Figure 2.

Mortality from (A) any SMNs and (B) gastrointestinal SMNs by the cumulative dose of platinum‐containing CT (mg/m² of body surface area). HR estimates (ERRs) were derived from models adjusted for age (continuous), smoking at testicular cancer diagnosis, supradiaphragmatic radiotherapy, and subdiaphragmatic radiation dose. Circles represent HR estimates for dose categories (no platinum‐containing CT and >0‐399, 400‐499, and ≥500 mg/m² of body surface area) and are plotted at the median dose in each category (0, 300, 400, and 600 mg/m², respectively). Dose‐response relationships were based on the categorical dose as an outcome, with the category set at the median dose within that category. Vertical lines reflect the 95% CIs around the HRs for dose categories. The dashed line in panel A is the best fitting dose‐response relationship and reflects a linear increase in the mortality risk from any SMN, with 0.29 (95% CI, 0.19‐0.39; P < .001) added to the HR for each additional platinum‐containing CT dose of 100 mg/m² body surface area. The dashed line in panel B is the best fitting dose‐response relationship and reflects a linear increase in gastrointestinal SMN mortality risk, with 0.66 (95% CI, 0.35‐0.97; P < .001) added to the HR for each additional platinum‐containing CT dose of 100 mg/m² of body surface area. CI indicates confidence interval; CT, chemotherapy; ERR, excess relative risk; HR, hazard ratio; SMN, second malignant neoplasm.