中國高危乳腺癌患者乳房切除術后

大分割放療的隨機非劣效非盲研究

　　眾所周知，乳腺癌術后放療可以顯著減少復發(fā)率和死亡率。常規(guī)放療將50戈分割為25次，通常需要5周。由于長時間住院或頻繁就診，對患者造成了很大的心理及經(jīng)濟壓力，故迫切需要減少治療次數(shù)、縮短治療時間，以提高生活質(zhì)量、減少治療費用。大分割是單次劑量大于常規(guī)劑量、總劑量和次數(shù)低于常規(guī)分割的放療分割方式。英國大樣本隨機對照研究（START）已經(jīng)證實，對于乳腺癌保乳術后，大分割放療與常規(guī)分割放療相比，有效性和安全性相似。不過，尚無隨機對照研究比較乳腺癌乳房切除術后的大分割放療與常規(guī)分割放療。

　　2019年1月30日，英國《柳葉刀》腫瘤學分冊在線發(fā)表美國霍普金斯大學醫(yī)學院西德尼綜合癌癥中心胡晨、中國醫(yī)學科學院北京協(xié)和醫(yī)學院腫瘤醫(yī)院國家癌癥中心國家腫瘤臨床醫(yī)學研究中心王淑蓮、房輝、宋永文、王維虎、劉躍平、金晶、劉新帆、余子豪、任驊、李寧、唐玉、唐源、李帥、陳波、李曄雄等學者的大樣本隨機對照研究報告，比較了乳房切除術后3周大分割放療與5周常規(guī)分割放療的有效性和安全性。

　　該單中心、隨機對照、非劣效、非盲、3期研究（NCT00793962）于2008年6月12日～2016年6月16日從中國醫(yī)學科學院腫瘤醫(yī)院入組年齡18～75歲乳房切除術后至少4個腋窩淋巴結(jié)陽性或原發(fā)腫瘤最大徑超過5厘米或已經(jīng)侵犯胸壁或皮膚（或術前化療后腋窩淋巴結(jié)病理陽性或臨床III期）單側(cè)乳腺浸潤癌患者820例，根據(jù)計算機生成的中心隨機化時間表按1∶1隨機分組接受胸壁和淋巴結(jié)放療：

• 常規(guī)分割放療組414例：50戈分割為25次共5周

• 大分割放療組406例：43.5戈分割為15次共3周

　　對調(diào)整后的意向治療人群（包括所有符合條件隨機入組患者，不包括不符合條件或隨機分組后退出研究的患者：常規(guī)分割放療組409例、大分割放療組401例）進行主要終點分析和安全性分析。主要終點為5年局部區(qū)域復發(fā)，預設非劣效臨界值為5%（相當于風險比<1.883）。

　　結(jié)果，隨訪時間中位58.5個月（四分位：39.2～81.8），出現(xiàn)局部復發(fā)60例，占7%。

　　大分割放療組與常規(guī)分割放療組相比：

• 局部復發(fā)數(shù)：31例比29例

• 局部復發(fā)率：8.3%比8.1%（90%置信區(qū)間：5.8～10.7、5.4～10.6）

• 絕對差：0.2%（90%置信區(qū)間：-3.0～2.6）

• 風險比：1.10（90%置信區(qū)間：0.72～1.69，非劣效P<0.0001）

• 急性和慢性毒性反應無顯著差異

• 除了三級急性皮膚毒性反應較少（14例比32例，3%比8%，P<0.0001）

　　因此，該研究結(jié)果表明，對于高風險乳腺癌患者，乳房切除術后大分割放療與傳統(tǒng)分割放療相比，有效性和安全性相似，三級急性皮膚毒性反應較少。大分割放療可以提供更方便的治療，并且可以節(jié)省時間，為更多患者提供服務。

　　對此，美國密歇根大學腫瘤放療專家雷斯瑪·賈吉教授發(fā)表同期評論：乳房切除術后——大分割放療的新領域。

相關閱讀

• 乳腺癌保乳術后大分割放療的研究進展

• 大分割與常規(guī)分割全乳放療的三年結(jié)局：非劣效性隨機臨床研究結(jié)果

• 早期乳腺癌保乳術后大分割放療Ⅱ期臨床研究中期安全性有效性分析

• 早期乳腺癌保乳術后大分割放療的研究進展

• 少而精：乳房切除術后低分割短療程大劑量放療安全且有效

• 中國學者發(fā)現(xiàn)早期乳腺癌患者能夠很好耐受瘤床大分割全乳放療同步加量

Lancet Oncol. 2019 Jan 30. [Epub ahead of print]

Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial.

Shu-Lian Wang, Hui Fang, Yong-Wen Song, Wei-Hu Wang, Chen Hu, Yue-Ping Liu, Jing Jin, Xin-Fan Liu, Zi-Hao Yu, Hua Ren, Ning Li, Ning-Ning Lu, Yu Tang, Yuan Tang, Shu-Nan Qi, Guang-Yi Sun, Ran Peng, Shuai Li, Bo Chen, Yong Yang, Ye-Xiong Li.

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

BACKGROUND: To our knowledge, no randomised study has compared postmastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy in patients with breast cancer. This study aimed to determine whether a 3-week schedule of postmastectomy hypofractionated radiotherapy is as efficacious and safe as a 5-week schedule of conventional fractionated radiotherapy.

METHODS: This randomised, non-inferiority, open-label, phase 3 study was done in a single academic hospital in China. Patients aged 18-75 years who had undergone mastectomy and had at least four positive axillary lymph nodes or primary tumour stage T3-4 disease were eligible to participate. Patients were randomly assigned (1:1) according to a computer-generated central randomisation schedule, without stratification, to receive chest wall and nodal irradiation at a dose of 50 Gy in 25 fractions over 5 weeks (conventional fractionated radiotherapy) or 43.5 Gy in 15 fractions over 3 weeks (hypofractionated radiotherapy). The modified intention-to-treat population (including all eligible patients who underwent randomisation but excluding those who were considered ineligible or withdrew consent after randomisation) was used in primary and safety analyses. The primary endpoint was 5-year locoregional recurrence, and a 5% margin was used to establish non-inferiority (equivalent to a hazard ratio <1.883). This trial is registered at ClinicalTrials.gov, number NCT00793962.

FINDINGS: Between June 12, 2008, and June 16, 2016, 820 patients were enrolled and randomly assigned to the conventional fractionated radiotherapy group (n=414) or hypofractionated radiotherapy group (n=406). 409 participants in the conventional fractionated radiotherapy group and 401 participants in the hypofractionated radiotherapy group were included in the modified intention-to-treat analyses. At a median follow-up of 58.5 months (IQR 39.2-81.8), 60 (7%) patients had developed locoregional recurrence (31 patients in the hypofractionated radiotherapy group and 29 in the conventional fractionated radiotherapy group); the 5-year cumulative incidence of locoregional recurrence was 8.3% (90% CI 5.8-10.7) in the hypofractionated radiotherapy group and 8.1% (90% CI 5.4-10.6) in the conventional fractionated radiotherapy group (absolute difference 0.2%, 90% CI -3.0 to 2.6; hazard ratio 1.10, 90% CI 0.72 to 1.69; p<0.0001 for non-inferiority). There were no significant differences between the groups in acute and late toxicities, except that fewer patients in the hypofractionated radiotherapy group had grade 3 acute skin toxicity than in the conventional fractionated radiotherapy group (14 [3%] of 401 patients vs 32 [8%] of 409 patients; p<0.0001).

INTERPRETATION: Postmastectomy hypofractionated radiotherapy was non-inferior to and had similar toxicities to conventional fractionated radiotherapy in patients with high-risk breast cancer. Hypofractionated radiotherapy could provide more convenient treatment and allow providers to treat more patients.

FUNDING: National Key Projects of Research and Development of China; the Chinese Academy of Medical Science Innovation Fund for Medical Sciences; and Beijing Marathon of Hope, Cancer Foundation of China.

DOI: 10.1016/S1470-2045(18)30813-1

Lancet Oncol. 2019 Jan 30. [Epub ahead of print]

Hypofractionated radiotherapy after mastectomy: a new frontier.

Reshma Jagsi.

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.

DOI: 10.1016/S1470-2045(19)30062-2