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Late Effects

Second Malignant Neoplasm



A second cancer or second malignant neoplasm (SMN) is defined as a histologically distinct second cancer that develops after the first.

There are several epidemiological studies which show that survivors of childhood cancer are at increased risk of a second primary cancer1,2.

Overall estimated cumulative probability is about 3% or so (3 – 10X risk of the general population) at 20 – 25 years after initial therapy.

Childhood cancer survivor cohort found that the absolute excess risk of SMN was 1.9 per 1000 patient years of follow up3.


Radiation Epidemiology Branch (REB) at the National Cancer Institute:

REB is involved in cancer survivorship research, particularly the role of radiation, chemotherapy, and hormonal treatments in second cancer risk.

To assess patterns and trends in the occurrence of second primary cancers, REB investigators collaborate with other researchers and monitor:

  • NCI’s Surveillance, Epidemiology, and End Results (SEER)
  • Cancer registry database

The overall objective is to identify cancer survivors who appear to be at increased risk for developing second primary cancers. These survivors can then be targeted for increased surveillance and primary and secondary prevention strategies.

REB has led the development of an interactive PC-based software module (“SIR”) to perform analyses of multiple primary cancers using NCI’s SEER database and used this new software tool to evaluate the risk of second cancers in SEER for childhood cancers.

The analysis module was added to the SEER*Stat program, a publicly available software package created by NCI that calculates SEER incidence, mortality, and survival rates (

The multiple primary cancer module calculates standardized incidence ratios by second cancer site, histology, treatment, sex, race, calendar year, age, time since diagnosis, and registry to:

  • Quantify risks for developing new malignancies among childhood cancer survivors in the general population
  • Identify links between particular types of first and subsequent cancer
  • Address the role of treatment

REB investigators evaluated the incidence of subsequent primary cancers in a SEER cohort of over 25,000 survivors of childhood cancer during 1973-2002.

Survivors were at nearly 6-fold risk of developing a new cancer relative to the general population with a cumulative incidence of second cancers after 25 years of 3.6%.

Most common were subsequent primary cancers of the:

  • Female breast
  • Brain
  • Bone
  • Thyroid gland
  • Soft tissues
  • Melanoma of the skin
  • Acute non-lymphocytic leukemia.

Because SEER includes large numbers of patients diagnosed in recent calendar years, researchers were able to evaluate the late effects associated with newer childhood cancer therapies. Preliminary data has shown that:

  • The risk for secondary leukemia increased with increasing calendar year of initial cancer diagnosis among survivors of bone or soft tissue sarcoma and non-Hodgkin lymphoma
  • Decreased among Hodgkin lymphoma survivors

Continued follow-up of this large childhood cohort will be critical to determine how the high relative risks seen for solid cancers through adolescence and early adulthood carry through into older ages, when incidence rates of carcinomas increase dramatically.




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