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Hodgkin Lymphoma

 

Late Effects

 

Both chemotherapy and radiotherapy (RT) are associated with early and long term side effects in Hodgkin lymphoma (HL) patients.

 

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 mantle RT.

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)

 

Combined chemotherapy and RT: 

  • Has improved survival rates very significantly
  • Though chemotherapy can increase the risk of RT induced toxicity - it has also enabled the RT dose and volume to be reduced and in many cases, RT can be omitted from therapy altogether

 

Treatment related long-term complications in HL:

Etiology

Long Term Effect

RT to neck/mantle field

 

Thyroid disease

  • Thyroid is very sensitive to the effects of RT

 

Hypothyroidism

 

Increased risk of thyroid cancer

 

Skeletal abnormalities:

  • Undergrowth and hyoplasia in region of RT
  • Clavicles and central chest likely to be underdeveloped in survivors who were treated as a young child with a mantle field
  • Risk of scoliosis as thoracic spine usually included in mantle field

 

Soft tissue abnormalities:

  • Patients may have under-development of breast tissue if this was included in the RT field

 

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

  • coronary artery disease
  • carotid artery stenosis and subsequent cerebrovascular event (stroke)

 

Cardiac disease:

  • RT can be associated with an early delayed pericarditis and long term pericardial fibrosis (used to be common when RT was delivered through anteriorly weighted beam arrangement)
  • The combination of RT can be associated with cardiomyopathy
  • Valvular disease has been described after moderately high dose mediastinal RT for HL

 

Pulmonary disease:

  • The combination of bleomycin and large RT fields from a mantle may combine to produce significant pulmonary fibrosis

 

Dental disease:

  • Standard mantle RT extended high enough to damage the parotid glands & cause xerostomia - with increased risk of dental decay
  • Mantle RT also affected development of teeth in mandible
  • RT to Waldeyer’s ring can affect development of teeth in a child

 

Second Cancers:

  • RT to mantle field in 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 of HL who had mantle RT and smoke are far more likely to develop lung cancer
  • RT and alkylating chemotherapy are both associated with an increased risk of secondary AML

 
RT to abdomen and pelvis

Non-functioning spleen

 

Infertility:

  • Gonads are very sensitive to RT and in combination with alkylating agents, HL patients are at risk of infertility

 

Gonadal failure:

  • Early menopause
  • Early onset for osteoporosis in women

 

Increased risk of second malignancy within RT field

  • Need early screening for colon cancer

 

Adriamycin chemotherapy

Cardiomyopathy

  • Dose dependent

 

Bleomycin chemotherapy

Pulmonary fibrosis

Alkylating agent chemotherapy

Secondary AML

 

Infertility

 

Splenectomy as part of a staging laparotomy

(or splenic RT)

 Increased risk of major sepsis

 

Childhood Cancer Survivor Study:

The Childhood Cancer Survivor Study published "Morbidity and mortality in long-term survivors of Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study" in Blood 2011 Feb 10; 117:1806 (Castellino SM et al).

Of 2742 survivors of HL in the current study, 96% were tracked via the National Death Index and 70% responded to a survey.

Initial therapy:

  • 76% had a splenectomy
  • 61% had RT and chemotherapy
  • 33% had RT alone
  • 6% had chemotherapy alone

The overall survival at 30 years post diagnosis was 74% (20% lower than the general population).  Late relapse was the most frequent cause of death.

Causes of death were:

  • Recurrent HL
    • 35% died of recurrent HL more than 5 years from diagnosis
    • 17% died of recurrent HL more than 10 years from diagnosis
  • 23% died of second malignant neoplasms
    • Secondary leukemia most frequent SMN (28% of all SMNs)
    • Breast cancer (18% of all SMNs)
    • GI cancer (18% of all SMNs)
    • Lung cancer (13% of all SMNs)
  • 14% died of cerebrovascular/cardiac disease

The excess adverse risk of a SMN increased with time as did the risks for cardiac and cerebrovascular disease.

Serious chronic health problems were reported in 27% of patients (included grade 3 - 5 cardiovascular condition in 11%)

Ongoing COG Late Effects studies:

 

External Link:

Late Effects from Childhood/Adolescent Hodgkin Lymphoma Therapy at the National Cancer  Institute

 

 

 

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