December 23, 2015
3 min read

Second malignancy rates remain high among Hodgkin’s lymphoma survivors

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The risk for a second solid cancer among survivors of Hodgkin’s lymphoma did not improve among patients treated in the 1990s compared with those treated in earlier periods, according to study results published in The New England Journal of Medicine.

Further, survivors of Hodgkin’s lymphoma appeared to remain at risk for developing second solid cancers up to 40 years after treatment with curative intent.

Although survivors of Hodgkin’s lymphoma are known to be at increased risk for treatment-related subsequent neoplasms, researchers hypothesized that less-toxic treatments introduced in the late 1980s would mitigate that risk among patients treated between 1989 and 2000.

“On the basis of increased knowledge of late effects, the treatment of Hodgkin’s lymphoma has changed, with a trend toward the use of smaller radiation target volumes, lower radiation doses, and more effective, generally less toxic chemotherapy schemes,” Flora E. van Leeuwen, PhD, professor and division head of psychosocial research and epidemiology at Netherlands Cancer Institute in Amsterdam, and colleagues wrote. “However, the effect of these changes on the risk of a second cancer is still unknown.”

The researchers conducted an observational study of 3,905 Dutch patients (median age at treatment initiation, 28.6 years; 56.5% male) treated between 1965 and 2000 for Hodgkin’s lymphoma. All patients included in the analysis survived at least 5 years after treatment initiation, and 48.7% of the cohort (n = 1,902) received treatment between 1989 and 2000. Radiation therapy plus chemotherapy served as the most common treatment (60.5%; n = 2,364); other treatment options included radiation therapy only (27.3%; n = 1,068) and chemotherapy only (12.1%; n = 473).

According to the researchers, patients treated in the most recent treatment period (1989-2000) received smaller radiation target volumes, anthracycline-containing chemotherapy, lower doses of alkylating agents and less frequent infradiaphragmatic irradiation than those treated during earlier periods (1965-1976 and 1977-1988).

The researchers compared the risk for second cancers among patients with Hodgkin’s lymphoma with the expected risk based on cancer incidence in the general public.

After a median follow-up of 19.1 years (range, 5-47.2; median age at end of follow-up, 50.4 years), the researchers observed 1,055 second cancers in 908 patients. Overall, the risk for a second cancer appeared higher in survivors of Hodgkin’s lymphoma than in the general public (standardized incidence ratio [SIR] = 4.6; 95% CI, 4.3-4.9).

The risks for a second cancer were more than 10-fold greater in the survivors than general public for thyroid cancer, soft-tissue sarcoma, mesothelial and non-Hodgkin’s lymphoma. The SIRs were 5 to 10 times as high among survivors for cancers of the esophagus, stomach, pancreas and lung, as well as for leukemia.

Breast cancer contributed most to the overall absolute excess risk (20.4% excess risk of any second cancer), followed by lung cancer (20.2%), gastrointestinal tract cancer (19.7%) and non-Hodgkin’s lymphoma (13.1%).

The risk for a second cancer remained elevated in survivors compared with the general population for 35 years or more following treatment (SIR = 3.9; 95% CI, 2.8-5.4). The cumulative incidence of a second cancer in the study cohort at 40 years was 48.5% (95% CI, 45.4-51.5).

The cumulative incidence of second cancers did not differ among patients treated from 1965 to 1976, 1977 to 1988, or 1989 to 2000.
Researchers noted that although patients treated with supradiaphragmatic-field radiotherapy not including the axilla appeared at a lower risk for developing breast cancer than patients exposed to mantle-field irradiation (HR = 0.37; 95% CI, 0.19-0.72), the risk for breast cancer did not improve in the most recent study period compared with the earlier periods.

Further, a cumulative procarbazine (Matulane, Sigma Tau) dose of 4.3 g or greater per square meter of body-surface area — which has been associated with early menopause — vs. no chemotherapy appeared associated with a significant reduction in breast cancer risk (HR = 0.57; 95% CI, 0.39-0.84). However, this treatment increased risk for gastrointestinal cancers (HR = 2.7; 95% CI, 1.69-4.3).

“For patients with newly diagnosed Hodgkin’s lymphoma, the risks for both radiation-related and chemotherapy-related late toxic effects must be carefully balanced against the risk of failing to control the primary disease,” van Leeuwen and colleagues wrote. “Awareness of the increased risk for subsequent malignant neoplasm remains of great importance for survivors of Hodgkin’s lymphoma and for their physicians.” – by Cameron Kelsall

Disclosure: Van Leeuwen reports grant support from the Dutch Cancer Society during the conduct of the study. Please see the full study for a list of all other researchers’ relevant financial disclosures.