ESTRO 2024 - Abstract Book

S2017

Clinical - Paediatric

ESTRO 2024

Among 25,723 five-year cancer survivors diagnosed <21 years of age between 1970-1999 in the Childhood Cancer Survivor Study (CCSS) with median follow-up of 29.9 years (range 5.0-48.9 years), 104 pathology-confirmed colorectal SMN were identified and occurred at median age of 39.7 years (range 19.3-66.6 years). For each survivor treated with RT (n=13,148), we reconstructed RT fields on a computational phantom scaled to their age at RT and estimated mean doses to the colorectum and its substructures (ascending, transverse, descending, sigmoid, and rectum). For the whole colorectum, we also calculated the percent volume receiving 5(V5), 10(V10), 20(V20), 30(V30) and 40(V40) Gy and maximum doses. Cyclophosphamide-equivalent dose (CED) and procarbazine-specific cumulative doses were calculated for survivors exposed to those agents. Piecewise exponential models estimated incident rate ratios (IRRs) of colorectal SMN. Models individually evaluated colorectal SMN risk associated with chemotherapy and RT as binary (yes/no) and ordinal categorical dose variables. All models were adjusted for attained age, age at primary cancer diagnosis, sex, and race. Additionally, RT- and chemotherapy-specific models were adjusted for alkylating agent dose and mean RT dose to the whole colorectum, respectively. RT and chemotherapy interactions were also investigated. The reference group for all models consisted of survivors who did not receive the treatment being assessed.

Results:

Compared to survivors not receiving RT, risk significantly (p<0.05) increased for mean RT doses ≥10 Gy in a dose dependent manner to the colorectum or any individual substructure (except sigmoid, where p=0.06). For mean RT doses 10-19.9Gy and ≥20Gy to the whole colorectum, the IRRs were 3.6 (95%CI 1.9-6.9) and 8.3 (95%CI 3.9 17.8), respectively. For mean RT doses 10-19.9Gy and ≥20Gy to colorectum substructures, IRRs ranged from 2.2 4.7 and 5.4-6.6, respectively. Colorectal SMN risk remained relatively constant for max doses from 10-40Gy to the whole colorectum with IRRs ranging from 2.1-2.6, but the IRR increased to 5.6 (95%CI 2.7-11.6) for doses ≥40Gy. For each dose-volume metric, the IRR increased with increasing irradiated volume of the colorectum above 20% volume ( Figure 1 ). For example, for V20 the IRR was 3.80 (95% CI 1.9-7.6), 4.9 (95% CI 2.0-12.0) and 8.70 (95% CI 3.5-21.6) for irradiated volumes of 20-39.9%, 40-79.9% and ≥80%, respectively.

For the chemotherapy associations, dose-response relationships were observed for CED and for procarbazine (a specific orally administered alkylating agent) alone. The IRR was 3.7 (95%CI 2.2-6.4) for alkylating doses ≥6.0g/m 2