Molecular profiling identifies targeted therapy opportunities in pediatric solid cancer

Alanna J. Church; Laura B. Corson; Pei Chi Kao; Alma Imamovic-Tuco; Deirdre Reidy; Duong Doan; Wenjun Kang; Navin Pinto; Luke Maese; Theodore W. Laetsch; Ae Rang Kim; Susan I. Colace; Margaret E. Macy; Mark A. Applebaum; Rochelle Bagatell; Amit J. Sabnis; Daniel A. Weiser; Julia L. Glade-Bender; Alan C. Homans; John Hipps; Haley Harris; Danielle Manning; Alyaa Al-Ibraheemi; Yvonne Li; Hersh Gupta; Andrew D. Cherniack; Ying Chun Lo; Gianna R. Strand; Lobin A. Lee; R. Seth Pinches; Lorena Lazo De La Vega; Maegan V. Harden; Niall J. Lennon; Seong Choi; Hannah Comeau; Marian H. Harris; Suzanne J. Forrest; Catherine M. Clinton; Brian D. Crompton; Junne Kamihara; Laura E. MacConaill; Samuel L. Volchenboum; Neal I. Lindeman; Eliezer Van Allen; Steven G. DuBois; Wendy B. London; Katherine A. Janeway

doi:10.1038/s41591-022-01856-6

Molecular profiling identifies targeted therapy opportunities in pediatric solid cancer

Alanna J. Church, Laura B. Corson, Pei Chi Kao, Alma Imamovic-Tuco, Deirdre Reidy, Duong Doan, Wenjun Kang, Navin Pinto, Luke Maese, Theodore W. Laetsch, Ae Rang Kim, Susan I. Colace, Margaret E. Macy, Mark A. Applebaum, Rochelle Bagatell, Amit J. Sabnis, Daniel A. Weiser, Julia L. Glade-Bender, Alan C. Homans, John HippsHaley Harris, Danielle Manning, Alyaa Al-Ibraheemi, Yvonne Li, Hersh Gupta, Andrew D. Cherniack, Ying Chun Lo, Gianna R. Strand, Lobin A. Lee, R. Seth Pinches, Lorena Lazo De La Vega, Maegan V. Harden, Niall J. Lennon, Seong Choi, Hannah Comeau, Marian H. Harris, Suzanne J. Forrest, Catherine M. Clinton, Brian D. Crompton, Junne Kamihara, Laura E. MacConaill, Samuel L. Volchenboum, Neal I. Lindeman, Eliezer Van Allen, Steven G. DuBois, Wendy B. London, Katherine A. Janeway

Pediatrics

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1581-1589
Number of pages	9
Journal	Nature Medicine
Volume	28
Issue number	8
DOIs	https://doi.org/10.1038/s41591-022-01856-6
State	Published - Aug 2022

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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Church, A. J., Corson, L. B., Kao, P. C., Imamovic-Tuco, A., Reidy, D., Doan, D., Kang, W., Pinto, N., Maese, L., Laetsch, T. W., Kim, A. R., Colace, S. I., Macy, M. E., Applebaum, M. A., Bagatell, R., Sabnis, A. J., Weiser, D. A., Glade-Bender, J. L., Homans, A. C., ... Janeway, K. A. (2022). Molecular profiling identifies targeted therapy opportunities in pediatric solid cancer. Nature Medicine, 28(8), 1581-1589. https://doi.org/10.1038/s41591-022-01856-6

Church, AJ, Corson, LB, Kao, PC, Imamovic-Tuco, A, Reidy, D, Doan, D, Kang, W, Pinto, N, Maese, L, Laetsch, TW, Kim, AR, Colace, SI, Macy, ME, Applebaum, MA, Bagatell, R, Sabnis, AJ, Weiser, DA, Glade-Bender, JL, Homans, AC, Hipps, J, Harris, H, Manning, D, Al-Ibraheemi, A, Li, Y, Gupta, H, Cherniack, AD, Lo, YC, Strand, GR, Lee, LA, Pinches, RS, Lazo De La Vega, L, Harden, MV, Lennon, NJ, Choi, S, Comeau, H, Harris, MH, Forrest, SJ, Clinton, CM, Crompton, BD, Kamihara, J, MacConaill, LE, Volchenboum, SL, Lindeman, NI, Van Allen, E, DuBois, SG, London, WB & Janeway, KA 2022, 'Molecular profiling identifies targeted therapy opportunities in pediatric solid cancer', Nature Medicine, vol. 28, no. 8, pp. 1581-1589. https://doi.org/10.1038/s41591-022-01856-6

@article{e50817823404491a9684837172999b4f,

title = "Molecular profiling identifies targeted therapy opportunities in pediatric solid cancer",

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.",

author = "Church, {Alanna J.} and Corson, {Laura B.} and Kao, {Pei Chi} and Alma Imamovic-Tuco and Deirdre Reidy and Duong Doan and Wenjun Kang and Navin Pinto and Luke Maese and Laetsch, {Theodore W.} and Kim, {Ae Rang} and Colace, {Susan I.} and Macy, {Margaret E.} and Applebaum, {Mark A.} and Rochelle Bagatell and Sabnis, {Amit J.} and Weiser, {Daniel A.} and Glade-Bender, {Julia L.} and Homans, {Alan C.} and John Hipps and Haley Harris and Danielle Manning and Alyaa Al-Ibraheemi and Yvonne Li and Hersh Gupta and Cherniack, {Andrew D.} and Lo, {Ying Chun} and Strand, {Gianna R.} and Lee, {Lobin A.} and Pinches, {R. Seth} and {Lazo De La Vega}, Lorena and Harden, {Maegan V.} and Lennon, {Niall J.} and Seong Choi and Hannah Comeau and Harris, {Marian H.} and Forrest, {Suzanne J.} and Clinton, {Catherine M.} and Crompton, {Brian D.} and Junne Kamihara and MacConaill, {Laura E.} and Volchenboum, {Samuel L.} and Lindeman, {Neal I.} and {Van Allen}, Eliezer and DuBois, {Steven G.} and London, {Wendy B.} and Janeway, {Katherine A.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2022",

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doi = "10.1038/s41591-022-01856-6",

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AU - Church, Alanna J.

AU - Corson, Laura B.

AU - Kao, Pei Chi

AU - Imamovic-Tuco, Alma

AU - Reidy, Deirdre

AU - Doan, Duong

AU - Kang, Wenjun

AU - Pinto, Navin

AU - Maese, Luke

AU - Laetsch, Theodore W.

AU - Kim, Ae Rang

AU - Colace, Susan I.

AU - Macy, Margaret E.

AU - Applebaum, Mark A.

AU - Bagatell, Rochelle

AU - Sabnis, Amit J.

AU - Weiser, Daniel A.

AU - Glade-Bender, Julia L.

AU - Homans, Alan C.

AU - Hipps, John

AU - Harris, Haley

AU - Manning, Danielle

AU - Al-Ibraheemi, Alyaa

AU - Li, Yvonne

AU - Gupta, Hersh

AU - Cherniack, Andrew D.

AU - Lo, Ying Chun

AU - Strand, Gianna R.

AU - Lee, Lobin A.

AU - Pinches, R. Seth

AU - Lazo De La Vega, Lorena

AU - Harden, Maegan V.

AU - Lennon, Niall J.

AU - Choi, Seong

AU - Comeau, Hannah

AU - Harris, Marian H.

AU - Forrest, Suzanne J.

AU - Clinton, Catherine M.

AU - Crompton, Brian D.

AU - Kamihara, Junne

AU - MacConaill, Laura E.

AU - Volchenboum, Samuel L.

AU - Lindeman, Neal I.

AU - Van Allen, Eliezer

AU - DuBois, Steven G.

AU - London, Wendy B.

AU - Janeway, Katherine A.

PY - 2022/8

Y1 - 2022/8

N2 - 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.

AB - 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.

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JF - Nature Medicine

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ER -

Molecular profiling identifies targeted therapy opportunities in pediatric solid cancer

Abstract

ASJC Scopus subject areas

UN SDGs

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