Abstract
Background: Although colorectal adenomas serve as prime target for colorectal cancer (CRC) surveillance in other high-risk
groups, data on adenoma risk after childhood cancer are lacking. We evaluated the risk of histologically confirmed colorectal
adenomas among childhood cancer survivors. A secondary aim was to assess CRC risk.
Methods: The DCOG-LATER cohort study includes five-year Dutch childhood cancer survivors and a sibling comparison group
(n ¼ 883). Colorectal tumors were identified from the population-based Dutch Pathology Registry (PALGA). We calculated cumulative incidences of adenomas/CRCs for survivors and siblings. For adenomas, multivariable Cox regression models were
used to evaluate potential risk factors. All statistical tests were two-sided.
Results: Among 5843 five-year survivors (median follow-up ¼ 24.9 years), 78 individuals developed an adenoma. Cumulative
incidence by age 45 years was 3.6% (95% confidence interval [CI] ¼ 2.2% to 5.6%) after abdominopelvic radiotherapy (AP-RT;
49 cases) vs 2.0% (95% CI ¼ 1.3% to 2.8%) among survivors without AP-RT (28 cases; Pdifference ¼ .07) and vs 1.0% (95% CI ¼ 0.3%
to 2.6%) among siblings (6 cases) (Pdifference ¼ .03). Factors associated with adenoma risk were AP-RT (hazard ratio [HR] ¼ 2.12,
95% CI ¼ 1.24 to 3.60), total body irradiation (TBI; HR ¼ 10.55, 95% CI ¼ 5.20 to 21.42), cisplatin (HR ¼ 2.13; 95% CI ¼ 0.74 to 6.07
for ; HR ¼ 3.85, 95% CI ¼ 1.45 to 10.26 for 480 mg/m2
; Ptrend ¼ .62), a hepatoblastoma diagnosis (HR ¼ 27.12, 95% CI ¼ 8.80 to 83.58), and family history of early-onset CRC (HR ¼ 20.46, 95% CI ¼ 8.10 to 51.70). Procarbazine was statistically
significantly associated among survivors without AP-RT/TBI (HR ¼ 2.71, 95% CI ¼ 1.28 to 5.74). Thirteen CRCs occurred.
Conclusion: We provide evidence for excess risk of colorectal adenomas and CRCs among childhood cancer survivors.
Adenoma risk factors include AP-RT, TBI, cisplatin, and procarbazine. Hepatoblastoma (familial adenomatous polyposisassociated) and family history of early-onset CRC were confirmed as strong risk factors. A full benefit-vs-harm evaluation of
CRC screening among high-risk childhood cancer survivors warrants consideration.
groups, data on adenoma risk after childhood cancer are lacking. We evaluated the risk of histologically confirmed colorectal
adenomas among childhood cancer survivors. A secondary aim was to assess CRC risk.
Methods: The DCOG-LATER cohort study includes five-year Dutch childhood cancer survivors and a sibling comparison group
(n ¼ 883). Colorectal tumors were identified from the population-based Dutch Pathology Registry (PALGA). We calculated cumulative incidences of adenomas/CRCs for survivors and siblings. For adenomas, multivariable Cox regression models were
used to evaluate potential risk factors. All statistical tests were two-sided.
Results: Among 5843 five-year survivors (median follow-up ¼ 24.9 years), 78 individuals developed an adenoma. Cumulative
incidence by age 45 years was 3.6% (95% confidence interval [CI] ¼ 2.2% to 5.6%) after abdominopelvic radiotherapy (AP-RT;
49 cases) vs 2.0% (95% CI ¼ 1.3% to 2.8%) among survivors without AP-RT (28 cases; Pdifference ¼ .07) and vs 1.0% (95% CI ¼ 0.3%
to 2.6%) among siblings (6 cases) (Pdifference ¼ .03). Factors associated with adenoma risk were AP-RT (hazard ratio [HR] ¼ 2.12,
95% CI ¼ 1.24 to 3.60), total body irradiation (TBI; HR ¼ 10.55, 95% CI ¼ 5.20 to 21.42), cisplatin (HR ¼ 2.13; 95% CI ¼ 0.74 to 6.07
for ; HR ¼ 3.85, 95% CI ¼ 1.45 to 10.26 for 480 mg/m2
; Ptrend ¼ .62), a hepatoblastoma diagnosis (HR ¼ 27.12, 95% CI ¼ 8.80 to 83.58), and family history of early-onset CRC (HR ¼ 20.46, 95% CI ¼ 8.10 to 51.70). Procarbazine was statistically
significantly associated among survivors without AP-RT/TBI (HR ¼ 2.71, 95% CI ¼ 1.28 to 5.74). Thirteen CRCs occurred.
Conclusion: We provide evidence for excess risk of colorectal adenomas and CRCs among childhood cancer survivors.
Adenoma risk factors include AP-RT, TBI, cisplatin, and procarbazine. Hepatoblastoma (familial adenomatous polyposisassociated) and family history of early-onset CRC were confirmed as strong risk factors. A full benefit-vs-harm evaluation of
CRC screening among high-risk childhood cancer survivors warrants consideration.
| Original language | English |
|---|---|
| Article number | djx266 |
| Pages (from-to) | 758-767 |
| Number of pages | 10 |
| Journal | Journal of the National Cancer Institute |
| Volume | 110 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jan 2020 |
Bibliographical note
Funding:This work was supported by the Dutch Cancer Society (grant
numbers DCOG2011-5027 and UVA2012-5517). Judith Kok
was appointed on a Flexible Onderzoeker in Opleiding (OiO)
grant awarded by the Academic Medical Center (AMC)
Executive Board to C. M. Ronckers/L. C. Kremer in 2012.
