Cumulative burden of 144 conditions, critical care hospitalisation and premature mortality across 26 adult cancers

Abstract

A comprehensive evaluation of the total burden of morbidity endured by cancer survivors remains unavailable. This study quantified the burden of 144 health conditions and critical care admissions across 26 adult cancers and treatment modalities in 243,767 adults. By age 60, top conditions ranked by fold difference (cumulative burden in survivors divided by cumulative burden in controls) were haematology, immunology/infection and pulmonary conditions. Patients who had all three forms of treatment (chemotherapy, radiotherapy and surgery) experienced a high cumulative burden of late morbidities compared with patients who received radiotherapy alone. The top five cancers with the highest cumulative burden of critical care admissions by age 60 were bone (12.4 events per 100 individuals [CI: 11.6-13.1]), brain (9.0 [7.5-10.5]), spinal cord and nervous system (7.2 [6.7-7.8]), testis (6.7 [4.9-8.4]) and Hodgkin lymphoma (4.4 [3.6-5.1]). Conditions that were associated with high excess years-of-life-lost were haematological conditions (9.6 years), pulmonary conditions (8.6 years) and immunological conditions or infections (7.8 years). As the population of cancer survivors continues to grow, our results indicate that it is important to tackle long-term health consequences through enacting data-driven policies.

Fig. 1. Cumulative burden of health conditions for cancer survivors and controls from the highest socioeconomic group based on the Index of Multiple Deprivation (IMD).

Health conditions were rank-ordered according to the fold difference at age 60 in individuals from the lowest socioeconomic group (see corresponding results for the lowest socioeconomic group in Supplementary Fig. 1). a Lollipop graphs depict the fold difference of cumulative burden in survivors versus controls for different age groups. The fold difference is annotated in each lollipop. Conditions that have a higher cumulative burden in survivors are shown on the right side within each age-specific plot, while conditions with a higher cumulative burden in controls are shown on the left. Where there are no events in either survivors or controls, the fold difference is not calculated. b Heatmaps depict cumulative burden counts per 100 individuals for survivors and controls. Each tile in the heatmap corresponds to cumulative burden count per 100 persons for each condition-specific outcome at different age groups. For example, a cumulative burden of 11.78 for venous thromboembolic disease in controls at age 80 corresponds to 11.78 events per 100 individuals. Cumulative burden values were separated into 10-quantiles (10 groups) resulting in quantile colour representation of the heatmaps. Source data are provided as a Source Data file.

Fig. 2. Cumulative burden of health conditions among cancer survivors at age 60 across 26 cancer types.

Circular dendrograms depict the fold difference of cumulative burden in survivors versus controls where conditions with a fold difference of ≥2 are shown. Fold difference for health conditions in patients with leukaemia, brain, breast and lung cancers are shown. The area of the nodes is proportional to the fold difference of each condition, and the conditions are ranked from the highest to lowest fold difference. For example, for brain cancer, neurological conditions exhibit the highest fold difference in cumulative burden in cancer survivors versus controls, and within this group, epilepsy has the highest fold difference. Dendrograms for all other cancer types are shown in the supplementary figures. Source data are provided as a Source Data file.

Fig. 3. Cumulative burden of health conditions among cancer survivors across organ systems.

Cumulative burden per 100 individuals according to follow-up time is shown. Circular dendrogram in the centre depicts the cumulative burden of health conditions at the organ system level at 5 years of follow-up. Within each organ system, cancer types are ranked from the highest to lowest burden. For example, when considering pulmonary conditions, patients who had lung cancer have the highest disease burden. The circular dendrogram only displays conditions with at least 20 events per 100 individuals. Area charts above and below the circular dendrogram display the cumulative burden of individual haematological conditions and endocrine conditions, respectively. Cumulative burden of individual conditions is shown according to follow-up time. Source data are provided as a Source Data file. Area graphs for other organ systems are provided as supplementary figures.

Fig. 4. Cumulative burden of health conditions among cancer survivors at age 60 by treatment type and chemotherapy agents.

Cumulative burden per 100 individuals is shown. Dendrograms depict the cumulative burden of conditions where the top hierarchy is organ system followed by a treatment type or b chemotherapy type. This allows the visualisation of the burden of health conditions for each treatment type or chemotherapy type ranked from the highest to lowest. The area of the nodes is proportional to the burden of health conditions within organ systems. Dendrograms depict the disease burden at the level of individual conditions by c treatment type or d chemotherapy type, and the conditions are ranked from highest to lowest burden. The area of the nodes is proportional to the burden of each condition. The treatment type dendrogram in c displays conditions with at least 5 events per 100 individuals. The chemotherapy agent dendrogram in d displays conditions with at least 10 events per 100 individuals. Source data are provided as a Source Data file.

Fig. 5. Multivariable logistic regression analysis of health condition outcomes among cancer survivors by different exposures.

a Treatment type. b Chemotherapy agent. Forest plots show data presented as odds ratios and error bars represent 95% confidence intervals. P values are indicated on the plot. The Wald test is employed. Source data are provided as a Source Data file. The number of patients within each treatment category were as follows: chemotherapy only (19,691), surgery only (80,491), radiotherapy only (20,662), chemotherapy and radiotherapy (12,399), chemotherapy and surgery (18,125), radiotherapy and surgery (25,909) and chemotherapy, radiotherapy and surgery (14,349). The number of patients within each chemotherapy category were as follows: alkylating agents (7795), anthracyclines (6858), antimetabolites (12,628), biological response modifiers (7852), hormonal agents (22,304), kinase inhibitors (1187), non-anthracycline antitumour antibiotics (727), plant alkaloids excluding vinca alkaloids (7707), platinum agents (9570), and vinca alkaloids (2821).

Fig. 6. Excess years of life lost (YLL) attributable to late morbidities in cancer survivors.

Circos plot depicts the difference in YLL between survivors who developed a health condition compared with survivors who did not develop a health condition. Bar chart depicts excess YLL for conditions grouped by organ system. Data are presented as excess years of life lost and error bars represent 95% confidence intervals. The number of cancer survivors was 243,767. Source data are provided as a Source Data file.