PMID- 36724417
OWN - NLM
STAT- MEDLINE
DCOM- 20230503
LR  - 20240502
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 41
IP  - 13
DP  - 2023 May 1
TI  - Circulating Tumor DNA Is Prognostic in Intermediate-Risk Rhabdomyosarcoma: A 
      Report From the Children's Oncology Group.
PG  - 2382-2393
LID - 10.1200/JCO.22.00409 [doi]
AB  - PURPOSE: Novel biomarkers are needed to differentiate outcomes in 
      intermediate-risk rhabdomyosarcoma (IR RMS). We sought to evaluate strategies for 
      identifying circulating tumor DNA (ctDNA) in IR RMS and to determine whether 
      ctDNA detection before therapy is associated with outcome. PATIENTS AND METHODS: 
      Pretreatment serum and tumor samples were available from 124 patients with newly 
      diagnosed IR RMS from the Children's Oncology Group biorepository, including 75 
      patients with fusion-negative rhabdomyosarcoma (FN-RMS) and 49 with 
      fusion-positive rhabdomyosarcoma (FP-RMS) disease. We used ultralow passage 
      whole-genome sequencing to detect copy number alterations and a new custom 
      sequencing assay, Rhabdo-Seq, to detect rearrangements and single-nucleotide 
      variants. RESULTS: We found that ultralow passage whole-genome sequencing was a 
      method applicable to ctDNA detection in all patients with FN-RMS and that ctDNA 
      was detectable in 13 of 75 serum samples (17%). However, the use of Rhabdo-Seq in 
      FN-RMS samples also identified single-nucleotide variants, such as MYOD1(L122R), 
      previously associated with prognosis. Identification of pathognomonic 
      translocations between PAX3 or PAX7 and FOXO1 by Rhabdo-Seq was the best method 
      for measuring ctDNA in FP-RMS and detected ctDNA in 27 of 49 cases (55%). 
      Patients with FN-RMS with detectable ctDNA at diagnosis had significantly worse 
      outcomes than patients without detectable ctDNA (event-free survival, 33.3% v 
      68.9%; P = .0028; overall survival, 33.3% v 83.2%; P < .0001) as did patients 
      with FP-RMS (event-free survival, 37% v 70%; P = .045; overall survival, 39.2% v 
      75%; P = .023). In multivariable analysis, ctDNA was independently associated 
      with worse prognosis in FN-RMS but not in the smaller FP-RMS cohort. CONCLUSION: 
      Our study demonstrates that baseline ctDNA detection is feasible and is 
      prognostic in IR RMS.
FAU - Abbou, Samuel
AU  - Abbou S
AD  - Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA.
AD  - Children and Adolescent Oncology Department, INSERM U1015, Paris-Saclay 
      University, Villejuif, France.
FAU - Klega, Kelly
AU  - Klega K
AUID- ORCID: 0000-0002-3424-2003
AD  - Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA.
FAU - Tsuji, Junko
AU  - Tsuji J
AUID- ORCID: 0000-0003-0139-3750
AD  - Broad Institute of Harvard and MIT, Cambridge, MA.
FAU - Tanhaemami, Mohammad
AU  - Tanhaemami M
AUID- ORCID: 0000-0002-6498-1181
AD  - Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA.
FAU - Hall, David
AU  - Hall D
AUID- ORCID: 0000-0003-1257-2316
AD  - QuadW-COG Childhood Sarcoma Biostatistics and Annotation Office, Children's 
      Oncology Group, Monrovia, CA.
FAU - Barkauskas, Donald A
AU  - Barkauskas DA
AUID- ORCID: 0000-0002-2339-719X
AD  - QuadW-COG Childhood Sarcoma Biostatistics and Annotation Office, Children's 
      Oncology Group, Monrovia, CA.
AD  - Department of Population and Public Health Sciences, Keck School of Medicine of 
      the University of Southern California, Los Angeles, CA.
FAU - Krailo, Mark D
AU  - Krailo MD
AD  - QuadW-COG Childhood Sarcoma Biostatistics and Annotation Office, Children's 
      Oncology Group, Monrovia, CA.
AD  - Department of Population and Public Health Sciences, Keck School of Medicine of 
      the University of Southern California, Los Angeles, CA.
FAU - Cibulskis, Carrie
AU  - Cibulskis C
AD  - Broad Institute of Harvard and MIT, Cambridge, MA.
FAU - Nag, Anwesha
AU  - Nag A
AUID- ORCID: 0000-0002-1947-7429
AD  - Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA.
FAU - Thorner, Aaron R
AU  - Thorner AR
AUID- ORCID: 0000-0002-9160-7881
AD  - Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA.
FAU - Pollock, Samuel
AU  - Pollock S
AUID- ORCID: 0000-0001-5173-5259
AD  - Broad Institute of Harvard and MIT, Cambridge, MA.
FAU - Imamovic-Tuco, Alma
AU  - Imamovic-Tuco A
AUID- ORCID: 0000-0003-4454-6868
AD  - Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA.
AD  - Broad Institute of Harvard and MIT, Cambridge, MA.
FAU - Shern, Jack F
AU  - Shern JF
AUID- ORCID: 0000-0001-5579-7625
AD  - Genetics Branch, Oncogenomics Section, Center for Cancer Research, National 
      Institutes of Health, Bethesda, MD.
AD  - Pediatric Oncology Branch, Center for Cancer Research, National Institutes of 
      Health, Bethesda, MD.
FAU - DuBois, Steven G
AU  - DuBois SG
AUID- ORCID: 0000-0003-0882-738X
AD  - Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA.
FAU - Venkatramani, Rajkumar
AU  - Venkatramani R
AUID- ORCID: 0000-0002-4785-106X
AD  - Division of Hematology/Oncology, Texas Children's Cancer Center, Baylor College 
      of Medicine, Houston, TX.
FAU - Hawkins, Douglas S
AU  - Hawkins DS
AUID- ORCID: 0000-0003-3602-1375
AD  - Hematology/Oncology, Seattle Children's Hospital, Seattle, WA.
FAU - Crompton, Brian D
AU  - Crompton BD
AUID- ORCID: 0000-0001-9404-6621
AD  - Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA.
AD  - Broad Institute of Harvard and MIT, Cambridge, MA.
LA  - eng
GR  - U24 CA196173/CA/NCI NIH HHS/United States
GR  - U10 CA098543/CA/NCI NIH HHS/United States
GR  - U10 CA180899/CA/NCI NIH HHS/United States
GR  - U10 CA180886/CA/NCI NIH HHS/United States
GR  - U10 CA098413/CA/NCI NIH HHS/United States
GR  - U24 CA114766/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230201
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Circulating Tumor DNA)
RN  - 0 (Nucleotides)
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - Humans
MH  - Child
MH  - Prognosis
MH  - *Circulating Tumor DNA
MH  - *Rhabdomyosarcoma/pathology
MH  - Nucleotides
MH  - *Rhabdomyosarcoma, Alveolar/genetics
MH  - Biomarkers, Tumor/genetics
PMC - PMC10150913
COIS- The following represents disclosure information provided by authors of this 
      manuscript. All relationships are considered compensated unless otherwise noted. 
      Relationships are self-held unless noted. I = Immediate Family Member, Inst = My 
      Institution. Relationships may not relate to the subject matter of this 
      manuscript. For more information about ASCO's conflict of interest policy, please 
      refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center. Open 
      Payments is a public database containing information reported by companies about 
      payments made to US-licensed physicians (Open Payments).
EDAT- 2023/02/02 06:00
MHDA- 2023/05/03 06:42
PMCR- 2024/05/01
CRDT- 2023/02/01 16:03
PHST- 2023/05/03 06:42 [medline]
PHST- 2023/02/02 06:00 [pubmed]
PHST- 2023/02/01 16:03 [entrez]
PHST- 2024/05/01 00:00 [pmc-release]
AID - JCO.22.00409 [pii]
AID - 10.1200/JCO.22.00409 [doi]
PST - ppublish
SO  - J Clin Oncol. 2023 May 1;41(13):2382-2393. doi: 10.1200/JCO.22.00409. Epub 2023 
      Feb 1.