Risk of Second Cancer in Hodgkin Lymphoma Survivors and Influence of Family History

Abstract

PurposeAlthough advances in Hodgkin lymphoma (HL) treatment have led to improved disease-free survival, this has been accompanied by an increased risk of second cancers. We sought to quantify the second cancer risks and to investigate the impact of family history.Patients and MethodsUsing the Swedish Family-Cancer Project Database, we identified 9,522 individuals with primary HL diagnosed between 1965 and 2012. We calculated standardized incidence ratios and cumulative incidence of second cancer in HL survivors and compared the standardized incidence ratios of lung, breast, colorectal, and all second cancers in HL survivors with and without a site-specific family history of cancer. Interactions between family history of cancer and HL treatment were evaluated under additive and multiplicative models.ResultsOverall, the risk of a second cancer in HL survivors was increased 2.39-fold (95% CI, 2.29 to 2.53). The 30-year cumulative incidence of breast cancer in women diagnosed with HL at younger than 35 years of age was 13.8%. We observed no significant difference in cancer risk over successive time periods. The risk of all second cancers was 1.3-fold higher for HL survivors with a first-degree relative with cancer (P < .001), with 3.3-fold, 2.1-fold, and 1.8-fold differences shown for lung, colorectal, and breast cancers, respectively. Moreover, a greater than additive interaction between family history of lung cancer and HL treatment was shown (P = .03).ConclusionHL survivorship is associated with a substantive risk of a second cancer. Notably, the risk is higher in individuals with a family history of cancer. This information should be used to inform risk-adapted therapy and to assist in screening to reduce long-term morbidity and mortality in patients with HL.

Second primary cancers in non‐Hodgkin lymphoma: Family history and survival

“…We hypothesize that family history of particular cancer may increase the risk of that cancer to appear as SPC; thus, a family history of breast cancer may increase the frequency of breast cancer as SPC in NHL patients. There is previous evidence on increased risk of SPC associated with family history in survivors of Hodgkin lymphoma and multiple myeloma . We further hypothesized that mortality of patients with SPC may be influenced by the type of SPC, which is in‐line with distinct mortality differences known for first primary cancers .…”

“…There is previous evidence on increased risk of SPC associated with family history in survivors of Hodgkin lymphoma and multiple myeloma. 18,19 We further hypothesized that mortality of patients with SPC may be influenced by the type of SPC, which is in-line with distinct mortality differences known for first primary cancers. 20,21 While family history may increase the numbers of SPCs we wanted, in addition, to test whether it also interferes with survival in NHL patients.…”

“…Previous evidence along the same lines was reported for rarer cancers, Hodgkin lymphoma and multiple myeloma. 18,19 Family history and testing for genetic susceptibility offer a strategy for prevention of fatal SPC when taken at NHL diagnosis, and relevant advice could be given, for example, regarding lung cancer (smoking cessation), colorectal, prostate and skin cancers (screening) and stomach and bladder cancer (early signs).…”

Early‐stage Hodgkin lymphoma in the modern era: simulation modelling to delineate long‐term patient outcomes

“…The risk of anthracycline‐related cardiomyopathy and radiation‐related secondary malignancies varies across individuals, based on clinical factors, such as age at exposure, cumulative chemotherapy dose and radiation dose and field (Schaapveld et al , ; van Nimwegen et al , ). Susceptibility (van Leeuwen & Ng, ) to late effects also differs by the extent and distribution of disease, gender, genetic predisposition (Best et al , ; Blanco et al , ; Visscher et al , ; Sud et al , ), and by survivor health behaviours, such as smoking status (Castellino et al , ; Schaapveld et al , ; van Nimwegen et al , ). Further, data suggest that risk inferred from childhood cancer survivors may not be consistent with older age (>21 years) at exposure, arguing for further work on risk ascertainment referable to treated adults.…”

The impact of prior malignancies on second malignancies and survival in MM patients: a population-based study

“…1 These studies have a small number of patients that developed second malignancies, 49 and 59 patients, respectively. Underlying explanation for our findings, that a prior malignancy increases the risk of second malignancies in MM patients, could include genetic susceptibilities, [17][18][19][20][21][22][32][33][34][35] immunosuppression, [36][37][38] and therapy-related cancers. 12,13,39 We found MM patients with a prior cancer diagnosis to have an increased risk of developing hematological malignancy, melanoma, nonmelanoma skin cancer, and respiratory malignancy compared with MM patients who did not.…”