Larotrectinib as an Effective Therapy in Congenital Infantile Fibrosarcoma: Report of Two Cases

 

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Abstract

Congenital infantile fibrosarcoma (CIF) is a rare tumor in children that occurs in the first years of life. It usually arises in the extremities but some cases affect the trunk, neck, abdomen, or retroperitoneum. Surgical resection has been traditionally the treatment of choice but the development of genomic analysis and targeted therapies has shed light on new therapeutic options.

We present two patients with a congenital mass, one in the abdominal cavity (1-month-old) and the second in the left lower extremity respectively (2-months-old). In both cases, the clinical and radiological findings showed heterogeneous masses with rapidly progressive growth. MRI in the first patient exhibited an abdominal mass surrounding the aorta and inferior vena cava associated with a giant infrarenal aortic aneurysm. CT-guided biopsy was performed with pathological findings of fibrosarcoma and ETV6-NTRK3 gene fusion. The second patient underwent open biopsy also with histopathological diagnosis of fibrosarcoma and the same mutation in the TRK gene (NTRK3). Targeted therapy with a specific TRK inhibitor, larotrectinib, was started in both patients. Periodical controls were made by ultrasound or MRI, and after a few weeks of treatment, both children showed significant decrease in the mass. By the second and third months after starting the treatment, both tumors disappeared. The first patient is now 15-months-old and the second one is 8-months-old.

Larotrectinib is a novel targeted therapy with excellent results in CIF but long-term outcomes are limited to establish it as a gold standard treatment.

Publication History

Received: 17 July 2021

Accepted: 18 January 2022

Article published online:
25 June 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

• References

• 1 Ferrari A, Orbach D, Sultan I, Casanova M, Bisogno G. Neonatal soft tissue sarcomas. Semin Fetal Neonatal Med 2012; 17 (04) 231-238 DOI: 10.1016/j.siny.2012.05.003.
  CrossrefPubMedGoogle Scholar
• 2 Caldwell KJ, De La Cuesta E, Morin C, Pappo A, Helmig S. A newborn with a large NTRK fusion positive infantile fibrosarcoma successfully treated with larotrectinib. Pediatr Blood Cancer 2020; 67 (09) e28330
  CrossrefPubMedGoogle Scholar
• 3 Orbach D, Rey A, Cecchetto G. et al. Infantile fibrosarcoma: management based on the European experience. J Clin Oncol 2010; 28 (02) 318-323
  CrossrefPubMedGoogle Scholar
• 4 Corral Sánchez MD, Galán Gómez V, Sastre Urgelles A. et al. Treatment of infantile fibrosarcoma associated to an abdominal aortic aneurysm with larotrectinib: a case report. Pediatr Hematol Oncol 2021; 38 (05) 504-509
  CrossrefPubMedGoogle Scholar
• 5 DuBois SG, Laetsch TW, Federman N. et al. The use of neoadjuvant larotrectinib in the management of children with locally advanced TRK fusion sarcomas. Cancer 2018; 124 (21) 4241-4247
  CrossrefPubMedGoogle Scholar
• 6 Laetsch TW, DuBois SG, Mascarenhas L. et al. Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study. Lancet Oncol 2018; 19 (05) 705-714
  CrossrefPubMedGoogle Scholar
• 7 Bielack SS, Cox MC, Nathrath M. et al. Rapid, complete and sustained tumour response to the TRK inhibitor larotrectinib in an infant with recurrent, chemotherapy-refractory infantile fibrosarcoma carrying the characteristic ETV6-NTRK3 gene fusion. Ann Oncol 2019; 30 (Suppl_8, Suppl_8) i31, i35
  CrossrefPubMedGoogle Scholar
• 8 Edwards TM, Duran MS, Meeker TM. Congenital infantile fibrosarcoma in the premature infant. Adv Neonatal Care 2017; 17 (06) 440-450
  CrossrefPubMedGoogle Scholar