Mortality

Several studies of large cohorts of survivors have reported early mortality among individuals treated for childhood cancer, compared with age- and sex-matched general population controls. Relapsed/refractory primary cancer remains the most frequent cause of death, followed by excess cause-specific mortality from subsequent primary cancers, and cardiac and pulmonary toxicity.[28-33]

A CCSS study evaluated specific health-related causes of late mortality and excess deaths, compared with the general U.S. population to identify targets to reduce future risk.[33]

A CCSS study evaluated specific health-related causes of late mortality and excess deaths, compared with the general U.S. population to identify targets to reduce future risk.[33]

At a median follow-up of 29 years from diagnosis, the 40-year cumulative all-cause mortality rate was 23.3%, with 51.2% of deaths attributed to health-related causes.

A CCSS study evaluated specific health-related causes of late mortality and excess deaths, compared with the general U.S. population to identify targets to reduce future risk.[33]

Survivors who were 40 or more years from diagnosis experienced 131 excess health-related deaths per 10,000 person-years (95% confidence interval [CI], 111–163). Excess deaths were most commonly related to cancer (absolute excess risk per 10,000 person-years, 54; 95% CI, 41–68), heart disease (27; 18–38), and cerebrovascular disease (10; 5–17).

A CCSS study evaluated specific health-related causes of late mortality and excess deaths, compared with the general U.S. population to identify targets to reduce future risk.[33]

Healthy lifestyle (assessed by smoking status, alcohol consumption, physical activity, body mass index, and absence of hypertension and diabetes) were each associated with a 20% to 30% reduction in health-related mortality, independent of other factors.

An analysis of the CCSS and Surveillance, Epidemiology, and End Results (SEER) Program data evaluated conditional survival. The study demonstrated a subsequent 5-year survival rate of 92% or higher among most diagnoses at 5 years, 10 years, 15 years, and 20 years. Among those who had survived at least 5 years from diagnosis, the probability of all-cause mortality in the next 10 years was 8.8% in the CCSS and 10.6% in the SEER study, with neoplasms accounting for cause of death in approximately 75% of survivors.[34]

Overall, the 20-year all-cause late mortality rate was 6.6%.

Compared with participants who were treated in the 1970s, patients who were treated with risk-stratified regimens in the 1990s experienced lower health-related late mortality (rate ratio: 1990s standard risk, 0.2; 1990s high risk, 0.3), which was comparable to the U.S. population (standardized mortality ratio [SMR]: 1990s standard risk, 1.3; 1990s high risk, 1.7).

Among 856 survivors, the 20-year late mortality cumulative incidence was highest after HSCT (13.9%; chemotherapy with CRT, 7.6%; chemotherapy only, 5.1%).

Mortality cumulative incidence decreased for survivors of HSCT diagnosed in the 1990s (8.5%) compared with the 1970s (38.9%), as did standardized mortality rates.

Self-reported health status was good to excellent for 88.2% of childhood AML survivors, regardless of treatment.

Most survivors did not experience any grade 3 to 5 chronic health conditions after 20 years (HSCT, 45.8%; chemotherapy with CRT, 23.7%; chemotherapy only, 27.0%).

A temporal reduction in chronic health conditions cumulative incidence was seen after HSCT (1970s, 76.1%; 1990s, 38.3%; P = .02), mirroring a reduction in total-body irradiation use.

Compared with non-Hispanic White children, hospitalization was 70% (hazard ratio [HR], 1.7) more common 5 or more years after diagnosis for American Indian and Alaskan Native children and 50% (HR, 1.5) more common for Black children.

Among survivors at 5 or more years from diagnosis, 2.3-fold to 3.6-fold statistically significant relative increases were observed for hospitalizations for specific conditions for American Indian and Alaskan Native children (HR, 2.3 for infection-related conditions; HR, 3.0 for hematologic-related conditions; HR, 2.6 for digestive-related conditions). The greatest increases were noted for mental health–related conditions (HR, 3.6), a pattern also noted for Black children (HR, 2.5).

Among 9,440 5-year childhood cancer survivors included in the analysis (median age at last follow-up, 27.5 years; median follow-up, 18.8 years), all-cause mortality (SMR, 7.6; 95% CI, 7.2–8.1) and health-related late mortality (SMR, 7.6; 95% CI, 7.0–8.2) was significantly higher than expected for U.S. mortality rates.

Among 3,407 adult participants who completed an on-campus assessment (median age at assessment, 35.4 years; median follow-up, 27.3 years), significant increases in late all-cause and health-related deaths were associated with the number of modifiable chronic health conditions, living in a U.S. census block associated with a high area deprivation index, and frailty.

Specific associations for excess health-related mortality included: one grade 2 modifiable chronic health condition (rate ratio [RR], 2.2; 95% CI, 1.1–4.4), two grade 2 modifiable chronic health conditions (RR, 2.5; 95% CI, 1.2–5.2), three grade 2 modifiable chronic health conditions (RR, 4.0; 95% CI, 1.9–8.4), area deprivation index in 51st to 80th percentile (RR, 9.2; 95% CI, 1.2–69.7), area deprivation index in 81st to 100th percentile (RR, 16.2; 95% CI, 2.1–123.7), and frailty (RR, 2.3; 95% CI, 1.2–4.1).

Among 12,469 participants (6,172 male and 6,297 female), including 4,402 from the SJLIFE cohort (median follow-up time since collection of first biospecimen, 7.4 years) and 8,067 from the CCSS cohort (median follow-up time since collection of the first biospecimen, 12.6 years), 641 (5.1%) carried cancer-predisposing variants.

Cancer-predisposing variants were significantly associated with an increased severity of SMNs (common terminology criteria for adverse events grade ≥4 vs. grade <4: odds ratio [OR], 2.15; 95% CI, 1.18–4.19).

SMN-related deaths occurred in 263 participants (2.1%), and other-cause deaths occurred in 426 survivors (3.4%).

At 10 years after the first biospecimen collection, the cumulative SMN-related mortality rate in carriers of cancer-predisposing variants was 3.7% (95% CI, 1.2%–8.5%) in SJLIFE and 6.9% (4.1%–10.7%) in CCSS. In comparison, the cumulative SMN-related mortality rate in noncarriers was 1.5% (1.0%–2.1%) in SJLIFE and 2.1% (1.7%–2.5%) in CCSS.

Carrying a cancer-predisposing variant was associated with an increased risk of SMN-related mortality (SJLIFE: HR, 3.40; 95% CI, 1.37–8.43; CCSS: HR, 3.58; 95% CI, 2.27–5.63).