Late effects after Wilms tumor therapy

Premature mortality after Wilms tumor diagnosis. Long-term morbidity and mortality among unilateral, nonsyndromic Wilms tumor survivors were evaluated in the Childhood Cancer Survivor Study (CCSS). Among 2,008 survivors, 142 deaths occurred (standardized mortality ratio [SMR], 2.9 [95% CI, 2.5–3.5]; 35-year cumulative incidence of death, 7.8% [95% CI, 6.3%–9.2%]). The most frequent causes of death were subsequent malignant neoplasms (SMNs) (n = 42), Wilms tumor relapse (n = 30), and cardiac related (n = 9). Survivors who were treated with vincristine and dactinomycin (VA) alone had comparable risk for all-cause mortality (SMR,1.0) and health-related late mortality (SMR, 1.5) relative to the general population.[317]

Chronic health conditions. Findings from the same CCSS study are as follows:[317]

Chronic health conditions. Findings from the same CCSS study are as follows:[317]

Of unilateral Wilms tumor survivors (n = 2,008), the 35-year cumulative incidence of any grades 3 to 5 chronic health condition was 34.1% among Wilms tumor survivors and 14.8% among siblings.

Chronic health conditions. Findings from the same CCSS study are as follows:[317]

Survivors treated with VA alone had a modestly increased risk of developing grades 3 to 5 chronic health conditions compared with siblings (RR, 1.5).

Chronic health conditions. Findings from the same CCSS study are as follows:[317]

Risks of grades 3 to 5 chronic health conditions, including intestinal obstruction (8.1%), kidney failure (2.4%), premature ovarian insufficiency (7.3%) and heart failure (4.0%), increased by treatment intensity in a dose-dependent manner and by exposure to doxorubicin and/or radiation therapy. This risk was most pronounced among survivors with high-risk disease, including those with early relapse (<5 years).

Chronic health conditions. Findings from the same CCSS study are as follows:[317]

Compared with siblings, survivors treated with VA showed a higher risk of intestinal obstruction (RR, 9.4) and kidney failure (RR, 11.9) but the magnitude of the risk was lower than that for more intensive treatment groups.

Chronic health conditions. Findings from the same CCSS study are as follows:[317]

Both whole-lung and whole-abdomen radiation therapy were associated with increased risks of SMNs, heart failure, and intestinal obstruction, and the magnitude of risk increased with rising doses.

Chronic health conditions. Findings from the same CCSS study are as follows:[317]

Whole-abdomen or flank radiation therapy higher than 20 Gy was associated with an increased risk of intestinal obstruction compared with no radiation therapy, whereas radiation therapy doses of 20 Gy or less were not associated with any chronic health condition.

SMNs.[318,319] In the CCSS study of Wilms tumor survivors (n = 2,008), 82 developed SMNs (standardized incidence ratio [SIR], 4.1), representing a cumulative incidence rate of 6.1%. Breast (SIR, 6.9), thyroid (SIR, 4.7) and intestinal/colorectal (SIR, 12.0) were the most frequently reported cancers.[317] The cumulative incidence of invasive breast cancer in Wilms tumor survivors who had received pulmonary radiation for metastatic Wilms tumor is nearly 15% by age 40 years.[320]

Congestive heart failure. The risk of congestive heart failure is influenced by dose of doxorubicin received, radiation to the heart, and female sex.[321] CCSS investigators reported that cumulative doxorubicin doses of 250 mg/m2 or higher were associated with a nearly 5-fold rate of development of heart failure, compared with no doxorubicin exposure.[317]

Infertility for patients who received whole-abdomen irradiation and/or cyclophosphamide.[322,323] The 35-year cumulative incidence rate of premature ovarian insufficiency was 7.3%. Whole-abdomen radiation therapy was associated with an increased risk of premature ovarian insufficiency, with a greater risk with increasing dose (≤20 Gy: RR, 13.1; >20 Gy: RR, 36.5).[317] Female survivors of Wilms tumor diagnosed before age 40 years from a St. Jude Lifetime Cohort Study experienced increased premature ovarian insufficiency compared with controls (9.3% vs. 0.6%; P < .01), likely because of abdominal irradiation that exposed the ovaries. None of the females exposed to hemiabdominal radiation therapy experienced premature ovarian insufficiency.[319]

Complications of pregnancy.[324] One study examined the effects of radiation therapy to the abdomen (partial or whole abdomen) on pregnancy and pregnancy outcomes in patients with a history of Wilms tumor. The investigators reviewed hypertension complicating pregnancy, early or threatened labor, malposition of the fetus, premature rupture of membranes, obstructed labor, abnormality of forces of labor, and umbilical cord complications. There were 1,021 pregnancies (with a duration of 20 weeks or longer), including 955 live births, from which there were 700 sets of maternal and offspring medical records. Female survivors of Wilms tumor who received radiation therapy are at an increased risk of hypertension complicating pregnancy, early or threatened labor, and fetal malposition. The offspring of these patients were more likely to be premature and have low birth weights.[324] For more information, see the Reproduction section in Late Effects of Treatment for Childhood Cancer.

Late kidney failure. Based on the CCSS study, the cumulative incidence of late kidney failure among survivors was 2.4% (approximately a 10-fold increased rate relative to siblings). No single chemotherapy or radiation therapy–related exposure was associated with kidney failure, which suggests that nephrectomy may be the primary risk factor.[317] Rates of late kidney failure increase with advancing age. This finding highlights the importance of long-term monitoring of kidney function in these patients, particularly when the patients have other comorbidities. The cumulative incidence of end-stage renal disease caused by chronic renal failure at 20 years from diagnosis of Wilms tumor is 3.1% for patients with bilateral Wilms tumor.[213]

Neurocognitive impairment. Among 264 long-term Wilms tumor survivors participating in a St. Jude Lifetime Cohort Study who completed neurocognitive testing, 19.7% had grades 2 to 3 executive function impairment, compared with 12% of controls (P < .01). In survivors, processing speed (19.7% vs. 8.4%) and memory (20.9% vs. 9.9%) showed a higher prevalence of moderate to severe impairments, compared with controls (P < .01). Only impairments in processing speed were associated with the presence of grades 2 to 4 cardiovascular disease.[319]

Physical performance. In the CCSS study, survivors were more likely to report poor physical functioning (OR, 2.9) than siblings.[317] In a St. Jude Lifetime Cohort Study, 270 long-term Wilms tumor survivors completed function testing and were observed to have excess impairments in aerobic function, mobility, strength, endurance and flexibility, compared with controls. There were no clear associations between these outcomes and treatment exposures.[319]

Children with WAGR syndrome or other germline WT1 pathogenic variants are monitored throughout their lives because they are at increased risk of developing hypertension, nephropathy, and renal failure.[213]

Patients with Wilms tumor and aniridia without genitourinary abnormalities are at lower risk but are monitored for nephropathy or renal failure.[325]

Children with Wilms tumor and any genitourinary anomalies are also at increased risk of late renal failure and are monitored. Features associated with germline WT1 pathogenic variants that increase the risk of developing renal failure include the following:[213]

Children with Wilms tumor and any genitourinary anomalies are also at increased risk of late renal failure and are monitored. Features associated with germline WT1 pathogenic variants that increase the risk of developing renal failure include the following:[213]

Stromal predominant histology.

Children with Wilms tumor and any genitourinary anomalies are also at increased risk of late renal failure and are monitored. Features associated with germline WT1 pathogenic variants that increase the risk of developing renal failure include the following:[213]

Bilateral disease.

Children with Wilms tumor and any genitourinary anomalies are also at increased risk of late renal failure and are monitored. Features associated with germline WT1 pathogenic variants that increase the risk of developing renal failure include the following:[213]

Intralobar nephrogenic rests.

Children with Wilms tumor and any genitourinary anomalies are also at increased risk of late renal failure and are monitored. Features associated with germline WT1 pathogenic variants that increase the risk of developing renal failure include the following:[213]

Wilms tumor diagnosed before age 2 years.