Second malignancies are a stochastic effect - that is, they can occur after any radiation or chemotherapy dose but become more likely with increasing dose.
Paediatric patients are at particularly high risk for the development of second malignancies. This is impacted on by:
- The dose used (higher doses = more potential for second cancers; e.g. in Ewing sarcoma doses over 60 Gy were associated with higher rates of second malignancies)
- The volume treated (bigger volume = more potential for second cancer induction)
- The age of the patient (younger patients = more potential for second cancers)
- The presence of germline mutations in tumour suppressor genes (e.g. patients with retinoblastoma treated with radiotherapy have a 40% risk of second malignancy, often osteosarcoma)
- The site treated (CNS = meningioma, glioma; thorax = breast, lung)
- Other health factors (e.g. cigarette smoking)
- Systemic therapy (e.g. alkylating agents and myelodysplastic syndromes)
Long term follow up of patients treated with curative therapy for Hodgkin's lymphoma demonstrate that:
- 10% of patients will develop a second malignancy at 10 years
- 25% of patients will develop a second malignancy by 30 years
- This is far greater than the expected rate (< 10% at 30 years)
Specific second cancers include:
- Leukaemia (usually acute myeloid leukaemia) which is strongly associated with MOPP (10% risk at 10 years) but less strongly with ABVD (1% risk) or radiotherapy (non-significant increased risk); particularly extended field techniques. The outcome is usually fatal with 10% 2 year survival
- Non-Hodgkin's lymphomas are also increased in survivors of Hodgkin's lymphoma; the exact mechanism of this is unclear. About 1% of survivors develop NHL. The role of chemotherapy or radiotherapy is unclear, and it may simply be a risk of Hodgkin's lymphoma rather than its treatment.
- Breast cancer, which is strongly associated with mediastinal radiotherapy. The risk is highly age dependent. The risk of breast cancer alone after radiotherapy treatment is 35% for those under 20, 20% for those 20-30, and 3.5% for those > 30 at the time of diagnosis.
- Lung cancer is influenced by radiation, chemotherapy and smoking. The relative risk with radiation is about 10; it is higher for doses > 10 Gy. Chemotherapy related malignancies occur at an earlier time than radiation malignancies, with a relative risk of about 4. Finally, smoking is associated with a 10-15 fold increase in risk. It is essential that patients with Hodgkin's lymphoma avoid smoking to prevent their risk factors multiplying together.
- Sarcomas account for 5-10% of second malignancies. The risk is radiation dose related. Chemotherapy may play a smaller role.
- Thyroid cancers are rare second malignancies (1-3%) and are associated with radiotherapy.
- Gastrointestinal malignancies form 10% of second malignancies. They are increased with radiotherapy (relative risk 2) and chemotherapy (relative risk for combined treatment is 4).
- Mesothelioma and melanoma are also possible malignancies but remain rare overall.
Screening of patients for second malignancies
Screening should take into account the age an treatment site for the patient:
- Breast screening should begin 10 years after treatment, or at age 40
- Yearly bloods to detect early signs of myelodysplastic syndromes
- Consider low dose chest CT for lung cancer (controversial)
- Standard screening for other cancers