Kevin Oeffinger

There is limited information addressing the occurrence of esophageal strictures among the growing population of survivors of childhood cancer. Using the Childhood Cancer Survivor Study, we analyzed data from 17,121 5-year survivors and 3400 siblings to determine the prevalence and risk factors for esophageal strictures. Prevalence among survivors was 2.0% (95% confidence interval [CI]: 1.8–2.2%), representing a 7.6-fold increased risk compared to siblings. Factors significantly associated with risk of esophageal stricture included diagnosis of Hodgkin lymphoma, greater chest radiation dose, younger age at cancer diagnosis, platinum chemotherapy, and hematopoietic stem cell transplantation. While uncommon, survivors are at risk for therapy-related esophageal strictures.

BACKGROUND: Treatment characteristics such as cranial radiation therapy (CRT) do not fully explain adiposity risk in childhood acute lymphoblastic leukemia (ALL) survivors. This study was aimed at characterizing genetic variation related to adult body mass index (BMI) among survivors of childhood ALL. METHODS: Genetic associations of BMI among 1458 adult survivors of childhood ALL (median time from diagnosis, 20 years) were analyzed by multiple approaches. A 2-stage genome-wide association study in the Childhood Cancer Survivor Study (CCSS) and the St. Jude Lifetime Cohort Study (SJLIFE) was performed. BMI was a highly polygenic trait in the general population. Within the known loci, the BMI percent variance explained was estimated, and additive interactions (chi-square test) with CRT in the CCSS were evaluated. The role of DNA methylation in CRT interaction was further evaluated in a subsample of ALL survivors. RESULTS: In a meta-analysis of the CCSS and SJLIFE, 2 novel loci associated with adult BMI among survivors of childhood ALL (LINC00856 rs575792008 and EMR1 rs62123082; PMeta < 5E-8) were identified. It was estimated that the more than 700 known loci explained 6.2% of the variation in adult BMI in childhood ALL survivors. Within the known loci, significant main effects for 23 loci and statistical interactions with CRT at 9 loci (P < 7.0E-5) were further identified. At 2 CRT-interacting loci, DNA methylation patterns may have differed by age. CONCLUSIONS: Adult survivors of childhood ALL have genetic heritability for BMI similar to that observed in the general population. This study provides evidence that treatment with CRT can modify the effect of genetic variants on adult BMI in childhood ALL survivors.

Development of personalized, stratified follow-up care pathways where care intensity and setting vary with needs could improve cancer survivor outcomes and efficiency of health-care delivery. Advancing such an approach in the United States requires identification and prioritization of the most pressing research and data needed to create and implement personalized care pathway models. Cancer survivorship research and care experts (n = 39) participated in an in-person workshop on this topic in 2018. Using a modified Delphi technique-a structured, validated system for identifying consensus-an expert panel identified critical research questions related to operationalizing personalized, stratified follow-up care pathways for individuals diagnosed with cancer. Consensus for the top priority research questions was achieved iteratively through 3 rounds: item generation, item consolidation, and selection of the final list of priority research questions. From the 28 research questions that were generated, 11 research priority questions were identified. The questions were categorized into 4 priority themes: determining outcome measures for new care pathways, developing and evaluating new care pathways, incentivizing new care pathway delivery, and providing technology and infrastructure to support self-management. Existing data sources to begin answering questions were also identified. Although existing data sources, including cancer registry, electronic medical record, and health insurance claims data, can be enhanced to begin addressing some questions, additional research resources are needed to address these priority questions.

PURPOSE: As new evidence is available, the International Late Effects of Childhood Cancer Guideline Harmonization Group has updated breast cancer surveillance recommendations for female survivors of childhood, adolescent, and young adult cancer. METHODS: We used evidence-based methods to apply new knowledge in refining the international harmonized recommendations developed in 2013. The guideline panel updated the systematic literature review, developed evidence summaries, appraised the evidence, and updated recommendations on the basis of evidence, clinical judgement, and consideration of benefits versus the harms of the surveillance interventions while attaining flexibility in implementation across different health care systems. The GRADE Evidence-to-Decision framework was used to translate evidence to recommendations. A survivor information form was developed to counsel survivors about the potential harms and benefits of surveillance. RESULTS: The literature update identified new study findings related to the effects of prescribed moderate-dose chest radiation (10 to 19 Gy), radiation dose-volume, anthracyclines and alkylating agents in non-chest irradiated survivors, and the effects of ovarian function on breast cancer risk. Moreover, new data from prospective investigations were available regarding the performance metrics of mammography and magnetic resonance imaging among survivors of Hodgkin lymphoma. Modified recommendations include the performance of mammography and breast magnetic resonance imaging for survivors treated with 10 Gy or greater chest radiation (strong recommendation) and upper abdominal radiation exposing breast tissue at a young age (moderate recommendation) at least annually up to age 60 years. As a result of inconsistent evidence, no recommendation could be formulated for routine breast cancer surveillance for survivors treated with any type of anthracyclines in the absence of chest radiation. CONCLUSION: The newly identified evidence prompted significant change to the recommendations formulated in 2013 related to moderate-dose chest radiation and anthracycline exposure as well as breast cancer surveillance modality.

As treatment evolves and the population who survive childhood cancer ages and increases in number, researchers must use novel approaches to prevent, identify and mitigate adverse effects of treatment. Future priorities include collaborative efforts to pool large cohort data to improve detection of late effects, identify late effects of novel therapies, and determine the contribution of genetic factors along with physiologic and accelerated aging among survivors. This knowledge should translate to individual risk prediction and prevention strategies. Finally, we must utilize health services research and implementation science to improve adoption of survivorship care recommendations outside of specialized pediatric oncology centers.