Radiotherapy, chemo, and second cancers: what is the risk in Hodgkin lymphoma?

This review explored the risk of developing a secondary cancer after being treated for Hodgkin lymphoma with chemotherapy and/or radiotherapy. The review concluded that intensified chemotherapy and radiotherapy are more effective but are associated with a greater risk of developing a secondary cancer. 

Hodgkin lymphoma (HL) is widely considered a curable disease. Most modern research focuses on reducing treatment intensity in order to reduce future problems. One potential negative outcome associated with HL treatment is the development of a secondary cancer.

HL is usually treated with chemotherapy (chemo) with or without radiotherapy (RT). Previous studies suggest that some types of treatment may lead to an increased risk of developing a secondary cancer. 

This review included 16 studies comparing different HL treatments. Individual patient data from these 16 studies was used in this review. For each treatment comparison, the information from 3 to 6 studies was used. This included data from between 1101 and 2996 patients. The average length of follow up was between 6.7 and 10.8 years

Chemo alone versus chemo plus RT: Patients treated with chemo alone were 57% less likely to develop a secondary cancer compared to chemo plus RT. Patients treated with chemo plus RT had a greater progression free survival rate (time from treatment to disease progression). However, the difference was not statistically significant. There was no difference in overall survival rates (time from treatment to death from any cause) between the two groups.

Involved-field RT vs. extended-field RT: There was no difference in progression free survival or overall survival between the two groups. Smaller radiation field (involved-field) did not decrease the risk of developing a secondary cancer.

Low dose RT vs. high dose RT: There was no difference in progression free survival or overall survival between the two groups. A lower dose of RT did not decrease the risk of developing a secondary cancer.

Fewer chemo courses vs. more chemo courses: There was no difference in progression free survival or overall survival between the two groups. Fewer courses of chemotherapy did not decrease the risk of developing a secondary cancer.

Dose-intensified vs. ABVD-like chemo: Follow-up in this comparison was too short to determine the effect of dose-intensified chemo on the risk of developing future solid tumors. Secondary blood cancers develop earlier and could be compared. Secondary acute leukemias were higher in patients treated with dose-intensified treatment. The 8-year progression free survival rate of dose-intensified chemo was 75% compared to 69% for ABVD-like chemo (adriamycin, bleomycin, vinblastine, dacarbazine). Dose-escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone) increased survival compared to ABVD-like chemo. 

The review concluded that receiving radiotherapy is associated with an increased risk of secondary cancer, and acute myeloid leukemia is more common in patients treated with intensified chemotherapy. 

The authors note that some studies are older, and modern radiotherapy techniques may not be as harmful as those used in these studies. For some of the comparisons, such as involved-field RT versus extended-field RT and low-dose versus high-dose RT, the evidence was not sufficient to make a conclusion about the risk of secondary cancers.