早期乳腺癌保留乳房手术后全乳腺大分割放射治疗与常规分割放射治疗的随机对照研究

doi:10.3877/cma.j.issn.1674-0807.2015.03.002

目的

比较早期乳腺癌患者保留乳房(简称保乳)手术后行全乳大分割并瘤床同步加量24 d 短疗程放射治疗(简称放疗)与44 d 常规分割方案的近期疗效、不良反应和美容效果。

方法

选择2011 年1 月至2011 年12 月天津医科大学肿瘤医院收治的保乳术后病理分期为pT₁_～2N₀_～1M₀ 的早期乳腺癌患者共80 例,应用随机数字表法将患者分为短疗程放疗组(40 例)和常规放疗组(40 例)。短疗程放疗组(简称短程组)患者行全乳两野切线放射治疗,单次剂量为2.4 Gy,共18 次,总剂量为43.2 Gy,同步行瘤床电子线推量照射,单次剂量为0.4 Gy,共18 次,瘤床总剂量为50.4 Gy,总疗程24 d;常规放疗组(简称常规组)患者行全乳两野切线放射治疗,单次剂量为1.8 Gy,共25 次,总剂量为45.0 Gy,后续行瘤床电子线推量照射,单次剂量为2.0 Gy,共7 次,瘤床总剂量为59.0 Gy,总疗程44 d。采用Kaplan-Meier 法计算患者的局部复发率和生存率,用Log-rank 检验比较两组间的差异,并用χ² 检验比较两组间不良反应及美容效果的差异。

结果

中位随访时间37 个月,随访率为100%。两组患者的3 年生存率均为100%(χ²＜0.001,P=1.000),且均无一例局部复发。短程组与常规组相比,0 ～1 级、2 级急性皮肤不良反应发生率均相似[82.5% (33/40)比77.5%(31/40),χ² =0.313,P=0.576;17.5%(7/40)比22.5%(9/40),χ²=0.313,P=0.576];1 级皮肤及皮下组织晚期不良反应发生率也相似[22.5%(9/40)与20.0%(8/40),χ²=0.075,P=0.785];美容效果优良率也相近[67.5%(27/40)与72.5%(29/40),χ²=0.238,P=0.626]。放疗引起的血液学毒性主要表现为1 ～2 级的中性粒细胞减少和1 级血小板下降,并且短程组与常规组的发生率接近[12.5%(5/40)比10.0%(4/40),χ² =0.125,P=0.724;2.5%(1/40)比5.0%(2/40),P=1.000]。

结论

早期乳腺癌患者保乳术后行全乳大分割并瘤床同步加量放疗可以缩短术后放疗疗程,近期疗效好,且不影响美容效果,也不加重皮肤不良反应,但远期效果还需进行长期随访,进一步研究。

关键词: 乳腺肿瘤, 外科学, 放射疗法, 放射治疗剂量, 治疗结果

Objective

To compare the short-term efficacy, adverse reaction and cosmetic outcome between whole breast irradiation of short-course (24 d) hypofractionated radiotherapy with concomitant tumor bed boost and conventional regimen (44 d) after breast-conserving surgery for early stage breast cancer patients.

Methods

A total of 80 patients with pT_1-2N_0-1M₀ breast cancer treated by breast-conserving surgery in Cancer Institute and Hospital, Tianjin Medical University from January 2011 to December 2011 were divided into short-course radiotherapy group (n=40) and conventional radiotherapy group (n=40) using a random number table method.In short-course radiotherapy group,40 patients received whole breast radiation of 43.2 Gy(2.4 Gy each fraction, 18 fractions) with concomitant tumor bed boost of 7.2 Gy (0.4 Gy each fraction, 18 fractions)(total dose:50.4 Gy, duration: 24 d).In conventional radiotherapy group, 40 patients received whole-breast radiation of 45.0 Gy (1.8 Gy each fraction,25 fractions) followed by tumor bed boost of 14.0 Gy(2.0 Gy each fraction,7 fractions)(total dose:59.0 Gy, duration:44 d).Kaplan-Meier method was used to calculate the local recurrence and overall survival, and the differences between two groups were analyzed by Log-rank test.χ² test was used to compare the differences in adverse reaction and cosmetic outcome between the two groups.

Results

All patients were followed up for median 37 months, and the follow-up rate was 100%.The 3-year overall survival rates in two groups were both 100%(χ² ＜0.001,P=1.000).No patient developed local recurrence.The incidence of grade 0-1 acute adverse reaction of skin was 82.5% (33/40) in shortcourse radiotherapy group and 77.5% (31/40) in conventional radiotherapy group (χ²=0.313,P=0.576),and the incidence of grade 2 adverse reaction was 17.5% (7/40) in short-course radiotherapy group and 22.5%(9/40)in conventional radiotherapy group (χ² =0.313,P=0.576).The adverse reaction of skin and subcutaneous tissue in grade l developed in 22.5% (9/40) of short-course radiotherapy group and 20%(8/40) of conventional radiotherapy group (χ² =0.075,P=0.785).Totally 67.5% (27/40) of patients in short-course radiotherapy group and 72.5% (29/40) of patients in conventional radiotherapy group had good cosmetic outcome (χ²=0.238,P=0.626).The radiotherapy-induced blood toxicity was mainly manifested as grade 1 to 2 neutropenia and grade 1 thrombocytopenia, the former occurred in 12.5% (5/40) of patients in short-course radiotherapy group and 10% (4/40)of conventional radiotherapy group (χ²=0.125,P=0.724),and the latter occurred in 2.5%(1/40) of short-course radiotherapy group and 5% (2/40) of conventional radiotherapy group(P=1.000).

Conclusion

Short-course whole breast hypofractionated radiotherapy with concomitant tumor bed boost can shorten the duration of postoperative radiotherapy, and obtain good short-term effect without affecting cosmetic effect or increasing the skin adverse reactions, however, long-term effects need to be confirmed by long-term follow-up and further study.

Key words: Breast neoplasms, Surgery, Radiotherapy, Radiotherapy dosage, Treatment outcome

表1 短程组与常规组乳腺癌患者的临床资料

组别	例数	平均年龄(岁)	T分期(例)		淋巴结状况(例)		病理类型(例)			ER(例)		PR(例)		HER-2(例)		化疗(例)		内分泌治疗(例)
组别	例数	平均年龄(岁)	T₁期	T₂期	N₀	N₁	浸润性导管癌	导管内癌	黏液癌	阳性	阴性	阳性	阴性	阳性	阴性	有	无	有	无
短程组	40	49.3±10.7	32	8	31	9	35	2	3	11	29	12	28	8	32	13	27	18	22
常规组	40	49.3±11.6	33	7	8	32	38	1	1	10	30	13	27	10	30	14	26	16	24
检验值		t=0.000	χ²=0.080		χ²=0.073		χ²=1.419			χ²=0.063		χ²=0.057		χ²=0.281		χ²=0.055		χ²=0.200
P值		0.992	0.778		0.788		0.237			0.802		0.812		0.598		0.816		0.656

表1 短程组与常规组乳腺癌患者的临床资料

组别	例数	平均年龄(岁)	T分期(例)		淋巴结状况(例)		病理类型(例)			ER(例)		PR(例)		HER-2(例)		化疗(例)		内分泌治疗(例)
组别	例数	平均年龄(岁)	T₁期	T₂期	N₀	N₁	浸润性导管癌	导管内癌	黏液癌	阳性	阴性	阳性	阴性	阳性	阴性	有	无	有	无
短程组	40	49.3±10.7	32	8	31	9	35	2	3	11	29	12	28	8	32	13	27	18	22
常规组	40	49.3±11.6	33	7	8	32	38	1	1	10	30	13	27	10	30	14	26	16	24
检验值		t=0.000	χ²=0.080		χ²=0.073		χ²=1.419			χ²=0.063		χ²=0.057		χ²=0.281		χ²=0.055		χ²=0.200
P值		0.992	0.778		0.788		0.237			0.802		0.812		0.598		0.816		0.656

图1 短程组与常规组乳腺癌患者的生存曲线注:两组间比较,χ² ＜0.001,P=1.000;两组患者3 年生存率均为100%

表2 短程组与常规组乳腺癌患者放射治疗后的不良反应及美容效果

组别	例数	急性皮肤不良反应[例(%)]		1级晚期皮肤及皮下组织不良反应[例(%)]	美容效果优良者[例(%)]	1～2级中性粒细胞减少[例(%)]	1级血小板下降[例(%)]
组别	例数	0～1级	2级	1级晚期皮肤及皮下组织不良反应[例(%)]	美容效果优良者[例(%)]	1～2级中性粒细胞减少[例(%)]	1级血小板下降[例(%)]
短程组	40	33(82.5)	7(17.5)	9(22.5)	27(67.5)	5(12.5)	1(2.5)
常规组	40	31(77.5)	9(22.5)	8(20.0)	29(72.5)	4(10.0)	2(5.0)
χ²值		0.313	0.313	0.075	0.238	0.125
P值		0.576	0.576	0.785	0.626	0.724	1.000^a

表2 短程组与常规组乳腺癌患者放射治疗后的不良反应及美容效果

组别	例数	急性皮肤不良反应[例(%)]		1级晚期皮肤及皮下组织不良反应[例(%)]	美容效果优良者[例(%)]	1～2级中性粒细胞减少[例(%)]	1级血小板下降[例(%)]
组别	例数	0～1级	2级	1级晚期皮肤及皮下组织不良反应[例(%)]	美容效果优良者[例(%)]	1～2级中性粒细胞减少[例(%)]	1级血小板下降[例(%)]
短程组	40	33(82.5)	7(17.5)	9(22.5)	27(67.5)	5(12.5)	1(2.5)
常规组	40	31(77.5)	9(22.5)	8(20.0)	29(72.5)	4(10.0)	2(5.0)
χ²值		0.313	0.313	0.075	0.238	0.125
P值		0.576	0.576	0.785	0.626	0.724	1.000^a

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Comparison between short-course whole breast hypofractionated radiotherapy and conventional fractionated radiotherapy after breast-conserving surgery for early stage breast cancer patients: a randomized controlled study

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Comparison between short-course whole breast hypofractionated radiotherapy and conventional fractionated radiotherapy after breast-conserving surgery for early stage breast cancer patients: a randomized controlled study