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 radiation therapy administered.[176] Patients who have received radiation therapy 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 multifactorial, with underlying genetic susceptibility, altered immune surveillance, and effects of radiation therapy and chemotherapy contributing. Alkylating agents increase the risk of secondary leukemia. Fortunately this is a relatively rare occurrence with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine).[162][163]
The risk of secondary acute myeloid leukemia and myelodysplastic syndrome is higher with escalated-dose BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) compared with ABVD.[89][90]
One Cochrane review reported an increased risk of secondary acute leukemias with consolidating radiation therapy compared with chemotherapy alone.[89]
The risk of secondary solid tumors (breast cancer and lung cancer in particular) is more closely related to radiation therapy and continues to rise with continued follow-up (as opposed to the risk of leukemia).[164][165][166] Studies suggest that smaller radiation fields and lower doses may be associated with lower risk, but current evidence is inconclusive.[89][167][168]
Risk reduction (smoking cessation) and routine breast screening (mammography and breast MRI) are recommended.[33][169]
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.[170]
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.[171][172][173] The effect of chemotherapy, particularly anthracycline-based regimens, on cardiac disease is unclear but it is likely a contributing factor.[174]
In patients treated with anthracyclines and/or mediastinal radiation therapy, aggressive management of cardiac risk factors is warranted. Using lower doses of radiation therapy and reducing the treatment volume (e.g., using involved-site radiation therapy [ISRT]) in modern combined-modality therapy regimens will likely decrease the risk of these complications.
Pulmonary toxicity is associated with both mediastinal radiation therapy 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.[175] Bleomycin is usually discontinued if significant pulmonary toxicity arises during treatment. Mediastinal radiation therapy to postchemotherapy tumor volumes reduces the volume of lung irradiated and likely decreases the risk of pulmonary complications.
Risk of ovarian dysfunction depends on the intensity of chemotherapy, dose of radiation therapy, and the age of the patient. Younger patients (<30 years) are less likely to develop ovarian dysfunction (with radiation therapy or chemotherapy) than older patients. Reduced recovery of ovarian function has been reported in older women (>35 years) receiving chemotherapy for advanced HL.[177] Patients should be counseled regarding the risk of infertility and options for fertility preservation.[178]
A PET/CT-adapted treatment approach (e.g., reducing the intensity of subsequent chemotherapy following a negative interim PET/CT scan) may minimize the risk of ovarian dysfunction in patients with advanced HL.[179]
Patients should be counseled regarding the risk of infertility and options for fertility preservation.[178]
Risk of sterilization is lower with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) compared with escalated-dose BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone), although temporary azoospermia is common with ABVD.[180]
A PET/CT-adapted treatment approach (e.g., reducing the intensity of subsequent chemotherapy following a negative interim PET/CT scan) may minimize the risk of testicular dysfunction in patients with advanced HL.[179]
Radiation therapy can cause sterilization, 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 counseled regarding the risk of infertility and options for fertility preservation.[178]
Patients with HL are known to have immune deficiencies at diagnosis, particularly with cell-mediated immunity. Following treatment with chemotherapy and/or radiation therapy, 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.
Use of this content is subject to our disclaimer