TY - JOUR
T1 - Second primary cancer risks in seminoma patients treated with current and previous radiotherapy protocols
T2 - a systematic literature review
AU - Heemsbergen, Wilma D
AU - Spampinato, Sofia
AU - Dirkx, Maarten
AU - Jahreiß, Marie C
AU - Boormans, Joost L
AU - Franckena, Martine
AU - Boersma, Liesbeth J
PY - 2025/8
Y1 - 2025/8
N2 - BACKGROUND AND PURPOSE: Postoperative radiotherapy (RT) with para-aortal (PAO) +/- para-iliac (dog-leg) fields in seminoma patients is an effective treatment, associated with a lifetime risk of developing infra-diaphragmatic radiation-induced second primary cancers (SPC). We performed a systematic review to investigate dose to organs at risk (OAR), associated SPC risks, and landmark changes in RT-protocols, with a special interest in proton therapy. METHODS: A systematic literature search (1990-2024) was conducted using PRISMA guidelines. RESULTS: We identified eleven cohort studies reporting consistently excess SPC risks for pancreas, kidney, stomach, and (for dog-leg field) bladder, and colorectum after RT. Important RT-landmarks during the past 60 years were: abandoning mediastinal and inguinal RT, PAO only in stage I, prescription-dose reductions from 30-40 Gy to 20-26 Gy, largely abandoning elective PAO for stage I seminoma in favour of active surveillance, and introduction of proton therapy. RT remains an option in stage II (dog-leg with boosting) and high-risk stage I seminoma. Two studies estimated the dose-response-relationship for pancreas and stomach. Five planning studies showed consistent OAR dose reductions with proton versus photon therapy. Similar or higher OAR doses were observed with intensity-modulated versus conventional RT, due to larger low-dose baths. CONCLUSIONS: Established SPC risks have changed clinical practice in seminoma patients, and remain relevant for current RT practice. Proton therapy has the potential to reduce dose in relevant OARs at risk for SPCs. Further research on dose-response relationships for SPCs with fractionated RT and protons is needed to improve SPC risk assessment.
AB - BACKGROUND AND PURPOSE: Postoperative radiotherapy (RT) with para-aortal (PAO) +/- para-iliac (dog-leg) fields in seminoma patients is an effective treatment, associated with a lifetime risk of developing infra-diaphragmatic radiation-induced second primary cancers (SPC). We performed a systematic review to investigate dose to organs at risk (OAR), associated SPC risks, and landmark changes in RT-protocols, with a special interest in proton therapy. METHODS: A systematic literature search (1990-2024) was conducted using PRISMA guidelines. RESULTS: We identified eleven cohort studies reporting consistently excess SPC risks for pancreas, kidney, stomach, and (for dog-leg field) bladder, and colorectum after RT. Important RT-landmarks during the past 60 years were: abandoning mediastinal and inguinal RT, PAO only in stage I, prescription-dose reductions from 30-40 Gy to 20-26 Gy, largely abandoning elective PAO for stage I seminoma in favour of active surveillance, and introduction of proton therapy. RT remains an option in stage II (dog-leg with boosting) and high-risk stage I seminoma. Two studies estimated the dose-response-relationship for pancreas and stomach. Five planning studies showed consistent OAR dose reductions with proton versus photon therapy. Similar or higher OAR doses were observed with intensity-modulated versus conventional RT, due to larger low-dose baths. CONCLUSIONS: Established SPC risks have changed clinical practice in seminoma patients, and remain relevant for current RT practice. Proton therapy has the potential to reduce dose in relevant OARs at risk for SPCs. Further research on dose-response relationships for SPCs with fractionated RT and protons is needed to improve SPC risk assessment.
KW - Proton therapy
KW - Radiation-induced cancer
KW - Radiotherapy
KW - Review
KW - Second primary cancer
KW - Seminoma
KW - Survivorship
U2 - 10.1016/j.radonc.2025.110955
DO - 10.1016/j.radonc.2025.110955
M3 - (Systematic) Review article
SN - 0167-8140
VL - 209
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
M1 - 110955
ER -