TEST:

Oncomine™ Childhood Cancer Research Assay

In this retrospective study, we analyzed a real-life cohort of Swedish patients with advanced ALK-positive NSCLC treated at the Karolinska University Hospital in Stockholm to evaluate survival outcomes and resistance mechanisms of ALK TKIs. This retrospective study included 150 patients treated with at least one line of ALK TKI (crizotinib, ceritinib, alectinib, brigatinib or lorlatinib), from January 2009 to December 2021. Patients with advanced ALK-positive NSCLC have prolonged survival after the introduction of ALK TKIs with a median OS that exceeds 5 years when ALK TKIs are used in the first-line setting. Re-biopsies during treatment are needed to enhance our understanding of resistance mechanisms and the tumor dynamics that develop during ALK TKI therapy and to increase individualized management of this disease within precision medicine.

In cases with intermediate degrees of staining, it is desirable to use a molecular technique to discern the state of the gene. NGS and MLPA show excellent agreement with FISH, however, cases with low levels of amplification or samples with low concentration of tumour cells, may show false negative results.

The variants found in NF1 and CDKN2A in two different patients were detected in the germline, confirming the diagnosis of a cancer predisposition syndrome. We have shown that the results of somatic testing can be used to identify those at risk of an underlying cancer predisposition syndrome.

Conclusions Overall, we detected biologically relevant molecular alterations in 42/58 (72%) of PECST and in 28/39 (72%) of PBT, most of which with clinical relevance, at the level of diagnosis, prognosis or therapy selection. A subset of the patients is already undergoing targeted therapy, mainly using BRAF or MEK inhibitors with good clinical response in general.

NGS-based genomic studies are useful and feasible in diagnosis and clinical management of pediatric sarcomas. Genomic characterization of these rare and heterogeneous tumors also helps in the search for prognostic biomarkers and therapeutic opportunities.

Germline variants in TP53 and RB1 were found in 5 of the 11 (45.5%) patients analyzed. Clinical variables and tumor histopathological characteristics were also collected and correlated with our molecular findings.

Molecular profiling by the OCCRA panel comprehensively addressed the most relevant genetic variants in gliomas of childhood and adolescence, as these tumors have specific patterns of molecular alterations, outcomes, and effectiveness to therapies.

Molecular profiling by the OCCRA® panel showed novel alterations in pediatric and adolescent EPNs, which highlights the clinical importance in identifying genetic variants for patients' prognosis and therapeutic orientation.

The genetic profiling based on a specific panel for children and adolescent cancer, including non-reported variants identification in patients diagnosed with OS in an unexpected age, is essential for a more accurate tumor profiling and the identification of risk groups. The investigation of mutations with clinical relevance can also contribute to a more precise therapeutic management. NGS strategy can lead into a better understanding about these questions.

Molecular profile investigation, based on NGS panel specific for pediatric tumors, can provide information about potential prognostic biomarkers for EPN. Thus, genomic profiling of childhood and adolescence EPN that appropriately integrate the clinical, radiologic, and histologic aspects of this tumor, is essential in order to define therapeutic strategies.