Late Toxicity

Late toxicity of Hodgkin's lymphoma management is an important talking point in the management of this otherwise highly curable disease. Late toxicities are highly dependent on the treatment used for cure. Over the last twenty years radiotherapy has become used less frequently, for smaller regions or omitted completely.

Secondary Malignancies

Second malignancies are stochastic effects that have a latent period - haematological malignancies are more related to alkylating agents and occur within 10 years. Solid malignancies usually have a latent period over 10 years and are more commonly seen with radiotherapy.
The risk of second malignancy after radiation is dependent on:

  • Age at exposure - young women passing through puberty are at highest risk of breast cancer
  • Dosage - there seems to be
  • Time - increases with increasing time
  • Site - breast, lung and gastrointestinal tract are important sites of cancer induction in adults. In children the thyroid, bone and soft tissues are also of importance; whereas lung cancer seems to be less common.
  • Gender - women have a higher rate of second malignancies; even if breast cancer is excluded
  • Radiation Quality - high LET radiations are more damaging (eg. orthovoltage)
  • Chemotherapy - chemotherapy can increase the likelihood and range of second malignancies seen.
  • Genetic factors

Breast Cancer

Risk of breast cancer after mediastinal irradiation between 10-29 years of age is similar to BRCA+ women. The amount of breast exposed to higher doses is falling as field sizes decrease.

Thyroid Cancer

5% risk of thyroid cancer after 30 years in irradiated children. The risk falls as dose increases, possibly due to cell kill of thyroid cells rendering them unable to develop into a malignancy.

Lung Cancer

An uncommon cancer induced in children but more common in adults, particularly in those who smoke, have asbestos exposure or receive chemotherapy.

Other Late Effects


Cardiac toxicity is of particular importance after mediastinal irradiation. The effects seen are similar to normal cardiovascular disease, including coronary artery disease or valvular disease (although the latter is controversial). Fibrosis of the myocardium or pericardium may also occur and lead to poor cardiac function. Patients who have received radiation are more likely to have a fatal infarct due to widespread damage to the smaller vessels within the heart creating a poor reserve. Like second malignancies, there is a long latent time before these effects become apparent. There is increased risk of cardiac toxicity with increasing dose, the amount of heart irradiated, use of anthracyclines, younger age or exposure to other cardiac agents (eg. tobacco, dyslipidaemia).
The risks are:

  • Relative risk of 3.6 for myocardial infarction
  • Relative risk of 4.9 for congestive cardiac failure (8% risk with radiation + anthracycline therapy)

Aleman B et al (2007) Blood 109 1878-1886


Becoming less common with newer chemotherapy regimens; radiotherapy is less commonly used in the pelvis and has minimal effect if this is not done.

Growth Restriction

Doses of under 30 Gy appear to have minimal effect on the growth of developing humans over 10.

Screening for Late Toxicity

  • Breast screening recommendations vary; mammograms after the age of 40 are a common recommendation
  • Cardiac screening is recommended every 5 years for low risk patients and more frequently if chemotherapy is used as well.