title: Portal hypertension in children with Wilms' tumor: a report from the National Wilms' Tumor Study Group.
abstract: 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.
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53326, USA. awarwick@mcw.edu
authors.forename: Anne B
authors.initials: AB
authors.lastname: Warwick
authors.forename: John A
authors.initials: JA
authors.lastname: Kalapurakal
authors.forename: San-San
authors.initials: SS
authors.lastname: Ou
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Green
authors.forename: Pat A
authors.initials: PA
authors.lastname: Norkool
authors.forename: Susan M
authors.initials: SM
authors.lastname: Peterson
authors.forename: Norman E
authors.initials: NE
authors.lastname: Breslow
mesh_terms: 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
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin
references.citation: J Pediatr. 1971 Jun;78(6):1031-4
references.pmid: 4325221
references.citation: Am J Roentgenol Radium Ther Nucl Med. 1969 Aug;106(4):750-65
references.pmid: 4308791
references.citation: J Clin Oncol. 2001 Apr 1;19(7):1926-34
references.pmid: 11283124
references.citation: Cancer. 1991 Jan 15;67(2):331-6
references.pmid: 1845940
references.citation: Radiology. 1972 Aug;104(2):389-91
references.pmid: 4339830
references.citation: Am J Clin Oncol. 1982 Aug;5(4):339-47
references.pmid: 6287836
references.citation: Cancer. 1976 Aug;38(2):633-46
references.pmid: 184912
references.citation: Gastroenterology. 1986 Apr;90(4):1054-6
references.pmid: 3005103
references.citation: Med Pediatr Oncol. 1993;21(3):172-81
references.pmid: 7680412
references.citation: J Clin Oncol. 1995 Aug;13(8):1851-9
references.pmid: 7636528
references.citation: J Clin Oncol. 2005 Oct 10;23(29):7312-21
references.pmid: 16129848
references.citation: Int J Radiat Oncol Biol Phys. 1983 May;9(5):651-7
references.pmid: 6303994
references.citation: Br J Cancer. 1990 Dec;62(6):1026-30
references.pmid: 2175212
references.citation: Am J Pathol. 1966 Apr;48(4):597-611
references.pmid: 5327788
references.citation: Am J Roentgenol Radium Ther Nucl Med. 1970 Feb;108(2):365-85
references.pmid: 4312896
references.citation: Cancer. 1989 Jul 15;64(2):349-60
references.pmid: 2544249
references.citation: J Clin Oncol. 2004 Apr 15;22(8):1366-72
references.pmid: 15084612
references.citation: Cancer. 1981 May 1;47(9):2302-11
references.pmid: 6164480
references.citation: Am J Pediatr Hematol Oncol. 1994 Aug;16(3):207-12
references.pmid: 8037337
references.citation: J Clin Oncol. 1998 Jan;16(1):237-45
references.pmid: 9440748