Recent Advances in Understanding and Managing Pediatric Rhabdomyosarcoma

Overview

Journal F1000Res

Specialties Biomedical Engineering
Science

Date 2020 Jul 23

PMID 32695311

Citations 21

Authors

Jessica Gartrell

Alberto Pappo

Affiliations

Soon will be listed here.

Abstract

Rhabdomyosarcoma (RMS) is a high-grade malignant neoplasm, with a morphologic appearance mimicking that of developing skeletal muscle. Over the last 30 years, patient outcomes have improved with the incorporation of multimodal therapies, including chemotherapy, radiation therapy, and surgery. The overall cure rates exceed 70%, with patients who have low-, intermediate-, and high-risk disease experiencing long-term survival rates of >90%, 70%, and <30%, respectively. Historically, RMS was classified according to histology; however, recent advances have revealed new molecular subgroups that allow us to more accurately identify high-, intermediate-, and low-risk disease. In this review, we discuss recent advances made in understanding RMS tumor biology and propose how this understanding can drive a new classification system that can guide clinical approaches for treatment de-escalation in patients with expected favorable outcomes and escalation for those with expected poor outcomes.

Citing Articles

Clinical outcomes and prognostic factors of parameningeal rhabdomyosarcoma in children and adolescents: results of two consecutive protocols.

Duan C, He S, Ma X, Wang S, Jin M, Zhao W Transl Pediatr. 2024; 13(7):1086-1096.

PMID: 39144439 PMC: 11320008. DOI: 10.21037/tp-24-41.

HDAC3 genetic and pharmacologic inhibition radiosensitizes fusion positive rhabdomyosarcoma by promoting DNA double-strand breaks.

Cassandri M, Porrazzo A, Pomella S, Noce B, Zwergel C, Aiello F Cell Death Discov. 2024; 10(1):351.

PMID: 39107280 PMC: 11303816. DOI: 10.1038/s41420-024-02115-y.

Therapeutic Targeting of DNA Repair Pathways in Pediatric Extracranial Solid Tumors: Current State and Implications for Immunotherapy.

Zhao S, Prior D, Heske C, Vasquez J Cancers (Basel). 2024; 16(9).

PMID: 38730598 PMC: 11083679. DOI: 10.3390/cancers16091648.

Event-free survival in relapsed and refractory rhabdomyosarcoma treated on cooperative group phase II trials: A report from the Children's Oncology Group.

Metts J, Xue W, Gao Z, Oberoi S, Weiss A, Venkatramani R Pediatr Blood Cancer. 2024; 71(7):e31009.

PMID: 38627882 PMC: 11180298. DOI: 10.1002/pbc.31009.

Case Report: Robotic pylorus-preserving pancreatoduodenectomy for periampullary rhabdomyosarcoma in a 3-year-old patient.

Liang Z, Lan M, Xu X, Liu F, Tao B, Wang X Front Surg. 2024; 11:1284257.

PMID: 38440415 PMC: 10910038. DOI: 10.3389/fsurg.2024.1284257.

References

Chisholm J, Merks J, Casanova M, Bisogno G, Orbach D, Gentet J . Open-label, multicentre, randomised, phase II study of the EpSSG and the ITCC evaluating the addition of bevacizumab to chemotherapy in childhood and adolescent patients with metastatic soft tissue sarcoma (the BERNIE study). Eur J Cancer. 2017; 83:177-184. DOI: 10.1016/j.ejca.2017.06.015. View

Yan C, Brunson D, Tang Q, Do D, Iftimia N, Moore J . Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish. Cell. 2019; 177(7):1903-1914.e14. PMC: 6570580. DOI: 10.1016/j.cell.2019.04.004. View

Butel T, Karanian M, Pierron G, Orbach D, Ranchere D, Cozic N . Integrative clinical and biopathology analyses to understand the clinical heterogeneity of infantile rhabdomyosarcoma: A report from the French MMT committee. Cancer Med. 2020; 9(8):2698-2709. PMC: 7163108. DOI: 10.1002/cam4.2713. View

McCluggage W, Apellaniz-Ruiz M, Chong A, Hanley K, Velazquez Vega J, McVeigh T . Embryonal Rhabdomyosarcoma of the Ovary and Fallopian Tube: Rare Neoplasms Associated With Germline and Somatic DICER1 Mutations. Am J Surg Pathol. 2020; 44(6):738-747. DOI: 10.1097/PAS.0000000000001442. View

Rudzinski E, Anderson J, Hawkins D, Skapek S, Parham D, Teot L . The World Health Organization Classification of Skeletal Muscle Tumors in Pediatric Rhabdomyosarcoma: A Report From the Children's Oncology Group. Arch Pathol Lab Med. 2015; 139(10):1281-7. PMC: 4651658. DOI: 10.5858/arpa.2014-0475-OA. View

Lupo P, Luna-Gierke R, Chambers T, Tavelin B, Scheurer M, Melin B . Perinatal and familial risk factors for soft tissue sarcomas in childhood through young adulthood: A population-based assessment in 4 million live births. Int J Cancer. 2019; 146(3):791-802. DOI: 10.1002/ijc.32335. View

Casey D, Wexler L, Pitter K, Samstein R, Slotkin E, Wolden S . Genomic Determinants of Clinical Outcomes in Rhabdomyosarcoma. Clin Cancer Res. 2019; 26(5):1135-1140. PMC: 8693250. DOI: 10.1158/1078-0432.CCR-19-2631. View

Stewart E, McEvoy J, Wang H, Chen X, Honnell V, Ocarz M . Identification of Therapeutic Targets in Rhabdomyosarcoma through Integrated Genomic, Epigenomic, and Proteomic Analyses. Cancer Cell. 2018; 34(3):411-426.e19. PMC: 6158019. DOI: 10.1016/j.ccell.2018.07.012. View

Casey D, Chi Y, Donaldson S, Hawkins D, Tian J, Arndt C . Increased local failure for patients with intermediate-risk rhabdomyosarcoma on ARST0531: A report from the Children's Oncology Group. Cancer. 2019; 125(18):3242-3248. PMC: 6717036. DOI: 10.1002/cncr.32204. View

10.

Walterhouse D, Pappo A, Meza J, Breneman J, Hayes-Jordan A, Parham D . Shorter-duration therapy using vincristine, dactinomycin, and lower-dose cyclophosphamide with or without radiotherapy for patients with newly diagnosed low-risk rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's.... J Clin Oncol. 2014; 32(31):3547-52. PMC: 4209105. DOI: 10.1200/JCO.2014.55.6787. View

11.

Pappo A, Lyden E, Breitfeld P, Donaldson S, Wiener E, Parham D . Two consecutive phase II window trials of irinotecan alone or in combination with vincristine for the treatment of metastatic rhabdomyosarcoma: the Children's Oncology Group. J Clin Oncol. 2007; 25(4):362-9. DOI: 10.1200/JCO.2006.07.1720. View

12.

Agaram N, LaQuaglia M, Alaggio R, Zhang L, Fujisawa Y, Ladanyi M . MYOD1-mutant spindle cell and sclerosing rhabdomyosarcoma: an aggressive subtype irrespective of age. A reappraisal for molecular classification and risk stratification. Mod Pathol. 2018; 32(1):27-36. PMC: 6720105. DOI: 10.1038/s41379-018-0120-9. View

13.

Williams L, Richardson M, Kehm R, McLaughlin C, Mueller B, Chow E . The association between sex and most childhood cancers is not mediated by birthweight. Cancer Epidemiol. 2018; 57:7-12. PMC: 6289597. DOI: 10.1016/j.canep.2018.09.002. View

14.

Jo V, Fletcher C . WHO classification of soft tissue tumours: an update based on the 2013 (4th) edition. Pathology. 2014; 46(2):95-104. DOI: 10.1097/PAT.0000000000000050. View

15.

Yohe M, Heske C, Stewart E, Adamson P, Ahmed N, Antonescu C . Insights into pediatric rhabdomyosarcoma research: Challenges and goals. Pediatr Blood Cancer. 2019; 66(10):e27869. PMC: 6707829. DOI: 10.1002/pbc.27869. View

16.

Compostella A, Affinita M, Casanova M, Milano G, Scagnellato A, DallIgna P . Topotecan/carboplatin regimen for refractory/recurrent rhabdomyosarcoma in children: Report from the AIEOP Soft Tissue Sarcoma Committee. Tumori. 2018; 105(2):138-143. DOI: 10.1177/0300891618792479. View

17.

Casey D, Wexler L, Wolden S . Worse Outcomes for Head and Neck Rhabdomyosarcoma Secondary to Reduced-Dose Cyclophosphamide. Int J Radiat Oncol Biol Phys. 2018; 103(5):1151-1157. PMC: 6441953. DOI: 10.1016/j.ijrobp.2018.11.049. View

18.

Vaarwerk B, Mallebranche C, Affinita M, van der Lee J, Ferrari A, Chisholm J . Is surveillance imaging in pediatric patients treated for localized rhabdomyosarcoma useful? The European experience. Cancer. 2019; 126(4):823-831. PMC: 7027831. DOI: 10.1002/cncr.32603. View

19.

Chen X, Stewart E, Shelat A, Qu C, Bahrami A, Hatley M . Targeting oxidative stress in embryonal rhabdomyosarcoma. Cancer Cell. 2013; 24(6):710-24. PMC: 3904731. DOI: 10.1016/j.ccr.2013.11.002. View

20.

Lucas Jr J, Pappo A . Optimal dosing of cyclophosphamide in rhabdomyosarcoma: It's complicated. Cancer. 2019; 125(18):3107-3110. PMC: 8721594. DOI: 10.1002/cncr.32205. View