively among different centers. There have been a lot of dosimetric researches on the beam energies [2,3,4,5], but consensus can hardly be made providing contradictory literature reports. Coming to the era of knowledge-based planning, the impact of beam energies on the model configuration and applications remains unknown, and is worthy of more investigations.

Varian RapidPlan (Varian Medical Systems, Pala Alto, CA) uses Principal Component Analysis (PCA) regression to fit the correlation between the geometric features (including patient anatomy and beam geometry) and the historical ‘achievable’ dose distribution without using the actual beam energy as regression input at the training stage. When the trained model is used to predict DVHs for upcoming cases, Geometry-Based Expected Dose (GED) metric was used to estimate the achievable dose to a voxel by considering patient anatomy (such as distance from the targets surfaces), dose prescriptions, and field geometry (such as in- vs. out-of-field) [6,7] and beam energy, etc. According to the manufacturer[8], the total dose-distance value in voxel v (ged_v) is defined as: (1)

Where m is number of target levels, δ_t is incremental target level, n is number of fields, C_TV is a scaling factor of modulation, d_fv is Euclidean distance from field f to voxel v, and λ_f is a parameter depending on the nominal photon beam energy of field f. A sum of the voxels yields a predicted dose volume histogram (DVH) range that can be used to generate patient specific optimization objectives. RapidPlan generated different objectives for the same patient in an automatic and mathematical manner if various beam energies were selected as input to the model prediction.

Previous studies on the dosimetric effects of photon energies were vulnerable to potential bias of different optimization objectives[9], or limitations of planner experience [5, 10]. By introducing λ_f, RapidPlan generates various energy-dependent and patient specific objectives without subjective manual iterative adjustment and inter-planner variability, hence provides a more objective comparison basis.

This study aims to evaluate the dosimetric impact of beam qualities on the sparing of normal tissues by applying a preconfigured RapidPlan model to various clinically available photon energies for rectal cancer patients.

Methods

This retrospective, anonymous and computation-based study is approved by Medical Ethics Committee of Peking University Cancer Hospital & Institute with exemption of informed consent. All experiments were conducted on Varian RapidPlan knowledge-based treatment planning system V. 13.5 with appropriate anonymization.

Results

Patient characteristics

Table 1 summarizes the tumor characteristics of 81 training cases (53 males) and 20 validation cases (14 males). The ranges and medium age of the training set were 39~89 and 62 year, and were 34~75 and 60 year for the validation set respectively. The concurrent chemotherapy regimen was capecitabine 825mg/m² twice daily, 5d/w.

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Table 1. Tumor volumes [cm³] of 81 training cases and 20 validation cases.

https://doi.org/10.1371/journal.pone.0213271.t001

Target dose coverage using various photon energies

Fig 1 plots the target DVHs of 20 patients, as optimized automatically using various photon energies. Subfigures (a-d) present the target DVHs of 6X, 6F, 8X and 10 F (dotted lines) relative to the reference 10X results (solid lines) respectively. The figure-in-figure shows the corresponding mean target DVHs of 20 patients, as optimized using the same beam energy. The target DVHs of 10X, 8X and 6X largely overlapped with each other, providing comparable basis for OAR dose evaluation. Echoing numerically, the mean CI values for 6X, 8X and 10X were 1.05, 1.05, 1.04 for planning target volume (PTV), and 1.14, 1.12, 1.10 for PTV_boost, respectively. The corresponding mean HI values for all flattened beams were 0.27 (PTV) and 0.05 (PTV_boost) respectively. However, the dosimetric features such as dose falloff and hot spots were severely worsened using 6F and 10 F beams, making those plans clinically unacceptable which were thus excluded from further OAR dose comparison. Specifically, the mean CI values for 6F and 10F were 1.10, 1.10 (PTV), and 1.29, 1.34 (PTV_boost) respectively. The corresponding mean HI values for 6F and 10F were 0.29, 0.30 (PTV) and 0.07, 0.08 (PTV_boost) respectively.

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Fig 1. The target DVHs of 20 patients, as optimized automatically using various photon energies.

Subfigures (a-d) present the target DVHs of 6X, 6F, 8X and 10 F (dotted lines) relative to the reference 10X results (solid lines) respectively. The figure-in-figure shows the corresponding mean target DVHs of 20 patients, as optimized using the same beam energy.

https://doi.org/10.1371/journal.pone.0213271.g001

Impact of photon energies on normal tissue sparing

The dosimetric statistics of OARs comparing the performance of 6X and 8X using 10X results as reference were listed in Table 2.

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Table 2. Dosimetric statistics of OARs comparing the results of 6X and 8X against 10X.

https://doi.org/10.1371/journal.pone.0213271.t002

Fig 2 displays the DVH differences of the OARs as optimized using various beam energies relative to 10X photons. The differences were calculated by subtracting the DVHs of evaluated energy from the DVHs of 10X, hence curves above zero horizontal levels indicate worsened OAR sparing than those using 10X beams. The dashed lines plot the data of 20 patients, and the solid lines are their average. The left and right column shows the results of 6X-10X and 8X-10X respectively. Subfigures (a-b), (c-d), (e-f), (g-h) and (i-j) plot the results for the urinary bladder, femoral heads, NTID, skin and small bowel respectively.

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Fig 2. The DVH differences of the OARs as optimized using various beam energies relative to 10X photons.

The dashed lines plot the data of 20 patients, and the solid lines are their average. The left and right column shows the results of 6X-10X and 8X-10X respectively. Subfigures (a-b), (c-d), (e-f), (g-h) and (i-j) plot the results for the urinary bladder, femoral heads, NTID, skin and small bowel respectively.

https://doi.org/10.1371/journal.pone.0213271.g002

Discussion

According to the manufacturer, RapidPlan does not estimate DVHs for the targets, which is determined by the fixed objectives as imbedded in the model template. It seems that these parameters can be shared by flattened beams of various energies, yielding comparable target dose coverage as suggested by the largely overlapping DVHs in Fig 1. These observations agreed with the reports that satisfactory deep-seated target coverage can be achieved by using lower photon energies if more fields were used [5]. Dramatically differed in beam characteristics, these settings did not work well for un-flattened beams of either 6F or 10F. The insufficient dose coverage induced unacceptable hot spot after renormalization (severely worsened CI for PTV_boost), suggesting that new optimization objectives for target dose should be configured before the RapidPlan model can be possibly used to optimize the modulation of un-flattened beams.

Although tremendous inter-patient varieties were observed for all OARs and beam energies in Fig 2, a majority of individual OAR curves and all the mean curves were overwhelmingly above zero, suggesting inferior OAR sparing using 6X and 8X than 10X. Excessive exposure was dominantly distributed in low dose regions (<20 Gy). The amplitudes of 8X curves were consistently lower than those of 6X, as echoed by the significantly higher dose to most OARs using lower beam energies in Table 2 (except for femoral heads, probably due to limited sample size), suggesting lower OAR exposures are associated with higher beam energies, at least for pelvic planning using a RapidPlan model configured with historical plans that were optimized using 10X photons. Individual lines of 8X showed more negative values and larger fluctuations than those of 6X, suggesting other factors started to play relatively more important roles in determining the OAR dose, when the energy difference reduces. These differences might be jointly contributed by multiple resources, such as beam energy (λ_f) in the modeling of ged_v, inherent photon behaviors, patient and beam geometries, etc., which can be hardly differentiated from each other. Due to relatively low values, the disparities of high dose volumes in Table 2 did not vary too much.

It should be noted that the skin and NTID are not typical OARs for rectal planning, hence were not configured in the RapidPlan model. They were analyzed in this work as indicators of superficial dose and normal tissue sparing in accordance with previous studies on beam energies[4,10]. Classical radiotherapy principle recommended higher beam energy for deep seated large tumors [1], but lower energy can reduce exit dose [22] and Pirzkall et al reported negligible difference among different energies when more than 9 IMRT fields were used [5]. In the context of knowledge-based planning, our results suggested that higher beam energies were still advantageous in normal tissue sparing for deep seated tumors of large volumes, even if many beam entries were used such as VMAT technique. Without potential bias from manual adjustments, the RapidPlan-generated optimization objectives assessed the beam quality collectively with other influential parameters such as patient anatomy and beam geometry in Eq (1), hence the dosimetric comparison between various beam energies were more objective.

Conclusion

In conclusion, a RapidPlan model configured with flattened high energy beams does not satisfy target dose coverage using un-flattened photons, and may increase normal tissue exposure if applied to optimize lower energy beams.

Acknowledgments

The authors thank Jianhao Geng, Kaining Yao and Fan Jiang for their assistance.