Impact of uncertainties in range and RBE on small field proton therapy

Abstract

The objective of this paper is to evaluate the clinical impact of biological uncertainties in small field proton therapy due to the assumption of using a constant relative biological effectiveness (RBE) value of 1.1 (RBE-fixed) compared to a variable RBE (RBE-weighted). In this context the impact of the applied range margin was investigated. Eight patients with arteriovenous malformation (AVM) treated with proton radiosurgery were selected due to the small target volume. Dose distributions were compared for RBE-weighted and RBE-fixed. The impact of RBE was assessed using Monte Carlo (MC) dose calculations for stereotactic doses and doses of 2 Gy(RBE). Four different α/β ratios were investigated. Additionally, dose distributions were recalculated with reduced range margins. Applying variable RBE values for stereotactic doses resulted in an increase in the mean dose of 1.6% for a low α/β of 2 Gy, but a decrease of 2.6% for an α/β of 10 Gy. However, the mean dose increased to 17.1% and 2.1% for doses of 2 Gy(RBE) and α/β of 2 Gy and 10 Gy, respectively. Reducing range margins from 3.5% + 1 mm to 2.5% + 1 mm resulted in negligible difference in the mean RBE within the target, or 0.1% for stereotactic doses and 0.3% for doses of 2 Gy(RBE). Larger differences were seen for a range reduction to 0% + 1 mm, i.e. 1.1% and 3.0% for stereotactic doses and doses of 2 Gy(RBE), respectively. Because potential RBE effects are typically more pronounced in the distal part of a field, a bigger clinical impact of RBE uncertainties in small fields is expected. Our study shows that this could be significant for tissues with low α/β and a small dose per fraction. The uncertainty in RBE due to the uncertainty associated with the α/β ratio seems larger than the impact of the applied range uncertainty margin on RBE.

Impact of range uncertainty on clinical distributions of linear energy transfer and biological effectiveness in proton therapy

“…The nominal arithmetic mean of LET d values in the target volumes of 2.7–2.8 keV/µm, 2.6–2.8 keV/µm, and 2.8–2.9 keV/µm agree with other studies on proton therapy in brain, 7,8,18,29,36 head‐and‐neck, 6,16,29,37 and prostate patients, 7,9,16,37 respectively. The slightly higher average LET d values in prostate cases can be explained by the smaller field sizes of prostate CTVs leading to less contribution from lower LET radiation in the target 38,39 . Within the range scenarios of each patient, lower beam ranges led to slightly but systematically increased LET d in the CTV.…”

“…The slightly higher average LET d values in prostate cases can be explained by the smaller field sizes of prostate CTVs leading to less contribution from lower LET radiation in the target. 38,39 Within the range scenarios of each patient, lower beam ranges led to slightly but systematically increased LET d in the CTV. This effect was largest, though still small, in smaller sized targets, for example, prostate, where a larger part of the target volume is located closer to the steep distal LET d gradients.…”

Proton stopping power prediction based on dual‐energy CT‐generated virtual monoenergetic images

“…found the combined SPR uncertainty from different treatment sites to be 3.0–3.4% 5 . To account for this uncertainty and ensure complete coverage, current clinical practice is to add a relative geometrical margin (3.0–3.5%), an absolute geometrical margin (2–7 mm), or a mix of the two, at both the proximal and distal end of the target volume 6‐8 . The additional dose delivered to healthy tissue due to this margin may reduce or eliminate the advantage of proton therapy over conventional radiotherapy with photons 6,8,9 …”

“…5 To account for this uncertainty and ensure complete coverage, current clinical practice is to add a relative geometrical margin (3.0-3.5%), an absolute geometrical margin (2-7 mm), or a mix of the two, at both the proximal and distal end of the target volume. [6][7][8] The additional dose delivered to healthy tissue due to this margin may reduce or eliminate the advantage of proton therapy over conventional radiotherapy with photons. 6,8,9 Multiple approaches have been proposed to improve SPR prediction by utilizing the extra information acquired with a dual-energy CT (DECT) scanner to extract the relative electron density (RED) and effective atomic number (EAN), or the RED and the mean ionization value (I-value).…”

“…[6][7][8] The additional dose delivered to healthy tissue due to this margin may reduce or eliminate the advantage of proton therapy over conventional radiotherapy with photons. 6,8,9 Multiple approaches have been proposed to improve SPR prediction by utilizing the extra information acquired with a dual-energy CT (DECT) scanner to extract the relative electron density (RED) and effective atomic number (EAN), or the RED and the mean ionization value (I-value). [10][11][12][13][14][15][16][17][18][19][20][21][22][23] Most of the methods use native low and high kilovoltage (kV) images, and have been evaluated on DECT systems where such images are accessible, with reported SPR root mean square errors (RMSE) ranging between 0.5% and 1.5 %.…”