Session Item

Radiotherapy (RT) and smoking are known as potential modifying and interactive factors affecting the risk of developing second primary cancer (SPC) after RT. Modern intensity-modulated RT (IMRT), with increased low-dose baths and out-of-field scattering, may increase such risks even more. Here we report on the impact of IMRT and smoking status in a single-center retrospective cohort study, using an internal reference group of 3-dimensional conformal RT (3DCRT) patients.

The study cohort comprised 1,468 prostate cancer survivors (mean age 70.0 years, 6.7 1SD) treated with either 3DCRT or IMRT in the period 2006-2012 (Table 1). IMRT was gradually introduced during the period 2007-2010. All patients received standard treatment at that time (72-78 Gy in 2Gy fractions) and had no previous or simultaneous RT to other pelvic areas. Data on SPC incidences (solid, non-skin) were retrieved from the Netherlands Cancer Registry. Only first SPCs were included in the analysis. The Fine and Gray model was applied  with death and non-solid SPC as competing risk, to estimate relative risks (Subhazard Ratios [sHRs]) for IMRT vs 3DCRT within smoking categories. Models were adjusted for age at RT, and calendar year of RT. Time was calculated from start RT and was maximized at 10 years to adjust for differences between both groups in maximum follow-up. A latency period of 6 months was considered, resulting in the exclusion of 3 SPCs.

Median follow-up was 7.5 (IMRT) and 9.5 years (3DCRT). We observed 236 SPCs in the period 0.5-10 years. Most frequent SPCs were bladder (n=44), lung (n=41), colon (n=35), and rectum (n=23). Vital status at the end of follow-up was: 62% alive, 37% died (13% after SPC), 1% emigrated. Distribution of smoking status was: 17% current, 20% previous, 31% never, 32% unknown. For the total cohort (regardless smoking status), the adjusted sHR with 95% CI to develop SPC (IMRT vs 3DCRT) was 1.4 (1.0-2.0). For never smokers,  1.0 (0.5-2.0), for previous smokers 1.4 (0.6-3.0), for current smokers 2.8 (1.3-5.8), Figure 1, and for unknown smoker status 1.2 (0.5-2.6). Interaction between smoking status (current y/n) and technique was significant (p<0.01). Within the “current smokers” subgroup, the adjusted sHR was 1.9 (0.5-7.6) for SPCs in the pelvis, 4.6 (1.0-20.9) for SPCs in the abdomen, and 2.7 (1.0-7.3) for SPCs in the remaining anatomical regions.

Our study suggests a complex relationship between IMRT, smoking status, and SPC risks. IMRT in current smokers was significantly associated with increased SPC risks, which potentially means that exposure of healthy tissue to low-dose baths and scatter should be minimized in current smokers needing cancer treatment. This observation is biologically plausible, since nicotine is known to promote the growth of cancer cells. Further validation in a multicenter setting with prolonged follow-up is currently ongoing.