For childhood cancer survivors, limited data are available on whether historical changes in therapeutic exposure have altered subsequent neoplasm (SN) risk. Researchers used the Childhood Cancer Survivor Study to evaluate the occurrence of SNs in 23,603 survivors who were diagnosed earlier than 21 years of age and have reached five years of survival. The researchers presented the study at the ASCO Annual Meeting.    

The researchers examined different eras (1970–1999) to determine cumulative SN incidence at 15 years from diagnosis and standardized incidence ratios (SIRs) for subsequent malignant neoplasms (SMNs).  

For the 365,757 per-years at risk, a total of 3,310 SNs were validated among 1,760 survivors, including 1,026 SMNs, 233 benign meningiomas, 1,855 non-melanoma skin cancers, and 196 classified as “other.” 

Exposure to therapeutic radiation decreased by treatment decade, from 77.3% in the 1970s to 57.5% in the 1980s and 42% in the 1990s, whereas the use of alkylating agents (41.5%, 53.6%, and 55.3%, respectively) and epipodophyllotoxins (2.1%, 13.6%, and 31.5%, respectively) increased. 

The cumulative incidence of SMNs at 15 years was lower for survivors diagnosed in the 1990s (1.6%; 95% confidence interval [CI] = 1.4–1.9) compared with those in the 1970s (2.3%; 95% CI = 2–2.7; p < 0.001). SIRs for SMNs declined significantly for survivors who were older (see Table 1 for breakdown of decade results). 

After adjusting for demographics and cancer diagnosis, the researchers determined that incidence rates declined every five-year era by 7% for SMNs (95% CI = 3–12; p = 0.001), 20% for non-melanoma skin cancers (95% CI = 14–25; p < 0.001), and 17% for meningiomas (95% CI = 8–27; p = 0.001). The researchers noted that the decline was at least partially attributable to changes in treatment exposure over time. 

The researchers concluded, “Although survivors remain at increased risk for SNs, risk is reduced for survivors diagnosed in more recent eras. Models suggest historical reductions in treatment exposure have contributed to the decreased risk.” 

Table 1. SIRs for SMNs According to Patient Age and Treatment Era at Primary Cancer Diagnosis

Age (years)

 1970-1974

1975-1979 

1980-1984 

 1985-1989

1990-1994 

1995-1999

p 

5-19 

 10.9

10.2 

 9.7

9.7 

10.2 

6.3 

0.077 

 20-29

 6.4

5.2 

5.0 

4.5 

3.6 

3.6 

0.002 

 30-39

 6.3

5.0 

5.5 

4.2 

2.7 

4.8 

0.006