Australian precision medicine success for Spitz naevus


By Mardi Chapman

16 Jun 2021

Multitargeted tyrosine kinase inhibition with crizotinib has been shown useful in a rare paediatric case of unresectable GOPC-ROS1 fusion agminated Spitz naevus.

The Australian case, published in JAMA Dermatology, was a female who first presented as an infant with progressive facial lesions consistent with Spitz naevus.

Following excision of the larger lesions, smaller lesions enlarged and new lesions appeared in the same facial segment. Further excisions and then an en bloc excision repaired with a cervicofacial flap were performed.

By 2.5 years of age and with further development of lesions on the right periorbital skin, right ear, and right postauricular scalp, the patient was referred for extended immunohistochemical evaluation and whole-genome sequencing of the resected lesions.

A GOPC-ROS1 fusion was identified.

Crizotinib, 280 mg/m2 twice daily, was given via a nasogastric tube with the antiemetic ondansetron hydrochloride owing to refusal of oral treatment by the patient.

The TK inhibitor was well tolerated apart from grade 1 nausea and vomiting.

“After 20 weeks of crizotinib treatment, the patient at 3 years of age showed complete flattening of the periocular, scalp, and auricular lesions to faint pigmented macules and no evidence of new lesions.”

“Although the treatment was well tolerated, the ongoing requirement for administration via nasogastric tube prompted the patient’s parents to cease treatment. Subsequently, slow regrowth of lesions was observed.”

The authors, led by Melbourne dermatologist Dr Susan Robertson, said ROS1 fusions have been found across a spectrum of spitzoid neoplasms, including Spitz naevus, atypical spitzoid tumours, and spitzoid melanomas.

“We posit that the GOPC-ROS1 fusion was functionally consequential in our patient’s agminated Spitz nevi because of the excellent response following treatment with crizotinib and because no other oncogenic driver mutations were identified by whole genome sequencing.”

“Our case highlights the roles of precision medicine and repurposing of established cancer therapies for novel neoplastic indications,” they concluded.

An editorial in the journal said the case was “an elegant demonstration of how precision medicine can transform patient care.”

They said the hope is that existing targeted therapies can be more readily repurposed to treat other types of neoplasms with similar genomic profiles.

“As next-generation sequencing is further integrated into the clinical setting, perhaps in the future even more patients could benefit from such an individualised approach.”

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