ediatric cancer is rare, with fewer than 10,000 solid tumors diagnosed in children annually in the United States 1. Previous studies interrogating germline predisposition broadly across pediatric cancer types have found heritable germline predisposition in 8-12% of patients. The yield of germline predisposition detected is dependent on the genes included for analysis and variant interpretation as well as the ascertainment biases found in each cohort. Iterative data are required to expand upon the understanding of susceptibility to pediatric cancer and determine the extent to which germline data may translate into clinical practice 2-7. Certain pediatric cancer diagnoses have well-established associations with germline mutations in specific genes and should automatically prompt clinical suspicion of a cancer predisposition, for example, retinoblastoma (RB1), pleuropulmonary blastoma (DICER1), optic pathway glioma (NF1), atypical teratoid/rhabdoid tumors (SMARCB1), small cell hypercalcemic ovarian tumors (SMARCA4), adrenal cortical tumors (TP53) and hypodiploid acute lymphoblastic leukemia (TP53) 8-10. Germline testing can also be critical for distinguishing between conditions like neurofibromatosis type 1 (NF1) and constitutional mismatch repair deficiency (CMMRD), which can be phenocopies of each other. For example, a child presenting with numerous café au lait spots and leukemia may have either of these conditions, but treatment and screening recommendations for the proband and family members will differ depending on the germline diagnosis 11. Besides the known associations of causal germline mutations, broad tumor-normal sequencing has revealed novel associations 9,12. While some of these findings likely represent population detection and do not play a role in the pathogenesis of the cancer in question 13 , other novel associations are likely causal. Population detection

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.

Background Cancer-related financial hardship can negatively impact financial well-being and may prevent adolescent and young adult (AYA) cancer survivors (ages 15–39) from gaining financial independence. This analysis explored the financial experiences following diagnosis with cancer among AYA survivors. Methods We conducted a cross-sectional, anonymous survey of a national sample of AYAs recruited online. The Comprehensive Score for Financial Toxicity (COST) and InCharge Financial Distress/Financial Well-Being Scale (IFDFW) assessed financial hardship (cancer-related and general, respectively), and respondents reported related financial consequences and financial coping behaviors (both medical and non-medical). Results Two hundred sixty-seven AYA survivors completed the survey (mean 8.3 years from diagnosis). Financial hardship was high: mean COST score was 13.7 (moderate-to-severe financial toxicity); mean IFDFW score was 4.3 (high financial stress). Financial consequences included post-cancer credit score decrease (44%), debt collection contact (39%), spending more than 10% of income on medical expenses (39%), and lacking money for basic necessities (23%). Financial coping behaviors included taking money from savings (55%), taking on credit card debt (45%), putting off major purchases (45%), and borrowing money (42%). In logistic regression models, general financial distress was associated with increased odds of experiencing financial consequences and engaging in both medical- and non-medical-related financial coping behaviors. Discussion AYA survivors face long-term financial hardship after cancer treatment, which impacts multiple domains, including their use of healthcare and their personal finances. Interventions are needed to provide AYAs with tools to navigate financial aspects of the healthcare system; connect them with resources; and create systems-level solutions to address healthcare affordability. Implications for Cancer Survivors Survivorship care providers, particularly those who interact with AYA survivors, must be attuned to the unique risk for financial hardships facing this population and make efforts to increase access available interventions.

Cell free DNA (cfDNA) and circulating tumor cell free DNA (ctDNA) from blood (plasma) are increasingly being used in oncology for diagnosis, monitoring response, identifying cancer causing mutations and detecting recurrences. Circulating tumor RB1 DNA (ctDNA) is found in the blood (plasma) of retinoblastoma patients at diagnosis before instituting treatment (naïve). We investigated ctDNA in naïve unilateral patients before enucleation and during enucleation (6 patients/ 8 mutations with specimens collected 5–40 minutes from severing the optic nerve) In our cohort, following transection the optic nerve, ctDNA RB1 VAF was measurably lower than pre-enucleation levels within five minutes, 50% less within 15 minutes and 90% less by 40 minutes.

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