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Wilms Tumor

 

 

Late Effects of Therapy

 

 

Radiotherapy (RT)

Late effects are generally defined as side effects which occur 5 years or more after therapy. All cancer treatment is associated with adverse effects. Treatment of Wilms tumor, however, is relatively mild and usually produces minimal toxicity.

 

Late Effects associated with flank and whole abdominal RT:

Organ at risk Toxicity

Musculo-skeletal

Growth abnormalities and hypoplasia:

  • Mild scoliosis and mild asymmetry of all musculoskeletal structures in the RT field can occur due to reduced growth of bone and paravertebral muscles
  • Scoliosis is certain if only half the width of the vertebral body is included in the RT treatment volume
  • There will be a decrease in sitting height and modest decrease in standing height after flank or abdominal RT
  • These effects are more pronounced the younger the patient is at the time of RT

 

Increased risk of osteoporosis (especially involving the spine) and degenerative disease:

  • Patients should avoid lifting very heavy weights
  • Bone density should be checked roughly 10 years before one would normally worry about osteoporosis
  • Important to maintain bone density (Vit D, calcium and dairy servings in diet together with regular exercise)

 

Pancreas

Metabolic syndrome is more common after RT to the upper abdomen. This is characterized by:

  • Weight gain and truncal obesity
  • Abnormal fasting blood lipid profile
  • Increased risk of hypertension
  • Increased risk of diabetes
  • Increased risk of vascular disease

Hepatic

There is a small long term risk of veno-occlusive disease which consists of the clinical triad:

  • hepatomegaly
  • ascites
  • icterus

 

Increased risk in children with right sided tumor (larger volume of liver irradiated in the flank field)

 

Renal

If included in the RT treatment volume, stenosis of the contralateral renal artery may produce hypertension.

 

It is very important to check Wilms tumor survivor's blood pressure on a regular basis

 

Patients with bilateral Wilms Tumor undergoing partial nephrectomy and RT are at significantly increased risk of chronic renal failure

 

Patients are likely to have sufficient renal tissue for normal growth and development for many years.

 

Gonadal

Ovary:
Whole abdomen RT:

  • All patients are very likely to have ovarian failure
  • 70% are amenorrheic

Ovarian failure very rare in females who receive abdominal RT to a volume that does not include both ovaries (risk of early menopause though).

Ovarian failure

    • in 14% of patients whose ovaries were at the edge of the abdominal treatment volume
    • in 68% of those whose ovaries were entirely within the treatment volume

     

Testis:

Even when the area is shielded or excluded, whole abdominal RT is associated with a risk of:
  • Testicular damage with elevated FSH
  • Azoospermia
  • Severe oligospermia
  • Pregnancy Outcome

    Female patients who had RT have a higher risk of premature births.

    • Underdevelopment of uterine wall - thinner wall and less vascular.
    • Surgical adhesions
    • Increased incidence of uterine anomalies.

     

    RT is also associated with:

    • Lower birth weight babies
    • Increased risk of perinatal deaths

     

    No significant increase of congenital anomaly or Wilms tumor in offspring of WT survivors.

     

    Secondary Neoplasms

    • Cumulative incidence of 10 years following diagnosis is 1% and 1.6% at 15 years.
    • Recent update indicates significant risk of second malignancies.
    • Patients who received both adriamycin and higher-dose radiation (35Gy) had the highest relative risk of 36.3%.
    • Early screening colonoscopy at the age of 35 years should be considered.

     

     

    Late Effects associated with pulmonary RT:

    Musculo-skeletal Growth

    Mild scoliosis and mild asymmetry of all musculoskeletal structures in the RT field can occur due to reduced growth of bone and paravertebral muscles

     

    There will be a decrease in sitting height and modest decrease in standing height after flank or abdominal RT

     

    If the child is very young there may be a mild restrictive problem due to reduced growth of the chest wall and ribs

     

    In female children there may well be subsequent breast hypoplasia (under-development)

     

    Pulmonary

    Bilateral whole-lung RT is associated with decreased:

    • Total lung capacity
    • Vital capacity

     

    12 to 14 Gy has been shown to reduce total lung capacity and vital capacity to about 70% of predicted values (and even lower if the patient had also had thoracotomy)

     

    Airways are relatively unaffected

     

    Patients who have received pulmonary RT are especially at risk for chronic obstructive airways disease and lung cancer if they smoke

     

    Thyroid

    If the lungs are irradiated then the thyroid will receive some scattered radiation

     

    Increased risk of hypothyroidism, thyroid nodules and papillary carcinoma of the thyroid.

     

    Cardiac

    RT-related heart damage is rare in survivors of Wilms tumor treated using current protocols.

     

    Incidence of cardiomyopathy is higher in children when they have received mediastinal RT or RT that included the ventricles

     

    Congestive heart failure in children:

    • 1% when did not include whole-lung RT
    • 5.4% among those whose treatment did include whole-lung volume

     

    Doxorubicin and thoracic RT for Wilms tumor results in a risk of congestive heart failure of 4.4% at 20 years after diagnosis

     

    Secondary Neoplasms

    • Cumulative incidence of 10 years following diagnosis is 1% and 1.6% at 15 years
    • Recent update indicates significant risk of second malignancies
    • Patients who received both adriamycin and higher-dose radiation (35Gy) had the highest relative risk of 36.3%
    • For females increased risk of breast cancer after pulmonary RT

     

     

    Surgery Late Effects:

    After unilateral nephrectomy in childhood, the remaining kidney generally adjusts its function and size: “compensatory hypertrophy of the kidney”

    A year after treatment, the glomerular filtration rate and effective renal plasma flow are around 90% of normal values.

    Children treated with surgery and chemotherapy alone have close to normal values for GFR.

    Proteinuria and hypertension may occur in the long term after a combination of nephrectomy, chemotherapy and significant radiotherapy.

    In long term follow up, it is important to check:

    1. Blood pressure (a solitary kidney is associated with an increased risk of hypertension)
    2. Renal function using routine blood tests and urinalysis

    It is also important to warn about the prompt treatment of urinary tract infections (there is no increased risk, but infection could potentially damage remaining renal tissue).

    Patients who have had a nephrectomy should avoid activities that might damage the remaining kidney and it is reasonable to avoid contact sports.

    COG Survivorship guidelines: Keeping your single kidney healthy

     

    Chemotherapy Late Effects:

    Adriamycin (ADR)

    • Significant cardiac toxicity is very infrequent in Wilms tumor survivors.
    • Risk following ADR administration is greater when the myocardium has been irradiated in the course of either whole lung or abdominal irradiation.
    • Damage may be pericardial, myocardial, and/or vascular.

    Vincristine (VCR)

    • Peripheral Neuropathy

    COG survivorship guidelines: Kidney health after childhood cancer

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