Links to Mortality in Adult Survivors of Childhood Cancer Cheryl L. Cox, RN, PhD Department of Epidemiology and Cancer Control
Jan 17, 2016
Links to Mortality in Adult Survivors of Childhood Cancer
Cheryl L. Cox, RN, PhDDepartment of Epidemiology and Cancer Control
DISCLOSURES
• The authors have no financial or other interests to disclose
Mortality in adult survivors of pediatric malignancies• Life expectancy reduced by 28%
• Mortality risk modified by:– era of treatment– type of treatment– diagnosis– demographic characteristics
Excess late mortality causes• 15-fold ↑ in death from
subsequent neoplasms
• 7-fold ↑ in cardiac deaths
• 9-fold ↑ in pulmonary deaths
New links to late mortality risk?• Beyond cancer-related treatment?
• Beyond severity of chronic health conditions?
• What about health behavior, perceived health status, and health worries?
Sample
• Childhood Cancer Survivor Study
– Retrospective cohort (n=20,691)
– Diagnosed between 1970-1986
– Derived from 27 institutions in US and Canada
Sample Selection
Analysis
• Conditional logistic regression (all-cause and cause-specific mortality)– 3 models
• Medical care• Lifestyle and self-care behaviors• Health concerns/worries
• Models adjusted for:– Race/ethnicity, sex, marital status,
education, health insurance status, income, #/severity of chronic conditions
Sample Characteristics• Cases (n=445) vs. Controls
(n=7162):– Slightly older (30.5 vs. 28.8 years)– Less likely to be college grads (p=<0.001)– Less likely to be married (p=0.007)– More likely to have income <$20K
(p=<0.001)– More likely to be African-American
(p=0.03)– More likely to have grade 3 or 4 chronic
health condition (p=<0.001)
Common causes of death
• Malignant neoplasm (42%)
• Cardiac (20%)
• Pulmonary (7%)
All-Cause Mortality
Medical care OR (95% CI) P value
Health care received No 1.00 Yes 1.99 (1.19–3.32) 0.008 No. doctor visits/year 1 – 2 1.00 3 – 4 1.09 (0.73–1.62) 0.68 5 – 6 2.07 (1.40–3.06) <0.001 7 – 10 2.21 (1.44–3.40) <0.001 11 – 20 2.26 (1.44–3.55) <0.001 More than 20 3.87 (2.55–5.87) <0.001 General physical examination Less than 1 year ago 1.00 1 – 2 years ago 0.90 (0.66–1.24) 0.53 3 – 4 years ago 0.92 (0.60–1.42) 0.71 5 or more years ago 0.90 (0.61–1.34) 0.61 Never 1.22 (0.77–1.93) 0.41 Recency of dental care Less than 1 year ago 1.00 1 year ago or more 0.91 (0.71–1.16) 0.43 Recency of Pap Smear Less than 1 year ago 1.00 1 – 2 years ago 0.94 (0.60–1.45) 0.77 3 – 4 years ago 1.32 (0.66–2.63) 0.44 5 or more years ago 1.54 (0.64–3.70) 0.34 Never 1.16 (0.57–2.34) 0.68 Professional breast examination Less than 1 year ago 1.00 1 – 2 years ago 0.60 (0.36–0.98) 0.04 3 – 4 years ago 0.84 (0.38–1.83) 0.66 5 or more years ago 0.66 (0.22–2.02) 0.47 Never 1.43 (0.65–3.12) 0.37 Mammography (ever) No 1.00 Yes 1.32 (0.84–2.09) 0.23
Lifestyle and self-care behaviors
OR (95% CI) P value
Health worry and concern
Current health status Good or excellent 1.00 Fair or poor 1.98 (1.45–2.71) <0.001 Future health Concerned/ very concerned 1.54 (1.10–2.15) 0.01 Not very concerned /not concerned at all 1.00 Ability to have children Concerned /very concerned 1.05 (0.81–1.36) 0.71 Not very concerned /not concerned at all 1.00 Development/recurrence of cancer Concerned /very concerned 1.05 (0.82–1.36) 0.69 Not very concerned not concerned at all 1.00 Ability to obtain health insurance Concerned /very concerned 1.27 (0.99–1.62) 0.06 Not very concerned/ not concerned at all 1.00 Ability to obtain life insurance Concerned /very concerned 1.33 (1.03–1.71) 0.03 Not very concerned /not concerned at all 1.00
OR (95% CI) P value
Time to death
Time from Enrollment to Death Tertile 1
<5.7 years Tertile 2
5.7-8.9 years Tertile 3
>8.9 years
OR (95% CI) P value OR (95% CI) P value OR (95% CI) P
value Health care received No 1.00 Yes 1.34 (0.60, 2.97) 0.47 3.46 (1.32, 9.08) 0.01 3.17 (1.23, 8.15) 0.02 No. doctor visits/year 1 – 2 1.00 1.00 1.00 3 – 4 0.80 (0.36, 1.79) 0.59 1.23 (0.61, 2.48) 0.57 1.51 (0.81, 2.84) 0.20 5 – 6 1.05 (0.43, 2.51) 0.92 3.03 (1.55, 6.00) 0.001 2.72 (1.45, 5.06) 0.002 7 – 10 3.82 (1.82, 8.04) <0.001 2.68 (1.28, 5.58) 0.009 2.00 (0.91, 4.42) 0.08 11 – 20 2.45 (1.12, 5.35) 0.02 4.29 (1.92, 9.58) <0.001 2.08 (0.94, 4.47) 0.07 More than 20 5.64 (2.78, 11.43) <0.001 5.52 (2.64, 11.54) <0.001 4.88 (2.4, 9.93) <0.001 Alcohol consumption Never 1.00 Ever 0.48 (0.24, 0.96) 0.04 0.56 (0.29, 1.10) 0.09 0.69 (0.36, 1.30) 0.25 Physical activity 0 days per week 2.06 (1.18, 3.61)) 0.01 1.53 (0.90, 2.60) 0.12 2.13 (1.27, 3.56) 0.004 1 - 2 days per week 1.24 (0.62, 2.50) 0.55 2.61 (1.50, 4.53) <0.001 1.43 (0.79, 2.57) 0.24 3+ days per week 1.00 1.00 1.00 BMI Underweight 3.94 (1.48, 10.48) 0.006 2.40 (1.04, 5.54) 0.04 2.65 (1.15, 6.10) 0.02 Normal 1.00 1.00 1.00 Overweight 1.02 (0.61, 1.72) 0.93 0.97 (0.58, 1.62) 0.90 1.12 (0.69, 1.81) 0.65 Obese 0.69 (0.33, 1.43) 0.32 1.09 (0.60, 1.98) 0.78 1.34 (0.72, 2.50) 0.35 Current health status
Good or excellent 1.00 1.00 1.00 Fair or poor 3.19 (1.86, 5.47) <0.001 1.72 (0.99, 2.97) 0.05 2.28 (1.33, 3.90) 0.003 Future health Concerned to very concerned
1.88 (0.98, 3.59) 0.06 1.87 (1.03, 3.41) 0.04 1.40 (0.83, 2.38) 0.21
Not very concerned to not at all concerned
1.00 1.00 1.00
Chronic Health Conditions
0-2 vs. 3 or 4 3.55 (2.21, 5.69) <0.001 1.99 (1.30, 3.06) 0.002 2.22 (1.44, 3.41) <0.001 0-3 vs. 4 6.34 (3.65, 11.01) <0.001 2.67 (1.51, 4.76) <0.001 2.82 (1.56, 5.09) <0.001
Cause-SpecificMortality
Medical care
SMN
(n = 187)
Cardiac/Pulmonary
(n = 121)
Other
(n = 137)
OR (95% CI) P value OR (95% CI) P value OR (95% CI) P value
Health care received No 1.00 1.00 1.00 Yes 3.85 (1.37–10.82) 0.01 2.11 (0.72–6.14) 0.17 1.37 (0.61–3.07) 0.44 No. doctor visits/year 1 – 2 1.00 1.00 1.00 3 – 4 1.08 (0.61–1.89) 0.80 0.85 (0.31–2.34) 0.75 1.34 (0.65–2.80) 0.43 5 – 6 1.83 (1.03–3.25) 0.04 2.14 (0.89–5.11) 0.09 2.03 (0.94–4.38) 0.07 7 – 10 1.40 (0.71–2.77) 0.33 3.16 (1.38–7.24) 0.007 3.19 (1.36–7.47) 0.008 11 – 20 1.60 (0.81–3.16) 0.18 3.11 (1.23–7.86) 0.02 2.72 (1.08–6.86) 0.03 More than 20 2.57 (1.37–4.80) 0.003 4.56 (1.81–11.47) 0.001 6.58 (2.98–14.54) <0.001 General physical examination
Less than 1 year ago 1.00 1.00 1.00 1 – 2 years ago 0.90 (0.56–1.47) 0.68 0.80 (0.42–1.54) 0.51 1.04 (0.57–1.90) 0.90 3 – 4 years ago 1.27 (0.70–2.31) 0.43 0.67 (0.24–1.88) 0.45 0.68 (0.27–1.69) 0.40 5 or more years ago 0.93 (0.51–1.67) 0.80 0.61 (0.25–1.48) 0.27 1.08 (0.53–2.21) 0.83 Never 1.69 (0.87–3.31) 0.12 0.55 (0.19–1.61) 0.28 1.51 (0.61–3.73) 0.37 Recency of dental care Less than 1 year ago 1.00 1.00 1.00 1 year ago or more 0.92 (0.63–1.33) 0.64 0.91 (0.53–1.55) 0.72 0.91 (0.57–1.45) 0.67 Recency of Pap Smear Less than 1 year ago 1.00 1.00 1.00 1 – 2 years ago 1.05 (0.53–2.08) 0.89 1.97 (0.80–4.84) 0.14 0.26 (0.08–0.83) 0.02 3 – 4 years ago 2.34 (0.82–6.63) 0.11 1.78 (0.45–7.13) 0.41 0.39 (0.07–2.29) 0.30 5 or more years ago 2.02 (0.54–7.51) 0.29 1.95 (0.33–11.57) 0.46 1.34 (0.17–10.44) 0.78 Never 0.70 (0.16–3.09) 0.64 0.92 (0.19–4.30) 0.92 1.93 (0.58–6.36) 0.28 Professional breast examination
Less than 1 year ago 1.00 1.00 1.00 1 – 2 years ago 0.66 (0.30–1.47) 0.31 0.47 (0.15–1.44) 0.19 0.46 (0.17–1.26) 0.13 3 – 4 years ago 0.98 (0.32–2.97) 0.97 2.20 (0.54–9.03) 0.27 - 5 or more years ago 1.38 (0.34–5.63) 0.65 0.60 (0.06—6.38) 0.67 - Never 2.26 (0.51–10.03) 0.28 0.98 (0.18—5.37) 0.98 1.44 (0.41–5.08) 0.57 Mammography (ever) No 1.00 1.00 1.00 Yes 1.39 (0.68–2.62) 0.39 1.14 (0.41–3.22) 0.79 1.06 (0.40–2.85) 0.90
Lifestyle and self-care behaviors
3+ days per week 1.00 1.00 1.00 Testicular self-examination Regularly (once a month) 1.00 1.00 1.00 Occasionally 1.13 (0.40–3.16) 0.82 0.83 (0.06–11.04) 0.89 2.14 (0.54–8.51) 0.28 Rarely or never 0.88 (0.33–2.32) 0.79 7.65 (1.36–42.95) 0.02 1.39 (0.39–4.94) 0.61 Breast self-examination Regularly (once a month) 1.00 1.00 1.00 Occasionally 0.53 (0.28–0.99) 0.05 0.46 (0.19–1.02) 0.08 1.20 (0.47–3.06) 0.71 Rarely or never 0.68 (0.34–1.34) 0.26 0.33 (0.10–1.11) 0.07 0.56 (0.19–1.65) 0.30 BMI Underweight 2.55 (1.10–5.90) 0.03 3.23 (1.08–9.57) 0.03 2.97 (1.23–7.18) 0.02 Normal 1.00 1.00 1.00 Overweight 0.90 (0.58–1.39) 0.63 2.44 (1.34–4.46) 0.004 0.80 (0.44–1.42) 0.43 Obese 0.95 (0.53–1.70) 0.85 1.72 (0.78–3.75) 0.18 0.97 (0.48–1.93) 0.92
SMN
(n = 187)
Cardiac/Pulmonary
(n = 121)
Other
(n = 137)
Smoking Never 1.00 1.00 1.00 Past 0.89 (0.53–1.49) 0.65 1.41 (0.69–2.89) 0.35 0.95 (0.46–1.97) 0.90 Current 1.15 (0.71–1.87) 0.58 0.94 (0.45–1.96) 0.86 1.19 (0.64–2.20) 0.58 Alcohol consumption Never 1.00 1.00 1.00 Ever 1.04 (0.55–1.99) 0.90 0.55 (0.22–1.36) 0.20 0.40 (0.20–0.79) 0.008 Drinks per month None 1.00 1.00 1.00 1 to 4 0.93 (0.56–1.53) 0.77 1.02 (0.51–2.06) 0.95 0.55 (0.28–1.08) 0.08 5 + 0.84 (0.55–1.31) 0.44 0.87 (0.45–1.68) 0.68 0.50 (0.27–0.90) 0.02 Physical activity 0 days per week 1.36 (0.88–2.09) 0.16 1.84 (0.92–3.68) 0.08 2.41 (1.29–4.52) 0.006 1 – 2 days per week 1.13 (0.68–1.88) 0.64 2.07 (1.00–4.30) 0.05 2.37 (1.19–4.71) 0.01
OR (95% CI) P value OR (95% CI) P value OR (95% CI) P value
Health worry and concern
SMN
(n = 187)
Cardiac/Pulmonary
(n = 121)
Other
(n = 137)
OR (95% CI) P value OR (95% CI) P value OR (95% CI) P value
Current health status Good or excellent 1.00 1.00 1.00 Fair or poor 1.47 (0.88–2.46) 0.14 1.71 (0.87–3.33) 0.11 3.56 (2.05–6.18) <0.001
Future health Concerned/ very concerned
1.57 (0.96–2.58) 0.07 1.42 (0.68–2.98) 0.35 1.81 (0.92–3.53) 0.08
Not very concerned /not concerned at all
1.00 1.00 1.00
Ability to have children Concerned /very concerned
0.97 (0.66–1.43) 0.88 0.85 (0.48–1.51) 0.58 1.35 (0.82–2.20) 0.24
Not very concerned /not concerned at all
1.00 1.00 1.00
Development/recurrence of cancer
Concerned /very concerned
1.23 (0.84–1.81) 0.29 0.88 (0.51–1.53) 0.65 0.92 (0.57–1.48) 0.73
Not very concerned not concerned at all
1.00 1.00 1.00
Ability to obtain health insurance
Concerned /very concerned
1.08 (0.74–1.56) 0.70 1.28 (0.75–2.19) 0.37 1.84 (1.14–2.96) 0.01
Not very concerned/ not concerned at all
1.00 1.00 1.00
Ability to obtain life insurance
Concerned /very concerned 1.26 (0.86–1.85) 0.23 1.41 (0.82–2.43) 0.22 1.52 (0.93–2.48) 0.10 Not very concerned /not concerned at all
1.00 1.00 1.00
Limitations• Inaccuracy in death certificates
• ↓N limits power - cause-specific mortality
• Changes in covariates since baseline
• Young age/short observation period inadequate to identify associations observed later in life (e.g., tobacco use)
• Findings may not generalize to more recently treated patients
Conclusions• Behavior, self-reported health,
worries/concerns, and medical care use impact mortality
• Clear trends between mortality and surveillance/lifestyle behaviors may emerge as predictive as observation continues
• These associations are established in the general population, but occur much earlier in childhood cancer survivors
Implications
• Increase awareness among community care providers
• Target specific demographic groups for risk-based care (African-Americans, low income)
• Interventions to support increased surveillance among survivors
Contributors• Vikki Nolan, DSc (University of Memphis)• Wendy Leisenring, ScD (Fred Hutchison Cancer
Research Center)• Yutaka Yasui, PhD (University of Alberta)• Susan Ogg, MSN (St. Jude)• Ann Mertens, PhD (Emory University)• Joseph Neglia, MD (University of Minnesota)• Kirsten Ness, PhD (St. Jude)• Greg Armstrong, MD (St. Jude)• Les Robison, PhD (St. Jude)
Support: National Institute of Health grants U24 CA55727 (LL Robison, PI) and P30 CA21765 (R Gilbertson, PI), and the American Lebanese Syrian Associated Charities (ALSAC).