Variation in relative biological effectiveness for cognitive structures in proton therapy of pediatric brain tumors

Figures & data

Table 1. Median RBE_d (range) across all BSCs for sorted model categories.

Category	Models	Median RBEd (range)
Type of model
Phenomenological	CAR, CHE, CHD, JON, MAI, MCN, PLR, TIL, WED, WIL, RORW/RORUW	1.21 (0.78–2.24)
Plan-based	FRE, UNK	1.09 (1.02–1.52)
Tissue dependency
Non-tissue dependent	CHE, WIL, UNK	1.21 (1.04–2.24)
Tissue dependent	CAR, CHD, FRE, JON, MAI, MCN, PLR, TIL, WED, RORW/RORUW	1.18 (0.78–1.93)
Number of cell lines
Single cell line	CAR, CHE, TIL, WED	1.22 (1.01–2.24)
Multiple cell lines	CHD, JON, MAI, MCN, PLR, RORW/RORUW	1.21 (0.78–1.93)

The second column shows which models are included in each category.

Figure 1. The calculated RBE_d of the analyzed BSCs across all models for the representative patient. The horizontal solid line shows RBE of 1.1. Open and closed symbols indicate (α/β)_x of 2 and 3 Gy, respectively, with exception of CHD, CHE, and WIL. Ent. Cor.: entorhinal cortex; L: left; R: right; LFWM: left frontal white matter; Hippo: hippocampus; SVZ: subventricular zone.

Table 2 . Overview of data point values in experimental databases used to fit the variable RBE models (phenomenological) along with model dependencies.

Models	Abbreviation	Number of data points [>20]	(α/β)x range (Gy) [2–3]	LETd range (keV µm^–^1) [2–20]	Dependencies
Carabe et al. [24]	CAR	44	2.0–2.8	1.0–20.0	LETd, (α/β)x
Chaudhary et al. [15]	CHD	12	1.8–8.7	1.1–25.9	LETd, (α/β)x
Chen and Ahmad [16]	CHE	14	2.2–2.8	7.7–37.8	LETd
Jones [18]	JON	28	0.5–∞	0.5–654 (5.1–33)^a	LETd, αx, βx
Mairani et al. [25]	MAI	25	2.7–69.5	7.7–37.8	LETd, (α/β)x
McNamara et al. [21]	MCN	285	0.1–29.5	0.2–20.0	LETd, (α/β)x
Peeler [26]	PLR	48	2.6–5.1	0.9–19.0	LETd, (α/β)x
Rørvik et al. [17]	RORW/RORUW	85	1.2–18.4	0.4–37.8	d(L), (α/β)x/LETd, (α/β)x
Tilly et al. [19]	TIL	7	2.7–2.8	7.7–20.0	LETd, (α/β)x
Wedenberg et al. [20]	WED	19	2.7–69.5	7.7–30.0	LETd, (α/β)x
Wilkens and Oelfke [23]	WIL	19	2.1–3.7	2.3–30	LETd

Required range defined by the selection criteria is given in square brackets. Table values in bold are within the required range.

^a Protons only.

Figure 2. Minimum and maximum RBE_d values for all models (filled green) and the selected set of models (filled yellow) calculated for the patient with target volume closest to the median value. Both input parameters of (α/β)_x were applied to the tissue-dependent models. The beige bars show the physical mean dose of each structure. Black dashed line show RBE 1.1, and the two other dashed lines show median values across all structures for all models (green) and the selected set (yellow). Ent. Cor.: entorhinal cortex; L: left; R: right; LFWM: left frontal white matter; Hippo: hippocampus; SVZ: subventricular zone.

Figure 3. RBE_d values of the studied BSCs, arranged in ascending order by the median physical mean dose (beige bars in background) across all patients and both input parameters of (α/β)_x. The horizontal dashed lines represent the median, quartiles, and range of the variable RBE models across all BSCs. Ent. Cor.: entorhinal cortex; L: left; R: right; LFWM: left frontal white matter; Hippo: hippocampus; SVZ: subventricular zone.

Figure 4. RBE_d values for the selected set of models across all patients and (α/β)_x of 2 and 3 Gy, in the supratentorial substructures (upper), temporal lobe substructures (middle), and ventricular substructures (lower). Corp.: corpus callosum; Ent. Cor.: entorhinal cortex; Front: frontal; L: left; R: right; Par: parietal; Temp: temporal; SVZ: subventricular zone.

Carabe A, Moteabbed M, Depauw N, et al. Range uncertainty in proton therapy due to variable biological effectiveness. Phys Med Biol. 2012;57(5):1159–1172.

 PubMed Web of Science ®Google Scholar

Chaudhary P, Marshall TI, Perozziello FM, et al. Relative biological effectiveness variation along monoenergetic and modulated Bragg Peaks of a 62-MeV therapeutic proton beam: a preclinical assessment. Int J Radiat Oncol Biol Phys. 2014;90(1):27–35.

 PubMed Web of Science ®Google Scholar

Chen Y, Ahmad S. Empirical model estimation of relative biological effectiveness for proton beam therapy. Radiat Prot Dosimetry. 2012;149(2):116–123.

 PubMed Web of Science ®Google Scholar

Jones B. Towards achieving the full clinical potential of proton therapy by inclusion of LET and RBE models. Cancers (Basel). 2015;7(1):460–480.

 PubMed Web of Science ®Google Scholar

Mairani A, Dokic I, Magro G, et al. A phenomenological relative biological effectiveness approach for proton therapy based on an improved description of the mixed radiation field. Phys Med Biol. 2017;62(4):1378–1395.

 PubMed Web of Science ®Google Scholar

McNamara AL, Schuemann J, Paganetti H. A phenomenological relative biological effectiveness (RBE) model for proton therapy based on all published in vitro cell survival data. Phys Med Biol. 2015;60(21):8399–8416.

 PubMed Web of Science ®Google Scholar

Peeler CR. Assessing the potential clinical impact of variable biological effectiveness in proton radiotherapy [PhD thesis]. USA: University of Texas; 2016.

 Google Scholar

Rørvik E, Thörnqvist S, Stokkevåg CH, et al. A phenomenological biological dose model for proton therapy based on linear energy transfer spectra. Med Phys. 2017;44(6):2586–2594.

 PubMed Web of Science ®Google Scholar

Tilly N, Johansson J, Isacsson U, et al. The influence of RBE variations in a clinical proton treatment plan for a hypopharynx cancer. Phys Med Biol. 2005;50(12):2765–2777.

 PubMed Web of Science ®Google Scholar

Wedenberg M, Lind BK, Hårdemark B. A model for the relative biological effectiveness of protons: the tissue specific parameter alpha/beta of photons is a predictor for the sensitivity to LET changes. Acta Oncol. 2013;52(3):580–588.

 PubMed Web of Science ®Google Scholar

Wilkens JJ, Oelfke U. A phenomenological model for the relative biological effectiveness in therapeutic proton beams. Phys Med Biol. 2004;49(13):2811–2825.

 PubMed Web of Science ®Google Scholar