Complications
Thyroid abnormalities have been reported after treatment of HL (e.g., hypothyroidism, Graves' disease, benign nodularity, and thyroid cancer). The most common is hypothyroidism, occurring in approximately 50% of patients depending on the dose of radiotherapy administered.[174] Patients who have received radiotherapy to the neck should be asked about symptoms of hypothyroidism and have thyroid studies checked regularly.
The increased risk of secondary malignancies after treatment for HL is likely to be multi-factorial, with underlying genetic susceptibility, altered immune surveillance, and effects of radiotherapy and chemotherapy contributing. Alkylating agents increase the risk of secondary leukaemia. Fortunately this is a relatively rare occurrence with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine).[160][161]
The risk of secondary acute myeloid leukaemia and myelodysplastic syndrome is higher with escalated-dose BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone) compared with ABVD.[89][90]
One Cochrane review reported an increased risk of secondary acute leukaemias with consolidating radiotherapy compared with chemotherapy alone.[89]
The risk of secondary solid tumours (breast cancer and lung cancer in particular) is more closely related to radiotherapy and continues to rise with continued follow-up (as opposed to the risk of leukaemia).[162][163][164] Studies suggest that smaller radiation fields and lower doses may be associated with lower risk, but current evidence is inconclusive.[89][165][166]
Risk reduction (smoking cessation) and routine breast screening (mammography and breast MRI) are recommended.[33][167]
Cardiac disease is an important cause of increased morbidity and mortality after treatment of HL. The risk of pericardial disease is related to the dose and volume of the heart irradiated, and is a rare complication with modern doses and fields.[168]
The risk of valvular disease and coronary artery disease is higher in patients treated for HL, and occurs earlier in life, compared with the general population.[169][170][171] The effect of chemotherapy, particularly anthracycline-based regimens, on cardiac disease is unclear but it is likely to be a contributing factor.[172]
In patients treated with anthracyclines and/or mediastinal radiotherapy, aggressive management of cardiac risk factors is warranted. Using lower doses of radiotherapy and reducing the treatment volume (e.g., using involved-site radiotherapy [ISRT]) in modern combined-modality therapy regimens will probably decrease the risk of these complications.
Pulmonary toxicity is associated with both mediastinal radiotherapy and chemotherapy, particularly bleomycin. Approximately 20% of patients treated with ABVD develop bleomycin pulmonary toxicity, necessitating careful monitoring of diffusing capacity for carbon monoxide during treatment.[173] Bleomycin is usually discontinued if significant pulmonary toxicity arises during treatment. Mediastinal radiotherapy to post-chemotherapy tumour volumes reduces the volume of lung irradiated and is likely to decrease the risk of pulmonary complications.
Risk of ovarian dysfunction depends on the intensity of chemotherapy, dose of radiotherapy, and the age of the patient. Younger patients (<30 years) are less likely to develop ovarian dysfunction (with radiotherapy or chemotherapy) than older patients. Reduced recovery of ovarian function has been reported in older women (>35 years) receiving chemotherapy for advanced HL.[175] Patients should be counselled regarding the risk of infertility and options for fertility preservation.[176]
A PET/CT-adapted treatment approach (e.g., reducing the intensity of subsequent chemotherapy following a negative interim PET/CT scan) may minimise the risk of ovarian dysfunction in patients with advanced HL.[177]
Patients should be counselled regarding the risk of infertility and options for fertility preservation.[176]
Risk of sterilisation is lower with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) compared with escalated-dose BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone), although temporary azoospermia is common with ABVD.[178]
A PET/CT-adapted treatment approach (e.g., reducing the intensity of subsequent chemotherapy following a negative interim PET/CT scan) may minimise the risk of testicular dysfunction in patients with advanced HL.[177]
Radiotherapy can cause sterilisation, even at low doses (1-2 Gy). Much higher doses are required to impact the testosterone-producing Leydig cells, such that with adequate blocking, testosterone levels should not be affected. Patients should be counselled regarding the risk of infertility and options for fertility preservation.[176]
Patients with HL are known to have immune deficiencies at diagnosis, particularly with cell-mediated immunity. Following treatment with chemotherapy and/or radiotherapy, patients have a blunted antibody response to antigenic stimulation and are at increased risk of infections that are normally controlled with the cell-mediated immune system (varicella, pneumocystis, fungi). Patients need to be educated about their susceptibility to infection and need for prompt evaluation if concerning symptoms develop.
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