Portal hypertension in children with Wilms' tumor: a report from the National Wilms' Tumor Study Group.
OBJECTIVE
This analysis was undertaken to determine the cumulative risk of and risk factors for portal hypertension (PHTN) in patients with Wilms' tumor (WT).


METHODS
Medical records were reviewed to identify cases of PHTN identified with late liver/spleen/gastric toxicities in a cohort of 5,195 patients treated with National Wilms' Tumor Studies (NWTS) protocols 1 to 4. A nested case control study (5 controls/case) was conducted to determine relationships among doxorubicin, radiation therapy (RT) dose to the liver, patient gender, and PHTN. Conditional logistic regression was used to estimate adjusted hazard ratios (HR) of PHTN associated with these factors.


RESULTS
Cumulative risk of PHTN at 6 years from WT diagnosis was 0.7% for patients with right-sided tumors vs. 0.1% for those with left-sided tumors (p = 0.002). Seventeen of 19 cases were evaluable for RT. The majority of cases (16/17 [94%]) received right-flank RT either alone or as part of whole-abdomen RT and received >15 Gy to the liver. Fifteen of 17 (88%) patients received a higher dose to the liver than they would have with modern WT protocols. Controlling for RT dose, the HR was 3.0 for patients who received doxorubicin (p = 0.32) and 2.8 for females (p = 0.15). Controlling for doxorubicin, the 95% lower confidence bound on the HR associating PHTN with a minimum liver RT dose of >15 Gy vs. <or=15 Gy was 2.5 (p = 0.001); it was 2.4 for a maximum liver dose of >15 Gy vs. <or=15 Gy (p = 0.001).


CONCLUSIONS
There was a strong association between higher doses of liver RT (>15 Gy) and the development of PHTN among WT patients.
Warwick
Anne B
AB
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53326, USA. awarwick@mcw.edu
Kalapurakal
John A
JA
Ou
San-San
SS
Green
Daniel M
DM
Norkool
Pat A
PA
Peterson
Susan M
SM
Breslow
Norman E
NE
D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy / Q000009:adverse effects; D004317:Doxorubicin / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000209:etiology*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000528:radiation effects*; D016015:Logistic Models; D008297:Male; D016016:Proportional Hazards Models; D011879:Radiotherapy Dosage; D012306:Risk; D013154:Spleen / Q000187:drug effects / Q000528:radiation effects; D009396:Wilms Tumor / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin
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