Abstract
Advances in genomic technologies and the development of targeted therapeutics are making the use of precision medicine increasingly possible. In this study, we explored whether precision medicine can be applied for the management of refractory/relapsed pediatric solid tumors by discovering actionable alterations using targeted panel sequencing. Samples of refractory/relapsed pediatric solid tumors were tested using a targeted sequencing panel covering the exonic DNA sequences of 381 cancer genes and introns across 22 genes to detect clinically significant genomic aberrations in tumors. The molecular targets were tiered from 1 to 5 based on the presence of actionable genetic alterations, strength of supporting evidence, and drug availability in the Republic of Korea. From January 2016 to October 2018, 55 patients were enrolled. The median time from tissue acquisition to drug selection was 29 d (range 14–39), and tumor profiling was successful in 53 (96.4%) patients. A total of 27 actionable alterations in tiers 1–4 were detected in 20 patients (36.4%), and the majority of actionable alterations were copy number variations. The tiers of molecular alterations were tier 1 (clinical evidence) in 4 variants, tier 2 (preclinical evidence) in 8 variants, tier 3 (consensus opinion) in 2 variants, and tier 4 (actionable variants with a drug that is available in other countries but not in the Republic of Korea) in 9 variants. In one patient with relapsed neuroblastoma with ALK F1174L mutation and ALK amplification, lorlatinib was used in a compassionate use program, and it showed some efficacy. In conclusion, using a targeted sequencing panel to discover actionable alterations in relapsed/refractory pediatric solid tumors was practical and feasible.
Highlights
The outcome of pediatric cancer has improved substantially over the past few decades; the prognosis of relapsed/refractory pediatric cancer remains poor, and a new approach is needed to improve the outcome
Several recent studies exploring the feasibility of a precision cancer medicine approach in pediatric oncology have been published [3,4,5,6,7,8], and these demonstrated that the application of clinical genomics was possible and that a substantial number of patients had actionable genetic alterations, indicating the potential for targeted therapy
The possibility of the use of precision medicine for the management of refractory/ relapsed pediatric solid tumors was assessed through a prospective study using a targeted sequencing panel
Summary
The outcome of pediatric cancer has improved substantially over the past few decades; the prognosis of relapsed/refractory pediatric cancer remains poor, and a new approach is needed to improve the outcome. The tremendous progress in molecular biology has enhanced our understanding of tumorigenesis and cancer cell survival at the molecular level [1]. These advances have led to the development of targeted therapeutics, which directly inhibit the pathways responsible for tumorigenesis. Several recent studies exploring the feasibility of a precision cancer medicine approach in pediatric oncology have been published [3,4,5,6,7,8], and these demonstrated that the application of clinical genomics was possible and that a substantial number of patients had actionable genetic alterations, indicating the potential for targeted therapy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
