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Late Effects


Chemotherapy, radiotherapy (RT) and surgery are all associated with early and long term side effects in rhabdomyosarcoma (RMS) patients.

Multimodality therapy has improved cure rates significantly, but chemotherapy enhances RT induced toxicity. 

Rhabdomyosarcoma patients have a relatively high risk of significant late effects.

Side Effects from RT can be classified into three groups :

1. EARLY (during treatment and the first month after RT)

2. EARLY DELAYED (up to 6 months after RT)

  • Lhermitte's phenomenon (electric shock sensation radiating down the spine or into the limbs with flexion of the neck) due to transient demyelination of the thoracic cord sometimes seen after RT to thoracic spine.

3. LATE (90 days to many years after RT) 

  • Fibrosis and vascular changes occur with endothelial cell loss, proliferation, capillary occlusion, degeneration and hemorrhagic exudates. 
  • In children normal growth is affected with growth reduction and subsequent atrophy in the area treated.  The severity depends on:
    • Age of the child treated
    • Total dose and fractionation of RT
    • Concurrent chemotherapy increases the risk of RT induced side effects
    • Treatment volume/organ treated (the larger the area is that is treated, the greater the risk of late effects and some organs are more sensitive to RT than others)


RT related long-term complications in rhabdomyosarcoma:

Region treated with RT

Long Term Effect

RT to head and neck RMS


Neurocognitive problems:

  • Depends on the amount of normal brain included in the RT volume
  • Poor short term memory
  • Difficulty with executive function


  • Usually related to multiple long-term health problems and neurocognitive dysfunction

Hearing loss:

  • Direct RT related damage to the cochlea


  • Lens of the eye very sensitive to RT
  • May have other orbital late effects depending on RT field placement and dose to orbital structures

Pituitary and hypothalamic dysfunction:

Thyroid disease

Skeletal abnormalities:

  • Undergrowth (hypoplasia) in region of RT
  • Skeletal structures and soft tissues in RT field likely to be underdeveloped - for example, facial deformity is common after RT for rhabdomyosarcoma of maxillary antrum
  • Cosmetic surgery to repair defect in future can be very problematic (high dose RT is characterized by fibrosis and reduced blood supply with impaired healing after trauma or surgery to tissues within the previous RT field)


Skin changes:

  • Fibrosis of skin and subcutaneous tissues
  • Increased pigmentation
  • Telangiectasia over skin surface
  • Increased vulnerability to sun related damage
  • Increased risk of skin cancer

Vascular disease (early atherosclerosis and fibrosis within blood vessels) with increased risk of:

  • Cerebrovascular events if brain included in RT field
  • Carotid artery stenosis

Dental disease:

  • Damage the parotid glands causes xerostomia - with increased risk of dental decay
  • Development of teeth affected (short roots, abnormal enamel)

Second Cancers:

RT to abdominal and pelvic RMS

Small bowel toxicity:

  • Intestinal strictures and scarring
  • Episodes of intestinal obstruction
  • Malabsorption

Large bowel toxicity:

  • Rectal scarring and stricture
  • Telangiectasia and rectal bleeding

Bladder damage:

  • Scarring and contracture
  • Increased risk of bladder cancer (RT and cyclophosphamide)

Renal damage:

Gonadal failure:

  • Infertility Gonads are very sensitive to RT and in combination with alkylating agents, RMS patients (females and males) are at significantly increased risk of infertility
  • Males may require testosterone replacement therapy after high dose RT to groin/inguinal region
  • Women are at risk for early menopause and secondary early onset of osteoporosis

Musculoskeletal abnormalities:

  • Hypoplasia (undergrowth) leading to asymmetry and possible scoliosis of the lumbar spine
  • Early onset of osteoporosis
  • Early onset of osteoarthritis
  • Radionecrosis of hip joint if included in RT field
  • Increased risk of pelvic fracture

Increased risk of second malignancy within RT field

  • Need early screening for colon cancer
  • Increased risk of RT induced osteogenic sarcoma
RT to limb RMS

Musculoskeletal abnormalities:

  • Hypoplasia leading to limb length discrepancy after RT to growing child
  • Scarring of a portion of limb circumference may lead to lymphedema
  • Subsequent increased risk of cellulitis in limb affected by lymphedema
  • Reduced ability to heal after trauma or surgery
  • Damage to joints with reduced mobility
  • Increased risk of bone fracture

Vascular insufficiency:

  • After high dose RT there can sometimes be reduced vascular supply to limb (especially if a large portion of the limb circumference was treated) with ischemic pain and non-healing ulcers

Gonadal failure:

  • Treatment of tumors in the thigh may cause damage to testes
  • Infertility
  • May require testosterone replacement therapy after high dose RT to groin/inguinal region

Second Cancers:

RT to thoracic RMS

Cardiac disease:

  • RT can be associated with an early delayed pericarditis and long term pericardial fibrosis
  • The combination of RT and adriamycin chemotherapy increases the risk of cardiomyopathy
  • Valvular disease has been described after moderately high dose mediastinal RT

Pulmonary disease:

  • Lung RT for RMS pulmonary disease may cause significant pulmonary fibrosis

Skeletal abnormalities:

  • Undergrowth (hypoplasia) in region of RT causes chest wall deformity with subsequent restrictive pulmonary disease.  This may be severe if a large portion of the chest wall receives RMS type doses in a growing child
  • Significant risk of scoliosis if growing thoracic spine is treated to a moderately high dose
  • Spine may be shorter after RT (leads to reduced sitting height)

Thyroid disease:

  • Thyroid is very sensitive to the effects of RT
  • Lung RT is associated with significant scatter to the thyroid and risk of hypothyroidism and thyroid cancer

Benign osteochondromas of ribs:

  • Rarely if ever undergo malignant transformation

Second Cancers:

  • RT to the chest of an adolescent girl is especially likely to be associated with an increased risk of breast cancer in young adult women. Early screening is very important
  • Survivors who had lung RT and smoke are far more likely to develop lung cancer
  • RT is associated with an increased risk of secondary solid tumors such as sarcomas and AML


Chemotherapy related long-term complications in Rhabdomyosarcoma:

Chemotherapy Agent

Long Term Effect

Actinomycin D
  • Enhances RT toxicity
  • RT recall reaction
  • Skin hyperpigmentation

Alkylating agent


  • Hemorrhagic cystitis with long-term increased risk of bladder cancer
  • Infertility
  • Secondary AML




(also called Etoposide)

  • Secondary AML (short latency period)


Alkylating agent


  • Secondary AML
  • Infertility
  • GI toxicity and diarrhoea


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