Molecular profiling identifies targeted therapy opportunities in pediatric solid cancer

Alanna J. Church, Boston Children's Hospital, Boston, MA, USA. Alanna.Church@childrens.harvard.edu.
Laura B. Corson, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Pei-Chi Kao, Boston Children's Hospital, Boston, MA, USA.
Alma Imamovic-Tuco, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Deirdre Reidy, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Duong Doan, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Wenjun Kang, University of Chicago, Chicago, IL, USA.
Navin Pinto, Seattle Children's Hospital, Seattle, WA, USA.
Luke Maese, Primary Children's Hospital, Salt Lake City, UT, USA.
Theodore W. Laetsch, University of Texas Southwestern Medical Center, Dallas, TX, USA.
AeRang Kim, Children's National Hospital, Washington, DC, USA.
Susan I. Colace, Nationwide Children's Hospital, Columbus, OH, USA.
Margaret E. Macy, Children's Hospital of Colorado, Aurora, CO, USA.
Mark A. Applebaum, University of Chicago, Chicago, IL, USA.
Rochelle Bagatell, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Amit J. Sabnis, University of California San Francisco Benioff Children's Hospital, San Francisco, CA, USA.
Daniel A. Weiser, Children's Hospital at Montefiore, New York, NY, USA.
Julia L. Glade-Bender, Columbia University Irving Medical Center, New York, NY, USA.
Alan C. Homans, University of Vermont Medical Center, Burlington, VT, USA.
John Hipps, University of North Carolina Medical Center, Chapel Hill, NC, USA.
Haley Harris, Boston Children's Hospital, Boston, MA, USA.
Danielle Manning, Brigham and Women's Hospital, Boston, MA, USA.
Alyaa Al-Ibraheemi, Boston Children's Hospital, Boston, MA, USA.
Yvonne Li, Harvard Medical School, Boston, MA, USA.
Hersh Gupta, Harvard Medical School, Boston, MA, USA.
Andrew D. Cherniack, Harvard Medical School, Boston, MA, USA.
Ying-Chun Lo, Boston Children's Hospital, Boston, MA, USA.
Gianna R. Strand, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Lobin A. Lee, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
R Seth Pinches, Boston Children's Hospital, Boston, MA, USA.
Lorena Lazo De La Vega, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Maegan V. Harden, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Document Type

Journal Article

Publication Date

6-23-2022

Journal

Nature medicine

DOI

10.1038/s41591-022-01856-6

Abstract

To evaluate the clinical impact of molecular tumor profiling (MTP) with targeted sequencing panel tests, pediatric patients with extracranial solid tumors were enrolled in a prospective observational cohort study at 12 institutions. In the 345-patient analytical population, median age at diagnosis was 12 years (range 0-27.5); 298 patients (86%) had 1 or more alterations with potential for impact on care. Genomic alterations with diagnostic, prognostic or therapeutic significance were present in 61, 16 and 65% of patients, respectively. After return of the results, impact on care included 17 patients with a clarified diagnostic classification and 240 patients with an MTP result that could be used to select molecularly targeted therapy matched to identified alterations (MTT). Of the 29 patients who received MTT, 24% had an objective response or experienced durable clinical benefit; all but 1 of these patients received targeted therapy matched to a gene fusion. Of the diagnostic variants identified in 209 patients, 77% were gene fusions. MTP with targeted panel tests that includes fusion detection has a substantial clinical impact for young patients with solid tumors.

Department

Pediatrics

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