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).