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Table 4.

Multivariable HRs and 95% CIs for the development of second malignant neoplasms (SMN) in pediatric cancer patients 0 to 14 years old in Ontario, by time since primary diagnosis

All SMNSMN within 5 yearsSMN after 5 years
VariableHR (95% CI)PHR (95% CI)PHR (95% CI)P
Sex  0.97  0.51  0.65 
 Female 1.01 (0.74–1.36)  0.85 (0.52–1.38)  1.10 (0.74–1.63)  
 Male 1.00  1.00  1.00  
Age at primary diagnosis (years)  0.09  0.16  0.06 
 0–4 1.00      
 5–9 0.69 (0.46–1.03)  0.53 (0.26–1.07)  0.77 (0.47–1.26)  
 10–14 0.67 (0.44–1.04)  0.97 (0.53–1.78)  0.50 (0.28–0.89)  
Treatment era  0.03  0.10  0.10 
 1985–1989 1.00  1.00  1.00  
 1990–1994 0.86 (0.55–1.63)  0.83 (0.33–2.07)  0.87 (0.53–1.45)  
 1995–1999 1.55 (0.97–2.47)  2.18 (1.00–4.76)  1.18 (0.65–2.17)  
 2000–2004 1.68 (0.98–2.86)  1.73 (0.78–3.86)  1.65 (0.73–3.72)  
 2005–2008 1.95 (0.99–3.84)  1.73 (0.71–4.18)  7.80 (1.49–40.93)  
Type of primary cancer diagnosis  0.01  0.06  0.21 
 Leukemia 1.00  1.00  1.00  
 Lymphoma and reticuloendothelial 2.02 (1.13–3.62)  1.93 (0.80–4.64)  2.13 (0.98–4.64)  
 CNS 1.93 (0.98–3.80)  1.03 (0.36–2.91)  2.90 (1.15–7.31)  
 Sympathetic nervous system 1.44 (0.64–3.24)  0.74 (0.18–3.10)  2.03 (0.72–5.69)  
 Kidney tumors 0.61 (0.20–1.85)  0.47 (0.06–3.96)  0.62 (0.16–2.33)  
 Liver tumors 1.66 (0.34–8.08)  4.76 (0.82–27.49)  0.00 (0.00–0.00)  
 Bone tumors 4.69 (2.11–10.44)  4.88 (1.52–15.60)  3.82 (1.23–11.89)  
 Germ cell tumors 3.13 (1.03–9.50)  3.85 (0.91–16.23)  1.24 (0.13–11.67)  
 Soft tissue sarcoma 1.92 (0.85–4.31)  1.73 (0.52–5.75)  1.86 (0.62–5.59)  
 Not elsewhere specified 3.05 (1.17–7.94)  2.44 (0.65–9.15)  3.28 (0.81–13.37)  
Radiotherapy  <0.01  0.04  <0.01 
 No 1.00  1.00  1.00  
 Yes 2.35 (1.66–3.33)  1.82 (1.02–3.22)  2.72 (1.72–4.30)  
Alkylating dose (mg/m2 0.50  0.17  0.28 
 None 1.00  1.00  1.00  
 >0–<4,000 1.13 (0.64–2.01)  0.52 (0.14–1.88)  1.43 (0.74–2.76)  
 ≥4,000–<8,000 2.08 (0.76–5.71)  0.85 (0.10–7.09)  3.07 (0.93–10.06)  
 ≥8,000 2.05 (0.27–15.60)  7.73 (0.93–64.19)  0.00 (0.00–0.00)  
Anthracycline score  0.70  0.30  0.46 
 0 1.00  1.00  1.00  
 1 0.89 (0.49–1.64)  0.42 (0.15–1.20)  1.50 (0.69–3.26)  
 2 1.24 (0.71–2.16)  0.93 (0.41–2.10)  1.53 (0.70–3.33)  
 3 1.18 (0.68–2.03)  0.61 (0.26–1.43)  1.82 (0.87–3.78)  
Epipodophyllotoxin score  0.06  <0.01  0.71 
 0 1.00  1.00  1.00  
 1 1.41 (0.79–2.54)  1.65 (0.61–4.45)  1.28 (0.62–2.68)  
 2 1.11 (0.61–2.03)  0.66 (0.19–2.26)  1.47 (0.73–2.98)  
 3 1.87 (1.18–2.96)  3.74 (1.88–7.42)  1.10 (0.56–2.14)  
Platinum score  0.16  0.54  0.24 
 0 1.00  1.00  1.00  
 1 1.65 (0.84–3.26)  1.19 (0.34–4.14)  2.00 (0.88–4.58)  
 2 0.58 (0.20–1.67)  0.57 (0.12–2.62)  0.59 (0.13–2.63)  
 3 1.52 (0.81–2.87)  1.66 (0.66–4.21)  1.52 (0.63–3.66)  
HSCT type  0.11  0.94  0.02 
 None 1.00  1.00  1.00  
 Allogeneic related 2.45 (1.11–5.41)  1.37 (0.30–6.16)  3.50 (1.35–9.05)  
 Allogeneic unrelated 1.95 (0.73–5.19)  0.76 (0.10–5.99)  3.35 (1.06–10.55)  
 Autologous 0.90 (0.36–2.24)  1.28 (0.33–4.90)  0.79 (0.22–2.86)  
Surgery  0.20  0.04  0.84 
 No 1.00  1.00  1.00  
 Yes 0.77 (0.52–1.15)  0.52 (0.28–0.96)  1.06 (0.62–1.79)  
All SMNSMN within 5 yearsSMN after 5 years
VariableHR (95% CI)PHR (95% CI)PHR (95% CI)P
Sex  0.97  0.51  0.65 
 Female 1.01 (0.74–1.36)  0.85 (0.52–1.38)  1.10 (0.74–1.63)  
 Male 1.00  1.00  1.00  
Age at primary diagnosis (years)  0.09  0.16  0.06 
 0–4 1.00      
 5–9 0.69 (0.46–1.03)  0.53 (0.26–1.07)  0.77 (0.47–1.26)  
 10–14 0.67 (0.44–1.04)  0.97 (0.53–1.78)  0.50 (0.28–0.89)  
Treatment era  0.03  0.10  0.10 
 1985–1989 1.00  1.00  1.00  
 1990–1994 0.86 (0.55–1.63)  0.83 (0.33–2.07)  0.87 (0.53–1.45)  
 1995–1999 1.55 (0.97–2.47)  2.18 (1.00–4.76)  1.18 (0.65–2.17)  
 2000–2004 1.68 (0.98–2.86)  1.73 (0.78–3.86)  1.65 (0.73–3.72)  
 2005–2008 1.95 (0.99–3.84)  1.73 (0.71–4.18)  7.80 (1.49–40.93)  
Type of primary cancer diagnosis  0.01  0.06  0.21 
 Leukemia 1.00  1.00  1.00  
 Lymphoma and reticuloendothelial 2.02 (1.13–3.62)  1.93 (0.80–4.64)  2.13 (0.98–4.64)  
 CNS 1.93 (0.98–3.80)  1.03 (0.36–2.91)  2.90 (1.15–7.31)  
 Sympathetic nervous system 1.44 (0.64–3.24)  0.74 (0.18–3.10)  2.03 (0.72–5.69)  
 Kidney tumors 0.61 (0.20–1.85)  0.47 (0.06–3.96)  0.62 (0.16–2.33)  
 Liver tumors 1.66 (0.34–8.08)  4.76 (0.82–27.49)  0.00 (0.00–0.00)  
 Bone tumors 4.69 (2.11–10.44)  4.88 (1.52–15.60)  3.82 (1.23–11.89)  
 Germ cell tumors 3.13 (1.03–9.50)  3.85 (0.91–16.23)  1.24 (0.13–11.67)  
 Soft tissue sarcoma 1.92 (0.85–4.31)  1.73 (0.52–5.75)  1.86 (0.62–5.59)  
 Not elsewhere specified 3.05 (1.17–7.94)  2.44 (0.65–9.15)  3.28 (0.81–13.37)  
Radiotherapy  <0.01  0.04  <0.01 
 No 1.00  1.00  1.00  
 Yes 2.35 (1.66–3.33)  1.82 (1.02–3.22)  2.72 (1.72–4.30)  
Alkylating dose (mg/m2 0.50  0.17  0.28 
 None 1.00  1.00  1.00  
 >0–<4,000 1.13 (0.64–2.01)  0.52 (0.14–1.88)  1.43 (0.74–2.76)  
 ≥4,000–<8,000 2.08 (0.76–5.71)  0.85 (0.10–7.09)  3.07 (0.93–10.06)  
 ≥8,000 2.05 (0.27–15.60)  7.73 (0.93–64.19)  0.00 (0.00–0.00)  
Anthracycline score  0.70  0.30  0.46 
 0 1.00  1.00  1.00  
 1 0.89 (0.49–1.64)  0.42 (0.15–1.20)  1.50 (0.69–3.26)  
 2 1.24 (0.71–2.16)  0.93 (0.41–2.10)  1.53 (0.70–3.33)  
 3 1.18 (0.68–2.03)  0.61 (0.26–1.43)  1.82 (0.87–3.78)  
Epipodophyllotoxin score  0.06  <0.01  0.71 
 0 1.00  1.00  1.00  
 1 1.41 (0.79–2.54)  1.65 (0.61–4.45)  1.28 (0.62–2.68)  
 2 1.11 (0.61–2.03)  0.66 (0.19–2.26)  1.47 (0.73–2.98)  
 3 1.87 (1.18–2.96)  3.74 (1.88–7.42)  1.10 (0.56–2.14)  
Platinum score  0.16  0.54  0.24 
 0 1.00  1.00  1.00  
 1 1.65 (0.84–3.26)  1.19 (0.34–4.14)  2.00 (0.88–4.58)  
 2 0.58 (0.20–1.67)  0.57 (0.12–2.62)  0.59 (0.13–2.63)  
 3 1.52 (0.81–2.87)  1.66 (0.66–4.21)  1.52 (0.63–3.66)  
HSCT type  0.11  0.94  0.02 
 None 1.00  1.00  1.00  
 Allogeneic related 2.45 (1.11–5.41)  1.37 (0.30–6.16)  3.50 (1.35–9.05)  
 Allogeneic unrelated 1.95 (0.73–5.19)  0.76 (0.10–5.99)  3.35 (1.06–10.55)  
 Autologous 0.90 (0.36–2.24)  1.28 (0.33–4.90)  0.79 (0.22–2.86)  
Surgery  0.20  0.04  0.84 
 No 1.00  1.00  1.00  
 Yes 0.77 (0.52–1.15)  0.52 (0.28–0.96)  1.06 (0.62–1.79)  
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