Radiotherapy Unit 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Medical Physics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Clin Breast Cancer. 2018 Jun;18(3):e363-e371. doi: 10.1016/j.clbc.2017.08.011. Epub 2017 Aug 24.
The purpose of this study was to examine the impact of trastuzumab on acute skin and cardiac toxicity in patients with breast cancer treated with chemotherapy with or without trastuzumab and adjuvant whole breast hypofractionated radiotherapy (hypo-RT).
The study was conducted on 727 patients treated from April 2009 to October 2016. Patients received 42.4 Gy in 16 daily fractions (2.65 Gy per fraction). A boost was only administered in cases with grade (G) 3 primary tumor and close or positive margins. Acute and late toxicity was assessed prospectively during and after hypo-RT, based on the Radiation Therapy Oncology Group scale. Multivariable logistic regression models were used to examine the onset of acute skin toxicity (≥ G2) in the whole study population, and the impact of trastuzumab on the onset of acute skin (≥ G2) or cardiac toxicity in the subgroup of 176 patients given chemotherapy.
A total of 176 patients received chemotherapy with anthracycline and taxane, and 51 (29%) of them were also treated with trastuzumab. Acute G1, G2, and G3 skin toxicity occurred, respectively, in 56.8%, 27.3%, and 1.1% of the patients given chemotherapy alone, and in 64.7%, 19.6%, and 0% of those given trastuzumab as well. Among the patients given chemotherapy, left ventricular ejection fraction (LVEF) toxicity developed with a severity of G1 (LVEF < 60%-50%) in 12 (6.8%) patients, G2 (LVEF < 50%-40%) in 2 (1.1%) patients, and G3 (LVEF < 40%) in 1 (0.6%) patient. Among the patients also given trastuzumab, 7 (13.7%) patients had G1 LVEF toxicity, and 1 (2%) patient had G2 LVEF toxicity. We found that patients given trastuzumab were at higher risk of cardiac toxicity ≥ G1 (odds ratio, 4.3; P = .01), and at lower risk of acute skin toxicity ≥ G2 (odds ratio, 0.4; P = .03) than patients given chemotherapy alone.
This analysis showed that trastuzumab with adjuvant hypo-RT for patients with breast cancer was generally well-tolerated in routine clinical practice. A longer follow-up will be necessary to assess late cardiac toxicity.
本研究旨在探讨曲妥珠单抗对接受化疗联合或不联合曲妥珠单抗及辅助全乳适形放疗(hypo-RT)的乳腺癌患者急性皮肤和心脏毒性的影响。
该研究纳入了 2009 年 4 月至 2016 年 10 月期间治疗的 727 例患者。患者接受 42.4Gy 的 16 次分割治疗(每次 2.65Gy)。仅在原发性肿瘤 G3 级和临近或阳性切缘的情况下给予局部加量照射。根据放射治疗肿瘤学组(Radiation Therapy Oncology Group)标准,在 hypo-RT 期间和之后前瞻性评估急性和晚期毒性。采用多变量逻辑回归模型,在接受化疗的 176 例患者亚组中,检验全研究人群中急性皮肤毒性(≥ G2 级)的发生,以及曲妥珠单抗对急性皮肤(≥ G2 级)或心脏毒性发生的影响。
共 176 例患者接受了蒽环类和紫杉类化疗,其中 51 例(29%)还接受了曲妥珠单抗治疗。单纯化疗组患者分别出现急性 G1、G2 和 G3 级皮肤毒性的比例为 56.8%、27.3%和 1.1%,而接受曲妥珠单抗治疗的患者则分别为 64.7%、19.6%和 0%。在接受化疗的患者中,左心室射血分数(LVEF)毒性的严重程度为 G1(LVEF < 60%-50%)的患者有 12 例(6.8%),G2(LVEF < 50%-40%)的患者有 2 例(1.1%),G3(LVEF < 40%)的患者有 1 例(0.6%)。在接受曲妥珠单抗治疗的患者中,有 7 例(13.7%)患者出现 G1 级 LVEF 毒性,1 例(2%)患者出现 G2 级 LVEF 毒性。我们发现,与单纯化疗相比,接受曲妥珠单抗治疗的患者心脏毒性≥ G1 的风险更高(比值比,4.3;P =.01),而急性皮肤毒性≥ G2 的风险更低(比值比,0.4;P =.03)。
本分析显示,曲妥珠单抗联合辅助 hypo-RT 治疗乳腺癌患者在常规临床实践中通常具有良好的耐受性。需要更长的随访时间来评估晚期心脏毒性。