Study on the safety of simultaneous integrated boost and the importance of cardiac substructural dose assessment of hypofractionated radiotherapy after early left breast cancer breast-conserving surgery

doi:10.19401/j.cnki.1007-3639.2022.05.008

Abstract

Abstract:

Background and purpose: Adjuvant radiotherapy for breast cancer after early breast-conserving surgery has been recommended by the guidelines. However, the feasibility of hypofractionated radiotherapy with simultaneous integrated boost is not available. In this randomized controlled study, the cardiac dosimetry parameters and cardiac ultrasound indexes of the two radiotherapy plans were compared to evaluate the safety of hypofractionated radiotherapy with simultaneous integrated boost plan in terms of cardiotoxicity. Methods: A total of 40 patients with breast cancer who received breast-conserving surgery were selected in Zhongshan Hospital, Fudan University from March 2017 to March 2018. They were randomly divided into two groups, including 20 patients reveiving hypofractionated radiotherapy with simultaneous integrated boost plan (whole breast 4 005 cGy/15 Fx, tumor bed 4 500 cGy/15 Fx) and 20 patients reveiving conventional fractionation with simultaneous integrated boost plan (whole breast 5 000 cGy/25 Fx, tumor bed 6 000 cGy/25 Fx). The cardiac dosimetric parameters and cardiac ultrasound indexes of the two groups were compared. The dosimetric parameters included the average doses (D_mean) of the whole heart, left ventricle, right ventricle, right ventricular free wall, ventricular septum and left anterior descending (LAD) coronary artery, and the relative volume fraction of each structure irradiated by 5-35 Gy (V_{5 Gy}-V_{35 Gy}). The follow-up indexes of echocardiography included aortic root diameter, left atrial diameter, left ventricular end diastolic diameter, left ventricular end systolic diameter, ventricular septal thickness, left ventricular posterior wall thickness, pulmonary artery systolic pressure, left ventricular ejection fraction, E peak, A peak, E-peak deceleration time (DT), E, A, E/A and S wave peak. In addition, the cosmetic effect on breast after radiotherapy in the two groups was also evaluated. Results: D_mean of the whole heart in the hypofractionated group and the conventional group were (471.86±170.54) and (733.07±79.11) cGy (P<0.05); V_{20 Gy} of the whole heart was (3.63±1.74) and (8.43±0.74)% (P<0.05), and V30 Gy was (1.55±1.15) and (4.48±1.01)% (P<0.05). D_mean of LAD were (1 250.17±600.33) and (1 847.20±933.23) cGy (P>0.05); D_mean of left ventricle were (908.64±865.60) vs (946.93±116.13) cGy (P>0.05). D_mean of right ventricle were (590.37±197.99) vs (905.73±180.82) cGy (P<0.05); D_mean of right ventricular free wall were (939.40±284.23) vs (1 597.30±446.3) cGy (P<0.05); D_mean of ventricular septum were (1 637.49±248.19) vs (988.60±159.77) cGy (P<0.05). After one year of follow-up, the cardiac ultrasound indexes in the hypofractionated group and the conventional group were in the normal range, and there was no significant difference between the two groups (P>0.05). There was no significant difference in cosmetic effect between the two groups (P>0.05). Conclusion: Compared with the conventional fractionation plan, hypofractionated radiotherapy with simultaneous integrated boost significantly reduced the radiation dose of the whole heart and some cardiac substructures, and there were no abnormal cardiac ultrasound indexes during one-year follow-up. The dose fractionation method in this study is safe and feasible. Limiting the whole heart dose alone can not effectively protect LAD, so it is recommended to outline the cardiac substructure and limit the dose alone to better protect the heart.

Key words: Early breast cancer, Breast-conserving surgery, Hypofractionated radiotherapy, Simultaneous integrated boost, Cardiac injury

CLC Number:

R737.9

ZHANG Qian, FANG Xiaoyan, LIU Juan, LIU Jin, CHENG Leilei, SUN Jing. Study on the safety of simultaneous integrated boost and the importance of cardiac substructural dose assessment of hypofractionated radiotherapy after early left breast cancer breast-conserving surgery[J]. China Oncology, 2022, 32(5): 427-435.

Figures/Tables 4

Tab. 1

Tab. 2

Comparison of normal tissue dose-volume parameters between two groups"

Item	Hypofractionated group	Conventional group	P value
Heart D_mean/cGy	471.86±170.54	733.07±79.11	0.027
Heart D_max/cGy	3 960.16±126.66	5 007.90±246.57	0.000
Heart D_min/cGy	62.32±22.82	96.17±35.51	0.063
Heart V_{5 Gy} /%	27.61±20.64	42.50±8.29	0.256
Heart V_{10 Gy} /%	11.46±8.41	18.72±4.59	0.184
Heart V_{20 Gy} /%	3.63±1.74	8.43±0.74	0.000
Heart V_{25 Gy} /%	2.45±1.44	6.12±0.85	0.002
Heart V_{30 Gy} /%	1.55±1.15	4.48±1.01	0.002
Heart V_{35 Gy} /%	0.70±0.64	3.05±0.98	0.000
Heart V_{50 Gy} /%	0.00±0.00	0.01±0.01	0.423
LAD D_mean /cGy	1 250.17±600.33	1 847.20±933.23	0.195
LAD V_{5 Gy} /%	67.70±24.38	89.52±9.00	0.163
LAD V_{10 Gy} /%	42.24±28.35	74.32±2.36	0.082
Left ventricle D_max/cGy	3 964.88±303.46	4 875.67±174.51	0.000
Left ventricle D_min /cGy	89.11±22.75	151.27±40.85	0.004
Left ventricle D_mean /cGy	908.64±865.60	946.93±116.13	0.942
Left ventricle V_{5 Gy} /%	47.19±22.09	54.73±6.44	0.58
Left ventricle V_{10 Gy} /%	23.59±21.99	29.12±9.07	0.685
Left ventricle V_{30 Gy} /%	9.63±3.75	6.31±2.89	0.818
Right ventricle D_max /cGy	3 730.65±381.30	4 638.93±107.23	0.002
Right ventricle D_min /cGy	142.23±71.05	154.37±19.47	0.780
Right ventricle D_mean /cGy	590.37±197.99	905.73±180.82	0.029
Right ventricle V_{5 Gy} /%	39.68±26.10	55.26±14.81	0.350
Right ventricle V_{10 Gy} /%	12.92±8.52	24.57±9.55	0.062
Right ventricle V_{30 Gy} /%	1.44±0.86	6.17±1.98	0.002
Right ventricular free wall D_max /cGy	3 854.95±197.13	4 640.00±109.46	0.000
Right ventricular free wall D_min /cGy	196.37±99.91	214.70±74.34	0.775
Right ventricular free wall D_mean /cGy	939.40±284.23	1 597.30±446.31	0.008
Right ventricular free wall V_{5 Gy} /%	58.05±23.43	82.22±16.03	0.123
Right ventricular free wall V_{10 Gy} /%	28.68±13.55	46.48±14.26	0.069
Right ventricular free wall V_{30 Gy} /%	5.60±3.29	21.60±8.89	0.002
Ventricular septum D_max /cGy	3 357.73±674.33	4 545.83±123.14	0.012
Ventricular septum D_min /cGy	158.70±103.14	156.17±25.98	0.968
Ventricular septum D_mean /cGy	637.49±248.19	988.60±159.77	0.041
Ventricular septum V_{5 Gy}/%	41.64±27.56	52.79±9.09	0.514
Ventricular septum V_{10 Gy}/%	17.06±13.97	32.48±11.55	0.107
Ventricular septum V_{30 Gy}/%	1.57±0.25	6.50±1.67	0.004
Ipsilateral lung D_max /cGy	4 211.42±174.87	5 347.97±578.57	0.073
Ipsilateral lung D_min /cGy	29.35±10.41	42.77±7.25	0.061
Ipsilateral lung D_mean /cGy	656.23±148.58	1 039.27±199.52	0.003
Ipsilateral lung V_{20 Gy}/%	10.65±3.53	17.39±3.90	0.014
Contralateral breast D_mean /cGy	168.52±78.54	292.27±95.21	0.038

Tab. 2

Tab. 3

Comparison of cardiac ultrasound indexes between the two groups"

Item	Hypofractionated group	Conventional group	P value
Aortic root diameter (before radiotherapy) D/mm	29.60±1.26	31.33±0.57	0.056
Aortic root diameter (after radiotherapy) D/mm	28.60±1.17	28.33±1.53	0.751
Aortic root diameter (1 year after radiotherapy) D/mm	29.70±1.41	30.33±2.31	0.564
Left atrial diameter (before radiotherapy) D/mm	33.60±4.09	32.00±2.00	0.535
Left atrial diameter (after radiotherapy) D/mm	34.50±3.92	33.00±1.00	0.537
Left atrial diameter (1 year after radiotherapy) D/mm	32.70±4.29	32.33±1.53	0.890
Left ventricular end diastolic diameter (before radiotherapy) D/mm	44.80±3.74	44.33±1.15	0.839
Left ventricular end diastolic diameter (after radiotherapy) D/mm	44.90±2.42	44.67±1.53	0.880
Left ventricular end diastolic diameter (1 year after radiotherapy) D/mm	42.80±2.15	44.67±0.58	0.176
Left ventricular end systolic diameter (before radiotherapy) D/mm	28.30±3.65	27.33±0.58	0.440
Left ventricular end systolic diameter (after radiotherapy) D/mm	28.10±2.02	27.67±1.53	0.741
Left ventricular end systolic diameter (1 year after radiotherapy) D/mm	27.10±2.18	29.33±2.31	0.152
Ventricular septal thickness (before radiotherapy) D/mm	9.00±1.41	8.33±0.58	0.453
Ventricular septal thickness (after radiotherapy) D/mm	8.40±1.26	9.00±1.00	0.471
Ventricular septal thickness (1 year after radiotherapy) D/mm	9.40±0.84	9.33±1.15	0.913
Left ventricular posterior wall thickness (before radiotherapy) D/mm	8.50±1.27	8.00±1.00	0.548
Left ventricular posterior wall thickness (after radiotherapy) D/mm	8.20±0.92	8.33±1.52	0.851
Left ventricular posterior wall thickness (1 year after radiotherapy) D/mm	9.00±0.82	8.67±1.53	0.617
Pulmonary artery systolic pressure (before radiotherapy)/mmHg	29.50±4.25	24.00±4.58	0.079
Pulmonary artery systolic pressure (after radiotherapy)/mmHg	27.90±5.36	27.33±3.21	0.868
Pulmonary artery systolic pressure (1 year after radiotherapy)/mmHg	27.10±3.54	35.00±12.28	0.381
Left ventricular ejection fraction (before radiotherapy)/%	65.30±5.96	68.33±1.53	0.414
Left ventricular ejection fraction (after radiotherapy)/%	67.20±3.22	68.33±4.16	0.624
Left ventricular ejection fraction (1 year after radiotherapy)/%	66.20±4.96	63.33±6.43	0.425
E peak (before radiotherapy)	70.06±11.81	71.27±10.58	0.877
E peak (after radiotherapy)	56.55±6.67	69.07±7.10	0.451
E peak (1 year after radiotherapy)	72.06±7.22	70.00±3.61	0.845
A peak (before radiotherapy)	69.60±18.46	61.70±20.36	0.537
A peak (after radiotherapy)	48.15±17.07	63.17±15.33	0.387
A peak (1 year after radiotherapy)	66.69±15.51	60.00±19.05	0.544
DT (before radiotherapy) t/ms	164.30±19.95	136.67±21.50	0.062
DT (after radiotherapy) t/ms	139.6±57.95	172.33±57.27	0.408
DT (1 year after radiotherapy) t/ms	157.00±37.28	149.00±26.51	0.739
E (before radiotherapy)	12.17±3.12	7.77±1.24	0.051
E (after radiotherapy)	10.25±4.87	8.2±1.04	0.496
E (1 year after radiotherapy)	10.90±3.41	9.97±3.07	0.681
A (before radiotherapy)	10.89±2.44	9.43±0.25	0.338
A (after radiotherapy)	8.47±3.45	9.50±0.35	0.626
A (1 year after radiotherapy)	9.88±2.82	8.83±1.42	0.557
S wave peak (before radiotherapy) / (cm · s^-1)	11.15±2.81	11.73±1.88	0.746
S wave peak (after radiotherapy) / (cm · s^-1)	8.22±3.28	11.10±0.85	0.172
S wave peak (1 year after radiotherapy) / (cm · s^-1)	10.05±1.99	9.57±0.84	0.696

Tab. 3

Tab. 4

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Item	Hypofractionated group	Conventional group	P value
Age/year			0.33
<60	19	20
≥60	1	0
Hypertension			0.33
Yes	1	0
No	19	20
Dyslipidemia			0.33
Yes	1	0
No	19	20
Diabetes			0.33
Yes	1	0
No	19	20
Pathological stage			0.757
Ⅰ	9	8
Ⅱ	11	12
Grade			0.48
1-2	17	18
3	3	2
Vascular tumor thrombus			0.33
Yes	0	1
No	20	19
Chemotherapy			0.55
Anthracycline drugs	4	2
Taxus drugs	4	6
Anthracycline + Taxus drugs	7	8
No	5	4
Targeted therapy			0.16
Trastuzumab	2	0
No	0	0

Item	Before radiotherapy	After radiotherapy	1 year after radiotherapy	P value
Item	Before radiotherapy	After radiotherapy	1 year after radiotherapy	Before radiotherapy vs after radiotherapy	Before radiotherapy vs 1 year after radiotherapy	After radiotherapy vs 1 year after radiotherapy
Aortic root diameter D/mm	29.50±3.34	29.50±2.97	29.65±2.17	0.992	0.902	0.881
Left atrial diameter D/mm	33.23±3.70	33.56±3.48	32.62±3.78	0.435	0.294	0.065
Left ventricular end diastolic diameter D/mm	44.69±3.28	44.85±2.19	43.23±2.05	0.824	0.123	0.185
Left ventricular end systolic diameter D/mm	28.08±3.20	28.00±1.87	27.62±2.33	0.92	0.654	0.641
Ventricular septal thickness D/mm	8.85±1.28	8.53±1.20	9.38±0.87	0.367	0.017	0.009
Left ventricular posterior wall thickness D/mm	8.38±1.19	8.23±1.01	8.92±0.95	0.549	0.11	0.022
Pulmonary artery systolic pressure/mmHg	28.23±4.78	27.77±4.83	28.92±6.82	0.82	0.753	0.636
Left ventricular ejection fraction/%	65.83±5.37	66.06±3.31	64.50±5.19	0.506	0.537	0.514
E peak	70.34±11.12	59.44±23.93	71.58±15.01	0.228	0.796	0.201
A peak	67.78±18.35	51.62±25.14	65.15±15.80	0.094	0.636	0.137
DT t/ms	157.92±22.86	147.15±57.20	155.15±34.23	0.519	0.808	0.602
E	11.15±3.36	9.77±4.33	10.68±3.24	0.141	0.627	0.45
A	10.55±2.20	8.71±3.02	9.63±2.55	0.159	0.311	0.515
E/A	1.10±0.33	1.22±0.39	1.16±0.37	0.193	0.501	0.478
S wave peak/(cm · s^-1)	11.28±2.57	8.88±3.13	9.94±1.77	0.058	0.187	0.344