Lin, Frank Y

ABSTRACT Background Decision‐making (DM) dynamics between adolescents and young adults (AYAs) with cancer, parents, and oncologists remain underexplored in diverse populations. We examined cancer treatment DM preferences among an ethnically and socioeconomically diverse group of AYAs and their parents. Procedure We surveyed AYAs with cancer ( n = 75) and their parents ( n = 52) participating in the Texas KidsCanSeq study. Among AYA‐parent pairs, we compared preferred and actual treatment DM roles. We explored associations among DM roles, having pediatric‐to‐adult care transition discussions, and clinical and sociodemographic characteristics. We report AYAs’ and parents’ preferences for involvement in shared decision‐making (SDM) with oncologists about cancer treatment. Results AYAs’ DM role preferences varied: 44% preferred to equally share DM with parents, 31% preferred AYA‐led DM, and 25% preferred parent‐led DM. Parents who preferred parent‐led DM had younger AYAs than parents who preferred equally shared DM ( p = 0.011). For actual DM, 48% of AYAs reported DM was equally shared, 24% reported DM was AYA‐led, and 28% reported DM was parent‐led. Most AYAs had their preferred role (73%). AYAs’ actual role did not significantly differ from their own or their parents’ preferences (both p > 0.05). Approximately half of AYAs reported recent pediatric‐to‐adult care transition discussions. AYAs’ DM preferences and participation in transition discussions did not significantly differ along clinical or sociodemographic characteristics (all p > 0.05). AYAs and parents perceived high importance across all aspects of SDM with oncologists. Conclusion In this diverse study population, AYAs desired engagement in treatment DM and SDM. Although specific role preferences varied, opportunities existed to increase discussion around pediatric‐to‐adult care transition.

Abstract Purpose: DROSHA, DGCR8, and DICER1 regulate miRNA biogenesis and are commonly mutated in cancer. Although DGCR8 and DICER1 germline pathogenic variants (GPV) cause autosomal dominant tumor predisposition, no association between DROSHA GPVs and clinical phenotypes has been reported. Experimental Design: After obtaining informed consent, sequencing was performed on germline and tumor samples from all patients. The occurrence of germline DROSHA GPVs was investigated in large pediatric and adult cancer datasets. The population prevalence of DROSHA GPVs was investigated in the UK Biobank and Geisinger DiscovEHR cohorts. Results: We describe nine children from eight families with heterozygous DROSHA GPVs and a diagnosis of pineoblastoma (n = 8) or Wilms tumor (n = 1). A somatic second hit in DROSHA was detected in all eight tumors analyzed. All pineoblastoma tumors analyzed were classified as miRNA processing–altered 1 subtype. We estimate the population prevalence of germline DROSHA loss-of-function variants to be 1:3,875 to 1:4,843 but find no evidence for increased adult cancer risk. Conclusions: This is the first report of DROSHA-related tumor predisposition. As pineoblastoma and Wilms tumor are also associated with DICER1 GPVs, our results suggest that the tissues of origin for these tumors are uniquely tolerant of general miRNA loss. The miRNA processing–altered 1 pineoblastoma subtype is associated with older age of diagnosis and better outcomes than other subtypes, suggesting DROSHA GPV status may have important clinical and prognostic significance. We suggest that genetic testing for DROSHA GPVs be considered for patients with pineoblastoma, Wilms tumor, or other DICER1-/DGCR8-related conditions and propose surveillance recommendations through research studies for individuals with DROSHA GPVs.