Potential skin morbidity reduction with intensity-modulated proton therapy for breast cancer with nodal involvement

Figures & data

Table 1. Planning Target Volume (PTV) and Organs-At-Risk (OAR) planning optimization objectives.

PTV/OAR	IMXT objectives	SFO-IMPT objectives
PTV	Dmin > 45 Gy	Dmin = 50 Gy (RBE)
	Dmax < 52 Gy	Dmax = 52 Gy (RBE)
	Min DVH 50% = 50 Gy
	Min DVH 95% = 47.5 Gy
	Uniform dose = 50 Gy
Boundary breast-PTV	–	D95% = 46.5 Gy(RBE)^a
		D98% = 45 Gy(RBE)^a
Heart	V25 Gy < 10%	Dmax = 48 Gy(RBE)
		D1% = 40 Gy(RBE)
		D10% = 10 Gy(RBE)
Left lung	V5 Gy < 75%	Dmax = 50 Gy(RBE)
	V20 Gy < 30%	D2% = 45 Gy(RBE)
	V30 Gy < 20%	V20% = 20 Gy(RBE)
Right lung	V5 Gy < 26%	–
	V15 Gy < 5%
Larynx	D2% < 47.5 Gy	Dmax = 12 Gy(RBE)
Esophagus	D2% < 47.5 Gy	Dmax = 40 Gy(RBE)
		D20% = 10 Gy(RBE)
Thyroid	D2% < 47.5 Gy	D1% = 45 Gy(RBE)
	Dmean < 35 Gy	Dmean ≤ 20 Gy(RBE)
Skin3mm	–	D1% = 40 Gy(RBE)^b
		D50% = 35 Gy(RBE)^b
Ring breast	D2% < 47.5 Gy	D1 = 50 Gy(RBE)
		Dose fall-off = 50–0 Gy(RBE), 2 cm
Ring LN	D2% < 47.5 Gy	D1 = 50 Gy(RBE)
		Dose fall-off = 50–0 Gy (RBE), 2 cm

^a Objectives used in IMPT2 plans but not in IMPT1 and IMPT3 plans.

^b Objectives used only in IMPT2 plans but not in IMPT1 plans. In IMPT3 plans D10%, D20%, D30%, …, D90% of the skin-like structure were set to the same dose value as in IMXT plans.

Figure 1. Median cumulative patients dose volume histograms for the PTV (a) and median cumulative patient dose–surface histogram for the skin (b).

Figure 2. Comparison of intensity modulated photon therapy (IMXT) plan (left), intensity modulated proton (IMPT₁) therapy (middle), and IMPT₂ (right) dose distributions in two representative patients.

Table 2. Dose distribution indices for the PTV and pseudo target volumes (Skin3mm and superficial PTV-breast structures).

		Treatment plan
Structure	Dose index	Median (range)
		IMXT	IMPT1	IMPT2	IMPT3
Skin3mm	Dmean (Gy)	32.0 (26.2–33.4)	36.9 (32.5–39.2)	30.0 (26.5–31.2)	31.6 (26.8–32.8)
	V30Gy (%)	65.2 (51.5–69.4)	71.3 (63.3–77.1)	63.9 (52.7–67.8)	65.4 (53.0–68.0)
	V40Gy (%)	39.6 (18.7–46.5)	63.4 (52.7–68.7)	35.3 (22.2–48.6)	40.5 (21.3–47.9)
	V45Gy (%)	21.0 (4.9–28.8)	52.0 (42.5–59.2)	0.1 (0.0–2.8)	21.4 (7.12–28.7)
Boundary breast-PTV	D95% (Gy)	46.0 (44.9–47.6)	50.0 (49.1–50.4)	46.0 (44.9–47.3)	47.9 (47.0–48.8)
	V50Gy (%)	55.5 (37.7–63.1)	95.3 (88.5–98.5)	55.6 (37.2-64.0)	70.0 (51.0–77.5)
PTV	D95% (Gy)	44.5 (43.6–47.1)	49.5 (49.0–50.1)	48.5 (48.1–49.6)	44.5 (48.1–49.6)
	V45Gy (%)	93.7 (91.3–99.0)	99.8 (99.1–100.0)	99.6 (98.9–100.0)	99.6 (98.9–100.0)
	V50Gy (%)	43.8 (36.7–51.1)	90.6 (85.1–95.7)	78.4 (54.2–88.1)	78.4 (54.2–88.1)

Table 3. Dosimetric parameters and comparative analysis for different organs for intensity modulated photon (IMXT) and intensity modulated proton without (IMPT₁) and with skin included in the cost function (IMPT₂).

		Treatment plan
Structure	Dose index	Median (range)			p Value <.05*
		IMXT	IMPT1	IMPT2	Photon vs. Proton	Proton vs Proton
		a	1	2
PTV coverage	HI	0.21 (0.14–0.27)	0.07 (0.05–0.09)	0.11 (0.08–0.16)	a > 1,2	1 < 2
	CI	0.81 (0.76–0.93)	0.99 (0.98–1.00)	0.96 (0.88–0.99)	a < 1,2	1 > 2
Skin	S30 (%)	55.7 (51.0–57.5)	58.0 (48.2–60.8)	52.7 (45.9–55.2)	a > 2	1 > 2
	Dmean (Gy)	12.3 (11.2–13.5)	9.6 (7.4–10.6)	8.0 (6.7-9.2)	a > 1,2	1 > 2
Skin5mm	V40Gy (cc)	136.9 (86.5–172.7)	176.4 (120.2–220.2)	122.5 (80.3–161.5)	a < 1, a > 2	1 > 2
Heart	Dmean (Gy)	9.4 (8.2–14.8)	2.7 (1.6–3.3)	2.4 (1.6–3.0)	a > 1,2	1 > 2
	V30 (%)	5.9 (5.0–6.3)	3.2 (1.4–3.9)	2.5 (1.2–3.2)	a > 1,2	1 > 2
Left ventricle	V5 (%)	57.6 (42.1–90.5)	8.4 (3.5–14.6)	7.1 (2.8–11.5)	a > 1,2	1 > 2
	Dmean (Gy)	10.4 (8.9–14.1)	1.6 (0.7–3.7)	1.3 (0.5–2.6)	a > 1,2	1 > 2
Left lung	Dmean (Gy)	15.4 (14.2–16.4)	7.2 (3.8–10.7)	6.5 (3.4–10.6)	a > 1,2	1 > 2
	V20 (%)	29.4 (25.1–30.9)	15.2 (7.3–23.6)	13.6 (6.6–23.0)	a > 1,2	1 > 2
	V5 (%)	70.4 (62.2–75.9)	26.5 (14.7–39.7)	24.7 (13.8–39.1)	a > 1,2	1 > 2
Thyroid	V30 (%)	51.2 (21.3–71.2)	31.1 (6.6–43.9)	32.7 (6.9–44.6)	a > 1,2	1 < 2
	Dmean (Gy)	31.3 (18.7–37.2)	20.4 (10.2–24.7)	21.4 (9.9–24.6)	a > 1,2	–
Contralateral breast	Dmean (Gy)	3.8 (3.2–4.2)	0.3 (0.1–0.6)	0.2 (0.1–0.5)	a > 1,2	1 > 2

* Friedman test plus post hoc analysis for multiple comparison between plans.

Figure 3. Patients normal tissue complication probability (NTCP), odds ratio (OR), and hazard ratio (HR) values for different organs and endpoints for intensity modulated photon therapy (IMXT) and for intensity modulated proton therapy plans without (IMPT₁) or with skin included in the cost function (IMPT₂).

Table 4. Relative risk (RR) ratios comparison according to normal tissue complication probability analysis for severe acute skin toxicity for intensity modulated proton plan without (IMPT₁) and with skin included in the cost function (IMPT₂).

		Median (range)		p Value < .05*
		RR
		IMPT1	IMPT2
OAR	Clinical endpoint [Reference]	1	2	IMPT1 vs. IMPT2
Skin	Severe acute toxicity [16]	2.72 (0.82–3.82)	0.34 (0.17–0.45)	1 > 2
	Acute moist desquamation [15]	1.37 (1.13–1.67)	0.91 (0.78–0.96)	1 > 2
Left lung	Radiation fibrosis [25]	0.43 (0.38–0.56)	0.42 (0.36–0.54)	1 > 2
Heart	Major coronary event [3]	0.71 (0.59–0.75)	0.70 (0.56–0.73)	1 > 2
Left ventricle	Heart valvular defect [26]	0.91 (0.76–0.99)	0.91 (0.76–0.99)	–
	Major coronary event [4]	0.42 (0.25–0.57)	0.42 (0.24–0.56)	1 > 2
Thyroid	Hypothyroidism [27]	0.77 (0.29–0.92)	0.77 (0.29–0.94)	–

* Wilcoxon test.

Figure 4. Relative risk (RR) ratio comparison for skin morbidity according to different normal tissue complication probability (NTCP) models for intensity modulated proton plans without (IMPT₁) and with skin included in the cost function (IMPT₂).

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