Hybrid planning techniques for early-stage left-sided breast cancer: dose distribution analysis and estimation of projected secondary cancer-relative risk

Figures & data

Table 1. Planning objectives for h-IMRT and h-ARC optimization.

Optimization priority	Structure	Planning goal
Highest priority	PTV	D95% ≥40.375Gy (95% of prescribed dose)
Second priority	Heart	V5Gy <30%
		V10Gy <10%
		Dmax <30Gy
		Dmean <4Gy
	LAD	Dmax <15Gy
		Dmean <8Gy
Lesser priority	Left lung	V5Gy <35%
		V10Gy <20%
		V20Gy <10%
		Dmean <10Gy
	Right lung	V10Gy <2%
		Dmean <2Gy
	Right breast	V5Gy <10%
		V10Gy <2%
		Dmean <3Gy

D_max: maximum dose; D_mean: mean dose; DX%: dose (Gy) received by X% of an organ; VXGy: volume (%) receiving dose of XGy.

Table 2. Dosimetric parameters comparison between 3D-CRT and hybrid (h-IMRT, h-ARC) techniques.

			PLAN			p Value
Parameter			3D-CRT	h-IMRT	h-ARC	3D-CRT versus h-IMRT	3D-CRT versus h-ARC	h-IMRT versus h-ARC
PTV
	Dmin	[Gy]	36.34±1.27	37.14±0.76	37.13±1.01	0.001	0.001	0.943
	Dmax	[Gy]	46.13±0.23	44.84±0.67	44.72±0.71	<0.001	<0.001	1.000
	D2%	[Gy]	45.17±0.33	43.76±0.20	43.78±0.46	<0.001	<0.001	1.000
	V95%	[%]	95.85±1.45	98.81±0.60	98.34±0.67	<0.001	<0.001	0.213
	D98%	[Gy]	39.97±0.28	40.77±0.29	40.57±0.44	<0.001	<0.001	0.082
CTV
	Dmin	[Gy]	36.34±1.23	37.47±0.77	37.60±0.96	<0.001	<0.001	0.549
	Dmax	[Gy]	46.11±0.23	44.77±0.66	44.63±0.77	<0.001	<0.001	1.000
	D2%	[Gy]	45.10±0.35	43.80±0.25	43.81±0.47	<0.001	<0.001	1.000
	V95%	[%]	97.25±1.22	99.16±0.46	99.19±0.47	<0.001	<0.001	1.000
	D98%	[Gy]	40.25±0.20	41.05±0.28	40.98±0.42	<0.001	<0.001	0.363
Heart
	Dmean	[Gy]	2.03±0.78	1.90±0.89	1.99±0.64	1.000	1.000	1.000
	Dmax	[Gy]	36.50±11.10	31.49±9.75	31.37±9.89	0.039	0.014	1.000
	D2%	[Gy]	8.15±6.90	7.20±4.35	6.65±3.78	1.000	1.000	1.000
	V5Gy	[%]	4.70±4.72	4.27±5.47	3.65±3.22	1.000	1.000	1.000
	V10Gy	[%]	1.37±2.40	1.25±1.45	1.24±1.46	1.000	1.000	1.000
	V20Gy	[%]	0.30±0.91	0.29±0.53	0.26±0.45	1.000	1.000	1.000
	V30Gy	[%]	0.06±0.37	0.01±0.17	0.00±0.12	0.976	0.697	1.000
LAD
	Dmean	[Gy]	7.81±5.70	7.37±4.84	6.99±4.09	1.000	1.000	1.000
	Dmax	[Gy]	32.08±13.04	27.69±11.57	27.37±11.16	0.235	0.070	1.000
	D10%	[Gy]	15.65±14.45	14.80±12.35	14.10±11.10	1.000	0.891	1.000
Left lung
	Dmean	[Gy]	7.98±1.87	7.36±1.88	8.37±1.67	0.128	0.330	0.013
	Dmax	[Gy]	42.51±0.79	41.84±1.11	41.09±0.83	0.001	<0.001	<0.001
	D2%	[Gy]	39.60±1.15	37.87±1.72	38.39±1.26	<0.001	0.001	0.096
	V5Gy	[%]	29.89±6.01	30.65±7.80	37.86±6.34	0.616	<0.001	<0.001
	V10Gy	[%]	20.50±5.76	19.51±5.79	21.49±5.31	0.437	0.429	0.118
	V20Gy	[%]	15.32±4.89	14.12±4.57	14.63±4.55	0.255	0.509	0.631
	V30Gy	[%]	12.34±4.21	10.05±3.90	10.96±3.91	0.012	0.127	0.312
	V40Gy	[%]	0.95±1.56	0.15±0.50	0.16±0.29	0.001	<0.001	1.000
Right Lung
	Dmean	[Gy]	0.30±0.10	0.28±0.15	0.82±0.17	1.000	<0.001	<0.001
	Dmax	[Gy]	3.75±2.46	3.61±1.87	5.00±1.63	1.000	0.023	0.130
	D2%	[Gy]	1.25±0.35	1.20±0.53	2.50±0.53	1.000	<0.001	<0.001
	V5Gy	[%]	0.00±0.06	0.00±0.00	0.00±0.11	1.000	0.702	0.148
	V10Gy	[%]	0.00±0.00	0.00±0.00	0.00±0.00	1.000	1.000	1.000
Right breast
	Dmean	[Gy]	0.57±0.23	0.60±0.31	1.12±0.28	1.000	<0.001	<0.001
	Dmax	[Gy]	7.62±9.43	8.24±11.19	5.28±10.30	1.000	1.000	1.000
	D2%	[Gy]	2.55±1.55	2.35±1.03	3.00±0.88	1.000	0.385	0.116
	V5Gy	[%]	0.07±0.91	0.05±0.62	0.00±0.63	1.000	1.000	1.000
MU			347.50±42.72	800.00±378.64	348.75±26.70	<0.001	0.977	<0.001
CI			1.43±0.71	1.27±0.09	1.18±0.09	<0.001	<0.001	0.001
HI			0.12±0.06	0.07±0.01	0.08±0.02	<0.001	<0.001	0.436

D_min: minimum dose; D_max: maximum dose; D_mean: mean dose; DX%: dose (Gy) received by X% of an organ; VXGy: volume (%) receiving dose of XGy; 3D-CRT: three-dimensional conformal radiotherapy plans; h-IMRT: hybrid intensity-modulated radiotherapy plans; h-ARC: hybrid Volumetric-Modulated Arc Therapy plans. For differences statistically significant (p < 0.05), p-values are presented in red color.

Figure 1. The average cumulative dose-volume histograms. Comparison of PTV (a), heart and LAD (b), contralateral breast (c), and ipsilateral and contralateral lungs (d) between 3D-CRT, h-ARC and h-IMRT plans.

Figure 2. Comparison of isodose distributions between three-dimensional conformal radiotherapy (3D-CRT), hybrid intensity-modulated radiotherapy (h-IMRT) and hybrid volumetric-modulated arc therapy (h-ARC). The color-wash thresholds are: 3, 5, and 40.375 Gy, which is 95% of the prescribed dose.

Table 3. Comparison of OED for left lung, right lung and right breast.

		Plan			p Value
Organ	Model	3D-CRT	h-IMRT	h-ARC	3D-CRT versus h-IMRT	3D-CRT versus h-ARC	h-IMRT versus h-ARC
Left lung	OEDlin-exp	3.61±0.52	3.68±0.67	4.33±0.54	0.618	<0.001	<0.001
	OEDplateau	3.66±0.56	3.66±0.68	4.30±0.56	0.997	<0.001	<0.001
	OEDmech	3.60±0.55	3.58±0.67	4.18±0.55	0.882	<0.001	<0.001
Right lung	OEDlin-exp	0.32±0.09	0.29±0.14	0.79±0.16	0.235	<0.001	<0.001
	OEDplateau	0.31±0.09	0.29±0.14	0.78±0.16	0.231	<0.001	<0.001
	OEDmech	0.31±0.09	0.29±0.14	0.82±0.23	0.226	<0.001	<0.001
Right breast	OEDlin-exp	0.53±0.21	0.65±0.33	1.07±0.31	0.874	<0.001	<0.001
	OEDplateau	0.52±0.20	0.63±0.32	1.04±0.29	0.837	<0.001	<0.001
	OEDmech	0.53±0.20	0.65±0.33	1.06±0.31	0.867	<0.001	<0.001

OED: organ equivalent dose; 3D-CRT: three-dimensional conformal radiotherapy plans; h-IMRT: hybrid intensity-modulated radiotherapy plans; h-ARC: hybrid volumetric-modulated arc therapy plans. For differences statistically significant (p < 0.05), p-values are presented in red color.

Figure 3. Relative risks ratios of secondary cancer based on the full mechanistic dose-response model for left lung, right lung and right breast, for each patient.

Table 4. Relative risk ratios for secondary carcinomas (left lung, right lung, right breast) assessed using the Schneider’s models.

	Left lung	Right lung	Right breast
h-IMRT/3D-CRT relative risk ratio
Linear-exponential	1.02±0.10	0.95±0.51	0.98±0.43
Plateau	1.00±0.10	0.95±0.51	0.98±0.44
Full Mechanistic	0.99±0.09	0.95±0.50	0.98±0.43
h-ARC/3D-CRT relative risk ratio
Linear-exponential	1.20±0.09	2.47±0.58	1.77±0.44
Plateau	1.18±0.09	2.46±0.58	1.77±0.43
Full Mechanistic	1.17±0.09	2.44±0.57	1.77±0.44

3D-CRT: three-dimensional conformal radiotherapy; h-IMRT: hybrid intensity-modulated radiotherapy; h-ARC: hybrid volumetric-modulated arc therapy.