Identifying causal relationships of cancer treatment and long-term health effects among 5-year survivors of childhood cancer in Southern Sweden.

Background: Survivors of childhood cancer can develop adverse health events later in life. Infrequent occurrences and scarcity of structured information result in analytical and statistical challenges. Alternative statistical approaches are required to investigate the basis of late effects in smaller data sets. Methods: Here we describe sex-specific health care use, mortality and causal associations between primary diagnosis, treatment and outcomes in a small cohort (n = 2315) of 5-year survivors of childhood cancer (n = 2129) in southern Sweden and a control group (n = 11,882; age-, sex- and region-matched from the general population). We developed a constraint-based method for causal inference based on Bayesian estimation of distributions, and used it to investigate health care use and causal associations between diagnoses, treatments and outcomes. Mortality was analyzed by the Kaplan-Meier method. Results: Our results confirm a significantly higher health care usage and premature mortality among childhood cancer survivors as compared to controls. The developed method for causal inference identifies 98 significant associations (p < 0.0001) where most are well known (n = 73; 74.5%). Hitherto undescribed associations are identified (n = 5; 5.1%). These were between use of alkylating agents and eye conditions, topoisomerase inhibitors and viral infections; pituitary surgery and intestinal infections; and cervical cancer and endometritis. We discuss study-related biases (n = 20; 20.4%) and limitations. Conclusions: The findings contribute to a broader understanding of the consequences of cancer treatment. The study shows relevance for small data sets and causal inference, and presents the method as a complement to traditional statistical approaches.

Development and Implementation of Survivorship Tools to Enable Medical Follow-Up After Childhood Cancer Treatment in Southern Sweden.

PURPOSE: Survival rates after childhood cancer have increased from 20% to 80% since the 1970s. The increased number of survivors emphasizes the importance of late effects and their monitoring. Late effects may have a strong impact on quality of life in survivors. The purpose of this study was to make key data in a quality registry available for direct clinical use, enabling health care professionals to perform efficient and appropriate long-term medical follow-up after childhood cancer treatment. METHODS: The population-based quality registry upon which this study is centered contains data on all individuals diagnosed with childhood cancer (diagnosed at 18 years of age or younger) in southern Sweden since January 1, 1970, and treatment data on 5-year survivors. Web tools, which were developed and implemented in a health care setting, generate a personalized treatment summary for each patient and enable risk group stratification of survivors. RESULTS: Generation of a personalized treatment summary and risk group stratification of survivors led to identification of women at risk for developing breast cancer as a consequence of childhood cancer treatment. Three novel cases of previously undiagnosed breast cancer were identified. CONCLUSION: The registry, together with the developed tools, enabled health care professionals to perform medical follow-up in this at-risk patient population.