Second cancer after radiotherapy ?
Is the induction of second malignancies after radiotherapy dose dependent? 12000 one-year survivors of cancer treated with radiotherapy at the University of Ulm between 1981 and 2007 were included in this retrospective analysis of Bartkowiak et al. (LINK1). The incidence of subsequent cancers (493 cases) was about 1% per year. The incidence of post-radiotherapy second cancer was compared with the spontaneous incidence of cancer according to the data of the Robert-Koch-Institute.
The cumulated relative risk (RR) was significantly increased in women after 4 years and in men after 9 years. A high proportion of 49.6 % among the 493 subsequent- cancers were treated after breast cancer as first malignancy. Contralateral breast cancer was the most frequent entity of subsequent cancer (relative risk RR=2.8). Retrospective dosimetry to determine the scattered dose to the second tumour site proved to be difficult with a reported inaccuracy up to 40-60%. The scatter-dose gradient (2-3Gy) across the contralateral breast did not cause a detectable risk gradient. No information about endogenous confounders, such as BRCA mutation, is available in this analysis. There was an increased risk for second head and neck cancer in both genders (pooled RR=5.1) and for male oesophageal cancer (RR=5.8). For both entities, dose response modelling with case-control data predicted maximum curves with peak induction at 1-5Gy and positive excess absolute risk values (EAR per 10.000 person years) at high doses.
In comparison, a study of the SEER cancer registries reported that the RR was highest for organs that typically received greater than 5 Gy. The authors estimated that in total a rate of 8% of the subsequent cancers are real secondary solid cancers that could be related to radiotherapy (≥1 year survivors) and 5 excess cancers per 1000 patients by 15 years after diagnosis (related article 1).
Conclusion: Given a greater irradiated volume with IMRT, the risk of inducing real secondary malignancies might be potentially enhanced compared to 3D-radiotherapy. Prospective out-of-field dosimetry during treatment planning is necessary to evaluate the risk of multiportal therapy. Furthermore, databanks should cover more than 5 years follow-up. Preston et al reported in their life span study of the Japanese atomic bomb survivors only 850 radiation induced solid cancer (of 45.000 persons exposed to 0,005-4Gy) 50 years after exposition, with a lag of at least 5 years between radiation exposure and solid-cancer induction (Related article 2). In summary, a high number of spontaneous second cancers must be expected irrespective of the radiotherapy due to other endogenous and exogenous factors. The benefit of IMRT clearly outbalances the relatively small risk of radiation induced second cancer.