Second Primary Malignancies Among Pediatric and Young Adult Survivors of Differentiated Thyroid Cancer: Real-World Evidence
Main finding · SPM incidenceResult — go to the resultHazard ratio 1.50 95% CI 1.34–1.67Authors' conclusion
Over four decades of follow-up, SPMs were identified as a significant long-term risk among CAYA DTC survivors, frequently manifesting many years after the initial diagnosis. Both SPM occurrence and higher cumulative RAI doses were associated with increased mortality.
Study context
- Population
- Children, adolescents and young adults with differentiated thyroid cancer (DTC) diagnosed <40 years who survived ≥2 years, Clalit Health Services records, 1982–2022matched cohort
- Participants
- 5,267 vs 21,062
- Exposure
- Children, adolescents, and young adults (CAYA) DTC survivors vs matched cancer-free controls
- DTC survivorsn = 5,267
- Matched controlsn = 21,062reference
- Outcome
- SPM risk
Methodological detailsmatched 1:4 to cancer-free controls by birth year, sex, ethnicity and socioeconomic status
- Matched 1:4 to cancer-free controls by birth year, sex, ethnicity and socioeconomic status
Main finding
SPM incidence
Hazard ratio
1.50
95% CI 1.34–1.67
By group
DTC survivors
500 per 100,000 person-years
Matched controls
360 per 100,000 person-years
DTC survivorsvs Matched controls
HR 1.50 (95% CI 1.34–1.67)
As reported in the abstract
Observational data: associations, not effects.
Further findings
| Outcome | HR for SPM (CI) | |
|---|---|---|
| SPM by number of RAI treatments (vs RAI-untreated survivors)One RAI treatmentvs RAI-untreated | 1.91 (1.52–2.40) | |
| SPM by number of RAI treatments (vs RAI-untreated survivors)≥2 RAI treatmentsvs RAI-untreated | 2.73 (2.13–3.50) | |
| 0.20.5125HR for SPM (log scale) |
| Outcome | DTC survivors | P value |
|---|---|---|
| SPM latencyDTC survivors vs Controls | 13.8 years | P = 0.042 |
| Age at data retrieval, by age at DTC diagnosis (<20 vs 20-40 years) | P < 0.001 | |
| SPM rates, by age at DTC diagnosis (<20 vs 20-40 years) | P = 0.012 | |
| All-cause mortality | 2.8% |
- All-cause mortality — Mortality significantly higher among survivors who developed second primary malignancies (SPMs) and/or received radioactive iodine (RAI)
- p < 0.001
- SPM latency: Controls 15.1 years
- Age at data retrieval, by age at DTC diagnosis (<20 vs 20-40 years): Diagnosed <20 years median 33 years
- Age at data retrieval, by age at DTC diagnosis (<20 vs 20-40 years): Diagnosed 20-40 years median 47 years
- SPM rates, by age at DTC diagnosis (<20 vs 20-40 years): Diagnosed <20 years 5.6%
- SPM rates, by age at DTC diagnosis (<20 vs 20-40 years): Diagnosed 20-40 years 9.0%
- All-cause mortality: Controls 2.5%
All-cause mortality
- Mortality similar to matched controls
Original publication
Second Primary Malignancies Among Pediatric and Young Adult Survivors of Differentiated Thyroid Cancer: Real-World Evidence. Thyroid. Published 16 August 2026. doi:10.
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