We were unable to identify either low or high weight- or BMI-for-age as prognostic factors for EFS in patients with FH WT in our very large cohort. This is in contrast to pediatric patients with acute myeloid leukemia and possibly in other pediatric cancers. For the subgroup of patients under 2 years of age, however, the width of the confidence intervals shown in makes clear that this study was not sufficiently powered to rule out the types of weight effects observed in other studies.
Underweight (body mass index [BMI] <18.5) and obesity (BMI >30) are associated with excess mortality from all causes in adults greater than 25 years of age [14
]. A number of studies in adult oncology cohorts have documented an association between obesity and inferior survival in women with breast cancer and colon cancer [16
] and on local recurrence in males with rectal cancer[18
]. There is conflicting evidence with respect to the contribution of excess toxicity to an overall inferior mortality seen in patients with obesity [19
The correlation between underweight and inferior outcome in some malignancies has a number of different potential explanations including increased toxicity and altered drug metabolism. A study in leukemia patients suggested that toxicity and relapse were not associated with BMI in a developed world setting [5
]. It is possible that more severe malnutrition may adversely affect outcomes. We are unable to determine if the lack of impact of low weight at diagnosis upon outcome was related to intensive nutritional intervention, as these data were not recorded on NWTS 5. Rickard examined 31 malnourished children with newly diagnosed WT in the Third National Wilms Tumor Study protocol [21
]. In patients who were termed high nutritional risk, adequate parental nutrition support reversed protein energy malnutrition and prevented chemotherapy and radiotherapy delays due to granulocytopenia.
Increased birth weight is associated with an excess risk for the development of certain cancers including WT [22
]. This is postulated to be related to growth factor excess. Overweight in normal children and adolescents without cancer has a variety of adverse health outcomes including Type II diabetes, obstructive sleep apnea, dyslipidemia, fatty liver disease and hypertension [24
]. All of these may decrease tolerance to complete chemotherapy delivery. In contrast to underweight patients, it is unlikely that nutritional interventions had a substantial impact upon the EFS given the relatively short time frame of therapy for WT (18-24 weeks). While excess drug toxicity in overweight patients may be related to altered metabolism, for example by prolonged clearance of doxorubicin [25
], it is possible that any altered metabolism is not sufficient to produce a detectable difference in EFS in a highly curable tumor such as WT.
We did not expect to find an excess of both high and low weight or BMI patients as compared to the CDC 2000 charts. Between 20-30% of those who were overweight at diagnosis may be explained by overgrowth syndromes or the known association of overweight with perilobar nephrogenic rests. An excess number of patients with high birth weight has previously been identified in WT, neuroblastoma and leukemia and it is possible that this anthropomorphic characteristic persists as the child matures [22
]. Likewise, the excess in low weight or BMI is inadequately explained by syndromes, such as WAGR or birth weight. We found no evidence that the excess in lower weight and BMI was explained by compromised nutrition secondary to a direct mass effect of left sided WTs on the stomach. Weight loss post-operatively and tumor-induced cachexia due to increased tumor related catabolism may also contribute to this finding.
Strengths of this secondary analysis study are that this represents the largest prospectively collected cohort used to study this question. Patients had central review histology to confirm diagnosis. Limitations include that we do not have information about any nutritional interventions that may have been implemented for this group of patients. There are also inherent possible errors in taking and recording anthropomorphic measurements, although there is unlikely to be a systematic bias in over- or under-estimating measurements.
Weight or BMI as a prognostic factor for children with FH WT would have potential significance as it is easily measured, and thus available at the time of protocol initiation[27
]. We found no evidence that such a prognostic factor exists in our cohort.