Asparaginase (ASP) therapy is associated with depletion of antithrombin (AT) and fibrinogen (FG).

IV PEG-ASP is associated with a significantly higher rate of allergic reactions than IM. The clinical preference for IV PEG-ASP may warrant re-evaluation.

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Purpose: The aim of our study was to compare whole-body diffusion-weighted MRI (WB-DWI-MRI) to fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the assessment of initial staging and treatment response in pediatric patients with Hodgkin lymphoma. Materials and Methods: This prospective study comprised 11 children with Hodgkin lymphoma. Whole-body DWI-MRI and FDG-PET/CT were obtained at baseline and after 2 cycles of chemotherapy. Two radiologists measured the apparent diffusion coefficient (ADC) values of the sites of involvement agreed upon in consensus and 1 nuclear medicine physician assessed the PET/CT. Reliability of radiologists’ ratings was assessed by intraclass correlation coefficients (ICC2,1). The sensitivity and positive predictive value (PPV) of DW-MRI relative to PET/CT were calculated for nodal and extranodal sites. The patients were staged according to both modalities. Association of treatment responses was assessed through the Pearson correlation between the ADC ratios and the change standardized uptake value (SUV) between baseline and follow-up. Results: There was good agreement between the raters for nodal and extranodal ADC measurements. The sensitivity and PPV of DW-MRI relative to PET/CT of nodal disease was 0.651 and 1.0, respectively, at baseline, and 0.697 and 0.885 at follow-up. The sensitivity and PPV of extranodal disease were 0.545 and 0.6 at baseline, and 0.167 and 0.333 at follow-up. Diffusion-weighted MRI determined correct tumor stage in 8 of 11 examinations. There was poor correlation between the ADC ratios and the absolute change in SUV between baseline and follow-up (0.348). Conclusion: Our experience showed that WB-DWI-MRI is inferior to PET/CT for initial staging and assessment of treatment response of Hodgkin lymphoma in pediatric patients.

Learning points► There should be a very low threshold to perform central nervous system imaging for worrisome or new neurological symptoms in patients with a history of acute leukaemia. ► An isolated cerebellar lesion is an unusual presentation of acute myeloid leukaemia relapse, thus confirmation of the diagnosis with tissue is necessary before initiating therapy.

Background: Over 4,300 children, adolescents, and young adults (CAYA) are diagnosed with cancer each year in Canada, 1/3 of whom have refractory/metastatic disease or will relapse. The PRecision Oncology For Young peopLE (PROFYLE) national, collaborative program, was created to provide equitable access to molecular profiling to identify novel targeted treatment options in a clinically relevant timeframe for all CAYA with hard-to-cure cancers in Canada. Design: Building upon 3 pre-existing regional precision oncology programs, PROFYLE now includes >20 institutions and has united an interdisciplinary team of experts, leaders, research teams, end-users and advocates from across Canada. The program has 14 domain specific nodes that are unified by a shared governance structure, and has harmonized biobanking, genomics, bioinformatics and reporting procedures. PROFYLE includes genomic and transcriptomic sequencing of paired germline and cancer fresh/frozen samples, proteomic analysis, and cancer modelling. Inclusion criteria: ≤29y; treatment at a Canadian center; diagnosis of a hard-to-cure cancer. Profiling results are reviewed by multidisciplinary Molecular Tumor Boards. A report including a results/recommendations summary of actionable findings (therapeutic, diagnostic, prognostic, cancer predisposition), potential targeted therapy options including available clinical trials, clarification of diagnosis, and genetic counseling recommendations is provided to the treating oncologist. Results: >1,000 CAYA are included from all of the provinces. Cancer diagnoses: 34% sarcoma, 16% leukemia/lymphoma, 16% CNS tumor, 11% neuroblastoma, 23% other. 17% of participants had a cancer-predisposing pathogenic/likely pathogenic germline variant, 45% had ≥1 potentially actionable somatic alteration, 22.6% had a therapeutically targetable somatic alteration. The most frequent classes of therapeutic alterations were RAS/MAPK (15%), cell cycle (14%), epigenetic (13%), RTK (12%), PI3K/AKT/mTOR (11%), DNA repair (9%), immune checkpoint (8%). Of clinicians who reported the utility of results, 55% indicated the findings were useful for clinical management. Future Directions: Collaborations with other national and international initiatives and data from this interdisciplinary, multi-institutional research program will inform the development of a framework to innovatively link research, clinical and system considerations with Canadian values relevant to multi-omic profiling and drug access for CAYA. In addition, we believe that with a comprehensive molecular view of cancer, PROFYLE will transform our understanding of underlying disease mechanisms, facilitate and improve diagnostic and prognostic indicators, and identify new therapeutic strategies and targets for CAYA patients with cancer. Citation Format: Stephanie A. Grover, Lesleigh Abbott, Jason N. Berman, Guillaume Bourque, Jennifer A. Chan, Avram E. Denburg, Rebecca J. Deyell, Conrad V. Fernandez, Cynthia Hawkins, Jan-Willem Henning, Meredith S. Irwin, Nada Jabado, Steven J. Jones, Philipp F. Lange, Paul Moorehead, Michael F. Moran, Daniel A. Morgenstern, Sapna Oberoi, Antonia Palmer, Shahrad R. Rassekh, Donna L. Senger, Adam Shlien, Daniel Sinnett, Caron Strahlendorf, Patrick J. Sullivan, Michael D. Taylor, Suzanne Vercauteren, Anita Villani, Stephanie Villeneuve, James A. Whitlock, David Malkin, on behalf of the PROFYLE Consortium. A pan-Canadian precision oncology program for children, adolescents and young adults with hard-to-cure cancer: The PRecision Oncology For Young peopLE (PROFYLE) Program. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4509.