Secondary malignancies in non-Hodgkin lymphoma survivors: 40 years of follow-up assessed by treatment modality

Cancer Med. 2023 Feb;12(3):2624-2636. doi: 10.1002/cam4.5139. Epub 2022 Aug 17.


Background: Survivors of non-Hodgkin lymphoma (NHL) have increased secondary malignancy (SM) risk. We quantified this risk by patient and treatment factors.

Methods: Standardized incidence ratios (SIR, observed-to-expected [O/E] ratio) were assessed in 142,637 NHL patients diagnosed from 1975 to 2016 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Comparisons were made between subgroups in terms of their SIRs relative to respective endemic populations.

Results: In total, 15,979 patients developed SM, more than the endemic rate (O/E 1.29; p < 0.05). Compared with white patients, relative to respective endemic populations, ethnic minorities had a higher risk of SM (white O/E 1.27, 95% CI 1.25-1.29; black O/E 1.40, 95% CI 1.31-1.48; other O/E 1.59, 95% CI 1.49-1.70). Relative to respective endemic populations, patients who received radiotherapy had similar SM rates to those who did not (O/E 1.29 each), but irradiated patients had increased breast cancer (p < 0.05). Patients who received chemotherapy had higher SM rates than those who did not (O/E 1.33 vs. 1.24, p < 0.05) including more leukemia, Kaposi sarcoma, kidney, pancreas, rectal, head and neck, and colon cancers (p < 0.05).

Conclusions: This is the largest study to examine SM risk in NHL patients with the longest follow-up. Treatment with radiotherapy did not increase overall SM risk, while chemotherapy was associated with a higher overall risk. However, certain subsites were associated with a higher risk of SM, and they varied by treatment, age group, race and time since treatment. These findings are helpful for informing screening and long-term follow-up in NHL survivors.

Keywords: adverse effects; chemotherapy; non-Hodgkin lymphoma; radiation; secondary malignancy.

MeSH terms

  • Follow-Up Studies
  • Humans
  • Incidence
  • Lymphoma, Non-Hodgkin* / epidemiology
  • Neoplasms, Second Primary* / epidemiology
  • Risk
  • Risk Factors
  • Survivors