Tubiana Maurice
Institute Gustave Roussy, Villejuif, France.
Radiother Oncol. 2009 Apr;91(1):4-15; discussion 1-3. doi: 10.1016/j.radonc.2008.12.016. Epub 2009 Feb 5.
Second primary malignancies (SPMs) occurring after oncological treatment have become a major concern during the past decade. Their incidence has long been underestimated because most patients had a short life expectancy after treatment or their follow-up was shorter than 15 years. With major improvement of long-term survival, longer follow-up, cancer registries and end-result programs, it was found that the cumulative incidence of SPM could be as high as 20% of patients treated by radiotherapy. This cumulative proportion varies with several factors, which ought to be studied more accurately. The delay between irradiation and solid tumor emergence is seldom shorter than 10 years and can be as long as half a century. Thus, inclusion in a cohort of patients with a short follow-up leads to an underestimation of the proportion of SPM caused by treatment, unless actuarial cumulative incidence is computed. The incidence varies with the tissue and organs, the age of the patient at treatment, hereditary factors, but also, and probably mainly, with dose distribution, size of the irradiated volume, dose, and dose-rate. An effort toward a reduction in their incidence is mandatory. Preliminary data suggest that SPMs are mainly observed in tissues having absorbed doses above 2 Gy (fractionated irradiation) and that their incidence increases with the dose. However, in children thyroid and breast cancers are observed following doses as low as 100 mGy, and in adults lung cancers have been reported for doses of 500 mGy, possibly due to interaction with tobacco. The dose distribution and the dose per fraction have a major impact. However, the preliminary data regarding these factors need confirmation. Dose-rates appear to be another important factor. Some data suggest that certain patients, who could be identified, have a high susceptibility to radiocancer induction. Efforts should be made to base SPM reduction on solid data and not on speculation or models built on debatable hypotheses regarding the dose-carcinogenic effect relationship. In parallel, radiation therapy philosophy must evolve, and the aim of treatment should be to deliver the minimal effective radiation therapy rather than the maximal tolerable dose.
在过去十年中，肿瘤治疗后发生的第二原发性恶性肿瘤（SPM）已成为一个主要问题。其发病率长期以来一直被低估，因为大多数患者在治疗后的预期寿命较短，或者他们的随访时间短于15年。随着长期生存率的大幅提高、更长时间的随访、癌症登记和最终结果项目，人们发现SPM的累积发病率在接受放射治疗的患者中可能高达20%。这个累积比例因几个因素而异，这些因素应该得到更准确的研究。放疗与实体瘤出现之间很少短于10年，最长可达半个世纪。因此，将随访时间短的患者纳入队列会导致对治疗引起的SPM比例的低估，除非计算精算累积发病率。发病率因组织和器官、治疗时患者的年龄、遗传因素而异，但也可能主要因剂量分布、照射体积大小、剂量和剂量率而异。必须努力降低其发病率。初步数据表明，SPM主要出现在吸收剂量高于2 Gy（分次照射）的组织中，其发病率随剂量增加而增加。然而，在儿童中，甲状腺癌和乳腺癌在低至100 mGy的剂量后就会出现，在成人中，肺癌在500 mGy的剂量下就有报道，这可能是由于与烟草的相互作用。剂量分布和每次分割的剂量有重大影响。然而，关于这些因素的初步数据需要得到证实。剂量率似乎是另一个重要因素。一些数据表明，可以识别出某些对放射性癌症诱导高度敏感的患者。应该努力将降低SPM的工作建立在可靠的数据基础上，而不是基于关于剂量致癌效应关系的有争议假设的推测或模型。与此同时，放射治疗理念必须发展，治疗的目标应该是给予最小有效放射治疗，而不是最大耐受剂量。
