Evaluation of late adverse events in long-term wilms' tumor survivors.
OBJECTIVE
To evaluate the prevalence and severity of adverse events (AEs) and treatment-related risk factors in long-term Wilms' tumor (WT) survivors, with special attention to radiotherapy.


METHODS
The single-center study cohort consisted of 185 WT survivors treated between 1966 and 1996, who survived at least 5 years after diagnosis. All survivors were invited to a late-effects clinic for medical assessment of AEs. AEs were graded for severity in a standardized manner. Detailed radiotherapy data enabled us to calculate the equivalent dose in 2 Gy fractions (EQD(2)) to compare radiation doses in a uniform way. Risk factors were evaluated with multivariate logistic regression analysis.


RESULTS
Medical follow-up was complete for 98% of survivors (median follow-up, 18.9 years; median attained age, 22.9 years); 123 survivors had 462 AEs, of which 392 had Grade 1 or 2 events. Radiotherapy to flank/abdomen increased the risk of any AE (OR, 1.08 Gy(-1) [CI, 1.04-1.13]). Furthermore, radiotherapy to flank/abdomen was associated with orthopedic events (OR, 1.09 Gy(-1) [CI, 1.05-1.13]) and second tumors (OR, 1.11 Gy(-1) [CI, 1.03-1.19]). Chest irradiation increased the risk of pulmonary events (OR, 1.14 Gy(-1) [CI, 1.06-1.21]). Both flank/abdominal and chest irradiation were associated with cardiovascular events (OR, 1.05 Gy(-1) [CI, 1.00-1.10], OR, 1.06 Gy(-1) [CI, 1.01-1.12]) and tissue hypoplasia (OR, 1.17 Gy(-1) [CI, 1.10-1.24], OR 1.10 Gy(-1) [CI, 1.03-1.18]).


CONCLUSIONS
The majority of AEs, overall as well as in irradiated survivors, were mild to moderate. Nevertheless, the large amount of AEs emphasizes the importance of follow-up programs for WT survivors.
van Dijk
Irma W E M
IW
Department of Radiation Oncology, Academic Medical Center, Amsterdam, the Netherlands. i.w.vandijk@amc.uva.nl
Oldenburger
Foppe
F
Cardous-Ubbink
Mathilde C
MC
Geenen
Maud M
MM
Heinen
Richard C
RC
de Kraker
Jan
J
van Leeuwen
Flora E
FE
van der Pal
Helena J H
HJ
Caron
Huib N
HN
Koning
Caro C E
CC
Kremer
Leontien C M
LC
D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000009:adverse effects*; D001842:Bone and Bones / Q000528:radiation effects; D002319:Cardiovascular System / Q000187:drug effects / Q000528:radiation effects; D002648:Child; D002675:Child, Preschool; D015981:Epidemiologic Factors; D005298:Fertility / Q000528:radiation effects; D006801:Humans; D007223:Infant; D007668:Kidney / Q000528:radiation effects; D007680:Kidney Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D008168:Lung / Q000528:radiation effects; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology; D016609:Neoplasms, Second Primary / Q000453:epidemiology; D011832:Radiation Injuries / Q000145:classification / Q000453:epidemiology* / Q000401:mortality; D011879:Radiotherapy Dosage; D012720:Severity of Illness Index; D017741:Survivors; D009396:Wilms Tumor / Q000401:mortality / Q000628:therapy*; D055815:Young Adult
D018943:Anthracyclines