早期乳腺癌保乳术后大分割放疗Ⅱ期临床研究——中期安全性及有效性分析

A phase Ⅱ study of hypofractionated whole breast irradiation in patients with early stage breast cancer after breast-conserving surgery: safety and efficacy analysis

背景与目的:乳腺癌保乳术后全乳大分割放疗的安全性和有效性在多项随机临床试验中已经得到证实,但全乳大分割瘤床同期加量的放疗模式目前仍不明确。本研究旨在探讨中国人群早期乳腺癌保乳术后大分割放疗同期瘤床加量的安全性及有效性。方法:前瞻性入组保乳术后切缘阴性、病理诊断为浸润性癌、分期pT_(1-2)N_0M_0、术中瘤床钛夹标记的患者接受全乳大分割同期瘤床加量放疗(ClinicalTrail.gov:NCT02617043)。放疗处方剂量为全乳计划靶体积(planned target volume,PTV) 40 Gy/15次/3周,同期瘤床加量至48 Gy/15次/3周。放疗后评估急性不良反应、美容效果以及预后。结果:2015年1月—2016年8月,共计358例患者前瞻性连续性入组本研究。患者中位年龄45岁(25～71岁),71.2%(255例)为绝经前的年轻女性,其中T_1和T_2患者分别为276例(77.1%)和82例(22.9%)。放疗期间及放疗后3个月内,53.6%和8.1%的患者出现Ⅰ～Ⅱ度的放射性皮炎,主要表现为放疗区红斑(38.8%)以及放疗后干性脱皮(41.3%)。13例(3.6%)患者出现湿性脱皮,主要位于乳头、乳晕区,无Ⅲ度以上放射性皮炎。4例Ⅰ度放射性肺炎,1例Ⅲ度放射性肺炎。美容效果自评"极好"和"好"率分别为37.0%和44.8%。中位随访28.3个月(6.0～40.7个月),3例患者出现局部区域复发,4例远处转移(2例合并复发),2年无病生存率(disease-free survival,DFS)为98.6%。结论:对于早期乳腺癌保乳术后患者,全乳大分割同期瘤床加量放疗不良反应轻、耐受性好,具有一定的安全性及有效性,其晚期不良反应以及对疾病局部控制的有效性仍需长期随访来证实。

Background and purpose： The long-term safety and efficacy of hypofractionated whole-breast irradiation （HF- WBI） have been well established in randomized trials, but little is known about the effect of HF-WBI with simultaneous boost of the tumor bed. This study aimed to assess the safety and efficacy of HF-WBI with simultaneous tumor bed boost after breast-conserving surgery in Chinese population. Methods： Patients with pTI.ENoM0 invasive breast cancer, negative margins, clips marked tumor bed after breast-conserving surgery were prospectively and consecutively enrolled in this study. All patients received total dose of 40 Gy/15 Fx/3 weeks for whole breast, combined with simultaneous boost of tumor bed, total dose of 48 Gy/15 Fx/3 weeks. The acute radiotherapy-induced toxicities, cosmetic effect and prognosis were followed up after the treatment. Results： From Jan. 2015 to Aug. 2016, 358 patients were enrolled in the study. The median age was 45 years （range, 25-71 years）, and 71.2% patients were premenopausal young women. A total of 276 （77.1%） patients had T~ tumors, and 82 （22.9%） patients had T2. During the treatment, 53.6% and 8.1% patients had Grade 1 and Grade 2 radiation dermatitis, respectively, mainly manifested as skin erythema （38.8%） or desquamation （41.3%）. Thirteen patients experienced moist desquamation mainly in the nipple and areola area. No grade/〉 3 radiation dermatitis was observed. Four patients had Grade 1 and one patient had Grade 3 radiation pneumonitis. 37.0% and 44.8% patients＇ self-assessed cosmetic effects were ＂Excellent＂ and ＂Good＂, respectively. With a median follow-up time of 28.3 months （range： 6.0-40.7 months）, three patients experienced locoregional recurrence and four patients had distant metastasis （two of them with locoregional recurrence）. The 2-year disease-free survival was 98.6%. Conclusion： Hypofractionated whole-breast irradiation combined with simultaneous boost of the tumor bed has few acute toxic effects and can be well tolerated in patients with early stage breast cancer after breast-conserving surgery. Long-term follow-up is needed to confirm its late toxic effects and efficacy of disease control.