Limb salvage of an infant with infantile fibrosarcoma using TRK inhibitor larotrectinib

Abstract

Infantile fibrosarcoma (IFS) is an extremely rare locally aggressive soft tissue tumour of childhood. Primary therapy involves complete surgical resection with or without chemotherapy. However complete surgical resection might not be feasible in all cases and so requires other modalities for further management. We report the case of a male infant from Bangladesh with a locally advanced IFS of the leg which was partially resected. The patient received adjuvant chemotherapy which was complicated by the development of chemotherapy-related veno-occlusive disease and had to be discontinued. Thereafter he was referred to our dedicated sarcoma oncology clinic in India for further management. The parents of the child refused amputation of the limb. The tumour tested positive for NTRK3-ETV6 gene fusion and after discussion in multidisciplinary clinic, targeted therapy using oral NTRK inhibitor larotrectinib was started. The patient had complete response at the end of 8 months of treatment with larotrectinib. This is the first report from the Indian subcontinent and we encourage that these children should be referred to specialist clinics for appropriate multidisciplinary management for best outcomes.

Keywords: NTRK3-ETV6; infantile fibrosarcoma; larotrectinib.

Figure 1.. Pre-operative MRI images of the left leg showing a large lobulated invasive soft tissue mass lesion of 3.5 × 5 × 6 cm size in the upper and mid-leg involving postero-medial compartment with anterior displacement of the tibia with its bowing without any abnormal marrow signal change. Mass is hypointense on T1WI and heterogeneously hyperintense on T2WI. Mass is mainly involving the muscular structures with evidence of neuro-vascular encasement.

Figure 2.. Pathological images from the resected tumour specimen. (a): Haematoxylin-eosin staining at 10× magnification. (b): Haematoxylin-eosin staining at 20× magnification. (c): Negative IHC for desmin. (d): Negative IHC for CD34.

Figure 3.. MRI scan images of the left leg showing local recurrence after wide local resection and 17 cycles of VAC-based chemotherapy.

Figure 4.. FISH on interphase cell showed evidence of ETV6 translocation/ rearrangement {ETV6-NTRK3: t(12;15) (p13;q25)}.

Figure 5.. Pre-chemotherapy; (a): axial T2W (fat saturated) and (b): contrast-enhanced T1W (fat-saturated) MRI images showing Ill-defined homogenously enhancing mass lesion in the Interosseous space (arrow) causing erosion of tibia and fibula. (c, d): Corresponding post-chemotherapy MR images showing significant reduction of the mass lesion with minimal enhancing residual soft tissue lesion at the end of 3 months of larotrectinib (Asterix) and (e, f) complete response after 8 months of therapy.