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美国临床肿瘤快讯:乳腺癌放疗研究却得出关于吸烟的重要结果

SIBCS2018-05-15 09:08:28


  放疗对于合适的女性可将乳腺癌死亡绝对风险降低若干百分点,但是几十年后可能导致第二癌症或心脏疾病。


  2017年3月20日,美国临床肿瘤学会官方期刊《临床肿瘤学杂志》在线发表英国牛津大学、美国纽约州由提卡地区癌症中心、匹兹堡大学、密歇根大学、乔治城大学医学中心、隆巴迪综合癌症中心、丹麦哥本哈根大学医院、南丹麦大学医院、瑞典卡罗林斯卡医学院、加拿大森尼布鲁克奥德特癌症中心、朱拉文斯基癌症中心、麦克马斯特大学的早期乳腺癌研究者协作组(EBCTCG)研究报告,根据来自现代心肺放射剂量和既往随机研究的证据,对现代乳腺癌放疗的绝对长期风险进行了估算。


  首先,该研究对2010~2015年发表的乳腺癌方案心肺放疗剂量进行系统文献回顾。随后,根据75项研究随机分配接受乳腺癌放疗或非放疗的4万781例女性个体患者数据,对每Gy发生肺癌和心源性死亡率增量比值比、特定原因死亡率、第二原发癌症发生率比值比进行荟萃分析。由于无法获得吸烟状态,最后将研究中的心或肺每Gy增量比值比和2010~2015年剂量,合并计入目前人群数据中的吸烟者和非吸烟者肺癌和心源性死亡率。


  结果发现,2010~2015年发表的647种方案平均剂量为全肺放疗5.7Gy、全心放疗4.4Gy。放射中位年份为2010(四分位距:2008~2011)。

  • 根据对134例癌症的荟萃分析得出放疗后≥10年发生肺癌风险增加2.1倍(比值比:2.10,95%置信区间:1.48~2.98,P<0.001),表明全肺放疗剂量每Gy使发生肺癌风险增加11%(增量比值比:0.11,95%置信区间:0.05~0.20)。

  • 根据对1253例心源性死亡的荟萃分析,心源性死亡风险增加1.3倍(比值比:1.30,95%置信区间:1.15~1.46,P<0.001),详细分析表明全心放疗剂量每Gy使心源性死亡风险增加4%(增量比值比:0.04,95%置信区间:0.02~0.06)。


  最后,根据目前人群数据中的吸烟者和非吸烟者肺癌和心源性死亡率,对目前现代放疗的绝对风险进行估算:

  • 长期持续吸烟者、不吸烟者肺癌绝对风险分别约为4%、0.3%

  • 吸烟者、不吸烟者心源性死亡绝对风险分别约为1%、0.3%



  因此,对于长期吸烟者,现代放疗的绝对风险可能超过获益,但是对于大多数非吸烟者(和戒烟者),放疗的获益远远超过风险。因此,吸烟可以确定放疗对死亡率的净效应,但是戒烟显著降低放疗风险


  对此,德克萨斯大学MD安德森癌症中心发表同期评论:吸烟对乳腺放疗晚期毒性的影响。


  评论认为,具有讽刺意味的是,虽然该研究可能是最大样本的乳腺癌局部疗法荟萃分析之一,包括了4万871例患者,但是其主要研究结果却强调了需要通过大力促进戒烟,并对乳腺癌患者进行个体化治疗,还需要审慎的放疗方案,并以循证方式小心地将放疗目标体积最小化。通过这些努力,在所有患者中几乎可以完全避免晚期放疗毒性,除了那些继续吸烟的吸烟者。


J Clin Oncol. 2017 Mar 20. [Epub ahead of print]


Estimating the Risks of Breast Cancer Radiotherapy: Evidence From Modern Radiation Doses to the Lungs and Heart and From Previous Randomized Trials.


Carolyn Taylor, Candace Correa, Frances K. Duane, Marianne C. Aznar, Stewart J. Anderson, Jonas Bergh, David Dodwell, Marianne Ewertz, Richard Gray, Reshma Jagsi, Lori Pierce, Kathleen I. Pritchard, Sandra Swain, Zhe Wang, Yaochen Wang, Tim Whelan, Richard Peto, Paul McGale, for the Early Breast Cancer Trialists' Collaborative Group.


University of Oxford, Oxford, United Kingdom; Regional Cancer Center, Utica, NY; Rigshospitalet, Copenhagen; Odense University Hospital, Odense, Denmark; University of Pittsburgh, Pittsburgh, PA; Karolinska Institutet and University Hospital, Stockholm, Sweden; University of Michigan, Ann Arbor MI; Sunnybrook Odette Cancer Centre, Toronto; Juravinski Cancer Centre and McMaster University, Hamilton, Ontario, Canada; Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC.


PURPOSE: Radiotherapy reduces the absolute risk of breast cancer mortality by a few percentage points in suitable women but can cause a second cancer or heart disease decades later. We estimated the absolute long-term risks of modern breast cancer radiotherapy.


METHODS: First, a systematic literature review was performed of lung and heart doses in breast cancer regimens published during 2010 to 2015. Second, individual patient data meta-analyses of 40,781 women randomly assigned to breast cancer radiotherapy versus no radiotherapy in 75 trials yielded rate ratios (RRs) for second primary cancers and cause-specific mortality and excess RRs (ERRs) per Gy for incident lung cancer and cardiac mortality. Smoking status was unavailable. Third, the lung or heart ERRs per Gy in the trials and the 2010 to 2015 doses were combined and applied to current smoker and nonsmoker lung cancer and cardiac mortality rates in population-based data.


RESULTS: Average doses from 647 regimens published during 2010 to 2015 were 5.7 Gy for whole lung and 4.4 Gy for whole heart. The median year of irradiation was 2010 (interquartile range [IQR], 2008 to 2011). Meta-analyses yielded lung cancer incidence ≥ 10 years after radiotherapy RR of 2.10 (95% CI, 1.48 to 2.98; P < .001) on the basis of 134 cancers, indicating 0.11 (95% CI, 0.05 to 0.20) ERR per Gy whole-lung dose. For cardiac mortality, RR was 1.30 (95% CI, 1.15 to 1.46; P < .001) on the basis of 1,253 cardiac deaths. Detailed analyses indicated 0.04 (95% CI, 0.02 to 0.06) ERR per Gy whole-heart dose. Estimated absolute risks from modern radiotherapy were as follows: lung cancer, approximately 4% for long-term continuing smokers and 0.3% for nonsmokers; and cardiac mortality, approximately 1% for smokers and 0.3% for nonsmokers.


CONCLUSION: For long-term smokers, the absolute risks of modern radiotherapy may outweigh the benefits, yet for most nonsmokers (and ex-smokers), the benefits of radiotherapy far outweigh the risks. Hence, smoking can determine the net effect of radiotherapy on mortality, but smoking cessation substantially reduces radiotherapy risk.


DOI: 10.1200/JCO.2016.72.0722




J Clin Oncol. 2017 Mar 20. [Epub ahead of print]


Effects of Smoking on Late Toxicity From Breast Radiation.


Simona F. Shaitelman, Rebecca M. Howell, Benjamin D. Smith.


The University of Texas MD Anderson Cancer Center, Houston, TX.


DOI: 10.1200/JCO.2017.72.2660