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Background For most adolescent and young adult (AYA) cancers, age-specific molecular features are poorly understood. SPECTA, an academic translational research infrastructure for biomaterial collection and molecular analysis, will explicitly recruit AYA patients and will therefore collect empirical data to bridge the molecular gap between pediatric and adult oncology. Trial Design The initial pilot study, activated in February 2019 across Europe, will recruit 100 patients aged 12-29 years with newly diagnosed or relapsed high-grade gliomas and high-grade bone and soft tissue sarcomas. The primary objective of the pilot is to determine feasibility and recruitment rates. Formalin-fixed tumor tissue, whole blood and clinical data from study participants will be prospectively collected; the biomaterial will be stored centrally at the Integrated BioBank of Luxembourg (IBBL). Whole exome sequencing (WES) of matched tumor and blood, and tumor RNA sequencing and DNA methylation profiling will be performed at the German Cancer Research Center (DKFZ), Heidelberg. Virtual central pathology review of scanned diagnostic slides will be undertaken by an international expert panel, and diagnostic material returned to the participating centers. A multidisciplinary molecular tumor board will release a clinically validated report to referring clinicians within 4-6 weeks after biopsy. SPECTA-AYA constitutes a major opportunity to gain knowledge about the tumor biology of this unique age group. It incorporates notable innovative aspects: AYA specificity, pan-European academic collaboration, centralized biobanking, comprehensive molecular profiling, and virtual central pathology review, among others. SPECTA-AYA will help untangle the tumor particularities of AYAs with cancer and aims to improve their access to novel drugs and personalized medicine. Legal entity responsible for the study EORTC (European Organisation for Research and Treatment of Cancer). Funding Walgreens Boots Alliance. Disclosure W. Van der Graaf: Research grant / Funding (self): Novartis; Honoraria (institution), Advisory / Consultancy: Bayer. F. Bielle: Research grant / Funding (self), Shareholder / Stockholder / Stock options, Spouse / Financial dependant: Celgene; Research grant / Funding (self), Shareholder / Stockholder / Stock options, Spouse / Financial dependant: Crossject; Research grant / Funding (self), Shareholder / Stockholder / Stock options, Spouse / Financial dependant: Sanofi; Research grant / Funding (self), Shareholder / Stockholder / Stock options, Spouse / Financial dependant: AbbVie. M. Preusser: Honoraria (self): Bayer; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Novartis; Honoraria (self): Gerson Lehrman Group (GLG); Honoraria (self): CMC Contrast; Honoraria (self): GlaxoSmithKline; Honoraria (self): Mundipharma; Honoraria (self): Roche; Honoraria (self): Astra Zeneca; Honoraria (self): AbbVie; Honoraria (self): Lilly; Honoraria (self): Medahead; Honoraria (self): Daiichi Sankyo; Honoraria (self): Merck Sharp & Dohme. S. Frohling: Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Travel / Accommodation / Expenses: Eli Lilly; Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: PharmaMar; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Pfizer. M.G. McCabe: Advisory / Consultancy: Ipsen Pharma. All other authors have declared no conflicts of interest.

Background Melanoma subtypes are increasingly defined by genetic alterations (BRAF mutations in 50% and NRAS in 20% of cutaneous, c-Kit aberrations in acral and mucosal and GNA11 mutations in uveal melanomas. Targeted therapies such as vemurafenib in cutaneous and imatinib in mucosal melanomas have emerged. CMCs are a potential biomarker to assess response to treatment, monitor disease relapse and provide new targets for drug development. Molecular characterisation of CMCs may provide utility as a predictive biomarker to drug treatment. Methods The CellSearch marker dependent platform (Veridex, USA) enriches for CMCs utilising Melcam antibody for CMC capture and High Molecular Weight Melanoma associated Antigen (HMW-MAA) antibody for CMC detection. MART-1 was used as an additional CMC kit detection marker. The ISET marker independent platform (Isolation by Cell Size, Rarecells, France) enriches for CMCs based on cell size. Immunohistochemistry with CD45 and CD144 (leukocyte and endothelial cell markers) and S100 (melanoma marker) was performed to identify CMC characteristic staining and morphology. Results Twenty-three patients with metastatic disease were recruited prospectively (mucosal n = 13, uveal n = 10). CellSearch detected CMCs in 6/11mucosal (range 0-125, mean 21 median 1) and 7/10 uveal (range 0-510, mean 57 median 3) melanomas. MART-1 positive CMCs were detected in both subtypes but circulating tumour microemboli (CTM) were found only in mucosal melanomas. ISET detected CMCs in 10/12 mucosal (range 0-26, mean 4 median 2) and 7/10 uveal (range 0-19, mean 7 median 3) melanomas. CMCs were both S100+ and S100-. No CTM were detected by ISET. Comparison of the platforms in 20 patients (n = 10 of each mucosal and uveal melanomas) revealed variability in CMC detection between platforms (Spearman's correlation p = 0.17). Conclusions This is the first report of CMC detection by CellSearch in mucosal and uveal melanomas. Comparison with ISET revealed no relationship between numbers of CMCs detected in the same patients by each platform thus indicating significant CMC heterogeneity in CMC marker expression and size. Circulating tumour microemboli may indicate collective cell migration thus probing the biology of metastases formation. Disclosure G. Clack: Ownes stocks in Astra-Zeneca pharmaceuticals. A. Hughes: ownes shares in Astra-Zeneca pharmaceuticals. All other authors have declared no conflicts of interest.