Molecular profiling identifies targeted therapy opportunities in pediatric solid cancer,Nature Medicine

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Molecular profiling identifies targeted therapy opportunities in pediatric solid cancer
Nature Medicine ( IF 82.9 ) Pub Date : 2022-06-23 , DOI: 10.1038/s41591-022-01856-6
Alanna J Church _{1,

2} , Laura B Corson _{3,

4,

5} , Pei-Chi Kao ₁ , Alma Imamovic-Tuco _{3,

4} , Deirdre Reidy _{3,

6} , Duong Doan _{3,

7} , Wenjun Kang ₈ , Navin Pinto _{9,

10} , Luke Maese _{11,

12} , Theodore W Laetsch _{13,

14,

15} , AeRang Kim _{16,

17} , Susan I Colace _{18,

19} , Margaret E Macy _{20,

21} , Mark A Applebaum _{8,

22} , Rochelle Bagatell _{14,

15} , Amit J Sabnis ₂₃ , Daniel A Weiser _{24,

25} , Julia L Glade-Bender _{26,

27} , Alan C Homans _{28,

29} , John Hipps _{30,

31} , Haley Harris ₁ , Danielle Manning ₃₂ , Alyaa Al-Ibraheemi _{1,

2} , Yvonne Li _{2,

3,

4} , Hersh Gupta _{2,

3,

4} , Andrew D Cherniack _{2,

3,

4} , Ying-Chun Lo _{1,

32,

33} , Gianna R Strand _{3,

34} , Lobin A Lee _{3,

14} , R Seth Pinches _{1,

35} , Lorena Lazo De La Vega ₃ , Maegan V Harden ₄ , Niall J Lennon ₄ , Seong Choi ₈ , Hannah Comeau ₃ , Marian H Harris _{1,

2} , Suzanne J Forrest _{2,

3} , Catherine M Clinton _{1,

3} , Brian D Crompton _{2,

3} , Junne Kamihara _{2,

3} , Laura E MacConaill _{2,

32} , Samuel L Volchenboum ₈ , Neal I Lindeman _{2,

32} , Eliezer Van Allen _{2,

4,

36} , Steven G DuBois _{2,

3} , Wendy B London _{1,

2} , Katherine A Janeway _{2,

3}

Affiliation

Boston Children's Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sema4, Stamford, CT, USA.
University of Connecticut School of Medicine, Farmington, CT, USA.
University of Massachusetts Medical School, Worcester, MA, USA.
University of Chicago, Chicago, IL, USA.
Seattle Children's Hospital, Seattle, WA, USA.
University of Washington, Seattle, WA, USA.
Primary Children's Hospital, Salt Lake City, UT, USA.
University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA.
University of Texas Southwestern Medical Center, Dallas, TX, USA.
Children's Hospital of Philadelphia, Philadelphia, PA, USA.
University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Children's National Hospital, Washington, DC, USA.
George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Nationwide Children's Hospital, Columbus, OH, USA.
Ohio State University College of Medicine, Columbus, OH, USA.
Children's Hospital of Colorado, Aurora, CO, USA.
University of Colorado School of Medicine, Aurora, CO, USA.
Comer Children's Hospital, Chicago, IL, USA.
University of California San Francisco Benioff Children's Hospital, San Francisco, CA, USA.
Children's Hospital at Montefiore, New York, NY, USA.
Albert Einstein College of Medicine, New York, NY, USA.
Columbia University Irving Medical Center, New York, NY, USA.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
University of Vermont Medical Center, Burlington, VT, USA.
University of Vermont, Burlington, VT, USA.
University of North Carolina Medical Center, Chapel Hill, NC, USA.
University of North Carolina-Chapel Hill School of Medicine, Chapel Hill, NC, USA.
Brigham and Women's Hospital, Boston, MA, USA.
Mayo Clinic, Rochester, MN, USA.
Loyola University, Chicago, IL, USA.
Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA.
Dana-Farber Cancer Institute, Boston, MA, USA.

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.

中文翻译：

分子谱分析确定了儿科实体癌的靶向治疗机会

为了评估分子肿瘤分析 (MTP) 与靶向测序面板测试的临床影响，颅外实体瘤的儿科患者被纳入 12 个机构的前瞻性观察队列研究。在 345 名患者的分析人群中，诊断时的中位年龄为 12 岁（范围 0-27.5）；298 名患者 (86%) 有 1 项或多项可能对护理产生影响的改变。具有诊断、预后或治疗意义的基因组改变分别出现在 61%、16% 和 65% 的患者中。返回结果后，对护理的影响包括 17 名具有明确诊断分类的患者和 240 名具有 MTP 结果的患者，可用于选择与已识别改变 (MTT) 相匹配的分子靶向治疗。在接受 MTT 的 29 名患者中，24% 有客观反应或经历了持久的临床获益；除了 1 名患者外，所有患者都接受了与基因融合相匹配的靶向治疗。在 209 名患者中发现的诊断变异中，77% 是基因融合。具有包括融合检测在内的靶向小组测试的 MTP 对年轻的实体瘤患者具有重大的临床影响。

更新日期：2022-06-23

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