The risk of developing a secondary cancer in patients treated for Hodgkin lymphoma

This review examined the risk of secondary cancer with different types of Hodgkin lymphoma treatment. The study concluded that combined modality treatment and more intense chemotherapy increase the risk of developing a secondary cancer, but also reduce the risk of early relapse.

Hodgkin lymphoma (HL) is widely considered a curable disease. Recent treatment has focused on reducing intensity to reduce the risk of getting a secondary cancer. However, less intense treatment may increase the risk of relapse. More research is needed to compare the risk of early relapse with the risk of a future secondary cancer. 

This review included 16 randomized controlled trials with a total of 9498 patients. All patents had newly diagnosed HL. The average length of follow-up was 7.4 years.

438 (4.6%) of patients experienced a secondary cancer. 276 (2.9%) of patients developed a solid tumor. 63 (0.7%) developed acute myeloid leukemia (AML). 96 (0.9%) patients developed a secondary non-Hodgkin lymphoma.

The probability of developing a secondary cancer was 23% 20 years after treatment.

Chemotherapy alone versus chemotherapy plus radiotherapy (combined modality treatment; CMT): 4.5% of patients treated with CMT developed a secondary cancer. 2.9% of patients treated with chemotherapy alone developed a secondary cancer. Patients treated with CMT, the more intense treatment, were more likely to develop a secondary cancer.

For patients with early-stage HL or those aged less than 50, the progression free survival time (time from treatment to disease progression) was significantly shorter for those treated with chemotherapy alone compared to patients treated with CMT.

Extended versus involved field radiotherapy: There was no significant difference in secondary cancer or survival rates between the two groups.

High dose versus lower dose radiotherapy: There was no significant difference in secondary cancer or survival rates between the two groups.

More versus fewer cycles of chemotherapy: There was no significant difference in secondary cancer or survival rates between the two groups.

Standard versus intensified chemotherapy: Standard chemotherapy is ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) treatment. Intensified chemotherapy includes Stanford V (doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, prednisone), escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) and others.

2.8% of patients who were treated with ABVD developed a secondary cancer. 3.5% of patients who were treated with the intensified chemotherapy developed a secondary cancer. This difference was not significant. However, patients treated with intensified chemotherapy were significantly more likely to develop AML specifically.

Patients treated with escalated BEACOPP had significantly better progression free survival rates and overall survival rates (time from treatment to death from any cause) compared to ABVD. Patients treated with the Stanford V had worse progression free survival compared to ABVD. There was no difference in progression free or overall survival between the other escalated treatments and ABVD.

The authors concluded that more intense chemotherapy regimens and combined modality treatment increase the risk of developing a secondary cancer, but these treatments also increase progression free survival times.

Solid tumors usually take longer to occur compared to secondary blood cancers, so longer follow-up times are needed to completely understand the rates of secondary solid tumors.