Second cancer risk in childhood cancer survivors treated with intensity‐modulated radiation therapy: An updated analysis of more than 10 years of follow‐up

Abstract

Background: It is unclear how intensity-modulated radiation therapy (IMRT) impacts long-term risk of second malignant neoplasms (SMNs) in childhood cancer patients. Procedure: Patients aged ≤21 years treated with IMRT between 1998 and 2009 and who survived ≥5 years after IMRT were included. SMN site in relation to isodose level (IDL) of IMRT was evaluated. Standardized incidence ratios (SIR) and excess absolute risks (EAR) were calculated. Cumulative incidences were estimated with death as a competing risk.Results: Three-hundred twenty-five patients were included with median follow-up of 11.2 years from IMRT (interquartile range: 9.4-14.0) among patients alive at the end of follow-up. Two hundred (62%) patients had ≥10 years of follow-up and 284 (87%) patients were alive at the time of analysis. Fifteen patients developed SMNs (11 solid, four hematologic). Median time from IMRT to solid SMN was 11.0 years (range: 6.8-19.2) with 10-and 15-year cumulative incidences 1.8% (95% CI: 0.7-3.9) and 3.5% (95% CI: 1.4-7.5), respectively; SIR was 13.7 (95% CI: 6.9-24.6) and EAR was 2.8 per 1000 person-years (95% CI: 1.0-4.6). Eight solid SMNs developed within the IMRT field (100% IDL [n = 5], 80% IDL [n = 1], 50% IDL [n = 1], 40% IDL [n = 1]), one within the 70%-80% IDL of a conventional field, one was out-of-field, and one could not be determined. Conclusions:With median follow-up of >10 years, many solid SMNs after IMRT in childhood cancer survivors develop in the high-dose region. These data serve as a foundation for comparison with other modalities of radiation treatment (e.g., proton therapy).

Risk of second primary cancer from proton arc therapy of pediatric brain tumors

“…Of note, a recent study reported a 10-year cumulative incidence of solid SPC of 1.8% after intensity modulated radiotherapy for pediatric cancer [4] , in line with estimates from conventional radiotherapy despite a larger low-dose volume. Therefore, more clinical evidence is required to understand the effect of low-doses on SPC risks [18] , when available clinical data are so far not indicating an increased risk.…”

“…However, the low-dose bath is higher with PAT compared to intensity modulated proton therapy (IMPT) [2] . Therefore, and in particular for pediatric patients, concerns exist with regards to radiation-induced second primary cancers (SPC) with PAT, as the impact of low doses on SPC risks is still unclear [3] , [4] .…”

“…Indeed, passive-scattering PAT necessitates complex beam modifying materials to shape each field during treatment delivery [6] , while active-scanning PAT could offer continuous spot delivery during gantry rotation [7] . Brain tumors have been considered good candidates to benefit from PAT [1] , but the risk of SPC has not yet been assessed, despite a recent study highlighting that pediatric brain tumor patients are at increased risk of developing a SPC [4] .…”

Recent Updates on Radiation Therapy for Pediatric Optic Pathway Glioma

“…However, long-term (11 years) follow-up data from a single center with 325 patients treated with intensity-modulated photon RT revealed that solid secondary malignancy developed in 11 patients and the 10- and 15-year cumulative incidence of secondary malignancy were 1.8% and 3.5%, respectively. Eight among 11 solid secondary malignancies developed within the intensity-modulated photon RT field, 1 within the intermediate-dose area, and only 1 was out-of-field [ 51 ]. Solid secondary malignancies included high-grade glioma (n= 3), osteosarcoma (n=3), colon cancer (n=2), thyroid cancer (n= 1), presumed sarcoma (n=1), and unknown primary (n=1).…”

“…Also, Indelicato et al [ 53 ] reported a 10-year cumulative incidence of 3.1% in 1,713 children treated with PBT and 1.7% in 1,676 children without germline mutation. They observed that all 5 high-grade gliomas (in children without genetic syndrome) developed in the high-dose region same as the intensity-modulated photon RT series [ 51 ]. A retrospective cohort study of 558 adult patients treated with PBT showed slightly reduced incidence of secondary neoplasm compared to matched cohort from the Surveillance, Epidemiology, and End Results cancer registry treated with X-rays (5.2% vs. 7.5%) [ 54 ].…”