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

Abstract

Second primary cancers (SPCs) account for an increasing proportion of all cancer diagnoses and family history of cancer may be a risk factor for SPCs. Using the Swedish Family‐Cancer Database on non‐Hodgkin lymphoma (NHL), we assessed the influence of family history on risk of SPCs and of SPCs on survival. NHL patients were identified from the years 1958 to 2015 and generalized Poisson models were used to calculate relative risks (RRs) for SPCs and familial SPCs. Among 14,393 NHL patients, a total of 1,866 (13.0%) were diagnosed with SPC. Familial risk of nine particular cancers was associated with risks of these cancers as SPCs, with twofold to fivefold increase in RRs. At the end of a 25‐year follow‐up period, the survival probability for persons with SPC was only 20% of that for patients without SPC; the hazard ratio for SPC was 1.59 (95% CI: 1.46–1.72). Survival could be predicted by the prognostic groups based on first cancers and HRs increase systematically with worse prognosis yielding a trend of p = 4.6 × 10−5. SPCs had deleterious consequences for survival in NHL patients. Family history was associated with increasing numbers of SPCs. Prevention of SPCs and their early detection is an important target in the overall strategy to improve survival in NHL patients. Counseling for avoidance of risk factors and targeted screening based on family history are feasible steps in risk reduction.

Immune checkpoint inhibitor treatment of a first cancer is associated with a decreased incidence of second primary cancer

“…Parameters tested were those published as risk factors for SPC, [1][2][3][4][5][6][7][8][9][10] age, sex, cancer types, metastatic disease at diagnosis as well as the application of immunotherapy and CC for the FPC. A backward selection procedure was used to determine the final model by removing non-significant variables (P > 0.05) one at a time.…”

“…The hazard ratio associated with the risk of SPC as compared with the general population are reported to range from 1.2 up to 30 depending on the FPC and its treatment. [1][2][3][4][5][6][7][8][9][10] We recently reported that the administration of ICIs, mostly PD-1/PD-L1 or CTLA4 antibodies for the FPC, was associated with a reduced risk of Time to 2nd cancer (months) A B Figure 1. Time to second primary tumor according to the treatment given for the first primary tumor.…”

“…Second primary cancers (SPCs) are increasingly diagnosed in the long term follow-up of children and adult patients cured of a first primary cancer (FPC). [1][2][3][4][5][6][7][8][9][10] In recent studies, over 10% of all incident cancers are SPCs. SPCs are among the important causes of early death in patients treated and cured of a first cancer, along with cardiovascular diseases and complications of the first cancer treatments.…”

“…SPCs are among the important causes of early death in patients treated and cured of a first cancer, along with cardiovascular diseases and complications of the first cancer treatments. [1][2][3][4][5][6][7][8][9][10] There are multiple risk factors for SPCs including genetic predispositions, carcinogens involved in the FPC (e.g. smoking, alcohol, sun exposure), lifestyle, overweight, low exercise.…”

“…The cytotoxic treatments given for the first cancer may also contribute to an excess risk of SPCs for cured patients. [1][2][3][4][5][6][7][8][9][10] This has been largely documented for secondary leukemias after alkylating agents, as well as for solid tumors in the irradiated field. 1,2,5,9 In recent years, immunotherapy for cancer using immune checkpoint inhibitors (ICIs), PD-1 or PD-L1 Ab as well as anti-CTLA-4 have transformed the management of patients with advanced cancers.…”