Fasting Intervention for children with Unilateral Renal Tumours to reduce Toxicity

Childhood renal tumours account for around 7% of all childhood cancers. The
majority of these cases (90%) are Wilms tumour (WT or Nephroblastoma). The
annual incidence of renal tumours is seven cases per million children younger
than 15 years. Most patients with a renal tumour are asymptomatic, or they
present with a painless abdominal mass or haematuria. In the Netherlands, the
SIOP-RTSG approach is considered standard of clinical care. The current
SIOP-RTSG-2016 UMBRELLA protocol (further referred to as *UMBRELLA*) consist of
pre-operative chemotherapy and surgical excision. Post-operative chemotherapy
and radiation therapy is advised by a risk based approach. For Wilms tumors,
the use of recent international SIOP-RTSG regimens has resulted in excellent
survival rates and efforts to decrease in toxicity are now being pursued. The
overall five-year survival rates approaching 90 percent.

Dietary restriction (DR), meaning reduced intake of food without malnutrition,
and intermittent fasting are associated with extended life span, lower risk of
age associated diseases, increased resistance against side-effects of
chemotherapy, improved fitness and increased resistance to acute stress.
Nutritional preconditioning (by DR or fasting) represents non-invasive,
non-expensive methods of mitigating the effects of acute surgery-induced
stress. Short-term DR and fasting increases expression of cytoprotective genes,
increases immunomodulation via increased anti-inflammatory cytokine production
and also decreases the expression of pro-inflammatory markers. Nutritional
preconditioning has been proven feasible and safe in well-nourished patients
before surgery.

As surgery is an important part of renal tumour treatment, nutritional
preconditioning could be introduced to further improve patients* therapy
outcomes. Since renal tumour patients undergo a well-defined therapeutic
regimen in which chemotherapy and surgery do not overlap, this leaves a
well-defined pre-operative time window required to perform pre-operative
fasting.

to investigate the effect of a pre-operative fasting diet on post-operative
recovery after renal tumour surgery

a single-centre, prospective, randomized, non-blinded, proof-of-concept
intervention study

Nutritional preconditioning by fasting for 10, 14 or 18 hours.

Age Group 1: 6-24 Months (0,5 to 2 years): 10 hours of fasting
Age Group 2: 25-84 Months (2 to 7 years): 14 hours of fasting
Age Group 3: 85-216 Months (7 to 18 years): 18 hours of fasting

The extent of the burden of our study is considered relatively low. DR and
fasting has been proven feasible and safe in previous studies. For this study,
no extra blood samples are taken besides the samples taken for routine
procedures. No extra visit to the hospital is needed in order to obtain all the
information required for this study. Biopsies acquired to investigate the
tissue are part of the routine procedure. Several standardized questionnaires
are asked to be filled in before and after the diet. Mentioned questionnaires
take +/-10 minutes to complete. The diet may give rise to discomfort in the
form of less satiety and possible light-headedness.

Based on earlier research we propose different fasting duration per paediatric
age group. We hypothesize that subjects of a younger age need significantly
less time to reach the protective state associated with fasting and we aim to
avoid unnecessary exposure to the risk of developing prolonged or severe
hypoglycemia.

Combining the low chance of post-operative complications, the small extent of
possible post-operative complications and our clear guidelines to avoid
hypoglycaemia, we do not expect a higher incidence of complications or any
compromises on subject safety. Conducting this research will bring invaluable
knowledge concerning a minimal invasive therapy with no extra cost and its
possible merits for pre-operative conditioning to reduce the post-operative
burden.