Second Solid Cancers After Radiation Therapy: A Systematic Review of the Epidemiologic Studies of the Radiation Dose-Response Relationship

Abstract

Rapid innovation in radiotherapy techniques has resulted in an urgent need for risk projection models for second cancer risks from high-dose radiation exposure, since direct observation of the late-effects of newer treatments will require patient follow-up for a decade or more. However, the patterns of cancer risk after fractionated high-dose radiation are much less well understood than those after lower-dose exposures (0.1–5 gray (Gy)). In particular, there is uncertainty about the shape of the dose-response curve at high doses, and the magnitude of the second cancer risk per unit dose. We reviewed the available evidence from epidemiologic studies of second solid cancers in organs that received high-dose exposure (>5Gy) from radiotherapy where dose-response curves were estimated from individual organ-specific doses. We included 28 eligible studies with 3,434 second cancer patients across 11 second solid cancers. Overall, there was little evidence that the dose-response curve was non-linear in the direction of a down-turn in risk, even at organ doses of ≥60Gy. Thyroid cancer was the only exception with evidence of a downturn after 20Gy. Generally the excess relative risk per Gy, taking account of age and sex, was 5–10 times lower than the risk from acute exposures of <2Gy among the Japanese atomic bomb survivors. However, the magnitude of the reduction in risk varied according to second cancer. The results from our review provide insights into radiation carcinogenesis from fractionated high-dose exposures, and are generally consistent with current theoretical models. The results can be used to refine the development of second solid cancer risk projection models for novel radiotherapy techniques.

Pediatric Cranio-spinal Axis Irradiation

“…This analysis also showed that HT is Figure 5 also indicates that overall, the ERR and LQ calculation models may be a more accurate and consistent means of calculation because they contain a narrower spread across the patient data as indicated by their thinner boxes and shorter distances between maximum and minimum data values, in general. This finding is in agreement with recent reports, which state that general risk models tend to overestimate secondary cancers compared to epidemiological studies of patients treated with radiation therapy (48).…”

Radiotherapy for benign disease; assessing the risk of radiation-induced cancer following exposure to intermediate dose radiation

“…They also confirmed that the risk varied according to the tissue of origin of the second cancer. 81 Since the evidence mostly confirms an approximately linear risk of RIC, the data obtained from patients with cancer treated with high doses can be used to give some guidance as to the lesser risks of RIC after exposure to intermediate doses. However, treatment protocols/fractionation regimens will often be different, so any extrapolation from highdose studies must be interpreted with caution.…”

Dosimetric trade-offs in breast treatment with VMAT technique

“…However, the quantitative relationship between low-medium dose levels and the induction of secondary cancer is not clinically proven. Risk models exist, [22][23][24] but the clinical validation is vague. Again, the ALARA principle should be applied.…”