Taylor Carolyn, Correa Candace, Duane Frances K, Aznar Marianne C, Anderson Stewart J, Bergh Jonas, Dodwell David, Ewertz Marianne, Gray Richard, Jagsi Reshma, Pierce Lori, Pritchard Kathleen I, Swain Sandra, Wang Zhe, Wang Yaochen, Whelan Tim, Peto Richard, McGale Paul
Carolyn Taylor, Frances K. Duane, David Dodwell, Richard Gray, Zhe Wang, Yaochen Wang, Richard Peto, and Paul McGale, University of Oxford, Oxford, United Kingdom; Candace Correa, Regional Cancer Center, Utica, NY; Marianne C. Aznar, Rigshospitalet, Copenhagen; Marianne Ewertz, Odense University Hospital, Odense, Denmark; Stewart J. Anderson, University of Pittsburgh, Pittsburgh, PA; Jonas Bergh, Karolinska Institutet and University Hospital, Stockholm, Sweden; Reshma Jagsi and Lori Pierce, University of Michigan, Ann Arbor MI; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre, Toronto; Tim Whelan, Juravinski Cancer Centre and McMaster University, Hamilton, Ontario, Canada; and Sandra Swain, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC.
J Clin Oncol. 2017 May 20;35(15):1641-1649. doi: 10.1200/JCO.2016.72.0722. Epub 2017 Mar 20.
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.
目的 放疗可使适合的女性乳腺癌死亡的绝对风险降低几个百分点，但数十年后可能引发第二种癌症或心脏病。我们评估了现代乳腺癌放疗的绝对长期风险。方法 首先，对2010年至2015年发表的乳腺癌治疗方案中的肺部和心脏剂量进行了系统的文献综述。其次，对75项试验中随机分配接受乳腺癌放疗与未接受放疗的40781名女性的个体患者数据进行荟萃分析，得出第二种原发性癌症的发生率比（RRs）、特定病因死亡率以及每Gy的额外RRs（ERRs），用于评估肺癌和心脏死亡率。吸烟状况数据不可用。第三，将试验中每Gy的肺部或心脏ERRs与2010年至2015年的剂量相结合，并应用于基于人群数据中的当前吸烟者和非吸烟者的肺癌及心脏死亡率。结果 2010年至2015年发表的647个治疗方案的平均剂量为全肺5.7 Gy，全心4.4 Gy。放疗的中位年份为2010年（四分位间距[IQR]，2008年至2011年）。荟萃分析得出，放疗后≥10年肺癌发生率的RR为2.10（95%CI，1.48至2.98；P<.001），基于134例癌症，表明全肺剂量每Gy的ERR为0.11（95%CI，0.05至0.20）。对于心脏死亡率，基于1253例心脏死亡，RR为1.30（95%CI，1.15至1.46；P<.001）。详细分析表明全心剂量每Gy的ERR为0.04（95%CI，0.02至0.06）。现代放疗的估计绝对风险如下：肺癌，长期持续吸烟者约为4%，非吸烟者约为0.3%；心脏死亡率，吸烟者约为1%，非吸烟者约为0.3%。结论 对于长期吸烟者，现代放疗的绝对风险可能超过益处，但对于大多数非吸烟者（以及已戒烟者），放疗的益处远超过风险。因此，吸烟可决定放疗对死亡率的净效应，但戒烟可大幅降低放疗风险。
